Exercise combined with postbiotics treatment results in synergistic improvement of mitochondrial function in the brain of male transgenic mice for Alzheimer's disease.

BACKGROUND: It has been suggested that exercise training and postbiotic supplement could decelerate the progress of functional and biochemical deterioration in double transgenic mice overexpresses mutated forms of the genes for human amyloid precursor protein (APPsw) and presenilin 1 (m146L) (APP/PS1TG). Our earlier published data indicated that the mice performed better than controls on the Morris Maze Test parallel with decreased occurrence of amyloid-ß plaques in the hippocampus. We investigated the neuroprotective and therapeutic effects of high-intensity training and postbiotic supplementation. METHODS: Thirty-two adult APP/PS1TG mice were randomly divided into four groups: (1) control, (2) high-intensity training (3) postbiotic, (4) combined (training and postbiotic) treatment for 20 weeks. In this study, the whole hemibrain without hippocampus was used to find molecular traits explaining improved brain function. We applied qualitative RT-PCR for gene expression, Western blot for protein level, and Zymography for LONP1 activity. Disaggregation analysis of Aß-40 was performed in the presence of Lactobacillus acidophilus and Bifidobacterium longum lysate. RESULTS: We found that exercise training decreased Alzheimer's Disease (AD)-related gene expression (NF-kB) that was not affected by postbiotic treatment. The preparation used for postbiotic treatment is composed of tyndallized Bifidobacterium longum and Lactobacillus acidophilus. Both of the postbiotics effectively disaggregated amyloid-ß/Aß-40 aggregates by chelating Zn2+ and Cu2+ ions. The postbiotic treatment decreased endogenous human APPTG protein expression and mouse APP gene expression in the hemibrains. In addition, the postbiotic treatment elevated mitochondrial LONP1 activity as well. CONCLUSION: Our findings revealed distinct mechanisms behind improved memory performance in the whole brain: while exercise training modulates NF-kB signaling pathway regulating immune response until postbiotic diminishes APP gene expression, disaggregates pre-existing amyloid-ß plaques and activates mitochondrial protein quality control in the region of brain out of hippocampus. Using the above treatments complements and efficiently slows down the development of AD.

Microbiota mitochondria disorders as hubs for early age-related macular degeneration.

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota-mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch's membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)-now called postbiotics-in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

Age related changes seen in human cornea in formalin fixed sections and on biomicroscopy in living subjects: A comparison.

The purpose of our experimental research was to assess the effects of aging on the main corneal structures in healthy corneas. Small, human cornea samples were collected from 20 Caucasian subjects during surgery for traumatic lesions to the eye. Ten subjects were adults (mean age 28 years) and 10 were elderly (mean age 76 years). Morphological analysis was carried out using light microscopy and electron microscopy. Another 40 patients (20 young: mean age < 30 years; 20 elderly: mean age > 70 years) were studied in vivo by confocal microscopy. The resulting images were analyzed qualitatively, quantitatively, and statistically. The basic light microscope revealed a decrease in endothelial cell density with age accompanied by an increase in endothelial cell size. Transmission electron microscopy revealed a corneal thinning and a decrease in the number of corneal stromal cells. A marked decrease in stromal nerve fibers was observed in the older subjects compared to the younger ones. Variable pressure scanning electron microscopy (VP-SEM) was used to make surface morphological observations and to determine the chemical composition of in vivo hydrated human corneas. Our results showed the effects of aging on normal corneal morphology highlighting the structural diversity of the corneal layers and revealing an age-related reduction in nerve fibers, thus explaining the decreased corneal sensitivity that may be observed in the elderly. Clin. Anat. 33:245-256, 2020. © 2019 Wiley Periodicals, Inc.

Ultrastructure of neurovascular changes in human diabetic retinopathy.

The previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures.

Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1ß within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes.

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.

[IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection]. / IL28B CC genotípus: védo tényezo és az interferonválasz prediktora krónikus hepatitis-C-vírus infekcióban.

INTRODUCTION: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. AIM: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. METHOD: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. RESULTS: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) CONCLUSIONS: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients.

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.

Pathological aspects of lipid peroxidation.

Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.

Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.

BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL). METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82 type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs) controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes"), 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests); NAFLD(NGTonly): 3.23 (p = 0.0013 vs CNTRL); NAFLD(IFG/IGT/type 2 diabetes): 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group). sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L) and abnormal glucose metabolism (30.38U/L) than in CNTRL (25.89U/L, p<0.001 and p = 0.013) or in T2D groups (23.97U/L, p<0.001 and p = 0.004). Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210. CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly suggests that serum DPP-4 activity should be considered as a novel liver disease biomarker.

