Iranian Journal of Pharmaceutical Sciences

Single chain Fragment variable (scFv) is an antibody fragment consisting variable regions of heavy and light chains. scFvs enhance their penetrability into tissues while maintaining specific affinity and having low immunogenicity. Insoluble inclusion bodies are formed when scFvs are expressed in reducing bacterial cytoplasm. One strategy for obtaining functionally active scFv is to translocate the scFv into the oxidized environment of the periplasm where the possibility for disulfide bond formation is increased. This can be achieved by cloning the gene in a vector containing N-terminal pelB leader peptide that exports foreign proteins to the periplasmic space. The aim of this study is to evaluate the influence of periplasmic localization using pelB leader peptide on the solubility of anti-HER2 scFv. Herein, anti-HER2 scFv gene was cloned between NcoI and XhoI sites of pET-22b (+) containing pelB leader peptide and in the same sites of pET-28b (+) (without pelB). The expression in BL21 (DE3) was induced using IPTG and was analyzed using SDS-PAGE and Western blot experiment. Then, the solubility of anti-HER2 scFv in BL21 (DE3) containing both pET-22 and pET-28 (anti-HER2 scFv) was determined. The results of the present study demonstrated that anti-HER2 scFv was expressed by both pET-22b (+) (+) and pET-28b (+) vectors in BL21 (DE3). The proper expression of anti-HER2 scFv was confirmed by appearance of a ~ 28 kDa band in Western blot analysis. The most anti-HER2 scFv expression from BL21 containing pET-28 (anti-HER2 scFv) was achieved when it was induced by 0.25 mM IPTG at 37 ᵒC, 24 h post-induction. The ratio of soluble/insoluble anti-HER2 scFv was significantly higher in BL21 containing pET22-(anti-HER2 scFv) than in that containing pET-28 (anti-HER2 scFv). Totally, the fusion of pelB signal sequence to anti-HER2 scFv resulted in solubility enhancement. Therefore, the production of functional anti-HER2 scFv with proper disulfide bond can be achieved by directing the recombinant protein to periplasmic space using pelB signal peptide in pET-22b (+) vector.

Although the biokinetics, metabolism, and chemical toxicity of methyl tert-butyl ether are well known, little attention was paid to the potential toxic effects of MTBE on reproduction and development in mammals. To evaluate the effects of MTBE on pregnant animals, two groups (control and test) of NMRI mice were chosen. In test group 500 and 1000 mg/Kg of it were administered intraperitonealy at 11 days of gestation and in control group no injection was made. Caesarean section was performed at 15 days of the gestation, and the fetus and placentas were examined externally. Based on our morphological results, MTBE caused significant increase (p < 0.05) in the weight of fetuses and the weight of placentas, the diameter of placentas and crown-rump length of fetuses. Also, our mitochondrial results showed significant (p < 0.05) increase in mitochondrial swelling, ROS formation and also significant (p < 0.05) decreased in MMP on mitochondria isolated from liver and brain in test group. These results suggest that MTBE through ROS formation may induce the mitochondrial dysfunction which in turn leads to inhibition of angiogenesis and morphological alterations in fetus of mouse.

Marine seaweeds synthesize different types of compounds with various biological activities, including antituberculosis and anticancer effects. The aim of this study was to evaluate anti tuberculosis of Padina australis and cytotoxicity of different fractions of this seaweed. Padinaaustralis was collected from Persian Gulf, identified and extracted by maceration with methanol-ethyl acetate. The extract was evaporated and partitioned by Kupchan method to yield Hexane, dichloromethane, Butanol and water partitions. The anti-tuberculosis activity of the crude extract and cytotoxicity of fractions were investigated using GFPMA and MTT methods. The cell survivals of HeLa cell were decreased by increasing the concentration of extracts. The IC50 value of hexane, dichloromethane, butanol and water partitions were 2.0, 20, 19.7, and 182.7μg/ml, respectively. The crude extract was not active against tuberculosis. This study reveals that different partitions of Padina australis have cytotoxic activity against cancer cell lines.

Myristica fatua var. magnifica (Beddome) Sinclair belongs to the family Myristicaceae. It is a tree used as an important plant to cure various diseases. In the present study, petroleum ether, ethyl acetate and methanolicextracts ofMyristica fatua were evaluated for its toxicity, potential analgesic, depressant and anti-inflammatory (invitro &in vivo) activities. The extracts of different concentrations wereused to evaluate the toxicity in albino rats and revealed that they are nontoxic at the studied concentration. The appropriate dose range for preclinical study was found to be 200 & 400 mg/kg and used for above said activities through oral administration and exhibited dose dependent response.In anti-inflammatory (in vitro) studies, the percentage of stabilization was found to be 79.66, 80.63 and 85.22 at concentration of 200 mg/ml of MF (Myristicafatua) leaves, bark and standard respectively. Hence present investigation has established some pharmacological evidences to support the folklore claim of MFas analgesic, depressant and anti-inflammatory.

