Podcasts about Fibrin

Kleine Verletzungen sind im Alltag ganz normal, kleine Schnittwunden beim Rasieren, bei der Gartenarbeit oder beim Hantieren mit scharfkantigem Papier. Instinktiv stecken wir den blutenden Finger in den Mund und unterstützen so die Blutgerinnung.  Das funktioniert auch mit dem Speichel von Blutern, hat Prof. Dr. Johannes Thaler von der MedUni Wien herausgefunden. Thaler ist an der Abteilung für Hämatologie und Hämostaseologie tätig. Eine Studie unter seiner Leitung hat sich mit Hämophilie-A-Patienten befasst - das ist die häufigste Form der Bluterkrankheit und betrifft einige hundert Patienten in Österreich. Die Ergebnisse zeigen, dass der Speichel dieser Patienten die Gerinnung des Blutes auslöst, was gerade bei an der Bluterkrankheit leidenden Menschen eine wichtige Information sein kann. Er finde es „hilfreich, seinen Patienten sagen zu können, dass auch ihr Gerinnungssystem teilweise sehr gut funktioniert. Also dass zum Beispiel der Speichel ein Hämostatikum ist, also ein blutstillendes Mittel ist, das sie immer bei sich haben." Und so funktioniert die Blutgerinnung bei gesunden Menschen: Im zirkulierenden Blut gibt es inaktive Vorstufen verschiedener Proteine, die sogenannten „Gerinnungsfaktoren". Um die Gefäße herum gibt es beispielsweise einen Gewebsfaktor, den Tissue-Faktor, und wenn es nun zu einem Gewebsschaden, zu einer Verletzung kommt, wird dieser Tissue-Faktor freigelegt, der kommt in Kontakt mit den anderen Gerinnungsfaktoren im Blut und dann wird die ganze Kaskade an Enzymen ausgelöst, die sich gegenseitig aktivieren und am Schluss steht dann die Bildung von Fibrin, eine Art Gewebskleber und die Aktivierung von Blutplättchen, auch Thrombozyten genannt. Diese verschließen die Wunde mit einem Thrombus, einem Pfropfen. Thaler: „Das ist ein ganz fein abgestimmter Prozess, denn es muss einerseits ausreichend gerinnen, sonst kommt es zu einer Blutung, es darf aber auch nicht zu viel gerinnen, denn sonst würde es zu einer Thrombose, Schlaganfall, Herzinfarkt etc. kommen."

Prescriptions for blood pressure, cholesterol, blood sugar, and blood clotting are doled out like candy these days. But there is a lot you can do to support these systems naturally and avoid the negative side effects of pharma drugs. On this episode of Vitality Radio, Jared invites a new guest, Ben Fuehrer, to share about a new product line we have at Vitality Nutrition - Utzy Naturals. While some of the ingredients in their formulas will sound familiar, like Nattokinase and Berberine, these aren't just “me too” products. They are well thought out, unique formulas, from a company that is meticulous in its sourcing and manufacturing. This company exceeds Jared's high standards and he's excited to share these products with you.Products:Utzy ProductsAdditional Information:#407: Deep Dive on Nattokinase: A Special Enzyme with Cardiovascular Benefits and More with Julia Craven#449: Suppressive Medicine: How Big Pharma and FDA Get It Wrong With StatinsVisit the podcast website here: VitalityRadio.comYou can follow @vitalitynutritionbountiful and @vitalityradio on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation. In today's episode, our guest Dr. Refaai  will help us understand the formation and function of fibrin monomers (FM) in hemostasis, highlighting their crucial role in coagulation and clot formation and the need for more prospective studies to validate this assay for clinical indications such as DIC, VTE and cancer. Literature sources: Refaai M.A. (2018) The Clinical Significance of Fibrin Monomers. Thromb Haemost, 118, 1856. Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Why You Should Listen:  In this episode, you will learn about the important role of hypercoagulation in chronic illness.  About My Guest: My guest for this episode is Ruth Kriz.  Utilizing her functional medicine background as well as experience in microbiology and teaching pharmacology, Ruth Kriz, MSN, APRN has spent the majority of her professional career as a Nurse Practitioner working with Chronic UTI and Interstitial Cystitis patients; as well as those dealing with hypercoagulation.  Her practice expanded to patients from almost all the states in the US as well as from 35 countries who came to her seeking answers beyond symptom management.  Through molecular testing, an understanding of the genetics common to these patients, and an understanding of how genetics contributes to chronic infection, hypercoagulation, and biofilms, she has been able to very successfully treat this population.  These factors have broad implications for other chronic infections (sinus, prostate, ear infections, wounds, etc.) as well as fibromyalgia, cardiovascular disease, and other conditions in which hypercoagulation and biofilms are an important contributor.  She has closed her medical practice, but she reinvented as a consultant to help practitioners learn how to utilize her approach for curing these patients and currently is working with MicroGenDX. Key Takeaways: What are the symptoms and conditions associated with hypercoagulation? Why is the "fibrinolytic pathway" a better term than "hypercoagulation"? What genetic predispositions are involved in coagulation disorders? Can hypercoagulation be treated naturally or are pharmaceutical interventions required? What is the role of vitamin K in coagulation? How might long-term antibiotics for chronic Lyme disease contribute to coagulation issues? What is the difference between fibrin and a biofilm? What are some of they key labs to explore in order to assess for the potential of hypercoagulation? Are statin drugs contraindicated in those with high Lp(a)? What role do platelets play in the coagulation discussion? What is the connection between long COVID and biofilms? How does lumbrokinase compare to nattokinase? Why are D-Dimer and PT/PTT not ideal tests for exploring hypercoagulation? Connect With My Guest:  http://RuthKriz.com Related Resources: To review additional resources mentioned in the episode, visit https://BetterHealthGuy.com/Episode207. Interview Date: October 29, 2024 Transcript: To review a transcript of this show, visit https://BetterHealthGuy.com/Episode207. Additional Information: To learn more, visit https://BetterHealthGuy.com. Disclaimer:  The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority. 

