Podcasts about Fibrinogen

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation. In this “back to basics” mini-series, Dr LaShanta Brice will discuss the clinical utility of the three most common parameters tested in the lab, the PT, APTT and Fibrinogen. Today we are going to cover the Prothrombin Time! We will discover why an order for a PT would be received by the lab, generally why the PT is used in practice and some emerging trends particularly when considering the INR clinic. Happy listening! Literature source: CLSI H47 One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test     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.

In this episode of the Heal with Kat Podcast, we have master foundation cell activation technology consultant, Darlene Greene, on to share her powerful health journey, starting with her husband's early Alzheimer's diagnosis. This journey led her to explore various treatments, including stem cell therapy. Darlene's use of healing patches activated foundational cells, bringing remarkable improvements to both her own healing and her husbands. Discover how the patches reflect the body's light to stimulate healing, reset genes, and address inflammation. Time Stamps: 00:00 - Introduction 06:03 - The Impact of Stem Cell Patches28:21 - The Power of Stem Cells and Cellular Activation31:40 - How Emotional Health and the Mind-Body are all connected 41:02 Incredible Healing Stories and the benefits of patchingConnect with Kat:

In der Episode erläutern Hans-Dieter Höltje und Bernd Rupp die Mechanismen der Blutgerinnung, von der primären und sekundären Hämostase bis hin zur Rolle von Serinproteasen und Vitamin K in der Gerinnungskaskade.

Darlene Greene - Master Foundation Cell Activation Technology Consultant, retired US Navy Commander, and Co-Author of the 2024 best selling book, "Become Empowered - Echoes of Grace and Strength." Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” https://iamreverseaging.com/

Phantom Electric Ghost With Darlene Greene: Cell Activation Technology Consultant Darlene Greene - Cell Activation Technology Consultant, retired US Navy Commander, and Co-Author of the 2024 best selling book, "Become Empowered - Echoes of Grace and Strength." Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more...   Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world.  A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology.  During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel.  Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today.   Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. Link: https://iamreverseaging.com/

Episode Title: Healing from Fluoroquinolone Damage – A Real-Life Case Studywww.drhughwegwerth.com/post/61-year-old-s-floxed-recovery-functional-medicine-triumph-over-antibiotic-damage-and-inflammationHello, community! This is Doctor Hugh. Today, I have a very special case study to share. One of my clients has given me permission to discuss his lab results. We'll keep him anonymous but give you the information you need to get better.Case Overview:Client: 61-year-old maleIssue: Damaged by fluoroquinolones (strong antibiotics)Symptoms: Chronic pain, inflamed joints, unable to get out of bedHere's what happened:Timeline:Hospitalization: Client was hospitalized for colitis and given levofloxacin (antibiotic).Pain and Inflammation: He experienced severe pain and inflammation, making daily activities impossible.Functional Medicine Program: He started my functional medicine program about 6-7 weeks ago.Key Lab Results:Initial Labs (April 27, 2024):CRP (C-reactive protein): 81.86 (very high, indicates severe inflammation)Fibrinogen: 8828 (extremely high, another marker of inflammation)Sed Rate: 55 (should be less than 11)Total Estrogens: High (excess estrogen in the body)Follow-Up Labs (May 25, 2024):CRP: Still highFibrinogen: Reduced to 697Sed Rate: Reduced to 36Total Cholesterol: Dropped from 145 to 125 (dangerously low)Our Approach:Diet Changes:Carnivore-ish Diet: Focused on meat and specific fruitsHigh Protein Intake: Essential for healing and recoveryAvoided Gluten: Gluten is highly inflammatorySupplements and Therapy:Custom Care Plan: Tailored to his specific needsConsistent Follow-Ups: Regular check-ins to adjust the planResults:Recovery:Improvement: 95% better, able to cut grass, golf, and return to workInflammation Reduced: Significant reduction in pain and swellingConclusion:Hope and Healing:You Can Heal: With the right plan and support, recovery is possibleCustom Care: Individualized plans tailored to your needsGet Help:Contact Me: Schedule a Zoom call to start your recovery journey

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Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities.After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?”When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photobiomodulation technology. Learn more about Darlene and her amazing alternative health solutions at: https://iamreverseaging.com/ This is Darlene's website where guests can dive into how the technology works to elevate your GHK-CU and activate your foundation cells, the multitude of benefits, the over 90 clinical studies, the patents, the photos, testimonials, and see details on the suite of products. Guests can request additional information as well as purchase products from this website. #holistic #holistichealth #holistichealing #holisticnutrition #holisticliving #terapiaholistica #holisticwellness #holisticlifestyle #holistico #holistichealthcoach #mujerholistica #holisticmedicine #holisticlife #holisticnutritionist #holisticbeauty #holisticskincare #holistica #promilholistic #holistictherapy #holisticmama #holisticcoach #holistichealer #wholistic #holisticapproach #sanacionholistica #wholistichealth #holisticmom #holistichealthcare #holisticlifecoach #holisticcare #holistictherapist #terapeutaholistico #holistichairtribe #holisticesthetician #holisticeducation #holisticfitness #nutricionholistica #programhamilholistic #holisticfood #medicinaholistica

Olivia Ostrow on the management of button battery ingestions, Brit Long on C difficile infection, Jesse McLaren on an approach to ECG's in the tox patient, Joe Mullally on the identification and treatment of bed bug bites, Andrew Petrosoniak on fibrinogen replacement in bleeding trauma patients, Justin Morganstern on Cold Air for Croup... The post EM Quick Hits 54 Button Battery Ingestion, C. difficile, ECG in Tox, Bed Bugs, Fibrinogen in Trauma, Cold Air for Croup appeared first on Emergency Medicine Cases.

Learn more about Darlene and reverse aging at: www.iamreverseaging.comFull Bio:Darlene Greene - Health and GHK-CU and Stem Cell Activation Technology Consultant and retired US Navy Commander. Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. Please leave a review or send us a Voice note letting us know what you enjoyed at:Back2Basics reconnecting to the essence of YOU (podpage.com)Follow us on IG and FB @Back2BasicsPodcast

In this episode of “The Journey of My Mother's Son” podcast, I sit down to talk with Darlene Greene. Darlene is a Health and GHK-CU and Stem Cell Activation Technology Consultant and retired US Navy Commander.  Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more...  Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world.  A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology.  During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel.  Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today.  Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. To find out more about Darlene and this life-altering patch, check out her website at https://iamreverseaging.com/.

Join 6AMRun.com  Ambassador and Host, Marc Paisant, as we welcome GHK-CU/ Stem Cell Activation Technology Consultant and US Navy Veteran, Darlene Greene. Darlene has over 26 years of experience in executive leadership and senior management positions across diverse industries, During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel.   Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world.  A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” Please visit: https://iamreverseaging.com/ to learn more. To be a guest, or share your story with the 6AM Run Community apply at: https://forms.gle/hBHCKpYKT6R9tH6m7 6AM Run believes in improving everyone's physical ability to not only have motion, but STAY IN MOTION. All this while creating an amazing supportive, surrounding community. Run Faster, Farther, & Recover For More Runs! Guest are found through PodPros (podmatch.com) and recorded through Riverside.fm. 6amrun.com #6amrunSee omnystudio.com/listener for privacy information.

Darlene Greene - Health and GHK-CU and Stem Cell Activation Technology Consultant and retired US Navy Commander. Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. Learn more about Darlene and her product at her website. Two Drunk Dudes is not affiliated with the brand or a representative of the brand. We only bring the information to the audience and always strongly recommend that you do your own research and consult your own physician prior to making any medical decisions. We have not tried the product and can not speak on the results of the product. To listen to music by our military veterans and military spouses check out ⁠⁠⁠⁠⁠Gun Room Radio⁠⁠⁠⁠⁠ You can also follow Gun Room Radio on ⁠⁠⁠⁠⁠Facebook⁠⁠⁠⁠⁠ You can follow Two Drunk Dudes in a Gun Room podcast on the following Platforms ⁠⁠⁠⁠⁠Website⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠Facebook⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠Twitter⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠ If you need help reach out to us or call 988 EXT 1 for veterans. Reach out to us at ddunn@twodrunkdudesinagunroom.beer

Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel in multiple departments. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. Website: Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains. ⁠Website: https://iamreverseaging.com⁠ --- Send in a voice message: https://podcasters.spotify.com/pod/show/new-mind-creator/message Support this podcast: https://podcasters.spotify.com/pod/show/new-mind-creator/support

Darlene Greene - Health and GHK-CU and Stem Cell Activation Technology Consultant and retired US Navy Commander. Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities.After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?”When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger?Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology.https://iamreverseaging.com/ https://www.facebook.com/darlene.bennett.greene https://www.linkedin.com/in/darlenegreene/