Because of the important role of parents’ socioeconomic condition in their children’s health, the present paper aimed to evaluate the relationship between the parents’ education and children’s healthful lifestyle, including breastfeeding, nutrition, supplement intake, smoking, and personal hygiene. Parents’ behavior is an important factor that affects children’s health status. Accordingly, a cross-sectional descriptive analysis was conducted using a self-administrated anonymous questionnaire. A total of 600 anonymous questionnaires were distributed among the children’s parents in primary schools in Tehran, Iran, of which 62% were returned. Responses showed that 89.2% of mothers intended to breastfeed and 69% of children had suitable nutrition. Additionally, the study result indicated a significant correlation between parents’ education and children’s personal hygiene. There was a significant relation between parents’ education and parents’ smoking as well. Furthermore, there was a significant relation between mothers’ education and supplement intake in their children. Therefore, parents’ education and health literacy are the main factors in children’s health that should be addressed by policymakers.

Intravenous immunoglobulin (IVIG) is an expensive medicine which is widely used for unlabeled indications. We conducted this drug utilization review (DUR) to evaluate the appropriateness of IVIG utilization in Tehran, Iran. This cross sectional study was conducted in a referral pediatric tertiary care hospital in Tehran. During a three month period in 2015, medical records of inpatients with IVIG order were evaluated. Appropriate indications for IVIG were determined based on the evidenced based guidelines and literature. Medical records of patients were reviewed and demographic data as well as the diagnosis, previous treatments, IVIG indication, dose, duration and the adverse drug reactions (ADR) were documented. Additionally, cost of therapy was calculated. During the study, 115 patients received IVIG. In 51 cases (44.4%), a total of 1338 gram IVIG was administered inappropriately. We found that in 32 cases (27.8%), intractable epilepsy was the inappropriate indication. The most frequent prescribers of IVIG were clinical specialists of pediatric neurology, pediatric asthma and immunology followed by pediatric hematology. In terms of safety, we found that 64 (55.6%) patients experienced at least one ADR. The most prevalent ADRs were hypotension (27.8%), fever (26.9%) and chills (18.3%). Total cost of IVIG during the study period was 6,075,500,000 Rials (approximately 215,872 $). Irrational use of IVIG is still a considerable issue that costs a considerable amount. Due to the high cost of therapy, multifaceted interventions are necessary to be implemented to improve the prescribing practice.

Prescribing pattern is also important factor to identify the problems related to prescribing and best tool to improve the quality of prescription and patient care. The aim of current study was to evaluate the quality of prescription and prescribing practices as per WHO drug core indicators in Lahore, Pakistan. A descriptive and cross- sectional study was carried out to access the prescribing pattern in Lahore, Pakistan. A sample of 300 prescriptions were collected from well –known Pharmacies and hospitals located in Lahore, Pakistan. A Structured data collection form was designed. The standard world health organization (WHO) drugs core prescribing indicators were used to determine the prescribing pattern of physicians. Data was analyzed using IBM SPSS V21.0. The name of patients was mentioned 93% of total prescriptions. While age and sex mentioned on prescriptions were 67% and 53% respectively. Only 22% prescriptions were containing patient weight description.32% of total prescriptions were mentioned prescriber address. 16% of total prescriptions were containing patient address. While 60% of total prescriptions were mentioned specliazation of prescribers. The total numbers of drugs prescribed on all encounter was 1122. The average number of drugs prescribed per encounter was 3.74(optimal value 1.6-1.8). The total number of drugs prescribed under generic name was 0% (optimal value 100%). Antibiotics were 42.5% of total drug prescribed (optimal value 20-26.8). Injections were 19.25% of prescriptions (optimal value less 10%). Prescription writing is a tough task. The results of current study show a poor compliance rate of legal requirement required for prescription writing. Most of prescribers were deviated from standard guidelines. There is dare need to improve the knowledge about prescription writing and prescribing practices. Continuous education is required to ensure the rational prescribing at Lahore, Pakistan in future.

Patients with impaired immunity are at particular risk of infections with Candida albicans. Antifungal drugs such as azoles commonly used for candidiasis treatment, but drug resistance is one of the most common problems for public health. The aim of this study was to evaluate the expression of lanosterol 14-demethylase (ERG11) gene for three-drug combinations in C. albicans. Disk diffusion and broth microdilution susceptibility tests were employed to evaluate the synergic effects of amphotericin B, fluconazole, voriconazole, ketoconazole and itraconazole. Quantification of ERG11 gene expression was carried out in C. albicans treated with threedrug combinations of fluconazole/ ketoconazole/ voriconazole and fluconazole/ ketoconazole/ itraconazole.Three-drug combinations revealed synergistic and partial synergistic effect for all tested isolates (FIC index range of 0.27-0.77). The expression levels of ERG11 were down-regulated by three-drug combination of fluconazole/ ketoconazole/ voriconazole treatment. Fluconazole synergizes with ketoconazole and voriconazole in three-drug combination against C. albicans by targeting of the ERG11 gene.