-Purpose: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. Methods: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. Results: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC. Conclusions: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC.

Current medical literature lacks any evidence of the protective effects of quince leaf on testes. Therefore, the aim of the present study was to assess the effect of quince (Cydonia oblonga Miller) leaf decoction on testicular injury and impaired spermatogenesis induced by hypercholesterolemia in rabbits. Eleven mature New Zealand white male rabbits were randomly divided into three groups: group 1 (hypercholesterolemia, n=3), group 2 (hypercholesterolemia plus quince treatment, n=6), and group 3 (control, n=2). Groups 1 and 2 received a cholesterol-enriched diet for six weeks. Group 2 received C. oblonga leaf decoction as drinking supplement as well. After six weeks, a normal diet was substituted in groups 1 and 2 for another six weeks. Group 3 (control group) was maintained throughout the study on a regular diet. At the end of the 12 th week, the left testes of the animals were resected for light microscopic study with particular attention to the maturity of germ cells in seminiferous tubules using Johnsen's score. Increase in intertubular connective tissue and diameter of vessels, abundant spermatogonia and primary spermatocytes along the reduced germinal epithelium were noted in all rabbits of the group 1. The remaining animals in groups 2 and 3 had no significant changes in their testicular sections. The mean Johnsen's score of group 1 (4.20±1.92) was significantly lower than that of group 2 (7.33±0.52) and group 3 (7.05±0.07). (P=0.01). In conclusion, quince leaf decoction (C. oblonga Miller) protected rabbit testes and spermatogenesis from damage induced by hypercholesterolemia.

Ramadan fasting may have beneficial effects on endothelial function and can modulate cardiovascular risks. Further studies are needed to confirm the clinical significance of Ramadan fasting on cardiovascular health.

Long-term exposure to opiates induces tolerance to the analgesic effect and dependence. The purpose of the present study is to investigate the effects of pioglitazone, a peroxisome proliferator-activated receptors gamma (PPAR-γ) agonist, on the morphine-induced tolerance and dependence. Groups of rats received morphine in combination with a vehicle or pioglitazone (5, 10, 20, and 40 mg/kg) daily. Thirty minutes before pioglitazone (40 mg/kg), GW-9662, a selective PPAR-γ antagonist, (2 mg/kg) was administrated in order to evaluate the possible role of the PPAR-γ. Nociception was assessed by a tail flick apparatus, and the percentage of the maximal possible effect was calculated as well. For 9 days, rats received additive doses of morphine to induce dependence. Naloxone was administrated 2 h after the morphine last dose, and withdrawal symptoms were recorded for 45 min. Morphine administration to rats over a duration of 17 days resulted in the development of tolerance, whereas pioglitazone (40 mg/kg) delayed the day of the established tolerance for 15 days. Administration of pioglitazone also prevented morphine-induced 50 % effective dose (ED50) shift to the right in the dose-response curve and increased the global analgesic effect of morphine. In addition, pioglitazone decreased the total withdrawal score significantly, whereas GW-9662 significantly reversed the pioglitazone effects on the morphine tolerance and dependence. The prevention of the morphine-induced glia activation and the proinflammatory responses were the possible mechanisms for pioglitazone effect on delaying the morphine tolerance and attenuating the dependence.

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