Development of the vertebrate pancreas is a complex stepwise process comprising regionalization, cell differentiation, and morphogenesis. Studies in zebrafish are contributing to an emerging picture of pancreas development in which extrinsic signaling molecules influence intrinsic transcriptional programs to allow ultimate differentiation of specific pancreatic cell types. Zebrafish experiments have revealed roles for several signaling molecules in aspects of this process; for example our own work has shown that retinoic acid signals specify the pre‐pancreatic endoderm. Time‐lapse imaging of live (...) zebrafish embryos has started to provide detailed information about early pancreas morphogenesis. In addition to modeling embryonic development, the zebrafish has recently been used as a model for pancreas regeneration studies. Here, we review the significant progress in these areas and consider the future potential of zebrafish as a diabetes research model. (shrink)

This article explores a new reading of an important section of Part II of Spinoza’s Ethics. It recognizes that Spinoza actually differentiates between the human mind conceived from the viewpoint of its cause and the human mind conceived from the viewpoint of its nature. It shows, most importantly, that Spinoza assigns different objects to those ‘minds’. Consequently they represent different knowledge of the body. It will appear that the human mind in respect of its cause represents non-conscious knowledge of the (...) human body and that the human mind in respect of its nature represents conscious knowledge of the human body. It will be shown that knowledge of the inner processes of the human body and of the body per se belongs to the domain of non-conscious knowledge. The same conclusion will be obtained in an analysis that starts from the distinction between the formal and the objective being of the human mind. (shrink)

Editor's suggested further reading in BioEssaysA new paradigm in cell therapy for diabetes: Turning pancreatic α‐cells into β‐cells Abstract.

The origin of insulin‐expressing β‐cells in the adult mammalian pancreas is controversial. During normal tissue turnover and following injury, β‐cells may be replaced by duplication of existing β‐cells.1 However, an alternative source of β‐cells has recently been proposed based on neogenesis from a Ngn3‐positive population present in regenerating pancreatic ducts.2 The appearance of β‐cells from Ngn3‐positive progenitors is reminiscent of normal pancreas development, and Ngn3‐expressing cells isolated from regenerating pancreas can generate the full repertoire of endocrine phenotypes. (...) The isolation and characterisation of the equivalent human progenitors may represent a significant step forward in the hunt for a cure for diabetes. BioEssays 30:617–620, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In 1925 a debate erupted in the correspondence columns of the British Medical Journal concerning the effectiveness of eating raw pancreas as a treatment for diabetes. Enthusiasts were predominantly general practitioners , who claimed success for the therapy on the basis of their clinical impressions. Their detractors were laboratory‐oriented ‘biochemist‐physicians,’ who considered that their own experiments demonstrated that raw pancreas therapy was ineffective. The biochemist‐physicians consistently dismissed the GPs' observations as inadequately ‘controlled’. They did not define the meaning (...) of ‘control’ in this context, although it clearly did not have the term's present‐day meaning of a trial employing an untreated comparison group of patients. Rather, the physician‐biochemists' ‘properly controlled’ experiments involved careful regulation of their patients' diet and other environmental factors, and evaluation of the therapy's success through biochemical, rather than just clinical, criteria. However, my analysis suggests that these factors alone are inadequate to account for the biochemist‐physicians' dismissal of the GPs' work as ‘uncontrolled’. I suggest that the biochemist‐physicians were deliberately exploiting the powerful rhetorical connotations of the term ‘control’. Ultimately, they implied that only a trial which they themselves had conducted could be deemed ‘adequately controlled’. (shrink)

Unraveling molecular and functional heterogeneity of niche cells within the developing endoderm could resolve mechanisms of tissue formation and maturation. Here, we discuss current unknowns in molecular mechanisms underlying key developmental events in pancreatic islet and intestinal epithelial formation. Recent breakthroughs in single‐cell and spatial transcriptomics, paralleled with functional studies in vitro, reveal that specialized mesenchymal subtypes drive the formation and maturation of pancreatic endocrine cells and islets via local interactions with epithelium, neurons, and microvessels. Analogous to this, distinct intestinal (...) niche cells regulate both epithelial development and homeostasis throughout life. We propose how this knowledge can be used to progress research in the human context using pluripotent stem cell‐derived multilineage organoids. Overall, understanding the interactions between the multitude of microenvironmental cells and how they drive tissue development and function could help us make more therapeutically relevant in vitro models. (shrink)

In the late seventeenth century, traditions in anatomy and chymistry came together to ground new theoretical and experimental approaches to understanding the animal body. The researches of Dutch experimenters Reinier de Graaf and his mentor Franciscus Sylvius provide keen insight into the ways experiments were constructed, negotiated, and thought about by leading anatomists and physicians of the time. The objects and approaches de Graaf used in the laboratory—ligature, inflation, injection, tubes, vessels, tasting—were derived from broadly Harveian anatomical and Helmontian chymical (...) traditions. Experimental traditions and a comprehensive and materialistic chymical theory of acid-alkali interactions unified the artificial and the natural and allowed de Graaf to create and use hybrid animal-apparatus constructions as tools to collect and assay the key ingredients of digestion and disease. (shrink)

Growing attention is being paid to the importance of trust, and its corollaries such as mistrust and distrust, in health service and the central place they have in assessments of quality of care. Although initially focussing on doctor-patient relationships, more recent literature has broadened its remit to include trust held in more abstract entities, such as organisations and institutions. There has consequently been growing interest to develop rigorous and universal measures of trust.

Dan Brock argues that since the unexploitable rich could sell their kidneys too, exploitation could not be an essential feature of organ vending. This paper takes his claim as the point of departure for a discussion on the locus of organ vending-associated oppression. While it accepts Brock's conclusion, it explores the possibility that such oppression is invariably found rather outside the sphere of exchange. It then analyses the implications of this possibility for the discourse surrounding the ethics of organ vending.

We recently discovered a novel subset of beta cells that resemble immature beta cells during pancreas development. We named these “virgin” beta cells as they do not stem from existing mature beta cells. Virgin beta cells are found exclusively at the islet periphery in areas that we therefore designated as the “neogenic niche.” As beta cells are our only source of insulin, their loss leads to diabetes. Islets also contain glucagon‐producing alpha cells and somatostatin‐producing delta cells, that are important (...) for glucose homeostasis and form a mantle surrounding the beta cell core. This 3D architecture is important and determines access to blood flow and innervation. We propose that the distinctive islet architecture may also play an important, but hitherto unappreciated role in generation of new endocrine cells, including beta cells. We discuss several predictions to further test the contribution of the neogenic niche to beta cell regeneration. (shrink)

Spinoza’s account of memory has not received enough attention, even though it is relevant for his theory of consciousness. Recent literature has studied the “pancreas problem.” This paper argues that there is an analogous problem for memories: if memories are in the mind, why is the mind not conscious of them? I argue that Spinoza’s account of memory can be better reconstructed in the context of Descartes’s account to show that Spinoza responded to these views. Descartes accounted for the (...) preservation of memories by holding that they are brain states without corresponding mental states, and that the mind is able to interpret perception either as new experience or as memory. Spinoza has none of these conceptual resources because of his substance monism. Spinoza accounts for memories as the mind’s ability to generate ideas according to the order of images. This ability consists in the connection of ideas, which is not an actual property, but only a dispositional one and thus not conscious. It is, however, grounded in the actual property of parts of the body, of which ideas are conscious. (shrink)

Diabetes is a major public health issue that affects the nations of our time to a large extent and is described as a non-communicable epidemic. Diabetes mellitus is a common disease where there is too much sugar (glucose) floating around in your blood. This occurs because either the pancreas can’t produce enough insulin or the cells in body have become resistant to insulin. The concentration in this paper is on diagnosis diabetes by designing a proposed expert system. The main (...) goal of this expert system is to get the appropriate diagnosing of the illness, dealing with it quickly, and tips for permanent treatment whenever possible is given out. SL5 object expert system language was used for designing and implementing the proposed expert system. (shrink)

Spinoza ' s understanding and understanding Spinoza -- Spinoza ' s understanding -- Understanding Spinoza -- The metaphysics of substance -- Descartes and substance -- Spinoza contra Descartes on substance -- Modes -- Necessitarianism -- The purpose of it all -- The human mind -- Parallelism and representation -- Essence and representation -- Parallelism and mind - body identity -- The idea of the human body -- The pancreas problem, the pan problem, and panpsychism -- Nothing but representation -- (...) Representation, will, and belief -- Skepticism -- Psychology : striving and self - preservation -- Conatus -- Desire, joy, and sadness -- Love, hate, and all that -- The ethics of the ethics -- The good notion of the good -- The right notion of the right -- Knowledge and morality -- Freedom and morality -- Helping others -- Lies and degrees of freedom -- The state, religion, and scripture -- Rights and power -- Religion and the state -- Scripture -- Prophecy and the truth of the Bible -- From PSR to eternity -- The aftermath of Spinoza -- Leibniz -- Bayle and Hume -- The pantheism controversy -- Hegel -- Nietzsche -- Prospects of spinozistic rationalism. (shrink)

Organ transplantation from living related donors in Bangladesh first began in October 1982, and became commonplace in 1988. Cornea transplantation from posthumous donors began in 1984 and living related liver and bone marrow donor transplantation began in 2010 and 2014 respectively. The Human Organ Transplantation Act officially came into effect in Bangladesh on 13th April 1999, allowing organ donation from both brain-dead and related living donors for transplantation. Before the legislation, religious leaders issued fatwa, or religious rulings, in favor of (...) organ transplantation. The Act was amended by the Parliament on 8th January, 2018 with the changes coming into effect shortly afterwards on 28th January. However, aside from a few posthumous corneal donations, transplantation of vital organs, such as the kidney, liver, heart, pancreas, and other body parts or organs from deceased donors, has remained absent in Bangladesh. The major question addressed in this article is why the transplantation of vital organs from deceased donors is absent in Bangladesh. In addition to the collection of secondary documents, interviews were conducted with senior transplant physicians, patients and their relatives, and the public, to learn about posthumous organ donation for transplantation. Interviews were also conducted with a medical student and two grief counselors to understand the process of counseling the families and obtaining consent to obtain posthumous cornea donations from brain-dead patients. An interview was conducted with a professional anatomist to understand the processes behind body donation for the purposes of medical study and research. Their narrative reveals that transplant physicians may be reticent to declare brain death as the stipulations of the 1999 act were unclear and vague. This study finds that Bangladeshis have strong family ties and experience anxiety around permitting separating body parts of dead relatives for organ donation for transplantation, or donating the dead body for medical study and research purposes. Posthumous organ donation for transplantation is commonly viewed as a wrong deed from a religious point of view. Religious scholars who have been consulted by the government have approved posthumous organ donation for transplantation on the grounds of necessity to save lives even though violating the human body is generally forbidden in Islam. An assessment of the dynamics of biomedicine, religion and culture leads to the conclusion that barriers to posthumous organ donation for transplantation that are perceived to be religious may actually stem from cultural attitudes. The interplay of faith, belief, religion, social norms, rituals and wider cultural attitudes with biomedicine and posthumous organ donation and transplantation is very complex. Although overcoming the barriers to organ donation for transplantation is challenging, initiation of transplantation of vital organs from deceased donors is necessary within Bangladesh. This will ensure improved healthcare outcomes, prevent poor people from being coerced into selling their organs to rich recipients, and protect the solidarity and progeny of Bangladeshi families. (shrink)