Darlene Greene, GHK-CU and Foundation Cell Activation Technology Consultant Iamreverseaging.com Biography Darlene Greene - Health and GHK-CU Activation Technology Consultant and retired US Navy Commander. Darlene Greene wants to help you take charge of your own health, get out of pain, improve your energy, increase the quality of your sleep, reduce systemic inflammation, increase mental clarity, improve your nervous system, lower your anxiety, enhance brain functioning, improve cardiovascular functioning, and elevate your GHK-Cu for a host of additional benefits to include increasing your own stem cells, producing growth factors, protect lungs, reset genes to their younger healthier state, repair damaged DNA, inhibit cancer, increase hair growth, improve skin, increase healing, accelerate wound healing, reduce Fibrinogen (top predictor of cardiovascular disease) and more... Having exhausted IV stem cells, hyperbaric chamber, ozone therapies and more to help her husband with his Early Alzheimer's, she FINALLY discovered an affordable technology that dramatically improved his symptoms within the first week, without drugs, without a prescription, and without any contra-indications to other treatments or therapeutic modalities. After experiencing the amazing results for herself, and watching family and friends have their own miracles, Darlene is passionate about sharing this technology with the world. A driving force for her remains, “Why didn't I know about this two years ago… where would my husband be if we had started using this technology two years ago…and who out there needs to know about this right now?” When an anesthesiologist says, “This is the most significant medical breakthrough in my lifetime…” and when over 300 Olympic Athletes use the technology in the 2008 Olympics, aren't you curious as to what it could do for you in addition to making you look and feel younger? Darlene Greene has over 26 years of experience in executive leadership and senior management positions across diverse industries, including positions such as: Vice President of Strategic Technology Partner at McAfee (Intel), Dean of Culver Girls Academy, Director of Client Services for HyeTech Networks and Security, and Senior Director LifeWave Foundational Cell Activation Technology. During her 20 years of military experience, she earned her MBA and held three Commanding Officer positions, including serving as base commander and overseeing over 1200 personnel. Darlene created the Returning Warrior Weekend Workshop in 2006 to help military members and their spouses reintegrate successfully – a program still supporting military across the country today. Darlene's passion today is helping people elevate their GHK-CU peptide to activate their stem cells, repair their DNA, reverse age, and get out of pain through the latest photo biomodulation technology. About The Guest(s): Darlene Green is a retired U.S. Navy commander and a G.H.K.C.U. and Foundational Cell Activation Technology Consultant. She is the founder of IamReverseAging.com and has helped establish the Returning Warrior Workshop, which supports warriors and their families in reintegrating after military service. Summary: Darlene Green shares her personal journey of discovering a patch that activates the copper peptide G.H.K.C.U., which in turn activates stem cells and provides a range of health benefits. She explains how the patch has helped her husband reverse the effects of Alzheimer's disease and improve his overall health. Darlene also discusses the various studies and scientific evidence supporting the effectiveness of the patch, as well as the positive impact it has had on her own health. Key Takeaways: The patch activates the copper peptide G.H.K.C.U., which in turn activates stem cells and provides a range of health benefits. The patch has been shown to improve memory, cognitive function, sleep, energy levels,

Profs Nikki Curry (Oxford) and Karim Brohi (London) present the results of the CRYOSTAT-2 trial, evaluated early & empiric high-dose cryoprecipitate in patients with major traumatic haemorrhage. The editorial is delivered by Susan Rowell (Chicago) and the session is chaired by Phil Gillen from Belfast. The panel discussing the trial are Russell Gruen (Canberra), Caroline Leech (Coventry), John Holcomb (Birmingham, USA), Andrew Althouse (Pittsburgh) and co-investigator Simon Stanworth from Oxford.

In this early pandemic study of COVID-19 confirmed hospitalized patients, researchers found two groups of individuals with biomarker profiles: the first had high fibrinogen levels in relation to C-Reactive proteins (CRP) and the second had an increase in D-Dimers in relation to CRP. These molecules generally increase in relation to CRP; however, here the researchers found that the fibrinogen and D-Dimers increased while the CRP stayed low. These cohorts were associated with higher likelihood of neurological long COVID. Let's review both the findings and the mechanisms. DrBeen: Medical Education Onlinehttps://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliancehttps://covid19criticalcare.com/ URL list (Sep. 7, 2023) Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization | Nature Medicinehttps://www.nature.com/articles/s41591-023-02525-y Clotting proteins linked to Long Covid's brain fog | Science | AAAShttps://www.science.org/content/article/clotting-proteins-linked-long-covid-s-brain-fog Physiology, Acute Phase Reactants - StatPearls - NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK519570/#:~:text=Acute%20phase%20reactants%20(APR)%20are,acute%20and%20chronic%20inflammatory%20states. Fibrin Polymerization - an overview | ScienceDirect Topicshttps://www.sciencedirect.com/topics/immunology-and-microbiology/fibrin-polymerization#:~:text=Cross%2Dlinked%20fibrin%20is%20an,that%20stabilizes%20the%20platelet%20plug.&text=Thrombin%20also%20activates%20a%20thrombin,%E2%80%9CFibrinolysis%2C%E2%80%9D%20below). Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study - The Lancet Regional Health – Europehttps://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00143-6/fulltext Role of C-Reactive Protein at Sites of Inflammation and Infection - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908901/#:~:text=Evidence%20suggests%20that%20CRP%20is,NO%20release%2C%20and%20cytokine%20production. Screening Tests in Haemostasis:Fibrinogen Assayshttps://practical-haemostasis.com/Screening%20Tests/fibrinogen.html D-Dimers • The Blood Projecthttps://www.thebloodproject.com/cases-archive/d-dimers/d-dimers/ Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial | Geriatrics | JAMA Network Open | JAMA Networkhttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2807630#:~:text=In%20this%20secondary%20analysis%20of,overall%20risk%20of%20intracranial%20bleeding. Disclaimer:This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional. dr beenfibrinogenflccclong covidlong story short

Postpartum hemorrhage remains an important and preventable cause of maternal mortality worldwide. In this interview, Dr. Michaela Farber provides us with a phenomenal timeline from the landmark study that highlighted the importance of fibrinogen as an early plasma biomarker to predict severe postpartum hemorrhage to the current evidence for the use of fibrinogen concentrate and … Read More Read More

In this conversation we will examine the principles of coagulopathy and novel approaches to coagulopathy within pre-hospital care. We will examine the utility of fibrinogen concentrate, the distinct features of fibrinogen concentrate with cryoprecipitate, its longevity of use compared to other blood products, how you constitute fibrinogen concentrate for use in the pre-hospital environment amongst other topics.    To do this I have Ross Davenport with me, Ross is a Consultant Trauma & Vascular Surgeon at the Royal London hospital in the UK. He is also a Senior Lecturer in Trauma Sciences and has previously worked in prehospital care for both London and Essex & Herts Air Ambulance. His research has focused on trauma-induced coagulopathy, acute response to injury and the treatment of major trauma haemorrhage. His work in traumatic coagulopathy and massive transfusion, inflammation and organ dysfunction has had international renown. In the episode we examine: ·      Coagulation and the pre-hospital evidence  ·      Are we getting a handle on hypothermic induced coagulopathy  ·      What is fibrinogen concentrate and its mechanism of action? ·      How it differs from cryoprecipitate and whether we still need cryoprecipitate. ·      What the initial empirical research shows from CRYOSTAT 2 research. ·      It's robustness within pre-hospital environments and how you reconstitute it for pre-hospital use.  ·      Current trials with Fibrinogen concentrate and early indications of effectiveness.  ·      ROTEM/thromboelastometry markers of effectiveness  ·      When to give it in the patient journey?  Please enjoy this episode.

If there's one physician I listen and trust it's Dr David Brownstein. I have followed his guidance and introduced protocols into my own practice like hydrogen peroxide to game-changing effect. So I wanted to talk to him again a year later and discuss where his thinking is and what novel ideas and therapies he is working with now that could again make a game-changing effect in my life and my work. Dr. David Brownstein, M.D., is a board-certified family physician who utilizes the best of conventional and alternative therapies. He is the Medical Director for the Center for Holistic Medicine in West Bloomfield, Michigan. He is a graduate of the University of Michigan and Wayne State University School of Medicine.Dr. Brownstein is a member of the American Academy of Family Physicians and serves on the board for the International College of Integrative Medicine. Dr. Brownstein has lectured internationally about his success using natural therapies. He has also authored sixteen books including Iodine: Why You Need It, Why You Can't Live Without It, and his newest book A Holistic Approach to Viruses.Join us as we explore:What unique lessons Dr Brownstein has learnt over the past 3 years about the immune system, including the need to move as well as keeping sweets in the cupboard.Fibrinogen - what it is and why we need to pay more attention to it.The big problem with ocean derived supplements and products, and why there is less of what we need and more of what we don't want!The biological mechanism of iodine, and why we need more than ever yet there is less than ever in nature.Ferritin, iron, zinc and copper – Dr Brownstein's view on ferritin and iron, the relationship between iron, zinc and copper, what are healthy levels and why birth control is an unknown part of the biological copper crisis.Robert F. Kennedy Jr's  presidential candidacy.Mentions:Study – Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19, https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100044Support the showSupport the show on Patreon:As much as we love doing it, there are costs involved and any contribution will allow us to keep going and keep finding the best guests in the world to share their health expertise with you. I'd be grateful and feel so blessed by your support: https://www.patreon.com/MadeToThriveShowSend me a WhatsApp to +27 64 871 0308. Disclaimer: Please see the link for our disclaimer policy for all of our content: https://madetothrive.co.za/terms-and-conditions-and-privacy-policy/

Today's Spectrum of Health podcast episode is short but packed full of pearls straight from Dr. Christine!  She talks about healthy blood flow and takes a deep dive into the factors that can impact healthy blood flow, such as EMF, modern-day toxicity, and spike proteins. Dr. Christine also shares some tools and practices, such as ozone and meditation, that can help create a more oxygen-rich environment within the body.    Listen in to learn more about today's conversation on healthy blood flow and how to optimize it for yourself: (0:00:02) - Factors that affect healthy blood flow (0:14:46) - The importance of being educated about the markers of blood flow (0:10:40) - Benefits of meditation on your health   To get the full show notes - www.drchristineschaffner.com/Episode184    

https://censored.news (Mike Adams)https://naturalnews.com (Mike Adams)https://theDrArdisShow.com (Dr Ardis)VISIT https://GiveSendGo.com/BaalBusters and HELP the Fam so I can do these shows.or https://www.tipeeestream.com/baal-busters/donationor https://paypal.me/BaalBustersGet Healthy and Independent: https://riseupintohealth.com/?=ndhealthSubscribe to my Rumble Channel: https://rumble.com/c/c-1121444Brighteon: https://www.brighteon.com/channels/baalbustersFull Channel: https://BaalBuster.JoshWhoTV.comTelegram: https://t.me/BaalBustersStudiosTik Tok: https://www.tiktok.com/@baalbusters (shadow banned)Twitter: https://twitter.com/DisguiseLimitsFREE Roku TV channel: https://channelstore.roku.com/details/a44cff88b32c2fcc7e090320c66c4d09/baal-busters-broadcast New Years Resolution? Resolve to be Resolute in attaining your goals! Have lasting success the only way you can. By doing it naturally. Click the Link and Learn what the established medical profession does not know. "My people perish [suffer] for a lack of knowledge." https://riseupintohealth.com/?=ndhealthDr Glidden has 34 years of natural, root cause addressing expertise to share with you. Go there. Don't wait. Begin your new year by becoming a New You. I did it, and that's why, and only why I recommend it. It helped me profoundly.For COPPERINE which my whole family uses, go here: https://BioChemScience.com and use BB2022 for Free ShippingLove Hot Sauce? Go Here! I make it: https://SemperFryLLC.com

