Hepatitis C virus RNA in the cutaneous eruption but not in the symptom-free skin from patient with prurigo simplex and chronic C hepatitis.
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Biomedical subjects
Publications and source records attributed to G Lengyel.
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BACKGROUND: Our previous results showed that hepatitis C virus (HCV) is detectable on erythrocytes by RT in situ PCR. The aims of the present study were to compare the sensitivity of this erythrocyte in situ PCR to routine serum solution phase HCV PCR as well as to obtain more data about the binding and cellular localization of HCV in the erythrocyte. METHODS: 105 previously HCV-infected patients and 20 control individuals were studied using RT in situ PCR on erythrocytes and solution phase RT-PCR from serum samples. Binding of HCV to erythrocytes was studied by in vitro inoculation. RT in situ PCR results were evaluated by fluorescence and confocal laser scanning microscopy. RESULTS: From 105 HCV cases, 78 gave positive, while 5-and all control cases-gave negative results by both PCR techniques. In 21 cases, only the in situ technique provided positive results, while in only I case did the solution phase method provide positive results. During in vitro inoculation, an early HCV-erythrocyte binding was detected followed by virus internalization. CONCLUSIONS: Erythrocyte-in situ PCR was found to show higher sensitivity for the detection of HCV compared to the generally applied serum PCR method. In vitro studies suggested a specific binding of HCV to erythrocyte and showed the virus to be capable of internalization.
OBJECTIVE: The metabolic effects of alcohol are due both to its direct action and to that of its first metabolite, and can also be connected with the changes in redox state. Differences in ethanol distribution, bioavailability and hepatic metabolism can provide insight into the protective and predisposing factors in alcoholism, as well as gender differences of alcohol toxicity. Oxidative stress occurs following various conditions of ethanol consumption. DESIGN: Twenty-six Caucasian patients with alcoholism and 32 healthy, abstinent controls of both sexes were investigated with special regard to reduction-oxidation status and ad hoc free-radical-antioxidant balance. METHOD: Plasma free SH-group concentration, H-donating ability, and reducing power property were measured by simple spectrophotometric methods. Total scavenger capacity was determined by a newly developed chemiluminometric method in plasma and erythrocytes. RESULTS: Alcoholics showed a decrease of free SH-group concentration, hydrogen-donating ability and an increase of reducing power property in plasma. A decreased total scavenger capacity of erythrocytes and plasma of alcoholic patients, combined with gender differences, could be detected. CONCLUSIONS: Alcoholic dependence causes gradual exhaustion of the antioxidant capacity of erythrocytes, therefore this non-invasive measurement may be useful as a follow-up of the evolution of alcoholic liver disease. The results also suggest a gender susceptibility of alcohol toxicity.
It has been established that the long term interferon therapy in patients with chronic hepatitis C is able to produce sustained remission only in about 20 per cent of the cases. According to the newest data the combined interferon and ribavirin therapy significantly increases the remission of patients in naive, non-responder or relapsed cases. Clinical remission was confirmed by enzyme activity of alaninamino transferase (ALT) and HCV-RNA-PCR tests. In order to get exact data of the remission rate and the symptom free period, a prospective multicenter study has been introduced in Hungary. Ten leading hepatologic units have been involved into the trial. Till now the combined therapy with interferon-alfa-2b (3 MU, three times a week) and ribavirin--(1000-1200 mg daily) for one year has been finished in 100 cases with chronic hepatitis C. The mean value of ALT activity decreased near to the normal level, in 58 patients it was in the normal range. Side effects with mild or moderate grades have been found in 31 cases. The interim report of this multicenter study confirm the efficacy of this combined therapy in chronic hepatitis C.
The authors are discussing hepatic and extrahepatic pathologic processes caused by hepatitis C virus (HCV) infection and they focus their interest to the skin disorders appearing in the presence of chronic, active HCV infections. The trigger of the immunologic processes leading to dermatologic manifestations are the activated T cells (CD8 + cytotoxic T lymphocytes), cytokins, and also the expansion of certain B cells. Pathologic immunologic phenomena may initiate various dermatologic manifestations. Immunoglobulins, immuncomplexes generated by the disease itself are manifested as various forms of cutan vasculitis. In the present series of patients (pts), HCV related skin disorders known from the literature were diagnosed in eleven cases and they were representing 7 different disease entities. These were palpable purpura (3 pts), urticaria, prurigo and alopecia areata (2-2 pts), lichen ruber planus, pruritus and vitiligo (1-1 patient respectively). The case reports of 2 pts, one with palpable purpura (vasculitis purpurica), one with prurigo and vitiligo are presented in details.