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and (...) pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available, which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal tissue from induced abortion (...) slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

Mr. Galanas, an eighty‐six‐year‐old man, intentionally shot himself in the chest and abdomen. Surprisingly, the bullet damaged only his distal pancreas and part of his colon, requiring a diverting colostomy to prevent leakage of bowel fluids into his abdomen. After being admitted, he lies intubated in the intensive care unit awaiting surgery to repair his colon. He is responsive but does not demonstrate clear decision‐making capacity. He grudgingly accepts pain medications but refuses antibiotics and antidepressants. He has a living (...) will that gives his wife durable power of attorney and also explicitly states a desire to refuse all medical interventions if he is permanently unconscious or in an end‐stage condition. Mrs. Galanas reports frequent conversations in which her husband said he would not want to be sustained on life support. She also says that he often mentioned he would not want an ostomy bag—a likely, albeit temporary, outcome of the proposed surgery.His physicians are nervous about withholding medical interventions when Mr. Galanas's injury is the result of a suicide attempt and his prognosis is good. Should the care team surgically repair his injured colon, regardless of the patient's capacity, his advance directive, and his wife's statement that he would not want surgery or other life‐sustaining treatment? (shrink)

Pam is an eighteen-year-old with a history of depression. She has been hospitalized for the past six months for severe weight loss and dehydration. When admitted, she was diagnosed with acute inflammation of the pancreas and gall bladder, but it became clear that these issues were secondary to a diagnosis of anorexia nervosa. Her weight upon admission was seventy-six pounds. Pam refuses to accept this diagnosis and will not cooperate with any provider who refers to “anorexia” or attempts to (...) discuss her eating disorder. As a pragmatic strategy for providing care, the medical team has largely avoided referring to anorexia or eating disorders when treating her. But Pam is not the only problem. Pam’s.. (shrink)

Les prélèvements et les transplantations de tissus et d'organes renvoient à des problèmes très variés au plan éthique en raison des types d'organes ou de tissus prélevés et transplantés, du statut du donneur et enfin de la finalité du prélèvement. Soyons plus précis: aujourd'hui, on prélève en vue d'une transplantation: les reins, le cœur, les poumons, le foie, le pancréas, la cornée mais aussi, la moelle osseuse, la peau. On prélève à diverses fins — thérapeutique ou de recherche — : (...) le sang, la rate, les cellules embryonnaires, les gamètes. Le donneur quant à lui, suivant les organes prélevés, sera: vivant ou mort, adulte, enfant, nouveau-né anencéphale ou embryon. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:What, Exactly, Does the Madperson Lack?Sofie Jeppsson, PhD (bio)Justin garson has already received well-earned recognition for his Madness: A philosophical exploration (2022), in which he distinguishes the view of madness as a dysfunction from madness as a strategy—a distinction that cuts across traditional distinctions between, for example, biological/neurological and psychological/social views. On the dysfunction view, going mad might be comparable to something like having an asthma attack or, more (...) long-term, developing type 1 diabetes. If the trachea closes up and prevents air from passing through, that is a dysfunction in the breathing apparatus. If the islets of Langerhans in the pancreas cease to produce insulin, making the person dependent on insulin shots to stay alive, that is a dysfunction. On the strategy view, going mad is rather like getting a fever when already infected with some pathogen. Given that you have the pathogen reproducing inside you, a rising body temperature provides a strategy (although not, of course, something the ill person chose) to keep the reproduction rate down, thus giving the immune system a better chance at vanquishing the infection. That does not mean that fevers are harmless—if a fever becomes high enough, it might itself do damage to the body. Still, it is a strategy, not a mere dysfunction. Analogously, on the Madness as strategy view, going mad might help a person deal with old traumas or an ongoing terrible situation, even as the madness may also be damaging in itself.In this paper, Garson introduces us to another interesting distinction: between seeing madness as a lack of reason, or as a perversion of or difference in reason. Garson writes that present-day psychiatry tends to see madness as a lack, whereas the late modern thinkers conceived of it as a perversion of reason. The late moderns clearly saw madness as something negative, but if we retain something like their basic view, merely change our evaluation from the negative perversion to the more neutral difference, we have a better basis for regarding Madness as a complicated and problematic but still cherished identity, and for Mad Pride.This is another interesting distinction well worth calling attention to. I’m uncertain how well the J.C.A. Heinroth example works—the text cited seems to show that he had a Madness as strategy view, but is it a Madness as a different kind of reason view?—but the other examples work better. Nevertheless, I want to push back a little against the claim that present-day psychiatry and philosophy of psychiatry tend to regard madness as a lack of something whereas the early moderns saw it as a difference. (Just a friendly little push, mind you, but still.)Arthur Wigan’s description of two brains, one functional and one dysfunctional, still seems to posit a lack of proper function in one of them. Sure, he does not say that the madperson lacks as much as the [End Page 313] idiot, who has two dysfunctional brains whereas the madperson has one functional and one dysfunctional. Still, there’s a lack. This two-brain picture also has its modern analogues: It brings to mind (albeit in a less biologically concrete and reified form) much psycho-educational material on, for example, how to live with bipolar disorder, according to which a supposed sane and rational part of the psychiatric patient’s mind should learn to handle and control the other, mad part (e.g., Miklowitz, 2012).According to John Locke, madpeople reason just fine, but they start from false premises. Is not this, too, something that madpeople are supposed to lack? Correct and realistic premises to start from? Locke writes that madpeople have “taken their fancies for realities,” but “make right deductions from them.” Moreover, Locke’s theory is reminiscent of modern bottom-up theories like Brendan Maher’s (1999)—madpeople have bizarre experiences on the basis of which they form bizarre beliefs, but we need not postulate that they suffer from any problems with, for example, reasoning and drawing inferences to explain why they believe what they do. Theorists who instead argue for a top-down or two-factor account of why madpeople stick... (shrink)