[Combined interferon, ribavirin treatment and the occurrence of hepatocellular carcinoma]. / Kombinált interferon-ribavirin kezelés és a hepatocellularis carcinoma elofordulása.

Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer-related death worldwide. Primary hepatocellular carcinoma can be found most frequently (80-90%) in patients with liver cirrhosis. The most frequent causes of liver cirrhosis are chronic hepatitis B and C virus infections and chronic alcohol consumption. The treatment and elimination of the etiological factors decreases the risk of HCC. The authors summarize the literary data, where effect of modern antiviral treatment has been examined according to the occurrence of HCC. It can be stated, that the antiviral therapy (interferon and nucleoside analogues) is able to decrease the risk of HCC or the recurrence of the tumor after curative treatment of HCC, in case of non responder state, as well. Drugs used for the insurance of equilibrium in redox state can also help in the decrease of HCC risk.

[Hepatocellular carcinoma: occurrence, risk factors, biomarkers]. / Hepatocellularis carcinoma: elofordulás, kórokok, biomarkerek.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Primary hepatocellular carcinoma can be found most frequently (80-90 %) in patients with liver cirrhosis. The most frequent causes of liver cirrhosis are chronic hepatitis B and C virus infections and chronic alcohol consumption. The occurrence of hepatocellular carcinoma is about 3-15 % in patients with alcoholic liver disease. Other predisposing causes can be: non-alcoholic steatohepatitis (NASH), obesity, diabetes mellitus, autoimmune hepatitis, intrahepatic biliary inflammations (primary biliary cirrhosis, primary sclerosing cholangitis), copper and iron metabolic diseases (Wilson-disease, haemochromatosis), congenital alpha-1-antitripsin deficiency. The causative role of hepatitis B és C viruses have been well established in the pathogenesis of liver cancer. Other pathogenic factors are smoking, and different chemical agents. Treatment options for these patients have previously been limited to best supportive care and palliative therapy. Beside surgical treatment (resection, liver transplantation) the invasive radiologic therapy also has been widely used. The effectiveness of targeted therapy with monoclonal antibodies or small-molecule kinase inhibitors has now been demonstrated for the treatment of different tumors. In year 2007, sorafenib, a multitargeted kinase inhibitor was introduced to clinical practice and found to prolong survival significantly for patients with advanced HCC.

Small bowel alterations in portal hypertension: a capsule endoscopic study.

BACKGROUND/AIMS: The endoscopic appearance in portal hypertension is well described in the stomach and the colon, but there is a limited number of data available on small bowel changes. The present retrospective, comparative study was aimed to analyse the diagnostic yield and describe the small bowel findings with capsule endoscopy in cirrhotic patients with gastrointestinal bleeding of unknown origin. METHODOLOGY: Capsule endoscopy findings of 11 cirrhotic patients with portal hypertension and 22 non-cirrhotic patients with gastrointestinal bleeding who had undergone non-diagnostic upper endoscopy and colonoscopy, which were then compared. RESULTS: In total, 9A and 2B cirrhotic patients were examined based on Child-Pugh score with a mean age of 66.2 (+/- 7.6) years. Lesions originated to portal hypertension were found in all cirrhotic patients, most frequently multiple angiodysplasias (63.6%), while in the control group multiple angiodysplasias were a seldom finding (18.2%). None of the radiological and endoscopic examinations of the small bowel before capsule endoscopy showed positive findings in cirrhotic patients. CONCLUSION: Capsule endoscopy is an effective diagnostic method with high diagnostic yield in portal hypertension. Multiple angiodysplasias are the most probable findings as the source of small bowel bleeding in these patients.

[Effectiveness and safety of biological therapy with adalimumab]. / Az adalimumab biológiai terápia hatékonysága és biztonságossága.

Adalimumab is a human, recombinant antibody, which is effective in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriasis, arthritis psoriatica, spondylitis ankylopoetica, as well as with Crohn-disease. Adalimumab has got a high affinity binding to tumor necrosis factor (TNF-alfa), this way it inhibits the interactions with TNF and its receptors (soluble and membrane associated). It is well tolerated and safe, it improves the the quality of life. Possible side effects can be decreased by the careful observation and usual control of patients. The authors discuss in detail the publications on adalimumab in the above mentioned diseases.

[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.