On today's episode of Red Pill Your Healthcast with Dr. Charlie and Nurse Practitioner Lauren-  Pharma talk! Statins and blood pressure medications.   Let's dive in!   Connect with Dr. Charlie Website Instagram Membership   Connect with Nurse Practitioner Lauren  Website Instagram Email List Cholesterol Recs:  Paleo Cardiologist Book- Shop CoQ10- Shop ReGenerZyme® Heart- Shop InspiraCell®- Shop NMR profile Test Study about the Risk of Low Cholesterol - Read   Dr. Charlie Scale for Cholesterol Labs Total Cholesterol between 220-250 LDL below 120 HDL between 55-80 Triglycerides below 100 — Blood Pressure Redmond Salt- Shop Trace Minerals- Shop Magnesium Glycinate- Shop Magnesium Malate- Shop Coconut Water- Shop Magnesium Bicarbonate- Shop Use code naturalnursemomma for 10% off Dr. Charlie's Rec- Astragalus Supreme - immune builder. master tonic of Chinese Medicine Cat's Claw- lyme, parasite, yeast, Heart Health, etc - one of our favorites. Dan Shen- red sage, lowers blood pressure Artichoke Extract- regulate blood sugar   Tests for Erectile Dysfunction Blood Test for Lipoprotein (a), Fibrinogen, CRP, Homocysteine.   NP Lauren's Rec- Daily cup of strong Hibiscus Tea - Shop I buy I loose leaf tea or organic paper tea bags. To make loose leaf tea I usually do 1-2 teaspoons loose herbs in hot water and steep for 5 minutes. Add sweetener of choice.  Magnesium Blog- Read NMR lab test ranges Small LDL-P below 530 ideally, LDL-P below 1000 and LDL size above 20.5. If LDL a particles are small and dense they are more likely to cause issues.  Search full library of our favorite supplements - Lauren's Fullscript- https://us.fullscript.com/welcome/naturalnursemomma Dr. Charlie's Fullscript- https://us.fullscript.com/welcome/cfagenholz   One thing not mentioned in this podcast is the amount of seed oils in our foods has increased exponentially. These are in fact linked to inflammation and a contributing factor to high cholesterol. I do not stress about never eating vegetable or canola oil but I do try to eat whole foods and cook with other fats. I use grassfed butter, beef tallow, duck fat, etc.   Here are the brands I use in my home https://a.co/bacW2OL         Thanks for listening y'all!

Angel grew up knowing she had Factor 1 Deficiency, having been diagnosed at a young age. Overall her symptoms have been mild to moderate, but like many women her journey has been a roller coaster. Listen in as we discuss her treatment journey from Cryoprecipitate to now being on prophylaxis with a factor concentrate, how she contracted Hepatitis C and successfully cleared it, and her experience of finding out she had endometrial cancer. She will always speak for awareness of investigating any unusual female symptoms...as she found out that symptoms and a bleeding disorder aren't always directly linked.   Music - reCreation by airtone (c) copyright 2019 Licensed under a Creative Commons Attribution (3.0) license. http://dig.ccmixter.org/files/airtone/59721 

PODCAST HIGHLIGHTS: 03:19 Simple Lab Testing 04:18 Ideal Functional Ranges 07:20 White Blood Cells 10:25 Hemoglobin 12:06 RDW 14:17 MCV 15:13 Platelets 20:05 hs-CRP 20:55 Homocysteine 21:19 D-Dimer 23:25 Fibrinogen 24:09 GGT  24:48 Ferritin 25:49 Can high platelets lead to menstrual cramps https://youtu.be/6V3L-DhKLEs Transcript from Webinar: Welcome to another edition of "Ask Dr. Neiters" here...... Continue Reading →

In this episode Dr. Troy Spurrill, owner of  Synapse Center for Health and Healing, Dr. Joshua Wallert, Lead Practitioner, and Marque Gant, Clinic Director have a conversation about Aches & Pains (Fibrinogen/Statins),

Welcome to Ask Stago, the podcast dedicated to provide expert answers to your expert questions in hemostasis. In today episode, our expert Lydie Nicoud, R&D reagent manager, will talk with us about the test of fibrinogen.  As usual, don't forget to send any question you may have to ask@stago.com, we will be glad to answer to it. Literature sources: Miesbach W, Schenk J, Alesci S, Lindhoff-Last E, Comparison of the fibrinogen Clauss assay and the fibrinogen PT derived method in patients with dysfibrinogenemia .Thromb Res. 2010; 126(6): e428-33 Karapetian H. Reptilase time (RT). Methods Mol Bio 2013; 992:273-7. Mackie IJ, Kitchen S, Machin SJ, Lowe GDO, Guidelines on fibrinogen assays, Br J Hematol 2003; 121: 396-404 Cunningham MT, Olson JD, Chandler WL, Van Cott EM, Eby CS, Teruya J, Hollensead SC, Adcock DM, Allison PM, Kottke-Marchant KK, Smith MD. External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation. Arch Pathol Lab Med. 2012 Jul;136(7):789-95. doi: 10.5858/arpa.2011-0322-OA. PMID: 22742551.Siriez R, Dogné JM, Gosselin R, Laloy J, Mullier F, Douxfils J Comprehensive review of the impact of direct oral anticoagulants on thrombophilia diagnostic tests: practical recommendations for the laboratory. Int J Lab Hematol 2021; 43(1): 7-20   Related podcasts: S1E9: How to manage HIL samples in the coagulation laboratory?  S1E15: Disseminated Intravascular Coagulation (DIC) and fibrin related markers.  S2E6: Prothrombin Time routine does not mean "simple".    S2E7: APTT, not a one-for-all purposes reagent.   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.

For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·Jubilee website·PrevMed's website·PrevMed's YouTube channel·PrevMed's Facebook page·PrevMed's Instagram·PrevMed's LinkedIn·PrevMed's Twitter ·PrevMed's Pinterest

In this, our 50th episode, we are in Austin, TX, for the Annual EAST Scientific Meeting where we are joined by Dr. Bryan A. Cotton who shares his expertise and knowledge regarding the use of whole blood (WB) in trauma patients. From the use of whole blood in prior military conflicts to the design and successful implementation of one of the only prospective randomized controlled trials of modified whole blood use in trauma patients, Dr. Cotton provides an incredible overview of the potential benefits of whole blood or as he refers to it - "the dying blood product". Also covered in expert fashion are the role of other hemostatic products and strategies including tranexamic acid, fibrinogen concentrates, and a plasma first resuscitation strategy. Time Stamps:01:16  The rationale for whole blood & a 1:1:1 transfusion strategy04:24  Military experience with WB: What's old is new again!05:44  Modified WB vs. Component Therapy RCT06:02  Leukoreduction of WB07:00  Type-specific WB09:38  Platelet function in WB vs. aphaeresis platelets11:58  Warm fresh WB vs. cold stored12:55  The whole is greater than the sum of its parts15:02  What do we mean by low-titer WB?19:14  O+ vs. O- WB & the potential for alloimmunization24:39  Transfusion reactions & safety of WB in trauma patients25:40  Prehospital WB for the win27:32  LITES Network28:27  Hemorrhage control, 1:1:1, viscoelastic assays, cryoprecipitate & fibrinogen               concentrate32:00  BAC's thoughts on tranexamic acid (TXA)34:47  BAC's thoughts on hypertonic saline (HTS) for COVID-1938:51  Final thoughts & future directionsRecommended Readings:Cotton BA, Podbielski J, Camp E, Welch T, del Junco D, Bai Y, Hobbs R, Scroggins J, Hartwell B, Kozar RA, Wade CE, Holcomb JB; Early Whole Blood Investigators. A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann Surg. 2013 Oct;258(4):527-32; discussion 532-3.Williams J, Merutka N, Meyer D, Bai Y, Prater S, Cabrera R, Holcomb JB, Wade CE, Love JD, Cotton BA. Safety profile and impact of low-titer group O whole blood for emergency use in trauma. J Trauma Acute Care Surg. 2020 Jan;88(1):87-93. McGinity AC, Zhu CS, Greebon L, Xenakis E, Waltman E, Epley E, Cobb D, Jonas R, Nicholson SE, Eastridge BJ, Stewart RM, Jenkins DH. Prehospital low-titer cold-stored whole blood: Philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury. J Trauma Acute Care Surg. 2018 Jun;84(6S Suppl 1):S115-S119. Sperry JL, Guyette FX, Brown JB, Yazer MH, Triulzi DJ, Early-Young BJ, Adams PW, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putnam AT, Duane TM, Alarcon LH, Callaway CW, Zuckerbraun BS, Neal MD, Rosengart MR, Forsythe RM, Billiar TR, Yealy DM, Peitzman AB, Zenati MS; PAMPer Study Group. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med. 2018 Jul 26;379(4):315-326. doi: 10.1056/NEJMoa1802345. PMID: 30044935.Yazer MH, Jackson B, Sperry JL, Alarcon L, Triulzi DJ, Murdock AD. Initial safety and feasibility of cold-stored uncrossmatched whole blood transfusion in civilian trauma patients. J Trauma Acute Care Surg. 2016 Jul;81(1):21-6. doi: 10.1097/TA.0000000000001100. PMID: 27120323.Websites:LITES Networkhttps://www.litesnetwork.orgSouthwest Texas Regional Advisory Councilhttps://www.strac.org/bloodSupport the show (https://www.patreon.com/traumaicurounds)

In this podcast, we will compare the utilization of fibrinogen concentrate and cryoprecipitate along with the pros and cons of each.