Oxidative stress plays an important role in the pathogenesis of toxic liver diseases and of other hepatic alterations. We summarize the pathomechanism of free radical reactions in liver diseases and the results of experimental and clinical observations. Most of the hepatoprotective drugs belong in the group of free-radical scavengers, their mechanism of action involving membrane stabilization, neutralization of free radicals and immunomodulation. We demonstrate the effects of the different drugs used in the therapy of liver diseases in animal experiments and in human clinicopharmacological studies. The scavenger effect of these drugs has been demonstrated in the subcellular fractions of liver cells in animal experiments. In vitro incubation with some hepatoprotective drugs inhibit lectin-induced lymphocyte transformation while others decrease the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. Dihydroquinolin-type antioxidants and silymarin enhanced the superoxide dismutase activity of erythrocytes and lymphocytes. In addition, in a 6-month double-blind clinical trial of patients with chronic alcoholic liver disease, we studied the effects of silymarin therapy on liver function tests, on the parameters characterizing the oxidative stress and immune reaction, on serum procollagen III peptide level, and on liver histology. A wide range of methods was used. The silymarin preparate corrected the altered immune reaction and the decreased superoxide-dismutase activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhosis. The results indicate that these drugs exert hepatoprotective activity and can improve liver functions in alcoholic patients and in toxic liver diseases. We found a correlation between the bilirubin concentration and lipid peroxidation in cases with toxic liver and biliary tract diseases, and assume that there are two kinds of bilirubin, an antioxidant and a prooxidant form, on the basis of diene conjugates in the bile.
The role of oxidative stress in the development of arteriosclerosis is well established. This pathogenetic explanation unificates in itself the lipid and thrombotic theories. The authors summarize the most substantial literary data in this relation, they discuss in details those therapic methods, in which the natural and synthetic antioxidants are involved as preventive drugs in the development and consequences of arteriosclerosis. Thus the effects of the dihydroquinoline type antioxidants as well as those of Vitamins A, C and E are discussed partly in experimental, partly in clinical studies. The authors conclude on the basis of own and literary data that the application of antioxidants could decrease the blood vessel alterations produced by arteriosclerosis, as well as the pathological tissue alterations developed in the consequences of ischaemia.
Six district hepatotrop viruses causing viral hepatitis have been identified. Hepatitis A and E viruses are enterically transferred with feco-oral transmission, the others (hepatitis B, C, D and G viruses) produce the infection parenterally with blood, blood products and body fluids. All the hepatitis viruses are able to cause acute hepatitis. Chronic carrier state and chronic hepatitis can develop in case of infections with hepatitis B, C, D, and G viruses. In the prophylaxis the hygienic rules should be applied in all forms of infections. Passive immunisation and active vaccination have been safety developed til now only in hepatitis A and B infections. To prevent the hepatitis C, D, E and G infections the modalities of prophylaxis are in experimental stages.
A number of hepatitis viruses have been newly identified belonging to the family hepatitis A-E, by their genome structure. The authors summarize and briefly demonstrate the most important molecular and epidemiological characteristics of te hepatitis GB and G viruses, and they discuss their clinical significance. They discuss the similarities and differences recording the three GB (GB-A, GB-B, GB-C) viruses, and also stress the high rate of similarity between the GB-C and G viruses. All the three GB viruses and G virus have RNA-genome, all of them are transferable with blood and blood preparates, they have been found both in acute and chronic hepatitis. They occur with higher rate in high risk population where the frequency of hepatitis B and C also increased.
The nontechnical complications following liver transplantation and the main therapeutical principles are summarised. The immunosuppressive therapy against rejection is discussed. The author gives a survey on the prevention of the hepatitis B, C and D virus infection in liver transplant recipients.
In chronic hepatitis C the interferon treatment given three times a week in a dosage of 3 million units (MU) normalizes the values of alanin-amino-transferase in a part of cases (25-40%), and produces bettering in the subjective complains of patients. In the short term therapy (3-6 months) the activity of ALT increases again after leaving the therapy, and the disease becomes active. The aim of this multicenter study in Hungary was to give newer data in the case of longterm efficacy with alpha-interferon. Ninety-one patients with chronic hepatitis C were selected into the open prospective clinical study in university and hospital departments. Treatment protocol was the following: Patients with chronic hepatitis C diagnosed by clinical and histological methods were treated with interferon-alpha 2B given 3 times a week in a dosage of 3 MU. Treatment period had lasted for one year and afterwards the patient had been on control for an other half a year. In non responder cases after 3 month treatment with interferon the dose of therapy was increased for 3 x 5 MU. In 37 cases (40.6%) out of 91 patients the authors found longterm sustained remission and in other 22 cases (24.2%) they observed a partial remission (among them 5 cases with late relapse). The rate of longterm sustained remission under 40 years was higher, than above 40. Higher rate was found when the treatment was started with a shorter chronicity of the disease. On te basis of the results the authors conclude: Interferon-alpha 2B is a good therapeutic modality for the treatment of patients with chronic hepatitis C. Efficacy of therapy is higher in younger patients and also in earlier application.
