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Aro Velmet is an associate professor of history at the University of Southern California, where he is a historian of modern Europe, colonialism, science, technology, and medicine with an overarching interest in gender studies. For Baltic Ways, he shares insights into the progression of LGBTQ+ rights in Estonia and the broader region and the path that has led to legislative change over the past decade.   Mentioned in this episode:Velmet, A. (2019). Sovereignty after Gender Trouble: Language, Reproduction, and Supranationalism in Estonia, 1980–2017. Journal of the History of Ideas 80(3), 455-478. Põldsam, Rebeka, et al. Kalevi Alt Välja: LGBT+ Inimeste Lugusid 19. Ja 20. Sajandi Eestist. Eesti LGBT Ühing : Rahva Raamat, 2023.Elisarion: Elisàr von Kupffer and Jaanus Samma at the Kumu Art Museum in Tallinn Irina Roldugina, UCIS Postdoctoral Fellow, History, Slavic Languages and LiteratureBaltic Ways is a podcast brought to you by the Association for the Advancement of Baltic Studies (AABS), produced in partnership with the Baltic Initiative at the Foreign Policy Research Institute (FPRI). The views and opinions expressed in this podcast are those of the authors and do not necessarily reflect the official policy or position of AABS or FPRI. 

Aro Velmet is an associate professor of history at the University of Southern California, where he is a historian of modern Europe, colonialism, science, technology, and medicine with an overarching interest in gender studies. For Baltic Ways, he shares insights into the progression of LGBTQ+ rights in Estonia and the broader region and the path that has led to legislative change over the past decade. Mentioned in this episode:Velmet, A. (2019). Sovereignty after Gender Trouble: Language, Reproduction, and Supranationalism in Estonia, 1980–2017. Journal of the History of Ideas 80(3), 455-478. Põldsam, Rebeka, et al. Kalevi Alt Välja: LGBT+ Inimeste Lugusid 19. Ja 20. Sajandi Eestist. Eesti LGBT Ühing : Rahva Raamat, 2023.Elisarion: Elisàr von Kupffer and Jaanus Samma at the Kumu Art Museum in TallinnIrina Roldugina, UCIS Postdoctoral Fellow, History, Slavic Languages and LiteratureTranscriptIndra Ekmanis: Hello, and welcome to Baltic Ways, a podcast bringing you interviews and insights from the world of Baltic studies. I'm your host Indra Ekmanis. Aro Velmet is an associate professor of history at the University of Southern California where he is a historian of modern Europe, colonialism, science, technology, and medicine, with an overarching interest in gender studies. Today in our conversation, we speak about recent changes to LGBTQ-plus issues in Estonia and the broader region and the path that has led to where we are today. Stay tuned. Dr. Aro Velmet, thank you so much for joining us on Baltic Ways. Your research interests are pretty varied, right? They stretch across the globe to look at how microbiology became a tool of French colonial governance, all the way to the history of digital statecraft in the Soviet Union and post-Soviet Estonia and in the global south. But today our conversation is going to focus a little bit on your work on gender and the current state of LGBTQ rights in the Baltic states. But before we get there, can you tell us a little bit about yourself and your academic interests?Aro Velmet: Well, thank you, Indra, for inviting me to the show. I am, as you said, primarily a historian of science and technology, and I'm interested in the ways that various kinds of experts make claims on politics and power: how they reformulate questions that we think of as essentially questions of politics—who gets to cross borders, who gets to have various kinds of rights—as questions of technological expertise.So this may mean formulating public health policy, right? If the pandemic breaks out, then who needs to be vaccinated? What kinds of populations need to be surveilled, monitored, and regulated? This is what the first decade of my academic career was dedicated to in the context of the French Empire. Or it may mean questions around gender and reproduction. It may mean questions around how democracy is conducted, which is sort of what I'm researching right now. But I guess at the heart of it really is this question, and really this kind of utopian vision, of using technological expertise to solve these political quagmires, these debates that Western societies have been wrestling with for well over a century, that lots of different scientists have had the idea that maybe the way to break these problems open is through the application of this or that novel technology. So that's kind of what I'm broadly interested in academically. IE: Thank you for sharing that is really interesting. I'm sure that there are many, many different ways you can take that too—a lot of those questions resonate in today's world. Well, returning to the subject at hand today: In the past year or so, we've had some significant legislative steps happen in the Baltic states around LGBTQ-plus rights, particularly in Estonia and Latvia. Estonia adopted a marriage equality bill. In Latvia, civil unions are legal as of July 1st this year. Efforts in Lithuania to recognize same-sex partnerships, however, were also kind of in the legislative mix, but ended up stalling. I wonder if you can give us some insights into where the Baltic states currently stand with regard to LGBTQ rights and, more of some of the historical context of those rights in the region.AV: So I should preface this by saying that I really am not an expert on the histories of Latvia and Lithuania, even though the three Baltic states get lumped into one category very often. They are quite different, particularly in this question of LGBTQ rights.IE: That's fair.AV: To start off, I think the one bit of historical context that is really important is just how rapid and dramatic the shift in public attitudes and the legal situation towards LGBTQ people has been all over the Baltics, and I can speak for Estonia, specifically. And just to give you some idea of that, in 2012—this is a couple of years before same-sex civil unions were legalized—popular support for marriage equality in Estonia stood at roughly about a third of the population. So it was a sort of minority position. And we've now, over the course of twelve years, come to a point where not just marriage equality is now legal, has been legal for just about a year, and it also enjoys growing popular support. It now has majority support and had majority support in 2023 when it was legalized in parliament. So the shift really has been quite dramatic; that's kind of one thing to keep in mind. And I sort of remember when I first started getting involved with this question in 2011, it really was the kind of topic that no mainstream publication, no mainstream politician wanted to touch with a ten-foot pole. We tried to poll legislators, at the time, on their opinion about same-sex marriage or same-sex civil partnerships. And the vast majority of legislators declined to answer the question; they just didn't want themselves to be associated with this. So this situation is now quite dramatically different. The other thing that I already alluded to is that the situation is quite different in different Baltic countries. So while Estonia now has broad majority support to same-sex marriage and overwhelming support, over 70 percent, to same-sex civil partnerships and kind of broad question of do you think homosexuality is acceptable, these numbers are quite different in the Baltic states.So the kind of contrast to this is Lithuania, where a recent survey showed that only barely a quarter of the population supports same-sex marriage: so dramatically different contexts. And to a degree, these are contexts that are explained by history, culture, and politics, right? Lithuania is a strongly Catholic country, and the kind of Catholic discourse that is global and particularly prominent in Poland, but also in other Catholic countries such as France, that really sees homosexuality as a sin and same-sex marriage as an affront to church doctrine, is really something that dominates in Lithuania.I think the situation in Latvia is a bit more complicated, and you probably can tell me more about this than I can tell you. But it seems to me that a lot of that discourse has to do with Russian-oriented political parties and the discourse that is connected to the Kremlin's official position on gay rights and the preservation of so-called traditional marriage.So there's lots of context here that makes these three countries in some ways quite different, but I think they are also similar in that the broad sort of direction of travel over the past two decades has been towards increasing acceptance of the LGBTQ community and increasing moves towards legislation that protects the rights of gay and queer people around the three Baltics states.IE: Thank you for sharing that background. I'm no expert on the situation in Latvia, but it's quite interesting. Edgars Rinkēvičs, the current president, is the first gay head of state in Europe. At the same time, you're right that the discourse is quite difficult and legislatures have taken quite a long time to implement some rulings from the Supreme Court, which has urged them to take steps towards approving civil unions and same-sex partnerships for a while. It's quite a mixed bag. You mentioned the situation in Lithuania and the kind of deep ties to Catholicism and faith. That's something that, I think often, is thought of when we think of resistance to LGBT rights. But you also wrote an article in 2019, called “Sovereignty After Gender Trouble,” where you look at, more specifically, Estonia, which is not really a particularly religious society in the same sort of way. And you look at how the opposition to LGBT rights drew arguments more broadly linking them to demography, state sovereignty, language, resistance to that kind of supranational authority: in this case, it was the European Union. And certainly, demography and language in the Baltic states are quite existential hot topics.So I would love it if you could tell us a little bit more about that research. I found that article really interesting.AV: I think the research was basically spurred by this question of why is this attack on what certain conservative groups called gender ideology—and we can characterize this as a sort of broadly homophobic sentiment—so popular? Not just in Estonia, but in a variety of different places where it seems that just saying that this is a movement that's grounded in religious sentiment doesn't quite explain its broad popularity among many different social groups. And it is true, it is true also in the Estonian case, that a lot of the leading activists of the so-called anti-gender movement, come from religious backgrounds. So in the case of Estonia, they are fundamentalist Catholics. This is particularly puzzling because Catholicism in Estonia is sort of small—there are very few people who are Catholics. Estonia in general is one of the least religious countries in the world. And yet at the same time, this movement gained a lot of traction in the 2010s during this debate over same-sex civil unions.Now, basically what I found in my research when I looked at the kinds of arguments that these anti-gender activists and conservative politicians were making, their arguments weren't really about religion. They weren't really about something like natural law—something that's often invoked in Catholic discussions.But they were really about a question of sovereignty. And the way this argument was made was roughly, like this: The symbol of health for the Estonian state is population growth, right? When the population is growing, then the state is healthy. When the population is declining, then this means that Estonian sovereignty is under attack.And we see this in the Soviet period when mass migration of Russophone citizens threatened the Estonian demographic situation in the 1980s. This is how this argument is made. AV: And we're seeing this in the 2000s where the Estonian population, the kind of natural birth rate is declining. And what this must mean is that Estonian sovereignty is under threat by this different supranational organization, the European Union. The links that these groups draw between the European Union and the Soviet Union are in some cases, very direct. There are cartoons where you have a kind of fat cat Estonian politician bowing toward Moscow in 1988 and then toward Brussels in 2014. And the problem with these kinds of supranational organizations is that they are out of touch with the will of the people. They're out of touch with what people consider to be a healthy way of living, and this is expressed through these programs supporting LGBT rights.So really I think that this tells us quite a bit about what draws the sort of broader population to this kind of rhetoric. It's not really Christian rhetoric, which is quite downplayed, about sinfulness and natural law and righteous living and things like that. It's really a language about giving away power to supranational entities. And in this