Module 3 Preston and Shaw discuss what we need to know about Platelet Receptors, Fibrin-Fibrinogen, and Extrinsic-Intrinsic Pathways for exam 3.

Lisa continues her conversation with author and medical researcher Christian Wilde on the show today. It is a fact that 50% of all heart attacks and strokes occur to people with normal cholesterol. Christian discusses the wonders of turmeric and how that helps tremendously in leading a healthy lifestyle. He also continues to talk about what fibrinogen is, what the appropriate levels should be, when it's dangerous, how you get tested, what you can do to bring your levels down and more. He also talks about his book, “The Hidden Causes of Heart Attack and Stroke.”  Tune in to this very important show!  Info: myheartbook.com

Did you know that 50% of all heart attacks occur to people with normal cholesterol? You hear so much about heart disease these days, but have you ever heard about fibrinogen? Maybe not, but it's important that you know about this! That's why Lisa is hosting author and medical researcher Christian Wilde on the show today. He'll tell you all about what fibrinogen is, what the appropriate levels should be, when it's dangerous, how you get tested, what you can do to bring your levels down and more. Pls listen to this very important show!  https://www.myheartbook.com/

Dr. Martin answers questions sent in by our listeners. Some of today's topics include: Reversing hardening of arteries Tanning beds Absorption of supplements Protein and fibroids Fibrinogen and arthritis Histamine intolerance Sties and fungus infections Necessity of tonsils Tune in to hear Dr. Martin's responses!  

Hypofibrinogenaemia is an independent risk factor for mortality after severe trauma.  How though should we manage it? Dr James Winearls is an Intensivist and researcher from the Gold Coast University Hospital.  In this special edition podcast from the 2021 Noosa ANZICS CTG meeting, he joins Todd to chat about the issue, and the FIESTY 2 study he leads See omnystudio.com/listener for privacy information.

Nuanced trauma care by the Queensland Ambulance Services High Acuity Response Unit (HARU). A brief outline of the capabilities of HARU and some key principles that make it successful. Could this be a model for other ambulance services to follow in the future? For more head to: codachange.org/podcasts

On this ID the Future, Michael Behe continues discussing his new book, A Mousetrap for Darwin, with host Eric Anderson. Here the focus is the blood clotting cascade. Behe has argued it’s irreducibly complex, like a mousetrap, and that blind evolution couldn’t build it one small functional step at a time. Behe says a better explanation is that it was intelligently designed. His critics have responded to his argument over the years. Here Behe returns the favor. His most prominent interlocutor on the matter is the recently deceased Russell Doolittle. Behe shows that Doolittle misread the paper he relied on to refute Behe. Professor Behe also responds to Kenneth Miller and Keith Robison. According to Behe, his critics have managed Read More › Source

Juanique and Tristin discuss the importance of detoxification, why it can stop working very efficiently, what happens to you when it stops working efficiently, and how you can supercharge it to get yourself back on a healing pathway. The liver is an essential piece of hormone management. The liver has over 500 functions in the body. Our modern environment seems to be terrible at making us healthy. Many foods that we eat have plenty of added chemicals and pesticides that our bodies are not meant to digest. Living a heavily stressful lifestyle can affect your liver negatively. Not only are foods unhealthy for us in modern society, but are also highly addictive. Three phases of detoxification. Phase 1) Bioactivation. Liver sends out enzymes to tag the toxins in your system letting your body know they are present. Phase 2) Conjugation phase. Your liver adds little molecules to the tagged toxins, so they are either water soluble or fat soluble. Phase 3) Flush toxins out of your body through urination or defecation. In some people, their phase two is not working properly, so their body will try and find the nearest exit, which can often be the skin. Phase 2 is very dependent on the foods you eat. When we eat unhealthy foods, oily, sugary foods, we aren’t giving our bodies the necessary tools it needs to digest properly, so things begin to shut down. Either you’re eating things that can contribute to eliminating toxins, or you’re eating things that your body needs to eliminate. Fiber is absolutely essential to the digestive system. If you don’t defecate regularly, your body is marinating in your feces. You need to get rid of those toxins. The liver produces bile, and bile is an emulsifier for fats, which help us to absorb fatty acids. So things can get caught in a vicious cycle when the liver isn’t doing well. Liver damage can happen from unhealthy fats and sugars. Your ears can indicate issues with your liver, such as ringing. Many issues around your body can be linked back to your liver. Even your sex hormones can be negatively impacted. There are three parts to healing your liver. Part 1 is nutrition. Start your first week eliminating fruits to help the liver get back on its feet because it will lighten the workload on your liver. Our program comes with meal plans for you. The other thing you’re eliminating is other things that are putting a lot of strain on your liver, such as coffee. Part 2 is supplements. SP Cleanse is an incredibly food based liver nutrient rich product that is entirely food based. You will be taking 7 of these per day. Part 3 is lifestyle factors. How are you taking care of what is in your heart and in your mind? Emotional toxicity in your life can create stress, which directly affects your physical health. The liver is the anger organ. When you get angry, your liver is impacted. Connect with people. Go outside. Do what will improve your mood and mental health. If you want meaningful and fundamental changes in your health, then you have to make meaningful and fundamental changes in your whole life. Not just in your digestive health. 3 phases of detoxification 17:05mygutsyhealth.com/liver-reset 26:10 gutsy.ch/liver 26:183 parts to healing the liver 38:15SP Cleanse 42:23Gutsy Health Program Testimonial 61:54“A blood test is not going to tell you [if something is wrong with your liver]… Your liver enzymes only get elevated when there is already damage going on. It is not a measure of liver function. It’s a measure of liver damage. So just because your liver isn’t damaged doesn’t mean your liver is doing what it’s supposed to do. So if your liver enzymes look totally normal, but all of your inflammation markers like CRP, Homocysteine, Fibrinogen, Ferritin. If they’re all super elevated, there’s a decent chance there’s someSupport the show (https://www.mygutsyhealth.com/gutsy-family)

Episode 2: Oren Friedman interviews Ken Rosenfield on catheter directed lytics. Oren Friedman MDAssociate Director, Cardiac Surgery ICU Pulmonary Critical Care Cedars-Sinai Medical Center Ken Rosenfield, MD, MHCDSSection Head, Vascular Medicine and Intervention Division of Cardiology Mass General Hospital   What is catheter directed thrombolysis (CDT)? Placing a catheter via femoral or IJs into pulmonary arteries and infusing low dose thrombolytic over extended period. Percutaneous mechanical thrombectomy differs as it involves extracting thrombus from pulmonary artery. (mostly from proximal pulmonary arteries, and no thrombolytic regimen used in this method) MOA of CDT compared to peripheral systemic thrombolysis More clot bound thrombolytic directly into the clot compared to around the clot with systemic tPA. Increased local thrombolytic concentration. Reduced tPA and longer duration of infusion—reason for increased safety profile for ICH and major bleeding compared to full dose systemic tPA. (dose is 100 mg, ICH rates 3-5%) CDT also allows improve tPA infusion to into distal pulmonary circulation bed. (Vs percutaneous mechanical embolectomy) Technical aspects of CDT: Pulmonary angiogram is not always needed at time of CDT or post CDT. Decision to place unilateral or bilateral catheters (right, left or both branches of pulmonary artery) depends on location of clot based on CTA. Patient are usually monitored in ICU while drugs are infusing, close monitoring and experienced clinical nursing staff should be involved. Heparin during CDT: fix dose 300-500 unit/per catheter sheaths. Hard to achieve targeted aPTT (40-60) given very short duration of infusion. Fibrinogen to guide tPA duration- limited to no data Catheter directed thrombolysis with (EKOS) ultrasound or without ultrasound: We just don’t know. The available data stems from prospective clinical trials with ultrasound catheters. Sedation: be careful with sedation. Use minimum. Avoid intubation for procedure itself. What is successful CDT? Goal is to improve hemodynamics, not to remove all thrombus. Drop in pulmonary artery pressures (if monitoring available) or improved RV/LV ratio in pre-vs Post intervention imaging. [Echo or CTA] Data on CDT Impact on RV/LV ratio, as primary goal of improvement in many trials (see Table below) ULTIMA trial: Heparin Vs CDT, with EKOS catheters. Rapid normalization of RV/LV ratio compared to heparin alone in immediate period. No difference at 90 days. Small numbers to show impact on mortality. SEATTLE II trial -- also included massive PE patients. PERFECT registry: prospective registry showing safety and efficacy of CDT. OPTALYSE trial: compared different CDT dosing regimens. Impact on long term disability like CTED or CTEPH remains to be seen. Dosing regimens for of CDT: (See Table below) Higher risk bleeding patients: use as low as dose possible. OPTALYSE trial: Lower dose (as low as 4-8 mg) and shorter duration are effective for hemodynamic improvement. Higher doses were associated with better Miller clot burden improvement with increased risk of bleeding. (2 ICH incidents) Rali P, Criner J. Am J Respir Crit Care Med. 2018 Sep 1;198(5):588-598  

Editor's Summary by Mary McDermott, MD, Deputy Editor of JAMA, the Journal of the American Medical Association, for the November 26, 2019 issue

