DARU, Journal of Pharmaceutical Sciences
Volume:20 Issue: 3, 2012

Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebo control group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial. 45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α), total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were also determined. Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024). Patient’s mortality (28 day) was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing any complications. No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to prevent microalbuminuria.

Background and of the study H. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium. 137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. 37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 mug/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum. The most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 mug/ml, respectively.

Deep venous Thrombosis is a serious, possible life threatening event which is often ignored in psychiatric Settings. In this paper three cases of deep venous Thrombosis (DVT) following the use of olanzapine and risperidone are presented. The data of Three patients was collected from hospital records. The patients were in good general physical health and had no personal or familial history of DVT. The patients were not overweight (BMI < 25) but they suffered from DVT after initiating risperidone and olanzapine. Risk of DVT exists in patients under treatment with atypical antipsychotics in spite of no pre existing risk factor.

Lead is a pervasive toxin that has been implicated in human poisonings throughout history. Exposure mitigation strategies in the United States and worldwide have led to a decline in symptomatic poisonings and population blood lead levels; however, lead remains a major health hazard. In this article, we review the history of lead toxicity, clinical manifestations ranging from subclinical and subtle features to life-threatening complications, and the subsequent public health interventions in the US. In addition, we explore common routes of lead exposure and the unique differences between the US and Iran. Although the US has made significant strides with regard to this public health issue, lead poisoning in both countries continues to be a health hazard in the adult and pediatric populations. It is also critical to consider natural disasters and reconstruction efforts as potential sources of lead contamination. In conclusion, we make recommendations that both the US and Iranian authorities can implement to eradicate lead as a public health hazard.

Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researcher's attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed. Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood. Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

Background of the study:The present investigation was designed with the intention to formulate versatile 5-fluorouracil (5-FU) matrix tablet that fulfills the therapeutic needs that are lacking in current cancer treatment and aimed at minimizing toxic effect, enhancing efficacy and increasing patient compliance. The manuscript presents the critical issues of 5-FU associate with cancer and surpasses issues by engineering novel 5-FU matrix tablets utilizing chitosan- polycarbophil interpolyelectrolyte complex (IPEC). Precipitation method is employed for preparation of chitosan and polycarbophil interpolyelectrolyte complex (IPEC) followed by characterization with Fourier transform infrared spectroscopy (FT-IR), Differential Scanning calorimeter (DSC) and X-ray Diffraction (XRD). 5-FU tablets were prepared by direct compression using IPEC. Six formulations were prepared with IPEC alone and in combination with chitosan, polycarbophil and Sodium deoxycholate. The formulations were tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release (buccal, vaginal and rectal pH), ex vivo permeation studies, mucoadhesive strength and in vivo studies. FT-IR studies represent the change in spectra for the IPEC than single polymers.DSC study represents the different thermo gram for chitosan, polycarbophil and IPEC whereas in X-ray diffraction, crystal size alteration was observed. Formulations containing IPEC showed pH independent controlled 5-FU without an initial burst release effect in buccal, vaginal and rectal pH. Furthermore, F4 formulations showed controlled release 5-FU with highest bioadhesive property and satisfactory residence in both buccal and vaginal cavity of rabbit. 3% of SDC in formulation F6 exhibited maximum permeation of 5-FU. The suitable combination of IPEC, chitosan and polycarbophil demonstrated potential candidate for controlled release of 5-FU in buccal, vaginal and rectal pH with optimum swelling approaching zero order release.

