Whites and African-Americans in headache specialty clinics respond equally well to treatment

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in 'real-world' headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30-day daily diaries that assessed headache frequency and severity at pretreatment and 6-month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1-, 2- and 6-month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6-month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.     

Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity

Estimates of the overall reducing capacity of hexavalent chromium(VI) in some human body compartments were made by relating the specific reducing activity of body fluids, cell populations or organs to their average volume, number, or weight. Although these data do not have absolute precision or universal applicability, they provide a rationale for predicting and interpreting the health effects of chromium(VI). The available evidence strongly indicates that chromium(VI) reduction in body fluids and long-lived non-target cells is expected to greatly attenuate its potential toxicity and genotoxicity, to imprint a threshold character to the carcinogenesis process, and to restrict the possible targets of its activity. For example, the chromium(VI) sequestering capacity of whole blood (187-234 mg per individual) and the reducing capacity of red blood cells (at least 93-128 mg) explain why this metal is not a systemic toxicant, except at very high doses, and also explain its lack of carcinogenicity at a distance from the portal of entry into the organism. Reduction by fluids in the digestive tract, e.g. by saliva (0.7-2.1 mg/day) and gastric juice (at least 84- 88 mg/day), and sequestration by intestinal bacteria (11-24 mg eliminated daily with feces) account for the poor intestinal absorption of chromium(VI). The chromium(VI) escaping reduction in the digestive tract will be detoxified in the blood of the portal vein system and then in the liver, having an overall reducing capacity of 3300 mg. These processes give reasons for the poor oral toxicity of chromium(VI) and its lack of carcinogenicity when introduced by the oral route or swallowed following reflux from the respiratory tract. In terminal airways chromium(VI) is reduced in the epithelial lining fluid (0.9-1.8 mg) and in pulmonary alveolar macrophages (136 mg). The peripheral lung parenchyma has an overall reducing capacity of 260 mg chromium(VI), with a slightly higher specific activity as compared to the bronchial tree. Therefore, even in the respiratory tract, which is the only consistent target of chromium(VI) carcinogenicity in humans (lung and sinonasal cavities), there are barriers hampering its carcinogenicity. These hurdles could be only overwhelmed under conditions of massive exposure by inhalation, as it occurred in certain work environments prior to the implementation of suitable industrial hygiene measures.      

Effect of proton pump inhibitors on the detection of Helicobacter pylori in gastric biopsies.

BACKGROUND: Proton pump inhibitors are known to decrease the activity of Helicobacter pylori organisms within the stomach and to shift their distribution proximally. This effect may reduce the sensitivity of histological examination and rapid urease testing for H. pylori on biopsies taken from recommended sites. It is of particular relevance if a proton pump inhibitor has been prescribed before the patient has undergone diagnostic endoscopy. METHODS: We studied patients referred to our open-access upper gastrointestinal endoscopy service who had either been on no medication (controls) or were already taking proton pump inhibitors. Biopsies taken from the gastric antrum and corpus were used for rapid urease testing and for histological examination. Sera, taken from patients who had no evidence of H. pylori in biopsies, were tested for IgG H. pylori antibodies as an alternative indicator of infection. RESULTS: H. pylori organisms were detected by histological examination in 27 of 40 controls (68%) and in 13 of 25 patients taking proton pump inhibitors (52%). Among patients with positive histology (organisms detected in either antral or corpus biopsies, or both), only the sensitivity of the antral urease test read at 1 h was significantly lower in patients taking proton pump inhibitors than in controls, with no significant difference in sensitivities of the antral urease test at 24 h, of the corpus urease test at 1 or 24 h, or of histology from the antrum or corpus. Of patients with negative histology, none of 13 controls compared with six of 12 patients taking proton pump inhibitors (50%) had positive serology (P = 0.005). Five (83%) of the six histology-negative, seropositive patients taking proton pump inhibitors had histological changes consistent with H. pylori gastritis even though no organisms were detected. CONCLUSIONS: Treatment with a proton pump inhibitor before endoscopy reduces the sensitivity of antral and corpus biopsies for H. pylori detection, both by urease testing and histological examination. If proton pump inhibitors already prescribed cannot be discontinued for an adequate period before endoscopy, patients should have biopsies taken from the corpus as well as from the antrum, and serum should be tested for H. pylori.     

On the mechanism of potentiation of the activity of acetylcholinesterase by some quaternary ammonium compounds

Tetraethylammonium iodide (TEA) increases the maximum velocity of acetylcholine hydrolysis nearly 2-fold whereas it shows purely competitive kinetics when the dipropyl-analogue of acetylcholine (2-acetoxyethyldi-n-propylmethylammonium iodide) is the substrate. Unlike acetylcholine, the dipropyl-analogue does not have deacetylation as its rate determining step and this is further evidence that quaternary ammonium compounds potentiate acetylcholinesterase by accelerating the deacetylation step. The effects of 22 quaternary ammonium compounds on the rate of hydrolysis of acetylcholine, phenyl acetate and dimethylcarbamylacetylcholinesterase have been examined. The acceleration of deacylation by quaternary ammonium compounds was found to have a high degree of structural specificity. Possible mechanisms for this phenomenon are discussed in the light of the structure-action results.     

Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component

Peroxisome proliferator-activated receptor (PPAR)-gamma activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-gamma mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-gamma mRNA and protein expression and increased PPAR-gamma-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-gamma is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF.     

Oxidative stress in term small for gestational age neonates born to undernourished mothers: a case control study

Background  

The objective of this study was to assess the status of oxidative stress in term small for gestational age (SGA) newborn infants born to undernourished mothers by estimating levels of erythrocyte superoxide dismutase (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord blood and comparing them to healthy appropriate for gestational age (AGA) controls. This was done in a case control design at a tertiary level teaching hospital.     

Effectiveness of Harpagophytum extracts and clinical efficacy

Various preparations from Harpagophytum procumbens are used for the treatment of pain in the joints and lower back. Studies published in peer reviewed journals were examined for their clinical evidence. The studies offering preparations with 50-60 mg harpagoside in the daily dosage are of better quality and provide more reliable evidence on efficacy than a proprietary ethanol extract with half the amount of harpagoside per day. However, confirmatory studies are required for all extracts before they can gain a place in treatment guidelines.     

Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects

M: The aim of this study was to investigate the effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin. METHODS: This was an open-label, three-way crossover randomized study in 12 healthy male subjects, who received a single 25-mg dose of warfarin alone or after 14 days' pretreatment with St John's wort, or 7 days' pretreatment with ginseng. Dosing with St John's wort or ginseng was continued for 7 days after administration of the warfarin dose. Platelet aggregation, international normalized ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured. Statistical comparisons were made using anova and 90% confidence intervals are reported. RESULTS: INR and platelet aggregation were not affected by treatment with St John's wort or ginseng. The apparent clearances of S-warfarin after warfarin alone or with St John's wort or ginseng were, respectively, 198 +/- 38 ml h(-1), 270 +/- 44 ml h(-1) and 220 +/- 29 ml h(-1). The respective apparent clearances of R-warfarin were 110 +/- 25 ml h(-1), 142 +/- 29 ml h(-1) and 119 +/- 20 ml h(-1) [corrected]. The mean ratio and 90% confidence interval (CI) of apparent clearance for S-warfarin was 1.29 (1.16, 1.46) and for R-warfarin it was 1.23 (1.11, 1.37) when St John's wort was coadministered. The mean ratio and 90% CI of AUC(0-168) of INR was 0.79 (0.70, 0.95) when St John's wort was coadministered. St John's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers. CONCLUSIONS: St John's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac-warfarin. Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin.