[Correlation of the microbiota and intestinal mucosa in the pathophysiology and treatment of irritable bowel, irritable eye, and irritable mind syndrome]. / A mikroflóra és a bélnyálkahártya kölcsönhatása az irritábilis bél, irritábilis szem és irritábilis elme szindróma kórtanában és kezelésében.

Accumulating clinical evidence supports co-morbidity of irritable bowel, irritable eye and irritable mind symptoms. Furthermore, perturbation of the microbiota-host symbiosis (dysbiosis) is considered a common pathogenic mechanism connecting gastrointestinal, ocular and neuropsychiatric symptoms. Consequently, maintaining or restoring microbiota-host symbiosis represents a new approach to treat these symptoms or to prevent their relapses. Current treatment approach assigned a primary role to live probiotics alone or in combination with prebiotics to enhance colonization of beneficial bacteria and to strengthen the symbiosis. However, several papers showed major benefits of heat-killed probiotics as compared to their live counterparts on both intestinal and systemic symptoms. Recently, in addition to killing probiotics, in a proof of concept study lysates (fragments) of probiotics in combination with vitamins A, B, D and omega 3 fatty acids were successfully tested. These findings suggested a conceptual change in the approach addressed to both the microbiota and host as targets for intervention.

Irritable eye syndrome: neuroimmune mechanisms and benefits of selected nutrients.

Previous studies showed comorbidity of some ocular, enteral, and affective symptoms comprising irritable eye syndrome. Aims of the present study were to learn more about the pathogenic mechanisms of this syndrome and to evaluate benefits of food supplements on these disorders. In in vitro assay, Lactobacillus acidophilus lysate inhibited interleukin (IL)-1ß and tumor necrosis factor (TNF)-α generation of lipopolysaccharide (LPS)-stimulated macrophages in dose- and size-dependent manner. For a prospective, open-label phase I/II controlled clinical trial, 40 subjects affected by ocular dysesthesia and hyperesthesia and comorbid enteral and anxiety-depression symptoms were randomly assigned either into the treated group, which received a composition containing probiotic lysate, vitamins A, B, and D and omega 3 fatty acids, or into the control group, which received vitamins and omega 3 fatty acids. For reference, 20 age- and sex-matched healthy subjects were also selected. White blood count (WBC) and lymphocyte and monocyte counts, as well as IL-6 and TNF-α levels, were significantly above the reference levels in both treated and control groups. After 8 weeks, WBC and lymphocyte and monocyte counts, and cytokine levels significantly decreased, and ocular, enteral, and anxiety-depression symptoms significantly improved in the treated group as compared to the control group. This proof-of-concept study suggested that subclinical inflammation may be a common mechanism connecting ocular, enteral, and anxiety/depression symptoms, and supplements affecting dysbiosis may be a new approach to treating this syndrome.

Silymarin in the prevention and treatment of liver diseases and primary liver cancer.

In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis, non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well.

[Role of gastrointestinal inflammations in the development and treatment of depression]. / A krónikus gyomor-bél gyulladások szerepe a depresszió kialakulásában és kezelésében.

Recent studies have revealed that inflammation, among other factors, may be involved in the pathogenesis of depression. One line of studies has shown that depression is frequently associated with manifest gastrointestinal inflammations and autoimmune diseases as well as with cardiovascular diseases, neurodegenerative diseases, type 2-diabetes and also cancer, in which chronic low-grade inflammation is a significant contributing factor. Thus depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome. Another line of studies has shown that the primary cause of inflammation may be the dysfunction of the "gut-brain axis". Although, this is a bidirectional mechanism, life style factors may primarily affect the symbiosis between host mucous membrane and the microbiota. Local inflammation through the release of cytokines, neuropeptides and eicosanoids may also influence the function of the brain and of other organs. Role of metabolic burst due to inflammation represents a new aspect in both pathophysiology and treatment of the depression. Finally, an increasing number of clinical studies have shown that treating gastrointestinal inflammations with probiotics, vitamin B, D and omega 3 fatty acids, through attenuating proinflammatory stimuli to brain, may also improve depression symptoms and quality of life. All these findings justify an assumption that treating gastrointestinal inflammations may improve the efficacy of the currently used treatment modalities of depression and related diseases. However, further studies are certainly needed to confirm these findings.

