DARU, Journal of Pharmaceutical Sciences
Volume:15 Issue: 1, Spring 2007

Bleomycin-induced pulmonary fibrosis is a widely used experimental model for human lung fibrosis. The severity of fibrosis varies among different strains of mice and investigation on different strains and finding the mechanisms of variation is important in understanding the pathogenesis of human lung fibrosis. In the present study, NMRI mice were used to investigate the severity and also time-course of bleomycin-induced pulmonary fibrosis in comparison with C57BL/6 mice. After single dose administration of intratracheal bleomycin, the fibrotic response was studied by biochemical measurement of collagen deposition and semiquantitative analysis of pathological lung changes. NMRI mice developed lung fibrosis from 1 to 4 week after bleomycin instillation, with significant increases in lung collagen content and significant morphological changes (P < 0.05). These findings indicate that NMRI mice might be suitable as an experimental model of bleomycin-induced lung fibrosis.

Arterial calcification, a regulated process similar to ossification in bone, is common in atherosclerosis. A subpopulation of bovine aortic media cells, have osteoblastic characteristics and form spontaneously mineralized nodules in vitro. To assess whether Benidipine Hydrochloride as a potent calcium-channel blocker modulates arterial calcification, the effect of this drug on bovine vascular aortic smooth muscle cells for formation of calcified nodules and alkaline phosphatase activity in the culture medium was determined. These cells were obtained from bovine thoracic aorta, treated with different concentrations (0, 0.01, 0.1, 1, 10 nmol/L) of Benidipine Hydrochloride. Twenty-one days of treatment in comparison with control cells resulted in a significant increase in number of calcified nodules visualized by von Kossa staining, as well as by increase in alkaline phosphatase activity, a marker for osteoblastic differentiation and decrease in cell number in a dose dependent manner, compared with control cells. These results indicate that treatment with Benidipine Hydrochloride treatment in long term may contributes to vascular calcification.

In the present study the kinetics of glutathione (GSH) concentration during in vitro maturation in the presence of Cysteamine in culture medium was examined. Also the effects of different doses of Cysteamine on Germinal Vesicle Breakdown (GVBD) and MetaphaseII (MII) development were investigated. Germinal vesicle (GV) oocytes was obtained from ICR mouse and cultured in Tissue culture medium (TCM199) supplemented with 0, 50, 100, 200 and 500 µM cysteamine. Number of GVBD and MII oocytes were recorded at 4 and 24 hours after culture respectively. For GSH assay 5, 5’-dithio-bis (2-nitrobenzoic acid)-glutathione disulfide (DTNB-GSSG) reductase recycling assay was employed. Our results showed that 100 µm cysteamine can improve GVBD and MII development significantly higher than control group (P<0.05). Also all Cysteamine groups increased GVBD and MII development compared to control group except 500 µm cysteamine groups. Developmental competence in 500 µm group was significantly lower than control group (P<0.05). In vivo GSH assay indicated that glutathione concentration in MII oocyte is significantly higher than GV stage and in vitro maturation MII oocytes. Also our results showed that 100 µm cysteamine in culture medium increased GSH level in MII oocyte significantly compared to control (P<0.05). GSH level in 500 µm cysteamine was lower than control group but it was not significant. Presence of cysteamine in culture medium affects oocyte development competence in vitro dose dependently. Cysteamine as a thiole is able to improve development of GVBD and MII via synthesis of gluthathione as a major antioxidane in the mammalian cells.

Metronidazole (MTZ) and its derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. In this investigation several novel imidazole and nitroimidazol derivatives namely: 2-(1H-1-imidazolyl)-1-phenyl-1-ethanol 1a, 2-(2-methyl-1H-1-imidazolyl)-1-phenyl-1-ethanol 1b, 2-(2-methyl-4-nitro-1H-1-imidazolyl)-1-phenyl-1-ethanol 1c, 2-(1H-1-imidazolyl)-1-cyclohexanol 2d and 2-(2-methyl-4-nitro-1H-1-imidazolyl)-1-cyclohexanol 2e were prepared by the reaction of the corresponding imidazoles with styrene oxide or cyclohexene oxide respectively and their biological activity against Giardia lamblia cyst in compareison with MTZ were determined by flotation technique based on Bingham method. These compounds were less active than metronidazole but showed significant antigiardiasis activity.

