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Zsolt Tulassay

Publications and source records attributed to Zsolt Tulassay.

At least 73 records · Page 4Linked to original sources

[Osteoporosis associated with inflammatory bowel diseases].

Inflammatory bowel diseases, most frequently Crohn's disease, are frequently accompanied by decreased bone mineral content (30-70%). The osteopenia is not explained by the side effects of treatment or the secondary malabsorption. There must be a common pathological pathway in the background. The mineral content of bones is most easily measured by dual-ray absorptiometry. The measurement should be performed at the time of the diagnosis of bowel disease. It is useful to perform some routine laboratory examinations (serum calcium and phosphate, urinary calcium excretion level, etc.) and some special tests (serum osteocalcin and crosslaps) to exclude some other pathological pathways as well as to plan the anti-osteoporotic therapy. Appropriate calcium and vitamin-D supplementation is essential in prevention and therapy as well. Several drug-classes have proven useful in the therapy of severe osteoporosis associated with inflammatory bowel diseases such as bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators and calcitonin. The authors provide an algorithm for the therapy of metabolic bone disease in inflammatory bowel disease.

Absorptiometry, Photon↗

[Use of DNA-chips technology in colorectal cancer].

The examination of gene expression in colorectal cancer may develop the bases of early diagnosis and of individual therapeutic strategies. With the few cDNA microarray examinations in colorectal cancer the expression of hundreds and thousands of genes were studied, although both the sample collection and the final results showed differences. Beside the exposition of the practical advantages of the chip technology our aims are the standardization of the currently available data in the international scientific literature and the description of the results in a comprehensible way. To summarize one can say that gene expression examinations in colorectal cancer show the accentuated role in carcinogenesis of not only the tumor suppressor, apoptosis- or cell-cycle regulation related genes, but of some mitochondrial, metabolic and cell-cell or cell-extracellular matrix conjunction gene families.

Colorectal Neoplasms↗

[Necessity of chip technology in stomach cancer].

Gastric cancer is one of the most frequent cancer type in the world today. This fact emphasises the importance of identification of useful diagnostic and prognostic markers for gastric cancers in their earliest stages. Aim of this review is to summarize the genetic knowledge related to gastric carcinogenesis and progression and to offer a survey of the gene expression pattern changes and their functional classification. Microarray results show that the gene expression pattern detected in gastric cancers highly depends on the histological type and heterogeneity of the sample, array type and data analyzing softwares. Recent experiments point out the changes of not just the alterations of tumor suppression, apoptosis, cell cycle regulation and signal transduction, but tumor cell metabolism and cell-microenvironment interactions, too. All results show connection to and complete the already known molecular background of gastric cancer.

Adenocarcinoma↗

[New considerations in the treatment of functional dyspepsia].

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Dyspepsia is a very common condition, with a high prevalence in the general population. The multifactorial pathogenesis of dyspeptic symptoms is poorly defined. However, several factors have been identified as relevant, including the role of gastric acid secretion, gastroduodenal dysmotility, visceral hypersensitivity and also the effects of stress and psychological factors. The role of Helicobacter pylori infection is more controversial, the infection plays only an irrelevant role in the pathophysiology of functional dyspepsia, nevertheless in a subgroups of patients eradication therapy is generally accepted as a preventive tool. The need for positive diagnosis is emphasized. The management of dyspeptic patients has a considerable impact on health services. As the costs of initial investigation are high, most patients receive empirical management (prescribing without a proven diagnosis), at least initially. Subgrouping of functional dyspepsia according to its predominant symptom into ulcer-like, dysmotility-like and non-specific dyspepsia has been attempted to tailor its treatment accordingly. This review aims to summarize the new aspects of pathophysiology, investigation and management strategies of functional dyspepsia.

Antacids↗

[Chemoprevention of colorectal cancer].

Although colorectal cancer is one of the most preventable forms of cancer, it remains the second leading cause of cancer death worldwide. Primary prevention involves the identification and elimination of factors, which cause or promote colorectal cancer. The goal of screening is to prevent colorectal cancer mortality through the detection and treatment of premalignant adenomas and curable-stage cancer. Most colorectal cancers are believed to arise from adenomatous polyps. Early identification and removal of adenomas can prevent the development of colorectal cancer. Chemoprevention is the use of specific chemical compounds to prevent, inhibit, or reverse carcinogenesis. Several chemoprevention options have been investigated and confirmed as effective. Aspirin and other nonsteroidal anti-inflammatory drugs are the most widely studied agents, their use has been consistently associated with reduction in the risk of mortality and the incidence of colorectal adenomas and cancers. The selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) have been demonstrated to decrease the number and the size of polyps in patients with familial adenomatous polyposis syndrome. Because the gastrointestinal toxicity of coxibs is lower, it might be safer than aspirin or other non-selective nonsteroidal anti-inflammatory drugs for long-term use. This review aims to summarize the recent theoretical and practical advances in the chemoprevention of colorectal cancer.

