Iranian Journal of Pharmaceutical Sciences
Volume:14 Issue: 3, Summer 2018

The aim of the present study is to investigate the preventive effect of pioglitazone on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Sprague-Dawley rats weighing 180-200 g were randomized into four groups. Rats of the 1st group received only saline and served as normal group. Colitis was induced in the remaining 3 groups by 1.5% DSS administered in drinking water for 8 days. Group 2 received only saline p.o. for 30 days and served as DSS control group. Groups 3 and 4 received pioglitazone (PIO; 10 mg/kg/day, p.o.) and sulfasalazine (SUL; 300 mg/kg) respectively for 30 days. All animals were sacrificed 24 h after the last treatment. Serum levels of interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-17 (IL-17) were measured. Levels of tumor necrosis factor-α (TNF-α), reduced glutathione (GSH) and malondialdehyde (MDA), were measured in colon tissue. Significant elevation in GSH levels and reduction in MDA and TNF-α levels in colon tissue were observed in pioglitazone and sulfasalazine treated group when compared with the DSS control group. Significant elevation in serum IL-2 and reduction in serum IL-6 and IL-17 were observed when compared with the DSS control group. Pioglitazone reduced DSS-induced colitis possibly via reduction of MDA, TNF-α, IL-6 and IL-17 levels.

Outer membrane of Gram-negative bacteria is a permeability barrier to many antibacterial agents, including the glycopeptide antibiotics such as vancomycin hydrochloride and as a result these antibiotics are ineffective against Gram negative bacteria. Different strategies have been described to overcome such limitation, including application of nanoparticles, as was shown in our previous studies for polymeric nanoparticles. On the other hand, some nanoparticles have the ability to reduce the permeation of drugs through biological barriers. Therefore, in this investigation, the effects of fusogenic liposomes, which are expected to interact well with biological barriers, toward antimicrobial effects of vancomycin in different bacteria, are investigated. Vancomycin-loaded liposomes were prepared by lipid film hydration method from a phospholipid mixture composed of either DPPC: DOPE: Chol or DPPC: DOPE: CHEMS, both in 1: 0.5: 1 molar ratios. Obtained liposomes were then assessed in regard to their antibacterial properties using broth microdilution method. Liposomes were prepared by lipid-film hydration followed by extrusion and probe sonication for size reduction. Encapsulation efficiency for large hydrophilic vancomycin in liposomes was found to be in the range 0.1 to 9 % for different formulations. Probes sonicated liposomes showed smaller size and were more stable than those prepared by extrusion. Antimicrobial results showed that encapsulation of vancomycin in liposomes decreased antibacterial efficacy of vancomycin and caused MIC increments, compared to those of free vancomycin. This might indicate negligible release of this large and charged molecule from liposomes into the bacterial preplasmic space (retention of vancomycin inside liposomal cavity or lipid-drug complexation) accompanied by inability of liposomes to permeate the bacterial barrier. Further investigations are needed to explain the interaction of liposomes with bacterial membranes.

This paper proposes the least-squares support vector machine (LS-SVM) as an intelligent method applied on absorption spectra for the simultaneous determination of paracetamol (PCT), caffeine (CAF) and ibuprofen (IB) in Novafen. The signal to noise ratio (S/N) increased. Also, In the LS - SVM model, Kernel parameter (σ2) and capacity factor (C) were optimized. Excellent prediction was shown using LS-SVM, with lower root mean square error (RMSE) and relative standard deviation (RSD). In addition, Regression coefficient (R2), correlation coefficient (r) and mean recovery (%) of this method obtained for PCT, CAF and IB. LS- SVM / spectrophotometry method is reliable for simultaneous quantitative analysis of components in commercial samples. The results obtained from analyzing the real sample by the proposed method compared to the high- performance liquid chromatography (HPLC) as a reference method. One-way analysis of variance (ANOVA) test at 95% confidence level used and results showed that there was no significant difference between suggested and reference methods.

