1,721,192 research outputs found
Measurement of sulfobromophthalein uptake in isolated rat hepatocytes by a direct spectrophotometric method.
No full textA spectrophotometric technique is described for the continuous recording of sulfobromophthalein uptake by isolated hepatocytes. The technique is based on the principle that sulfobromophthalein behaves as a pH-indicator and may be followed photometrically when moving from the medium at pH 7.8 into the interior of the cell. Data show that upon addition of cells to a sulfobromophthalein solution, an absorbance change can be recorded. The kinetics of the process is biphasic and the initial rate is linearly related to the amount of cells added. By this technique it was confirmed that the substrate dependence of the initial velocity of transport is a compound function including a saturable portion with an apparent Km in the mu molar region. Experiments carried out either in the presence of valinomycin or of high concentrations of potassium chloride indicate that the presence of a membrane potential opposes the entry of sulfobromophthalein into isolated hepatocytes. This finding is in agreement with previous observations in isolated plasma membrane vesicles and in liposomes reconstituted with purified bilitranslocase which indicate a rheogenic type of transport for the dye. Low concentrations of nicotinate (1.6 microM) efficiently inhibit the saturable transport. It is suggested, in addition, that the sensitivity of the transport to valinomycin could be used as an early indication of the functional integrity of cell preparations
Antiviral therapy: Why does it fail in HCV-related chronic hepatitis?
No full textHCV infection is a very common cause of chronic viral hepatitis. It is a worldwide health problem with approximately 170 million persons infected and areas of high endemicity in which the percentage of the population infected reaches 30%. It is a progressive disease that can lead to complications such as severe liver fibrosis and cirrhosis, ascites, esophageal varices, gastrointestinal bleeding and, in 30-50% of patients with cirrhosis, hepatocellular carcinoma. Extrahepatic pathologies such as mixed cryoglobulinemia, non-Hodgkin lymphoma and membrano-proliferative glomerulonephritis have been associated with HCV infection. Effective treatment exists, and is based on IFN-α. Sustained disappearance of the virus (sustained virological response) radically changes the natural history of chronic hepatitis C, with reduced or no disease progression and complications. Interferon-based treatment has improved over the years owing to the association with ribavirin and subsequently with 'pegylation' of interferon molecules. The present standard of care results in a response rate of up to 80% in some subpopulations. Nevertheless, some patients do not respond to this therapy. Several factors predicting nonresponse to interferon therapy have been investigated since it became available. These factors include the characteristics of the virus and of the subject infected, and the therapy used. The aim of this article is to provide an overview of these factors, and insights into the newly recognized causes of nonresponse to help clinicians select the most appropriate therapy for HCV viral hepatitis. © 2011 Expert Reviews Ltd
Steatosis as a co-factor in chronic liver diseases
No full textThe finding of lipid accumulation in the liver, so-called hepatic steatosis or non-alcoholic fatty liver disease, is a common condition frequently found in healthy subjects. Its prevalence, in fact, has been estimated by magnetic resonance studies to be about 35% in the general population and 75% in obese persons. Nevertheless, its presence generates liver damage only in a small percentage of subjects not affected by other liver diseases. It should be defined as a “co-factor” capable of affecting severity and progression, and also therapeutic perspectives, of liver diseases to which it is associated. Herein we will evaluate the impact of hepatic steatosis and obesity on the most common liver diseases: chronic viral hepatitis C and B, and alcoholic liver disease
Hepatitis C Virus Infection and Non-Hepatocellular Malignancies in the DAA Era: A Systematic Review and Meta-Analysis
No full textDirect antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. HCV is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma(B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation". In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases
Electrophysiological evidence for Na+-coupled bicarbonate transport in cultured rat hepatocytes