Adenomatous Polyposis Coli↗

[Endoscopic treatment of liver tumors].

In cases of patients of high operation risk the endoscopic stent implantation has the smallest morbidity and mortality as well as it ensures acceptable life quality in non-resec table neoplastic stenosis of liver portal region. In better life expectancy the more expensive metallic stents can be recommended because they are committed with less complications.

Cholangiopancreatography, Endoscopic Retrograde↗

[Gene therapy in pancreatic cancer].

Pancreatic cancer is the fifth cause of cancer death in the developed world. It is a highly malignant disease, characterised by aggressive local spread and early locoregional and hepatic metastasis. Surgery offers the only prospect of long-term survival, but the resectability ratio is very low at the time of diagnosis. Conventional chemo- and radiotherapy are relatively ineffective, that is why development of newer therapeutic alternatives are encouraged. Gene therapy came into the limelight of interest. Authors discuss the fundamental scientific principle and clinical experience in connection with gene therapy of pancreatic cancer. Different targets include antisense strategies, gene-replacement, gene-directed prodrug activation therapy, promoter gene strategies, as well as oncolytic viruses.

DNA, Antisense↗

Scanning fluorescent microscopy is an alternative for quantitative fluorescent cell analysis.

BACKGROUND: Fluorescent measurements on cells are performed today with FCM and laser scanning cytometry. The scientific community dealing with quantitative cell analysis would benefit from the development of a new digital multichannel and virtual microscopy based scanning fluorescent microscopy technology and from its evaluation on routine standardized fluorescent beads and clinical specimens. METHODS: We applied a commercial motorized fluorescent microscope system. The scanning was done at 20 x (0.5 NA) magnification, on three channels (Rhodamine, FITC, Hoechst). The SFM (scanning fluorescent microscopy) software included the following features: scanning area, exposure time, and channel definition, autofocused scanning, densitometric and morphometric cellular feature determination, gating on scatterplots and frequency histograms, and preparation of galleries of the gated cells. For the calibration and standardization Immuno-Brite beads were used. RESULTS: With application of shading compensation, the CV of fluorescence of the beads decreased from 24.3% to 3.9%. Standard JPEG image compression until 1:150 resulted in no significant change. The change of focus influenced the CV significantly only after +/-5 microm error. CONCLUSIONS: SFM is a valuable method for the evaluation of fluorescently labeled cells.

Fluorescent Dyes↗

Scanning fluorescent microscopy analysis is applicable for absolute and relative cell frequency determinations.

BACKGROUND: Flow cytometry (FCM) and laser scanning cytometry (LSC) are the routine techniques for fluorescent cell analysis. Recently, we developed a scanning fluorescent microscopy (SFM) technique. This study compares SFM to LSC (two slide-based cytometry, SBC, techniques) and FCM, in experimental and clinical settings. METHODS: For the relative cell-frequency determinations, HT29 colorectal cancer cells and Ficoll separated blood mononuclear cells (FSBMCs) were serially diluted (from 1:1 to 1:1,000) and measured by each of the three techniques. For the absolute cell number determinations (only for SBC) FSBMCs were smeared on slides, then HT29 cells were placed on the slide with a micromanipulator (5-50 cells). Tumor cells circulating in the peripheral blood were isolated by magnetic separation from clinical blood samples of colorectal cancer patients. All samples were double-stained by CD45 ECD and CAM5.2 FITC antibodies. For slides, TOTO-3 and Hoechst 33258 DNA dyes were applied as nuclear counter staining. RESULTS: In the relative cell frequency determinations, the correlations between the calculated value and measured values by SFM, LSC, and FCM were r(2) = 0.79, 0.62, and 0.84, respectively (for all P < 0.01). In the absolute cell frequency determinations, SFM and LSC correlated to a high degree (r(2) = 0.97; P < 0.01). CONCLUSIONS: SFM proved to be a reliable alternative method, providing results comparable to LSC and FCM. SBC proved to be more suitable for rare-cell detection than FCM. SFM with digital slides may prove an acceptable adaptation of conventional fluorescent microscopes in order to perform rare-cell detection.

Antiporters↗

Cardiac gene expression of natriuretic substances is altered in streptozotocin-induced diabetes during angiotensin II-induced pressure overload.

