Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody level: results and possible population-level consequences.

Due to the European measles epidemic and the increased number of imported cases, it can be theorised that the risk of exposure among Hungarian healthcare workers (HCWs) has increased. In 2017, the increased measles circulation in the region led to the emergence of smaller local and hospital epidemics. Therefore, our objective was to determine the herd immunity in the high-risk group of HCWs. A hospital-based study of detecting anti-measles IgG activity was performed in 2017 and included 2167 employees of the Military Medical Centre (Hungary). The screening of HCWs presented a good general seropositivity (90.6%). The highest seroprevalence value (99.1%) was found in the age group of 60 years or older. The lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age group, indicating a significant herd immunity gap between groups. Regarding the Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs, implying that susceptible HCWs may generate healthcare-associated infections. This study suggests that despite the extensive vaccination and high vaccine coverage, it is still important to monitor the level of protective antibodies in HCWs, or in a representative group of the whole population of Hungary, and possibly in other countries as well.

Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.

Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes.

Human blood monocytes normally express the interleukin-6 receptor. Treatment of cultured monocytes with endotoxin, interleukin-1 beta, or interleukin-6 results in a decrease in interleukin-6 receptor mRNA levels. Glucocorticoids aso cause a drop in monocytic interleukin-6 receptor mRNA levels. We also found interleukin-6 receptor expression in cultured human hepatocytes, but in contrast to monocytes, where interleukin-6 receptor mRNA is presented by the ligand and by interleukin-1, treatment of hepatocytes with interleukin-6 or interleukin-1 resulted in increased interleukin-6 receptor mRNA levels. Induction of interleukin-6 receptor mRNA in hepatocytes was less pronounced when glucocorticoids were omitted from the culture medium. We conclude that during noninflammatory homeostasis, blood monocytes are involved in binding of trace amounts of circulating interleukin-6. During inflammatory events, the main target of interleukin-6 may be changed from the monocytic population not only to activated B-cells, but also to the hepatocytes.

The role of central corticoliberin in the ether stress-induced secretion of neurohypophyseal hormones and corticosterone in the rat.

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.

Oxidative damage in alcoholic liver disease.

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.

A new approach to drug therapy in non-alcoholic steatohepatitis (NASH).

Liver steatosis is a common human disease, most often caused by long-term alcohol consumption. Non-alcoholic steatohepatitis (NASH) is characterized by similar histopathological features to those observed in alcoholic liver disease, but occurs in the absence of significant alcohol consumption. Several aetiological factors contribute to NASH: obesity, type 2 diabetes mellitus, hyperlipidaemia, pregnancy, different chemical intoxications, parenteral nutrition, jejeuno-ileal bypass, chronic inflammatory bowel disease, nutritional protein deficiency and congenital metabolic disorders. Biochemically, oxidative stress and lipid peroxidation and their ensuing damage are implicated in the pathogenesis of NASH and alcoholic steatohepatitis (probably resulting from free fatty acids in the mitochondria, and induction of the cytochrome P450 isoform CYP2E1 in hepatocytes and Kupffer's cells). This paper deals with the pathomechanisms, clinical findings and currently available therapies for NASH. The potential use of metadoxine in the treatment of NASH is also discussed.

[Rennet as a source of Salmonella occurrence in various dairy products]. / Syridlo ako zdroj výskytu salmonel v niektorých mliecnych výrobkoch

During a microbiological examination of foodstuffs, frequent occurrence of salmonellas of S. agona serotype was found in milk products, namely in ewe's milk cloddy cheese, ewe's milk curd and hard cheeses. The rennet produced by one enterprise was a source of salmonella spreading. To solve this problem, 1268 different samples were examined in which salmonellas were isolated in 69 cases. The Veterinary Service worked out and in cooperation with other bodies took steps to liquidate the occurrence of salmonellas in a short time; the level of that serotype in the population was not increased.

[Therapeutic principles after liver transplantation]. / Kezelési elvek májtranszplantációt követóen.

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.

[Famotidine in the treatment of gastroduodenal ulcer]. / A famotidin alkalmazása fekélybetegségben.

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.

[Thymostimulin in clinical practice]. / Thymostimulin a klinikai gyakorlatban.

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.

[Possibilities and perspectives of the prevention of viral hepatitis]. / A vírushepatitis megelözésének lehetöségei és perspektívái.

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.

[Epidemiology and clinical significance of the newly discovered GB,G hepatitis viruses]. / Az újonnan felfedezett hepatitisvírusok--GB,G--epidemiológiája és klinikai jelentósége.

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.

[Interferon therapy in chronic active viral hepatitis]. / Interferon kezelés vírus okozta krónikus aktív hepatitisben.

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.

[Experience with combined interferon alpha-2b and ribavirin in the therapy of chronic hepatitis C. Experience with one-year therapy of 100 patients. Multicenter study]. / Interferon-alfa-2b és ribavirin kombinált kezelés krónikus C hepatitisben. 100 Beteg egy évig tartó kezelése során szerzett tapasztalatok. Multicentrikus Tanulmány Munkacsoport.

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.

Oxidative stress in the liver and biliary tract diseases.

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 interleukin-1 beta in the regulation of liver-specific gene expression in human hepatoblastoma cells]. / Az interleukin-1 béta szerepe a májspecifikus génexpressziók szabályozásában humán hepatoblastoma sejtekben.

The authors studied the function of liver cells--on level of DNA and gene regulation--by methods of molecular biology. They found that treating human hepatoma (Hep G2) cells with interleukin-1 (IL-1) leads to the induction of alpha-1-acidglycoprotein (AGP) and complement 3 (C3) mRNA synthesis, and to a concomitant downregulation of albumin (alb), alpha-fetoprotein (AFP) and alpha-2-macroglobulin (alpha 2M) mRNA synthesis. Levels of specific mRNA were measured by Northern-blot analysis. They conclude that Hep G2 cells may serve as a suitable in vitro model for study of the liver specific gene expression, and IL-1 is one of the mediators of these gene control. The regulation is pretranslational as the direction of change in specific mRNA corresponds to the changes in synthesis of the respective proteins.

[Liver specific gene expressions in human fetal hepatocyte culture]. / Májspecifikus génexpressziók vizsgálata humán embrionális májszövettenyészetben.

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.

[The role of oxidative stress and the preventive effect of free radical scavengers in arteriosclerosis]. / Az oxidatív stressz szerepe és a szabadgyökfogók preventív hatása arteriosclerosisban.

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.

[Skin diseases associated with chronic hepatitis C]. / Krónikus C hepatitishez társult börbetegségek.

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.