Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori, a higher eradication rate for H. pylori was found after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori to metronidazole. In this study, we have found that nizatidine, an H(2)-receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could be an inhibition of a proton pump in H. pylori. Reversal of antimicrobial resistance with the help of different non-antibiotics seems to be possible by using quite different compounds, and is therefore to be explained by different molecular mechanisms.     

Memantine attenuates the increase in striatal preproenkephalin mRNA expression and development of haloperidol-induced persistent oral dyskinesias in rats

Tardive dyskinesia (TD) is a serious motor side effect of long-term neuroleptic treatment that may persist after drug withdrawal. Alterations in striatal enkephalinergic neurons due to excessive glutamatergic activity is a possible pathogenetic mechanism. We studied the effect of the NMDA antagonist memantine in a rat model of TD, in which vacuous chewing movements (VCM) were induced by 20 weeks of haloperidol administration. The striatal density of preproenkephalin mRNA was measured and the number of neurons estimated. Haloperidol induced persistent VCM that was associated with increased striatal expression of preproenkephalin mRNA. Memantine inhibited the development of haloperidol-induced persistent VCM and attenuated the increase in preproenkephalin mRNA expression. This suggests that glutamate-mediated up-regulation of striatal enkephalin plays a role in the development of haloperidol-induced persistent oral dyskinesias.     

Total length of nerve fibers in prefrontal and global white matter of chronic schizophrenics

It has been suggested that the dysfunction of the prefrontal cortex in schizophrenics is due to dysfunctional connections between the prefrontal cortex and more posterior structures. The present study uses a recent stereological method that allows quantitation of the myelinated nerve fibers in the brain white matter. As especially the prefrontal region is of interest in schizophrenics, the prefrontal white matter was quantitated separately. The total length of nerve fibers in post-mortem brains was estimated from eight male chronic schizophrenics and nine male controls (age-range: 40–81 years). Samples were taken systematically and randomly from both the entire white matter and selectively from the prefrontal white matter. The biopsies were rotated randomly before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at about 10,000× magnification and the fiber diameter of each counted fiber was measured to get the size distribution of the fibers. The schizophrenics had a total of 129,000 km myelinated fibers in the white matter and 25,700 km in the prefrontal white matter, which was non-significantly different from a total of 137,000 km in the entire white matter and 27,600 km in the prefrontal white matter in controls. The size distribution of the fibers in schizophrenics was within normal limits compared to controls. Our results do not show a larger loss of nerve fibers in neither the white matter globally or in the prefrontal white matter of schizophrenics.     

Application of survival analysis to carious lesion transitions in intervention trials

OBJECTIVE: To demonstrate the usefulness of a survival-time regression model for the analysis of data from two 3-year trials of the caries-preventive effect of sugar-substituted chewing gums and fluoride toothpaste, carried out among 892 Lithuanian children. METHODS: A caries onset was defined as a transition from sound to carious and a caries recovery was defined as a transition from carious to sound. The time at risk for each type of transition was calculated. Using an exponential survival-time regression model, the hazard ratios for the covariates experimental group (control, sugar substitute, fluoride), age, gender, surface type and posteruptive surface age was estimated. This analysis was repeated using two alternative definitions of the caries transitions. RESULTS: The analyses confirmed that caries rates are higher in occlusal surfaces, and that posteruptive surface age influences caries rates. Moreover, it also confirmed that fluoride affects the outcome of ongoing caries activity more than the initiation of caries. CONCLUSIONS: Survival-time analysis of caries transitions allows for the extraction of much more information from caries trials than does the traditional DMF-based analysis, and traditional DMF incremental values may easily be derived from the models.     

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.     

Validity of the aphasia item from the Scandinavian Stroke Scale

We studied the validity of the aphasia item of a widely used stroke scale - the Scandinavian Stroke Scale (SSS) - in discriminating between aphasia and normal language function in 33 stroke patients of an acute stroke unit. They were assessed by a nurse using the aphasia item from the SSS and by a speech and language therapist carrying out a full evaluation of the language function. The latter served as the 'gold standard'. The agreement between the nurses' and the speech and language therapist's scoring was good (weighted kappa = 0.74, 95% CI 0.51-0.97), and the sensitivity and specificity of the SSS aphasia item were also satisfactory. However, the predictive value of a positive test was as low as 0.55 (95% CI 0.23-0.83), indicating nearly every second of the positives being false positive. Using the aphasia score of the SSS as a diagnostic aid for aphasia after stroke results in a high rate of false positives and inflates the prevalence figures for aphasia in epidemiological studies of stroke.     