telling, the support of the political class, of Estonian liberals and social democrats, towards LGBT rights then becomes a kind of proxy for saying, “Look, these are people whose interests lie with Brussels and not with the people in Tallinn or in Paide or in Kohtla Järve or in these small towns that are being forgotten.”And I think actually that move—where gay rights become a stand-in for a kind of liberal alienation and a representation of a loss of sovereignty to supranational institutions—is actually quite revealing because I think that is broadly the same kind of argumentation that is being put forth in Poland by the Law and Justice Party, by Viktor Orban's Fidesz, with a sort of heavy dollop of anti-Semitism thrown in for good measure, and by the Rassemblement National in France as well. And by peeling away the religious layers of this rhetoric, we really get to what is at the heart of the matter.IE: Yeah. Maybe the supranational part is also perhaps not as intensive in the United States, but the idea of the kind of alienation, especially of the rural population and the areas that are underserved, and homosexuality as a kind of stand-in there for politicians is—I think it's instructive also there. As you noted, this article focuses on the backlash to the European Union's more progressive stance. You know, you mentioned Poland and Hungary—these are also the close neighbors of the Baltic states in some ways. But on the other side, you have Finland, Sweden, and Northern Europe—decidedly more progressive in their stances. So I wonder if you could perhaps tell us a little bit about how the international community—be it organizations or be it close neighbors or even further neighbors—have influenced the trajectory for the Baltic states on these questions.AV: Yeah, of course. It's interesting that you bring up the Nordics because I think something that has made a very substantial difference in Estonia's trajectory compared to Latvia and Lithuania is the very close economic and cultural ties to Sweden and Finland and Norway as well. And therefore they were able to benefit from many of the resources of these countries and in ways that are quite material. So Norway's gender equality fund, for instance, has financed a lot of Estonian NGOs, and had for a long time financed the office of gender equality at the Ministry of Social Affairs. Lots of activists, who've been working at this in Estonia for a long time, have either family in Finland or Sweden or hail from there, or sort of Estonian Swedes or something like that, and generally the sort of links and networks with Nordic organizations have been very tight. And so there's always been a lot of people who are willing to do advocacy work in Estonia when in moments where local politicians have not been willing to speak up for gay rights it has been quite easy to get someone like Alexander Stubb, the current Finnish president, to give an interview on the issue, you know, way back in 2011. So I think that has made quite a big difference. I mean, this, in some ways, also opens up the local community to the criticism that they're astroturfing, right: that these organizations are EU-funded organizations that, again, are somehow alienated from the rest of the population. I just want to make very, very clear that this is a very misleading argument. Because it hasn't been for a lack of wanting or a lack of initiative that these organizations have evolved over the time that they have. It's been primarily due to a lack of funding. It's been due to the fact that there simply haven't been funding sources for people to build these organizations within Estonia. So they've gone to supranational organizations like the EU, like the Soros Foundation or various Nordic sources of funding to do it. IE: Maybe we can continue on—because I think we're already on this path—that you can tell us a little bit more about local activism, local organizations, and how that's impacting both the political side legislation but also the social side. That's quite a dramatic statistic that you cited for Estonia, right? In just a handful of years moving general acceptance of same-sex marriage.AV: So the support for same-sex marriage right now is just over half of the population. And you can break this down demographically and see some interesting things there. The below-25-year-olds overwhelmingly support it. Russian-language speakers tend to be more skeptical, but they are, the growth has been, perhaps the fastest over the past couple of years. So yeah, the changes have been quite dramatic. And thinking about the organization and the kind of activists seen in Estonia, some things appear quite different if you look at it, particularly from an Anglophone or an American's perspective, which is that, by and large, organizations in Estonia tend to be more oriented towards either internal community building or kind of professional policy work. Really sort of working together with the Minister of Social Affairs with legislators in the parties who are broadly favorable to LGBT rights, with various ministries and state organizations, rather than having a kind of strong on the streets presence, right? This putting bodies on the streets and really pushing in that form hasn't been a particularly big part of political activism and certainly not in Estonia. I know less about Latvia and Lithuania. And in some sense this has been, I think, both a positive and a negative aspect. Certainly, we've seen how quickly and well conservative organizations have organized, precisely around big public meetings and building a kind of mass base of support for their agenda. And this certainly made the fights in 2014, and to a lesser extent last year, quite complicated. The other thing I think that's worth mentioning, that some researchers like Pauliina Lukinmaa have pointed out, is that the LGBTQ community and the organizations in particular tend to be quite divided along ethnic lines, right? There are many different communities that for a long time didn't really talk to one another and have had very different experiences. In Estonia this has been compounded by the arrival of folks who are fleeing persecution in Russia and also Ukrainian LGBTQ people who have arrived in Estonia with the ongoing war in the past two years. So thinking about how to bring these communities together has generally been one of the challenging aspects. Again, I'm relying here on research that I've read, more than direct experience. IE: Yeah, that is interesting to see how those cleavages also carry over into this type of work and activism. I wonder, what do you see as the future for LGBT rights in the Baltic states? Do you see this growing convergence, this very rapid kind of shift that you've already pointed to continuing and will convergence with Northern Europe may be on the horizon? Is it tangible?AV: Yeah, I think it depends a lot on political contingency. One thing to keep in mind is that, for instance, both the same-sex civil partnership law that was passed in Estonia in 2014, and the marriage equality law that was passed in 2023—these were not foregone conclusions. These were narrow votes, products of a lot of lobbying that could have gone in a different direction had a few things here and there been different. So they were really kind of utilizing the opportunity handed in a moment. And we need to keep this in mind, right? I think the Baltics are broadly in a similar situation all around where small shifts in the political makeup of the country can dramatically change the situation on rights. I think one of the challenges that all three countries will face, and certainly Estonia is seeing this unfold right now, is that generally, the parties that have most steadfastly supported queer rights have been liberal parties in the sense of being sort of broadly on the right, economically speaking. So the Reform Party in Estonia—that's the current prime minister's party—at a certain point, can only go so far in that direction, right? And already after the last elections, we saw quite a bit of debate over whether the winning of marriage equality was really—well, let me think of how to sort of put this, in the best way. That there's a trade-off if you sacrifice, for instance, progressive healthcare policy or progressive taxation policy for something like marriage equality. Because, of course, queer people also need healthcare. In fact, they are more likely to require healthcare. They are more likely to be vulnerable to social dislocation. They are more likely to need government services. They are more likely to experience workplace discrimination. So, they also need stronger labor protections. So, this question of how much do you want to hitch your ride to the liberal bandwagon is one that I think is going to become increasingly acute now that these basic questions of civil rights have been more or less settled. I don't think these are going to be turned back.But now we're starting to see that actually the experience of middle-class queer people in Tallinn can be quite different from poor queer people in the countryside. We are starting to think more about what is the difference between the experience of queer people who speak Estonian versus those who speak Russian. And I think figuring this out is going to be quite the challenge because there is not nearly as much consensus on issues of social policy than there is emerging on this sort of broader question of civil rights. IE: Yeah, that's a really good point to make. Thank you for highlighting it. Well, we're nearing the end of our time, but I want to ask you to tell us a little bit about what you are currently working on and if you have any recommended reading for listeners.AV: Sure, the answer to the first question is going to take us quite far from this conversation since gender and gender studies are a part of all of my research. You know, it's a fundamental part of the human condition, so anything one studies, I think, should have a gender component to it, but it's not the primary topic of my research right now. I'm interested in the history of information processing and governance and the idea of solving politics through computers. I'm following the story from the 1960s and the foundation of various institutes of cybernetics in places like Tallinn, Kyiv, Vilnius, and elsewhere, to the story of the Estonian digital state that emerged in the 1990s and is still kind of the main branding exercise. IE: E-stonia.AV: Yeah, E-stonia, exactly. The digital republic. And, you know, it's still asking questions about the relationship of expertise to power. The way people imagine political communities and the way people imagine bodies. So it carries many of the themes of the stuff that I've researched before, but taking it a little bit closer to the Baltic states.And then as for reading recommendations, I really would love for people to engage with the work of Irina Roldugina, who is, I think, currently at the University of Pittsburgh. She's a fantastic scholar of Soviet social queer history, really a kind of queer history written from the bottom up. And it's this really phenomenal reading. She's found archives that are just astounding in what they reveal, but also in how difficult it is to really discover queer voices in the archive, which have tended to marginalize them throughout the 20th century. Folks who read Estonian, I really would like to recommend the collected volume titled Kalevi Alt Välja, which is edited by my friend and colleague Uku Lember and Rebeka Põldsam and Andreas Kalkun, which chronicles again, sort of, bottom-up queer histories in Estonia from the 19th century to the present. And I think it'd be a very nice companion to this exhibit on queer Balto-German art that's right now running at the National Art Museum in Tallinn. So, also really, really interesting stuff—again, uncovering a part of Baltic queer history that I had no idea about, personally. And it's great art to boot. So yes, lots of good stuff out there. IE: Those are excellent recommendations. We'll be sure to link them in the bottom of our podcast notes. And I want to thank you so much for taking the time to speak with us, for sharing your perspective on your vast array of research topics, and for honing in on this subject with us this time. But perhaps we'll have to speak again on some of your other work. So I just want to thank you. Thank you so much.AV: I would be happy to talk more. Thank you for inviting me. IE: Thank you for tuning into Baltic Ways, a podcast from the Association for the Advancement of Baltic Studies, produced in partnership with the Baltic Initiative at the Foreign Policy Research Institute. A note that the views and opinions expressed in this podcast are those of the authors and do not necessarily reflect the official policy or position of AABS or FPRI. I'm your host Indra Ekmanis. Subscribe to our newsletters at aabs-balticstudies.org and FPRI.org/baltic-initiative for more from the world of Baltic studies. Thanks for listening and see you next time. Image: Facebook | Baltic Pride This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit fpribalticinitiative.substack.com

