DARU, Journal of Pharmaceutical Sciences
Volume:16 Issue: 1, Spring 2008

Background and purpose of the study: Several polymeric systems have been used to fabricate ocular inserts for better ocular bioavailability and retention to drug of which gelling systems have shown advantages of convenient administration and increased contact time. The purpose of the present study was to develop a bioadhesive in-situe gelling ocular insert of Gatifloxacin using polymeric system of sodium alginate as gelling and chitosan as bioadhesive agent. Polymeric ocular inserts of Gatifloxacin sesquehydrate (GS) were composed using sodium alginate and chitosan with glycerin as plasticizer by solvent casting method. The ocular inserts were investigated for physicochemical properties (thickness, weight variation, folding endurance and surface pH), mechanical strength (tensile strength, elongation at break), swelling index, and bioadhesion parameters. In vitro release studies were carried using a fabricated donor-receptor compartment model. Cumulative drug released from the formulation ranged from 95-99% within 8-12h. The formulation D (2% sodium alginate and 1% chitosan) sustained the drug release for the longest period of time (12h). Zero-order release of the drug was from optimized formulation D. A high correlation coefficient (r=0.9845) was recorded between in vitro and in vivo drug release. Gatifloxacin sesquehydrate inserts have appreciable film forming properties and were found to posses good antimicrobial efficacy.

Background and the purpose of the study: Dihydropyridines having carboxamides in 3 and 5 positions show anti-tuberculosis activity. The purpose of the present study was to synthesize new DHPs having possible anti-tuberculosis activity. 4,5-Dichloroimidazole-2-carboxaldehyde was condensed with N-arylaceto-acetamides and ammonium acetate in methanol to give N,N-diaryl-4-(4,5-dichloroimid-azole-2-yl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxamides. All compounds were screened for their antitubercular activity against Mycobacterium tuberculosis (H37Rv). Results and major Some of the new synthesized compounds exhibited a moderate activity in comparison to rifampicin.

Background and purpose of the study: There is no report on the effect of seeding-medium ingredients on Saccharopolyspora erythraea growth and erythromycin production. In this study, the enhancing effects of seeding-media which have been used routinely for screening, isolation or identification of actinomycetes, on Saccharopolyspora erythraea growth and erythromycin production were investigated. The control medium contained soybean meal, glucose, glycerol, (NH4)2SO4 and CaCO3 as the major constituents and several media (I, II, III, ISP2, ISP3 and ISP4) were used for production of the antibiotic. Concentrations of biomass and erythromycin were measured by spectrophotometry, HPLC and bioassay methods and the effects of the composition of seeding media on pH were also determined. The concentration of erythromycin in medium II was 2.71g/l (1.33 times more than that of the control medium) and trends in production were: medium II > ISP4 = ISP2 = Control > ISP2 = Control = ISP3 > ISP3 = medium III = medium I. In the media containing starch and casein, the hyphae of S. erythraea were star-shaped and much branched. Major By virtue of other technical and economical characteristics of the seeding media used for erythromycin production, it is concluded that medium II is the best seeding medium formulation for erythromycin in comparison to others.

Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA) is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs) in hippocampus dependent spatial memory in place avoidance task in male rat. Long Evans rats (n=150) were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter) arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors) agonist norepinephrine (NE, 0.5 and 1 µg/µl) and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl) before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

Increase in the nitric oxide in the spermatic veins of men by varicocele has been reported. Although Several studies have considered the relationship between varicocele and semen NO concentrations, no study on the effects of nitric oxide synthase inhibitor (L-NAME) on epididymal sperm count, motility and morphology which are important in fertility of the individual has been reported. The aim of study was to evaluate the effects of nitric oxide synthase inhibitor (L-NAME) on epididymal sperm count, motility, and morphology in varicocelized rat. Twenty four Wistar male rats divided into four groups. The group A and B underwent a left experimental varicocele (by 20-gauge needle). Group C, underwent a procedure similar to groups A and B without any change on spermatic vein (as sham group). Group D referred to as control. Animals in group A were killed 10 weeks after the operation and both left and right epididymal sperm were counted and their morphology and motility were analyzed. Animals in group B received 10mg/kg L-NAME intraperitoneally daily for ten weeks. In group A, Sperm count decreased and the morphology changed significantly in comparison with the groups C and D. The sperm morphology in groups A and B showed statistically significant differences (P<0.0001). Sperm motility decreased significantly in the group A in comparison with the groups C and D. Although motility in group A of animals were different in comparison with group B, it was not statistically significant. These findings suggest that nitric oxide synthase inhibitor (L-NAME) improved sperm count and morphology.

Background and the purpose of the study: Trigonella foenum-graecum (TFG) has demonstrated beneficial effects in both Insulin-dependen and non- Insulin-dependen diabetic animals. This study was conducted to evaluate the effects of the alcoholic seed extract of this plant on aortic reactivity and underlying mechanisms in streptozotocin-diabetic rats. Male Wistar rats were divided into control, extract-treated control, diabetic, and extract-treated diabetic groups. Diabetes was induced by a single i.p. injection of streptozotocin (STZ; 60 mg/kg). Treatment groups received TFG extract (200 mg/kg; i.p.) every other day for 1 month. Then, contractile responsiveness of thoracic aorta to KCl and noradrenaline (NA) and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was determined. For determination of the involvement of NO and prostaglandins in relaxation response to ACh, rings were incubated 30 min before the experiment with N(ω)-nitro-L-arginine methyl ester)L-NAME(and/or indomethacin (INDO). Diabetic state significantly increased maximum contractile responses to KCl and NA (p<0.01-0.005) and reduced maximum relaxation due to ACh (p<0.01) as compared to controls and treatment with TFG extract in diabetic group significantly improved these changes relative to untreated diabetic group (p<0.05). Meanwhile, pretreatment with L-NAME did not produce any significant change between diabetic and extract-treated diabetic groups. On the other hand, there was a significant difference in both of these two groups following pretreatment with INDO (p<0.01). Major Intraperitoneal administration of alcoholic seed extract of TFG for one month could improve some functional indices of the vascular system in diabetic state and endothelium-derived prostaglandins are involved in this response.

