ABSTRACT
BACKGROUND: Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations. AIM: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups. METHODS: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g. RESULTS: The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients. CONCLUSIONS: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Colitis, Ulcerative/drug therapy , Mesalamine/administration & dosage , Adolescent , Adult , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Recurrence , Tablets , Treatment OutcomeABSTRACT
AIM OF THE STUDY: Investigation of the relationships between the grade and stage of chronic liver diseases irrespective of their etiology using some novel serum markers of liver fibrogenesis, the "classical" serum markers of liver necro-inflammatory injury (such as transaminases), and the histomorphological evaluation of liver biopsies. METHODS: Markers of liver fibrogenesis: serum metalloproteinase 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1), and N-terminal propeptide of the procollagen III (PIIINP); "liver function tests" (LFTs): bilirubin, transaminases ALT, AST; ALP, GMT; and liver morphology findings: necro-inflammatory activity, fibrosis; were studied in the series of 32, 'naive', i.e. yet untreated patients (women/men--11/21) with various CLDs: chronic viral hepatitis B or C 13 (CHB 3, CHC 10), non-alcoholic steatohepatitis 9, liver steatosis 4, primary biliary cirrhosis 5, drug-induced hepatitis. The diagnoses were based on the clinical, laboratory and liver imaging (ultrasonography) findings and confirmed by the liver biopsy. CONCLUSIONS: Investigation of liver fibrogenesis serum markers (PIIINP, MMP-1, TIMP-1) in patients with various CLDs has shown statistically significant correlations of these parameters with "classical" serum markers of liver necro-inflammation (ALT, AST) and the results of histomorphological evaluation of the necro-inflammatory activity (parameters NAI, MEF) and fibrosis (parameter FI) in liver biopsies. (Tab. 4, Ref. 31.)
Subject(s)
Liver Diseases/pathology , Liver/pathology , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , Chronic Disease , Female , Fibrosis , Humans , Male , Matrix Metalloproteinase 1/blood , Middle Aged , Peptide Fragments/blood , Procollagen/blood , Tissue Inhibitor of Metalloproteinase-1/bloodABSTRACT
Within an open, non-randomized clinical study, the authors investigated the effect of a three-month therapy by a standard product of so-called essential phospholipids in a group of patients (31 men and 2 women, average age being 45.6 +/- 10.8 years) with toxic liver damage--steatosis and steatohepatitis which have developed after exposure to the polychlorinated phenols and cresols, or other potentially toxic chemical substances occurring in working environment and/or exposition to alcohol. The therapy included a recommended change in life routine with a decrease in alcohol consumption, or entire exclusion of alcohol abuse. Within the process of observation, the authors used non-invasive methods (clinical examinations, laboratory examinations, ultrasonographic examination). A special attention was paid to the evaluation of the biotransformation capacity the liver and the assessment of spartein-debrisoquin-dextromethorphan metabolic fenotype. The results of investigation indicated: (1) significant improvement of the subjective status of the treated patients associated with an improvement of ultrasonographic findings of liver steatosis, trend of withdrawal of biochemical activity indices and favourable development of the biotransformation capacity of the liver in a majority of the investigated patients. (2) A very good tolerance of the administered drug without adverse effects. The use of non-invasive surrogate markers in coincidence with clinical investigation of the effect of applied medicamentous therapy in patients with chronic liver diseases represents a methodic increase in current modest options of evaluation of effectively and safety of the new therapeutic procedures in clinical hepato-pharmacology. (Tab. 5, Ref. 42.)
