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6-Prenylnaringenin (6PN) is a chiral prenylflavonoid found most prevalently in hops (Humulus lupulus) and present in hops and hop products. It is an isomer of the potent phytoestrogen, 8-prenylnaringenin. An enantiospecific method for quantitation 6PN by LC-ESI-MS has been developed. Baseline enantiomeric resolution of 6PN was attained on a Chiralpak® AD-RH column with an isocratic mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 8.5) (39:61, v/v) and a flow rate of 1.25 mL/min. Quantitative MS data were obtained by selected ion monitoring of the [M-H]--ion of both enantiomers of 6PN (m/z 339.10) and the internal standard, 4-acetamidobenzoic acid (m/z 178.05). The method was found to be accurate and precise for enantiospecific quantification of 6PN. The method was successfully applied to the content analysis of 39 commercially available natural health products and dietary supplements reported to contain H. lupulus plant material, extracts and label claims of 6PN. 6PN was present in 25 of 34 products containing plant material or extracts of H. lupulus. Of the five products with claimed amounts of 6PN, all were found to possess <50% of label claims. Results of the content analysis indicated a lack of uniformity in botanical nutraceuticals claiming 6PN content. [ABSTRACT FROM AUTHOR]

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Purpose: To study the influence of inspiratory flow rate on the fine particle mass and the particle size distribution for metered dose inhaler (MDI) and dry powder inhaler (DPI) glucocorticoid products, in vitro. To compare the performance of MDI and DPI inhalers containing the same drug and strength at an impaction flow rate of 60 L/min., Methods: The Marple Miller cascade impactor model 150 and 160 were used to characterise several glucocorticoid MDI and DPI products at different simulated inspiratory flow rates (30 L/min, 60 L/min and 90 L/min). Following the actuation of one single inhaler puff the amount of drug deposited in each stage of the impactor was quantified using high performance liquid chromatography with UV detection at 242 nm. The size distribution of the primary particles of DPI products was measured by laser diffraction., Results: DPIs were significantly more dependent on impaction flow rate than MDIs. Except for Pulmicort(R), the fine particle mass FPM delivered from the MDI products was significantly higher than that delivered from the DPI aerosols., Conclusions: Although the metered dose inhaler is the older technology it exhibits greater respirable dose in vitro than newer dry powder inhaler devices. Care should be taken when shifting from one inhaler dosage form to another because this may affect the actual dose delivered to the lung. Further in vivo studies may be warranted in light of these findings.

Non-steroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the duodenum. We reviewed the prevalence, clinical spectrum, assessment, pathogenesis, and treatment of adverse effects of NSAIDs on the small intestine. NSAIDs can cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs produce inflammation of the small intestine in 40 to 70% in long-term users, and the associated complications of blood loss and protein loss are difficult management problems. The pathogenesis of NSAID enteropathy is a multi-stage process involving specific biochemical and subcellular organelle damage followed by inflammatory tissue reaction. Various suggested treatments of NSAID-induced enteropathy (e.g., sulphasalazine, misoprostol, and metronidazole) have yet to undergo rigorous clinical trials. Cyclo-oxygenase-2 inhibitors appear to be safer to the small intestine than traditional NSAIDs. Pre-clinical and clinical data suggests meloxicam, celecoxib, nimesulide and rofecoxib may have less small intestine toxicity than traditional non-selective NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) have commonly been associated with upper gastrointestinal (GI) tract side effects including a high incidence of gastric and duodenal ulceration. Recent reports implicate NSAID use and mucosal injury in the small and large intestine. A trend in NSAID development has been an attempt to improve therapeutic efficacy and reduce the severity of upper GI side effects through modified release dosage forms of NSAIDs such as enteric-coating (EC) or sustained release (SR) formulations. It is possible that modified release formulations may increase the exposure of active drug to the mucosa distally to the duodenal bulb, and thereby increase toxicity to distal GI regions where the effects are difficult to monitor. A systematic literature review through Medline, Embase, and Index Medicus was made to identify toxicological effects induced by modified release formulations of NSAIDs in the small and large intestine. An analysis of the identified toxicological effects of these formulations was made. SR and EC NSAID use has been associated with both small and large intestinal bleeding, anaemia, strictures, ulcerations, perforations, and death. Modified release NSAIDs may cause significant morbidity in some patients. NSAID modified release delivery systems are not guarantors of GI safety. Since SR and EC NSAIDs are widely prescribed and some EC products are available without a prescription, heightened awareness of these toxicological manifestations in more distal sites of the GI tact may reduce morbidity.

Background & Aims: The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains poorly understood. The aim of this study was to examine the relative importance of the three suggested components of the pathogenesis of NSAID enteropathy, namely, epithelial permeability, enteric bacterial numbers, and enterohepatic recirculation, using an NSAID derivative (nitrofenac) that does not cause small intestinal damage., Methods: Rats were given diclofenac or nitrofenac at 12-hour intervals. Epithelial permeability to [51Cr]-ethylenediaminetetraacetic acid and enteric bacterial numbers were determined after 1-4 doses of the drugs. Serum levels and biliary excretion of the two drugs were determined by high-performance liquid chromatography., Results: Diclofenac caused a progressive increase in epithelial permeability, marked increases in enteric gram-negative bacterial numbers, and frank intestinal ulceration. Nitrofenac caused similar changes in intestinal permeability after a single dose but no further increase with repeated administration. Moreover, nitrofenac had no effect on enteric bacterial numbers and did not cause frank ulceration. Unlike diclofenac, nitrofenac did not undergo extensive enterohepatic recirculation. Two other NSAIDs that do not undergo enterohepatic recirculation (nabumetone and aspirin) also did not modify enteric bacterial numbers or cause intestinal ulceration., Conclusions: Enterohepatic recirculation of NSAIDs is of paramount importance in the pathogenesis of enteropathy caused by these drugs, whereas suppression of prostaglandin synthesis is relatively unimportant.

This report describes the case of a woman who was admitted to the hospital with severe anemia and refractory rheumatoid arthritis. She had been transfusion dependent for 8 years and was receiving a combination of indomethacin and naproxen. An indium-111 white blood cell scan revealed small bowel inflammation. Salsalate was substituted for her previous nonsteroidal antiinflammatory drugs (NSAIDs), and metronidazole was initiated. This resulted in maintenance of a normal hemoglobin level for at least 1 year after discharge. Small intestine inflammation and bleeding (enteropathy) due to NSAIDs must be considered in the evaluation of anemia in patients with arthritis.

The long-term results of 300 laparoscopic inguinal hernia repairs are reported with 11 cases followed up more than 3 years, 104 cases more than 2 years, and 225 cases more than 1 year. There were five early failures owing to the use of too small a piece of mesh. There have been no long-term recurrences. The results indicate that transabdominal preperitoneal laparoscopic mesh repair of hernias is a satisfactory technique with a low recurrence rate and a low major complication rate (4%). Patients have found the procedure to be remarkably pain free and 51% have taken no analgesics after discharge from hospital. Of the patients, 78% returned to work within 2 weeks of the operation. These results suggest that laparoscopic hernia repair can be performed safely with excellent long-term results.