Superimposed on an impressive body of work on the blood-brain-barrier and immune system, Prof Akassoglou and her collaborators just published an elegant study in Nature that centered on the direct binding os the SARS-CoV-2 spike protein to fibrin with marked downstream pro-inflammatory effects. The findings and potential treatments have implications beyond Covid, Long Covid to other neurologic diseases.Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to audio and to relevant papers, graphicsEric Topol (00:07):Well, hello this is Eric Topol with Ground Truths, and with me today is Katerina Akassoglou. She is at the Gladstone Institute and she is a remarkable neuroimmunologist who has been doing extraordinary work for three decades to unravel the interactions between the brain, blood vessels and the role of inflammation. So Katerina, there's a lot to discuss, so welcome.Katerina Akassoglou (00:40):Thank you. Thank you so much. It's a great pleasure to join.By Way of BackgroundEric Topol (00:43):It's really interesting going back in your career. First of all, we're thankful that you immigrated here from Greece, and you have become one of the leading scientists in this discipline of important discipline of neuroimmunology, which is not just about Covid that we're going to talk about, but Alzheimer's and neurodegenerative diseases. This is a really big hot area and you're definitely one of the leaders. And what I was impressed is that all these years that you've been working on the integrity of the blood-brain barrier, the importance of fibrinogen and fibrin, and then comes along the Covid story. So maybe what we can do is start with that, which is you've made your mark in understanding this whole interaction between what can get into the brain, through the blood-brain barrier and incite inflammation. So this has been something that you've really taken to the extreme knowledge base. So maybe we can start with your work there before we get into the important seminal Nature paper that you recently published.Katerina Akassoglou (01:57):Yes, of course. So since very early on, I was still a graduate student when we made the first discovery and at the time was like mid-90s, so it was really ahead of its time. That dysregulation of cytokine expression in the brain of mice was sufficient to induce the whole cascade of events, triggering neurodegeneration, demyelination in pathological alterations, very reminiscent of multiple sclerosis pathology. And it was really hard to publish that study at the time because it was not yet accepted that this regulation of the immune system modeling the brain can be linked to neurodegeneration. So that was 1995 when we made that discovery, and I became really interested, what are the pathogenic triggers that actually polarized the immune cells in the brain? So with this, of course, this transgenic animal was expressing TNF, it was an artificially made animal that we made, but naturally what were the triggers that would polarize the innate immune cells? So I looked really early on in this mice and what I found was that the very first event was leaks of blood-brain barrier. It was opening of the blood-brain barrier in this mouse before inflammation, before demyelination, before neuronal loss. And this is really what shaped the question that, is it possible that these blood leaks that happened very early in the pathology, could this be the instigators of pathogenic inflammation in the brain?Eric Topol (03:34):Yeah. So in a way, you got at this question because of the chicken-and-egg and what happens first, and you got to the temporal saying, which happened first as you said, the leak before you could see evidence of inflammation and being able to study this of course in the experimental model, which you couldn't really do in people. And what I love about the description of your career, which has been quite extraordinary contributions is connecting the dots between the blood, the inflammatory response and the brain. Perhaps no one has done that like you have. And before we get into the recent paper, a lot of people are not aware that a year ago, a group in the UK known as PHOSP-COVID, they published a really important paper in Nature Medicine of over 1,800 people who were hospitalized with Covid and they found that fibrinogen was the best marker for cognitive deficits at 6 and 12 months (Figure below)(04:40):So that's just one of many papers, but it's a particularly well done study that already before you got into this work that recently published had emphasized fibrinogen. And by the way, again, having spent a lot of years in clots in the arteries, for me, we have to just get it down to fibrinogen plus thrombin gets you to fibrin. Okay, so fibrin is a major player here when fibrinogen is cleaved. So here we have the basis that you established, which is the fibrinogen leakage into the brain, activating inflammation, activating microglia, which like the macrophages of the brain and inciting the whole process. And before we close, I want to not just talk about Covid, but Alzheimer's too. But now let's get into the study that you did, [Fibrin drives thromboinflammation and neuropathology in COVID-19] which is striking, I mean really striking. And can you kind of take us through, because you not only demonstrated the importance of fibrin in inciting neuroinflammation in this model, but also how you could reverse it or prevent it. So this, and you looked at it in many different ways, this was a systematic approach. Maybe you can take us through how you were able to make such compelling evidence.The Multimodal EvidenceKaterina Akassoglou (06:09):Yes, thank you. First of all, thank you for bringing up the human relevance because this was also our inspiration for the work that we did in the Covid study. So as you mentioned in Covid patients, fibrinogen unbiased mass spec analysis was identified as the predictive biomarker for cognitive impairment in Long Covid patients. And this was in addition to also neuropathology data about the abundance of fibrin deposition in the brain. And these were studies that were done by NIH that have found deposition of fibrin in the brain and the reports for the abnormal and puzzling coagulation in Covid that is not setting other infections and also in many cases not always relating with the severity of symptoms. So even mild cases of Covid also had increased coagulation. I was really intrigued by this human, all this evidence in human data, and I thought that maybe the way that we're thinking about this, that it's systemic inflammation that drives the clotting.(07:24):Maybe there's another aspect to this. Maybe there is a direct effect of the virus with the coagulation cascade, and in this way maybe this can be an instigator of inflammation. So this was the original idea to be able to reconcile this data from the clinic about why do we have this prevalence of coagulopathy in Covid. And of course, the second question is, could this also be a driver of the disease? And of course, we're in a unique position because we have been studying this pathway now for over 20 years to have all the toolbox, the genetic toolbox, the pharmacologic toolbox to be able to actually really address these questions with genetic loss of function studies, with a blood innate immunity multiomics pipeline that we have set up in the lab. And of course, with preclinical pharmacology in our ABSL3 facility. So we had the infrastructure in place and the source in place to actually really dissect this question with both genetic tools as well as also technology platforms.Eric Topol (08:29):And you had in vivo imaging, you're the director of in vivo imaging for Gladstone and UCSF. So you do have the tools to do this.Katerina Akassoglou (08:38):Yes. The imaging that you mentioned is really important because this is, we employed that very early in our studies over now 15 years ago. And the reason was sometimes from snapshots of histopathology, you cannot really understand the sequence of events. So by being able to image these processes, both neuronal activity, microglia activation, infiltration of peripheral cells in the brain, this is how we could see the steps that what happens early on and to be able to answer these chicken-and-egg questions that you mentioned. So these were very, they're very important experiments, especially at the beginning because they were hypothesis driving and we were able to ask the right questions to drive our research program.Eric Topol (09:26):Now was the binding of the spike protein to one key site in fibrinogen, was that known before? [See outstanding Figure below from Trends in Immunology]Katerina Akassoglou (09:36):No, this was not known. So there was evidence that there are abnormal clots in Covid, but it was not known whether the spike protein would directly bind to protein to the coagulation cascade. So one of the key discoveries in our study was to use peptide array mapping and be able to identify not only the binding, but exactly the domains on fibrin that spike binds too. And what we found was two key domains, one the inflammatory domain and the other the plasmin binding site, which is important for fibrin degradation. So this suggested a potential dual deleterious role for this interaction, both by maybe affecting inflammation, but also delaying fibrinolysis, which is the degradation of this toxic protein from the brain. And indeed, we found that this interaction was responsible for all these two aspects, including decreased degradation, more inflammation, but also at the same time increased, increased coagulation. So it was a really pathogenic interaction.Eric Topol (10:47):Yeah, actually it's pretty striking. You have these two sites, the plasmin cleavage site of fibrinogen, which as you say, we knew there was a problem with clots. We knew that, but we didn't know exactly the spike protein how exactly it was implicated, particularly with fibrinogen. And then this other site, the CD11b-C18, now that's fancy for surface receptors of macrophages. And basically, this is critical because it's this microglia activation in the brain, and I know you saw it in the lungs as well through this other site that spike protein activated. So you had a twofer here of things that you discovered that the SARS-CoV-2 spike protein was capable of doing. This was a really big revelation. And then you also looked at mice that were genetically manipulated. So maybe you can, because before we get to your antibody monoclonal, the ways that you proved this were, I mean, one thing after another is really systematic. So maybe you can teach us about that.Thanks for reading Ground Truths! This post is public so feel free to share it.Establishing CausalityKaterina Akassoglou (12:08):Yeah, sure. So the first was about chemistry experiment. So this of course, we had to get to the next step to see is there any causality for this pathway. So we employed genetic loss of function studies and we had knockout mice, either fibrinogen knockout mice, this mice have all blood proteins except fibrinogen, and they have a delay in coagulation so they don't clot properly. But we also had a mutant mouse, which is a fibrinogen NK mouse. And this was a mutation only within this inflammatory domain that you mentioned, inflammatory domain that binds to C11b-C18. Other names for this is of course complement receptor 3, Mac-1 (αMβ2). It's the same, many names for this receptor, that as you mentioned, is expressed not only in microglial in the brain, but also peripheral immune cells including macrophages as well as also neutrophils which are CD11b expressing.(13:12):So we now have genetic models to be able to look at both complete depletion of fibrinogen, but also a very specific mutation and very selective mutation that only blocks the inflammatory properties without affecting the properties of fibrin in hemostasis. And these mice were made many years ago by a very close collaborator, Jay Degen at the University of Cincinnati. So what we found is that when we block either the inflammatory domain or we completely deplete fibrinogen, there was this profound protection after infection in internasal infection with the virus in lung inflammation. And this was both suppression of oxidative stress and this pathogenic inflammation in the lung, but also decreasing fibrosis, which has been associated with also Long Covid. And the surprise came from the transcriptomic data. So when we did transcriptomic analysis in this mice in the lungs, we found perhaps the expected decrease in the immune signatures in macrophages. This was in line with our previous work in, as you mentioned, Alzheimer's models, multiple sclerosis models. But what also was really surprising is there was that genes that are associated with activation of NK cells were upregulated. And of course this was the first time we had infected these mice, previously we had not done an infection before. So I think that maybe because of this region we had not seen before in our data this immunomodulatory role of fibrin that not only surprises the macrophage response, but also increases these NK cells that are important for viral clearance.Eric Topol (15:00):So again, the finding another important unique finding is the natural killer (NK) cells and effect there from the activation of this, as you said, the inflammation site or the CD11b-C18 that we've been talking about. So now another layer of this, a dimension of your Nature paper was that you tested an antibody that you already had developed so-called 5B8. A monoclonal that specifically binds to the domain of the one we're talking about this inflammation domain of fibrinogen. So can you tell us about what that showed?Katerina Akassoglou (15:45):Yes, so we tested this antibody in different models of Covid, which were both models with neuroinvasion and models without neuroinvasion. So we used both transgenic mice for hACE2, the human ACE2 infected with Delta, but we also use mouse adapted viruses like Beta that is just in the wild type mice with no transgenic being involved that these are without neuroinvasion. And we wanted to see if the antibody had any potential protective effects. And what we found is that the antibody protected from inflammation in the lung. So the data looked so similar with a genetic mutation of this pathway, protection from inflammation, decreased fibrosis, increased viral clearance, so decreased spike and viral proteins in the lungs. But we also found a protection in the brain. So the brains of this mice, including both the models we used with neuroinvasion and without, they both have had microglia activation in the brain. And we also found neuronal loss in the Delta infected mice and the antibody protected from both neuroinflammation but also improved neuronal survival in the mice. Showing that there can be this despite regardless of which model we used, there was this protective effect suggesting that by blocking fibrin, either the periphery or in the brain, this could be protected for these models.Eric Topol (17:28):Yeah, so I mean this is fascinating because until now, until this report of yours and your colleagues at Gladstone, there was knowledge that there would be neuroinflammation from Covid, both in patients from various biomarkers and imaging as well as in experimental model. But what this did was take it to the fibrin story, and I guess that's one of the questions you nailed that how important fibrin is, but that doesn't necessarily rule out other triggers of neuroinflammation, right?Katerina Akassoglou (18:04):Oh, absolutely not. So I think that this is one of the mechanisms that can be very important, especially in some patients. But we know that there are additional of course mechanisms of neuroinflammation including auto-antibody responses, as well as also endotheliopathy that are persistent endotheliopathy, this can be interacting also with each other. So I think that it's important for future research that we understand how do these mechanisms feed into each other? Are there a positive feedback loops between autoimmune mechanisms and coagulopathy and endothelial dysfunction with inflammation? But I think most importantly, I think that if we're thinking of this in the context of patients, can we identify patients with mechanism that might be more prevalent in specific cases of Long Covid and tailor our potential future clinical trials towards the needs of Long Covid patients?Towards TreatmentEric Topol (19:06):Absolutely. I did interview some months back on Grounds Truths, Michelle Monje at Stanford, who I'm sure and interact with, and she's also works not so much on the fibrin side, but on neuroinflammation and the likeness between this condition in people and chemo brain because of the inflammation that's seen there. So we've talked about the multiple triggers that could contribute to brain inflammation, which I think most people would say in Long Covid this is one of the most, besides obviously the lack of energy, the profound fatigue and disability, but the cognitive function hit, not just brain fog is often profound. And we've just seen some reports about that, and particularly in hospitalized patients, how bad that can be. So that gets us to a potential treatment. Now, one of the things that's out there dangling, there's many things that people have talked about in terms of why can't we have a treatment for Long Covid?(20:13):And now of course this fibrin pathway, if you will, lends itself to many possibilities, whether it's anticoagulants or fibrinolytics like a tPA or things like nattokinase, which is a Japanese food enzyme that you could get at the nutrition centers or whatever. What are your thoughts? Because we don't have any good studies. There are all these little, tiny studies and they don't provide much conclusion, and you have an antibody that could potentially be effective. As I understand it, you set up a company some years ago, Therini Bio and used to be called MedaRed. You're the first woman scientist at Gladstone to develop a spin out company, which is another point of congratulations on that. But could the antibody be tested in patients or what do you think about these other possibilities?Katerina Akassoglou (21:15):Yes, yes. These are great questions. So first of all, the different approaches that you mentioned have very different mechanism of action. So degrading fibrin, the degradation products of fibrin also can have deleterious effects. The dimer, for example, can be very pro-inflammatory. So at the same time, blocking coagulation can also have a diverse effects because this can lead to excessive hemorrhage. So the approach that we took was to selectively block the inflammatory properties of fibrin without affecting beneficial effects of the molecule in normal hemostasis. So the challenge when I made the antibody was to be able to dissect these two functions of fibrin. It's our most important clotting factor, but at the same time, a molecule with profound pro-inflammatory capacity. So the observation that these two domains, the clotting domain and inflammatory domain were not overlapping, was really the foundation of this invention was that we could maybe create this antibody to be able to target them in a selective way.Other Neurologic Conditions (22:31):So the antibody I developed is neutralizing blood toxicity by blocking the inflammatory domain of fibrin without adverse coagulation effects. And it's now completing phase one trials. So it has already completed the single ascending dose at 40 milligram per kilogram. It's interim data were announced already for this trial, with no safety signals. So if the antibody completes this year, the phase one trials, then it should be possible to be tested in different patient populations. You mentioned before chemo brain, and I think it's important that we think that blood-brain barrier disruption occurs among many neurological conditions, and it's an early event associated with early disease onset and worse prognosis in multiple sclerosis, Alzheimer's disease, traumatic injuries. So I think that it's by developing a strategy, therapeutic strategy to neutralize blood toxicity, this can have applications in a wide range of neurological conditions with vascular dysfunction.Eric Topol (23:54):Yeah, no. In your Nature Immunology 2020 piece [Figure below], you started with the 1883 identification of multiple sclerosis (MS) lesions were “engorged with blood”, the first link between blood leaks and brain inflammation. So this has enormous potential. And what I like about this Katerina is that you've dissected the clot component versus the inflammatory trigger of the fibrinogen and fibrin story. And this is so vital because if you keep throwing these things that just going to work on the clot and not deal with the pro-inflammatory consequences, then you're going to get the wrong impression that clots are not that important. And by the way, you did mention, and I want to come back to that too, endothelial inflammation, which is another feature of Long Covid is another kind of interactive part of this because when the lining of the blood vessel is inflamed, it will attract microthrombi and also be a participant in this whole affair. What do you think about Alzheimer's and the prospects of being able to interfere with Alzheimer's? We have 20 years in someone before this process takes hold and meets clinical manifestations. Would an antibody like this ever be useful along the way?Katerina Akassoglou (25:29):Yeah, so well, our antibody was tested first in Alzheimer's, this models when it was originally published, and we performed reversal trials in Alzheimer's models. So we dosed mice when they have established amyloid plaques, microglia activation, neuronal loss, and we could reverse this effect so it could increase cholinergic neurons in mice, reduce inflammation in a very selective way, only the neurotoxic part of inflammation and for genetic depletion of this pathway with akin mice in Alzheimer's disease. Also, improves from cognitive impairment, and we now have a new paper in Cell Press that is showing this effects also with really nice and unbiased machine learning models for behavioral segmentation [Figure below].So I think that there is the data both from genetic studies and the antibody show projection in Alzheimer's disease. And of course, as you might have read the recent Lancet report from the Lancet committee on dementia that identified the vascular risk factors as the key contributors, especially post sporadic cases of Alzheimer's disease that is over 90% of Alzheimer's disease that is not genetically linked.(26:58):So I think that there is a real need in Alzheimer's disease to be able to block this vascular induced pathology. And an antibody like the fibrin neutralizing therapy could be positioned to be protective from the vascular induced immune-mediated neurodegeneration in this disease as well. I mean, ultimately, I think that we need to be thinking the terms of efficacy. So we want to have a drug that is efficacious, but we also want it to be selective. And the selectivity is really important because the immune system has so many protective functions. So if we block phagocytosis, we end up with more debris, decrease of neurorepair, anti-myelination. So by blocking a ligand here and not blocking, not eliminating a cell type or blocking a global pathway in this cell, but biologic a single ligand, I think we have been able to achieve this balance between efficacy, but also safety because we only block this neurotoxic populations and not the entire innate immune response that also has been beneficial for metastatic functions in the brain.Blocking NeuroinflammationEric Topol (28:19):So you're bringing up another critical concept about targeting the inflammation, this kind of goldilocks story of how much you interfere with the immune response and how much you are able to reduce the adverse pro-inflammatory effects. So that gets me to what if we don't know in any given patient how much fibrin is having a role in their Long Covid. Although we know it has to be a prominent feature because we saw it in, not just a hospitalized patient series that I mentioned we reviewed, but other papers as well. But what about if you just try to take on inflammation like through a GLP-1 drug or cGAS–STING or any of these really strong anti-inflammatory pathways. Do you see a difference in a generalized approach versus a specific approach that is really fibrin centered?Katerina Akassoglou (29:22):Yeah, so we have a focus actually on both because we wanted to dissect the downstream intracellular pathways of fibrin, and it's interesting that we can find specific inflammatory mediators that potentially can also be targeted as well, to be able to preserve that specificity, which I think is really important because if we don't preserve the specificity, we'll end up with a lot of adverse effects by eliminating major immune responses. But the point that you raised I think is really important because it's not enough to have an efficacious and selective drug if you don't know the patient population that will benefit from this drug. So I think that in addition to the drug discovery studies, it's important to develop also biomarker programs with both fluid biomarkers, but also imaging biomarkers to be able to identify the patient populations that will benefit from such treatment.(30:25):So if for example, a patient population has a fibrin deposition, blocking only downstream might not be enough, and it might be really important to neutralize this fibrin toxicity in the brain of patients. And with our target engagement studies, we show that at least in animal models, the antibody can be there. So I'm very encouraged by also programs that are going on now in the scientific community to develop noninvasive ligands to be able to image fibrin in the brain that are already tested in different patient populations like multiple sclerosis. Because I think we're going to learn so much from the biology as we start interrogating and asking these questions now in different patient populations.Eric Topol (31:14):I think that's a vital point you're making because the success of a clinical trial here in a clinical syndrome that is mosaic with lots of different types of pathways. If you can nail down the patients that would have the most to stand to benefit from a particular intervention, that the chance of you not missing the benefit that is matching the marker, what image marker or other markers is so vital. Well, we've talked, I think, about some fascinating discoveries that you and your colleagues have made. I mean, it's really extraordinary, and obviously we need this in Long Covid. But you know what, Katerina, it's almost made me think that you were warming up to this for three decades, that somehow or other you were working on all this stuff and then came Covid. Is that how you see it, that somehow or other you didn't know that all the work you were doing was going to wind up in this space?Katerina Akassoglou (32:18):Oh, I never thought I would work in a virology project. This collaboration started over Zoom with Warner Greene. We were both sheltering in place. It was the beginning of the pandemic, and the first reports were coming out about this puzzling coagulopathy. And our labs were hardly operational at the time, as you know, we had to close down our labs for a while. And however, this was a very big problem, and we thought that this is our role as scientists. If we feel that we can contribute and we have the tools to contribute, we felt that it's important that we pivot some part of our research, and even we wouldn't be doing this before, but it was important to pivot a part of our research and collaborate. And I think studies like this, this study would have been impossible without a team of collaborators. As you know, there were over 50 scientists involved at Gladstone, UCSF, UCLA, UCSD, Stanford University. Without collaboration, this study wouldn't be possible. So I'm really grateful to everyone who came together to solve this problem because I think that's what scientists should be doing. We should be solving problems as they arise.Eric Topol (33:41):Well, and also, I think a lot of people don't realize that, for example, when the Covid vaccines came along, people think, oh, well, it all got done in 10 months since the sequence of the virus, when in fact it took 30 years at least between all the factors that went into having an mRNA and sequencing virus and nanoparticles. And in many ways, your arc of this work is like that because it took three decades to have all the tools and the basic understanding, the antibody that you had developed for different reasons and this fascinating unraveling of what's going on in the model and undoubtedly in some patients at least as well. So before we wrap up, have I missed anything about this just remarkable work you've done?Katerina Akassoglou (34:33):Oh, thank you. I just want to thank you for this discussion and thank you for emphasizing the different areas and the different decisions that this pathway can have implications both for our understanding, our basic understanding of the blood brain immune interface, as well as also potential translation. And I think that the curiosity sometimes of how things work, I never thought it would work on Covid, like you mentioned at the beginning, but I think that basic science and curiosity driven science can sometimes lead to discoveries with translational implications that hopefully might benefit patients one day.Eric Topol (35:21):Yeah, well, undoubtedly it will. We're indebted to you, Katerina and all the folks that you have teamed up with, connecting the dots at the neurovascular interface. Phenomenal work and will follow the subsequent with great interest and it will likely not just a story about Long Covid, but other areas as well, so thank you.*********************************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly help fund our summer internship programs.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

4184 風とあそぶ：） 20240913FRI 今日のCOVID-19・・・1398回目 空気感染・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4181 風とあそぶ：） 20240912THU 今日のCOVID-19・・・1397回目 戦争・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4178 風とあそぶ：） 20240911WED 今日のCOVID-19・・・1396回目 無策の上に・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4175 風とあそぶ：） 20240910TUE 今日のCOVID-19・・・1395回目 検査・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4172 風とあそぶ：） 20240909MON 今日のCOVID-19・・・1394回目 あらためて・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4169 風とあそぶ：） 20240908SUN 今日のCOVID-19・・・1393回目 乖離・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4166 風とあそぶ：） 20240907SAT 今日のCOVID-19・・・1392回目 注意喚起は・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4163 風とあそぶ：） 20240906FRI 今日のCOVID-19・・・1391回目 出来る事を・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

4160 風とあそぶ：） 20240905THU 今日のCOVID-19・・・1390回目 血栓・・・ ■Fibrin drives thromboinflammation and neuropathology in COVID-19 https://www.nature.com/articles/s41586-024-07873-4 ■札幌市下水サーベイランス https://www.city.sapporo.jp/gesui/surveillance.html ■新型コロナ・季節性インフルエンザの流行状況速報値の活用例監修モデルナ https://moderna-epi-report.jp/ ■全員が安全になるまで、誰も安全ではない Nobody is safe until everybody is safe ●WHOコロナ後遺症の方のためのガイドライン ⁠http://bit.ly/3kteZFv⁠ 日本語 ●職場復帰に関するガイドラインー英国産業衛生学会 ⁠http://bit.ly/3ZWmipo⁠ 日本語 ■Flowflex フロウフレックス 抗原検査キット https://amzn.to/46LQ3wY ■株式会社 CLEAIR https://cleair-w.com/ 気合・気愛で555!!! アラキ：） KOJI ARAKI Art Works Copyright KOJI ARAKI Art Works All Rights Reserved

