Increased renal ENaC subunits and sodium retention in rats with chronic heart failure

The goal of this study was to examine acute morphological changes, edema, muscle damage, inflammation, and hypoxia in urethral and vaginal tissues with increasing duration of vaginal distension (VD) in a rat model. Twenty-nine virgin Sprague-Dawley rats underwent VD under anesthesia with the use of a modified Foley catheter inserted into the vagina and filled with saline for 0, 1, 4, or 6 h. Control animals were anesthetized for 4 h without catheter placement. Urogenital organs were harvested after intracardiac perfusion of fixative. Tissues were embedded, sectioned, and stained with Masson's trichrome or hematoxylin and eosin stains. Regions of hypoxia were measured by hypoxyprobe-1 immunohistochemistry. Within 1 h of VD, the urethra became vertically elongated and displaced anteriorly. Edema was most prominent in the external urethral sphincter (EUS) and urethral/vaginal septum within 4 h of VD, while muscle disruption and fragmentation of the EUS occurred after 6 h. Inflammatory damage was characterized by the presence of polymorphonuclear leukocytes in vessels and tissues after 4 h of VD, with the greatest degree of infiltration occurring in the EUS. Hypoxia localized mostly to the vaginal lamina propria, urethral smooth muscle, and EUS within 4 h of VD. Increasing duration of VD caused progressively greater tissue edema, muscle damage, and morphological changes in the urethra and vagina. The EUS underwent the greatest insult, demonstrating its vulnerability to childbirth injury.     

Nocturnal hypoglycaemia in patients receiving conventional treatment with insulin.

The prevalence of nocturnal biochemical hypoglycaemia--that is, blood glucose concentrations below 3 mmol/l (55 mg/100 ml)--was evaluated in a random sample of 58 insulin dependent diabetics receiving twice daily insulin. Seventeen patients had at least one blood glucose value below 3 mmol/l (55 mg/100 ml) and five a value below 2 mmol/l (36 mg/100 ml) during the night. Both bedtime (2300) and fasting morning (0700) blood glucose concentrations were significantly lower in the group with nocturnal hypoglycaemia compared with the group without (p less than 0.00001). If the bedtime blood glucose concentration was below 6 mmol/l (108 mg/100 ml) the risk of nocturnal hypoglycaemia was 80% (95% confidence limits 51-96%). If the bedtime blood glucose concentration was above 6 mmol/l the likelihood of hypoglycaemia not occurring during the night was 88% (74-96%). The mean glycosylated haemoglobin A1c (HbA1c) concentration in the group with nocturnal biochemical hypoglycaemia (8.2 (range 5.0-12.4)%) was significantly lower than that in the group without (9.4(7.0-14.2)%) (p less than 0.02). The prevalence of nocturnal hypoglycaemia in the patients receiving twice daily insulin (29%) was compared with that in 15 patients receiving thrice daily insulin (47%) and was not found to be significantly different. The likelihood of this risk being greater with thrice daily insulin was, however, 88%. No patient with nocturnal biochemical hypoglycaemia woke up during the night with symptomatic hypoglycaemia. Nocturnal biochemical hypoglycaemia is common during twice daily treatment with insulin, and low values of HbA1c might be associated with a higher risk of such hypoglycaemia. The blood glucose concentration at bedtime is a significant predictor of nocturnal biochemical hypoglycaemia, and HbA1c values might be of help in identifying patients at risk.     

Cytokinome profile of patients with type 2 diabetes and/or chronic hepatitis C infection

Both type 2 diabetes (T2D) and chronic hepatitis C (CHC) infection are associated with increased risk of developing hepatocellular carcinoma (HCC). Cytokines are known to play an important role not only in the mechanisms of insulin resistance and glucose disposal defects but also in the pathological processes occurring in the liver during viral infection. We evaluated the serum levels of many cytokines, chemokines, adipokines and growth factors in patients with type 2 diabetes, CHC, CHC-related cirrhosis, CHC and type 2 diabetes and CHC-related cirrhosis and type 2 diabetes by BioPlex assay. The obtained data evidenced that the serum levels of some proteins are significantly up-regulated in all the patients or in those with only one disease and are often higher, even if in different amounts, when both diseases are associated. In particular, our results can be useful for the clinical monitoring of patients because they give specific information in regard to the progression from CHC to LC and CHD to LCD. Moreover, some molecules have shown significant correlations with clinical/biochemical data, suggesting the possibility to define mini-panels that can be used as specific markers for the different disease staging. However, our observations demonstrate that an integrated approach is much more powerful than isolated measurements to evaluate specific stages of these two complex pathologies (type 2 diabetes and chronic CHC hepatitis) alone or when they are concomitant in a patient. In fact it has emerged as an accurate, simple, specific, noninvasive, reproducible and less expensive method that, in future, could be included in routine clinical practice to monitor the association of type 2 diabetes and/or CHC to liver cirrhosis and, possibly, to cancer, and to improve the prognosis of these diseases.     