Development and validation of an enzyme-linked immunosorbent assay to measure vitellogenin in the zebrafish (Danio rerio)

In this study, an enzyme-linked immunosorbent assay (ELISA) was developed to quantify vitellogenin (Vtg) in zebrafish (Danio rerio). Zebrafish Vtg (zf-Vtg) was purified from whole-body homogenates of estradiol-exposed zebrafish, and polyclonal antibodies against zf-Vtg were raised. Using purified zf-Vtg as a standard and anti-zf-Vtg antibodies (DR-264), a competitive ELISA method was set up and validated. The working range of the assay is from 1 to 30 ng/ml (20-80% binding), and the detection limit is 0.4 ng/ml for purified zf-Vtg. In whole-body homogenates samples, the practical detection limit is higher than that for purified Vtg (40 ng/ml) due to matrix effect. The intra- and interassay variations were 4.7% and 14%, respectively, at 50% binding (n = 36). Its usefulness to detect changes in Vtg concentration in other cyprinid fish was also tested. In addition, the assay was used to assess Vtg induction in male zebrafish exposed to 17beta-estradiol (E2). Exposure of male zebrafish to 0.1, 1, 10, and 100 microg/L of E2 for 7 d led to a Vtg induction from the lowest concentration. The results show the suitability of the developed ELISA to quantify Vtg inductions in zebrafish, the cross-reactivity of DR264 antibodies with commonly used cyprinids, and the potential of zf-Vtg induction as a sensitive biochemical endpoint that could be used to detect estrogenic properties of chemical substances.     

Sexual socialization and motives for intercourse among Norwegian adolescents

The impact of gender differences in sexual socialization on early sexual experiences among Norwegian adolescents is discussed. The material comprises a stratified sample of 920 adolescents ages 16–20 years in a Norwegian county. Data were collected by means of questionnaires. Of the respondents, 55.5% were girls and 44.5% were boys. 52.3% of girls and 41.4% of the boys had coital experience. The most common reasons for having had the first sexual intercourse were being in love, curiosity or excitement, and sexual arousal. Findings from a discriminant analysis showed that emotional reasons were more important to girls, whereas boys seemed more practical in sexual matters. More boys than girls reported that the reason for having had their most recent intercourse was that the partner wanted it. This indicates that if girls do not want sex, boys seldom use pressure. Girls set the premises for sexual interaction but are not as sexually skilled as boys.     

Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway)

Objective Previous studies of predominantly ecological design have indicated a possible elevation of gastrointestinal cancer risk in population groups exposed to drinking water contaminated with asbestos from natural sources or asbestos–cement containing water pipes. In the present study the possible effect of ingested asbestos fibers on gastrointestinal cancer risk was investigated in an occupational group where a proportion of the employees was exposed to asbestos in their drinking water.Method A cohort of 726 lighthouse keepers first employed between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002. The standardized incidence ratio (SIR) was calculated as the number of new cancer cases divided by the expected number based on five-year age and sex specific incidence rates in the general rural population of Norway. A 95% confidence interval (CI) was calculated for all SIR values assuming a Poisson distribution of the cancer cases.Results Risk of stomach cancer was elevated in the whole cohort (SIR: 1.6, CI: 1.0–2.3), in the subgroup with definite asbestos exposure (SIR: 2.5, CI: 0.9–5.5), and when the group was followed for 20 years and more after first possible exposure (SIR: 1.7, CI: 1.1–2.7). Less consistent results were found for colon cancer; SIR was 1.5 (CI: 0.9–2.2) overall, 0.8 (CI: 0.1–2.9) among the exposed, and 1.6 (CI: 1.0–2.5) twenty years and more after first possible exposure.Conclusion The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically.     

Variability in dust exposure in a cement factory in Tanzania

Dust exposure levels were studied in a cement factory in Dar es Salaam, Tanzania, as part of an epidemiological study assessing chronic respiratory health effects. One hundred and twenty personal 'total' dust samples were collected from 80 randomly selected workers from eight a priori occupational groups (OGs) based on work areas using a 37 mm Millipore sampler. The between-group, within-group and within-worker variances were determined to assess the contrast in exposure level between the OGs and to estimate the attenuation and standard error of the theoretical exposure-response slope. Using mixed-effect model estimates, the probability of overexposure relative to the occupational exposure limit (OEL) was assessed for each OG. The geometric means of total dust exposure were higher in the cranes (38.64 mg m(-3)), packing (21.30 mg m(-3)) and crusher (13.48 mg m(-3)) than in the cement mill (3.23 mg m(-3)), kiln (2.87 mg m(-3)), raw mill (1.85 mg m(-3)), maintenance (1.16 mg m(-3)) and administration (0.29 mg m(-3)). The a priori grouping scheme seems to be an efficient scheme because of the high contrast in exposure level between the OGs (0.78) and minimal attenuation of the theoretical exposure-response slope (1.0%). When using the reduced mixed-effect model, the probabilities of overexposure () relative to the OEL of 10 mg m(-3) for total cement dust were higher in the crane (96%), packing (88%) and crusher (73%) than in the cement mill (16%), kiln (14%), raw mill (5%), maintenance (2%) and administration (0.01%).