Acute rejection of non-functional allograft in kidney transplant recipients with hepatitis C treated with peginterferon alpha-2a: Reply

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Effect on the canine Eck fistula liver of intraportal TGF‐β alone or with hepatic growth factors

Transforming growth factor‐β canceled the hepatocyte proliferation caused by transforming growth factor‐α when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast, transforming growth factor‐β had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor‐2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected, but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor‐α and transforming growth factor‐α in the modulation of liver growth control. (HEPATOLOGY 1992;16:1267–1270.) Copyright © 1992 American Association for the Study of Liver Disease

Effect of spironolactone and potassium canrenoate on cytosolic and nuclear androgen and estrogen receptors of rat liver

Spironolactone and potassium canrenoate are diuretics that are used widely for management of cirrhotic ascites. The administration of spironolactone frequently leads to feminization, which has been noted less frequently with the use of potassium canrenoate, a salt of the active metabolite of spironolactone. The use of these two drugs has been associated with decreases in serum testosterone levels and spironolactone with a reduction in androgen receptor (AR) activity. This decrease in AR has been cited as the cause of the antiandrogen effect of these drugs. We therefore assessed the effect of both drugs on levels of androgen and estrogen receptors (ER) in the liver, a tissue that is responsive to sex steroids. Three groups of male rats (n = 12 rats each) were studied. Group 1 (control) received vehicle only; group 2 received spironolactone (5 mg/day); group 3 received potassium canrenoate (5 mg/day). After 21 days of treatment, the animals of all groups were killed and liver tissue was assayed for nuclear and cytosolic AR and ER, and for male specific estrogen binder (MEB), an androgen-responsive protein. Both drugs drastically decreased the nuclear AR content, as compared with the control group, but only spironolactone decreased cytosolic AR. When the total hepatic content of AR is considered, a highly significant decrease is observed only in rats treated with spironolactone. This reduction in hepatic AR content suggested loss of androgen responsiveness of liver. We confirmed this by assessing levels of MEB, and found that livers from group 2 animals had no detectable MEB activity, whereas livers from both group 1 and 3 had normal MEB activity. No changes were observed in nuclear ER and cytosolic ER of group 3 as compared with group 1. Nuclear estrogen receptor decreased and cytosolic ER increased in group 2, but with no change in total ER content. These results indicate that (a) only spironolactone appears to act as an antiandrogen in liver, resulting in a decrease in both AR and male specific estrogen binder content, and (b) neither drug results in elevated hepatic ER content, although spironolactone-treated animals show an altered subcellular localization. © 1987

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third‐party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140–143.) Copyright © 1991 American Association for the Study of Liver Disease

Irrigation with treated municipal wastewater on artichoke crop: assessment of soil and yield heavy metal content and human risk

Industrial and municipal wastewaters are often used for irrigating agricultural fields in arid and semi-arid countries, representing the most attractive option to alleviate pressure on fresh-water resources. However, the wastewater may contain various potentially toxic elements and organic matters with highly harmful effects on human and animal health. During two growing seasons of globe artichoke, the effects of irrigation with secondary (SWW) and tertiary (TWW) municipal wastewater on heavy metal soil and plant content were evaluated together with the consequent human risk from artichoke head consumption. The heavy metal contents (i.e., Al, Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn, and Mn) of the irrigation water, soil, plant and yield were analyzed. Total and extractable heavy metals were quantified to determine the bioaccumulation factors, and the health risks to adults and children were determined according to hazard indices. The heavy metal contents of the artichoke heads harvested after SWW and TWW irrigation were lower than the international threshold values and low bioaccumulation factors suggested that these heavy metals did not accumulate in the edible part of the artichoke crop. The hazard indices based on the consumption of the artichoke heads remained <1.0 for both adults and children, thus indicating that the health risks involving the different heavy metals are not significant

The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D‐galactosamine

Galactosamine induces a dose‐dependent hepatic injury in rats and many other animals. The toxicity of D‐galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D‐galactosamine‐induced hepatic necrosis in rats. D‐Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after D‐galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000 subfraction attained statistical significance with respect to the saline control. Copyright © 1986 American Association for the Study of Liver Disease

Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis

Glucagon was tested for its effect on plasma adenosine 3′,5′-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation. © 1978

Liver regeneration in dogs: Morphologic and chemical changes

Forty-four percent and 72% hepatectomy were carried out in dogs and the animals were sacrificed for biochemical and pathologic studies from 0.5 to 6 days later. Compensatory hypertrophy and hyperplasia ("regeneration") were evident within 1 day, reached a maximum in 3 days, and were almost complete by 6 days. Coincident with the histologic events of regeneration were decreases in responsiveness of receptor adenyl cyclase to glucagon stimulation, increases of cyclic AMP, inconsistent changes in plasma insulin, and increases in plasma glucagon. These studies have standardized hepatic resection in dogs and they have focused attention upon some possible mechanisms that will require further study. © 1978 Academic Press, Inc. All rights of reserved