The genus Salvia, with nearly 900 species, is one of the largest members of Lamiaceae family. In the Flora of Iran, the genus Salvia is represented by 58 species of which 17 species are endemic. Salvia hypoleuca Benth., is one of these species growing wildly in northern and central parts of Iran. Salvia species are well known in folk medicine and widely used for therapeutic purposes. Literature review shows that there is no report on phytochemical investigation of the roots of S. hypoleuca. The separation and purification process were carried out using various chromatographic methods. Structural elucidation was on the basis of NMR and MS data, in comparison with those reported in the literature. The isolated compounds were identified as sitosteryl oleate (1), β-sitosterol (2), stigmasterol (3), manool (4), 7α-acetoxy royleanone (5), ursolic acid (6), oleanolic acid (7), 3-epicorosolic acid (8), 3-epimaslinic acid (9) and coleonolic acid (10). In the present study, three sterols, two diterpenes and five triterpenes were isolated from the ethyl acetate extract of the roots of S. hypoleuca. As the chemotaxonomic significance, some of the isolated compounds (1–7, 9) have not been previously reported from the species S. hypoleuca, while the triterpenes 8 and 10 are now documented from Salvia genus for the first time.

An important medical disorder that is common but not successfully managed in the present day is cancer. In fact, cancer has been known in medicine for many centuries. Continuous attempt to find anti-neoplastic drug leads to several ant-cancer drugs at present. However, as noted, the actual effective drug is still not available. Hence, cancer is still a deadly disease. Finding for new anti-neoplastic drug is the focus in cancer research at present. In the process, after developing of new drug alternatives, the next step is to study on its efficacy. Basically, the evaluation on pharmacological and toxicological effects has to be done for confirming the effectiveness and safety of the new drug. To serve this purpose, the in vitro model study is generally gone as the pioneer step. It is also the basic requirement for further drug registration [1]. Focusing on the vitro model study, there are some facts to be addressed. First, the model is not an actual thing. It is only the attempt to simulate the real phenomenon. Second, the study is generally in vitro. This is for the safety reason. In vitro study means the experiment outsides the living things. Hence, an in vitro study is totally not the real case in human beings. In general, the better study can be done based on in vivo study only if the safety is completely confirmed. It should be further noted that in vivo study can also be either in animal model or real human subjects. The best interpretation has to be based on finding for human study. Nevertheless, the human study has the highest risk comparing to the other techniques. Focusing on the new anti-neoplastic drug, it is perceived as a dangerous chemical agent. Hence, it is rarely studied in human subjects. Also, it is very hard to include cancerous patients to enroll in such study and it should be unethical to perform such experiment in normal subjects. Furthermore, any studies have to follow the good research guideline. The use of randomized control trial is usually preferable for final acceptance on registration process [2]. Finally, the present in vitro model study also poses the pitfall. Most in vitro model for the novel anti-neoplastic drug test is based on the cell culture, which is usually transformed neoplastic cell type [3]. Those transformed cell is not normal physiological cells, hence, the normal physiological response to the studied chemical agent cannot be expected. Those cancerous cells might not respond well or tolerate to side effect [3].

Background and the purpose of the study: Adenosine deaminase (ADA) inhibition not only may be applied for the treatment of ischemic injury, hypertension, lymphomas and leukaemia, but also they have been considered as anti- inflammatory drugs. On the other hand according to literatures, ADA inhibitors without a nucleoside framework would improve pharmacokinetics and decrease toxicity. Hence we have carried out a rational pharmacophore design for non-nucleoside inhibitors filtration. Methods A merged pharmacophore model based on the most potent non-nucleoside inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and natural products were generated and applied for compounds filtration. The effects of filtrated compounds based on pharmacophore and docking studies investigated on ADA by UV and Fluorescence spectroscopy techniques. Extracted compounds were find efficiently inhibit ADA, and the most potent (2) shows an inhibition constant equal to 20 μM. Besides, Fluorescence spectroscopy studies revealed that enzyme 3D structure bear further change in lower concentrations of compound 2. 3 non-nucleoside inhibitors for ADA are presented. According to obtained results from UV and fluorescence spectroscopy, such interesting pharmacophore template with multiple approaches will help us to extract or design compound with desired properties.