OBJECTIVE: To gain insight into the cardiac adaptive mechanisms in diabetes, we studied whether angiotensin II (Ang II) alters expression of the atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and adrenomedullin (AM) genes in the left ventricle of the diabetic rat heart. METHODS: Diabetes was induced by streptozotocin (STZ; 60 mg/kg body weight intravenously). During the last 24 h of 2.5 or 7 weeks of treatment of male Wistar rats with STZ or vehicle, Ang II (33 microg/kg per h) was administered via osmotic minipumps. RESULTS: Diabetes was associated with an increased left ventricular weight to body weight (LV/BW) ratio, an index of left ventricular hypertrophy, at week 7 but not at week 2.5, and with increased ANP mRNA content at 2.5 weeks, but not with altered expression of the AM and BNP genes. Mean arterial pressure and LV/BW ratio were increased by Ang II in all groups except in the 7-week diabetic group. Levels of ANP mRNA were increased fourfold (P < 0.001) and threefold (P < 0.05) by Ang II at 2.5 and 7 weeks in control animals, respectively, and 11-fold (P < 0.001) and sevenfold (P < 0.001) at 2.5 and 7 weeks in diabetic animals, respectively. Ang II increased ventricular concentrations of BNP mRNA in control and diabetic animals at 2.5 weeks (1.3-fold, P < 0.001; and 1.6-fold, P < 0.001) and at 7 weeks (1.3-fold, P < 0.05; and 1.8-fold, P < 0.001), respectively. Left ventricular levels of adrenomedullin mRNA were increased by treatment with Ang II for 24 h in 2.5-week diabetic animals. CONCLUSION: Ang II markedly increased the levels of natriuretic peptide mRNAs in the left ventricle of normal and diabetic rat hearts, whereas it increased adrenomedullin mRNA levels only in 2.5-week diabetic rats and failed to cause hypertension in 7-week diabetic rats. Left ventricular levels of ANP and BNP mRNA were increased by Ang II in diabetic animals more than the additive effects of diabetes and Ang II alone, showing that Ang II induced an amplified response with respect to cardiac concentrations of ANP and BNP in diabetes.

Adrenomedullin↗

Bone mineral density and bone acquisition in children and young adults with cystic fibrosis: a follow-up study.

OBJECTIVE: To investigate bone mineral density and bone homeostasis in cystic fibrosis (CF) and to assess changes in a 2-year period. METHODS: Thirty-eight patients with clinically stable CF (11 children, 16 adolescents, 11 young adults) were enrolled. No patient was treated with corticosteroids before or during the study. Weight and height Z scores and bone mineral density (BMD) Z-score at the femoral neck and the lumbar spine were recorded at the beginning of the study and after 2 years. Osteocalcin and cross-link excretion, both measurements of bone turnover were also measured. Correlations between BMD, bone turnover parameters, disease severity, pubertal stage, and nutritional state were calculated. The maternal BMD was also determined and related to that of the child. RESULTS: Height and weight Z scores were normal in children and below normal in adolescents. Puberty was delayed in most patients. Bone age was lower than chronological age in adolescents. Lumbar spine and femoral neck BMD Z scores were below normal in each age group. Disease severity determined by Schwachman score correlated with lumbar BMD (r = 0.45, P < 0.02). BMD Z scores did not change during 2 year follow-up. Maternal and patient lumbar and femoral BMD correlated significantly (r = 0.51, P < 0.01, and r = 0.54, P < 0.01, respectively). CONCLUSIONS: Bone deficit is present in patients with CF who have never received steroid treatment. Delay of puberty, chronic inflammation, or genetic susceptibility might be responsible for this phenomenon which was found in patients who had never received steroids and who were in relatively good clinical state.

Absorptiometry, Photon↗

Partial protection against dextran sodium sulphate induced colitis in histamine-deficient, histidine decarboxylase knockout mice.