[Cod liver oil. A natural Vitamin D for preserving health]. / Csukamájolaj. Egy természetes D-vitamin az egészség megorzésére.

Vitamin D deficiency is pandemic in industrialized countries due to life-style changes. Recent studies suggest that besides bone-metabolism, vitamin D plays a central role in basic cell function like multiplication, differentiation and metabolism. This may explain that low vitamin D levels represent a risk factor for several apparently different diseases such as infective, autoimmune, neurodegenerative and cardiovascular diseases, as well as diabetes, osteoporosis and cancer. Accumulating evidences suggest that an adequate intake of vitamin D may significantly decrease prevalence and clinical outcome of these diseases. Estimated reduction of the economic burden might reach about 10 percent through normalizing vitamin D levels for these diseases. However, high doses of vitamin D monotherapy needs precaution for potential adverse effects and it should be substituted with the recommended doses of vitamin D in combination with synergistic vitamin A and omega 3 fatty acids, such as cod liver oil.

Increased total scavenger capacity and decreased liver fat content in rats fed dehydroepiandrosterone and its sulphate on a high-fat diet.

BACKGROUND: Weak androgens have an antioxidant effect in vitro which is represented as a beneficial change in the antioxidant status. OBJECTIVE: Our aim was to clarify whether dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo. METHODS: Groups of experimental animals were fed a high-fat or a normal-fat diet and treated with DHEA or DHEAS in the drinking fluid. The control group was fed a high-fat diet together with untreated drinking fluid. Total scavenger capacity (TSC) was measured before and after 4 weeks of treatment in blood samples using a chemiluminometric assay. Fat content, superoxide dismutase (SOD), catalase and glutathione S-transferase (GST) activity in the liver were determined by Sudan staining and spectrophotometric assessments, respectively, from the fresh frozen tissue. RESULTS: DHEA and the DHEAS treatment showed significantly increased TSC in the groups fed a high-fat diet. The control group and the DHEA- or DHEAS-treated groups on normal diets showed no significant changes in TSC. The total score of liver fat content in the high-fat diet groups showed a marked positivity with Sudan staining, and the groups treated with DHEA or DHEAS had a markedly decreased amount of fat in the liver slides compared to the untreated group on the high-fat diet. Liver SOD activity was decreased in all high-fat diet groups and elevated only in the groups on a normal diet with DHEA or DHEAS treatment. Liver catalase and GST activities were decreased in the groups where TSC was significantly increased. CONCLUSION: Our results support the hypothesis that DHEA and DHEAS supplementation can improve the antioxidant status in lipid-rich dietary habits.

[Silymarin in the treatment of chronic liver diseases: past and future]. / Silymarin az idült májbetegségek kezelésében: múlt és jövo.

In the treatment of chronic liver diseases adequate therapy can be chosen only in the knowledge of pathogenetic processes. In the liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver and steatohepatitis, drug and compound induced liver toxicity) the antioxidant drugs, like silymarin, in chronic hepatitis caused by hepatitis B and hepatitis C virus, combined peginterferon and nucleosid treatments are the primary therapy modalities to be selected. The main effects of silymarin are the membrane stabilising and antioxidant effects, it is able to help the liver cell regeneration, it can decrease the inflammatory reaction and inhibit the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies, the long administration of silymarin significantly increased the survival time of patients with alcohol-induced liver cirrhosis. Recently it was demonstrated that high-dosage silibinin infusion treatment could significantly decrease the number of hepatitis C viruses after four-week application. On the basis of the results with the methods of molecular biology, silymarin is able to decrease significantly tumor cell proliferation, angiogenesis as well as insulin resistance. These results support the administration of silymarin preparations in the therapy of chronic liver diseases, especially in alcoholic and non-alcoholic steatohepatitis in current clinical practice, and as it can be awaited, also in the future. In some neoplastic diseases they could also be administered as adjuvant therapy.

[Influence of weight reduction on the effectiveness of combined peginterferon and ribavirin treatment in chronic HCV hepatitis]. / A testsúlycsökkentés hatása a kombinált interferon-alfa-2a + ribavirin kezelésre adott válaszra idült HCV-hepatitisben.