Abstract:This symposium includes thirteen personal narratives from people who have received at least one organ transplant from a living or deceased donor. These narratives foster better understanding of the experiences of life-saving organ recipients and their families, including post-transplant difficulties experienced—sometimes requiring multiple transplants. This issue also includes three commentaries by Macey L. Levan, Heather Lannon, and Vidya Fleetwood, Roslyn B. Mannon & Krista L. Lentine. Dr. Levan is a living kidney donor and associate professor of surgery and population health. (...) She writes and teaches on organ transplant and has expertise and experience in governance at the federal level as a member of the board of directors for the U.S. Organ Procurement and Transplantation Network. Dr. Lannon is a social worker and transplant advocate. Her work and interest in the topic were inspired by her husband who needed a heart transplant. Dr. Fleetwood is a surgeon specializing in liver transplantation, pancreas transplantation, kidney transplantation, as well as living donor nephrectomy. Dr. Mannon is a nephrologist and professor of medicine, pathology and microbiology. Her work focuses on understanding and improving long-term kidney transplant outcomes for patients, donors, and caregivers. Dr. Lentine is a nephrologist specializing in treatment of adult patients with kidney disease. She is a researcher and co-chaired the international work group that developed guidelines for living donor kidney transplantation. (shrink)

Mr. Galanas, an eighty‐six‐year‐old man, intentionally shot himself in the chest and abdomen. Surprisingly, the bullet damaged only his distal pancreas and part of his colon, requiring a diverting colostomy to prevent leakage of bowel fluids into his abdomen. After being admitted, he lies intubated in the intensive care unit awaiting surgery to repair his colon. He is responsive but does not demonstrate clear decision‐making capacity. He grudgingly accepts pain medications but refuses antibiotics and antidepressants. He has a living (...) will that gives his wife durable power of attorney and also explicitly states a desire to refuse all medical interventions if he is permanently unconscious or in an end‐stage condition. Mrs. Galanas reports frequent conversations in which her husband said he would not want to be sustained on life support. She also says that he often mentioned he would not want an ostomy bag—a likely, albeit temporary, outcome of the proposed surgery.His physicians are nervous about withholding medical interventions when Mr. Galanas's injury is the result of a suicide attempt and his prognosis is good. Should the care team surgically repair his injured colon, regardless of the patient's capacity, his advance directive, and his wife's statement that he would not want surgery or other life‐sustaining treatment? (shrink)

Mr. Galanas, an eighty‐six‐year‐old man, intentionally shot himself in the chest and abdomen. Surprisingly, the bullet damaged only his distal pancreas and part of his colon, requiring a diverting colostomy to prevent leakage of bowel fluids into his abdomen. After being admitted, he lies intubated in the intensive care unit awaiting surgery to repair his colon. He is responsive but does not demonstrate clear decision‐making capacity. He grudgingly accepts pain medications but refuses antibiotics and antidepressants. He has a living (...) will that gives his wife durable power of attorney and also explicitly states a desire to refuse all medical interventions if he is permanently unconscious or in an end‐stage condition. Mrs. Galanas reports frequent conversations in which her husband said he would not want to be sustained on life support. She also says that he often mentioned he would not want an ostomy bag—a likely, albeit temporary, outcome of the proposed surgery. His physicians are nervous about withholding medical interventions when Mr. Galanas's injury is the result of a suicide attempt and his prognosis is good. Should the care team surgically repair his injured colon, regardless of the patient's capacity, his advance directive, and his wife's statement that he would not want surgery or other life‐sustaining treatment? (shrink)