Plasma derived medicines (PDM) including immunoglobulins, clotting factors and albumin are life saving medicines which due to their high costs are inaccessible for many patients living in developing countries. By contrary substantial volume of plasma as raw materials for production of these medicines are discarded worldwide. Good quality recovered plasma, as a result of separation of donated blood into its components, could be used for production of PDM. In 2011 Iranian donors donated about 2 million units of blood. A shift from administration of whole blood to components therapy has resulted in the generation of over 250,000 liters of surplus of recovered plasma. This created a good opportunity for Iran’s health care system to use this plasma for production of PDM. Therefore Iran national transfusion service has started a contract fractionation program for converting recovered plasma into PDM. This program not only provided essential PDM for Iran pharmaceutical market but also has created a direct saving of about 8.5 million Euros in 2011 for national health sector. In addition this program has drastically contributed to improvement of overall quality of working procedures and services provided by Iran national blood transfusion organization.

Background and purpose of the study:Pharmacies as direct providers of medicine and pharmaceutical services to patients have an important role in the health status of a society. The assessment of their financial situations by healthcare policy makers is necessary to prevent any negative effects on population''s health. In this study we aim to analyze the financial status of pharmacies in Tehran, Iran. This study is a cross-sectional study based on a survey. Two-hundred and eighty-eight private community daytime pharmacies in Tehran were selected by random sampling. We used two questionnaires to collect data regarding cost, expense and income factors of private pharmacies and the significance of each of them from these selected pharmacies. The data was collected in 2011 from Tehran pharmacies. Profitability of pharmacies in Tehran, Iran was calculated in its current situation and then estimated for three defined scenarios: 1. The dispensing fee is omitted (ceteris paribus), 2. Pharmacies are prohibited from selling hygienic & cosmetic products (ceteris paribus), 3. Scenarios 1 and 2 together (ceteris paribus). These data were analyzed by using SPSS and descriptive-analytic statistics. About 68% of interviewees responded to our questionnaires. Our analysis indicated that the average annual costs (and expenses), income and profits of pharmacies are 73,181; 106,301; and 33,120 United States Dollar (USD), respectively. The analysis indicated that omission of dispensing fee (scenario 1) and prohibition of pharmacies from selling hygienic & cosmetic products (scenario 2) would decrease income of pharmacies to 18438 and 14034 USD/year, respectively. According to respondents, the cost (or expense) of properties and buildings, energy, taxes, delays in reimbursement by insurance companies, and renting the place of pharmacy could be considered as cost factors and prescription medicines, OTC medicines, dispensing fees, hygienic & cosmetic products, and long-term payment to pharmaceutical distribution companies as income factors, which have significant effects on a pharmacy''s economy. Major According to the results of this study, regarding the pharmacies'' cost (and expenses) and incomes, the omission of dispensing fees for prescriptions has considerable negative effects on the profitability of pharmacies and likely on society''s health.

In the recent years, there has been a mounting interest on the use of natural products with antioxidant effect in the management of cancer. If one evaluates search engines will find a burden of papers that have tried to test natural products having anti free radical effects in the management of cancer. But the sense does not seem rational because in cancer we need a compound to kill cancer cells. As a matter of fact, free radicals induce oxidative stress in the body and their deleterious effect in many deliberating diseases that have no exact cure such as diabetes [1], colitis [2], osteoporosis [3], environmental toxins [4] or cancer [5] has been well documented. In spite of this fact, many examples can be given that some although produce free radicals but do not induce cancer such as paraquat toxicity [6] and Alzheimer disease [7]. Superoxide dismutase (SOD) changes superoxide anion radical to hydrogen peroxide which in turn, decomposes to water and oxygen by glutathione peroxidase (GPx) and catalase (CAT). An imbalance between production of free radicals in one side and activities of SOD, GPx and CAT on the other side determines the fate of the cells [4]. Free radicals especially superoxide anion radicals are produced in cancer cells more than what seen in normal cells. Production of free radicals in cancer cells seems a defense mechanism by which body tries to fight against cancer cells. Free radicals especially oxygen species provide a supply for hydrogen peroxide which eventually decomposes to water and oxygen. Oxygen, in turn, reduces neovascularization and metastasis [8]. Thus, cancer is a condition which is accompanied with a decrease in intracellular oxygen. It look likes that every drug or plant extract which can increase intracellular hydrogen peroxide and further decomposition to water and oxygen may be effective in treatment of cancer [5]. On the other hand, hydrogen peroxide can convert to hydroxyl anion and hydroxyl radical via a process called Fenton reaction. Thus, we need a compound to produce free radicals not scavenge free radicals to overwhelm cancer. Although beneficial role of antioxidants in cancer prevention has been well described, it is still in doubt whether or not antioxidants are effective in treatment of cancer. Theoretically, antioxidants scavenge superoxide anion radical and thus deplete the supply of intracellular hydrogen peroxide which may deteriorate cancer conditions. On the other hand, they scavenge hydroxyl radicals which have beneficial effects.