La pérdida de peso puede ser un proceso complejo, y hay varios factores que pueden dificultar o impedir que logres tus objetivos de peso. Aquí te detallo algunos de los factores más comunes:1. Alimentación Inadecuada:Exceso de Calorías: Aunque comas alimentos saludables, si consumes más calorías de las que quemas, no perderás peso.Composición de la Dieta: Dietas ricas en azúcares, grasas saturadas y carbohidratos refinados pueden dificultar la pérdida de peso.Tamaño de las Porciones: Subestimar las porciones puede llevarte a consumir más calorías de las necesarias.2. Falta de Ejercicio o Actividad Física:Estilo de Vida Sedentario: La falta de actividad física disminuye el gasto calórico, dificultando la creación de un déficit calórico.Ejercicio Ineficaz: Un tipo de ejercicio que no sea lo suficientemente intenso o duradero puede no ser suficiente para quemar calorías en exceso.3. Metabolismo Lento:Factores Genéticos: Algunas personas naturalmente tienen un metabolismo más lento, lo que significa que queman menos calorías en reposo.Edad: A medida que envejecemos, nuestro metabolismo tiende a ralentizarse, lo que puede hacer que sea más difícil perder peso.4. Desequilibrio Hormonal:Problemas de Tiroides: Hipotiroidismo, una condición donde la glándula tiroides es menos activa, puede ralentizar el metabolismo.Resistencia a la Insulina: Las personas con resistencia a la insulina o diabetes tipo 2 pueden encontrar más difícil perder peso debido a la alteración en la forma en que el cuerpo maneja los azúcares.Estrés y Cortisol: El estrés crónico puede aumentar los niveles de cortisol, lo que promueve la acumulación de grasa, especialmente en la zona abdominal.5. Privación del Sueño:Alteración de las Hormonas del Hambre: La falta de sueño afecta las hormonas grelina y leptina, que regulan el hambre y la saciedad, aumentando el apetito y las ganas de comer alimentos poco saludables.Disminución de la Energía: Menos horas de sueño pueden llevar a menos actividad física y mayor fatiga, dificultando la quema de calorías.6. Estrés y Salud Mental:Comer Emocional: El estrés, la ansiedad o la depresión pueden llevar a comer en exceso, particularmente alimentos ricos en calorías y pobres en nutrientes.Motivación Baja: Problemas de salud mental pueden afectar tu motivación y consistencia en seguir una dieta o un régimen de ejercicio.7. Consumo de Alcohol:Calorías Vacías: El alcohol es alto en calorías pero bajo en nutrientes, y su consumo puede sumar calorías significativas a tu dieta diaria.Efectos en el Metabolismo: El cuerpo prioriza la quema de alcohol sobre la quema de grasas, lo que puede ralentizar la pérdida de peso.8. Medicamentos:Efectos Secundarios: Algunos medicamentos, como los antidepresivos, corticosteroides o ciertos tratamientos para la diabetes, pueden causar aumento de peso o dificultar la pérdida de peso.9. Expectativas Irrealistas:Impaciencia: Esperar resultados rápidos puede llevar a la frustración y al abandono del esfuerzo.Comparación con Otros: Compararte con el progreso de otras personas puede ser desmotivador, ya que cada cuerpo responde de manera diferente.10. Factores Ambientales y Sociales:Accesibilidad a Comida Rápida: Vivir en un entorno donde hay fácil acceso a alimentos poco saludables puede hacer más difícil mantener una dieta equilibrada.Falta de Apoyo Social: No contar con el apoyo de amigos, familia o un grupo de apoyo puede dificultar mantener los cambios en el estilo de vida.11. Problemas de Digestión o Microbiota Intestinal:Desequilibrio en la Microbiota: Un desequilibrio en las bacterias intestinales puede influir en la forma en que el cuerpo almacena grasa y en la regulación del hambre.Si sospechas que algunos de estos factores pueden estar afectando tu capacidad para perder peso, es recomendable hablar con un profesional de la salud, como un nutricionista o un médico, para recibir orientación personalizada.Cuando la pérdida de peso es difícil a pesar de los esfuerzos en dieta y ejercicio, una analítica de sangre puede revelar ciertas alteraciones que podrían estar contribuyendo a este problema. Aquí te detallo los parámetros que podrían estar alterados y cómo podrían estar influyendo:1. Hormonas Tiroideas:TSH (Hormona Estimulante de la Tiroides): Un nivel elevado de TSH puede indicar hipotiroidismo, una condición en la que la glándula tiroides no produce suficiente hormona tiroidea. Esto ralentiza el metabolismo y puede dificultar la pérdida de peso.T4 Libre y T3 Libre: Son las hormonas tiroideas principales. Niveles bajos de T4 o T3 libre también sugieren hipotiroidismo.2. Cortisol:Cortisol (hormona del estrés): Niveles crónicamente elevados de cortisol, asociados con el estrés, pueden llevar a la acumulación de grasa abdominal y aumentar el apetito, especialmente por alimentos altos en azúcar y grasa.3. Insulina y Glucosa:Insulina en Ayunas: Niveles elevados de insulina pueden ser indicativos de resistencia a la insulina. Esta condición puede hacer que sea más difícil perder peso, ya que el cuerpo almacena más grasa.Glucosa en Ayunas: Niveles elevados de glucosa en sangre pueden ser un signo de prediabetes o diabetes tipo 2, condiciones que a menudo se asocian con la dificultad para perder peso.4. Perfil Lipídico:Colesterol Total, LDL, HDL, y Triglicéridos: Un perfil lipídico alterado, especialmente niveles elevados de triglicéridos y LDL (colesterol "malo") junto con bajos niveles de HDL (colesterol "bueno"), puede ser indicativo de resistencia a la insulina o síndrome metabólico, lo que puede dificultar la pérdida de peso.5. Hemoglobina Glicosilada (HbA1c):HbA1c: Este parámetro refleja el nivel promedio de glucosa en sangre durante los últimos 2-3 meses. Niveles elevados pueden sugerir diabetes o prediabetes, condiciones que pueden complicar la pérdida de peso.6. Hormonas Sexuales:Estrógenos: Niveles anormalmente altos o bajos de estrógenos pueden afectar la distribución de la grasa corporal, especialmente en mujeres, y pueden estar relacionados con dificultad para perder peso.Testosterona: En hombres, niveles bajos de testosterona pueden estar relacionados con un aumento de grasa corporal y una disminución de masa muscular, lo que puede dificultar la pérdida de peso.7. Vitamina D:Vitamina D: Niveles bajos de vitamina D se han asociado con un mayor riesgo de obesidad y pueden interferir con la pérdida de peso. Además, la deficiencia de vitamina D puede afectar negativamente la función tiroidea y la sensibilidad a la insulina.8. Función Hepática:ALT y AST (Transaminasas): Elevaciones en estos marcadores pueden indicar problemas hepáticos, como hígado graso no alcohólico, que está asociado con la obesidad y la resistencia a la insulina.GGT (Gamma Glutamil Transferasa): Un marcador elevado también puede ser un indicativo de estrés hepático, relacionado con la acumulación de grasa en el hígado.9. Perfil de Inflamación:Proteína C Reactiva (PCR): Es un marcador de inflamación en el cuerpo. Niveles elevados pueden estar asociados con resistencia a la insulina y un mayor riesgo de obesidad.Fibrinógeno: Un nivel alto puede indicar un estado proinflamatorio, lo que está relacionado con la obesidad y la dificultad para perder peso.10. Leptina y Grelina:Leptina: Es la hormona que regula el apetito y el gasto energético. Niveles elevados pueden indicar resistencia a la leptina, lo que puede llevar a un aumento del apetito y dificultad para perder peso.Grelina: Es la hormona que estimula el apetito. Niveles anormales pueden afectar la regulación del hambre y contribuir al aumento de peso.Si alguno de estos parámetros está alterado, puede ser necesario un tratamiento específico o ajustes en tu enfoque para perder peso. Es fundamental que estas evaluaciones sean interpretadas por un médico o un especialista en endocrinología, quien podrá ofrecerte un diagnóstico y tratamiento adecuado.Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/comiendo-con-maria-nutricion--2497272/support.

Send Dr. Caroline a MessageDO YOU EXPERIENCE LOTS OF MUCOUS IN YOUR BODY, DIFFICULTY HEARING, INDIGESTION? SOME OF THESE SYMPTOMS JUST MAY BE HELPED BY THE TISSUES SALT, KALI MUR 6X.INTRODUCTION TO TISSUE SALTS: https://www.buzzsprout.com/103155/15246915-tissue-cell-salt-introduction.mp3?download=trueCATALYN IS STANDARD PROCESS ALL PURPOSE VITAMIN FOR ALL YOUR TISSUE SALTS.  LEARN ABOUT and order CATALYN HERE: https://carolinewalrad.standardprocess.com/products?page=1&searchTerm=Catalyn%C2%AE&sortOrder=relevanceStandard Process Whole Food Supplements, Organically Grown in the United States. "Changing lives since 1929"Order directly from Standard Process here:carolinewalrad.standardprocess.com/products

In this part 2 episode, we dive into the pathology and symptoms of Babesiosis, exploring how the Babesia parasite infects red blood cells and evades the immune system. We discuss various labs and biomarkers to look out for. We then address various treatment protocols featuring anti-malarials including herbal supplements such as artemisinin and cryptolepis, and proteolytic enzymes like lumbrokinase and nattokinase. Additionally, we cover the use of methylene blue and its impact on Babesia parasites. Topics: 1. Introduction - Brief overview of Babesiosis and previous discussion - Overview of Babesia infection and its impact on red blood cells (RBCs) 2. Pathology of Babesiosis - Infection and multiplication within RBCs - Mechanisms of immune evasion - Expression of specific proteins on RBC surface - Adherence to capillary endothelial cells - Avoidance of spleen clearance - Antigenic variation and immune system evasion 3. Symptoms of Babesiosis - Air hunger - High fever - Severe fatigue - Muscle and joint pain - Persistent headaches - Jaundice - Dark urine - Organ failure (in severe cases) 4. Labs and Markers for Babesiosis - Hematological markers - Hemolytic anemia - Thrombocytopenia - Leukopenia - Hemoglobinuria - Hyperbilirubinemia - Elevated LDH levels - Reticulocytosis - Other markers - High C4a levels - Low CD57 count 5. Protocols - Importance of medical supervision and potential Herxheimer reaction - Overview of treatment approaches 6. Anti-Malarial Protocols for Babesiosis - Prescription Medications - Mepron (Atovaquone), Mechanism of action: inhibition of mitochondrial electron transport chain. - Azithromycin, Mechanism of action: blocking protein synthesis. - Herbal Approaches for Babesiosis - Artemisinin: Derived from sweet wormwood plant. Mechanism of action: production of reactive oxygen species (ROS). - Cryptolepis: Bioactive compound is Cryptolepine, Mechanism of action: disruption of DNA synthesis. 7. Proteolytic Enzymes - Lumbrokinase - Nattokinase 8. Methylene Blue - Synthetic dye - Mechanism of action: disrupting mitochondrial function and generating ROS within Babesia - Administration methods and effects 9. Conclusion - Recap of supplements and treatments discussed - Emphasis on individualized treatment plans, bioindividuality, and working with a medical physician Thank you to our episode sponsor: ⁠Liver Medic⁠ Use code Chloe20 to save 20% on ⁠⁠"Leaky Gut Repair"⁠⁠ ⁠⁠Brendan's YouTube Channel⁠⁠ ⁠⁠https://x.com/livermedic⁠⁠ Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Did you know there is an enzyme that can help you break down abnormal cells and proteins in the body like cysts, scar tissue, and blood clots, as well as detoxifying your blood at a cellular level? On this episode of Vitality Radio, Jared interviews our favorite enzyme educator, Julia Craven, VP of Education for Enzymedica. They do a deep dive on all of the amazing things Nattokinase can do in the body. You'll learn how it works and why it can replace baby aspirin for cardiovascular health and so many other amazing functions in the body. Wondering if it's something you should add to your regimen? Listen and decide if it's best for you!Products:Enzymedica Natto-KEnzymedica Enzyme DefenseSource Natural NattoAdditional Information:#383: The Incredible Benefits of Enzymes For Digestion, Immunity, and Overall Health With Julia Craven#301: Systemic Enzymes for Mucus, Candida, Immune Support, Heart Health and more. Also a Brand New Magnesium! Guest, Julia Craven#292: Food Sensitivities and Digestive Enzymes. How to Ease The Burden with Julia CravenVisit the podcast website here: VitalityRadio.comYou can follow @vitalityradio and @vitalitynutritionbountiful on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Please also join us on the Dearly Discarded Podcast with Jared St. Clair.Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

In this week's episode we'll explore the role of fibrinogen polymerization in thrombosis. Then, we'll discuss preventing CD19-negative relapse after CAR T-cell therapy in acute lymphoblastic leukemia. Finally, we'll learn how increased levels of the RNA-binding protein FUS has been identified as an effector of hematopoietic stem cell aging. 

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Dr. Elizabeth Maxwell and Molly Cohen, authors of "Endoscopic application of fibrin glue may be a feasible method of treatment for postintubation tracheal lacerations in cats in: American Journal of Veterinary Research Volume 84 Issue 3 (2023) (avma.org)," discuss how the endoscopic application of fibrin glue may be a feasible method of treatment for postintubation tracheal lacerations in cats. Hosted by Associate Editor Dr. Sarah Wright and Editor-in-Chief Dr. Lisa Fortier.INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA OR AJVR?JAVMA: https://avma.org/JAVMAAuthorsAJVR: https://avma.org/AJVRAuthorsFOLLOW US:JAVMA:Facebook: Journal of the American Veterinary Medical Association - JAVMA | FacebookInstagram: JAVMA (@avma_javma) • Instagram photos and videosTwitter: JAVMA (@AVMAJAVMA) / Twitter AJVR: Facebook: American Journal of Veterinary Research - AJVR | FacebookInstagram: AJVR (@ajvroa) • Instagram photos and videosTwitter: AJVR (@AJVROA) / TwitterJAVMA and AJVR LinkedIn: https://linkedin.com/company/avma-journals#VeterinaryVertexPodcast #JAVMA #AJVRINTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA ® OR AJVR ® ? JAVMA ® : https://avma.org/JAVMAAuthors AJVR ® : https://avma.org/AJVRAuthorsFOLLOW US:JAVMA ® : Facebook: Journal of the American Veterinary Medical Association - JAVMA | Facebook Instagram: JAVMA (@avma_javma) • Instagram photos and videos Twitter: JAVMA (@AVMAJAVMA) / Twitter AJVR ® : Facebook: American Journal of Veterinary Research - AJVR | Facebook Instagram: AJVR (@ajvroa) • Instagram photos and videos Twitter: AJVR (@AJVROA) / Twitter JAVMA ® and AJVR ® LinkedIn: https://linkedin.com/company/avma-journals