The natural source for new pancreatic beta cells is an important issue both for understanding the pathogenesis of diabetes, and for possibly curing diabetes by increasing the number of beta cells. Dor et al.1 investigated beta‐cell renewal and regeneration by genetic lineage analysis in mice during physiological growth and after partial pancreatectomy. The data conclusively showed that beta‐cell replication was the only source for new beta cells without contributions from stem cells or other non‐beta cells. This underlines the capacity for (...) beta‐cell self‐renewal and casts doubt that other cell types are able to generate new beta cells in the intact pancreas. BioEssays 26:1156–1159, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Jehovah’s Witnesses should be required to sign transfusion contracts in order to be eligible for transplant.Human donor organs continue to be in short supply, and many potential transplant recipients die while waiting for an allograft to become available.1 Because the organ supply is so limited and the offering of organs is based on the generosity of patients and families, proper stewardship of these organs is an ethical obligation for transplant teams, as well as organ recipients. Preventable graft loss must be (...) protected against, and factors that foster preventable graft loss—for example, non-compliance must be proactively contemplated when patients are reviewed as potential transplant candidates. Post-transplant treatment refusal is one example of behaviour that can compromise transplant success.JEHOVAH’S WITNESSES AS TRANSPLANT RECIPIENTSIt is widely known that one of the most significant teachings of the Jehovah’s Witness church is abstinence from receiving blood transfusions.2 Believers derive this tenet from the Bible verse: “You are to abstain from …blood”.3 While blood loss is a risk of transplant surgery, some centres do not view patient refusal of blood transfusion as a transplant exclusion criterion. The first published case of transplantation of a Jehovah’s Witness appeared in 1986 from the University of California Los Angeles heart transplant team.4 Since then, numerous other cases have been published, including liver,5 kidney,6 pancreas,6 and lung.7 For experienced centres with superior blood management skills, transplant can indeed be a surgical success; however, optimal blood management before and during surgery are only two thirds of the patient’s clinical time clock. In the remaining third, the post-transplant period, the patient has received his/her organ, yet the potential for clinical need of blood transfusion remains.THE DILEMMAWhether due to postoperative complication, or future illness or trauma, all transplant recipients have …. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Organ Transplant AllocationPat Milmoe McCarrick (bio)The introduction of the antibiotic, cyclosporin, which enhances the success rate of transplantation surgery, has resulted in the steady growth of organ transplantation since the mid-1980s. This growth increasingly focuses ethical interest on both the procurement and the allocation of human organs. Not everyone who might benefit from organ transplants can receive them since the number of patients in need of organs far exceeds (...) the number of organs available. Each year the waiting list for transplants increases by 20 percent, but the number of donated organs has remained stable for the past five years (Lawry 1994).Organ transplantation surgery performed on rock stars, sports heroes, politicians, and television celebrities brings questions about the fair allocation of scarce resources to the attention of everyone. Abigail Trafford, editor of Washington Post Health, wonders whether "new livers for hard livers" can be deserved when not enough organs are available for everyone who needs them. Writing about the dilemma of just allocation of organs, she calls famous recipients "poster patients" or "health care celebrities of medical catastrophe" (Trafford 1994). Personal responsibility—the viewpoint that "medical treatment should not be an entitlement program for profligate living"—is an emerging moral consideration according to Trafford. Deciding whose standards and values should apply to the allocation of organs raises many questions. Popular arguments for keeping the current criteria for allocation include: these patients are sick and therefore should be treated, regardless of the cause of their illness; former substance abusers should be able to benefit from their present abstention; physicians should treat anyone who is ill; and although many human illnesses may be caused by individual behavior, such behavior is not always used as a reason to deny care (Trafford 1995).Prior to 1984, when the government established regulations governing organ transplantation, organs routinely were given to the patients of the surgeons who excised them (Prottas 1994). In an effort to achieve a more equitable method of distribution, Congress passed the National Organ Transplant Act of 1984 (Pub. [End Page 365] L. No. 98-507, amended by Pub. L. No. 100607 and Pub. L. No. 101-616), which established a national Organ Procurement and Transplantation Network (OPTN) to improve the effectiveness of organ procurement, organ distribution, and transplant activities. The United Network for Organ Sharing (UNOS) received the federal government contract to be the OPTN.UNOS and its 66 regional organ procurement organizations (OPOs) around the nation have carried out the mandate since 1986. It requires hospitals that receive Medicare or Medicaid funds and perform transplants to belong to the network and to allocate organs according to network policies. UNOS maintains the national computer registry to match donor organs with individual recipients. In distributing organs, UNOS is required by law to use a fair and equitable system based on accepted medical criteria. UNOS regularly reevaluates its policies to ensure that organ donation and recipient selection meet criteria of efficiency and equity (UNOS Update 11 (8), 1995).At the end of June 1995, 278 transplant centers were in operation in the United States: almost all of them (247 centers) transplanted kidneys; 167 did hearts; 119, pancreases; 114, livers; 93, heart-lung; 88, lungs; 26, intestines; and only 19 centers performed pancreas islet cell transplants (UNOS Update 11 (8): 28, 1995). The number of patients waiting for organ transplants in July 1995 totalled 41,075: 29,274 were waiting for a kidney transplant; 4,937, liver; 3,298, heart; 1,816, lung; 1,223 kidney-pancreas; 240, pancreas; and 211, heart-lung (UNOS Update 11 (8): 40-41, 1995).OPOs are located in different geographic areas across the country, each with different organ needs, lengths of waiting lists, or with lists in areas with large older populations making it more difficult to find suitable donors. Black recipients often wait longer due to complex reasons including sensitization or rarer blood and antigen types (UNOS 11 (8): 31-32, 1995). When an organ becomes available, the OPO involved identifies a potential recipient from the UNOS list and offers it to the patient's surgeon. If no match can be made locally, the organ is next offered within a UNOS region, and finally, to... (shrink)

Richard Rorty nació el 4 de octubre de 1931 y murió el 8 de junio de 2007. Fue profesor de filosofía en la universidad de Wellesley y de Princeton, cargo al que renunció en 1983 para ocupar el puesto de profesor de humanidades en la Universidad de Virginia y posteriormente de literatura comparada en la universidad de Stanford. Murió de cáncer de páncreas igual que Jacques Derrida, uno de sus interlocutores más destacados de la filosofía europea.