In this episode, we explore the science behind microplastics (MPs) and nanoplastics (NPs), focusing on their effects on the liver and gut microbiome. We'll examine how these particles can disrupt cellular functions in hepatocytes, leading to oxidative stress and inflammation, and we will also discuss recent research findings related to MP exposure and gut dysbiosis. We will finish by addressing several strategies to reduce exposure. Topics: 1. Introduction - Introduction to microplastics (MPs) and nanoplastics (NPs) - Overview of their impact on the body, focusing on the liver and gut microbiome 2. Understanding Microplastics and Nanoplastics - Definition and differentiation of MPs and NPs - MPs: Plastic particles less than 5 millimeters (mm) in length - NPs: Subset of MPs, less than 1 micrometer (µm) in size - Sources of MPs and NPs - Primary MPs: Intentionally manufactured small particles (e.g., microbeads, nurdles, microfibers) - Secondary MPs: Degradation of larger plastic objects (e.g., cutting boards) 3. Chemical Composition of Microplastics - Overview of common polymers found in MPs - Polyethylene (PE), Polypropylene (PP), Polyethylene Terephthalate (PET), Polyvinyl Chloride (PVC), Polystyrene (PS), Polyurethane (PU), Nylon, Acrylic - Examples of products containing these polymers (e.g., bottled water, cutting boards, clothing) 4. Health Implications: Impact on Liver Cells - Cellular impact of MPs and NPs - Intracellular and extracellular presence - Specific polymers studied: PET, PE, PP - Mechanisms of cellular disruption - Disruption of mitochondrial membranes - Loss of membrane potential - Decreased ATP production and energy deprivation - Generation of reactive oxygen species (ROS) and oxidative stress - Activation of Kupffer cells and chronic inflammation - Concern for fatty liver disease and insulin resistance 5. Health Implications: Impact on Gut Microbiome - Overview of gut dysbiosis caused by MPs - Physical interaction with gut microorganisms - Chemical effects and associated additives - MPs as carriers for other pollutants or pathogens - Consequences of dysbiosis beyond the gut 6. Practical Tips to Reduce Exposure to MPs and NPs - Use reusable shopping bags - Use a water filter - Avoid single-use plastic products - Choose glass or stainless steel containers - Buy products with minimal plastic packaging - Opt for natural fiber clothing - Use biodegradable or eco-friendly cleaning products - Avoid personal care products with microbeads - Replace plastic kitchen utensils with wooden or metal alternatives - Choose bar soap instead of liquid soap - Avoid plastic cutting boards; opt for wood - Use alternatives to plastic wrap (e.g., beeswax wraps) Thank you to our episode sponsors: ⁠Hardy Nutritionals⁠ ⁠Hardy Nutritionals' Daily Essential Nutrients ⁠Liver Medic⁠⁠ Use code Chloe20 to save 20% on ⁠⁠⁠"Leaky Gut Repair"⁠⁠⁠ ⁠⁠⁠Brendan's YouTube Channel⁠⁠⁠ ⁠⁠⁠https://x.com/livermedic⁠⁠⁠ Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.21.525037v1?rss=1 Authors: Martinez, D., Maldonado, V., Perez, C., Yanez, R., Candia, V., Kalaidzidis, Y., Zerial, M., Morales-Navarrete, H., Segovia-Miranda, F. Abstract: Three dimensional (3D) geometrical models are not only a powerful tool for quantitatively characterizing complex tissues but also useful for probing structure-function relationships in a tissue. However, these models are generally incomplete due to experimental limitations in acquiring multiple ( greater than 4) fluorescent channels simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we performed deep-tissue immunostaining, multiphoton microscopy, deeplearning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatio-temporal singlecell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the structural role of KCs in the murine liver homeostasis. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs alters the number and morphology of the HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, under both physiological and pathological conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Nicoletta Mongini, Chiara Gatta, Sergio Risaliti"Monte Verità Back to Nature"Edizioni Lindauhttps://lindaut.itUn viaggio alla ricerca della libertà, in un luogo dove respirare l'utopia e sognare un mondo diverso. All'alba del '900, la colonia di Monte Verità, stanziata fra i boschi rigogliosi e le dolci colline affacciate sul Lago Maggiore, ha anticipato in modo profetico temi oggi vitali, fra ecologia dell'abitare ed ecologia dell'anima. I suoi fondatori sono stati pionieri assoluti del vivere bio e dell'eco-friendly, della cultura vegetariana e della cura del corpo in senso naturale.Monte Verità. Back to Nature nasce dalla mostra che il Museo Novecento di Firenze e la Fondazione Monte Verità di Ascona hanno dedicato a questa affascinante avventura, ai suoi ideali e ai tanti illustri personaggi che vi furono in diversa misura coinvolti. Dall'anarchico Kropotkin al coreografo Rudolf von Laban, dal dadaista Hugo Ball all'architetto del Bauhaus Walter Gropius, da artisti come Jean Arp e Paul Klee allo scrittore Hermann Hesse, dalla danzatrice Mary Wigman allo psicanalista Carl Gustav Jung, molti intellettuali videro infatti in questo luogo un buen retiro sospeso nel tempo e lontano dal dramma delle guerre e dallo scontro ideologico fra capitalismo e comunismo che stava scuotendo l'Europa. Culla di un'esistenza impostata su ritmi primigeni, Monte Verità divenne così il laboratorio di una contro-cultura alternativa al conformismo borghese e al pensiero dominante.Questo libro raccoglie testi di approfondimento su temi centrali come la pratica vegetariana e i bagni di sole della Lebensreform, la nascita della teosofia e le espressioni libere del genio umano attraverso i linguaggi della danza, della pittura, della poesia, fino allo studio dell'architettura in rapporto con la natura del Monte, dal primo insediamento selvatico alle geometrie rigorose negli anni del Bauhaus.A cavallo fra Otto e Novecento, il Ticino diventò meta di visionari e sognatori che trovarono nella regione terreno fertile per piantare i semi di un'utopia, lontani dal mondo industrializzato, in cerca di un santuario per lo spirito. I fondatori della colonia giunsero dal Nord Europa nel 1900. Uniti da un ideale comune, si insediarono sul Monte Monescia, ribattezzato simbolicamente Monte Verità. Vestiti con gli indumenti «della riforma», lavorarono campi, costruirono capanne, rilassandosi con l'euritmia e i bagni di sole. Adoravano la natura, predicandone la purezza e interpretandola come un'opera d'arte ultima. Nel tempo, il Monte fu frequentato da teosofi, anarchici, psicoanalisti, scrittori e artisti. Acquistato nel 1926 dal banchiere Eduard von der Heydt, il Monte visse una seconda straordinaria stagione culturale, legata anche all'approdo dei maestri del Bauhaus. Oggi è proprietà del Cantone Ticino, gestito dall'omonima fondazione ed è un albergo, un centro culturale e congressuale. Il complesso museale include le capanne aria-luce Casa Selma e Casa dei Russi, Casa Anatta, sede della storica esposizione di Harald Szeemann Monte Verità. Le mammelle della verità, oltre al Padiglione Elisarion con il dipinto panoramico Il Chiaro Mondo dei Beati di Elisàr von Kupffer.IL POSTO DELLE PAROLEAscoltare fa Pensarehttps://ilpostodelleparole.itQuesto show fa parte del network Spreaker Prime. Se sei interessato a fare pubblicità in questo podcast, contattaci su https://www.spreaker.com/show/1487855/advertisement

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514532v1?rss=1 Authors: Aljiboury, A. A., Ingram, E., Krishnan, N., Ononiwu, F., Pal, D., Manikas, J., Taveras, C., Hall, N. A., Da Silva, J., Freshour, J., Hehnly, H. Abstract: An essential process for cilia formation during epithelialization is the movement of the centrosome to dock with the cell's nascent apical membrane. Our study examined centrosome positioning during the development of Danio rerio's left-right organizer (Kupffer's Vesicle, KV). We found that when KV mesenchymal-like cells transition into epithelial cells that are organizing into a rosette-like structure, KV cells move their centrosomes from random intracellular positions to the forming apical membrane in a Rab11 and Rab35 dependent manner. During this process, centrosomes construct cilia intracellularly that associated with Myo-Va while the centrosomes repositioned towards the rosette center. Once the centrosomes with associated cilia reach the rosette center, the intracellular cilia recruit Arl13b until they extend into the forming lumen. This process begins when the lumen reaches an area of approximately 300 m2. Using optogenetic and depletion strategies, we identified that the small GTPases, Rab11 and Rab35, regulate not only cilia formation, but lumenogenesis, whereas Rab8 was primarily involved in regulating cilia length. These studies substantiate both conserved and unique roles for Rab11, Rab35, and Rab8 function in cilia formation during lumenogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr Kosuke Minaga and Masayuki Kitano discuss their article, "Improved liver metastasis detection using Kupffer-phase imaging in contrast-enhanced harmonic EUS in patients with pancreatic cancer" from the February issue.