Christie Grace is a specialist in RNA and lipid nanoparticles and was a project manager at the top plasmid company in the world manufacturing recombinant proteins such as monoclonal antibodies, CRISPR, SpCas9, gene editing, and IVT mRNA production. For two years Christie has been raising the alarm over harms that can be caused by lipid nanoparticles and has concerns over cold chain management, vaccine production quality assurance/control and the medical community's unwillingness to look at the scientific data. This is a deep and specific conversation delving into the science of lipid nanoparticles which may become the next target for scientific investigation of vaccination injuries and death. *Apologies for the host repeatedly slipping and calling LNPs 'liquid nanoparticles'. Full reference list is available at: https://discernable.io/lipid-nanoparticles-the-real-danger-of-mrna-vaccines We discussed: Lipid nanoparticles (LNP) The structure of an LNP Mass manufacturing LNPs Zeta potential of LNPs leading to leakage into the vascular system and the heart Are lipid nanoparticles safe? The Ostwald effect on lipids How to cause clots and aneurysms Dying suddenly in the absence of metals means lipid growth Why harms were immediately obvious years ago Fibrin, protease reactions and photos of rapid clotting Claims from morticians of long, stringy clots Photos of branching clots in lungs Why clots are only associated with AstraZeneca and not Pfizer Excess of negatively charged mRNA resulting in clots CDC issues new warning advisory for clots Why adverse reactions are rare 'Death batches' and TGA (Aust) FOI releases showing fragments of junk mRNA How cold chain transport of mRNA vaccines works How to make a vaccine Protein misfolding in the lab and in the body What is the definition of 'vaccine'? Genetic therapeutics How do our cells know when to stop producing spike protein? Finding spike protein around the body Gaslighting women over disruptions to their menstrual cycles Japanese FOI data on lipids concentrating in organs Cardiac myocytes that take up lipids How the vaccine rollout could have been done better Steel-manning the other side Extrapolating LNP damage into the future Linearised DNA (helix straightened) that could cause long term impacts Lean body composition associated with higher risk of inflammation response Distinguishing Long Covid from vaccine injury 'The spawning pit of degradation' 'The amygdala of the internet' Malfeasance and culture inside Big Pharma Silencing of scientists The Fauci emails Directed evolution and the Pfizer leaks Is the Chinese CCP propaganda correct for once? Confirmation bias, self reflection and epistemological query Comparing the scientific honesty of both sides How does science progress if it won't question itself? Hope for the future of medicine

Have you heard all about PRP but not PRF? Tune in to learn why PRF is the new "Hot" treatment! Learn all the differences between PRP and PRF! PRF (platelet-rich fibrin) is processed a little differently than PRP. It is not spun as long or as fast. That leaves other growth factors like white blood cells and stem cells. No additives or anti-coagulants are injected which means the PRF needs to be injected quickly after being spun down. Once it is injected, clots form and the fibrin in the clot keeps the platelets in place. A slow release of growth factors occurs in the next 7-10 day period. Our goal is to help you regain confidence and achieve your best self! Visit www.revitalyzemd.com and check out our blog and schedule your consultation today! View our social media: YouTube: www.youtube.com/channel/UCshDBnd5KdZ7x4GK4i6fTVA Facebook: www.facebook.com/RevitalyzeMD Instagram: www.instagram.com/revitalyzemd TikTok: www.tiktok.com/@revitalyzemd Want to schedule a consultation? Call or text us at 865-293-5828 and we will help you comprehensively look, feel, and function better!

Have you heard all about PRP but not PRF? Tune in to learn why PRF is the new "Hot" treatment! Learn all the differences between PRP and PRF!PRF (platelet-rich fibrin) is processed a little differently than PRP. It is not spun as long or as fast. That leaves other growth factors like white blood cells and stem cells. No additives or anti-coagulants are injected which means the PRF needs to be injected quickly after being spun down. Once it is injected, clots form and the fibrin in the clot keeps the platelets in place. A slow release of growth factors occurs in the next 7-10 day period. Our goal is to help you regain confidence and achieve your best self!Visit www.revitalyzemd.com and check out our blog and schedule your consultation today!View our social media:YouTube: www.youtube.com/channel/UCshDBnd5KdZ7x4GK4i6fTVAFacebook: www.facebook.com/RevitalyzeMDInstagram: www.instagram.com/revitalyzemdTikTok: www.tiktok.com/@revitalyzemdWant to schedule a consultation? Call or text us at 865-293-5828 and we will help you comprehensively look, feel, and function better!

This week on The Red Light Report, we have two more remarkable pieces of photobiomodulation research to cover and, to top it off, both are figuratively hot-off-the-press  —  being published only this past summer! You've heard me say it before, but I'll say it again... while the information may be on particular topics, the takeaways are far-reaching and can be applicable to virtually everyone.​ The first article covered has to do with the ability for red light therapy to improve the tissue regeneration capabilities of fibrin application. Who doesn't want more effective and efficient wound healing and tissue/organ healing? The second piece of research is especially interesting, as it has to do with red light therapy's impact on the brain. However, the article goes even deeper and analyzes the benefits of photobiomodulation temporally, meaning the therapeutic affects it has during wakefulness versus asleep. Needless to say, they have some interesting speculations as to how near-infrared light can impact the brain during sleep that has potentially profound implications for the glymphatic system. This new research continues to expand our awareness on some exciting, novel utilities of red light therapy that can positively impact our health.  As always, light up your health and enjoy this solosode! - Dr. Mike Belkowski discusses the following:  1:43 - Yoga red light therapy 2:49 - Therasage 5:41 - Improving regeneration in tissue via photobiomodulation 8:34 - Fibrin and photobiomodulation 9:10 - Management of the healing process via photobiomodulation 12:34 - Gold nanoparticles 13:31 - The effect of photobiomodulation during wakefulness and sleep 18:54 - Photobiomodulation influences functional activity 23:32 - Increasing mitochondrial activity 26:29 - Photobiomodulation and sleep 31:16 - Transcranial photobiomodulation 32:17 - Photobiomodulation mechanisms during sleep 35:52 - Mornings vs Day/ night for Increasing mitochondrial function and ATP levels 37:33 - Anti-inflammatory effects during sleep 43:40 - How to use near-infrared light while sleeping - Research articles: Application of Fibrin Associated with Photobiomodulation as a Promising Strategy to Improve Regeneration in Tissue Engineering: A Systematic Review   The effect of photobiomodulation on the brain during wakefulness and sleep - Check out the newest innovative device from BioLight... the Matrix! - Check out the Kindle version of Red Light Therapy Treatment Protocols eBook, 4th Edition - To learn more about red light therapy and shop for the highest-quality red light therapy products, visit https://www.biolight.shop - Stay up-to-date on social media: Instagram

Tune in on Sunday, November 13th at 7am EST, for a new episode of The 13th Ave Show featuring Donna Gonzalez, B.S.N., M.S., A.P.R.N. Donna is the Owner and Founder of Artisan Face & Body, which is located in Dunedin, FL. Find out more about Donna on her website: https://www.artisanfacebody.com/home ▪︎ ▪︎ ▪︎ ︎ABOUT OUR GUEST: Graduating with a Bachelor of Science in Nursing and a Master of Science in Anesthesiology, Donna Gonzalez is not only an Advanced Practice Registered Nurse and Nurse Anesthetist, but a skilled and experienced advanced aesthetic practitioner. Proudly, she is also a national trainer of aesthetics with the American Institute of Aesthetic Medicine (AIAM). More than 20 years ago, Donna graduated nursing school with honors and began her career as a trauma and ICU specialist at Miami Jackson Memorial Hospital and Doctor's Hospital in Coral Gables. She worked closely with some of the country's finest doctors, surgeons and nurses. These colleagues include some of the most prominent oral maxillofacial surgeons as well as nationally recognized plastic surgeons. Always thirsting for more knowledge, Donna, broadened her scope of nursing practice to incorporate neuroscience and post anesthesia care. It wasn't long before she found herself enrolled in one of the finest nurse anesthesia programs in the country and graduated as a nurse anesthetist. Subsequent training and practice in neuroscience and anesthesiology afforded her the ability to work with aesthetics for medical treatments, which later blossomed into cosmetic aesthetics. The culmination of her educational background and clinical experience has given Donna the opportunity to implement theoretical and practical experience in creatively combining the art and science of aesthetic treatments to her repertoire. In many circles “DG” is known as “the cannula queen”, for using a highly skilled technique to minimize bruising, bleeding and overall downtime. Donna's focus and passion is completely on the field of aesthetic medicine. It is her belief that both men and women of all ages deserve to look their best, whether it be for cosmetic reasons or sometimes even medical. Donna understands aesthetic medicine at a cellular level to combine therapies with the latest skin rejuvenating techniques providing naturally beautiful results that are reproducible with each treatment! Take note that treatments are not exclusive to the face but to the body as well! DG's results are achieved by utilizing any combination of wrinkle relaxers, dermal fillers, PDO threads, Stem Cell and Fibrin therapy (PRF/PRP), collagen stimulation therapy (CST), skin brightening and resurfacing with laser therapy and the use of medical grade cosmeceuticals…let us not forget skillful technique and expert knowledge! --- Send in a voice message: https://anchor.fm/13th-ave-media/message Support this podcast: https://anchor.fm/13th-ave-media/support

I am thrilled to share with you some information on systemic enzymes. I take them myself and recommend them to many people in my chiropractic practice. Michael has been working with enzymes for over 20 years. He works closely with top researchers, enzymologists, and formulators around the world. These are brilliant people in their field. He has done hundreds of radio shows and podcasts over the years and has personally trained thousands of practitioners on the use of enzymes in their practices. He currently works with HCP Formulas. He talks about how his falls on his mountain bike don't have long-lasting deleterious effects because of his use of Fibrenza. The research demonstrates that post-workout muscle soreness can be greatly reduced with the enzyme bromelain and the yellow chemical from turmeric called curcumin…nature nurtures. We all have enzymes in our bodies and cannot live without them. They help digest food, catalyze reactions, modulate inflammation, maintain and repair cells, and more. Your body makes over 3000 types of enzymes. They are crucial for human existence. Here we cover systemic enzymes: What are they, the benefits in your body, how to take them as supplements, what they do in your bloodstream and can they help with symptoms of aging? Inflammation is a vital to the healing process. However, due to our diets, toxic load and other factors, we can have trouble with inflammation resolution. Enzymes have natural inflammation-fighting properties. In fact, the natural role of enzymes within your body is to help reduce and eliminate inflammation. Taking enzymes helps with inflammation resolution and reduces the fibrosis of repair. From wound healing, fibromyalgia, a sprained ankle, or even inflamed organs can be helped. Enzymes like nattokinase, serrapeptase (Study shown to accelerate healing in patients recovering from dental surgery), papain, bromelain (shown to speed up recovery from cosmetic surgery), lumbrokinase or others help reduce local & systemic inflammation. Systemic enzymes have been clinically proven to speed up the rate at which wounds heal. Animal studies found that bromelain and papain accelerate wound healing when applied to the skin. Take osteoarthritis, irritable bowel syndrome, Crohn's disease or just being bloated after a meal, for instance. All of these conditions have a large inflammatory component that can be helped. I often pair enzymes with extracorporeal shockwave therapy (ESWT). ESST breaks up scar tissue and is great for conditions like tennis elbow, frozen shoulder, arthritic knees, post-surgical scar tissue, and more. The scar tissue divides into calcium and fibrin in the blood. The fibrin can make people fatigued if I am doing a large area and a lot of pulses in one visit. When I have people take the enzymes, they notice no rebound fatigue after aggressive shockwave treatments and better results. There are conditions of too much fibrin, like cystic fibrosis or uterine fibroids. Also, the bloodstream can become clogged with fibrin with age as we become less efficient at clearing the fibrin out. Fibrin is a protein, and proteolytic enzymes are great at counteracting too much of the fibrin as they “eat” protein. Imagine how happy your heart, immune system, arteries, and inflammatory pathways & your life will be with less fibrin in the way. Strokes and heart attack risk go down by decreasing the likelihood of blood clots, and the blood is “thinned.” If it sounds too good to be true, well, they are good and even non-toxic and safe. I would caution about mild nausea and the mild blood thinning component of taking systemic enzymes on an empty stomach. Thank you for your interest, and I wish you the best on your journey of health throughout your lifetime. Adam Fields, DC, is a practicing chiropractor in Northern California and can be reached for an online or telehealth appointment by going to www.fieldsfamilychiro.com and clicking “book online.”

Tune in on Monday, 8/15/22 at 6:30am EST, for a new episode The Doctor Whisperer Show featuring Donna Gonzalez, B.S.N., M.S., A.P.R.N. Donna is the Owner and Founder of Artisan Face & Body. Find out more about Donna on her website: https://www.artisanfacebody.com/home ▪︎ ▪︎ ▪︎ ︎ABOUT OUR GUEST: Graduating with a Bachelor of Science in Nursing and a Master of Science in Anesthesiology, Donna Gonzalez is not only an Advanced Practice Registered Nurse and Nurse Anesthetist, but a skilled and experienced advanced aesthetic practitioner. Proudly, she is also a national trainer of aesthetics with the American Institute of Aesthetic Medicine (AIAM). More than 20 years ago, Donna graduated nursing school with honors and began her career as a trauma and ICU specialist at Miami Jackson Memorial Hospital and Doctor's Hospital in Coral Gables. She worked closely with some of the country's finest doctors, surgeons and nurses. These colleagues include some of the most prominent oral maxillofacial surgeons as well as nationally recognized plastic surgeons. Always thirsting for more knowledge, Donna, broadened her scope of nursing practice to incorporate neuroscience and post anesthesia care. It wasn't long before she found herself enrolled in one of the finest nurse anesthesia programs in the country and graduated as a nurse anesthetist. Subsequent training and practice in neuroscience and anesthesiology afforded her the ability to work with aesthetics for medical treatments, which later blossomed into cosmetic aesthetics . The culmination of her educational background and clinical experience has given Donna the opportunity to implement theoretical and practical experience in creatively combining the art and science of aesthetic treatments to her repertoire. In many circles “DG” is known as “the cannula queen”, for using a highly skilled technique to minimize bruising, bleeding and overall downtime. Donna's focus and passion is completely on the field of aesthetic medicine. It is her belief that both men and women of all ages deserve to look their best, whether it be for cosmetic reasons or sometimes even medical. Donna understands aesthetic medicine at a cellular level to combine therapies with the latest skin rejuvenating techniques providing naturally beautiful results that are reproducible with each treatment! Take note that treatments are not exclusive to the face but to the body as well! DG's results are achieved by utilizing any combination of wrinkle relaxers, dermal fillers, PDO threads, Stem Cell and Fibrin therapy (PRF/PRP), collagen stimulation therapy (CST), skin brightening and resurfacing with laser therapy and the use of medical grade cosmeceuticals…let us not forget skillful technique and expert knowledge! ▪︎ ▪︎ ▪︎ Thank you to our sponsors, TieTechnology and REVA Global MD, for sponsoring the show! --- Send in a voice message: https://anchor.fm/thedoctorwhisperer/message

A significant number of fatalities are due to blood loss following accidents, injuries or medical procedures. While many methods can stop catastrophic bleeds, they take time and are not always successful. This episode explores the process of inducing bleeding cessation with Joe Landolina of Cresilon. The company has devised a polymer from algae that is applied topically, and immediately stops the bleed. The science behind this innovation and potential applications are discussed. # COLABRATalking Biotech is brought to you by Colabra – an R&D platform that brings your lab's world-changing research together in one shared space. Learn more at https://www.colabra.app/# TALKING BIOTECHTwitter: https://twitter.com/talkingbiotechWebsite: https://www.colabra.app/podcasts/talking-biotech/Instagram: https://www.instagram.com/colabrahqThe Talking Biotech podcast is distinct from Dr. Kevin Folta's teaching and research roles at the University of Florida. The views expressed on the show are those of Dr. Folta and his guests, and do not reflect the opinions of the university or Colabra.