Penicillin G extraction by an emulsion liquid membrane was studied under various operational conditions in a batch system. Span 80 (sorbitan monooleate), TOA (Trioctylamine) and a mixture of n-butyl acetate and paraffin were used as surfactant, carrier and diluent, respectively. The effects of stirrer speed, volume ratio of membrane to external phases, initial penicillin G concentration, pH and buffer concentration in the external phase, sodium carbonate concentration in the internal phase, surfactant, volume ratio of diluents and carriers on the extraction rate were examined. Extraction rate was nearly 95% and a concentration greater than 12.67 times of the initial concentration of penicillin G in the external phase was obtained in the internal phase. The pH of external phase, containing a basic salt was theoretically calculated by the amount of penicillin G which was transported in the internal phase. The calculated results agreed well with the experimental data and extraction of penicillin G was successfully performed by the emulsion liquid membrane process through adjustment of the pH of both internal and external phases to an optimum values.

The aim of this study was to examine the effect of mechanical milling time on physicochemical properties and stability of Cefotaxime sodium (CS). CS was micronized by ball milling in five period of time: 30, 60, 120, 240, and 360 min. The powder properties of the samples were examined by HPLC assay, laser diffraction, helium densitometery, IR spectrophotometery, X-ray diffraction (XRD), scaning electron microscopy (SEM), differential scanning calorimetery (DSC), thermogravimetric analysis (TGA) and Karl-Fisher titrimetery. The results showed that ball milling was not an appropriate method for particle size reduction to make solid dosage form such as dry powder inhaler formulation (DPI) of CS and by increase in milling time, degradation of CS increased.

Previous studies have suggested that drug metabolism may be altered in patients with severe neurotrauma. The purpose of this prospective study was to observe the alteration of phenytoin pharmacokinetic and the resulting drug plasma level among these patients. Twenty patients with severe head injury (Glasgow Coma Scale≤8) requiring intravenous phenytoin were included in the study. Phenytoin sodium was diluted to a concentration of 25mg/ml and infused for 20 minutes at the rate of not faster than 25mg/min. Maintenance dose of phenytoin sodium was administered in the first day of head trauma and vital signs were monitored at hourly intervals while the patients remained in the neurosurgical intensive care unit. Blood samples were obtained for peak and trough concentrations. Free and total phenytoin levels were determined by both liquid chromatography and fluorescence polarization immunoassay (Éclair) of plasma samples after ultrafiltration and deproteinization respectively. Based on the reported Km (Km = 5.4 mg/l), predicted population Vmax was calculated to be (7.3  0.4 mg/kg/d) which was significantly lower than calculated individual Vmax (9.3  3.2 mg/kg/d) (P=0.026). Moreover, significant differences was found between mean daily dose of phenytoin administered to patients (257  4 mg/d) and calculated mean daily dose based on individual Vmax (479  3 mg/d) (p=0.0015). Mean plasma concentrations determined by fluorescence polarization immunoassay (FPIA) (6.11  2.9 mg/l) and HPLC method (5.78 ± 2.8 mg/l) were not statistically different Metabolic rate increased non-proportionally with increase in phenytoin concentration, and as a result decrease in clearance. Significant alteration in the metabolism of phenytoin occurred after severe neurotrauma. Based on our results, to keep phenytoin concentrations in the range of 10-20 mg/l, an increase in the phenytoin maintenance dose and more frequent monitoring of concentration is commonly required.

Essential oil of Eremostachys laevigata Bung. (Lamiaceae) was obtained by hydrodistillation of the aerial parts of the plant and analyzed by GC/MS. Forty-two components representing 92.6% of the oil constituents were identified. The major components of the oil were dodecanal(13.4%),germacrene-D (11.5%), β- caryophyllene (10.7%) and caryophyllene oxide (7.2%).

The objective of this study was to investigate the antimicrobial activity of ethanol extract of Iranian propolis on some microorganisms using disc diffusion method. The chemical composition of the propolis was also investigated using thin layer chromatography and spectrophotometric methods. Ethanol extract of propolis showed activity only against Gram-positives and fungi, whereas no activity was observed against Gram-negatives. Thin layer chromatography screening revealed the presence of pinocembrine, caffeic acid, kaempferol, phenethyl caffeate, chrysin, and galangin in Iranian propolis. The total flavonoid and phenolic contents were 7.3% and 36%, respectively, which suggests that the strong antimicrobial activity of Iranian propolis may be due to high levels of phenolic and flavonoid compounds.

From MeOH extract of aerial parts of Achillea millefolium L. collected from Golestan province of Iran, three glycosylated phenolic compounds, luteolin 7-O-glucoside, apigenin 7-O-glucoside and caffeic acid glucoside were isolated and identified by spectroscopic analyses. Immunological properties of different fractions of plant extract were studied on humoral immune system of BALB/c mice by Microhaemagglutination test. Among these fractions only two fractions at 125 mg kg-1 and 61.5 mg kg-1 showed a significant decrease in the anti- SRBC titer of mice (P<0.05). The immunological properties of the latter fractions may be due to glycosylated derivatives of caffeic acid.