OBJECTIVES: Chemically induced mucosal inflammation in animal models is a suitable tool for studying factors in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine whether absence of histamine has an effect on the development of experimental colitis. METHODS: Histamine-deficient, histidine decarboxylase (HDC) knockout Balb/c mice and genetically identical control animals with intact HDC were studied. Colitis was induced by the administration of 2% dextran sodium sulphate in drinking water. Mice were killed after 5 days and disease activity assessed by clinical, histologic, and immunohistologic parameters. Bacterial components of stool were examined. RESULTS: Clinical disease activity was higher in the mice with intact HDC (disease activity index, 2.21) than in the histamine-deficient knock-out mice (1.88). Histologic findings were similar in the two groups. On day 5, the inflammation score of the HDC sufficient group was 5.25 (+/-1.055) and the crypt score was 5.00 (+/-1.128). The scores in the HDC knock-out group were 4.667 (+/- 0.707) and 4.667 (+/- 0.86), respectively. There was a significant difference in the number of interleukin (IL-10)-producing lymphocytes in colon mucosa. Large numbers of IL-10-positive lymphocytes were observed in wild type mice both those with DSS induced colitis and untreated controls. Only sporadic IL-10 positivity was found in histamine-deficient mice. Significant differences were found in the composition of the fecal bacterial flora between the two groups. CONCLUSION: The reduced number of IL-10-positive lymphocytes in the intestinal mucosa of histamine-deficient, histidine decarboxylase knockout mice and the altered fecal bacterial flora in these animals suggest that histamine may play a role in the pathophysiology of inflammation in the colon of normal animals by upregulating local IL-10 production and stimulating a local shift to Th2 response.

Animals↗

Lower prevalence of Helicobacter pylori infection in patients with inflammatory bowel disease but not with chronic obstructive pulmonary disease - antibiotic use in the history does not play a significant role.

BACKGROUND: Patients with inflammatory bowel disease have lower prevalence of Helicobacter pylori infection, but the exact reason for this is not yet clear. AIM: To examine whether the antibiotics frequently used in inflammatory bowel disease are responsible for the lower prevalence of H. pylori infection. Patients with chronic obstructive pulmonary disease on prolonged previous antibiotic therapy were used for comparison. METHODS: Presence/absence of H. pylori infection was detected by a (13)C-urea breath test in 133 patients with inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and compared with that of 135 patients with chronic obstructive pulmonary disease and with two age-matched control groups (200 patients each). Primary disease location, duration of disease and detailed analysis of previous and current medication (dose and duration of antibiotics, steroids, 5-aminosalicylic acid) were analysed in each cases. RESULTS: Seventeen of the 133 patients with inflammatory bowel disease [12.2% (10/82) of ulcerative colitis and 13.7% (7/51) of Crohn's disease] and 90/135 patients with chronic obstructive pulmonary disease (66.7%) were positive for H. pylori. A total of 78/200 (39%) for the inflammatory-bowel-disease-group-matched controls and 110/210 (55%) for the chronic-obstructive-pulmonary-disease-matched controls were positive for H. pylori. The history of any antibiotic or steroid therapy had no influence on H. pylori status of patients with inflammatory bowel disease. CONCLUSION: The prevalence of H. pylori compared to the age-matched controls is significantly lower in patients with inflammatory bowel disease but not in those with chronic obstructive pulmonary disease. Antibiotic use is not responsible for the lower prevalence of H. pylori infection in patients with inflammatory bowel disease.

Adolescent↗

Helicobacter pylori and molecular mechanisms of gastric carcinogenesis: targets for prevention and therapy.

Gastric cancer is still a leading cause of cancer death worldwide. It is frequently diagnosed in an advanced stage and the overall prognosis is dismal. A major improvement will only be reached with a better understanding of the genetic changes underlying gastric cancer, which may provide us with effective prevention and treatment strategies. This review will highlight the present knowledge on the role of Helicobacter pylori in gastric carcinogenesis and the molecular pathogenesis of gastric cancer, as well as provide a brief overview of possible future targets for more specific and successful treatment options.

Angiogenesis Inhibitors↗

[Possibilities of investigation and clinical application of adult human stem cells].

Multipotent adult tissue stem cells have high plasticity and transdifferentiation ability. The stem cell therapy can be the solution of curing many severe diseases such as osteogenesis imperfecta, hepatic failure, heart muscle damage after myocardial infarction, I-type diabetes, variety of central nervous system disorders such as brain injury, stroke, Parkinson's disease and other neurodegenerative disorders. Isolation of certain types of stem cells is solved nowadays, but low frequency of these cells and lack of special identification markers make their isolation and search more difficult. The more and more developed in vitro cell culture technologies, the widespread macromolecule amplification and examination techniques of molecular biology and the gene technology tools for genetic modification of stem (and other) cells contribute to research and therapeutic applications of stem cells. Transfer of new genetic material to stem cells and expression of the gene product in daughter cells--because missing or damaged genes can be replaced--is an exiting approach of the treatment of congenital (enzyme deficiencies) and acquired human diseases (cancers).

Adult↗

[New medical therapies for the treatment of systolic heart failure].

Heart failure is characterized by sodium and fluid retention, sympathetic overactivation, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1000 patients in numerous clinical investigations, it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosteron receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.

Calcium Channels↗