Interventional Neuroradiologist Dr. Hannes Nordmeyer and Biomedical Engineer Dr. Matt Gounis discuss compositions of tough clots, approaches to stroke thrombectomy, and bailout stenting. --- CHECK OUT OUR SPONSOR CERENOVUS https://www.jnjmedicaldevices.com/en-US/companies/cerenovus --- SHOW NOTES In this episode, interventional neuroradiologist Dr. Hannes Nordmeyer, biomedical engineering professor Dr. Matt Gounis, and our host Dr. Michael Barraza discuss compositions of tough clots, approaches for stroke thrombectomy, and bailout stenting. Dr. Nordmeyer believes that interventionalists are still struggling to find the most effective method for pulling clots. He says that the use of double stent retrievers has shown high success rates, but it would be ideal to have one retriever that can work on its own. He describes his equipment setup for a standard large vessel occlusion. Dr. Nordmeyer notes clot location and behavior within the first two passes determines whether or not the operator should continue with the stent retrieval approach or change the approach. Dr. Gounis evaluates various devices by defining “success” as achievement of TICI 3 with the first pass. He comments on the current development of very large bore aspiration catheters, such as the 088 Millipede catheter and the Tenzing catheter. He also emphasizes that the success of the procedure relies largely on the composition of the embolus. Fibrin-rich clots are less likely to integrate with the stent retriever. We discuss Dr. Nordmeyer's technique, which utilizes a microcatheter and the NIMBUS device to pin and retrieve the challenging clot. We also cover bailout stenting and the benefits of recanalization when clot removal is not possible. --- RESOURCES SWIFT DIRECT Trial: https://www.swift-direct.ch/the-swift-direct-trial/ Preclinical Evaluation of Millipede 088 Intracranial Aspiration Catheter: https://pubmed.ncbi.nlm.nih.gov/32606100/ The Novel Tenzing 7 Delivery Catheter Designed to Deliver Intermediate Catheters to the Face of Embolus Without Crossing: https://jnis.bmj.com/content/13/8/722 Factors Influencing Recanalization After Mechanical Thrombectomy With First-Pass Effect for Acute Ischemic Stroke: https://www.frontiersin.org/articles/10.3389/fneur.2021.628523/full NIMBUS Geometric Clot Extractor: https://www.jnjmedicaldevices.com/en-EMEA/news-events/cerenovus-launches-nimbustm-geometric-clot-extractor-remove-tough-clots

Capitulo 18 - Fisiología Humana de Boron y Boulpaep 3ra edición --- Send in a voice message: https://anchor.fm/las-poderosas-celulas-nk/message

In Episode #67, Dr. Jill interviews Dr. Ann Corson about issues with hypercoagulation in chronic illness, and how Inflammation and infection may cause excess fibrin production. Excess fibrin production impairs oxygen getting to tissues and vital organs.

In this episode, I had the pleasure to chat with professor Stephanie Willerth at the University of Victoria, also the founder of Axolotl Biosciences.Stephanie is not only an expert in bioprinting and bioinks in general, but also one of a few scientists in the world focusing on using 3D cell models on common but devastating neurological diseases such as GBM, Parkinson's Disease, and Alzheimer's Disease. We started with some basic concepts related to bioprinting, bioinks, organoids, and organ-on-a-chip, and some of the general current applications and ongoing researches. All of these technologies, however, require sophisticated bioink formulation to achieve structural and functional goals. Also, who are the major players in commercial bioprinting? Other versions of this episode: WebsiteInstagramAxolotl BiosciencesWillerth LabYoutubePast blog by prof. Willerth: 3D Bioprinting Glioblastoma Models for Drug Screening3D Bioprinting Personalized Brain TissuesAbout Our Guest:Dr. Willerth holds a Canada Research Chair in Biomedical Engineering at the University of Victoria where she has dual appointments in the Department of Mechanical Engineering and the Division of Medical Sciences as an Associate Professor.She serves as the Acting Director for the Centre for Biomedical Research at the University of Victoria and on the steering committee of the B.C. Regenerative Medicine Initiative. She also served as the President of the Canadian Biomaterials Society from 2017-2018. Her honors include being named the 2018 REACH award winner for Excellence in Undergraduate Research-inspired Teaching, a Woman of Innovation in 2017, one of the 2015 Young Innovators in Cellular and Biological Engineering, and a “Star in Global Health” by Grand Challenges Canada in 2014. She spent the Fall of 2016 on sabbatical at the Wisconsin Institute for Discovery supported by the International Collaboration on Repair Discoveries International Travel Award where she wrote her book “Engineering neural tissue using stem cells” published by Academic Press.She completed her postdoctoral work at the University of California-Berkeley after receiving her Ph.D. in Biomedical Engineering from Washington University. Her undergraduate degrees were in Biology and Chemical Engineering from the Massachusetts Institute of Technology.Support the show (https://www.paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=STF9STPYVE2GG&source=url)

Did you know that you can speed up the healing process using your own body? In this episode the dentist explains PRF (Platelet-Rich Fibrin) and how it can help speed up healing in certain dental procedures. Do you want to get healthier teeth? Join us routinely with Dr. Yeh, a Dentist, Implant Specialist and Prosthodontist who has practiced for over 30 years. Ask any question about dentistry, and we will get Dr. Yeh to answer them! It is our goal to make oral hygiene easy and understandable while helping you get healthier teeth. TIK TOK: @HealthyTeethTV INSTAGRAM: @HealthyTeethTV DR. YEH'S INSTAGRAM: @DrMichaelYeh

Happy Friday Beauty Byters!In this week’s Five Minute Friday, I am talking about PRP and PRF, and the amazing benefits of both! While the two enhance natural growth factors, a larger quantity of blood is needed in PRF than PRP, therefore there is a longer duration of healing associated with PRF. Both PRP and PRF are used in aesthetics to treat hair loss and aging, but can also help with tendon injuries, acute injuries, post surgical repairs, and osteoarthritis! Want to find out how it is used in micro-needling, and the KD skincare products, then tune in to todays podcast! If you have a question or something you’d like covered on the podcast, send me a DM or email info@beautybydrkay.com and I’d be happy to respond!Click Here to follow my Instagram!Click Here to shop my KD Skincare!

Happy Friday Beauty Byters!In this week’s Five Minute Friday, I am talking about PRP and PRF, and the amazing benefits of both! While the two enhance natural growth factors, a larger quantity of blood is needed in PRF than PRP, therefore there is a longer duration of healing associated with PRF. Both PRP and PRF are used in aesthetics to treat hair loss and aging, but can also help with tendon injuries, acute injuries, post surgical repairs, and osteoarthritis! Want to find out how it is used in micro-needling, and the KD skincare products, then tune in to todays podcast! If you have a question or something you’d like covered on the podcast, send me a DM or email info@beautybydrkay.com and I’d be happy to respond!Click Here to follow my Instagram!Click Here to shop my KD Skincare!

Here we are at the 6-letter F words and they include the beautiful and mellifluous fogbow (pictured here).  We hope you are enjoying our words and word podcast.  Feel free to drop us a note and let us know what you think at scrabbledabbledoopodcast@gmail.com    | FAECAL  |  | FACULA  | FAUCAL | FAVELA  |  | FANEGA  |  | FRAENA  |  | FAENAS  |  | FARFEL  | FARFAL | FABBER  |  | FORBAD  | FORBID | FABLER  | FERBAM  |  | FANBOY  |  | FARCED  |  | FACILE  | FECIAL | FARCIE  | FIACRE | FACIES  |  | FALCES  |  | FECULA  |  | FANFIC  |  | FARDED  |  | FAFFED  |  | FASHED  |  | FADEIN  |  | FAERIE  | FERIAE | FAKEER  | FAKIR | FEATER  |  | FEASES  | FEAZES | FEIJOA  |  | FAKIES  |  | FAILLE  |  | FERIAL  |  | FERIAS  | FRAISE | FLEAMS  | FLAMES | FLORAE  |  | FOETAL  | FOLATE | FERULA  |  | FESTAL  |  | FRATER  | RAFTER | FEUARS  |  | FAMING  |  | FAYING  |  | FLAGON  |  | FORGAT  |  | FUGATO  |  | FULHAM  | FULLAM | FINIAL  |  | FAMULI  |  | FOLIAR  |  | FRAZIL  |  | FIRMAN  |  | FAVISM  |  | FINNAN  |  | FANION  |  | FUSAIN  |  | FRIARY  |  | FLYMAN  |  | FULMAR  | ARMFUL | FLATUS  | FAULTS | FLYWAY  |  | FANTOM  |  | FANUMS  |  | FUSUMA  |  | FURANS  |  | FARROS  |  | FARROW  |  | FUBBED  |  | FIMBLE  |  | FORBYE  | FOREBY | FOGBOW  |  |   |  | FIBRIL  |  | FIBRIN  |  | FYNBOS  |  | FLOCCI  |  | FLECHE  | FLEECH | FENNEC  |  | FESCUE  |  | FETICH  |  | FLENCH  |  | FLETCH  | FLEDGE | FELSIC  |  | FICOES  |  | FECKLY  | FLECKY | FUCOSE  |  | FUNGIC  |  | FLITCH  |  | FITCHY  |  | FICHUS  |  | FLYSCH  |  | FICINS  |  | FISTIC  |  | FICKLY  |  | FORMIC  |  | FRICOT  |  | FUSTIC  |  | FLOCKY  |  | FUCOUS  |  | FONDED  |  | FORDID  |  | FELIDS  | FIELDS | FOETID  | FETID | FOGDOG  |  | FIORDS  | FJORDS | FEIRIE  |  | FELLOE  |  | FERREL  | FERULE | FOEMAN  | FOEMEN | FEOFFS  |  | FEUING  |  | FOEHNS  |  | FLOOIE  | FLOOEY | FILOSE  |  | FUSILE  |  | FERITY  |  | FUNKER  |  | FOLLES  | F

Optimale Wundheilung und wenig Schwellung nach OPs oder Implantationen erreichen? PRP / PRF oder Platelet Rich Plasma bzw. Fibrin macht es möglich. Bei diesem Verfahren aus der Biologischen Zahnmedizin wird das körpereigene Material zur Optimierung der Wundheilung nach Zahn-OPs, Weisheitszahnentfernung und Implantationen genutzt. Wir erklären Euch in diesem Video genau: Wie dieses Verfahren funktioniert, was es kostet und was es bringt! ✔️ Wie dieses Verfahren funktioniert und bei wem es anwendbar ist ✔️ Bei welchen Eingriffen und OP PRF sinnvoll ist ✔️ Welche positiven Effekte man durch PRF erwarten kann ✔️ Was das Verfahren kostet Und nun viel Spaß mit dem Video! Und wenn Euch der Kanal gefällt, abonnieren nicht vergessen! Euer Dr. Stefan Helka ___________________________________________________________

Welcome to Ask Stago, the weekly podcast for Hemostasis laboratory professionals.   This week, with our expert Paul Riley, Scientific Business Development Manager, Cécile Hourquet and Audrey Carlo will cover the usage of fibrin related markers in the diagnosis of disseminated intravascular coagulopathy.   Litterature: Baglin T. Disseminated intravascular coagulation: diagnosis and treatment. BMJ 1996; 312: 683-7 Iba T, Di Nisio M, Thachil J, Wada H, Asakura H, Sato K, Kitamura N, Saitoh D. Revision of the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) diagnostic criteria using antithrombin activity. Crit Care. 2016 Sep 14;20:287 Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001 Nov;86(5):1327-30 JAAM; Iba T, Di Nisio M, Thachil J, Wada H, Asakura H, Sato K, Kitamura N, Saitoh D. Revision of the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) diagnostic criteria using antithrombin activity. Crit Care. 2016 Sep 14;20:287 Boral BM, Williams DJ, Boral LI. Disseminated Intravascular Coagulation. Am J Clin Pathol 2016; 146: 670-80 Wada H, Sakuragawa N. Are fibrin-related markers useful for the diagnosis of thrombosis? Semin Thromb Hemost 2008; 34: 33-8 Toh JMH, Ken-Drorb G, Downey D, Abram ST. The clinical utility of fibrin-related biomarkers in sepsis Blood Coagulation and Fibrinolysis 2013, 24:00–00 Gris JC, Cochery-Nouvellon E, Bouvier S, Jaber S, Albanese J, Constantin JM, Orban JC, Morel J, Leone M, Deras P, Elotmani L, Lavigne-Lissalde G, Lefrant JY. Clinical value of automated fibrin generation markers in patients with septic shock: a SepsiCoag ancillary study. Br J Haematol. 2018 Nov;183(4):636-647 (Singh N, Prasad Pati H, Tyagi S, Datt Upadhyay A, Saxena R. Evaluation of the Diagnostic Performance of Fibrin Monomer in Comparison to D-Dimer in Patients With Overt and Nonovert Disseminated Intravascular Coagulation. Clin Appl Thromb / Hemost 2015; 1-6.). (Park KJ, Kwon EH, Kim HJ, Kim SH. Evaluation of the diagnostic performance of fibrin monomer in disseminated intravascular coagulation. Korean J Lab Med. 2011; 31: 143-7.).

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.205005v1?rss=1 Authors: Wang, Y., Kumar, S., Nisar, A., Bonn, M., Rausch, M. K., Parekh, S. H. Abstract: Blood clots are essential biomaterials that prevent blood loss and provide a temporary scaffold for tissue repair. In their function, these materials must be capable of resisting mechanical forces from hemodynamic shear and contractile tension without rupture. Fibrin networks, the primary load-bearing element in blood clots, have unique nonlinear mechanical properties resulting from their hierarchical structure, which provides multiscale load bearing from fiber deformation to protein unfolding. Here, we study the fiber and molecular scale response of fibrin under shear and tensile loads in situ using a combination of fluorescence and vibrational (molecular) microscopy. Imaging protein fiber orientation and molecular vibrations, we find that fiber orientation and molecular changes in fibrin appear at much larger strains under shear compared to uniaxial tension. Orientation levels reached at 150% shear strain were reached already at 60% tensile strain, and molecular unfolding of fibrin was only seen at shear strains above 300%, whereas fibrin unfolding began already at 20% tensile strain. Moreover, shear deformation caused progressive changes in vibrational modes consistent with increased protofibril and fiber packing that were already present even at very low tensile deformation. Together with a bioinformatic analysis of the fibrinogen primary structure, we propose a scheme for the molecular response of fibrin from low to high deformation, which may relate to the teleological origin of its resistance to shear and tensile forces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/205005v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@d72dfborg.highwire.dtl.DTLVardef@10bed75org.highwire.dtl.DTLVardef@12d33aorg.highwire.dtl.DTLVardef@1e9b40f_HPS_FORMAT_FIGEXP M_FIG C_FIG Copy rights belong to original authors. Visit the link for more info

Why You Should Listen: In this episode, you will learn about the role of hypercoagulation in complex, chronic illnesses such as Lyme disease and mold illness. About My Guest: My guest for this episode is Dr. Ann Corson. Ann Corson, MD grew up in Southeastern Pennsylvania and obtained her MD degree from the University of Pennsylvania School of Medicine in Philadelphia, PA in 1982. Dr. Corson has residency training in Internal Medicine, Neurology, and Family Medicine. She has been Board Certified in the practice of Family Medicine since 1993. In 2005, she began studying and practicing Integrative Medicine and was Board Certified in Integrative Holistic Medicine in 2011. Dr. Corson became member of the International Lyme and Associated Diseases Society (ILADS) in 2003. She has studied with Dr. Joe Burrascano and Dr. Charles Ray Jones. Her practice in Chester County, PA is devoted full time to the treatment of patients suffering from chronic vector borne diseases and environmental illnesses. She has a wealth of knowledge and experience in treating these kinds of patients and is passionate about finding solutions for her patients. Key Takeaways: - What is hypercoagulation? - What are the key symptoms of hypercoagulation? - What are the triggers and exacerbating factors for hypercoagulation? - Do genetics play a role in hypercoagulation? - Can detoxification attempts worsen hypercoagulation? - What are the three systems that control coagulation? - What factors impact platelet activation and aggregation? - What factors are involved in the formation of and degradation of fibrin? - What tests are used to explore the potential for hypercoagulation? - What is the approach to treatment for hypercoagulation? Connect With My Guest: http://AnnFCorsonMD.com Related Resources: "What's the Fuss About Fibrin?" presentation slides from TFIM 2020 "What's the Fuss About Fibrin?" Presentation Notes from TFIM 2020 Role of Hypercoagulation & Biofilms in Chronic Illness Conference – 4 DVD Set Decoding the Mystery of Chronic Illnesses – 5-DVD Set Interview Date: July 10, 2020 Transcript: To review a transcript of this show, visit http://BetterHealthGuy.com/Episode123 Additional Information: To learn more, visit http://BetterHealthGuy.com. Disclaimer: The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.

O QUE TODOS DEVEM SABER SOBRE COVID-19 E TROMBOEMBOLISMO VENOSO. O tromboembolismo e uma doença séria, de alta prevalência e ainda hoje sub diagnosticada e tratada. Atualmente, todos nós temos acompanhado, que os pacientes acometidos por COVID-19, são especialmente propensos a desenvolver tromboembolismo venoso.Qual é a sua etiopatogenia? Qual a sua prevalência? Como fazemos seu diagnóstico, em tempos de pandemia? Como fazer o tratamento? A anticoagulação deve ser profilática? Terapêutica? Qual a prevalência da embolia pulmonar grave? Estaria ela relacionada com a mortalidade nos casos graves? Como fazer o tratamento? Nesses casos? Fibrinólise sistêmica ? Trombectomia farmacomecânica? Trilha sonora: sidewalk-shade---slower-by-kevin-macleod-from-filmmusic-io.mp3

Drs Sheean and Yanke discuss In Vitro Analysis of Micronized Cartilage Stability in the Knee: Effect of Fibrin Level, Defect Size, and Defect Location

Drs Sheean and Yanke discuss In Vitro Analysis of Micronized Cartilage Stability in the Knee: Effect of Fibrin Level, Defect Size, and Defect Location

Los pacientes en shock hemorrágico comúnmente requieren transfusión de sangre para restablecer el volumen sanguíneo y la capacidad de transporte de oxígeno. Aunque es relativamente común tener que transfundir sangre cuando una persona tiene un sangrado severo, el término "transfusión masiva" consiste en la transfusión de: 10 unidades de sangre en menos de 24 horas, o 5 unidades de sangre en menos de 3 horas Cada unidad de sangre tiene aproximadamente 450 mL. Cada unidad de PRBC (packed red blood cells o paquete de glóbulos rojos) contiene 200 mL y eleva el hematocrito en un 3% a menos que no haya sangrado concurrente. El manejo del paciente de trauma está moviéndose cada vez más a iniciar la transfusión de sangre de forma temprana y oportuna. Las recomendaciones del ATLS y el PHTLS recomiendan que la sangre es el mejor fluido para resucitar al paciente con shock hemorrágico. Debido a que ahora más pacientes reciben sangre de forma temprana, nuevos estudios (y este otro) sugieren que el término transfusión masiva pueden incluir pacientes que reciban: 3 unidades de sangre en 1 hora, o 4 componentes sanguíneos en 30 minutos ¿Qué pacientes requieren una transfusión masiva? Aunque puede resultar difícil predecir quién requiere una transfusión masiva, existen diferentes puntuaciones que miden la probabilidad de que un paciente requiera una transfusión masiva. Es importante señalar que estas escalas no definen si alguien necesita o no sangre. Solamente buscan predecir quiénes necesitan sangre a través de un protocolo de transfusión masiva. Para efectos prácticos, se recomienda la escala Assessment of Blood Consumption (ABC) para predecir los pacientes que requieren transfusión masiva de sangre debido a su simplicidad y su alta sensitividad. La escala tiene cuatro componentes. La presencia de dos o más criterios implica la necesidad de transfusión: Presencia de trauma penetrante FAST positivo Presión arterial sistólica < 90 mmHg a la llegada al hospital Frecuencia cardiaca > 120 lpm a la llegada al hospital Se debe activar el protocolo de transfusión masiva cuando el paciente cumple con dos o más de los siguientes: Puntuación ABC de dos o más Inestabilidad hemodinámica persistente Sangrado activo que requiere cirugía o angioembolización Transfusión en el cuarto de reanimación Los pacientes que NO cumplen con dos o más de estos criterios probablemente NO van a necesitar una transfusión masiva, aunque si pudieran necesitar sangre en cualquier momento desde su llegada hasta el control definitivo del sangrado. ¿Cuál es la meta en la resucitación con fluidos? La meta en el manejo del paciente que requiere resucitación con fluidos es: Detener el sangrado El tratamiento con fluidos no debe retrasar el control definitivo del sangrado. Restablecer el volumen circulante La sangre no se mueve fácilmente cuando los vasos sanguíneos están colapsados. Es necesario mantener cierto tono vascular para facilitar el flujo. Mantener la composición normal de la sangre El término "sangre" es el colectivo de varios componentes que llevan a cabo tareas diferentes. Este líquido está compuesto de elementos que sirven para producir hemostasis (plaquetas), otros que transportan oxígeno (hemoglobina), otros que mantienen la presión oncótica (plasma) y electrolitos asociados. La pérdida de sangre produce la pérdida equitativa de estos componentes. Es decir, el hemograma de una persona agudamente y activamente sangrando no muestra un desequilibrio en los primeros minutos u horas porque se está perdiendo una cantidad igual de componentes. El problema ocurre cuando se reemplazan estos componentes. Hay que reemplazarlos todos. Si se provee solamente Lactato de Ringer (o cloruro de sodio), el hematocrito va a disminuir porque va a haber menos glóbulos rojos en la solución...¡los estás diluyendo! ¿Cuál es el mejor fluido para resucitar el paciente en shock hemorrágico? Sangre completa Paquete globular + plasma + plaquetas (1:1:1) Cristaloides El paciente con un sangrado activo está perdiendo sangre completa. La mejor solución es la sangre completa. El problema es que desde la década de los 1980s se ha comenzado a fraccionar la sangre en sus respectivos componentes para eficientizar su uso en pacientes que tienen problemas específicos. La recomendación actual es administrar una unidad de cada uno de los tres componentes. A esto se le conoce como una transfusión a razón de 1:1:1. La triada fatal del paciente que está sangrando es: Acidosis Hipotermia Coagulopatía La resucitación con cristaloides produce coagulopatía por dilución. Luego de 1,000 mL de cristaloides en un paciente con un sangrado no controlado, y en donde se anticipa la necesidad de mayor cantidad de fluidos para mantener cierta estabilidad hemodinámica, se debe comenzar con sangre indistintamente de la necesidad de activar el protocolo de transfusión masiva o no. Es importante tener en cuenta que la transfusión masiva no debe afectar otros principios del manejo del paciente previo a la cirugía de control de daño, como lo es la resuscitación controlada de fluidos, o inclusive la hipotensión permisiva si el paciente estuviese hipotenso pero con relativamente buena perfusión (buen estado mental y presencia de pulsos periféricos). El aumento rápido y/o drástico de la presión sanguínea en pacientes con un sangrado no controlado está asociada a mayor mortalidad. ¿Por qué tener un protocolo de transfusión masiva? Aunque hoy día las transfusiones de sangre son seguras, toda transfusión trae consigo un riesgo inherente de efectos secundarios al transfundir un componente sanguíneo. El protocolo de transfusión masiva busca reducir la morbilidad y mortalidad de los pacientes que están expuestos a grandes cantidades de productos sanguíneos en corto tiempo. No todas las transfusiones de sangre requieren la activación del protocolo de transfusión masiva. Dependiendo del volumen de pacientes, la activación del protocolo de transfusión masiva es un evento esporádico. Sin embargo, cuando ocurre, puede acabar con las reservas disponibles en un banco de sangre en relativamente corto tiempo y tiene mayor riesgo de eventos adversos en el paciente. Por lo tanto, es importante una buena coordinación entre todas las partes envueltas. Este modelo de transfusión masiva puede ser utilizado como referencia. ¿Qué debe tener el protocolo de transfusión masiva? Según el Colegio Americano de Cirujanos, cada institución debe contar con un protocolo de transfusión masiva para pacientes de trauma que incluya: Criterios de activación del protocolo de transfusión masica Disponibilidad de productos sanguíneos para resuscitación inicial en unidad de trauma Continuación de transfusión en Sala de Operaciones, sala de angiografía o unidad de cuidados intensivos Metas de transfusión Uso de adyuvantes durante la transfusión Terminación de la transfusión Monitoreo de calidad del programa y protocolo de transfusión masiva Algunas recomendaciones específicas incluyen: Comenzar con productos de sangre, en vez de cristaloides, cuando sea posible. Los productos sanguíneos deben llegar del servicio de transfusión en proporción de 1:1:1. Las siguientes entregas de productos sanguíneos deben continunar a intérvalos de 15 minutos hasta que se determine detener el protocolo de transfusión masiva. Debe haber siempre un producto sanguíneo adicional listo y disponible en la cabecera del paciente en todo momento mientras el protocolo de transfusión masiva esté activado. Logística del protocolo El hecho de que las unidades de sangre tienen que llegar de forma regular y constante hace que se deba preparar un listado de lo que debe entregarse cada 15-30 minutos. El siguiente ejemplo muestra una secuencia práctica: 3U de sangre completa Caja 1: 2 paquetes globulares, 2 plasmas Caja 2: 4 paquetes globulares, 4 plasmas, 1 plaquetas Caja 3: 4 paquetes globulares, 4 plasmas, 3 Crioprecipitado Considerar FVIIa 90mcg/kg si está indicado Caja 4: 4 paquetes globulares, 4 plasmas, 1 plaquetas Cajas subsiguientes alternan la Caja 3 y 4 Repetir hemograma, coagulación, plaquetas, gases arteriales, y calcio cada 30 minutos (LITFL) Puede ver otro ejemplo y gráfica del protocolo aquí y una versión del protocolo pediátrico aquí. https://youtu.be/mv7ljhJoci8 Adyuvantes durante la transfusión masiva Algunos medicamentos pueden ayudar a disminuir la necesidad de más productos sanguíneos. El único que consistentemente tiene una recomendación en trauma es el uso del ácido tranexámico luego del famoso estudio CRASH-2. Otros medicamentos con potencial incluyen el factor VIIa recombinado, sin embargo, el American College of Surgeons sugiere que hace falta más data sobre el efecto y beneficio a largo plazo para llegar a una conclusión sobre su utilidad. Sin embargo, el uso de otras combinaciones de factores de coagulación tales como los PCC (prothombin complex concentrate) pueden tener utilidad en el manejo de pacientes con sangrados asociados al uso de warfarina. Ácido tranexámico (TXA) durante la transfusión El ácido tranexámico debe comenzarse dentro de las primeras 3 horas del inicio del sangrado. La dosis inicial es 1 gramo intravenoso en una infusión de 100 mL a bajar en 10 minutos. Luego se administra una infusión de mantenimiento de 1 gramo en 8 horas. Monitoreo durante transfusión Se deben verificar los siguientes parámetros cada 30 minutos: Temperatura > 35C pH > 7.2, exceso de base 1.1 mmol/L Hemoglobina Plaquetas > 50,000 (>100,000 si el sangrado es intracraneal) PT / APTT ≤ 1.5x de lo normal Fibrinógeno ≥ 1.0 g/L INR ≤ 1.5 Monitoreo de complicaciones Las siguientes complicaciones están asociadas a la transfusión masiva. Es importante que se documente la incidencia de estas para así identificar cuáles prácticas pueden mejorarse en la prevención y/o el tratamiento oportuno de estas: Coagulopatías Hipocalcemia Complicaciones trombóticas ARDS Sobrecarga de volumen Lesión pulmonar aguda por transfusión (TRALI) Reacciones hemolíticas Muerte Hipocalcemia La hipocalcemia es la una de las complicaciones más peligrosas asociadas a la transfusión masiva. El citrato en los paquetes globulares y plasma sirve de preservativo y anticoagulante. Aunque el hígado puede metabolizar el citrato sin ningún problema en transfusiones normales, los pacientes que reciben transfusiones masivas tienen una acumulación rápida de citrato y un hígado pobremente perfundido que no lo metaboliza con la misma rapidez con la que se acumula. El citrato provoca hipocalcemia mediante la quelación del calcio. El gluconato de calcio puede ser utilizado para corregir niveles peligrosamente bajos de calcio. Protocolo de transfusión masiva en acción El siguiente video muestra una simulación del protocolo de transfusión masiva: https://youtu.be/90VaiaA5xVs Y ahora el protocolo en acción... https://youtu.be/-LHybRRt_AU ¿Cuándo detener el protocolo de transfusión masiva? Es importante tener criterios específicos de cuándo se debe detener el protocolo de transfusión masiva para no malgastar recursos imporantes y vitales. Detener el protocolo de transfusión masiva no significa que el paciente no pueda recibir más sangre, o que no pueda volver a ser activado. Simplemente significa que no se van a tener neveras con más sangre llegando cada 15 minutos de forma continua. Existen dos razones principales para detener el protocolo: Se logra detener el sangrado de forma definitiva. La resucitación del paciente es futil. Otros criterios que pueden servir de guía para decidir que se puede desactivar el protocolo de transfusión masiva y continuar las transfusiones según los criterios regulares son: Hgb ≥ 10 g/dL PT < 18 segundos Plaquetas > 150 x 10ˆ9 Nivel de fibrinógeno > 180 g/L Hay vida después del protocolo de transfusión masiva Si el lugar donde se encuentra el paciente no cuenta con los recursos necesarios para el control definitivo del sangrado, la coordinación para el transporte del paciente a la facilidad donde pueda recibir el cuidado definitivo debe comenzar de forma concurrente con el inicio del protocolo de transfusión masiva. Muchos hospitales cuentan con reservas relativamente pequeñas de sangre. La activación de un protocolo de transfusión masiva de un solo paciente puede acabar las reservas del hospital. Cada vez es más común que el equipo de transporte crítico interhospitalario tenga la capacidad de traer sangre para la transfusión del paciente durante el transporte. Una vez se detiene el protocolo de transfusión masiva, se continua monitorizando al paciente según su estatus de coagulación y se deciden productos sanguíneos adicionales según sea necesario de forma tradicional. Se debe monitorizar los siguientes parámetros cada 30 minutos a 1 hora: INR aPTT Niveles de fibrinógeno Hgb y Hct Conteo de plaquetas Calcio Gases arteriales Monitoreo de calidad Todo protocolo o programa tiene que tener marcadores de calidad e indicadores de complicaciones. Estas incluyen: Tiempo de inicio de primera unidad de sangre luego de la activación del protocolo Adherencia a proporción predeterminada de productos sanguíneos luego de las primeras 2 horas después de haber iniciado el protocolo Informar al servicio de transfusión que se termina el protocolo dentro de la primera hora de haberlo terminado Taza de desperdicio de productos sanguíneos Referencias https://www.facs.org/~/media/files/quality%20programs/trauma/tqip/massive%20transfusion%20in%20trauma%20guildelines.ashx http://scielo.isciii.es/pdf/medinte/v35n9/original3.pdf https://www.ncbi.nlm.nih.gov/pubmed/25647203 http://www.tamingthesru.com/blog/diagnostics/massive-transfusion Scott Weingart. Podcast 71 – Critical Questions on Massive Transfusion Protocols with Kenji Inaba. EMCrit Blog. Published on April 16, 2012. Accessed on April 15th 2019. Available at [https://emcrit.org/emcrit/massive-transfusion-kenji/ ]. http://www.eccpodcast.com/6/ https://www.ncbi.nlm.nih.gov/pubmed/23477634 https://www.ncbi.nlm.nih.gov/pubmed?term=25757105 https://www.ncbi.nlm.nih.gov/pubmed?term=29985236 https://broomedocs.com/clinical-resources/massive-transfusion-protocol/ https://litfl.com/massive-blood-loss/