Most countries are using some kinds of pharmaceutical policies, like external reference-based pricing, to control the costs of medicines. This policy could be implemented in different ways and there is no systematic method for selecting reference countries. In this study, we tried to identify and classify the factors affecting the selection of reference countries in Iran. Delphi method was employed to elicit experts’ opinion in pharmaceutical sector on the parameters affecting the choice of reference countries. Members of the panel were experts in the field of policymaking, manufacturing, distribution and importation of medicines, insurance companies, and academics who were more familiar with the purpose of the research. Panels were run in three rounds. The results of this study reveal that the impact of pharmaceutical, economy and health sectors characteristics has been more effective, in selecting reference countries. Health insurance coverage was the most important index among all the different sectors. Other important indexes included pharmaceutical pricing system, mechanism of drug registration, gross national income (GNI) per capita, health expenditure per capita, health expenditure (share of GDP) and the out-of-pocket health expenditure. To have an efficient pharmaceutical external reference-based pricing, it is important to select reference countries with more similar important parameters. Obviously, any change in these parameters has to be considered and adjusted during the time.

 Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from either defect in insulin secretion, insulin action, or both. Postprandial hyperglycemia is a prime characteristic of diabetes mellitus and has been a focus in the therapy for diabetes. One of the therapeutic approaches which involve decreasing hyperglycemia aims at lowering blood glucose by decreasing insulin resistance, raising insulin sensitivity at the tissues and inhibiting the carbohydrate absorbance in the intestine. Plants contain different chemical constituents with potential for insulin mimetic action, decrease in insulin resistance and of α-amylase inhibitory activity may be used as therapeutic agents in the treatment of diabetes mellitus. The present study investigates the hypoglycemic activity and insulinomimetic action of aqueous and ethanolic extracts of Citrullus colocynthis by invitro α-amylase enzyme inhibition and by histopathological studies in streptozotocin (STZ) induced diabetic rats. Male Wistar rats weighing about 180- 250g were taken and divided into fifteen groups. Diabetes was induced by giving streptozotocin (STZ) (30-50mg/kg) intraperitoneally. Rats that showed blood glucose levels > 250mg/dl were selected for the study. Metformin (45mg/kg) was given as standard oral hypoglycemic agent. The aqueous and ethanolic extracts of Citrullus colocynthis (AECC and EECC) at 100mg/kg, 200mg/kg and 300mg/kg were administered to the normal and diabetic rats. The invitro α – amylase inhibitory activity was done by spectrophotometric method. Blood glucose levels were measured by glucose oxidase method. Estimation of glycogen in the lever was carried out with anthrone method. Liver and pancreas were isolated and subjected to histopathological studies. Serum insulin was monitored through chemiluminescence assay. Oral administration of both extracts showed significant inhibition of α-amylase enzyme in-vitro and decrease in blood glucose also. Glycogen and Insulin levels too were found to increase in extract treated groups which attributed for its insulinomimetic activity. The findings revealed that Citrullus colocynthis possess a very strong anti-hyperglycemic potential justifying the use of the drug for the treatment of diabetes mellitus.

Production of human proteins in Pichia pastoris has significant advantages. However, there is still need for improvement in various stages of its downstream processing like clarification and purification. In fact downstream processes are usually the most critical part of production of biotech products. This work aimed to evaluate the effect of two steps added to the downstream processes of human growth hormone (hGH) production in Pichia pastoris. Firstly the effect of clarification, with activated carbon, on capture of hGH by ion exchange chromatography (IEC) was investigated. For this purpose, a clarification process using activated carbon was used to remove process contaminants like pigments. The clarified sample was applied to the IEC column and the recovery of hGH, following IEC, was assessed using SDS-PAGE, Bradford protein assay and area under the curve (AUC). The obtained results showed that the AUC values were 2.81 and 5.61 for the with- and without-treatment samples, respectively. Protein recovery of clarified sample with activated carbon was 541 mg in comparison with 328 mg for the sample without treatment. The yield of IEC was also improved from 50.46% to 83.23% following treatment with activated carbon. Secondly, the effect of three concentrations of ammonium sulfate in the binding buffer on resolution of hGH upon elution on hydrophobic interaction chromatography (HIC) was investigated. Biological activity was used as the main criterion for evaluation of purified hGH using HIC. The obtained results indicated that by increasing the concentration of ammonium sulfate form 1 to 3 mol/L, resolution of hGH was improved, as the purified fraction using 3 mol/L of ammonium sulfate showed a specific activity of 3.1IU/mg. So the results of the present study demonstrated that activated carbon is a promising candidate for efficient clarification of recombinant hGH and improving the efficiency of the capture step. Therefore, it can be considered by biotech companies as a cost-effective and sustainable clarification procedure of recombinant proteins from high cell density cultures. This study also revealed that 3% ammonium sulfate has a positive effect on the separation of hGH variants with the desired biological activity.

