Altered cytokine profile under control of the serotonergic system determines the regulation of CYP2C11 and CYP3A isoforms.

The aim of this study is to assess a potential mechanism by which the serotonergic system can control the expression and activity of cytochrome (CYP) 2C11 and CYP3A isoforms during liver insufficiency. A rat model of diethylnitrosamine (DEN)-induced liver insufficiency was developed by administering 50 mg/kg of DEN twice a week for 7 weeks. Dysfunction of the serotonergic system was evoked by feeding the rats with a tryptophan-free diet for three weeks. Dysfunction of the serotonergic system during liver insufficiency decreased the level of proinflammatory cytokines (TGF-ß and IL-1ß) and increased the level of an anti-inflammatory cytokine (IL-4). Simultaneously, activation of the repressive mechanism IL-4/JAK1/STAT6/SOCS1 of the JAK2/STAT5b-mediated signal transduction pathway and the pERK1/2/GR/STAT6 signal transduction pathway resulted in the suppression of the CYP2C11 and CYP3A isoforms. Moreover, dysfunction of the serotonergic system during liver insufficiency equalized the level of testosterone to the basal level, did not change the steady state of the corticosterone level and significantly enhanced the reduced level of growth hormone. An altered cytokine profile under control of the serotonergic system determines the regulation of CYP2C11 and CYP3A isoforms during liver insufficiency through mechanisms based on posttranscriptional and posttranslational processes.

[Predictors of hepatic insufficiency in obstructive jaundice]. / Prediktory pechenochnoi nedostatochnosti pri mekhanicheskoi zheltukhe.

AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice. MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency. RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%. CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.

Preoperative Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Perioperative Liver-Related Complications Following Liver Resection for Colorectal Cancer Metastases.

BACKGROUND AND AIMS: There are limited data on the potential role of preoperative non-invasive markers, specifically the aspartate-to-alanine aminotransferase ratio and the aspartate aminotransferase-to-platelet ratio index, in predicting perioperative liver-related complications after hepatectomy for colorectal cancer metastases. METHODS: Patients undergoing liver resection for colorectal cancer metastases in a European institution during 2003-2010 were retrospectively enrolled. Relevant data, such as neoadjuvant chemotherapy, preoperative liver function tests, and perioperative complications, were collected from medical records. The nontumorous liver parenchyma in the surgical specimens of 31 patients was re-evaluated. RESULTS: Overall, 215 patients were included. In total, 40% underwent neoadjuvant chemotherapy and 47% major resection, while 47% had perioperative complications (6% liver-related). In multivariate regression analysis, the aspartate aminotransferase-to-platelet ratio index was independently associated with liver-related complications (odds ratio: 1.149, p = 0.003) and perioperative liver failure (odds ratio: 1.155, p = 0.012). The latter was also true in the subcohort of patients with neoadjuvant chemotherapy (odds ratio: 1.157, p = 0.004) but not in those without such therapy (p = 0.062). The aspartate-to-alanine aminotransferase ratio was not related to liver-related complications (p = 0.929). The area under the receiver operating characteristics curve for the aspartate aminotransferase-to-platelet ratio index as a predictor of liver-related complications was 0.857 (p = 0.008) in patients with neoadjuvant chemotherapy. Increasing aspartate aminotransferase-to-platelet ratio index was observed with an increase in degrees of sinusoidal obstruction syndrome (p = 0.01) but not for fibrosis (p = 0.175) or steatosis (p = 0.173) in the nontumorous liver in surgical specimens. CONCLUSION: The preoperative aspartate aminotransferase-to-platelet ratio index, but not the aspartate-to-alanine aminotransferase ratio, predicts perioperative liver-related complications following hepatectomy due to colorectal cancer metastases, in particular after neoadjuvant chemotherapy. The aspartate aminotransferase-to-platelet ratio index is related to sinusoidal obstruction syndrome in the nontumorous liver.

In vivo antioxidant and biochemical evaluation of Sphenocentrum jollyanum leaf extract in P. berghei infected mice.

Recent approach in treatment and drug development suggested that the control of oxidative stress in malarial infected patients may be an added advantage. In this study, effect of methanolic leaf extract of Sphenocentrum jollyanum pier (S. jollyanum) on liver damage, markers of oxidative stress and alteration in lipid profile in P. berghei infected mice was assessed. Oxidative stress was induced by intravenously inoculation of mice with 1 × 107 sporozoites P. berghei. Treatment of parasitized mice with leaf extract of S. jollyanum had a significant (p<0.05) reductions in elevated levels of total protein, globulin, AST, ALT, ALP, GGT and total bilirubin, serum, kidney and liver malondialdehyde (MDA) concentrations, but caused a significant (p<0.05) increased in the activities of serum and liver catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) level when compared with parasitized non-treated group (PNT). The extract treated group also showed significant (p<0.05) improvement in the levels of HDLc, total cholesterol, LDL and reduction in triglyceride compared with parasitized non treated group. Our results revealed that the protective capacity and antioxidant activity of the extract is dose dependant. The findings suggest that antioxidant property of Sphenocentrum jollyanum leave extract might be an added advantage to it anti-malarial activity.

Relationship between indocyanine green clearance test and feed intake and impaired hepatic function in dairy cows.

The purposes of this study were 1) to examine changes in the indocyanine green (ICG) clearance by feeding and 4-day fasting in dry cows, and (2) to investigate the relationship between ICG clearance and blood chemistry profile in postpartum cows. In 3 dry cows, post-feeding ICG half-life (T(1/2)) was shorter than the pre-feeding value, and post-fasting T(1/2) was longer than pre-feeding and post-feeding values. In 16 lactating cows, T(1/2) value at 2 weeks postpartum showed positive correlations with AST, T-Bil and γ-GTP. These results suggested that ICG clearance correlated with T-Bil and liver enzymes can be sensitive and accurate diagnostic marker for impaired liver function in dairy cows. In addition, ICG clearance is greatly affected by feeding and fasting.

[Effectiveness of nutritional support for the liver-cell deficiency in the liver cirrhosis].

THE AIM: To study the efficiency of enteral nutritional support and its impact on clinical-laboratorial markers of hepatocellular failure of the patients with Child-Pue's hepatic cirrhosis type B suffering from trafologic impairment. MATERIAL AND RESEARCH METHODS: 61 patients with Child-Pue's hepatic cirrhosis type B suffering from trafologic impairment took part in the randomized prospective study. The control group (31 patients) got the conventional treatment with lactulose, beta-blocker, spironolactone on the basis of 1.2 g/kg protein weight and 30 kcal/kg body weight per day. There were 30 patients in the second group (the principal one) and in addition to conventional treatment they got the multisubstrate nutritional cocktail of dietary fibers on the basis of 0.3 g/kg protein weight, 7.5 g fibers per day and 10 kcal/kg body weight during 30 days. To evaluate the efficiency of the treatment we analyzed the clinical presentation and the intensity of blood cholinesterase. The stage of hepatic encephalopathy was defined with the affinity numbers test of Retainer. The parameters under study were checked before the treatment, 30 days and 60 days later after the treatment began. RESULTS: It was found out during the prospective randomized study that the patients under nutritional support showed the positive clinical dynamics (asthenia and hepatic encephalopathy retrogression and the accurate increase of blood cholinesterase from 4365.4 +/- 1028.6 ME up to 5502.7 +/- 1142.6 ME (p < 0.05). CONCLUSION: Nutritional support of the patients with Child-Pue's hepatic cirrhosis type B suffering from trafologic impairment is effective and has an accurate impact upon clinical-laboratorial markers of hepatocellular failure.