  This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from recent issues of Circulation Research and talks with Denisa Wagner and Nicoletta Sorvillo about their article on how PAD4 in blood promotes VWF strings and thrombosis. Article highlights: Goodyer et al: ScRNA-seq of the Cardiac Conduction System   Xiong et al: Chemotaxis Mediated Second Heart Field Deployment   Ranchoux et al: Pulmonary Hypertension and Metabolic Syndrome   Rühl et al. Thrombin/APC Response in FVL and FII 20210G>A   Mahmoud et al. LncRNA SMILR’s Mechanism and Therapeutic Potential   Transcript   Cindy St. H:                         Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you some highlights from the recent articles published in the August 2nd and August 16th issues of Circulation Research. Cindy St. H:                         After I discuss some highlights, we'll also have an in-depth conversation with Drs. Denisa Wagner and Nicoletta Sorvillo, from Boston Children's Hospital and Harvard Medical School, who are the lead authors of one of the exciting discoveries from the August 16th issue. Cindy St. H:                         The first article I want to share with you today is titled Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution. The first author is William R. Goodyer, and the corresponding author is Sean Wu. They are both located at the Cardiovascular Institute and the Department of Pediatrics at Stanford University. Cindy St. H:                         Have you ever wondered how your heart beats, and why there's always this glub-glub pattern, and where did it come from? How is the heart able to initiate that pattern, from cells that don't contract to cells that contract? Well, the beating of the heart is regulated by what's called the cardiac conduction system, and this is an area in the heart of specialized cells, and these cells establish the rhythmic beating by coordinating the contraction of the chambers of the heart. Cindy St. H:                         There's several components to the CSS. The sinoatrial node acts as the pacemaker in the right atrium. The arterial ventricle node is the electrical relay that slows down the pulse from the SA node. A His bundle helps to transmit those impulses, and the Purkinjie fibers are the terminus of the electrical signal. Between all of these different components are a heterogeneous population of what are called transitional cells. There are several studies that have linked these somewhat amorphous or heterogeneous transitional cells to different arrhythmic disorders. Cindy St. H:                         For the normal function of the heart, all of these parts must come together, and when they don't, there's severe clinical manifestations such as arrhythmias, like I said, but also you can get decreased cardiac output and even sudden cardiac death. While important, the cells of the CSS are rather elusive, and that's because they're in a relatively small number compared to the rest of the cells in the heart, and there also aren't very clear markers to identify the cells in the CSS. Cindy St. H:                         To address this, Goodyer and colleagues harvested cells from embryonic mouse hearts and performed single-cell RNA sequencing on 22,000 individually barcoded cells. What they were looking for is learning what type of cells they are, but more importantly, they had the goal of identifying what these elusive transitional cells are, and can we find a marker for these cells to study them? And in some, yes. Together, the sequencing and spatial data provided gene expression atlas of the mouse CSS. Hopefully, this atlas will guide future studies into the essential electrical system that regulates the heartbeat. Cindy St. H:                         The next article I'd like to highlight is titled Single-Cell Transcriptomics Reveals Chemotaxis-Mediated Intra-Organ Crosstalk During Cardiogenesis. We're really going to hit you over the head with some single-cell transcriptomics in this month's podcast. The first authors of this article are Halqing Xiong, Yingjie Lou, Yanzhu Yue, Jiejie Zhang and the corresponding author is Aibin He and they're all from the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine and the Peking-Tsinghua Center for Life Sciences, all at Peking University in Beijing, China. Cindy St. H:                         During development, the mammalian heart originates from two distinct areas in the early embryo and they're called the first heart field and the second heart field. Progenitor cells from these regions give rise to very different structures. From the first heart field comes the atria and the left ventricle, and the second heart field forms the right ventricle and the outflow tract. While we know the outcomes of these different developmental layers, a full understanding of how the first and second heart fields are regulated and how they actually interact with one another is actually lacking a lot of detail and we're not exactly sure how those structures can influence one another. Cindy St. H:                         So to learn more, Xiong and colleagues utilized two different murine models that were engineered to label cells coming from either the first or second heart fields red, and by labeling these cells red, it allows for their very pure isolation and then downstream studying at the single-cell level. So from each of these two models, they collected about 600 red-labeled cells and they collected these cells at four different time points, that were essentially at 12 hour intervals, and they did this starting at embryonic day 7.5, and that's because that's the time point in the mouse where these second and first heart fields are starting to develop. Cindy St. H:                         What they found, by using single-cell RNA sequencing, is that the first heart field cells differentiated into cardiomyocytes, in what they called a gradual, wave-like manner, while the second heart field cells differentiated in what they referred to as a more stepwise, defined pattern. The team also found high expression of migration factor MIF in first heart field cells and they found MIF's receptor CXCR2 in the second heart field progenitor cells. This suggests that perhaps the first heart field cells could regulate the migration of the second heart field cells. Sure enough, blocking MIF- CXCR2 interaction in cultured mouse embryos prevented second heart field cell migration and also prevented normal development of the right ventricular outflow tract structures. So together these results provide insight into both normal heart development and also suggest what might go awry in certain congenital heart malformations. Cindy St. H:                         The next paper I want to highlight is titled Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease. The first author is Benoit Ranchoux and the corresponding author is Francois Potus, and they are from the Pulmonary Hypertension Research Group at Laval University in Quebec City in Quebec, Canada. The disease pulmonary hypertension can arise from a number of causes, but one of the main drivers of what's called group two pulmonary hypertension is left heart disease. Left heart disease itself is caused by several conditions, such as diastolic dysfunction, aortic stenosis, which is a disease that I study, or mitral valve disease. All of these pathologies result in the left heart not beating efficiently or exerting too much energy. Cindy St. H:                         More than half of all group 2 PH patients also have metabolic syndrome, and metabolic syndrome is a condition that is ever increasing in the modern age, especially in America, and it's characterized by obesity coupled with pathology such as dyslipidemia, type 2 diabetes and high blood pressure. Metabolic syndrome is also marked by elevated levels of the inflammatory cytokine IL6. Rat studies have shown that IL6 can induce proliferation of the pulmonary artery smooth muscle cells and consequently, pulmonary hypertension. Cindy St. H:                         In this study Ranchoux and colleagues pulled together all these different pieces in a rat model and essentially want to test left heart disease coupled with metabolic syndrome coupled with does pulmonary hypertension happen or get worse? What they found was really interesting. Left heart disease was induced in a rat model using super coronary aortic banding and then metabolic syndrome was induced with a high fat diet feeding, or with treatment with Olanzapine, which is a second generation anti-psychotic agent, and it's known to induce metabolic syndrome not only in rats, but also in humans. The data from this paper show that inducing metabolic syndrome in rats coupled with left heart disease resulted in elevated IL6 levels and also greatly exacerbated pulmonary hypertension. Cindy St. H:                         Digging into this mechanism, they found that inhibition of IL6, using either an anti-IL6 antibody or by reducing IL6 secretion from macrophages, using the diabetes drug Metformin, ameliorated the pulmonary hypertension in the rats. They then went on and looked at human samples and they found that IL6 was higher in the lungs of pulmonary hypertension patients and that this IL6 could induce proliferation of human pulmonary artery smooth muscle cells. So together these data suggest that the observation in rats holds true for humans, but further goes on to suggest that perhaps Metformin, which is a well-known, well-used diabetic drug, could perhaps be used for the potential treatment of Group 2 pulmonary hypertension patients.   Cindy St. H:                           In the August 16th issue, we have an article titled Increased Activated Protein C Response Rates Reduce the Thrombotic Risk of Factor V Leiden Carriers but not of Prothrombin 20210G>A Carriers. That is some title. The first authors are Heiko Rühl, and Christina Berens, and Dr Rühl is also the corresponding author, and they are at the Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, in Bonn, Germany. Genetic studies have found two mutations that convey particularly increased risk for venous thrombo-embolism, and VTE is also more commonly referred to as deep vein thrombosis. These mutations are called factor five Leiden mutations, or FVL, and the prothrombin 20210G>A mutation we're just going to call F2. Interestingly, the penetrance of these mutations, or how likely they are to exhibit a phenotype, is variable. Some individuals with mutations never experience deep vein thrombosis, while others experience multiple episodes. Cindy St. H:                         As a group, the FVL carriers produce a higher than normal level of an anticoagulation factor called APC, or activated protein c. They also produce high levels of the pro-coagulation factor thrombin, and the authors of this study wondered if it was the balance, or rather perhaps an imbalance, of these factors that could explain the phenotypic variations in the patients that harbor the same mutation. To test this, they collected 58 patients. 30 were FVL and 28 were F2 carriers, and they injected these patients with clotting factors and examined their response rates. In both of the groups, about half of the individuals had no history of deep vein thrombosis, while the other half had had at least one episode. Cindy St. H:                         The team found that while both types of mutations were associated with increased APC and thrombin levels after coagulant injection compared with a control group, in the FVL group lower APC levels correlated with a much higher risk of deep vein thrombosis. In other words, the FVL carriers who had never experienced deep vein thrombosis produced higher levels of APC. Translating this to the clinic, perhaps APC testing could help identify individuals who are carriers of the FVL mutation and determine which of them are at higher risk due to lower levels of APC. Cindy St. H:                         The last paper we're going to highlight before switching to our interview is titled The Human- and Smooth Muscle Cell Enriched lncRNA, SMILR, Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling. Now that is a crazy title! We’ve got to limit these names here this is difficult. The first authors are Amira Mahmoud and Margaret Ballantyne and the corresponding author is Andrew Baker, and they're all from Queens Medical Research Institute, BHF Center for Cardiovascular Sciences at University of Edinburgh in Edinburgh, UK. Cindy St. H:                         Before we dive into this article, I think it's important that we give a quick explanation of what is a lncRNA? lncRNA, or L-N-C RNA, stands for long non-coding RNA, and these are described as being transcripts which are made into RNA that are in lengths exceeding 200 nucleotides. So that differs them from micro RNAs or peewee RNAs or snRNAs, and they are classically or, I guess originally, considered not to be translated into protein. However, I think now more and more studies are finding that perhaps they are made into peptide sequences. However it's not fully clear what the function of those sequences are. Similar to micro RNAs, they also harbor regulatory functions that can control cellular functions by helping to fine tune the regulation of gene transcription and translation. Cindy St. H:                         Largely speaking, vascular smooth muscle cells are quiescent, but they can be stimulated to proliferate and migrate following injury to the vessel wall. While such activation of smooth muscle cells is essential for wound healing, these same processes are operative in vascular disease or after a cardiovascular procedure. Often what happens is an excess of proliferation of the smooth muscle cell wall can lead to dangerous occlusion of the blood vessel. The long non-coding RNA, SMILR, was recently identified as a promoter of smooth muscle cell proliferation and now in this article, Mahmoud and colleagues have defined its mechanism of action. Through transcriptome analysis of human smooth muscle cells, in which the levels of SMILR were either modulated to be increased or suppressed, the team found that lncRNA regulated expression of several genes involved in mitosis, or cell division. Furthermore, RNA interaction experiments revealed that the messenger RNA encoding the mitotic centromere protein, CENPF, was a direct interaction partner of SMILR. So just like the suppression of SMILR, the inhibition of CENPF resulted in reduced mitosis of the smooth muscle cells. Cindy St. H:                         The team then went on to show the inhibition of SMILR via RNA interference could block the smooth muscle cell proliferation ex-vivo, and they did this using intact sections of human saphenous vein. These results suggest