Nach dem Tod einer am Corona-Virus erkrankten Patientin am Lausanner Universitätsspital ist in der Romandie die Verunsicherung gross. Veranstaltungen wie Schulreisen werden abgesagt. Weil auch die Tessiner zuhause bleiben, sind Einkaufszentren in Nord-Italien regelrechte Geisterstädte. Weitere Themen: * Schwangere sollen im Kanton Waadt entlastet werden bei den Gesundheitskosten. * Der Streit um den Wohnsitz des Bürgermeisters von Romont hat Konsequenzen. * Auf dem Tessiner Monte Verità wird bald das Rundgemälde von Elisàr von Kupffer wieder zu sehen sein.

The importance of the liver for overall healthThe liver is the second largest organ (after the skin) of the human body and probably has the most diverse metabolic activity. It is part of the digestive system and performs many vital functions. Many of these processes happen on membranes, either the plasma membrane or internal membranes of organelles, which are thought to add up to 33,000 square meters of the surface area [Kidd, 1996]. This is one probable reason why supporting healthy membranes through phospholipids may have such a protective effect on the liver.The blood supply of the liver is different from other organs in that it receives oxygenated blood through the hepatic artery, but also deoxygenised blood from the digestive tract through the hepatic portal vein which is rich in absorbed nutrients and other, potentially harmful, substances which have been absorbed from the intestines. From the hepatic artery and portal vein, blood flows into sinusoids which are endothelium-lined spaces (rather than capillaries), from there into central veins and on into the hepatic vein towards the heart and circulation around the body. In the sinusoids oxygen, nutrients and other substances are absorbed into the hepatocytes (liver cells) lining them, whilst compounds manufactured in the liver and nutrients needed elsewhere are excreted into the blood [Tartora and Grabowski].This hepatic circulation system is the main reason for the so-called “first-pass effect” of drugs, the concentration and bioavailability of which can be greatly reduced due to the liver metabolising it post absorption [Pond and Tozer, 1984].The sinusoids also contain Kupffer cells which are part of the immune system. As specialised macrophages, they “tidy up” old white and red blood cells, bacteria and other foreign compounds... continue readingIf you are vegan, this article may be of interest click here