The authors give a short review of the recent data about the types of interferons and their biological activity. The role of interferons in the therapy of B, C and D chronic viral hepatitis is discussed. Interferon treatment means a substantial progress in the therapy of chronic viral hepatitis, however it represents a final recovery from chronic B or C hepatitis only in 25-40 percent or 40-45 percent of the cases, respectively. The authors refer to the combination therapy which seems to be promising in the future.
In insufficient function of bone marrow thymostimulin has an important role in the proliferation of haemopoetic cells, take part in the regeneration of lymphocytes, as well as in the normalisation processes of T lymphocytes. Its advantageous effect has been demonstrated in different viral infections, thus in herpes simplex, hepatitis B and C, as well as in AIDS virus induced diseases. It has also an important role in correction of the immunodeficiency of organism in various malignant diseases.
In the treatment of gastroduodenal ulceration both the reduction of gastric acidity and the defence of mucosal membrane have an important role. The development of H2-receptor antagonist has brought a significant change in the decrease of acid secretion in the last two decades. After the development and clinical application of cimetidine and ranitidine, a newly developed H2-receptor blocker, the famotidine has been introduced. Both the pharmacological and clinical investigations demonstrated the efficacy of this drug either in gastric or in duodenal ulcerations. The clinical pharmacological studies expressed mainly the advantageous character, that in the achievement of therapeutic effect smaller quantity is required than that of the other H2-receptor blocker. In the dosage of 40 mg (bedtime once, or daily twice) significantly decreases the basal and the stimulated gastric acid secretion as well as the daily and the nocturnal pains of the patients. Experience for several years have demonstrated efficacy in a 20 mg dosage of this drug in defence of ulceration relapses. It can be very well tolerated without significant side effects. Its long term applications is safety and economically advantageous.
As corticotropin-releasing factor (CRF) and oxytocin (OXT) are released in response to various stressors and a role of CRF in stress-induced OXT secretion has been proposed by previous authors, the present experiments were scheduled to investigate the participation of the brain CRF system in the stress-evoked release of OXT, arginine-8-vasopressin (AVP) and corticosterone. CRF-antiserum (AS) was given into the lateral ventricle of the brain of Wistar male rats, and 24 h later, the injection was repeated 30 min prior to ether stress followed by decapitation in 5 min. Plasma OXT and AVP were measured by radioimmunoassay and corticosterone by fluorimetry. Ether stress increased the levels of corticosterone and OXT, but not that of AVP. CRF-AS alone did not change the secretion of these hormones. CRF-AS pretreatment blocked the corticosterone-releasing action of ether stress, whereas it exerted no influence on the stress-induced OXT secretion into the circulation. There was no effect of a combined application of CRF-AS and stress on the plasma AVP level. These results suggest that the central CRF system is involved in the ether stress-elicited corticosterone response, however CRF is unlikely to be connected with the regulation of OXT secretion under these experimental conditions.
A case of carcinoid tumour of the small intestine has been reported, which caused hormone producing multiple hepatic metastases. The 45 year old man had flush syndrome several times a day, that was caused by a carcinoid tumour originated from the jejunum. After the operation of the primary tumour he was treated by Sandostatin (Sandoz, Basel), which significantly reduced the symptoms and slowed down the progression. The neural elements containing substance P, neuropeptide Y, vasoactive intestinal polypeptide, serotonin, dopamine-beta-hydroxylase and somatostatin, which are thought to cause the symptoms, were investigated in the small intestine and the liver metastasis by an immunocytochemical method. It seems to be an interesting observation, that a large number of neuropeptide Y immunoreactive nerve fibers and some substance P and vasoactive intestinal polypeptide immunoreactive nerve processes and cell bodies were observed however, no trace of somatostatin and serotonin immunoreactive nerve elements could be detected in the hepatic metastasis. That can be a novel addition to the possible aetiology of the carcinoid syndrome and to the way how the somatostatin treatment acts.
The authors describe a case of an adult patient having Gaucher's disease, who had hepatosplenomegaly and pancytopenia. The diagnosis was established by the low level of leukocyte beta-glucosidase and by histology of bone marrow, liver and spleen. The patient had no bone pain, but MRI described characteristic lesions of the femur. Serum acid phosphatase was characteristically elevated. The hypersplenism was reduced after splenectomy. The patient has a daughter with central nervous system dysfunction. Her chromosome examination is normal, but she has lower leukocyte beta-glucosidase activity too. She may have a Gaucher's disease of type II, the acute neuropathic form.
The authors studied the function of human fetal liver cell--on level of DNA and gene regulation--by methods of molecular biology. Experiments were done under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee. They conclude that human fetal liver culture may serve as a suitable in vitro modell for study of the liver specific gene expressions. They found that cultured human fetal liver cells from second trimester express albumin and AFP. They demonstrate that fetal hepatocytes--like adult hepatocytes--respond to the inflammatory mediators, IL-1, IL-6 and TNF, by induction of CRP and alpha-1-Ach expression and regression of albumin synthesis proving the ability of fetal hepatocytes to produce an acute phase response.