No full textRecent observations suggest that hepatocytes exhibit basolateral electrogenic Na+-coupled HCO3- transport. In these studies, we have further investigated this transport mechanism in primary culture of rat hepatocytes using intracellular microelectrodes to measure membrane potential difference (PD) and the pH-sensitive fluorochrome 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein to measure intracellular pH (pH(i)). In balanced media containing 25 mM HCO3-, PD averaged -32.1 ± 0.6 (SE) mV and pH(i) averaged 7.22 ± 0.03. PD became more negative (hyperpolarized) when extracellular [HCO3-] was increased and less negative (depolarized) when extracellular HCO3- was decreased. Acute replacement of extracellular Na+ by choline also resulted in membrane depolarization of 18.0 ± 1.6 mV, suggesting net transfer of negative charge. This decrease in PD upon Na+ removal was HCO3--dependent, amiloride insensitive, and inhibited by the disulfonic stilbene 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). PD also decreased upon acute exposure to SITS. The degree of depolarization seen with removal of Na+ or HCO3- correlated directly with resting PD (r = 0.81 and 0.95, respectively), suggesting a voltage-dependent mechanism. Removal of extracellular Na+ also decreased pH(i) to 7.06 ± 0.02, and this acidification was decreased in the absence of HCO3- or in the presence of SITS or amiloride. These studies provide direct evidence for electrogenic Na+-coupled HCO3- transport in rat hepatocytes. Further, they suggest that it represents a major pathway for conductive movement of Na+ across the membrane and that it contributes, along with Na+-H+ exchange, to the intracellular acidification observed upon removal of extracellular Na+. Thermodynamic considerations as well as the acute effect of SITS on PD suggest that this mechanism may mediate influx of Na+, HCO3-, and net negative charge under basal conditions and that it may be regulated in part by the membrane PD
Adiponectin in hepatology
No full textadiponectin is a protective adipocytokine, involved in the regulation of glucose and lipid metabolism, produced by adipocytes. adiponectin levels are inversely related to insulin resistance and are lower in obese subjects and in patients with insulin resistance. the hepato-protective effects of adiponectin are largely mediated by the coordination of multiple signalling pathways, leading to enhanced fat oxidation, reduced lipid synthesis and prevention of hepatic steatosis. literature recently highlighted the role played by adiponectin in the development and progression of liver diseases, in particular non-alcoholic fatty liver disease and chronic hepatitis C. In this context, genetic predisposition influences the evolution of hepatic injury. adiponectin and its pathways are promising candidates for future development in both the pharmacotherapy and the prediction of liver and metabolic diseases
Responsiveness to phenobarbital in an adult with Crigler-Najjar disease associated with neurological involvement and skin hyperextensibility.
No full textWe present the case of a 23-yr-old man who had had since birth marked and sustained unconjugated non-hemolytic hyperbilirubinemia and who had had several attacks of grand mal seizures. Analysis of serum bilirubin by diazoreactive methods showed serum levels of unconjugated bilirubin as high as 445 mumol/L that were not affected by phenobarbital administration. However, analysis of serum bile pigments by high-pressure liquid chromatography demonstrated marked decrease of unconjugated bilirubin after phenobarbital treatment (from 432.4 mumol/L to 291.0 mumol/L) associated with slight increase of bilirubin monoconjugates and disconjugates (from 0.25 mumol/L to 0.42 mumol/L). Furthermore, in the past few years the patient had exhibited striking skin hyperextensibility and diaphragm eventration. This case confirms that alkaline methanolysis-high-pressure liquid chromatography is the most reliable method for assessment of serum fraction bilirubin levels; that clinical parameters such as neurological signs do not unequivocally discriminate between type I and II Crigler-Najjar disease and that response to phenobarbital treatment remains the main diagnostic tool
Thrombocytopenia as a sensitive marker of immunologic activity in a patient with autoimmune chronic active hepatitis.
No full textThe case of autoimmune chronic active hepatitis in a 57-year-old female is reported. Onset was signalled by an abrupt and dramatic thrombocytopenia, which was also the only laboratory parameter able to monitor treatment and progression of the disease. It is concluded that thrombocytopenia together with the presence of antiplatelet-antibodies might be useful markers to monitor the treatment and evolution of the disease
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