In this episode, Elaina and Kate talk about why it's crucial to do a liver flush. Can you imagine never changing the oil in your car? How about never cleaning your toilets? Things would start to build up. We discuss how the liver functions, and what happens when your liver is clogged. I also discuss in detail how to do your own flush and all the tools and practices that will help your body and organs be as healthy as possible. Here is a link on how to do the cleanse and our guided course: https://online.purejoyplanet.com/p/guided-liver-flush   Is Your Liver Toxic? Toxins are everywhere! Our food, our air, our water, our environment, our thoughts, and our own body's waste create a constant barrage. Let's face it…there is no getting away from the toxins that we all encounter on a daily basis unless maybe you are a monk on a hilltop breathing pristine air. Here are some symptoms of an overloaded liver:   constipation/bloating/digestive problems bad breath skin problems: When the liver is overwhelmed with toxins, the skin (detox organ) takes over by eliminating toxins through its surface in the form of: Eczema, acne, blemishes, skin cancer and rashes weight gain weight loss (inability to absorb nutrients or keep weight on) irritability/anger/rage brain fog/ poor concentration/ poor memory depression/mood disorders/bi-polar estrogen dominance/hormone problems/PMS slow metabolism allergies/ sensitive to everything (chemicals/pollens/foods) hypoglycemia excess gas coated tongue poor protein absorption gallbladder problems/gallstones chronic fatigue high cholesterol and blood pressure frequent colds/ excess mucus/ low immune system fatty liver poor or worsening eye sight itching   Elaina and Kate discuss: When your body is fed a clean diet and the blood, intestines, liver and gallbladder and other organs are encouraged to detoxify 4 times a year or more, you can and will respond with more energy, a longer life, a disease-free life, happier thoughts and loving emotions. We share with you some of the knowledge and information we have gained through doing our own cleanses over the years as well as accumulated knowledge from others. What you use in your house and  put on your skin can affect your health, too. Intention of a liver flush To easily and lovingly clear gravel, stones and sand from the gallbladder and liver and adjoining ducts and vessels, improving overall health and well-being. To compassionately release emotional debris that inhibits personal transformation and our birth right of pure joy. To balance body-mind-spirit, freeing you to live a life in complete confidence and power. To support yourself by nurturing, resting, using tools and seeking emotional, physical and spiritual help as needed.   This is a powerful detoxifying process, which releases liver and gallstones and other debris from the gallbladder and liver, helping restore proper functioning of these organs. Those who have been eating rancid fats, packaged goods, and animal products for years may choose to do a number of flushes to flush out the hardened layers of undigested cholesterol, minerals, and salts that form gallstones and intrahepatic stones. For those who are new to eating high plant based diet, longer preparation (7 -14 days) should be followed to ensure a successful liver flush. The stones and debris need time to soften and dislodge. Think of a dry piece of clay. One would have to pour water over it for some time to begin to break if up. .   Make it fun and easy You can have a great time creating more energy in your body and enjoying very satisfying, delicious food during a cleanse or flush. When you know you are doing something amazing for yourself, it becomes more enjoyable and food will taste better. Keep in mind that during this program your body will experience a cleansing process and de-bulking (weight loss) will occur. It will be fun to look in the mirror and see your face lines diminishing, your skin and eyes getting clearer and your waistline shrinking. Drink plenty of fluids such as the recipes in the back of this book to stay hydrated and content. If you make and eat the recipes provided you will not feel deprived!   Any level of the Purification and Cleanse program is a good cleanse. Better out than in! It is recommended by Dr. David Jubb that the organs above the diaphragm are to be cleansed first. This is called upstream cleansing. This can be accomplished by performing 3 to 12 liver-gallbladder flushes in a row (1 per month). Once the stones are flushed out, you may choose to do a 30-day intestinal cleanse followed by a parasite flush (see table of contents for alternate cleanses). You may also follow your liver flush with a parasite cleanse. Some experts say that doing a parasite cleanse at the same time as your Liver-Gallbladder flush can be very beneficial. I highly recommend doing a 1- month kidney flush (see kidney flush in table of contents) after performing 3 Liver-Gallbladder flushes, at least 2 times a year.   Why Is The Liver So Important? The liver preforms over 500+ functions Carbohydrate metabolism: converts carbs to glucose to be used as energy throughout the body and brain. Creates (synthesizes) amino acids to build proteins Secretes bile and bile salts needed for fat digestion Metabolizes toxins so they can be excreted by the body- DETOX mechanism. Contains special blood cells (Kupffer's Cells) to neutralize bad bacteria and antigens. Keeps blood glucose in balance. Liver cells break down fatty acids which then generates ATP Synthesizes cholesterol and triglycerides within cells Converts ammonia (left over from too many amino acids) into urea, which can then excreted by the urine. (Ammonia is much more toxic then urea) Ability to change and process hormones (thyroid converts T4 into active T3, estrogen, and aldosterone) Detoxes drugs, medications, pesticides, dangerous vaccine components, and environmental toxins Stores and releases (when needed) glycogen, vitamin A, D, E, K (fat soluble), vitamin b-12, copper and iron. Along with the skin and kidneys, the liver forms active vitamin D for the body to use Detoxes and filters everything that comes into the intestines and blood (the only organ that can do this)   After the liver “deals” with the toxins where do they go?   The liver is able to metabolize or change many toxins so they can be eliminated from the body. Some toxins are shunted into the bloodstream and then removed by the kidneys. Some move to the bile, which is a secretion of the liver. Bile flows to the gallbladder for storage and more transformation. Then the bile flows into the small intestine and the toxins are eliminated in the feces. That is, if everything is functioning optimally.   Basics of Purification & Cleansing By choosing to cleanse you are entering into a new phase of your life. You are among a very small percentage of the population who has chosen to take your health and well-being into your own hands and to make purification a way of life.   Your benefits will be beyond measure and may include: Prolonged Life Weight loss Mental clarity Confidence Stronger intuition More love in your life and your heart Compassion for yourself and others More energy Sound sleep Leaner body Better Sex Improvement and/or Healing of numerous conditions including but not limited to arthritis, anxiety, Crohn's disease, eczema, candida, diabetes, chronic fatigue and parasites. Pure Joy!   How Does The Body Become Toxic? Processed (packaged) foods Eating Out Fried Foods Meats and dairy products Overeating! (Even nutritious foods become toxic when overeaten) Shallow Breathing: oxygen creates energy, carbon dioxide is acidic Stress from daily living Lack of Exercise- We need to sweat, move the lymph and oxygenate our cells Dehydration-Eating processed foods and not drinking enough pure water Exposure to chemical, bacterial or physical entities Arguing or fighting (toxic relationships) What to Consume On This Liver Flush Choose from Option 1, 2 or 3 in the back of the manual and create your menu plan from there. If you are able to take some time off work, I recommend Option 1. If you have a busy life, you will want to choose a combination of Option 1 and 2 or even some solid food from Option 3. You cannot get it wrong! Whichever you choose will be perfect for you right now. You can always do another flush next month and pick another option. Don't rush it!   Food and juices to consume on your detox   Enjoy in Abundance: Herbal tea Warm water with lemon Hot veggie broths Raw, unpasteurized green juice (see recipes)   Moderate Amounts of (for a moderate cleanse): Beet and Carrot Juice (use as a condiment by adding ¼ cup into your green juice) Low glycemic smoothies Blended soups Light salads Raw or lightly steamed green, non-starchy vegetables with tasty dressings (see recipes) Low glycemic fruits (berries) Some fat (avocado, coconut and coconut oil) 1 TBS ground sunflower/pumpkin/flax or chia seeds as needed   Why raw, plant-based foods? High in Vitamins and Minerals Enzymes Life Force Alkalizing Highest Vibration of all foods The fiber in raw foods will help naturally cleanse the colon A raw, vegan diet has been shown to reverse many diseases and promote longevity Liquids and Juices provide nourishment and give the digestive tract a rest Green Juices are highly mineralized and are natural diuretics (especially cucumbers and lemons), which flush the kidneys   Foods to avoid on this cleanse Sugar Processed foods Vegetable oils (olive, coconut and sesame oil is okay in moderation) Animal foods (meat, dairy, eggs) Fried foods All vinegar, except apple cider vinegar Store bought condiments Caffeine Processed starches (rice, flour, breads) Baked goods All grains Beans (to hard to digest on a cleanse)   How The Supplements Work Malic Acid (in the form of malic acid powder, apple cider vinegar or apple juice) dissolves and softens gallstones.   Enzymes help dissolve the undigested fats and “blood sludge” in the body.   Magnesium Oxide (Oxy-OxC) helps to oxygenate old debris in the bowels and to keep the bowels flushing, which enables toxins to leave the body quickly. This can create a potentially major release of excess debris, which may have been impacted in the intestines for years.   Epsom Salt (taken only the day of and the day after the flush) relaxes the sphincter of the gallbladder and bile ducts, allowing for the easy passage of the softened, shrunken stones without dehydrating the body as regular salt flushes can.   Olive Oil causes a strong contraction of the gallbladder and liver, forcing out stored wastes, bile, and stones. These wastes and stones are then excreted through the colon as excrement.   PART 2---- SECOND PODCAST REGARDING DETOX Tools And Life Practices The following are items in your Liver/Gallbladder Flush Toolbox, all of which are important practice elements for the week, and some of which we can consider Life Practices that you can count on as permanent acquisitions for your whole life!   Castor Packs with Castor Oil and Cotton Flannel You have one 8 oz. bottle of castor oil and a cotton flannel in your kit. You can use either an ace bandage or a roll of plastic wrap to secure the flannel in place. A heating pad or hot water bottle will be very handy to have. Pour oil onto the flannel on one side until it is saturated with castor oil - about 5 tablespoons or 1/4 cup (once you have used the flannel once, you will only need 2-3 tablespoons each time after that).   You can use the flannel over and over again for years, just wash it once every 3 months or so. Be sure you store it at room temp and not it in the refrigerator as the extra moisture will cause mold.   Warm it in the oven for a few minutes, if desired, or heat the oil in a mini crockpot. Lay the flannel over the midsection of your body especially over the liver, which is on your right side in the lower ribcage area. Wrap the plastic or ace bandage wrap around your waist making sure all the flannel is covered to prevent leaking and to hold the wrap in place. Put the hot water bottle or heating pad on top of the wrap and then wrap a towel around your midsection and lay down with your feet up, or on your right side. This will loosen and soften gallstones and open the lymph system and gall ducts. Be prepared to lie there for 20-30 minutes. Massage your liver and gallbladder in a circular motion. You can leave the pack on for 1 1/2 hours or longer if desired.   Enzymes Food enzymes occur naturally in raw foods and juices. These are not supplements. These enzymes digest food to make nutrients more available in the body so it has the raw materials it needs to run optimally. Digestive enzymes are what are provided for you to take during your cleanse. The ones we take are vegan and are made from healthy bacteria. These enzymes specifically break down nutrition for the organism (human, animal or fungi) to use for nourishment. They improve digestion, and put more energy into your body. Having more energy in the body improves metabolism, lessens fatigue, and helps you function better overall. It also helps to clean out your “blood sludge” which consists of undigested proteins. Metabolic enzymes - These enzymes are exponentially more expensive than digestive enzymes. They are very powerful. They help build various tissues, transfer compounds from one molecule to another, reduce inflammation and reduce or dissolve scar tissue and unclog arteries. Taking metabolic enzyme supplements keeps the sludge and pathogen levels down. Taking any kind of enzyme supplements to help digest your food and keep the body cleaned out means that your own metabolism doesn't have to do this. Your immune system and metabolism can focus on better on other areas of running the body when they aren't bogged down with food digestion. That is why fasting is so important. The body needs all the energy and raw materials it can muster to fight off pathogens and clean the body, so during a fast or sickness, the person temporarily loses their appetite and lays low.   Oxy-OxC or Oxy Magnesium Magnesium Oxide with Vitamin C (Oxy OxC) is an excellent oxygen and magnesium supplement, which keeps the toxins moving out through the bowels during the liver and gallbladder flush. Stir ½-1 teaspoon Oxy--OxC or 3-5 pills into 6-8 oz. water or juice or with your apple cider vinegar or malic acid drink, up to 3 times per day between juices or meals. You should be having 3 bowel movements a day. If you start to have liquid stools, back off or eliminate the Oxy OxC for a day or so. If you are using this in pill form, take between 2 and 4 pills 3x/day and ease up as needed.   Malic acid or Apple Cider Vinegar or Apple Juice If you are taking apple cider vinegar (ACV), stir 3-4 tablespoons. into 1 glass of water and drink this amount 3-4x/day each day. You may also drink 32 oz. of apple juice a day either straight or mixed with water or green juice. If you cannot stomach the ACV and are sensitive to sugars in juice, take 1/2 to 1 tsp. malic acid in 32 oz. of water or tea a day. The more malic acid you take, the more trips to the toilet you will make.   High Quality Olive Oil Use ¾ - 1 cup of an extra virgin organic olive oil for the night of the flush only. Some find that this is delicious and very pleasant to drink when gently mixed in your blender with citrus juice, and drank from a glass through a straw.   Epsom Salts The sulfates in Epsom salts stimulate the release of digestive enzymes from the pancreas. These enzymes help to detoxify the body of drug residues and toxins.   Epsom Drink Recipe (enough for 4 doses) 4  Tbsp.Epsom salts 3cupsWater (1 Tbsp. of Epsom salts to 3/4 cups of water x 4)   *Optional: several drops of stevia and the juice of ½ lemon You can use less Epsom salts if it is too strong for you or you feel it is acting too quickly. You can use more Epsom salts if it is not working well (you will know this by the morning). This will be taken in 4 doses before and after drinking the citrus-oil concoction.   At 6 pm and 8 pm on day 4 and 2 more at 6 am and 8am on day 5 (the morning after drinking the olive oil). The Epsom salts will create a soap-like action in the digestive tract as well as opening the bile ducts to make them wider for the stones to pass through. Stay near the bathroom until your bowels move, which can be anywhere from 30 minutes to 2 hours.   Hot Baths and Light Exercise Take hot baths at least every other day (be sure not to make it too hot or that you have help getting out of the bath if you are prone to light headedness). An Epsom salts bath, with 1 cup of the salts and few drops of essential oil, can bring much relief and promote detoxification through the skin. Stay in the bath 20 minutes. Be sure to rinse the salty water off your body when you are finished. If you have access to steam room or sauna, that will help eliminate toxins also. Keep exercise light, such as walking and yoga.   Sweating Either a sauna or a hot bath are ideal, to help eliminate even more toxins and help eliminate toxic overload. You have 2 different sweat glands: eccrine sweat glands, which are distributed over your entire body, and apocrine sweat glands, located on your scalp, armpits and genital area.   Dry Skin Brushing When cleansing, it is imperative to allow your body to fully detoxify through your skin. The skin is our largest eliminative organ, so use it! Dry skin brushing is an excellent way to not only eliminate excess skin which is blocking proper elimination, but it will help to actually balance hormones and meridian points in the body while stimulating the immune system. This only takes 5 minutes a day. (See skin brushes instructions)   Morning Water Life Practice This is an excellent life practice advocated by David Rainoshek in his Juice Feasting program. David reports that students of Juice Feasting have returned to him year after year remarking on what an important life practice this continues to be, physiologically, mentally, and emotionally.   We are 60-80 percent water (depending on age and lifestyle), and we rely on water for oxygenation, proper blood chemistry, digestion, brain function, reducing inflammation, elimination, etc. When we wake up in the morning, our body has lost 1 to 1.5 quarts of water during the night from perspiration, breathing, and urine production. Drinking a hydrating quart of water with lemon in the first few minutes of the morning helps to wake up our brain, flush our urinary system and bowel, stimulates our digestive system, oxygenates our blood, and generally gets all systems online. Many of us are chronically dehydrated, and this morning water life practice can make a huge difference in the experience and expression of your life!   Morning Lemon Water Recipe 2-4 cups filtered water 1 1/2 Tbsp. lemon or lime juice   FOR FUTURE FLUSHES One month from this flush, you may choose to begin with another. The best time to do a liver- gallbladder flush is after the full moon and before the new moon (a two-week window). Continued flushing will produce darker and older stones that are hanging out in back of the liver and gallbladder. Continue to do flushes until you can do two consecutive flushed with no stones being released.   As with any cleanse, take it easy   Continue to drink water and lemon daily (64 oz. or more) Regular green juices (3x a week or more) Blended foods often (as a meal replacement 1-3x per week) Soaking in Epsom salts when you feel tired or achy Enemas as needed (when feeling toxic or having a cleansing reaction) Continue taking enzymes with meals   Disclaimer “Let food be thy medicine, thy medicine shall be thy food.” ~Hippocrates   Your health is your responsibility, and your body has the power to heal itself. This cleanse is not a treatment for any particular disease, but rather an opportunity to educate yourself as to what I have found to be a way of supporting your health through diet and cleansing. I make no claims for the outcome of your cleanse.   As with any action in life, there are risks involved when starting a cleanse. I have coached hundreds of students through this process, and each person has responded uniquely. Testimonials of people regaining Joy occur frequently.   Your health is your choice. Elaina Love or any members of Pure Joy Planet Inc. do not claim legal responsibility for the outcome of your well-being. Please consult a certified physician if you are on medication as going on a cleanse may decrease, or entirely eliminate the need for medication. This manual has not been reviewed by the FDA. I am not a medical doctor, and make no claims to the treatment of any disease. This podcast is for informational purposes only. It is simply guiding you on your own path to health, which is ultimately your choice.     HOW TO DO THE CLEANSE AND GUIDED COURSE: https://online.purejoyplanet.com/p/guided-liver-flush   HOW TO MAKE YOUR OWN GREEN JUICE- FREE JUICING COURSE: https://online.purejoyplanet.com/p/free-master-juicing-recipe-course   WHERE TO BUY MALIC ACID, CASTOR OIL AND ALL THE LIVER FLUSHING TOOLS: https://store.purejoyplanet.com/collections/cleanseandrejuvenate   ELAINA'S INFO: Facebook: https://www.facebook.com/elainalove Instagram https://www.instagram.com/rawchefelainalove/   KATELYN'S INFO Instagram: https://www.instagram.com/klcuisine/   Our Website: http://purejoyplanet.com/   If you like this episode and want to hear more, please head to itunes, subscribe, rate, and review this podcast. If you'd like us to explore more on any of the topics above, right to us! We'd love to hear from you. Subscribe here:  http://bit.ly/purejoypodcast RESOURCES