Co-infections with hepatitis G and TT virus in patients with chronic hepatitis C in Hungary

The significance of co-infections with novel hepatitis viruses Hepatitis G (GBV-C, HGV) and TT virus (TTV) in chronic hepatitis C is not clear. We determined the prevalence of HGV RNA and TTV DNA in chronic hepatitis C patients and in asymptomatic hepatitis C virus (HCV) carriers, and assessed the influence of these agents on the course of HCV infection. Seventy-seven patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. Previous HBV infection was detected by testing serum HBsAg and aHBc. HGV RNA and TTV DNA were detected by PCR. In the healthy population, the prevalence of anti-HCV was 0.3%, HGV RNA 8.0% and TTV DNA 18.5%. In chronic hepatitis C HGV RNA occurred in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of HGV RNA was 9.09% and TTV DNA 75.7%. Neither HGV RNA nor TTV DNA had apparent effect on the HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.     

Immunomodulators in combined therapy of patients with chronic hepatitis

The efficacy of the use of triple schemes in combined therapy of chronic virus hepatitis was estimated and its safety was monitored. The problems of therapy of mixed hepatitis in drug addicts are discussed. Immunotropic agents, increasing the efficacy of the standard therapy of chronic affections of the liver, are suggested to be used as the third remedy in the combined therapy.     

Prognosis for the patients with chronic hepatitis B

The purpose of the research was to determine the influence of the hepatitis B virus on the progression of the chronic liver disease. In the present paper, 127 patients who were followed up for five years and who had histologically verified chronic liver disease, are described. Fifty two of them were carriers of HBsAg, 75 patients were HBsAg negative, but had other markers typical for a previous infection of HBV in the sera. All the patients were nonalcoholics and no drug addicts. In the sera of these 127 patients markers of HBV were prospectively followed up: HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe, HBVDNA, antiHCV for C virus and anti-D for D virus. It was proved by these investigations that HBV provokes very severe chronic hepatitis: CAH (chronic active hepatitis) and CH (cirrhosis hepatis). It was also proved that HBV replicated in 44.20% patients, namely, HBVDNA was positive in the sera of those patients. In 26.08% of such patients the mutant form of HBV was present. In spite of progressive liver disease and without any antiviral therapy all the patients with chronic HBV cirrhosis hepatis were, after five year-follow-up, in Child-Pugh A grade. It was found that the patients who were HBsAg negative, but had one or more markers of HBV positive in the sera, had also a severe chronic hepatitis. That group of patients remains our object of further research. The five-years follow-up of all these patients demonstrates that it is necessary to find out an efficient medicament against HBV chronic hepatitis. Obligatory vaccination of the risk population against virus B remains the only prevention against this severe disease.     

Sleep in chronic chorea patients after therapy with sodium valproate

In previous researches spontaneous nocturnal sleep in chronic chorea showed short total sleep time, prolonged sleep latency, several awakenings, reduction of REM sleep time, decrease in slow waves sleep, strong increase in sleep spindles. Some of these alterations improved after therapy with lithium, haloperidol and lithium, pimozide. Since the concentration of GABA has been found to be reduced in patients with Huntington's chorea, we studied the effect of sodium valproate, a drug that enhances GABA inhibition in cerebral cortex, on nocturnal sleep of six patients with chronic chorea, aged 35 to 60 years (mean 47,3). Nocturnal polygraphic records (EEG, EOG, EMG of chin muscles) were carried out after two consecutive adjustative nights, both before therapy and after sixty days of treatment with sodium valproate (800-2000 mg four times a day, orally). Moreover, chorea, finger dexterity and gait were each rated once a week by three members of the research team and by one independent observer, using a five points rating scale from 0 (normal) to 4 (very severely abnormal). Before therapy the sleep parameters were in accordance with our previous results in chronic choreic patients. After two months therapy we observed a statistically significant (P less than 0.05) reduction of awakenings and of wake time. Sodium valproate produced no objective change in any of the parameters of motor function studied. If singularly examined, however, a reduction of chorea was obtained only in a patient, whose favourable response to therapy was also demonstrated by the normalization of other sleep parameters. These data stress the importance of sleep study in extrapyramidal disorders and suggest a different involvement of GABA-mediated transmission in various patients with chronic chorea.     

