Pharmacologic modulation of experimental postischemic hepatic function

The present study, evaluated and compared the effects of SRI 63-441, a potent platelet activating factor antagonist, superoxide dismutase (SOD), an oxygen free radical scavenger, and ibuprofen, a cyclooxygenase inhibitor on hepatic function after 90 minutes of warm ischemia. After warm ischemia, livers were harvested and underwent 90 minutes of warm, oxygenated, sanguinous perfusion on an isolated liver perfusion apparatus. Pretreatment of donor animals with 20 mg/kg intravenous (I.V.) SRI 63-441 5 minutes before induction of total hepatic ischemia resulted in significantly increased bile production, a significant decrease in transaminase release, and a higher tissue adenosine triphosphate (ATP) content when compared with ischemic non-treated controls. SOD resulted in improved bile production and decreased transaminase liberation only when present in the perfusate at the time of in vitro reperfusion. Ibuprofen did not improve postischemic hepatic function in this model. Electron microscopy revealed patchy hepatocellular vacuolization with an intact sinusoidal endothelium in all ischemic livers. However, the degree of damage was less severe in the livers from those rats pretreated with 20 mg/kg SRI 63-441. This study demonstrates that SRI 63-441 pretreatment significantly reduces hepatic warm ischemic injury, and in the present model, appears superior to two other agents that have been advanced in the treatment of ischemic injury. The use of such agents singly or in combinations have important implications as regards gaining a better understanding of he basic mechanisms in organ ischemia, and moreover, for therapeutic applications in organ ischemia and preservation

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions

Orthotopic liver transplantation for massive hepatic lymphangiomatosis

Lymphangiomatosis is a rare malformation of the lymphatic system that causes severe symptoms secondary to progressive growth into or close to vital structures. A case report of liver failure related to this space-occupying intrahepatic mechanism is taken as a starting point for a discussion of the problems of liver transplantation related to large hepatomegalies. © 1988

Hepatotrophic effects of FK506 in dogs

Portacaval shunt (Eck fistula) in dogs causes hepato- cyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this pro-cedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of he- patocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506’s efficacy for the treatment of chronic liver rejection. Also, the observa-tions support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cy-tosolic binding sites of FK506, repamycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.© 1991 by Williams & Wilkins

Intermediate Valence Model for the Colossal Magnetoresistance in Tl_{2}Mn_{2}O_{7}

The colossal magnetoresistance exhibited by Tl_{2}Mn_{2}O_{7} is an interesting phenomenon, as it is very similar to that found in perovskite manganese oxides although the compound differs both in its crystalline structure and electronic properties from the manganites. At the same time, other pyrochlore compounds, though sharing the same structure with Tl_{2}Mn_{2}O_{7}, do not exhibit the strong coupling between magnetism and transport properties found in this material. Mostly due to the absence of evidence for significant doping into the Mn-O sublattice, and the tendency of Tl to form conduction bands, the traditional double exchange mechanism mentioned in connection with manganites does not seem suitable to explain the experimental results in this case. We propose a model for Tl_{2}Mn_{2}O_{7} consisting of a lattice of intermediate valence ions fluctuating between two magnetic configurations, representing Mn-3d orbitals, hybridized with a conduction band, which we associate with Tl. This model had been proposed originally for the analysis of intermediate valence Tm compounds. With a simplified treatment of the model we obtain the electronic structure and transport properties of Tl_{2}Mn_{2}O_{7}, with good qualitative agreement to experiments. The presence of a hybridization gap in the density of states seems important to understand the reported Hall data.Comment: 8 pages + 5 postscript fig

Rapid flush technique for donor hepatectomy: Safety and efficacy of an improved method of liver recovery for transplantation

This report describes a 2-year retrospective review of 437 donor hepatectomies comparing our experience with both the conventional and rapid flush techniques. In this retrospective review we have compared this new rapid technique to that of the conventional. The population of donors comprising the two groups were not significantly different, although there was a trend to use slightly more compromised donors when the rapid technique was used. Despite this trend, overall graft function, as assessed by peak flush group. Finally, the rate of primary nonfunction of hepatic grafts was reduced by the use of this new technique. In summary, the rapid flush technique yields high quality organs, is well accepted by the transplant community, and has become the procedure of choice for organ procurement

Lack of evidence does not justify neglect. how can we address unmet medical needs in calciphylaxis

Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare disease predominantly occurring in comorbidity with dialysis. Due to the very low frequency of CUA, prospective studies on its management are lacking and even anecdotal reports on treatment remain scarce. Therefore, calciphylaxis is still a challenging disease with dismal prognosis urgently requiring adequate strategies for diagnosis and treatment.In an attempt to fill some of the current gaps in evidence on various, highly debated and controversial aspects of dialysis-associated calciphylaxis, 13 international experts joined the 1st Consensus Conference on CUA, held in Leuven, Belgium on 21 September 2015. The conference was supported by the European Calciphylaxis Network (EuCalNet), which is a task force of the ERA-EDTA scientific working group on Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD). After an intense discussion, a 9-point Likert scale questionnaire regarding 20 items on calciphylaxis was anonymously answered by each participant. These 20 items addressed unsolved issues in terms of diagnosis and management of calciphylaxis. On the one hand, the analysis of the expert opinions identified areas of general consensus, which might be a valuable aid for physicians treating such a disease with less experience in the field. On the other hand, some topics such as the pertinence of skin biopsy and administration of certain treatments revealed divergent opinions. The aim of the present summary report is to provide some guidance for clinicians who face patients with calciphylaxis in the current setting of absence of evidence-based medicin

Dynamical Mean-Field Solution for a Model of Metal-Insulator Transitions in Moderately Doped Manganites

We propose that a specific spatial configuration of lattice sites that energetically favor {\it 3+} or {\it 4+} Mn ions in moderately doped manganites constitutes approximately a spatially random two-energy-level system. Such an effect results in a mechanism of metal-insulator transitions that appears to be different from both the Anderson transition and the Mott-Hubbard transition. Correspondingly, a disordered Kondo lattice model is put forward, whose dynamical mean-field solution agrees reasonably with experiments.Comment: 4 pages, 2 eps figures, Revtex. First submitted to PRL on May 16, 199