That the gastrointestinal tract exerts an important, but unseen role in the pathogenesis of human disease has been a recurring theme over recorded human history. The Egyptians believed that a factor from the gut known as “ukhedu”, or “something disgusting”, was a factor in disease. At the turn of the century, and based on the ideas of Elie Metchnikoff, the gut was held responsible for the process of aging, and multiple innovative approaches were tried to arrest the passage of time. Following World War II, the gut was proposed to contain a factor (later shown to be endotoxin) that contributed to the hemodynamic arrangements of shock, and 30 years ago, we and others proposed that the gut was the motor of multiple organ failure. Today the focus of studies of the gut in critical illness is on the microbiome, and the way in which illness alters it. Each of these paradigms has generated new pathologic and therapeutic insights. The human GI tract contains a remarkable number and diversity of microorganisms in intimate proximity to a complex immune network in the gut wall, the liver, and the spleen. It also contains 25 grams of endotoxin – enough to kill 6 million people. Acute critical illness results in striking changes in this flora, reducing the diversity, and increasing the concentrations of many of the species that predominate in ICU-acquired infections. These organisms can invade normally sterile tissues through aspiration or translocation across an intact gut wall. The flora can be altered not only in its composition, but also in the inherent virulence of its constituents, changes that are induced by interactions with the local intestinal environment. A normal flora is essential to the normal development and maturation of the metabolic and immunologic function of the gut. Conversely, an altered flora can contribute to systemic alterations in immune responsiveness, perhaps through interactions with Kupffer cells in the liver. Moreover endotoxin from Gram-negative bacteria can be absorbed following trauma or other states associated with altered splanchnic perfusion. The spectrum of interventions based on a knowledge of the role of the gut in critical illness is broad. Simple interventions such as early feeding to maintain mucosal integrity are widely used. The impact of other gut-directed measures such as stress ulcer prophylaxis is undergoing re-evaluation. Selective digestive tract decontamination (SDD) has been shown to reduce both rates of nosocomial infection and mortality following ICU admission, but is not widely used for reasons that are not entirely clear. The converse approach – selective colonization either with probiotics or even fecal transplants – is also showing evidence of clinical efficacy. The gut is one of the most complex, yet one of the most elusive organs of the body. As the locus of the most important interactions between the human and microbial worlds, it remains a source of continuing discovery in critical illness.

Hør denne podcast med Katrine og Kim og bliv introduceret til de hvide blodlegemer. Lidt en tilsnigelse, for der snakkes også om celletyper, der findes ude i vævet. Hør om Kupffer og Langerhans celler, hør om Natural Killer Cells og Clint Eastwood.

Background: Portal pressure (PP) results from the interplay ofvasoconstrictors and vasodilators. Recently, we have shown that Kupffercell (KC) activation increases PP. Aims: The role of the vasodilatingcompounds nitric oxide (NO) and carbon monoxide (CO) was studied. Thehypothesis of the present study was that these vasodilators counteractthe PP increase following KC activation. Methods: Livers of ratsweighing 180-200 g were isolated and perfused. KCs were activated byzymosan A (cell wall particles from yeast; 150 mu g/ml). The effects ofNO and guanylate cyclase (GC) were evaluated by the NO synthaseinhibitor N-G-nitro-L-arginine methylester (L-NAME; 0.3 m M, and the GCinhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one(NS-2028, 1.0 mu M); the effects of the heme oxygenase (HO) derivedcompound CO were evaluated by direct administration of CO or inhibitionof HO by zinc protoporphyrin IX (ZnPP IX, 1.0 mu M). Results: Inisolated perfused rat livers, administration of L-NAME or NS-2028further raised PP increase following KC activation. This effect could bereduced by the cGMP analogue 8-Br-cGMP. Inhibition of HO caused markedamplification of PP increase in zymosan-treated organs. CO preventedthis PP increase cGMP independently. Interestingly, KC activation andsimultaneous inhibition of HO augmented the production of prostaglandinsD-2 and F-2 alpha and of thromboxane A(2). Accordingly, indomethacinblunted the increase of PP in zymosan/ZnPP-treated livers. Conclusions:NO restricts the initial PP increase after KC activation by GC-mediatedcGMP. CO from heme degradation limits the increase of PP after KCactivation eicosanoid dependently, but cGMP independently.

Sat, 1 Oct 2011 12:00:00 +0100 http://gut.bmj.com/content/60/10/1307.long https://epub.ub.uni-muenchen.de/21936/1/oa_21936.pdf Steib, Christian J. ddc:610, Medizin

Objective This study aimed to investigate the effect of amiloride on portal hypertension. Amiloride is known to inhibit Na(+)/H(+) exchangers on activated hepatic stellate cells. Methods Liver cirrhosis in rats was induced by bile duct ligation (BDL) or thioacetamide (TAA) administration. The effects of zymosan for Kupffer cell (KC) activation or a thromboxane (TX) analogue (U46619) were tested in isolated perfused livers of cirrhotic rats and in vivo. Downstream mechanisms were investigated using Rho kinase inhibitor (Y-27632) or amiloride. Acute and chronic effects of amiloride and canrenoate on portal pressure were compared in perfused livers and in vivo. TXB(2) efflux was measured by ELISA. The phosphorylation state of moesin (p-moesin) as an indicator of Rho kinase activity and expression of the thromboxane synthase were assessed by western blot analyses. The activity of hepatic stellate cells was analysed by western blot and staining for alpha-smooth muscle actin (alpha-SMA). Results In BDL rats, KC activation via zymosan increased portal pressure. This was attenuated by the Rho kinase inhibitor Y-27632. Increased thromboxane efflux following zymosan infusion remained unaltered by Y-27632. The infusion of amiloride attenuated zymosan- and U46619-induced increases in portal perfusion pressure. In vivo, direct administration of amiloride, but not of canrenoate, lowered portal pressure. In TAA and BDL rats, treatment with amiloride for 3 days reduced basal portal pressure and KC-induced increases in portal pressure whereas canrenoate had no effect. In livers of amiloride-treated animals, the phosphorylation state of moesin and the number of alpha-SMA positive cells were reduced. Conclusions Amiloride lowers portal pressure in rat liver cirrhosis by inhibition of intrahepatic vasocontraction. Therefore, patients with cirrhosis and portal hypertension may benefit from amiloride therapy.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion.