Fábio Alves dos Santos (1954-2013) cursou Pedagogia, Ciências Sociais e Teologia, era Especialista em Filosofia da Religião (PUC Minas), Advogado (PUC Minas) e Mestre em Direito Constitucional (UFMG). Lecionou na PUC Minas como professor de Cultura Religiosa e depois como professor no Curso de Direito, atuando principalmente no Serviço de Assistência Judiciária – SAJ, especialmente cuidado de causas populares como as da ASMARE (Associação dos Catadores de Papel, Papelão e Material Reaproveitável de Belo Horizonte), da Pastoral de Rua, da Pastoral (...) Carcerária, de movimentos de “Sem Casa”, de ocupações e tantos outros grupos. Fábio sofria de grave problema de visão há mais de 15 anos. Quase ficou cego depois de diversas cirurgias de miopia. Isso, porém, não o impedia de seguir seu constante compromisso com as lutas populares. Na última entrevista que concedeu, menos de um mês antes de sua morte (19 de outubro de 2013), depois de duro sofrimento de quase dois anos, no tratamento de um câncer no pâncreas, conta um pouco de sua vida, sua luta e sua percepção de várias realidades, especialmente da Igreja e da pastoral. Militante formado na Teologia da Libertação, de profunda espiritualidade, marcada por traços da religiosidade popular nordestina e comprometida com a libertação, Fábio Alves também buscou em sua vida abrir-se à teologia do pluralismo religioso, especialmente com o Santo Daime, em cuja tradição religiosa chegou a ser “fardado”, mantendo uma profunda atitude espiritual aberta ao diálogo inter-religioso. Sua primeira publicação foi “Começo de mundo novo: sofrimento, luta e vitória dos posseiros de Santana dos Frades”, Sergipe, numa versão popular em 1981 e outra pela Editora Vozes (1990). Fruto de sua dissertação de mestrado, publicou o livro “Direito Agrário: política fundiária no Brasil (1995). Em 2001 saiu seu último livro, uma coletânea de artigos publicados em diversos jornais: “Em defesa da vida”. Num artigo em Horizonte (2004), juntamente com o advogado, amigo e colega Prof. Cristiano de Melo Bastos, discutiu “A prática jurídica na missão da PUC Minas”. Palavras-chave : Teologia da Libertação. Militância. Igreja Católica. Pastoral. Lutas populares. (shrink)

Recent studies have yielded new insights into the critical importance of adequate vitamin D3 intake and metabolism. Investigations of the actions of 1,25‐dihydroxyvitamin D3 (calcitriol) on novel target tissues has revealed that this hormone has functions other than its recognized action in regulating blood calcium and phosphate levels. Reports have characterized calcitriol receptors and activities in organs and tissues as diverse as pancreas, skeletal and heart muscle, blood cells, brain, skin, pituitary, parathyroid, kidney, bone and intestine. These studies suggest (...) functions for calcitriol as varied as the regulation of insulin and prolactin secretion, muscle contractility, immune cell metabolism, melanin synthesis and differentiation of blood cells. This information may ultimately help us to understand the etiologies of several kinds of organ dysfunction and lead to the development of tissue‐specific agents for new therapies. (shrink)

In this paper I shall be arguing against the claim made by Erin and Harris and others, that creating a “regulated market” in organs for transplantation taken from living vendors is both viable practically and a moral imperative. No-one can doubt that there is currently a crisis in the provision of organs for transplantation, with a massive gap between supply and demand. There are a number of reasons for this crisis. Since its development as a life-saving measure in the second (...) half of the last century, organ transplantation has expanded exponentially, both in terms of survival rates, the number of people on the waiting list for the procedure, and the range of transplantable organs. Advances in immuno-suppression and in prevention of infection have led to improvement in both the survival of the recipients and of the transplanted organs. At the same time, there has been an increase in repeat transplantations and in multiple organ transplants. The range of conditions for which transplantation is offered has widened, and transplantable organs now include: kidney, liver, pancreas, heart and lung. Brain-dead donors can provide all of these organs, while the kidney and sections of the liver and pancreas can also be obtained from living donors. Survival outcomes are better from living donors than from cadaveric donors, and, in the case of kidney failure, better from transplantation than from dialysis. [End Page 164] The relevant question, however, is whether permitting a market in human organs is morally justifiable, and, even if it were, whether it would provide a solution to the current crisis. I argue in this paper that organ trading is wrong in principle, since it commodifies the human body and inevitably exploits the poor and the socially vulnerable, and that, far from alleviating the crisis, it is likely to make it worse. First we should note that there is an uncompromising opposition to all forms of organ trading from two major international healthcare organisations. (shrink)

This article describes new aspects of hysteresis dynamics which have been uncovered through computer experiments. There are several motivations to be interested in fast-slow dynamics. For instance, many physiological or biological systems display different time scales. The bursting oscillations which can be observed in neurons, β-cells of the pancreas and population dynamics are essentially studied via bifurcation theory and analysis of fast-slow systems (Keener and Sneyd, 1998; Rinzel, 1987). Hysteresis is a possible mechanism to generate bursting oscillations. A first (...) part of this article presents the computer techniques (the dotted-phase portrait, the bifurcation of the fast dynamics and the wave form) we have used to represent several patterns specific to hysteresis dynamics. This framework yields a natural generalization to the notion of bursting oscillations where, for instance, the active phase is chaotic and alternates with a quiescent phase. In a second part of the article, we emphasize the evolution to chaos which is often associated with bursting oscillations on the specific example of the Hindmarsh–Rose system. This evolution to chaos has already been studied with classical tools of dynamical systems but we give here numerical evidence on hysteresis dynamics and on some aspects of the wave form. The analytical proofs will be given elsewhere. (shrink)

The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes that shares many immunogenetic features with human insulin-dependent diabetes mellitus (IDDM), type 1 diabetes. The mononuclear cell infiltrates in the islet, which results in the development of insulitis (a prerequisite step for the development of diabetes) are primarily composed of T cells. It is now well accepted that these T cells play important roles in initiating and propagating an autoimmune process, which in turn destroys insulin-producing islet β cells in the (...) pancreas. T cells are subdivided into CD4+ helper T cells and CD8+ cytotoxic T cells. CD4+ T cells are further subdivided into Th1 and Th2 cells based on profiles of cytokine production, and these two T-cell populations counterregulate each other. Because many autoimmune diseases are Th1 T-cell mediated, current studies have focused on manipulating the Th1/Th2 imbalance to suppress the autoimmune process in the NOD model. Furthermore, the incidence of disease is much higher in females than that in males, suggesting an involvement of sex-steroid hormones in the development of diabetes. Understanding insights of the mechanism of immune-mediated islet cell destruction and the interaction between the immune and the neuroendocrine system may, therefore, provide new therapeutic means of preventing this chronic debilitating disease. BioEssays 20:750–757, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Back to the Future:Obtaining Organs from Non-Heart-Beating CadaversRobert M. Arnold (bio) and Stuart J. Youngner (bio)Organ Transplantation requires viable donor organs. This simple fact has become the Achilles' heel of transplantation programs. Progress in immunology and transplant surgery has outstripped the supply of available organs. Between 1988 and 1991, for example, the number of transplant candidates on waiting lists increased by about 55 percent, while the number of donors (...) increased only about 16 percent.1 By the end of March 1993, more than 30,000 potential recipients awaited transplantation (United Network for Organ Sharing Database (UNOS) 1993). Every day six of these patients die prior to receiving a heart or liver transplant, while patients needing kidney transplants must tolerate a lower quality of life on dialysis (Grenvik 1992; Evans, Orians, and Ascher 1992).This scarcity is likely to get worse. As transplantation becomes more successful, it is being offered to sicker and older patients. Attempts to transplant other solid organs, such as small bowel and pancreas, will only fuel the demand for donors. However, the current source of organs is unlikely to grow. Most organs come from patients who have been declared dead by neurologic criteria (commonly referred to as "brain dead" or heart-beating cadaver donors (HBCDs) because their hearts are beating at the time of procurement). Estimates of the potential pool of HBCDs have been revised downward from 20,000-27,000 to roughly 10,000-12,000 (Nathan et al. 1991). Improvements in automobile safety and handgun legislation will likely lead to further reductions. Moreover, the rate of procurement from HBCDs has remained relatively flat despite extensive public awareness campaigns and legislation requiring hospitals to routinely request donation from families of dead patients (Caplan et al. 1992).If organ transplantation is going to continue to flourish, alternative [End Page 103] sources of organs must be found. Recently the University of Pittsburgh Medical Center (UPMC) proposed procuring organs from patients who have been declared dead by traditional cardiopulmonary rather than brain-oriented criteria after they or their families have decided to forgo life-sustaining treatment—hereafter referred to as the Pittsburgh protocol (UPMC Policy 1993). These patients are typically referred to as non-heart-beating cadaver donors (NHBCDs) because their hearts are no longer beating at the time of organ procurement.Although NHBCDs were a major source of transplantable kidneys prior to the institution of death by neurologic criteria, their usefulness was limited by "warm ischemia time." This term refers to the injury to tissues that occurs when the blood supply is interrupted and before the organs are cooled and reperfused. Under the Pittsburgh protocol, therapy is withdrawn in the operating room where a waiting surgical team removes organs immediately after death is declared. By controlling the place and time of death, it has been possible to minimize warm ischemia time and thus solve the technical problems previously associated with procurement from NHBCDs.The potential contribution of NHBCD organs is significant. Nathan (1992), using data from Delaware Valley Transplant Program, concludes that the use of severely brain injured, but not "brain dead" patients, would increase the donor pool by 20-25 percent. Moreover, unpublished data from the Pittsburgh organ procurement organization, the Center for Organ Recovery and Education (CORE), suggests that these organs, particularly kidneys, function as well as those procured from HBCDs (Broznick 1993).This volume is devoted to the ethical, psychosocial, and public policy implications of procuring organs from non-heart-beating cadaver donors after a discussion to forgo life-sustaining treatment. The genesis of this volume was a project in which we invited leading experts in transplantation, ethics, and public policy to use the Pittsburgh protocol as a starting point for exploring a broad range of issues associated with attempts to procure organs from NHBCDs. The issues raised by NHBCDs turned out to have important implications about the fundamental conceptual and moral assumptions underlying organ procurement.Although each of the papers in this volume can be read separately, we intend the volume to be read as a whole. Many of the latter pieces on the ethical implications of the policy are best understood in light of the earlier background papers... (shrink)