Subject(s)
Chemical and Drug Induced Liver Injury/therapy , Fatty Liver/therapy , Occupational Diseases/therapy , Phosphatidylcholines/therapeutic use , Temperance , Adult , Aged , Chemical and Drug Induced Liver Injury/etiology , Fatty Liver/chemically induced , Female , Humans , Male , Middle Aged , Occupational Diseases/chemically inducedABSTRACT
The aim of this study was to estimate the occurrence of the phenotype of poor metabolizers of sparteine (in the frame of sparteine-debrisoquine-dextromethorphane polymorphism) in Slovakia. The authors examined a group of 216 of healthy volunteers (73 women and 143 men, average age of the group 24, 9 +/- 0.4 years), university students coming from various regions of Slovakia. The test substance-sparteine (1 x 100 mg tbl.) was administered perorally to all probands, in the evening after fasting. A 12-hour gathering of urine was subsequently performed. A sample of urine was subdued to examination. Isolation, separation, identification and assessment of the concentration of sparteine and its metabolites (2- and 5-dehydrosparteine) were performed by the method of gas chromatography. The metabolic MR ratio calculated from the ratio of the detected concentrations of sparteine and (2- and 5-dehydrosparteine) served for the assessment of the phenotype of poor (MR > 20), or rapid (MR < 20) metabolizers of sparteine in 8 authors found the poor metabolizer phenotype of 216 examined probands (i.e. in 3.75%). Its prevalence of the presented phenotype was lower than that anticipated on the basis of epidemiologic studies performed in other European countries. Study represents the first data on the phenotype of poor sparteine metabolizers in Slovakia. (Tab. 4, Fig. 1, Ref. 24.)
Subject(s)
Polymorphism, Genetic , Sparteine/metabolism , Adult , Female , Humans , Male , Oxidation-Reduction , Pharmacogenetics , Phenotype , Reference ValuesABSTRACT
Local ethics committees (institutional review boards, or similar bodies) were established during the last decades at (bio)medical research institutions worldwide to serve as review bodies of the proposed research projects (inclusive protocols of clinical trials), and also to monitor if the ethical principles, including the requirements of good practice (clinical, laboratory, and scientific) are respected and fulfilled during the conduct of research projects. Existing pluralism of the philosophical background on which contemporary bioethics theories are developed is questioning seriously the ancient traditions of Hippocratic, non-utilitarian medical ethics, trying to promote more utilitarian and secular approaches. Individual physicians, or researchers, as well as the ethics committee itself, are faced today with complicated ethical dilemmas, that frequently have to be solved in the atmosphere of considerable social, collegiate, economical, and time pressures, and sometimes without helpful guidance of appropriate legislation. An interesting possibility of how to overcome some of the pitfalls of the ethics review process is to express a common ethical responsibility for the research project or trial protocol in a statement of most (or all) parties involved (such as the principal investigator, sponsor, ethics committee, the patient, "society'). Such an approach has proven helpful in enhancing concrete deliberations of ethics committees-established in Slovakia since 1991 according to the requirements of the national guidelines issued by the Slovak Ministry of Health.
Subject(s)
Ethics Committees , Practice Patterns, Physicians' , Clinical Trials as Topic , Decision Making , Humans , Informed Consent , Research , Slovakia , Social ResponsibilityABSTRACT
A method is presented for the isolation, separation and determination of sparteine and its metabolites in urine. The isolation is based on rapid extraction with dichloromethane and pentane in a glass separator. For the separation and determination, capillary gas chromatography with nitrogen-phosphorus detection was used. The recovery of the method ranged from 81.6% to 94.8%, and the limit of determination varied between 0.2 and 0.5 microgram ml-1. For quantification, 17-ethylsparteine was used as the internal standard.
Subject(s)
Sparteine/urine , Adult , Chromatography, Gas , Humans , Middle Aged , Oxidation-Reduction , Phenotype , Slovakia , Sparteine/analogs & derivativesABSTRACT
In a simple uncontrolled toxicological study 27 workers of an anesthesiology-resuscitation department of a hospital type III were examined. Besides detailed clinical examination, determination of basic hematological and biochemical parameters as well as ultrasonography, also selected parameters of proteosynthetic function of the liver, some so-called proteins of the acute phase and the biological half-life of antipyrine were established in the workers under study. The occurrence of pathological findings in the picture of the examinations performed was related to long-term professional exposure to halothane over the period of one year before the examination. With regard to the possibility of chronic hepatotoxic damage, appropriate attention should be paid to workers of anesthesiology-resuscitation departments, concerning particularly entrance medical examinations and regular screening and follow-up of their health condition, including check-ups hepatic parameters. (Tab. 4, Ref. 23.)