Background and the purpose of the study: Local people of Lakshmipur district of Bangladesh use leaves of Peperomia pellucida in the treatment of excited mental disorder but its neuropharmacological effect has not yet been explored. In the present study depressant effects of leaves of this plant was investigated. Petroleum ether and ethyl acetate soluble fractions of ethanol extract of Peperomia pellucida leaves were administered to mice intraperitonealy and their effects on duration of diazepam-induced sleep, nikethamide-induced toxicity, light-dark test and force swimming test were determined. Results and major The duration of diazepam-induced sleep was extended by administration of these fractions. Nikethamide at high doses caused death of mice and administration of these fractions delayed the time that nikethamide caused the death of animals. In light-dark test and force swimming test these fractions showed diazepam type effects. The changes in doses (50-200 mg/kg) resulted in modification of efficiency of these effects. These results suggest that both fractions of P. pellucida leaves have dose dependent depressant effects.

99mTc-MAG3 is a standard radiotracer for renal dynamic functional study. Despite itsproperties for clinical uses, it has numerous technical limitations. 99mTc-EC is also a tubularradiotracer for renal imaging, which has not been used worldwide. In this study, the use of 99mTc-ECand 99mTc-MAG3 for renal functional study were compared. Thirty five patients (20 male, 15 female; mean age of 34.63 ±10.69 years) were entered inthe study. About 10 mCi of 99mTc-EC and 99mTc-MAG3 were administered in different days within 7days intervals and serial images were obtained for 30 minutes. Serum creatinine and visualscintigraphic findings of all patients were within normal limits. In this study, the renal uptake of 99mTc-EC was significantly higher than 99mTc-MAG3 (6.20%vs 4.39% of the injected dose), while the hepatic activity of 99mTc-EC was significantly lower (307 vs439 mean pixel count, p<0.0001). Also the absolute values for some other quantitative parameterssuch as right and left kidney transit times and ERPF were different for each radiotracer. In spite ofthese differences most quantitative parameters (except for right kidney transit time, liver uptake andTmax of both kidneys) showed good correlations for both agents. The calculated ERPF with 99mTc-EC as compared to 99mTc-MAG3 is in closer proximityto the true values. Also the use of 99mTc-EC compared to 99mTc-MAG3 in clinic due to simplicity ofpreparation, higher stability, higher renal uptake, and lower hepatobiliary activity is better. Thereforethe use of 99mTc-EC as an appropriate substitute or ever preferred radiopharmaceutical for 99mTc-MAG3 radiopharmaceutical for renal function studies is recommended.

Background and the purpose of the study: Tuberculosis is curable if patients take sufficient uninterrupted therapy. Most experts acknowledge importance of patient adherence in efforts to control of the disease. This cross-sectional study was designed to evaluate the rate of compliance to anti-tuberculosis regimens by means of urine tests in newly diagnosed tuberculosis patients. Investigation was carried out in Tehran University of Medical Sciences Teaching Hospitals, Tehran, IRAN. Fifty patients completed the study. The patients'' urine samples were obtained at 0, 1, 2, 4 and 6 months of the study. Simple chemical methods were used to detect Isoniazid, Rifampin, and pyrazinamide, the three main drugs in tuberculosis treatment regimens. Urine tests at months of 0 and l of the study were considered as control tests. After the first month, the patients'' compliance was about 96%. At months of second, fourth and sixth, the whole adherence rates were 56 %, 76% and 81% respectively. About 30% of patients were non-compliant with treatment regimen which was more frequent than presumed; therefore detection of non-adherent patients is an essential subject in developing countries.

Osteoporosis is a disease of high prevalence with increased bone loss. Free radicals have been proved to be involved in bone resorption. Glutathione reductase (GR) plays an essential role in cell defense against reactive oxygen metabolites by sustaining the reduced status of an important antioxidant, glutathione. In the present study GR activity of plasma as an antioxidant enzyme in relation to Bone Mineral Density (BMD) was investigated. GR activity was measured spectrophotometrically at 339 nm in 138 women. Participants were selected by inclusion and exclusion criteria from those who were referred to Jamie Clinic in Tehran for BMD evaluation. Plasma activity of GR (Mean± SD) was: 64.44 ± 37.68 U/L in the control group, 75.49 ± 54.84 U/L in the total patients [(mild Osteopenia + severe Osteopenia and Osteoporosis) (Tscore<-1)] and 80.48 ± 61.91 U/L in the patients with severe Osteopenia and Osteoporosis respectively (Tscore <-1.7). The results show that plasma activity of GR in patients with bone deficiency was higher than the control group. The difference was more pronounced between controls and the patients with severe Osteopenia and Osteoporosis, than those differences between controls and the total patients. Femur Tscore adjustment with age and BMI showed significant negative correlation with the plasma activity of GR in all subjects.