Glucose, immunoreactive insulin and C-peptide immunoreactivity in patients with acute viral hepatitis

Carbohydrate intolerance with high insulin levels are a consistent finding in acute and chronic liver diseases. It has been recently clarified that in cirrhotic patients hyperinsulinism is related to decreased hepatic clearance, but the role of liver cell damage or portal systemic shuntings is still unclear. Therefore, we assessed glucose, immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR), in the basal state and after oral and intravenous glucose load, in fifteen patients with acute viral hepatitis (AVH), a liver disease where cell necrosis is prominent. CPR is a useful tool for investigation of hyperinsulinism as, according to previous reports, it is not - or is only to a limited degree - metabolised by the liver. Our results confirm the carbohydrate intolerance, with high IRI levels, in the early stage of AVH. CPR levels were significantly increased before and after glucose load. This study suggests that liver cell damage plays a key role in the pathogenesis of hyperinsulinism in liver diseases and high CPR values seem also to be related to liver damage.     

Cytogenetic disorders iin patients with chronic hepatitis B and C

The chromosomal apparatus of peripheral blood lymphocytes was studied in 19 patients with chronic hepatitis B (CHB) and 17 patients with chronic hepatitis C (CHC). Significant changes in cytogenetic indices were revealed in the both groups. Incidence of aberrant cells in CHC exceeded significantly that in CHB (15.3 +/- 1.5% vs 11.1 +/- 0.9% respectively; P < 0.05). Frequencies of aberration per cell and chromatid fragments were also significantly higher in CHC compared with both CHB and practically normal donor groups.     

Efficacy and safety of insulin glulisine in patients with type 1 diabetes.

Insulin glulisine (glulisine), a human insulin analogue with a rapid-acting time-action profile, has been developed to fulfil the mealtime (bolus) insulin requirement in patients with diabetes. The aim of this multinational, multi-centre, controlled, open-label, randomized, parallel-group study was to compare the efficacy and safety of insulin glulisine (glulisine) to that of insulin lispro (lispro) in adults diagnosed with Type 1 diabetes. Of the 683 patients randomized, 672 received treatment (339 patients received glulisine, 333 patients received lispro). Over the 26-week study, a similar reduction in mean HbA1c occurred in both groups (adjusted mean change from baseline -0.14% in both groups). The basal insulin dose was relatively unchanged from baseline in the glulisine group but increased in the lispro group (glulisine: 0.12 IU vs. lispro: 1.82 IU; p = 0.0001). As a consequence, total daily insulin dose decreased in the glulisine group but increased in the lispro group (glulisine: -0.86 IU vs. lispro: 1.01 IU; p = 0.0123). There was no relevant difference between the two groups in the reporting of symptomatic hypoglycaemia (overall, nocturnal and severe). This study demonstrates that glulisine provides equivalent glycaemic control to lispro. The clinical relevance of any difference in total daily insulin dose remains to be established.     

Prevalence of hepatitis B virus in chronic hepatitis B patients

The aim of the current study was to detect HBV by Real time - PCR in chronic hepatitis B patients. Fifty-eight sera of chronic hepatitis B patients were subjected during the period March 2009 to April 2010 in Ilam cities in West of Iran. Sera assayed by real-time PCR and ELISA methods. Twenty serum samples from healthy volunteers and non-hepatitis B patients and negative for hepatitis B seromarkers served as negative controls for the study. Among fifty-eight sera, ELISA showed fifty-five (94.8%) of the samples were positive for HBsAg and three (5.2%) negative results obtained while real-time PCR specified fifty-eight (100%) positive results in chronic hepatitis B patients. HBsAg status did not necessarily reflect HBV DNA level in the serum, as 5.2% of chronic Hepatitis B patients were positive for HBV DNA but negative for HBsAg. HBV DNA was not found to be positive amongst any of the negative controls. Real time - PCR is a sensitive and reproducible assay for HBV DNA quantization.     

Levels of some cytokines and antibodies to hepatitis C virus in patients with chronic hepatitis C

The comparison of the levels of some cytokines (tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-2, IL-4) in the blood serum of patients with chronic hepatitis C (CHC) having different antibody spectrum was carried out. In CHC patients increased levels of the serum cytokines IL-1beta, TNF-alpha under study in comparison with cytokine levels in donor sera was noted. In patients with detected antiNS5 and antiHCV IgM and antiNS5 HCV the level of IL-1beta was significantly higher than that in CHC patients without antibodies in sera. A change in the levels of proinflammatory and anti-inflammatory cytokines in the blood sera of CHC patients may be of significant diagnostic and prognostic importance.