Down regulation of epidermal growth factor receptors in liver proliferation induced by a mixture of triiodothyronine, amino acids, glucagon, and heparin (TAGH).

This study investigated the mechanisms by which TAGH solution (a mixture of triiodothyronine, amino acids, glucagon, and heparin) induces DNA synthesis in hepatocytes in the liver of intact rats, with particular reference to events at the epidermal growth factor (EGF) receptor. Both partial hepatectomy and infusion of TAGH stimulated DNA synthesis at 24 hours and both procedures resulted in a reduction of EGF receptors assessed in plasma membranes isolated from rat liver at this time. In cell cultures, while EGF strongly stimulated DNA synthesis and started EGF receptor down regulation, TAGH had only a minor effect (1.5 x basal) on DNA synthesis and did not interact with or down regulate the EGF receptor. Membrane phosphorylation studies, however, showed that TAGH induced phosphorylation of tyrosine residues in the EGF receptor. The in vivo action of TAGH seems to entail recruitment of similar changes in the EGF receptor to those that occur after partial hepatectomy

Protein-bound uremic toxins, inflammation and oxidative stress: A cross-sectional study in stage 3-4 chronic kidney disease

Background and Aims: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro- and cardiovascular toxins, produced solely by the gut microbiota, which have pro-inflammatory and pro-oxidative properties in vitro. We undertook this study to investigate the associations between IS and PCS and both inflammation and oxidative stress in the chronic kidney disease (CKD) population. Methods: In this cross-sectional observational cohort study, participants with stage 3-4 CKD who enrolled in a randomized controlled trial of cardiovascular risk modification underwent baseline measurements of serum total and free IS and PCS (measured by ultraperformance liquid chromotography), inflammatory markers (interferon gamma [IFN-γ], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx] activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave velocity (PWV), a marker of arterial stiffness. Results: There were 149 CKD patients (59% ma≤ age 60 ± 10 years; 44% diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m2 (range 25-59). Serum free and total IS were independently associated with serum IL-6, TNF-α and IFN-γ, whereas serum free and total PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were additionally independently associated with serum GPx but not with TAC or F2-isoprostanes. Conclusions: IS and PCS were associated with elevated levels of selected inflammatory markers and an antioxidant in CKD patients. PCS was also associated with increased arterial stiffness. Inflammation and oxidative stress may contribute to the nephro- and cardiovascular toxicities of IS and PCS. Intervention studies targeting production of IS and PCS by dietary manipulation and the subsequent effect on cardiovascular-related outcomes are warranted in the CKD population

Cryogenic target development for fast ignition with Z-pinch-driven fuel assembly

We are developing an alternative approach to indirect-drive fast ignition fusion targets in which a liquid cryogenic fuel layer is condensed in situ from a low pressure external gas supply and confined between a thick outer ablator shell and a thin inner shell. The shape and surface quality of the liquid fuel layer is determined entirely by the characteristics of the bounding shells. Liquid fuel targets of this type have a number of potential advantages including greatly reduced temperature control requirements and drastically reduced cost and complexity of the cryogenic support system compared to $\beta$-layed DT targets. This liquid fuel concept is particularly appropriate for a hemispherical capsule configuration with single-sided x-ray drive by a z-pinch source. Technology issues for concentric-shell liquid cryogenic target development and progress in thin inner hemispherical shell fabrication are discussed

Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure

Administration of human recombinant erythropoietin ( EPO) at time of acute ischemic renal injury ( IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa ( DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats ( N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation ( T0), or post-treated ( 6 h after the onset of reperfusion, T6) with EPO ( 5000 IU/kg), DPO ( 25 mu g/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.08 +/- 0.03mmol/l vs EPO-IRI 0.04 +/- 0.01mmol/l, P = 0.01). Delayed administration of DPO or EPO ( T6) also significantly abrogated subsequent renal dysfunction ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.06 +/- 0.01mmol/l vs EPO-IRI 0.03 +/- 0.03mmol/l, P = 0.01). There was also significantly decreased tissue injury ( apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult

Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors.

The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA synthetic response of rat livers to toxic injury induced by a 350 or 800 mg/kg ip injection of galactosamine and that caused by 70% hepatectomy, comparing the changes in epidermal growth factor receptor status. Both resulted in down regulation of epidermal growth factor receptors, suggesting similar ligand epidermal growth factor receptor binding occurs during the proliferative response after galactosamine administration and after partial hepatectomy. In vitro studies on isolated hepatocytes showed that epidermal growth factor receptor down regulation was not a direct effect of galactosamine on hepatocyte membranes

In vitro

The in vitro antimicrobial and in vivo heavy metal abatement properties of aqueous extracts of Garcinia kola Heckel (bitter cola) were investigated using opportunistic pathogens and Wistar rats as experimental models. A marked inhibitory activity against Aspergillus niger, Aspergillus flavus and Candida albicans was recorded at 100 mg/ml of the crude relative to ketoconozole and fluconazole drugs. Similarly, different concentrations (25 mg/ml, 50 mg/ml and 100 mg/ml) of the crude extracts of bitter cola inhibited species of Escherichia coli and Pseudomonas aeruginosa almost as effectively as the control drug of streptomycine used. Chronic lead acetate poisoned wistar rats in groups B, C, D, E exposed to G. kola supplemented feed and water ad libitum showed variable decrease in the serum alkaline phosphatase level while aspartate and alanine aminotransferases level reduces in C and D groups compared to the negative control group. The kidney biomarkers; serum creatinine and urea concentrations were not significantly different at P â¤Â 0.05 for rat groups C, D, E when compared with the positive and negative control groups respectively. Mild infiltration and cell distortion were observed in the liver and kidney sections of the rats exposed to uncoated bitter cola supplemented feed while suggesting an overriding effect from the nut coats. The study reaffirms the medicinal potential of coated and uncoated bitter cola to act as abatement of lead toxicity and alternative antimicrobial. Furthermore, G. kola could be a double-edged drug for the spontaneous amelioration of lead toxicity and secondary infections due to lead poisoning. Keywords: Garcinia kola, Antimicrobial, Lead abatement, Histopathology, Opportunistic pathogen