La hemostasia es indispensable para evitar la hemorragia. Pero, a menos que esté estrechamente regulada, los mismos procesos podrían predisponer a la trombosis. Por ello, existen mecanismos humorales y físicos en el endotelio para prevenir la coagulación cuando esta no es requerida y, ya cuando se instaura un proceso de hemostasia primario y secundario, existen elementos que permiten regularlo y limitarlo, tanto espacial como temporalmente, para que ejecuten sus acciones solamente en el lugar correcto, por el tiempo necesario. Además, se necesita de un mecanismo que pueda disolver el coágulo y resolver el proceso en general. Este es la fibrinólisis, y también está sujecto a una serie de mecanismos de control. ¿Quieres enterarte de las nuevas publicaciones, episodios próximos y recibir la Newsletter mensual cargada de contenido exclusivo? Únete a la lista de correo de Leucocitos isotópicos. Para suscribirte al Podcast de Medicina, estas son las opciones más recomendadas: Apple Podcasts Google Podcasts Spotify Si prefieres explorar más alternativas, haz clic aquí. ¿Te gustó el episodio? Seguro disfrutarás este también: Coagulación (056) Además, puedes acceder a la lista curada y actualizada de los episodios con mayor aceptación. Este show es para ti. Puedes apoyarlo entrando a iTunes y dejando allí una calificación positiva. Encuentra las notas de este episodio y dirige a tus amigos a isotopicos.com/057 El objetivo de Leucocitos isotópicos es entretenerte mientras complementas lo que recibes en tu Escuela o Facultad de Medicina. Soy Médico Internista, y comprendo lo demandante que puede ser nuestra Carrera. Por eso decidí crear el Podcast como un curso de Medicina ameno y sin una estructura rígida, que despierte tu interés y curiosidad por esta maravillosa Ciencia. Nunca reemplazará a la Universidad, ni a los libros, pero cumplirá con la misión que lo fundamenta: Ser el lugar donde descansamos de leer, sin dejar de aprender. No olvides que la mejor manera de ayudar a que el proyecto crezca, es contarle a todos de él. ¡Gracias por compartir este episodio con alguien!

Heparin is an interesting drug with a lot of unique clinical quirks. This drug ultimately inhibits the formation of fibrin. Fibrin is an essential component of a blood clot. Because heparin has blood thinning effects, it is critical to assess a patient's bleed risk. Look out for other agents that may increase the risk of bleeding. Examples include; NSAIDs, antiplatelet agents, and other anticoagulants. One classic test question about heparin that often comes up is the reversal agent. Protamine can be used to help reverse the effects of heparin. Heparin-induced thrombocytopenia is a critical adverse effect to understand. I discuss both subtypes on the podcast and let you know what to look out for. Rarer side effects of heparin include hyperkalemia and osteoporosis (only with long term use).

A pioneering new integrated approach that systematically combines facial rejuvenation techniques using PDO Threads, Microcanulas for filler injection and Platelet Rich Fibrin injected with a needle, cannula or used with a microneedling pen has been developed by Kian Karimi, MD, FACS. Dr. Karimi of Rejuva Medical Aesthetics based in Los Angeles, CA is a double board certified facial plastic/head and neck surgeon and head faculty of the American Institute of Aesthetic Medicine (AIAM) which is the only aesthetic organization currently training and teaching this integrated approach to facial aesthetics. In this interview with Aesthetic Insider™ Dr. Karimi who has an impressive record of academic and scientific achievement discusses how this new integrated and systemized aesthetic approach in facial rejuvenation is being rapidly adopted throughout the aesthetic medical community. To learn more about Dr. Karimi and Rejuva Medical Aesthetics, visit www.rejuvamedical.org. To learn more about the American Institute of Aesthetic Medicine, visit www.handsontrainings.com.

Here's a scary statistic: over 40% of the American population dies of some form of heart disease. 40%? That's a really big number! Atherosclerosis, or "hardening of the arteries", is the primary cause of heart disease; however, it can be prevented!!!!! In addition to healthy diet and exercise, take 400 IUs of Vitamin E , which prevents atherosclerosis by entering the LDL (BAD cholesterol, there are good ones too!) molecule and inhibiting hazardous oxidation. Now isn't that interesting! Tune in to Eve's latest show with her guest Dr. Fred Harvey, to hear more heart facts and get your jump start on keeping your heart healthy and happy.

Özet: Previously on "Metin'in Parmak Yarası"... (1. Bölüm'den devam) Metin, henüz 13 yaşında yaramaz bir çocuktur. Sanat merakı yüzünden aldığı maket bıçağı ile başparmağını kesmiştir. Bu bıçak, Metin'in epidermisini ve dermisini kesmiş, yolu üzerindeki bir çok kılcal damarı ve dokuyu parçalamıştır. Metin'in refleksi sayesinde daha büyük hasarlar önlenmiş olsa da, yara çoktan oluşmuştur ve Metin'in vücudunun yapması gerekenler daha yeni başlıyordur. İlk emir: Dengeyi yeniden kur! Metin'in vücudunda hasar sonrasında oluşturulan kriz masası, birçok adımdan oluşan bir koruma-onarma planını hemen devreye sokuyor. Bu adımlar bir an önce hayata geçirilmeli; Çünkü kısa zamanda, çok işler yapılması gerek... Hasarlı dokunun onarılmasındaki ilk basamak, kriz bölgesindeki dengenin tekrar kurulması ile başlıyor. Metin, henüz "Homeostazi" adlı terimden bihâber olsa da, vücudu bu terimin ne anlama geldiğini gayet iyi biliyor. Homeostazi, yani hücrelerin (ya da bir dokunun) çevresel olaylar karşısında, kendi düzenini koruma ve tekrar sağlama eğilimi, yaranın kapatılması için önemli basamaklardan biri. Ancak, bu dengenin sağlanmasında önemli bir engel var. Parçalanan damarlardan sızan kan... Sızıntı az gibi gözükse de, bu damarlardan her saniye 5 milyon kadar alyuvar, 10 bin kadar akyuvar vücut dışına akıyor. Bu kaybın bir şekilde önlenmesi gerek. Sızıntılar Kapatın! Hasar bölgesindeki bir kanamanın durdurulmasında bir protein grubu önemli görev üstleniyor: Kolajen'ler... Metin'in vücudundaki hemen hemen her bölgede kolajen adlı proteinleri bulmak mümkün. Nitekim, maket bıçağı dermis'i parçalarken de bu kolajen proteinleri ile karşılaşmıştı. Bu proteinler, vücut dokuları içinde bir çelik halat görevi görerek yapısal bütünlük sağlıyor. Normal koşullarda, dokular içerisinde bulunan kolajenler, damar içinde dolaşan kan ile hiç temas etmiyor. Ta ki, o damarlar yırtılıp, damar dışına yani doku içerisine kan sızmaya başlayana kadar... Farklı tiplerde kolajen lifleri Kanın içerisinde yer alan trombosit adı verilen hücreler, kolajen proteinlerine değdiği anda, bir şeylerin ters gittiği anlaşılıyor. Kolajene temas eden o trombositlerden şu cümleleri duyuyoruz: "Bir dakika bu kolajen de nereden çıktı? Demek ki ben artık damar içinde değilim. Demek ki bir sızıntı var. Benim bu sızıntıyı durdurmam gerek. ". Bu hücreler,  temas ettiği kolajen proteinine sıkıca tutunuyor. Hasar bölgesindeki tüm trombositler de benzer yollarla, kolajenlere yapışarak orada bir kümeleşme gerçekleştiriyor. Ancak bu kümeleşme yeterli değil... Yara açılalı şimdiden 5 dakika oldu ve hala sızıntı devam ediyor. Artık bu sızıntının kapatılması için Metin'in vücudunun daha büyük kozları oynamak gerek: Fibrinojen'leri... Kan plazmasının neredeyse %5'ini oluşturan büyük bir protein topluluğu fibrinojen'ler. Normal koşullarda kan içerisinde çözünmüş şekilde dolaşan bu proteinler, hasar bölgesine geldiğinde, çevresel uyarıların yardımı ile fibrin adı verilen başka bir proteine dönüştürülüyor. Fibrin, kanda çözünmüyor ve hasarlı bölge üzerinde bir ağ şeklinde çökerek sarıyor. Gelecek günlerde, Metin'in habire koparmak için uğraşacağı yara kabuğunun da bu şekilde temelleri atılmış oluyor. Fibrin ağı ile tutulmuş olan alyuvarlar Yara oluşalı 10 dakika oldu. Ve sızıntılar büyük ölçüde kapatıldı. Bu noktada yara oluşumu sırasında parçalanan hücrelerden çıkan thromboxan ve prostaglandin gibi moleküller, o bölgedeki damarlar büzüşmesine neden oluyor. Bu sayede hasarlı bölgedeki kan akışı da azalıyor. 15.dakikada kan sızıntıları büyük ölçüde duruyor. Ve nihayet Metin'in ağlaması da... Olay Yeri İnceleme Daralan damarlar her ne kadar kanamayı azaltsa da, Metin'in artık daha önemli bir sorunu var: Enfeksiyon. Metin'in kendini kestiği o maket bıçağı, alındığından beri sokağa, okul bahçesine, banyoya defalarca düştü. Şu anda üzerinde onlarca farklı türde mikroorganizma ve spor yer alıyor. Normalde, Metin'in derisi bu organizmalara karşı müthiş bir savunma sağ...

Fibrinogen is a target of autoimmune reactions in rheumatoid arthritis (RA). Fibrin(ogen) derivatives are involved in inflammatory processes and the generation of a stable fibrin network is necessary for sufficient inflammation control. As the density and stability of fibrin networks depend on complex interactions between factor XIIIA (F13A) and fibrinogen genotypes, the authors studied whether these genotypes were related to C-reactive protein (CRP) levels during acute-phase reactions.

Is standing or reclining best for the perfect suntan? Can we see atoms? Why add pennies to Big Ben's pendulum? It's a question and answer show so we shoulder your scientific conundra! We'll find out how web companies keep up with growing data demands, what causes white ridges on fingernails, and why a clean glass keeps cola fizzier. Plus, in Kitchen Science, we find out how to balance a broom whilst blindfolded! Like this podcast? Please help us by supporting the Naked Scientists

Is standing or reclining best for the perfect suntan? Can we see atoms? Why add pennies to Big Ben's pendulum? It's a question and answer show so we shoulder your scientific conundra! We'll find out how web companies keep up with growing data demands, what causes white ridges on fingernails, and why a clean glass keeps cola fizzier. Plus, in Kitchen Science, we find out how to balance a broom whilst blindfolded! Like this podcast? Please help us by supporting the Naked Scientists

Die Exposition mit Umweltstäuben, ultrafeinen Partikeln und Gasen wird als Ursache akuter kardiovaskulärer Morbidität und Mortalität angesehen. Epidemiologische und toxikologische Studien der letzten Jahre weisen auf die Bedeutung von ultrafeinen Partikeln als Auslöser für die lokalen pulmonalen und systemischen Entzündungsreaktionen hin, die durch Veränderungen in der kardiovaskulären Funktion gekennzeichnet sind. Dazu gehören endotheliale Dysfunktion und prothrombotische Prozesse, die letztlich zum akuten Herztod führen können. Die Mechanismen, die dazu führen, sind derzeit nur unzureichend geklärt. Es konnte in zahlreichen Studien gezeigt werden, dass ultrafeine Partikel von der Lunge in die systemische Blutzirkulation translozieren können. Als Ursache kardiovaskulärer Negativ-Effekte werden entweder die Freisetzung von löslichen Mediatoren aus der Lunge und direkte Effekte von translozierten, ultrafeinen Partikeln in die systemische Blutzirkulation diskutiert. Unsere Tierexpositionsstudie wurde durchgeführt, um die Hypothesen zu prüfen, dass „translozierte“ ultrafeine Kohlenstoffpartikel (UfCP) eine signifikante extrapulmonale Entzündung induzieren können. Zu diesem Zweck wurden die systemischen Effekte von zwei verschiedenen Expositionsmodellen verglichen. Die Versuchsmäuse wurden mittels der Inhalation von UfCP (48 nm; 440 µg/m3) bzw. gefilterter Luft für 4 oder 24 Stunden oder durch die intraarterielle Infusion mit der berechneten äquivalenten Dosis von innerhalb einer 24-Stunden- Inhalation translozierten UfCP (5 × 10E7 UfCP) exponiert. Die Versuchsmäuse wurden hinsichtlich systemischer Effekte in der Blutzirkulation mittels automatisierter hämatologischer Untersuchung von Zellzahlen und Plasma-Zytokin-Konzentrationen untersucht. Darüber hinaus wurden Aktivierungsmarker auf peripheren Monozyten und Granulozyten mit FACS analysiert. Zur Untersuchung der lokalen, entzündlichen, mikrovaskulären Effekte in den Geweben von der Lunge, vom Herz, von der Aorta und von der Leber wurde eine quantitative Genexpressionsanalyse und eine multianalytische Proteinexpressionsanalyse durchgeführt. Die Inhalation von UfCP war durch eine leichte pulmonale Entzündungsreaktion mit endothelialer Aktivierung und einer leicht erhöhten Fibrin(ogen)deposition auf Endothelzellen von kapillaren Blutgefäßen der Lunge gekennzeichnet, wohingegen die intraarterielle Infusion von UfCP keine signifikanten Reaktionen in der Lunge aufwies. Auf systemischer Ebene verursachten beide Expositionsmodelle nach der Partikelexposition einen Anstieg von neutrophilen Granulozyten- und Monozytenzellzahlen und zugleich eine Abnahme der pro-entzündlichen Plasma-Zytokin-Konzentrationen, jedoch mit einem stärkeren Effekt nach der Inhalation von UfCP. Hinsichtlich dieser Endpunkte lassen diese Ergebnisse auf einen adjuvanten Effekt von „translozierten“ Partikeln schließen. Jedoch zeigte sich nur nach der Inhalation von UfCP eine signifikante Abnahme von Aktivierungsmarkern auf der Oberfläche der zirkulierenden Leukozyten-Populationen, was auf eine Retention/Transmigration von aktivierten Zellen über die Adhäsion des aktivierten Endothels in der Lunge hinweist. Das Zytogramm der Thrombozyten ergab ebenso nur nach der Inhalation von UfCP einen Anstieg der Zellzahlen und ihres Aktivierungszustandes und dessen der Riesenthrombozyten. Diese Tatsache lässt auf die notwendige pulmonale Entzündungsreaktion schließen, die für die Rekrutierung und Aktivierung der Thrombozyten ausschlaggebend war. In beiden Expositionsmodellen mit UfCP zeigte innerhalb der extrapulmonalen Organe die Aorta die stärkste entzündliche und prothrombotische Reaktion auf, wobei im Vergleich zur intraarteriellen Exposition ein stärkeres pro-entzündliches Reaktionsbild nach der Inhalation von UfCP zu erkennen war. Die Inhalation von UfCP induzierte in der Leber eine frühe, vorübergehende pro-entzündliche Reaktion mit einer endothelialen Aktivierung und einer geringfügigen Reaktion im Herzen, die mit steigender Expositionsdauer zunahm, während die intraarterielle Infusion von UfCP in diesen Organen keine offensichtlichen Effekte verursachte. Die Ergebnisse dieser Studie weisen darauf hin, dass die systemisch verfügbaren UfCP teilweise förderliche Effekte auf spezifische biologische Endpunkte haben mögen. Jedoch zeigen die Ergebnisse eindeutig, dass die Entzündungsreaktion in der Lunge entscheidender für die meisten extrapulmonal beobachteten Effekte ist. Im Rahmen der vorliegenden Arbeit kann die wichtigste Aussage getroffen werden, dass die Lungenentzündung und nicht die Translokation ultrafeiner Partikel entscheidend für die extrapulmonalen Effekte ist.

Ziel der vorliegenden Arbeit war die detaillierte Beschreibung von Anzahl, Lokalisation, Morphologie und Perforationwegen von perforierenden Labmagengeschwüren bei der Kuh. In einer vorgeschalteten retrospektiven Studie wurden die Selektionskriterien für diese Untersuchung erarbeitet. Die Mehrzahl der Patienten waren Rinder der Rasse Deutsches Fleckvieh mit einem Alter zwischen zwei und vier Jahren. Bei den sieben Kühen mit Typ III- Geschwüren (lokal begrenzte Peritonitis) und 16 Kühen mit Typ IV- Geschwüren (generalisierte Peritonitis) dieser Untersuchung lagen alle Perforationen im Korpus des Labmagens. Die Mehrzahl (n=11) der perforierenden Geschwüre vom Typ IV (generalisierte Peritonitis) lag im Pylorusregion-nahen Drittel des Korpus. Bei vier Tieren befand sich die Perforation im „mittleren Drittel“ des Korpus. Bei nur einem Tier mit Typ IV-Geschwür lag die Perforation im Psalter-nahen Drittel. Häufig lagen die Perforationen in den ventralen Labmagenbereichen. So waren bei 13 Patienten die perforierenden Geschwüre in dem Bereich der großen Kurvatur bis zum zentralen Labmagen lokalisiert. Bezüglich der Lokalisation der Geschwüre vom Typ III (lokal begrenzte Peritonitis) konnte keine Häufung innerhalb der Korpusregionen gefunden werden. Die Typ III-Geschwüre traten häufig gleichzeitig mit einer Labmagenverlagerung auf. Meist war nur ein perforierendes Geschwür pro Labmagen zu finden. In nur einem Fall waren zwei perforierende Geschwüre zu finden. Bei zwei Tieren konnte ein Geschwür mit zwei beziehungsweise vier Perforationen nachgewiesen werden. Die Morphologie der Geschwüre war meist oval bis rund mit wallartig aufgeworfenen Rändern. Die Geschwüre hatten meist eine Größe von einem bis vier Zentimeter(n). Bei allen Tieren mit Typ IV-Geschwüren erfolgte die Perforation in der Facies parietalis. Bei den Probanden mit Typ III-Geschwüren war nur einmal eine Perforation in der Facies visceralis zu finden. Hier erfolgte die Perforation also in die Bursa omentalis. Häufig konnte in der Bauchhöhle grün-sulziges Fibrin gefunden werden.

Die Behandlung zerstörter Gewebe- und Organstrukturen nach akuten Verletzungen oder chronischen Krankheitsverläufen hat sich zu einer enormen Belastung für das heutige Gesundheitswesen entwickelt. Neue Konzepte der Geweberekonstruktion durch Tissue Engineering führten in den letzten Jahren zu einer erheblichen Verbesserung der Behandlungsmöglichkeiten. Die vorliegende Arbeit beschreibt die Entwicklung und Charakterisierung einer genaktivierten Fibrinmatrix zur lokalen Expression des Wachstumsfaktors epidermal growth factor (EGF). Das Konzept beinhaltet die gemeinsame Applikation autologer Keratinozyten und nicht-viraler Genvektoren mit PEI in Form einer injizierbaren Fibrinkleberzubereitung. Durch Variationen von PEI-Struktur, N/P-Ratio und dem Zusatz des abschirmenden Hüllpolymers P6YE5C wurde das Transfektionsverhalten unterschiedlicher Genvektorformulierungen in der Fibrinmatrix untersucht. Durch den Einsatz von fluoreszenzmarkierten Genvektoren wurde der Transfektionsverlauf innerhalb der Matrix visualisiert und dokumentiert. Größere Mengen ungeschützter Genvektoren führten in Fibrin trotz ihres toxischen Potentials zu hohen Genexpressionen. Ein protektiver Effekt durch den Zusatz des schützenden Hüllpolymers P6YE5C schien in Fibrin als nicht zwingend notwendig. Daraufhin wurde ein möglicher Einfluss der Fibrinmatrix auf Genvektorformulierungen untersucht. Erste Vorversuche in Zellkultur zeigten eine Steigerung des Transfektionspotentials nicht-viraler Genvektoren mit PEI nach Vorinkubation mit einer Fibrinogen-Lösung. Aus der Perspektive einer kommerziellen Anwendung heraus wurde ein lagerungsfähiges Lyophilisat aus genaktiviertem Fibrinogen entwickelt, das zum Versuchszeitpunkt als Fibrinklebervorstufe mit Wasser rehydratisiert und gemeinsam mit Thrombin zur Herstellung der genaktivierten Fibrinmatrix eingesetzt werden konnte. Der Einsatz des schützenden Hüllpolymers P6YE5C hatte dabei einen entscheidenden Einfluss auf die unmittelbare Verfügbarkeit der eingesetzten Genvektoren. Für die Regeneration von Knochenbrüchen bleibt dagegen der Einsatz medizinischer Implantate von entscheidender Bedeutung. In der vorliegenden Arbeit wird in einem weiteren Ansatz die Entwicklung und Charakterisierung genaktivierter Polymerfilme aus PDLLA und PLGA zur Beschichtung medizinischer Implantate beschrieben. Die neue Grenzfläche zwischen Implantat und Knochenstruktur soll zur lokalen Transfektion und Expression therapeutischer Gene dienen. Dafür wurden nicht-virale Genvektoren lyophilisiert und als Dispersion in organischen Lösungen der Polymere PDLLA und PLGA auf resistente Oberflächen aufgetragen und getrocknet. Die Besiedelung der verbliebenen Polymerfilme mit Zellen führte über den direkten Kontakt mit genaktivierten Polymerstrukturen zur Expression des eingesetzten Gens. Durch Variation von Polymer- und Genvektormenge wurde anhand der gemessenen Genexpressionen sowie der metabolischen Aktivität transfizierter Zellen das System optimiert. Die Bestimmung der Transfektionseffizienz sowie des Freisetzungsverhaltens formulierter Genvektoren diente zur Charakterisierung der genaktivierten Polymeroberflächen aus PDLLA und PLGA. Trotz struktureller Ähnlichkeiten der eingesetzten Filmbildner zeigte sich das Freisetzungsverhalten aus PDLLA gegenüber PLGA abhängig der eingesetzten Polymer- und Genvektormengen. Das Beschichtungsprinzip konnte ebenfalls für die Aktivierung von Folien aus Aluminiumlegierung eingesetzt werden und führte zur Expression des therapeutischen Gens bone morphogenic protein-2 (BMP-2). Die Verwendung von Poly-[Tyrosincarbonaten] als strukturelle Alternative zu PDLLA bzw. PLGA führte zu keiner Genexpression. Hohe medizinische Anforderungen und individuelle Interaktionen einzelner Matrixkomponenten machen genaktivierter Biomaterialien zu komplexen Applikationsformen der regenerativen Medizin. Kleinste Veränderungen im komplexen Verbund aus Matrixstrukturen, Genvektoren und Zielzellen können drastische Effekte im Gesamtsystem verursachen. Abhängig von Indikation und Materialeigenschaften müssen die Formulierungen individuell angepasst und optimiert werden. Wird dieser Arbeitsaufwand investiert, bietet der Einsatz genaktivierter Biomaterialien gegenüber herkömmlichen Behandlungsformen großes therapeutisches Potential.

Subject: Fibrin Glue for Conjunctival Grafts Paper Discussed: Uy HS, Reyes JM, Flores JD, et al. Comparison of fibrin glue and sutures for attaching conjunctival autografts after pterygium excision. Ophthalmology, April 2005, 112(4) p667-71 Guest: Harvey  Uy, MD Clinical Associate Professor of Ophthalmology The University of the Philippines Subject: Pyogenic Granulomas Associated with Punctal Plugs Paper Discussed: Kim BM, Osmanovic SS, Edward DP Pyogenic granulomas after silicone punctal plugs: A clinical and histopathologic American Journal of  Ophthalmology, Apr 2005, 139(4) p678-84 Guest: Smajo S. Osmanovic, MD, PhD Clinical Assistant Professor Department of Ophthalmology and Visual Sciences Illinois Eye & Ear Infirmary University of Illinois at Chicago

96 Der hepatische Ischämie-Reperfusionsschaden stellt ein relevantes klinisches Problem nach Lebertransplantation und Leberteilresektion sowie nach hämorrhagischem Schock dar. Es gibt zunehmend Hinweise darauf, daß Thrombozyten an der Ausbildung des hepatischen Ischämie-Reperfusionsschadens beteiligt sind. Bislang liegt jedoch keine Studie vor, in welcher die Mechanismen der Interaktion von Thrombozyten mit dem postischämischen hepatischen Endothel in vivo analysiert wurden. Insbesondere ist nicht geklärt, inwiefern diese Interaktion die Induktion und den Schweregrad des hepatozellulären Schadens beeinflußt. Ziele der Studie waren daher (1) die Thrombozyten-Endothelzell-Interaktion nach hepatischer I/R mittels intravitaler Fluoreszenzmikroskopie systematisch in Abhängigkeit von der Ischämie- und Reperfusionszeit quantitativ zu analysieren, (2) zu untersuchen, welche Mechanismen die Thrombozyten-Endothelzell-Interaktion in der Leber vermitteln und (3) zu analysieren, welchen Einfluß diese Interaktion auf den Ischämie-Reperfusionsschaden der Leber hat. An einem etablierten murinen Modell der warmen hepatischen Ischämie-Reperfusion wurde die Thrombozyten-Endothelzell-Interaktion mittels intravitaler Videofluoreszenzmikroskopie untersucht. Thrombozyten wurden von separaten syngenen Spendertieren isoliert, ex vivo mit Rhodamin-6G markiert, intravenös zu den jeweiligen Reperfusionszeitpunkten appliziert und bezüglich ihrer Interaktion mit dem Endothel der hepatischen Mikrogefäße quantitativ analysiert. Zur begleitenden Analyse des hepatischen Ischämie-Reperfusionsschadens wurden die sinusoidale Perfusionsrate, die Aktivität der Leberenzyme GOT/GPT im Serum und die Apoptosemarker Caspase-3- Aktivität und Anzahl TUNEL-positiver Zellen im Lebergewebe bestimmt. Durch Verwendung P-Selektin-defizienter Tiere (sowohl Thrombozytenspender als auch Thrombozytenempfänger) wurde die Rolle von endothelialem vs. thrombozytärem PSelektin für die Thrombozyten-Endothelzell-Interaktion untersucht. Des weiteren wurde versucht, durch Applikation eines Fibrinogen-Antikörpers die differentielle Bedeutung von Thrombozyten im Vergleich zu Leukozyten an der Ausbildung des Organschadens der Leber nach I/R in vivo aufklären. Es konnte gezeigt werden, daß hepatische Ischämie-Reperfusion eine Interaktion von Thrombozyten mit dem Endothel in präsinusoidalen Arteriolen, Sinusoiden und postsinusoidalen Venolen induzierte. Das Ausmaß dieser Interaktion war von der Ischämiedauer abhängig, während hingegen die Reperfusionsdauer keinen wesentlichen Einfluß hatte. Die vermehrte Thrombozytenadhäsion ging mit einem signifikanten Anstieg des mikrovaskulären und zellulären Organschadens einher. Untersuchungen an P-Selektin-defizienten Tieren demonstrierten, daß das endotheliale und nicht das thrombozytäre P-Selektin das Rollen und die nachfolgende Adhärenz von Thrombozyten in Arteriolen und Venolen der Leber vermittelte. Darüberhinaus war der postischämische Organschaden in P-Selektin-defizienten Tieren signifikant reduziert. Mittels der Blockade von Fibrinogen während der Reperfusionsphase konnte gezeigt werden, daß Fibrin(ogen) die postischämische Thrombozytenadhäsion vermittelte, an der Leukozytenadhärenz jedoch nicht beteiligt war. Die selektive Hemmung der Thrombozyten-Endothelzell-Interaktion führte zu einer signifikanten Reduktion des mikrovaskulären Schadens sowie der Apoptoseinduktion in der Leber nach Ischämie- Reperfusion. Somit demonstriert diese Studie erstmals in vivo, daß den Thrombozyten bei der Ausbildung des hepatischen I/R-Schadens eine wichtige Bedeutung zukommt.

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 [mu]g/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 [mu]mol, was given IV during 8 hours, resulting in plasma levels above 10 [mu]mol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.

Bei der Ohrmuschelrekonstruktion werden vom Transplantat hohe Formbeständigkeit und gute Verträglichkeit verlangt. Es wurde untersucht, ob diese Forderungen von einem Gemisch aus geraspeltem, konserviertem Knorpel und gerinnungsaktivem Plasmaprotein erfüllt werden, dem durch Einpressen in eine Silikonform die Gestalt einer Ohrmuschel gegeben wurde. Solche Nachbildungen sind formstabil und zeigen histologisch einen dichten Verbund zwischen Knorpelfragmenten und Fibrin. Nach Implantation bei Meerschweinchen und Ratten findet jedoch nach Tagen bis Wochen eine Lysis des Fibrins, Knorpelresorption und Organisation statt, die zum Verlust der Struktur führt. Werden statt Knorpel Kunststoffspäne aus porösem Polyäthylen verwendet, läßt sich die Festigkeit der gepreßten Formen aber deutlich erhöhen. Die histologische Untersuchung dieser Transplantate zeigte nach 35 Tagen eine stabile Einbettung im Bindegewebe, makroskopisch blieben Form und Konsistenz erhalten.