Effect of antiandrogen flutamide on measures of hepatic regeneration in rats

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. © 1989 Plenum Publishing Corporation

Characterization of the Plasmidic or Chromosomal cpe Gene and Metabolic Activities in Clostridium perfringens Isolates from Food in San Luis - Argentina

Food poisoning and non-food poisoning illnesses due to C. perfringens (by enterotoxin production) have been associated to chromosomal or plasmidic location of the cpe gene, respectively. Clostridial pathogenicity has been correlated to protease and azoreductase production.The aim of this work was: i) to assess the sanitary-hygienic quality of dehydrated soups (100 samples) consumed in San Luis – Argentina; ii) to verify the presence of C. perfringens in these food products using the "Most Probable Number" method (MPN) and plate-counting methods; iii) to characterise enterotoxigenicity in strain isolates by RPLA; iv) to determine the chromosomal or plasmidic location of the cpe gene in enterotoxigenic strains previously isolated from food in our lab, using PCR; v) to correlate chromosomal cpe and spore heat-resistance; vi) to compare protease activity in cpe+ and cpe– strains; and vii) to compare azoreductase activity in cpe+ and cpe– strains. Twenty-six isolates had a count a 3–43 bacteria g-1 count using MPN; 7.7% exceeded the Argentine Food Code (CAA) limit. All isolates showed protease activity: enterotoxigenic isolates had higher protease activity than non-enterotoxigenic isolates. All isolates showed azoreductase activity: enterotoxigenic isolates had higher activity and shorter reducing times. Enterotoxigenic isolates showed chromosomal location for the gene responsible for the enterotoxin.Fil: Corigliano, Mariana Georgina. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Guzmán, Ana María Stefanini. Universidad Nacional de San Luis; ArgentinaFil: Stagnitta, Patricia Virginia. Universidad Nacional de San Luis; Argentin

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

Optimization of a yeast estrogen screen and its applicability to study the release of estrogenic isoflavones from a soygerm powder.

Here we describe a redesigned protocol of the yeast estrogen screen developed by Routledge and Sumpter. The redesigned test comprises two steps. First, a large amount of yeast with estrogenic compounds is incubated for 24 hr. Subsequently, a mixture of cycloheximide and the chromogenic substrate chlorophenol red-beta-d-galactopyranoside (CPRG) is added. The cycloheximide stops protein synthesis and allows for an end-point measurement of beta-galactosidase activity generated during the first 24 hr. CPRG is converted to chlorophenol red and reflects beta-galactosidase activity, which is indicative of the estrogenic activity. The modifications shorten the duration of the assay at least 1 day and avoid interference of the estrogenic CPRG or chlorophenol red. The redesigned and the original protocol were used to study the estrogenic activity of bisphenol A, methoxychlor, p,p'-DDT, and isoflavones (genistein, daidzein, and glycitein). Bisphenol A, methoxychlor, and genistein triggered higher levels of beta-galactosidase activity in the redesigned protocol. Estrogenic activity of p,p'-DDT could only be demonstrated with the redesigned protocol. Glycitein and daidzein failed to give a response with both protocols. We also studied deconjugation of beta-glycosidic isoflavones present in soygerm powder. Treatment of the soygerm powder with beta-glycosidase released isoflavones. The estrogenic response of the samples was confirmed with the redesigned protocol and correlated with the amount of genistein present. The release of isoflavones under conditions prevailing in the intestines was studied. Bacterial beta-glycosidase present in the large intestine released isoflavones, and moderate estrogenic activity could be demonstrated

Role of estrogens and epidermal growth factor in hepatocellular carcinoma (HCC)

Estrogen (E) and epidermal growth factors (EGF) receptors were assayed in the liver of nine patients with hepatocellular carcinoma (HCC). Total E and nuclear E receptors were decreased significantly in neoplastic tissue as compared to the levels found in surrounding nonneoplastic tissue. The EGF receptor was decreased also in neoplastic tissue. On the basis of binding data, a decrease in the number but not in affinity of both the E and EGF receptors was found. © 1991 Plenum Publishing Corporation

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Examining the effects of sodium ions on the binding of antagonists to dopamine D2 and D3 receptors

Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo

Assessing weight perception accuracy to promote weight loss among U.S. female adolescents: A secondary analysis

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity have become a global epidemic. The prevalence of overweight and obesity among U.S. adolescents has almost tripled in the last 30 years. Results from recent systematic reviews demonstrate that no single, particular intervention or strategy successfully assists overweight or obese adolescents in losing weight. An understanding of factors that influence healthy weight-loss behaviors among overweight and obese female adolescents promotes effective, multi-component weight-loss interventions. There is limited evidence demonstrating associations between demographic variables, body-mass index, and weight perception among female adolescents trying to lose weight. There is also a lack of previous studies examining the association of the accuracy of female adolescents' weight perception with their efforts to lose weight. This study, therefore, examined the associations of body-mass index, weight perception, and weight-perception accuracy with trying to lose weight and engaging in exercise as a weight-loss method among a representative sample of U.S. female adolescents.</p> <p>Methods</p> <p>A nonexperimental, descriptive, comparative secondary analysis design was conducted using data from Wave II (1996) of the National Longitudinal Study of Adolescent Health (Add Health). Data representative of U.S. female adolescents (N = 2216) were analyzed using STATA statistical software. Descriptive statistics and survey weight logistic regression were performed to determine if demographic and independent (body-mass index, weight perception, and weight perception accuracy) variables were associated with trying to lose weight and engaging in exercise as a weight-loss method.</p> <p>Results</p> <p>Age, Black or African American race, body-mass index, weight perception, and weight perceptions accuracy were consistently associated with the likeliness of trying to lose weight among U.S. female adolescents. Age, body-mass index, weight perception, and weight-perception accuracy were positively associated (<it>p </it>< 0.05) with trying to lose weight. Black/African American subjects were significantly less likely than their White counterparts to be trying to lose weight. There was no association between demographic or independent variables and engaging in exercise as a weight-loss method.</p> <p>Conclusions</p> <p>Findings suggest that factors influencing weight-loss efforts, including age, race, body-mass index, weight perception, and weight-perception accuracy, should be incorporated into existing or new multi-component weight-loss interventions for U.S. adolescent females in order to help reduce the national epidemic of overweight and obesity among U.S. female adolescents.</p

Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn)

This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion