Peroxisome proliferator-activated receptors and hepatitis C virus.

The prevalence of type 2 diabetes mellitus and insulin resistance are higher among people chronically infected with hepatitis C (CHC) when compared with the general population and people with other causes of chronic liver disease. Both insulin resistance and diabetes are associated with adverse outcomes across all stages of CHC, including the liver transplant population. CHC is also associated with the development of hepatic steatosis, a common histological feature present in approximately 55% (32-81%) of cases. There is a complex interrelationship between insulin resistance and hepatic steatosis and both are postulated to aggravate each other. The peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in the regulation of glucose, lipid homeostasis, inflammatory response, cell differentiation, and cell cycle. The relationship between hepatitis C virus replication and PPARs has been the focus of recent study. Given the availability of potent agonists, PPARs may represent a novel pharmacological target in the treatment of CHC.

Meta-analysis: insulin resistance and sustained virological response in hepatitis C.

BACKGROUND: A higher baseline homeostasis model assessment of insulin resistance (HOMA-IR) score has sometimes predicted a poorer sustained virological response (SVR) rate to peginterferon/ribavirin therapy in treatment-naïve chronic hepatitis C patients. AIM: To perform a meta-analysis to evaluate the impact of HOMA-IR on SVR in hepatitis C. METHODS: Relevant studies were identified by searching Medline and EMBASE. We identified 17 publications that addressed the influence of insulin resistance on SVR. The random effect model of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4, Madrid, Spain. RESULTS: Normal insulin sensitivity was associated with a higher rate of SVR [odds ratio (OR) 2.86 (95%CI: 1.97-4.16)] in comparison with insulin resistance. Moreover, in separate analysis by genotype selecting studies that used HOMA-IR > 2 as cut-off defining insulin resistance, SVR was higher in patients with HOMA-IR < 2 in all genotypes: HCV-1 [OR: 2.16 (95%CI: 1.51-3.08)], HCV-2&3 [OR: 3.06 (95%CI: 1.06-8.82)] and HCV-4 [OR: 6.65(95%CI: 2.51-17.61)]. Studies reporting no association between HOMA and SVR included easy-to-cure cohorts, analysed variables strongly related with insulin resistance like body mass index, steatosis, hyper γGT, age and fibrosis and reported differences in handling and interpretation of HOMA-IR. CONCLUSION: Elevated HOMA-IR was associated with a lower cure rate of patients with hepatitis C treated with Peg-IFN-α/ribavirin irrespective of genotype, and the more difficult-to-treat cohort, the better the HOMA-IR prediction. HOMA-IR is, as a surrogate marker of insulin resistance, susceptible to some biases derived from both handling and interpretation.

The epidemiology of schistosomiasis in Egypt: Minya Governorate.

Risk factors, prevalence, and intensity of infection with Schistosoma sp. and prevalence and magnitude of morbidity caused by schistosomiasis was assessed in a stratified random sample of 16,433 subjects from 2,409 households in 33 rural communities in Minya Governorate, Egypt. The prevalence of S. haematobium ranged from 1.9% to 32.7% among the communities and averaged 8.9%. The average intensity of infection was a geometric mean egg count (GMEC) of 8.5 per 10 ml of urine and ranged from 1.6 to 30.9. Prevalence was maximum (18-20%) in those 10-20 years of age and higher in males than in females. Intensity of infection followed the same pattern. Infection with S. mansoni was present almost exclusively in a single village, confirming spread of this species up the Nile River and its focality in Minya. Risk factors for S. haematobium infection were an age from 11 to 20; male gender; males bathing in, women washing clothing or utensils in, and children swimming or playing in canals; and a history of, or treatment for, schistosomiasis. Recent history of burning micturition was associated with infection in children but not in adults, while a history of blood in urine correlated with S. haematobium infection in both age groups. Reagent strip-detected hematuria and proteinuria were highly associated, particularly in children, with S. haematobium infection. The presence of hepatomegaly or splenomegaly on physical examination was not associated with S. haematobium ova in the urine. Hepatomegaly, as measured by ultrasonography in the midclavicular line or the midsternal line, or ultrasonography-detected splenomegaly were not present more frequently in infected subjects than in uninfected subjects. Schistosoma ova were not detected more frequently in urine of subjects with ultrasonography-detected periportal fibrosis than in the urine from subjects without this finding. Ultrasonography-detected urinary bladder wall lesions were detected in only 6 (0.3%) subjects and obstructive uropathy was observed in 54 (2.7%) subjects. The absence of an association between prevalence of urinary tract morbidity and S. haematobium infections was surprising. Two possible explanations are 1) that repeated chemotherapy has reduced the prevalence of urinary tract morbidity and 2) that morbidity was not being detected by the ultrasonographic operators.

The in vitro characterisation and biodistribution of some non-ionic surfactant coated liposomes in the rabbit.

The degree of adsorption of some novel silicone glycol copolymers onto polystyrene microspheres was studied and compared with the sorption onto small unilamellar vesicles (SUVs) composed of egg phosphatidylcholine (EPC) and prepared by the detergent dialysis technique. These non-ionic surfactants are 'comb' polymers of the ABn type where A is a silicone chain with n pendant polyglycol chains (B). Photon correlation spectroscopy was used to measure the adsorbed layer thickness (delta h) following polymer sorption from aqueous solutions. delta h on latex particles was a function of the length of the polymer hydrophilic chains. Upon incubation with SUVs, delta h of the different polymers was similar (3 nm) and significantly less (two sample t-test, p < 0.01) than the corresponding delta h on the polystyrene latex which could be attributed to the penetration of the polymers into the outer phospholipid bilayer. The glycol chains of the silicone polymers are assumed to be in a helical and planar position. Efflux of 5(6)-carboxyfluorescein from EPC liposomes was increased by the presence of these polymers. The highest retention (49% at 5 h) was obtained with SUVs coated with the silicone polymer possessing the highest glycol content and the longest ethylene oxide chains. Sterically stabilised vesicles were also formed by coating dipalmitoyl phosphatidyl-choline (DPPC)/cholesterol (Chol) (molar ratio 1:1) with two of these silicone glycol copolymers and Poloxamer 338. The liposomes were labelled with 67gallium-desferrioxamine (67Ga-DF). Incubation of radiolabelled Poloxamer 338-coated vesicles in saline or serum at 37 degrees C for 24 h resulted in less stable liposomes compared to the more stable non-coated or silicone coated vesicles. Following intravenous (i.v.) administration in rabbits, free 67Ga-DF rapidly disappeared from the circulation (half-life = 41.4 min) and accumulated in the bladder. Two populations of vesicles were prepared (136 +/- 2.9 nm and 100 +/- 1.4 nm). 24 h after i.v. injection of the different formulations of the 100 nm liposomes in rabbits, 20-27% of the activity was retained in blood. The silicone polymer with the highest glycol content and the longest ethylene oxide chains showed the longest half-life (21.4 h). Using gamma scintigraphy, the liver/spleen uptake of the 136 nm non-coated vesicles was 57% which was significantly reduced to 37% upon coating the liposomes with the silicone glycol copolymers. At 30 min post i.v. injection, approximately 10% of the activity was associated with the heart/lung region irrespective of liposome size or polymer coating.(ABSTRACT TRUNCATED AT 400 WORDS)