Toxicopathological effects of herbs have always been a major concern. There is scant information available about the toxicopathological effects of barberry in the fetus. Since the embryogenesis in chicken is similar to human beings, the objective of this study is to evaluate the lesions of the various dosages of Berberis vulgaris using a chicken embryonic model. Fertile chicken eggs were divided into four equal treatment groups; phosphate buffered saline-injected group and barberry-injected groups whose individuals were injected with Berberis vulgaris fruit-extract at dosages of 10, 50 and 100 mg per Kg egg-weight, respectively. Embryos were re-incubated post-treatment and allowed to develop until day 18, after which they were examined for macroscopic and microscopic lesions. Results showed that embryos were stunted in the barberry-injected groups. Defect in feather growth and general congestion was accompanied by pathological changes in brain, liver, kidney, heart and lung. Histopathological lesions include congestion, hemorrhage, edema and micro-thrombosis in the affected organs. Based on findings, it is concluded that Berberis vulgaris at the above-mentioned concentrations is toxic to the chicken embryo in a dose dependent manner. Further studies are needed to clarify the toxic effects of this herb on the development of human fetus.

Nanobody (Nb) or VHH is the smallest binding domain of camelid heavy chain antibody (HcAb). Light chains of HcAb naturally removed and because of some evolutionary changes, Nbs have unique properties rather than conventional antibodies. The size of Nb is about one-tenth (0.1) of whole antibodies and this size improved some problems of four chains antibodies such as high yield of expression in prokaryotic systems and penetration to tissues. Some other characterizes of Nb like close homology to human VH, high stability in the extended range of pH and temperature, the capability to the identification of unusual epitope is very attractive for research and development of new Nb candidates for diagnosis, research, and therapeutic applications. Discovery of Nb almost coincided with advancement in phage display technology that was used along with Hybridoma technology in monoclonal antibody development. Currently, many of research groups focused on high-quality Nbs development against different targets especially in cancers and fortunately there are many of Nbs in clinical trial stages for use in extended ranges of diseases such as cancers, autoimmune and inflammatory diseases and infectious diseases. Recently two of them were approved for clinical use. Big companies like Ablynx and Merck have been invested in this field and in future, further drugs base Nbs were approved in different areas of health science. In this review, we focused on production, features, and clinical application of Nbs and will be noted to Nbs in clinical trials.

The aim of present study is to investigate neuroprotective and nootropic activity of Petroleum Ether Extract of Carica papaya seeds (PEECPS) on diabetic induced cognitive decline rats. Rectangular maze and morris water maze models were used to evaluate nootropic activity and neuroprotective effects were studied by estimating acetyl cholinesterase (AchE), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in the brains of diabetic rats. In rectangular maze and morris water maze models, 400 mg/kg of PECPS were shown the significant effect when compared with diabetic control on day 75. Significant decrease in AchE (P<0.001), MDA (P<0.01), NO (P<0.05) and significantly (P<0.01) increased levels of SOD, CAT and GSH with PECPS (200 and 400 mg/kg) when compared with diabetic control. There is a need of further studies on Carica papaya seeds as it showed protection against diabetes induced cognitive decline to reveal its mode of action.

Vacuum dried Metronidazole hydrochloride (MTZ) loaded Crosslinked polymeric blend of Poly(vinyl)alcohol (PVA) and Gelatin(GE) in different ratios by 30 freeze/thaw cycles (FTC) tested for stimuli sensitivity and crosslinking at various pH, temperature, ionic concentration and oscillatory test along with dye absorption test showed maximum swelling in alkaline pH and decreased swelling with increased ionic concentration. Digital scanning calorimetry(DSC) thermograms of the blank crosslinked sample showed a sharp endothermic peak at 160.57 0C and MTZ loaded samples showed two sharp endothermic peaks at 159.95 0C and 324.74 0C indicating the entrapment of drug in the polymeric network. Scanning electron microscopy(SEM) showed the rough polymeric texture. Fourier Transformation Infrared Spectroscopy(FTIR) confirmed the presence of new peaks in the cross-linked and drug-loaded sample. In-vitro drug release studies showed 98.253%± 0.363 and 92.248%±0.244 release in the first 6 hours. Biodegradability and bactericidal studies of the blank film indicated that the crosslinked sample is biodegradable and does not inhibit any microbial growth.