Hepatocellular carcinoma (HCC) is a very frequent tumor worldwide. Its incidence is linked to the distribution of liver cirrhosis and viral hepatitis, which are the main risk factors for the development of HCC. For the evaluation of the cirrhotic liver and for the diagnosis of HCC, multidetector computed tomography (MDCT) proved to be a robust and reliable tool. In MDCT the diagnosis of HCC can be made based on neovascularization with increased arterial and decreased portal venous supply. With modern magnetic resonance imaging (MRI), spatial resolution and robustness increased dramatically. Beside the evaluation of neovascularization by means of gadolinium-enhanced early dynamic MRI, the main advantages of MRI are additional information on tissue composition and liver-specific function. With diffusion-weighted imaging or plain T(1)- and T(2)-weighted sequences, different tissue elements like fat, hemorrhage, glycogen, edema and cellular density can be evaluated. Liver-specific contrast agents give insight into the Kupffer cell density or the hepatocellular function. The integration of all these parts into the MR examination allows for a very high detection rate for overt HCC nowadays, although very small HCCs are still a challenge. Moreover, insight into the different stages of hepatocarcinogenesis can be possible with MRI. Despite its limited availability in some countries, it has to be rendered to be the modality of choice for the distinct evaluation of the cirrhotic liver. Copyright (C) 2009 S. Karger AG, Basel

The ischemia/reperfusion injury (IRI) of the liver is a crucial pathologic process encountered in several clinical situations such as hemorrhagic shock, liver resection and transplantation which can lead to a significant amount of liver dys-function, liver non-function or possible mortality. Despite several promising interventions both pharmacological and physical in nature, including antioxidant therapy, storage manipulation and pre-conditioning, there are no clearly established methods available to prevent hepatic IRI at present. Only through a better understanding of the complex ischemia/reperfusion process one can find interesting targets to develop new strategies to combat this serious injury. This study is aimed at using products of natural and synthetic origin to examine their molecular function and their impact on hepatic IRI. The three approaches are as follows: a. EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) is a standardized extract from the dried leaves of the Ginkgo biloba tree. Its different constituents drawn from the plant offer a wide range of approved medicinal applications.6 Due to its diverse molecular activities affecting the redox system, microcirculation, mitochondrial function to name a few, EGb 761 might be an interesting candidate to be challenged in the multifunctional IRI process. b. Dietary flavonoids have shown to have beneficial therapeutic effects, attributed mainly to their antioxidant capacity. Xanthohumol, the prominent flavonoid of the hop plant, Humulus lupulus L., and its metabolic derivative 3-Hydroxyxanthohumol, both posses promising antioxidant properties in vitro.10, 11 The IRI of the liver is a complex injury process driven by oxidative stress, in which these compounds might be interesting. c. Selective NF-κB inhibition in Kupffer cells using NF-κB decoy nanoparticles is an approach shown to be of great value in the model of warm IR by Dr. Florian Hoffmann in his recent Ph.D. thesis. The cold IR model used in this case was assigned as Kupffer cells are vigorously activated and as it is solely influenced by hepatic factors. Therefore, it is an appropriate model to specify the role of selective NF-κB targeting in the liver in the best possible way.

Kupffer cells, the resident macrophages of the liver, play an important role in host defense and immune system. Moreover, they are also involved in several pathological conditions, like the hepatic ischemia/reperfusion injury. The transcription factor NF-kB is activated during this event. However, to date it was not possible to evaluate the consequence of this upregulation, as NF-kB possesses both detrimental and beneficial properties, regarding of the liver cell type affected. An activation in Kupffer cells is thought to lead to an increased inflammatory response. This hypothesis could not be proven in vivo, as a selective inhibition of NF-kB in Kupffer cells was not possible due to technical difficulties. In this work, solid nanoparticles made of gelatin were chosen to deliver NF-kB inhibiting decoy oligonucleotides exclusively to Kupffer cells in order to block the activation of NF-kB. Confocal scanning laser microscopy showed selective uptake of gelatin nanoparticles into the Kupffer cells without affecting hepatocytes. An increase in NF-kB binding activity during postischemic reperfusion could be diminished by the delivery of decoy oligonucleotides to the resident liver macrophages. In addition, a rise in TNF-alpha mRNA expression assessed by real time RT-PCR was also reduced, thus providing evidence for the effectiveness of this selective targeting. Thus, this work established a novel carrier for a specific Kupffer cell targeting.

The present work follows a course of analytical description, formulation development, and practical application of (NF-κB decoy oligonucleotide-loaded) gelatin nanoparticles. The introduction of asymmetrical flow field-flow fractionation (AF4) in the analysis of colloidal drug carrier systems was exemplarily described for gelatin nanoparticles (CHAPTER I), stable freeze-dried formulations of empty and oligonucleotide loaded gelatin nanoparticles were successfully developed (CHAPTER II), and gelatin nanoparticles were proven as effective tool for the targeted delivery of an NF-κB decoy oligonucleotide to Kupffer cells within a hepatic ischemia reperfusion rat model (CHAPTER III).

Ischemia-reperfusion injury (IRI), which is unavoidable in liver transplantation, is a multifactorial process that can cause non-function or dysfunction of the graft. These complications are the major cause for retransplantation and mortality. An understanding of the mechanisms involved in IRI is essential for the design of therapeutic strategies to prevent IRI and thus improve the outcome of liver transplantation. In recent years, the Atrial Natriuretic Peptide (ANP) has been demonstrated to posses potential in protection against IRI. Nevertheless, many questions remain to be answered about signaling pathways involved in ANP-mediated effects and the processes responsible for its protective properties. The isolated perfused rat liver is a well-investigated model for examination of treatment-mediated effects during ischemia and reperfusion (IR) in the liver. Using this setting, Kiemer et al. demonstrated that ANP-preconditioning increases the activity of p38 MAPK in isolated perfused livers during IR. Functional consequences of an activation of p38 MAPK are widely unknown. This protein kinase has been shown to participate in the regulation of cytoskeletal structures in various cells. Thus, our field of interest was to find a causal connection between ANP-mediated effects and possible cytoskeletal changes during IR in this model. In respect of IRI in the liver, ANP was evidenced to exhibit protective effects also in vivo, but so far nothing is known about signaling pathways responsible for this action. Apototic cell death in the liver during IR is discussed controversial and ANP was demonstrated to mediate anti-apoptotic effects in the isolated perfuse rat liver. We therefore aimed to determine whether ANP mediates effects in the liver in vivo regarding apoptotic death during IR. ANP has not only been shown to have protective properties in IRI but also anti-inflammatory effects in vitro. In previous studies we were able to show that ANP prevents TNF-α production in murine macrophages and whole human blood after LPS-stimulation. Moreover, we ddemonstrated that ANP also inhibits TNF-α-induced aactivation of NF-κB in human endothelial cells and reduces LPS-induced TNF-α secretion in Kupffer cells (KC). With regard to inflammatory processes during LPS-induced endotoxemia TNF-α has been demonstrated to be one of the prototypic pro-inflammatory cytokines mediating many of the immunopathological features of this disease. During sepsis endogenous ANP is suggested to be a regulatory mediator, as the level of its precursor Pro-ANP in blood from septic patients has been demonstrated to be an important rognostic marker for the outcome of sepsis. Another topic discussed in this work is therefore the disease pattern of sepsis. This life-threatening disorder results from a harmful host response to infection and is the leading cause of death for patients in intensive care units. Despite intensive research on the mechanisms involved in the fatal outcome of this disease, few is known about potential therapies preventing death of patients suffering from sepsis. Based on the knowledge of ANP-mediated protective effects during deleterious processes in IRI and its anti-inflammatory properties we therefore aimed to answer the following questions: 1. Does pretreatment with ANP cause cytoskeletal changes in the liver during IR in the isolated perfused rat liver? Which cell type is affected? What are the underlying signaling mechanisms for these changes? 2. Is apoptosis of liver cells during liver transplantation influenced by ANP? Which anti-apoptotic pathway is involved? 3. Are anti-inflammatory properties of ANP able to maintain survival after LPS-induced septic shock? How does ANP influence inflammatory processes during endotoxaemia?

