Time trends in neural tube defects prevalence in relation to preventive strategies: an international study

OBJECTIVE: To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries. DESIGN: Retrospective time trends analysis of NTD prevalence. SETTING: 11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from 1 July 1987 to 30 June 1996. SUBJECTS: 8207 live births, stillbirths and terminated pregnancies affected by anencephaly or spina bifida registered by the 11 participating centres 1987-1996. OUTCOME MEASURES: Prevalence rate ratios based on the annual rates, using the Poisson regression model. RESULTS: During the study period a significant fall in prevalence rates for all NTD is present in Atlanta (USA), England and Wales, Hungary and Japan, and a significant rise in Norway and South America. After adjusting for the secular trends observed in the earlier years of the study, no significant trend can be attributed to preventive strategies. Data on NTD prevalence are supplemented with information on folate awareness among some of the populations studied. CONCLUSION: There is no evidence that, up to the middle of 1996, any change in time trend was attributable to the introduction of national folate supplementation policies. The possible effectiveness of folate supplementation policies for the reduction of NTD clearly needs to be tried and studied for several more years. Considering that in the Western world about 50% of pregnancies are unplanned, a policy that rests on action taken before conception can only have limited success. Strategies based on food enrichment, such as was introduced in the USA from the beginning of 1998, may prove to be more successful.     

The blood enzymatic antioxidative potential in bronchial asthma patients

This study aims at assessing the ability of asthma patients to defend themselves against the noxious effects of oxidative stress, known being the inflammatory nature of this disorder. As the anti-radical defence ability of the body is reflected by the antioxidative potential of blood and tissues, our study was based on the determination of the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and CAT/SOD and GPx/SOD ratios in the blood. Except for SOD, the activity of which was lower in asthma patients by -34.08%, CAT and GPx had values increased by +32.18%, respectively, with a resulting increase of CAT/SOD and GPx/SOD ratios. Our data, demonstrating a change in per-oxidants/antioxidants balance in favour of the first ones, seem to suggest that in the treatment of bronchial asthma the association of some compounds with antioxidants effects would be beneficial.     

Optimizing Glioblastoma Temozolomide Chemotherapy Employing Lentiviral-based Anti-MGMT shRNA Technology

Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor''s overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM.     

Prediction of improvement of ventricular function after revascularization: 18F-fluorodeoxyglucose single-photon emission computed tomography vs low-dose dobutamine echocardiography

AIMS: To compare assessment of myocardial flow and glucose metabolismby single-photon emission computed tomography (SPECT) with low-dosedobutamine echocardiography in predicting improvement in regionaland global left ventricular function after coronary artery bypassgrafting. METHODS AND RESULTS: Thirty patients with regional wall motion abnormalities (meanejection fraction 32±19%) were studied with low-dosedobutamine echocardiography (5 and 10 µg . kg^–1.min^–1) and thallium-201/ ¹⁸F-fluorodeoxyglucose(FDG) SPECTprior to surgery. For comparative analysis, a 13-segment modelwas used. Postoperative improvement was predicted if the echocardiogramshowed that wall motion abnormalities were reversible duringthe dobutamine infusion and there was normal perfusion or relativelyincreased FDG uptake in perfusion defects (mismatch) in dyssynergicsegments on SPECT. After surgery, ventricular function was reassessed.An echocardiogram was taken at the 3 month follow-up with thepatient at rest. Regional wall motion had improved in 62/168(37%) revascularized segments. In predicting functional outcome,low-dose dobutamine echocardiography reached a sensitivity of89% and a specificity of 82%, with a positive predictive valueof 74% and a negative predictive value of 93%, whereas for thallium-201/FDGSPECT these values were 84%, 86%, 78% and 90%, respectively.In patients with more than two viable segments on either technique,the wall motion score index, a surrogate of global ventricularfunction, improved significantly. CONCLUSION: For the optimal prediction of functional out-come, combinedassessment of flow and FDG imaging is needed. Both thallium-201/FDGSPECT and low-dose dobutamine echocardiography appear comparableand similarly accurate in predicting improvement of left ventricularfunction after surgical revascularization.     

Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100?mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.