[Successful elimination of hepatitis C virus after hepatic lobectomy in a patient with hepatocellular carcinoma]. / Hepatitis C-vírus sikeres eliminálása hepatocellularis carcinoma miatti lobectomiát követôen.

Hepatocellular carcinoma develops frequently after chronic hepatitis C and B virus infections. Hepatitis B virus has a direct, while hepatitis C virus an indirect role in hepatocarcinogenesis. THE AIM OF OUR WORK: To demonstrate a very unique and interesting case where after the elimination of early detected duplex hepatocellular carcinoma with a combined therapy of PEG-interferon and ribavirin, hepatitis C virus could be eliminated. CASE PRESENTATION: A 53-year-old male patient had chronic hepatitis C infection in his anamnesis. In 1995 histological examination confirmed cirrhosis in his liver. One year later he was non-responder for conventional interferon therapy. In 2002 CT examination confirmed a process with multiple plexus in the liver. With cytologic proof of hepatocellular carcinoma, a resection of the tumor by left-lobectomy of the liver was carried out. Four years after the operation a one-year PEG-interferon-alfa-2a and ribavirin combined therapy was instituted. The patient became virologically negative. CONCLUSION: In chronic liver diseases carcinoma can develop from multiple center at the same time. PEG-interferon and ribavirin combined therapy can be effective in chronic liver disease, as well as after resection of established hepatocellular carcinoma.

[Small intestine capsule endoscopy in the diagnostics of coeliac disease]. / A vékonybél kapszulás endoszkópos vizsgálata. A coeliakia diagnosztikája.

Coeliac disease is an autoimmune enteropathy precipitated by the gluten content of cereals. It had for long been considered a childhood condition as clinical symptoms manifested when gluten was introduced into the diet. The introduction of specific serological markers changed our understanding of the epidemiology and semiology of the syndrome. The main difficulty of the diagnostics arises from the fact that over 50% of patients with gluten-sensitive enteropathy show atypical symptoms, while coeliac-disease patients with extra-gastrointestinal manifestations show no gastrointestinal symptoms at all. Diagnostics of coeliac disease is currently based on the detection of specific antibodies and the histological assessment of the duodenum. Macroscopic signs of villous atrophy (reduction in the number or loss of Kerking's folds, vascular pattern visible through the mucosa, "mosaic or micronodular" pattern, "scalloped" folds) are clearly visible in untreated patients. Capsule endoscopy, contrary to conventional endoscopic approaches, enables non-invasive, pain-free investigation of the entire small intestine. Duodenal mucosa is visualised at an 8:1 magnification during the investigation, enabling the assessment of villous atrophy by an experienced investigator. Based on preliminary experience, standard upper tract endoscopy and capsule endoscopy appear to exhibit equal levels of sensitivity and specificity for coeliac disease. The advantage of CE versus upper tract endoscopy lies in the complete assessibility of the small intestine, thus also enabling the assessment of the spread and severity of the disease. The disadvantage associated with the approach is the lack of histological biopsy samples. CE is recommendable as a first line approach for patients with proven coeliac disease when alarm conditions appear.

[Capsule endoscopy for the diagnostics of small intestine tumours]. / A kapszulás endoszkópia jelentosége a vékonybéltumorok diagnosztikájában.

Three to six percent of all gastrointestinal tumours and one to two percent of all malignant gastrointestinal tumours develop in the small intestine. These occur more frequently in men than in women and the peak of occurrence is at the age of 50 to 60 years. According to epidemiological investigations to date the most frequently developing primary tumours in the small intestine are adenocarcinomas, carcinoid tumours, lymphomas and small bowel gastrointestinal stromal tumours. Clinical appearance of the tumours is the same, independent of their histological type. Fifty percent of the benign tumours is asymptomatic and is only discovered incidentally at autopsy. In comparison, 80% of malignant tumours is symptomatic. The prognosis of small intestine malignant tumours is very poor as at the time of diagnosis they have already formed metastases in 45-75% and at the time of surgery they are in 20-50% irresectable. The reason for the late diagnosis is on the one hand the non-specific nature of the symptoms, on the other hand, the limited visualisation of the entire small intestine via traditional radiological and endoscopic methods. Capsule endoscopy (CE) revolutionised the diagnostics of the small intestine by enabling non-invasive, pain-free investigation of the entire small intestine. The timely application of CE may replace a range of expensive assays with limited diagnostic value. Initial results indicate a higher prevalence of small intestine tumours than it had been estimated based on earlier epidemiological investigations. The new method provides an early diagnosis, enabling a definitive therapy, eventually significantly improving patient survival.