UNLABELLED: Overweight/obesity is an independent negative predictive factor of steatosis in chronic hepatitis C virus infection. The nonresponse to combined peginterferon and ribavirin treatment in infection caused by genotype 1 is associated with the waist circumference, body mass index (BMI), diabetes, steatosis, and degree of fibrosis. The obesity is an independent negative predictive factor of inefficacy of antiviral treatment. CASE REPORT: The authors summarize the case of a 59-year-old obese (BMI = 46.47 kg/m 2 ) male patient with chronic HCV infection. The weight reduction--after two ineffective antiviral treatments--helped the biochemical and virological response to combined peginterferon-alpha-2a and ribavirin treatment. Between the combined peginterferon and ribavirin therapy, the patient was treated with amantadine and silymarin. DISCUSSION: The authors summarize the importance of steatosis and insulin resistance in chronic HCV hepatitis as well as review the impact of weight reduction and the improvement of insulin sensitivity. CONCLUSION: Body-weight reduction and hepatoprotective drugs might have increased the effectiveness of combined peginterferon and ribavirin treatment and thus the sustained virological response.

[Metabolic therapy for early treatment of age-related macular degeneration]. / Metabolikus terápia az idoskori makuladegeneráció korai kezelésére.

Currently, age-related macular degeneration is one of the most common eye diseases causing severe and permanent loss of vision. This disease is estimated to affect approximately 300-500 thousand Hungarians. While earlier no treatment was available, in the recent decade an antioxidant therapy became very popular using combinations of high dosage antioxidant vitamins C, E, beta carotene and zinc. Based on theoretical concepts and mostly in vitro experiences, this combination was thought to be effective through neutralizing reactive oxygen species. According to a large clinical trial (AREDS) it reduced progression of intermediate state disease to advanced state, but did not influence early disease. This original combination, due to potential severe side effects, is not on the market anymore. However, the efficacy of modified formulas has not been proved yet. Recently, the metabolic therapy, a combination of omega-3 fatty acids, coenzyme Q10 and acetyl-L-carnitine has been introduced for treating early age-related macular degeneration through improving mitochondrial dysfunction, specifically improving lipid metabolism and ATP production in the retinal pigment epithelium, improving photoreceptor turnover and reducing generation of reactive oxygen species. According to a pilot study and a randomized, placebo-controlled, double blind clinical trial, both central visual field and visual acuity slightly improved after 3-6 months of treatment and they remained unchanged by the end of the study. The difference was statistically significant as compared to the base line or to controls. These functional changes were accompanied by an improvement in fundus alterations: drusen covered area decreased significantly as compared to the base line or to control. Characteristically, all these changes were more marked in less affected eyes. A prospective case study on long-term treatment confirmed these observations. With an exception that after slight improvement, visual functions remained stable, drusen regression continued for years. Sometimes significant regression of drusen was found even in intermediate and advanced cases. All these findings strongly suggested that the metabolic therapy may be the first choice for treating age-related macular degeneration. Currently, this is the only combination of ingredients corresponding to the recommended daily allowance, and at the same time, which showed clinically proved efficacy.

[Nutrition and cardiovascular mortality]. / Táplálkozás és a szív- és érrendszeri betegségek miatti halálozás.

About 17 million persons die in cardiovascular disease yearly in the world. Most part of this disease can be prevented by the elimination of primary risk factors, thus by the abolishment of unhealthy nutrition, physical inactivity and by the absence of smoking. The cost-effective national program, as well as the life style with decreasing individual risk factors can give a trend to decrease the cardiovascular mortality. Individually the usual blood pressure and cholesterol control, the inhibition of obesity and the life style without smoking are able to decrease the organic changes, which produce the lethal consequences of this disease. The different kinds of diets can significantly influence the development of human diseases. The Western diet has atherogenic effect, increases the risk of myocardial infarction. The Mediterranean diet beneficially influences the life expectancy at birth. The Far-East Japanese diet could specially be important from the viewpoint of nutrition, because the longest life expectancy at birth and the smallest cardiovascular mortality can be found there. The quality nutrition factors (vitamins, vitamin like materials, polyphenols in wine and fruit juices, trace elements, omega-3 fatty acids) play an important role in the decreasing of oxidative stress and cardiovascular mortality.

[The role of antioxidants in prevention]. / Antioxidánsok szerepe a prevencióban.