The long-term toxicological effects of hepatic iron overload on the cancer initiating and promoting properties of fumonisin B1 (FB1) were investigated in male Fisher 344 rats. An initial pilot (dose response) study over 15 weeks was performed to determine a level of dietary iron that achieves a high hepatic iron concentration in the absence of significant side effects, to be used in the subsequent long-term carcinogenesis study with FB1. Doses of 1%, 1.5% and 2% dietary carbonyl iron (Fe) were used for 10 weeks, followed by a level of 0.5% Fe for another 5 weeks. After 10 weeks of feeding 1% Fe, the hepatic iron level was 30-fold that of controls. Following the reduction in dietary iron to 0.5%, the hepatic iron level was maintained and side effects were minimal. Irrespective the dose of iron, the iron deposition was initially confined to zone 1 (periportal region), but with increased iron loading, extended to zone 2 (mid-zonal region) and zone 3 (perivenular region). Iron overload was shown to increase hepatocellular proliferation as seen in labelling of cells with 5-bromo-2’-deoxy-uridine (BrdU). Lipid peroxidation, measured as MDA, was also significantly enhanced by excess iron and levels correlated the iron dosage. In the long-term study, half of the rats were submitted to an iron-loading regimen with 1% Fe for 10 weeks, while the other half received the powdered AIN-93M diet only. The iron was then reduced to 0.5%; the rats were divided into four treatment groups: FB1/Fe (n=15); Fe (n=14); FB1/AIN (n=15); and control group (n=15), respectively. FB1 was fed at 250 mg/kg AIN-93M diet for 5 weeks, followed by 100 mg/kg for 20 weeks. The effect of iron on FB1-induced initiation and promotion was assessed in 5 rats from each group at week 35. FB1 was removed from the diet of the remaining rats but iron supplementation continued for 25 weeks. The rats were terminated and the effect of dietary iron on the progression phase of FB1-induced carcinogenesis was assessed. The feed intake of rats from the Fe group (weeks 4-10), and FB1/Fe and FB1/AIN groups (weeks 10-60) was measured daily and the other groups were given averaged feeding accordingly; thus, the total body weight gain (tBWG) gain did not differ significantly between groups. Excess iron significantly increased the liver to body weight (LW/BW) ratio; however, iron could not counteract the mitoinhibitory effect of FB1 on hepatocyte proliferation and the LW/BW ratio of the FB1/Fe group was significantly lower than the Fe group. During the 25-week FB1-treatment period, more foci and nodules of dysplastic cells developed in the FB1/Fe group than in the FB1/AIN group. After removal of FB1, the number of nodules remained constant in the FB1/Fe group, while increasing in the FB1/AIN group. Initially, the pattern of iron deposition was the same as in the pilot study. Hepatocyte necrosis caused by FB1 then resulted in a shift of iron from hepatocytes to Kupffer cells and portal tract macrophages. FB1/Fe resulted in increased hepatocellular proliferation as demonstrated by increased BrdU labelling at 35 weeks. The withdrawal of FB1 reversed this effect and the index of BrdU labelling decreased to even lower levels than the Fe and FB1/AIN groups. Hepatic iron was almost 9-fold that of controls at 10 weeks; a significant increase in the hepatic iron levels in the FB1/Fe group was noticed as compared to all other groups. However, after removing FB1, the hepatic iron decreased to the same level as seen in the Fe group. During the FB1 treatment period, MDA increased in the FB1/Fe group to levels significantly higher than in the FB1/AIN and control groups. The present study suggests a dual role of iron overload in cancer development during FB1-induced carcinogenesis. During the cancer initiation/promotion phase, iron overload in combination with FB1 enhanced the susceptibility of the liver to the formation of foci and nodules; but after removal of FB1, continued supplementation of iron impaired the progression of pre-neoplastic hepatic lesions.

This work characterizes the protective effects of ANP preconditioning in ischemia-reperfusion injury of the isolated perfused rat liver. It was of particular interest to evaluate the influence of ANP on the mode of cell death occurring during cold ischemia and reperfusion and to elucidate the involved signal transduction pathways. Apoptotic cell death was mainly seen after cold liver storage, whereas necrosis was predominant in the reperfusion period. It could be demonstrated for the first time that preconditioning with ANP was able to reduce both apoptotic as well as necrotic cell death. After cold ischemia, in particular hepatocytes were protected against apoptosis. After reperfusion, protection against necrosis comprised hepatocytes and sinusendothelial cells predominantly in the periportal liver areas. As target molecules for ANP action, the cGMP-dependent protein kinases did not seem to be responsible for the conferred cytoprotection. In the liver, no expression of these kinases could be detected and a functional connection could not be derived. In contrast, the cAMP-dependent protein kinases were identified to promote survival. This was further supported by the ability of ANP to directly activate cAMP-dependent protein kinases in livers and hepatocytes. An early transcriptional induction of HO-1 by ANP independent of cGMP could be demonstrated. The induction of heme oxygenase-1 by ANP might not be responsible for the observed hepatoprotection, since inhibition of HO-1 activity did not abrogate the ANP effect. Interestingly, cell-type specific evaluation detected that induction of HO-1 in livers by ANP is exclusively restricted to Kupffer cells. In summary, this thesis gives new insights into the actions of the cardiovascular hormone ANP in IRI of the rat liver. This data helps to understand the mechanisms of how ANP mediates cytoprotection by illuminating effects and potential pathways, an important prerequisite for a rational application in therapy. This work was supported by the Deutsche Forschungsgemeinschaft (DFG: Ge 576/14-2 and FOR 440/1, TP2).

107 Ischemia reperfusion injury (IRI) represents a major clinical problem in liver transplantation and resection. Main pathophysiological events during this injury comprise depletion of ATP, Kupffer cell activation with subsequent formation of reactive oxygen species and inflammatory response. Depending on the severity of IRI, cell damage leads to necrotic or apoptotic liver cell death, resulting in organ dys- or even nonfunction. The present work investigated the potential of α-lipoic acid (LA), a well established agent in the therapy of diabetic polyneuropathy, to reduce IRI of the rat liver. In the system of the isolated perfused rat liver, an experimental model of hepatic IRI, LA was utilized in different treatment protocols and concentrations. As a key result of this study, pre- as well as postischemic treatment with LA was shown for the first time to markedly reduce hepatic IRI. Further investigations characterized the underlying mechanisms of LA action, focussing on the preconditioning protocol. Thereby, LA was shown to increase hepatic ATP content during ischemia and reperfusion, suggesting a better energy availability in these organs. Activation of the redox-sensitive transcription factors NF-κB and AP-1 was reduced by LA, suggesting a decreased inflammatory response of the liver. Most importantly, this work describes for the first time that the protein kinase Akt plays a crucial role in IRI. The cytoprotective kinase was activated by LA preconditioning during ischemia and reperfusion. Blocking Akt activation by simultaneous application of wortmannin, a selective PI-3 kinase inhibitor, abrogated the LA preconditioning effect, showing a causal involvement of Akt in LA-mediated protection from IRI. Therefore, Akt activation can be regarded as a new protective mechanism in hepatic IRI. To conclude, LA treatment might represent a new pharmacological approach in attenuating IRI of the liver.

Background/Aim: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity. Methods: Isolated perfused rat livers were subjected to 1 h of warm ischemia followed by 90 min of reperfusion without (n = 5) or with GSH or catalase (n = 4-5 each). Selective KC activation by zymosan (150 mug/ml) in continuously perfused rat livers was used to investigate KC-related liver injury. Results: Postischemic infusion of 0.1, 0.5, 1.0 and 2.0 mM GSH, but not 0.05 mM GSH prevented reperfusion injury after warm ischemia as indicated by a marked reduction of sinusoidal LDH efflux by up to 83 +/- 13% (mean +/- SD; p < 0.05) and a concomitant significant improvement of postischemic bile flow by 58 +/- 27% (p < 0.05). A similar protection was conveyed by KC blockade with gadolinium chloride indicating prevention of KC-related reperfusion injury by postischemic GSH treatment. Postischemic treatment with catalase (150 U/ml) resulted in a reduction of LDH efflux by 40 +/- 9% (p < 0.05). Accordingly, catalase as well as GSH (0.1-2.0 mM) nearly completely prevented the increase in LDH efflux following selective :KC activation by zymosan in continously perfused rat livers. Conclusion: Postischemic administration of GSH protects the liver against reperfusion injury after warm ischemia. Detoxification of KC-derived hydrogen peroxide seem to be an important feature of the protective mechanisms. Copyright (C) 2002 S. Karger AG, Basel.

The distribution of the functional subsets of porcine T cells, the cytolytic/suppressor (Tc/s) and the helper/inducer (Th/i) cells was studied in cryostat sections of thymus, lymph nodes, tonsils, Peyer's patches, spleen and liver using the indirect immunoperoxidase technique. Three murine monoclonal antibodies (mAb) were used. The mAb 8/1 reacts with an antigen present on all T cells and on cells of the myeloid lineage; the antigen has not yet been characterized biochemically. The mAb 295/33 (anti-T8) binds to the porcine T8 antigen and defines the Tc/s subset, while mAb PT-4 (anti-T4) detects the porcine T4 antigen and defines the Th/i subset. Practically all thymocytes were stained by mAb 8/1. The majority of cortical thymocytes apparently co-expressed T8 and T4, whereas distinct fractions of medullary cells were labelled by either anti-T8 or anti-T4. In peripheral lymphoid organs all three mAb reacted with cells in the thymus-dependent areas and with cells scattered in the lymphoid follicles. In lymph nodes, tonsils and Peyer's patches, anti-T8 and anti-T4 each labelled approximately half of the cells stained by mAb 8/1. In the periarteriolar lymphoid sheath of the spleen, anti-T4 labelled more cells than did anti-T8. The reactivity of mAb 8/1 with the Kupffer cells of the liver demonstrated the expression of the 8/1 antigen on cells of the monocyte lineage. The T8 and T4 antigens could not be detected in acetone-fixed and paraffin-embedded sections, while the antigen recognized by mAb 8/1 remained preserved. Altogether, despite an inverted microanatomical structure of porcine lymph nodes, the frequency and distribution of T8+ and T4+ cells in thymus-dependent areas proved to be similar to those found in other species.