that targeting this lncRNA could be a potential clinical treatment in situations where vessel occlusion is at risk. Cindy St. H:                       Okay, so now we're going to switch and have our interview with Drs Denisa Wagner and Nicoletta Sorvillo, and we're going to discuss their paper entitled Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis after Vessel Injury. Thank you Drs. Wagner and Sorvillo for joining us today. I think a funny thing is that between Nicoletta in Switzerland, me and you on the East coast and my producer on the West coast, I think we're spanning about nine hours of time zones here. Thank you all for taking the time, whatever time of day it is, wherever you are. Dr Wagner:                         Thank you. Cindy St. H:                         I was wondering, Denisa, if you could please introduce yourself and tell us a little bit about your background. Dr Wagner:                         I am a vascular biologist. I was always interested in platelets, endothelial cells, and leukocyte. I started with a background of von Willebrand factor research. Von Willebrand factor is the most important adhesion molecule for platelets and it is stored in endothelial cells as we have found very early on, in an organelle called Weibel-Palade bodies. So my work on this paper is actually related to the first observation I ever made scientifically of showing that von Willebrand factor is released from endothelium. Cindy St. H:                         Wow, that's wonderful. And Nicoletta, could you please introduce yourself and tell us a little bit about your background? Nicoletta:                            I'm Italian, I studied in Italy and I did my PhD in the Netherlands, and I've always worked on inflammation and thrombosis during my PhD. One of the major proteins I was working on is ADAMTS13. That is again a protagonist of our paper. Then I moved to Boston, where I had the pleasure to be able to work in Denisa Wagner's lab, and there I continued working on inflammation and ADAMTS13 and now currently I moved here to Bern and I'm bringing my expertise here, but I moved a little bit towards ischemia and reperfusion injury and transplantation. Cindy St. H:                         Interesting. Wow. Denisa, I want to circle back to this factor being one of the first findings that you worked on. How does it feel to still be working on it? Is it still exciting? Dr Wagner:                         It is nice and it's refreshing to come back to it. I did a lot of stuff in between. We did a lot of adhesion molecule work, leukocyte rolling. We made the early knockouts like b-selectin, p-selectin, and von Willebrand factor knockout as well. So it's fun. And by the way, since Nicoletta said that she was Italian, I am originally Czech, from Prague. Cindy St. H:                         Interesting. I did not know that. And actually, Denisa, I don't know if you remember, but when I was a graduate student in Katya Ravid’s lab, we collaborated with you to use some of this intravital imaging on one of our JCI papers. Dr Wagner:                         Oh right, right. I was wondering where I knew your name from. That's funny. Cindy St. H:                         Yes. Yeah, yeah. So it's wonderful to speak to you again. Really I wanted to interview you because I loved this paper, not only because it was a really interesting mechanism that actually I wasn't very well aware of, this citrullination and also because of the beautiful intravital imaging you could do and then link it to patient disease states. Maybe you can start by telling me what's the clinical unmet need or the question that your paper was trying to address? Nicoletta:                            So Denisa Wagner's lab always has worked on neutrophils and NETs and it has been shown that these NETs are involved in thrombosis. So we were curious what happens when even the enzyme that is important to make these NETs, this extracellular DNA, does when it's in the circulation. And this enzyme is of course PAD4 and it is known that it can modify our [inaudible] residues on protein through this process of citrullination. So we went to see if it could modify plasma proteins and as Denisa already said, an important molecule that initiates thrombotic processes is vWF that can be released during inflammation or when there's a damage to the endothelium .  So we went to see what happens if the enzyme that is involved in removing this vWF that is ADAMTS13 happens if it gets modified by this enzyme path. So our question was more like what happens if you have the release of an enzyme that is normally intracellular? What would happen if it gets outside of the cell? Cindy St. H:                         Interesting. So before we get too deep in the weeds, what is citrullinization and why is it important? What do these modifications do? Nicoletta:                            It changes the charge of a protein. It goes and modifies arginine, and it transforms it into citrulline. It changes the charge of a protein and therefore you can imagine if you change a charge of protein it can change even the structure of a protein and if you change the structure then you can change the function. So this is what this modification can do. Cindy St. H:                         And that's what it's doing on the ADAMTS13? It's essentially altering or inhibiting its function? Nicoletta:                            Yes. What we saw is that we can find these citrullinated residues on ADAMTS13 and we identify them by mass spectrometry and then we saw that if it is modified by citrullination, it loses its activity so it doesn't function anymore. Cindy St. H:                         Interesting. Very neat. Could you talk a little bit about the process of where this is happening naturally and where it goes wrong in a diseased state such as either sepsis or aging or just general clotting? Dr Wagner:                         These neutrophil extracellular traps are generated often more during a disease state when there is either an infection or exacerbated inflammation that would be like in sepsis or for example, in a metabolic disorder like diabetes. So there is a lot more of them being generated. Also, for example, in diabetes, PAD4 is elevated inside the neutrophil four-fold. If it's released from diabetic neutrophils , then there would be really a lot more of it. And in aging also, then a NETosis becomes much more prominent. We have done this only with mice, but I believe that it will be also, unfortunately, the case with humans that old mice make a lot more NETs than young mice. Therefore this is relevant to look. Since thrombosis increases both with aging, the incidence of thrombosis, thrombosis increases with a disease like diabetes or in sepsis, you will have micro thrombosis. We thought it would be interesting to study those processes as well, then. Cindy St. H:                         That's really neat. One of the techniques that you utilize heavily in this paper and several of your papers that I'm familiar with is this intravital imaging or intravital microscopy. Just so people can get a sense of what it is you're actually doing, could you maybe describe what that experiment is? Maybe Nicoletta, you could describe that for us? Nicoletta:                            During intravital microscopy, we are able to image in vivo, a vessel in a live mouse. And in this case we use mice and we can label leukocytes and platelets and then look at them in the vessel in vivo and you can then look for a thrombus forming or you can look at the [inaudible 00:23:43] already had leukocyte rolling and you can see what is happening inside the vessel during a proper blood flow and you can damage the vessel in some cases. In our case, in our paper, we do a ferric chloride injury where we damaged the vessel with ferric chloride and therefor you initiate a thrombus development and you can visualize it in vivo and real time. Cindy St. H:                         Excellent. Yes. And hopefully our listeners will look and see the beautiful pictures because those are some serious clots you get forming in the vessels. Yeah. Yeah. And so the other thing that you did was confirming the modification on ADAMTS13, you use mass spectrometry. How difficult was it to confirm that what you thought was happening was happening using that technique? Nicoletta:                            It was very difficult and challenging, I have to say. Dr Wagner:                         See, I would love to hear more about it because you often read, Oh, then we did mass spec and we got this beautiful whatever. Could you tell us a little bit about the struggles? Nicoletta:                            It was quite a struggle. I mean I think trying to identify such a modification that is very, first of all, novel and it changes the math only of one thousandth it's very difficult. To identify you can confuse it with a deiminasion again because of the increase of mass is the same. And another problem was that ADAMTS13, our plasma protein, is low abundance in plasma compared to other plasma proteins like Fibrinogen, that is very, very much abundant. It was a challenge for this reason. So trying to pinpoint out a small, tiny modification already in a protein that is not so abundant in plasma and therefore we have to use this probe, this Biosyn PG program. And we did this in collaboration with Paul Thompson's lab and we were able to then fish out what was modified by the citrullination, but it was very challenging. We tried several different types of techniques that were different types of approaches before being able to show that in vivo. So in human samples we can find this modification. Dr Wagner:                         Nicoletta grew a lot of gray hair during that period. (laughs) Dr Wagner:                         It took us about a year to figure out how we could detect it in vivo because also some antibodies to ADAMTS13 don't work so well. It's a minor protein, but she figured it out. Cindy St. H:                         Wow. That's amazing. Well, congratulations on that. That's excellent. I guess what I'm wondering now is what are the next steps and what might your findings mean in terms of future potential therapeutic options or treatment strategies for different detrimental thrombotic events? Dr Wagner:                         I think what we have really verified that the PAD4 remains active when it circulates in circulation, when the release, and there are several diseases in which PAD4 levels were found to be elevated, like rheumatoid arthritis and what it means in general. That is PAD4 is actually causing havoc. It is citrullinating probably quite indiscriminately. Several proteins may be finding the exposed parts. Maybe it could have some binding sites, but I think it just affects proteins in general and for some of them like, ADAMTS13, this had a very detrimental effect. So in diseases where there is a lot of PAD4, one has to worry about the consequences of citrullinating things and perhaps spot for inhibitors should be used. What do you think, Nicolleta? Nicoletta:                            I totally agree with you. Yes, I totally agree. I mean PAD4 outside the cell could be dangerous, of course. However, we never know if there's something good that it can do that protects by citrullinating proteins so there's so much more to discover about extracellular PAD4 and its effect on the environment. Dr Wagner:                         However, Nicoletta when she wrote a paper at the end she decided to talk about ADAMTS13 as a therapeutic because both she and I, we are convinced that ADAMTS13 it's a possible future therapeutic and it's already given to patients who are lucky in ADAMTS13 and may be given to patients who have thrombotic events in the future, like stroke or myocardial infarction. And these situations are highly pro-inflammatory. Therefore, we would anticipate that in these situations, NETs, and we know NETs are released and therefore, what Nicolleta suggests at the end, is that introducing together with ADAMTS13 an inhibitor of citrullination would be a good thing so that the protein, the ADAMTS13, remains active in circulation. Cindy St. H:                         Wow. So a two-hit strategy. I mean I can think of a handful of potential diseases this would be good for. You know, patients with sickle cell, there's a lot of NETs released then thrombotic events or even stroke. I mean, do you see that this is a potential mechanism that's common to all thrombotic disease or just kind of specific subsets? Nicoletta:                            All is a big word I think, but I think that there are many disorders where together with a thrombotic event, you can find also low levels or low activity of ADAMTS13 and in many of these disorders, nobody knew really why you have a reduction of ADAMTS13 activity, what is happening? Why do you lose this ADAMTS13? What we believe, but of course further studies are needed, is that maybe in these disorders, what is causing the loss of ADAMTS13 is this release of PAD4 because in stroke or in some DIC sepsis, you can find patients or many patients who do have low levels of ADAMTS13 activity and we believe that it's due to maybe citrullination by PAD4. So in that case, I agree with you maybe then that this therapy can be used in different thrombotic events as you suggested. Cindy St. H:                         So what does PAD4 normally do when it's intracellular? What is its, I guess healthy role, in a cell, if it has one? Nicoletta:                            So what is known now is that it really regulates transcription. So that's very important because it citrullinates transcription factors to facilitate transcription. And what Denisa Wagner's lab has identified is that it's extremely important to form these NETs because it citrullinates histone and allows the unraveling of the chromatin and then the NET release. However, it's extremely interesting. We are very interested to understand what else does it do within the cell. Cindy St. H:                         Interesting. That is so neat. I love this story. Dr Sorvillo and Dr Wagner, thank you so much for joining us and congratulations again on a wonderful paper. Dr Wagner:                         Thank you. Nicoletta:                            Thank you for having us and inviting us. Thank you. Cindy St. H:                         So that's it for the highlights from our August issues of Circulation Research. Thank you for listening. This podcast is produced by Rebecca McTavish and edited by Melissa Stoner and supported by the editorial team of Circulation Research. Copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Cindy St Hilaire and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