The imbalance between free radical formation and the mechanisms involved in eliminating them results in oxidative stress which lies at the baseline of many diseases. There are many pathological conditions that can be prevented or even be cured by the application of antioxidants. Food containing plenty of natural antioxidants is very important in the maintenance of health and in the prevention of many illnesses. In some diseases supplementation of antioxidants in the proper form and dosage may be irrelevant. According to nutrigenomics the biologically active components of nutrition, including antioxidants, have an influence on the body in every single cell at all levels. Therefore the quality of nutrients is one of the important factors determining the appropriate cell function.

[Cultural history of wine, the theoretical background of wine therapy]. / A bor kultúrtörténete, a borterápia elméleti háttere.

The knowledge of wine and grapes as old as the cultural history of human population. The small consumption of wine could be advantageous. Also it has been well established for several thousands of years, that it could cause acute and chronic injuries after higher consumption. Its antiinfectious effect in dermatological drugs had been known in the archeological ages. The unguents containing wine polyphenols are advantageous in some dermatological injuries and also in the treatment of muscular and articular alterations. Moderate consumption of wine may decrease the mortality rate of cardiovascular diseases. In healthy individuals consumption of one-two dl of wine can decrease the mortality rate of cardiovascular diseases. This quantity, however, may be injurious in pregnancy, in children, and in various organic diseases, especially in liver disease, as well as if combined with common drugs.

[Redox homeostasis in inflammatory bowel diseases]. / Redox-homeosztázis gyulladásos bélbetegségekben.

Janus faced oxygen radicals are secondary messengers of intracellular signal transduction pathways but also cytotoxic agents of cells. Activation of signal transduction proteins on mild oxidant stress and metal elements are still not clearly understood. Oxygen free radicals may have several functions in the expression of cytokines associated with inflammatory bowel disease. The molecular mechanism between activation, and inhibition participants of signal transduction are delicately controlled. Antioxidant-prooxidant balance of the cells can be traced back to the concentration of free-SH and its oxidised form,-S-S-. Healthy erythrocytes and plasma are rich in antioxidants, but their type of protection, differs significantly. The balance of free radicals and antioxidants is disturbed in inflammatory bowel disease. The antioxidant defence mechanism depends on concentration of metal elements, which determines enzyme activities. It seems that nutritional supplementation and adequate therapy restore the ion homeostasis, although, Zn overdose may cause disturbance in iron metabolism and consequently may influence erythrocyte functions.

[Effect of ubiquinone and other scavengers on alterations caused by oxidative stress]. / Ubikinon és más gyökfogók hatása oxidatív stressz okozta károsodásokban.

In the development of several diseases the oxidative stress is a significant aetiological or important pathogenetic factor. Its significance has been proved in the pathogenesis of several diseases, among them in arteriosclerosis and reperfusion, in inflammation and immunological disorders, as well as in toxic alterations and in carcinogenesis. The increased incidence of malignant tumors may be attributed to smoking, intemperate alcohol abuse, as well as inappropriate nutrition. Inappropriate nutrition is thought to be responsible for the development of about 30-50% of malignancies. In this paper the authors review the processes of the development of free radicals based on oxygen and nitrogen. They discuss the modalities which are able to decrease the oxidative stress, like the low oxygen tension in the tissues, the enzymatic and antioxidant protections, and the different repair mechanisms. In details the roles of ubiquinone, with other name of coenzyme Q, as well as of the selenium are discussed in the antioxidant defence processes. As a conclusion they suppose that oxidative stress in the organism and the alterations caused by them can be decreased by adequate nutrition or nutriceuticals.

Extrahepatic biliary obstruction: can silymarin protect liver function?

The hepatoprotective property of silymarin is well known. However, it is not known whether the antioxidant silymarin might have a beneficial effect in extrahepatic cholestasis in common bile duct ligated rats. Malonaldehyde property concentrations, the hydrogen-donating ability and reducing power were measured in liver homogenates by spectrophotometry, as well as free SH-group levels and glutathione-reductase activities in sera. The total scavenger capacity of the livers was quantified by a chemiluminometric method. The elevated lipid peroxidation and decreased antioxidant capacity of liver homogenates and sera could be observed in ligated rats. Silymarin pretreatment improved the antioxidant capacity of the liver, diminished the direct bilirubin concentration and caused an increase of liver enzyme activities compared with the groups without treatment. These effects of silymarin suggest that it may be a useful agent for improving the antioxidant defensive system in extrahepatic cholestasis, but its choleretic property should be considered.