Apoptotic pathways have always been regarded as a key‐player in preserving tissue and organ homeostasis. Excessive activation or resistance to activation of cell death signaling may indeed be responsible for several mechanisms of disease, including malignancy and chronic degenerative diseases. Therefore, targeting apoptotic factors gained more and more attention in the scientific community and novel strategies emerged aimed at selectively blocking or stimulating cell death signaling. This is also the case for the TMEM219 death receptor, which is activated by a (...) circulating ligand, the Insulin‐like growth factor binding protein 3 (IGFBP3) and induces a caspase‐8‐dependent apoptosis of the target cells. Interestingly, stimulation of the IGFBP3/TMEM219 axis exerts an anti‐proliferative effect, while blockade of the TMEM219 deleterious signal protects TMEM219‐expressing cells of the endocrine pancreas, lung, and intestine from damage and death. Here, we summarize the most updated reports on the role of the IGFBP3/TMEM219 apoptotic axis in disease conditions, including intestinal disorders and diabetes, and we describe the advancements in designing and testing novel TMEM219‐based targeting approaches in emerging potential clinical applications. (shrink)

This paper examines human-nonhuman splices from a multidisciplinary approach, involving bioengineering and literary studies. Splices are hybrid beings, created through gene-splicing—a process which combines the DNA of the two species, resulting in a hybrid or chimeric being. A current trend in biotechnological research is the use of spliced pigs for xenotransplantation. Hiromitsu Nakauchi’s pancreas study that splices pigs with human iPS [induced pluripotent stem] cells in order to grow human organs inside pigs is being compared to a highly similar (...) case of porcine hybrids: the pigoon from Margaret Atwood’s fictional MaddAddam trilogy. Atwood’s pigoons are pigs, genetically modified with human stem cells to facilitate the growth of various human organs for use in organ transplants with no risk of rejection. The case studies from science and science fiction overlap significantly and thus allow for a critical reading of the two highly different sources with a focus on ethical and moral questions regarding the use and abuse of nonhuman animals for human purposes. Furthermore, the context of the fictional works adds new layers of knowledge and new perspectives to the problematic issue of animal “enhancement.” Through the dynamic agency that can be detected within Atwood’s novels and that encompasses human, animal, and hybrid agency, the reader can develop empathy for other-than-human experiences and use this new perspective for a critical reflection of actual technoscientific developments that affect both human and nonhuman animal life. The combination of the two discourses reveals a value of science fiction for both the scientific community and society at large, demonstrating how its critical reception can result in enhanced ethical standards. (shrink)

Book reviewed in this article: Practical Medical Ethics. By Alastair Campbell, Grant Gillett, and Gareth Jones. If I Were a Rich Man Could I Buy a Pancreas? and Other Essays on the Ethics of Health Care. By Arthur L. Caplan. Bloomington Ethics on Call: A Medical Ethicist Shows How to Take Charge of Life and Death Choices in Today's Health Care System. By Nancy Dubler and David Nimmons.

Book reviewed in this article: Practical Medical Ethics. By Alastair Campbell, Grant Gillett, and Gareth Jones. If I Were a Rich Man Could I Buy a Pancreas? and Other Essays on the Ethics of Health Care. By Arthur L. Caplan. Bloomington Ethics on Call: A Medical Ethicist Shows How to Take Charge of Life and Death Choices in Today's Health Care System. By Nancy Dubler and David Nimmons.

Insulin is stored within the pancreas in an inactive Zn2+‐bound hexameric form prior to release. Similarly, clinical insulins contain Zn2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn2+. The Zn2+‐binding properties of HSA are (...) attenuated by non‐esterified fatty acids (NEFAs) also transported by HSA. Elevated NEFA concentrations are associated with obesity and type 2 diabetes. Here we present the hypothesis that higher NEFA levels in obese and/or diabetic individuals may contribute to insulin resistance and affect therapeutic insulin dose‐response profiles, through modulation of HSA/Zn2+ dynamics. We envisage this novel concept to have important implications for personalized treatments and management of diabetes‐related conditions in the future. (shrink)

In recent years, there have been a number of well‐documented examples demonstrating that one cell type can be converted to another. Two such examples are the appearance of ectopic pancreas in the liver and formation of hepatic tissue in the pancreas. The conversion of liver to pancreas raises the intriguing possibility of generating insulin‐producing β cells for therapeutic transplantation into diabetics. There is now a striking addition to the growing list of pancreatic conversions: the formation of pancreatic (...) tissue in the developing biliary system.1 BioEssays 26:932–937, 2004. © 2004 Wiley Periodicals, Inc. (shrink)