The anti-inflammatory effects of 1,1 dimethyl-4-phenylpiperazinium (DMPP) compared to dexamethasone in a guinea pig model of ovalbumin induced asthma.

BACKGROUND AND AIM: Inflammatory cells involved in the pathophysiology of asthma express nicotinic receptor. Therefore 1,1 dimethyl(-4-)phenylpiperazinium (DMPP) in two doses were compared to dexamethasone in asthmatic guinea pigs. MATERIALS AND METHODS: Six groups were included; Normal control and five asthmatic (OVA-sensitized and challenged) groups; which were treated for 10 days as follows: two vehicles, dexamethasone (DEXA, 1 mg/kg) and DMPP (0.4 and 0.8 mg/kg) groups. Pulmonary functions and airway hyper-responsiveness were assessed. Leukocytic count, tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and immunoglobulin E (IgE) were measured in both blood and bronchoalveolar lavage fluid (BALF). Histopathological examination of the lung tissues was conducted. RESULTS: Asthmatic untreated animals exhibited significant increase in early and late airway resistance (RxV) and airway hyper-responsiveness, with reduction in tidal volume. Both blood and BALF showed significant increase in total leukocytic count (TLC), eosinophils, lymphocytes, monocytes, TNF-α, IL-6 and IgE with significant decrease in neutrophils. Airway inflammatory cell infiltration and smooth muscle thickness significantly increased. DMPP 0.4 mg/kg significantly decreased late phase RXV, TLC, BALF lymphocytes, TNF-α, smooth muscle thickness and increased neutrophils in BALF over both DEXA and DMPP 0.8 mg/kg. Moreover, DMPP 0.4 mg/kg significantly decreased IL-6 and BALF eosinophils than DMPP 0.8 mg/kg and decreased serum IgE and parenchymal inflammatory infiltration than DEXA. CONCLUSIONS: Low dose DMPP has more anti-inflammatory effect than a high dose in most parameters and sometimes than dexamethasone. Cholinergic anti-inflammatory pathway may therefore represent a potential drug target for allergic asthma. The dose related effect of DMPP and the mechanism underlying this effect require further evaluation.

Impact of omeprazole on bone remodeling in normal and ovariectomized Wistar rats.

BACKGROUND: Several epidemiologic studies have suggested the association between therapy with proton pump inhibitors (PPIs) and bone fractures. AIM: This study aimed at evaluating the effect of omeprazole on bone in normal and ovariectomized Wistar rats and the possible mechanisms involved. MATERIALS AND METHODS: 56 rats were divided into 3 main groups. Normal group; further subdivided into normal control group and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Sham operated group. Ovariectomized group; further subdivided into ovariectomized control group, and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Rats were treated for the last 4 weeks of the total 8 weeks of the experiment. Urine hydroxyproline, serum osteocalcin, TNF-α and IL-6 and bone mineral content were assessed. Omeprazole effects on the endothelial dependent and independent relaxation were determined. RESULTS: Omeprazole in normal and ovariectomized rats produced significant reduction in bone formation, tibia calcium content and serum TNF-α and IL-6. Omeprazole in ovariectomized rats produced a dose dependent decrease in bone resorption. Isolated aortic rings from ovariectomized/omeprazole treated rats exhibited reversal of the endothelial dysfunction that observed with ovariectomized rats. CONCLUSIONS: PPIs might induce both positive and negative effects on bone remodeling. Although these drugs might have the potential to inhibit bone resorption, through suppression of pro-inflammatory cytokines and improvement of endothelial function, yet these effects are counteracted by their inhibitory effects on the gastric proton pump with reduction in calcium absorption and bone formation.