Continuing education episode! Are we ignoring the most important coag factor when transfusing bleeding patients? Melissa Cushing thinks the contribution of replacing critically low fibrinogen levels to survival of bleeding patients may be under-recognized. She describes the current evidence for early fibrinogen replacement in the bleeding patient, logistical challenges transfusion services face, studies providing insights to desired fibrinogen target levels, and future options to provide early fibrinogen replacement with increased efficiency and safety.

A talk about David Foster Wallace, evolution, and what do when the thrombolysis bisque hits the fan.

You phone goes off - you roll over it is 2am - when you pick up it is a theatre nurse calling to ask if you can urgently come to the hospital immediately - the team are too busy to talk to you. The nurse tells you a woman has just arrived via ambulance from another small peripheral hospital. She had an emergency caesarean about 6 hours ago and hasn't stopped bleeding since. She has had 4 units of red cells and 4-5 litres of saline but nothing else. When you arrive 15min later surgery is underway but the surgical team tell you "everything we touch is bleeding" and you notice that she is even bleeding from the skin around her iv...... The anaesthetic registrar turns to you and says - "lets give her the fibrinogen concentrate -  we need to get on top of this coagulopathy right now!......" (*Fictitious case example) Hi Everyone, This week we are joined by a colleague and a great friend of mine Dr Hamish Mace, one of the co-authors of an article in the 2017 edition of Australasian Anaesthesia (aka the Blue Book) entitled "Fibrinogen concentrate for the treatment of acquired hypofibrinogenaemia". Hamish is a consultant anaesthetist working in Western Australia - he works at Fiona Stanley Hospital a large tertiary centre in metropolitan Perth - but has also worked in the past in remote regional centres in WA, in retrieval medicine for the RFDS (Royal Flying Doctor Service) and spent time on fellowship in Toronto Canada. Hamish co-ordinates the preoperative anaemia correction service, is on the hospital transfusion committee, has a strong interest in many aspects of patient blood management. In the interview we briefly discuss the role of fibrinogen in the acquired coagulopathy that often develops during major haemorrhage, the historical treatments used (FFP, cryoprecipitate), the history of fibrinogen concentrate and where we think fibrinogen concentrate might fit into the current management of major haemorrhage - both in tertiary but also remote, regional and retrieval situations. For those of you who are interested in reading on this topic in detail here is the link to the ANZCA website page where you can access the article written by Hamish and Mansi - the article itself has many great references. Their article is in the 2017 edition. Check out all the other great critical care and anaesthesia articles in this book - a quick shout out to Richard Riley the editor of this great biannual publication. http://www.anzca.edu.au/resources/college-publications In the interview we also talk about the value of measuring fibrinogen an coagulation rapidly with point of care viscoelastic tests. Check out our ROTEM learning package right here on this website (of which Hamish was also a co-author). ROTEM learning package Advice on mixing and administering fibrinogen concentrate: https://youtu.be/7UP2Y1dH9QI  

From scabby knees to life-threatening strokes, this important protein is the fundamental link in the complex molecular chain that forms blood clots.

Listen in as Dr. Mike provides the answers to a wealth of health and wellness questions.Here you'll find the answers to a wealth of health and wellness questions posed by Healthy Talk fans.Listen in because what you know helps ensure healthy choices you can live with. Today on Healthy Talk, you wanted to know:Dr. Sinatra has been suggesting nattokinase for some time to help reduce the amount of fibrin in the bloodstream to prevent clotting, thereby reducing the chance of a heart attack. Ralph Holsworth talks about other things to use, like serrapeptase for heart attack prevention. Do you have an opinion on nattokinase or serrapeptase?Dr. Mike things that there should be more research on both of these types of therapies. Inflammation is part of most diseases, and Dr. Mike believes it's crucial to get inflammation under control to help prevent disease. Inflammation occurs when there are too many proteins within your blood. Blood clotting also happens because of the excessive amount of proteins that are in your blood. Fibrinogen is what doctors target to help reduce blood clotting with enzymes like nattokinase or serrapeptase.In Dr. Mike's opinion, nattokinase is the better therapy, because it targets fibrinogen more specifically and more potently.If you have a health question or concern, Dr. Mike encourages you to write him at askdrmikesmith@radiomd.com or call in, toll-free, to the LIVE radio show (1.844.305.7800) so he can provide you with support and helpful advice.

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.

Atherosklerotische Krankheitsbilder, insbesondere die koronare Herzerkrankung und der akute Myokardinfarkt sind die häufigsten Todesursachen in Deutschland. Dementsprechend häufig sind diese der Grund für die Alarmierung eines Notarztes. Bisher konnten einige Risikofaktoren für das Auftreten atherosklerotischer Veränderungen identifiziert werden (z. B. arterieller Hypertonus, Nikotinabusus, Diabetes mellitus). Diese etablierten Risikofaktoren werden aber nur bei 30-50% der kardiovaskulären Erkrankungen nachgewiesen (113). In den letzten Jahren wurden vermehrt Untersuchungen zum Einfluss der Blutviskosität auf die Pathophysiologie der Atherosklerose durchgeführt. Diese zeigten Veränderungen der rheologischen Eigenschaften des Blutes bei koronarer Herzerkrankung, peripherer arterieller Verschlusserkrankung und arteriellem Hypertonus. Die Blutviskosität stellt die visköse Komponente des peripheren Gesamtwiderstandes dar. Ihr Einfluss auf die Perfusion in diversen Bereichen des Gefäßsystems mit niedrigen Scherraten, z.B. den Koronarien, gewinnt an Bedeutung, wenn die vasomotorische Autoregulation limitiert ist, wie beispielsweise bei der koronaren Herzerkrankung. Um diese lokale Hyperviskosität zu kompensieren ist eine Steigerung des Blutflusses nur schwerlich oder gar nicht möglich. Im Bereich subtotaler Stenosen kann so eine Erhöhung der Blutviskosität potentiell einen rheologischen Verschluss des Blutgefässes auslösen. Pectanginöse Beschwerden sind die Folge. Im akuten Stadium eines pectanginösen Anfalls oder eines Myokardinfarkts wurde die Blutviskosität bisher jedoch noch nicht bestimmt. Deswegen führten wir eine prospektive präklinische Observationsstudie im Notarztdienst durch, um die Rolle der Blutviskosität, die mit einem neuartigen Kapillarviskosimeter (Rheolog®) bestimmt wurde, in der Initialphase eines akuten Koronarsyndroms näher untersuchen zu können. Hierbei wurden 113 Notfallpatienten in die Studie eingeschlossen. Bei 33 der Patienten wurde ein akutes Koronarsyndrom gemäß der Leitlinien der deutschen Gesellschaft für Kardiologie diagnostiziert (91; 92). 60 Notfallpatienten dienten als Kontrollkollektiv. 20 Patienten, deren akute Erkrankungen mit rheologischen Störungen einhergehen, eigneten sich nicht für das Kontrollkollektiv. Sie wurden jedoch in die Multivarianzanalyse der Studie einbezogen, um keine Vorselektion der Studiendaten vorzunehmen. Wir konnten zeigen, dass Patienten in der Initialphase eines akuten Koronarsyndroms ein verändertes Viskositätsprofil aufweisen. Bei allen untersuchten Scherraten konnten im Vergleich zur Kontrollgruppe von Notfallpatienten tendenziell erhöhte mittlere Viskositätswerte festgestellt werden. Das Signifikanzniveau wurde hierbei jedoch nicht erreicht. Die Mediane der Viskositätswerte bei einer Scherrate von 100 s-1 lagen bei den Patienten mit einem akuten Koronarsyndrom mit 5,3 mPa.s [4,8-6,5] höher als bei der Kontrollgruppe mit 4,9 mPa.s [4,2-5,79] (p= 0,059). Die Prävalenz der kardiovaskulären Risikofaktoren arterieller Hypertonus (79% vs. 40%; p

Introduction: The appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates. Methods: This retrospective analysis included trauma patients who received >= 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM(R)). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was < 10 mm. Prothrombin complex concentrate (PCC) was given in case of recent coumarin intake or clotting time measured by extrinsic activation test (EXTEM) > 1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score. Results: Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014). Conclusions: ROTEM(R)-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.

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.

Mon, 1 Jan 2007 12:00:00 +0100 https://epub.ub.uni-muenchen.de/17017/1/10_1159_000113084.pdf Schiffl, Helmut ddc:610, Medizin

Mit transkraniellem Doppler wird die zerebrale Reservekapazität gemessen. Die Probanden werden vor und nach der HELP Lipid Plasmapherese untersucht, dabei wird LDL, Fibrinogen und Lipoprotein A gefiltert. Dadurch verbessert sich die Fähigkeit des Endothels auf höheren Sauerstoffbedarf zu reagieren. Patienten mit Schlaganfall könnten durch diese Behandlung profitieren.

Trotz des kleinen Läsionsvolumens lakunärer Schlaganfälle ist die Progression neurologischer Defizite bei diesem durch Mikroangiopathie verursachten Schlaganfall-Subtyp ein häufiges Problem in der klinischen Praxis. Ziel dieser prospektiven klinischen Studie war, die Häufigkeit, den zeitlichen Verlauf, mögliche zugrunde liegende Pathomechanismen sowie die Prognose der klinisch-neurologischen Verschlechterung bei lakunären Schlaganfällen zu untersuchen. Es wurden 46 Patienten mit akutem lakunärem Syndrom innerhalb von 12 Stunden nach Beginn der Schlaganfallsymptome in die Studie eingeschlossen. Die Beurteilung des Schweregrads der neurologischen Ausfälle erfolgte anhand der National Institutes of Health Stroke Skala (NIHSS) täglich an den ersten drei Tagen nach Beginn der Symptomatik sowie bei Entlassung. Für die Evaluation der Prognose wurde der Barthel Index bei Entlassung und telefonisch nach 90 Tagen erhoben. Die Progression der neurologischen Symptomatik wurde als Verschlechterung um ≥ 1 Punkt im NIHSS im Bereich der motorischen Funktionen definiert. Die Patienten mit progredienten und nicht-progredienten lakunären Schlaganfällen wurden hinsichtlich demographischer Daten, Vorerkrankungen, Vormedikation, der Häufigkeit der lakunären Syndrome, der Lokalisation der lakunären Läsionen, des zeitlichen Verlaufs der klinischen Progression, des NIHSS und Barthel Index sowie hinsichtlich Entzündungsparametern (Leukozyten, Körpertemperatur, C-reaktives Protein, Fibrinogen), Gerinnungsparametern (D-Dimer, von Willebrand Faktor, PTT), der Glutamatplasmakonzentration, des Blutzuckers und Blutdrucks miteinander verglichen. Diese prospektive klinische Studie zeigte, dass ungefähr ein Viertel (23,9%) der Patienten mit lakunärem Schlaganfall eine frühe klinische Verschlechterung innerhalb der ersten 72 Stunden, 81,8% davon sogar innerhalb der ersten 24 Stunden nach Beginn der Symptomatik erfahren. Bei Aufnahme bestand kein signifikanter Unterschied im Schweregrad der neurologischen Ausfälle –quantitativ erfasst durch den NIHSS- zwischen den Patienten mit progredientem und nicht-progredientem Verlauf. 24 Stunden nach Beginn des Schlaganfalls bis hin zur Entlassung war der NIHSS-Score bei den Patienten mit progredienten lakunären Schlaganfällen signifikant höher als bei den Patienten mit stabilem Verlauf. Die Patienten mit progredientem Verlauf hatten eine deutlich schlechtere Langzeitprognose als die Patienten, die sich in der Frühphase stabilisierten oder sogar verbesserten. Lakunäre Schlaganfälle mit progredientem Verlauf waren signifikant häufiger im Bereich der Capsula interna lokalisiert. Die frühe Progression war signifikant mit einer höheren Leukozytenzahl, einer höheren Körpertemperatur und einer höheren Fibrinogenplasmakonzentration bei Aufnahme assoziiert. Diese Ergebnisse sprechen für eine Rolle der Akuten-Phase-Reaktion bei der Progression des lakunären Schlaganfalls. Die Parameter der Akuten-Phase-Reaktion, die reaktiv auf die cerebrale Ischämie erhöht sind, können über komplexe Pathomechanismen den ischämischen Schaden verstärken und somit zur klinischen Progression führen. Die Ergebnisse lassen die Leukozytenzahl, die Körpertemperatur und die Fibrinogenplasmakonzentration bei Aufnahme als Prädiktoren für eine frühe klinische Verschlechterung beim lakunären Schlaganfall vermuten. Für den Blutzucker fanden sich erst am Tag 3 nach Beginn des Schlaganfalls signifikant höhere Werte bei den Patienten mit progredientem Verlauf im Vergleich zu den Patienten mit nicht-progredienten lakunären Schlaganfällen, so dass dies eher als Folge der klinischen Verschlechterung zu interpretieren ist. Bezüglich der demographischen Faktoren, der Häufigkeit der lakunären Syndrome, der Gerinnungsparameter (D-Dimer, vWF, PTT), der Glutamatplasmakonzentration und des Blutdrucks wurden keine signifikanten Unterschiede zwischen Patienten mit progredienten und nicht-progredienten lakunären Schlaganfällen gefunden. Die Aussagekraft dieser Analyse ist durch die kleine Fallzahl mit 46 Patienten eingeschränkt. Weiterführende statistische Berechnungen des positiv prädiktiven Werts der signifikanten Faktoren, insbesondere eine Regressionsanalyse konnten daher nicht durchgeführt werden. Die Ergebnisse sind somit zur Hypothesengenerierung geeignet, um weitere klinische Studien mit größeren Patientenzahlen anzustoßen, die die Rolle der Akuten-Phase-Reaktion bei der Progression des lakunären Schlaganfalls bestätigen und zur Entwicklung therapeutischer, z.B. antiinflammatorischer Strategien zur Verhinderung der frühen Progression beim lakunären Schlaganfall beitragen sollen.

Ziel der vorliegenden Arbeit war es zu zeigen, ob Fibrinogen im reperfundierten Herzen die Interaktion von Thrombozyten und polymorphkernigen Granulozyten (PMN), sowie die Ausbildung von Thrombozyten-PMN Koaggregaten vestärkt. Zudem war von Interesse, ob diese Koaggregate zum Reperfusionsschaden beitragen und inwieweit der GPIIb/IIIa Rezeptor Antagonist Abciximab (c7E3Fab) die PMN-Thrombozyten Interaktion inhibiert und dadurch den myokardialen Reperfusionsschaden vermindert. Die Expression von MAC-1 auf PMN und GPIIb/IIIa auf Thrombozyten wurde mit Hilfe monoklonaler Antikörper gegen CD11b und CD41 im FACS gemessen. Die Versuche erfolgten vor und nach der Koronarpassage durch ein postischämisches isoliertes Meerschweinchenherz, sowie mit und ohne c7E3Fab/LPM19c Inkubation. PMN/Thrombozytenkoaggregate wurden im koronaren Effluat mittels Flusszytometrie und im koronaren Gefäßsystem durch Videofluoreszenzmikroskopie quantitativ und qualitativ untersucht. Die Erholung der externen Herzarbeit wurde an Herzen ohne Zellinfusion, mit Infusion von Thrombozyten und PMN, sowie mit zusätzlicher c7E3Fab beziehungsweise LPM19c Inkubation bestimmt. In der vorliegenden Arbeit konnte gezeigt werden, dass die Reperfusion von ischämischem Myokard die fibrinogenabhängige Interaktion von PMN und Thrombozyten verstärkt. Über die Fibrinogenrezeptoren GPIIb/IIIa auf Thrombozyten und MAC-1 auf PMN kommt es zur Ausbildung von Koaggregaten. Die Analysen der epikardialen Mikrozirkulation mit Hilfe der Doppelfluoreszenzmikroskopie zeigten, dass sowohl homogene Thrombozytenaggregate, als auch heterogene PMN–Thrombozyten Koaggregate im Kapillarsystem reteniert werden. Der durch die PMN–Thrombozyten Interaktion verursachte funktionelle Schaden, konnte in Anwesenheit der Fibrinogenrezeptor Antikörper c7E3Fab (GPIIb/IIIa, Thrombozyten) und LPM19c (MAC-1, PMN) verhindert werden. Die dargestellten Untersuchungen bestätigten die Beteiligung von Thrombozyten am Reperfusionsschaden. Im Mittelpunkt stand dabei die Bindung von GPIIb/IIIa auf Thrombozyten über Fibrinogen als Brückenmolekül an MAC-1 auf PMN. Allerdings wurde die Bildung von Koaggregaten auch in Abwesenheit von Fibrinogen beobachtet, was auf mögliche alternative Interaktionsmechanismen schließen lässt. Weiterhin wurde beobachtet, dass c7E3Fab zwar nicht direkt mit dem für die MAC-1 Detektion verwendeten Antikörper konkurriert, aber die Hochregulation von MAC-1 nach Koronarpassage und die Bindung von Fibrinogen an PMN abschwächt. Eine Erklärung für den Abfall der MAC-1 Detektion nach c7E3Fab Inkubation könnte sein, dass es durch die Blockade der fibrinogenabhängigen Interaktion der beiden Zellkompartimente zu einer verringerten Aktivierung der Leukozyten durch Thrombozyten kommt und damit weniger MAC-1 exprimiert wird. c7E3Fab verhindert die Thrombozytenaggregation, inhibiert die fibrinogenabhängige Interaktion von Thrombozyten und Leukozyten und trägt so möglicherweise zu einer verringerten Aktivierung von MAC-1 auf PMN bei.

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.