Background: Nitrogen‐containing bisphosphonates have been shown to be effective for the treatment of osteoporosis and Paget’s disease of bone. Unfortunately, these drugs also have the capacity to irritate the upper gastrointestinal mucosa. In this study we investigated the ability of alendronate and pamidronate to directly damage the gastric epithelium and attempted to determine whether these drugs caused injury through gastric microcirculatory alterations. Methods: An ex vivo gastric chamber model was used. Effects of topically applied alendronate and pamidronate on transmucosal potential difference and epithelial integrity (histology) were determined. Also, the effects of agents capable of preventing microvascular injury in the stomach (PGE2 and two nitric oxide donors) were examined for their ability to prevent gastric injury induced by the two N‐bisphosphonates. Results: Alendronate and pamidronate caused a concentration‐dependent decrease in transmucosal potential difference, widespread epithelial injury and infiltration of neutrophils into the mucosa. PGE2 and the two nitric oxide donors did not prevent the changes in potential difference or the epithelial injury, but did reduce neutrophil infiltration. Significant release of PGE2 into the lumen was observed following application of the two bisphosphonates, but neither drug altered mucosal blood flow. Conclusions: These results suggest that these N‐bis‐ phosphonates directly damage the gastric epithelium independent of actions on the microvasculature.

Recent years have witnessed an increase in the prevalence of maternal obesity during pregnancy in the United States and worldwide. Obese women have increased risks for gestational problems, such as diabetes, hypertension, and pre-eclampsia. Further, gestational obesity can adversely impact fetal growth and result in macrosomia, congenital abnormalities, and even fetal death. Measures must be taken to reduce maternal adiposity, as even a modest weight loss during pregnancy is beneficial for the health of mothers and fetus. Calorie restriction and moderate exercise are proven safe methods of stopping weight gain and/or inducing white-fat loss in these subjects. Additionally, therapeutic drugs that activate the AMP-activated protein kinase signaling pathway may be effective in ameliorating pathological conditions in obese patients. Finally, dietary supplementation with L-arginine or its effective precursor (L-citrulline) may be beneficial for managing overweight or obese gestating women by reducing white-fat accretion. Because of ethical concerns over human studies, animal models (e.g., sheep, pigs, baboons, rats, and mice) are warranted to test novel hypotheses with enormous biological significance and clinical applications.

Plant based products represent a promising alternative to conventional treatments for inflammation. Moringa oleifera Lam is a tree rich in proteins, vitamins, minerals and a variety of phytochemcals with health benefits. Among the reported health benefits are antioxidant and anti-inflammatory properties. The purpose of this study was to investigate whether tea brewed from dried Moringa leaves would abrogate inflammation in a mouse model of acute lung inflammation induced by LPS or extracts prepared from dust collected from a swine confinement facility (DE). Mice were offered water or Moringa tea for seven days. Tea consumption was significantly greater than that of water consumption on days 1 and 6, but there were no significant differences in weight gain or food consumption. On day seven, mice from both groups were forced to inhale, via intranasal challenge, either Phosphate Buffered Saline (PBS), Lipopolysaccharide (LPS) [10 µg mLCompared to mice that drank water, mice that drank Moringa tea had significantly less protein (p<0.05) and cellular influx (p<0.0001) into the lung after inhalation of 10% DE. No difference in neutrophil migration into the lungs of water and M. tea groups after LPS or DE challenge was detected. But mice that drank tea had significantly (p<0.05) more neutrophils with apoptotic morphology after DE challenge. TNF-α expression 24 h after inhalation of 10% DE, was significantly higher (p<0.05) in lungs of M. tea mouse group as compared to water group. This increase in TNF-α was accompanied by higher levels of pro and anti-inflammatory cytokines. Finally, activation of c-Jun N-terminal Kinase (JNK) in lungs of M. tea+DE group 24 h post inhalation was decreased. Taken together these results suggest that Moringa oleifera leaf tea exerts antiinflammatory properties on acute lung inflammation induced by swine confinement dust through a mechanism involving neutrophil regulation and JNK activation.

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