Background and Malnutrition is a common problem in patients who are hospitalized in surgical and medical wards. Surgical patients, geriatric populations and individuals with severe illness are more vulnerable to malnutrition during their hospitalization course. The purpose of this study was evaluation of parenteral nutrition services in a referral teaching hospital, Tehran, Iran. Medical records of 72 patients who received parenteral nutrition during one year period in different surgical and medical wards of Imam Khomeini hospital were reviewed retrospectively by clinical pharmacists. Criteria for initiation of parenteral nutrition, selection of appropriate formulation and monitoring parameters were assessed based on the American Society of Parenteral and Enteral Nutrition recommendations. Based on the patients'' anthropometric parameters and serum albumin levels, 4.2%, 75% and 20.8% of the patients were well-nourished, moderately malnourished and severely malnourished respectively at the hospital admission and before nutritional support. Adequate calorie, protein, carbohydrate and lipid supports were achieved in 21.1%, 32.4%, 23.7% and 10.5% of the patients respectively. About 91% of the patients experienced at least one complication of the nutritional support. In this evaluation, several errors in assessment, establishing goals, and monitoring of parenteral nutrition regimens have been detected. Approximately all of the patients did not receive to the trace elements supports goals.

This paper presents the methodology for assessing and selecting the most appropriate procedure for the preparation of nanoparticles by implementing the analytical network process. The commonly utilized nanoparticle preparation methods are Polymer Precipitation, Interfacial polymer deposition, Complex Coacervation, Cross linking, Emulsion solvent diffusion, Homogenization and Polymerization method. There are numerous parameters to be considered in groundwork of nanoparticles that departs the conclusion manufacturer in bias. One has to address a number of components in alignment to determine and choose the optimum conclusion choices, because an unsuitable conclusion could lead to the eventual merchandise having to be formulated and developed again. For this cause in this paper, we study selecting the most appropriate procedure for the preparation of nanoparticles utilizing one of the multi criteria-decision making techniques, Analytic Network Process. Methodology The main goal was determined. The criteria and sub-criteria that affect the main goal were determined. The alternatives for the problem were determined. The interactions between criteria, sub-criteria, and alternatives respect to the main goal were determined. The super matrixes according to the network were assembled and then weighted super matrix and limit super matrix were then constructed. The values of this limit matrix are the desired priorities of the elements with respect to the goal. The alterative with the highest priority was finally chosen as the best alternative. The emulsion solvent diffusion technique (M-5) has the highest value (0.434379) among the alternative methods that are applicable to the preparation of the nanoparticles. The second highest is Polymer Precipitation (M-1) with a value of 0.178798, and the lowest value or last choice is Cross Linking (M-4) with a value of only 0.024516. The alternative with the highest priority would achieve the goal, i.e., the best method for the preparation of the nanoparticles. The alternative M5 emulsion solvent diffusion technique, scoring 0.434379 was the one with largest main concern amidst all the other alternatives and thereby judged to be the most apt procedure for the preparation of nanoparticles.

Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1h, 2h, and 8h and for 24h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p < 0.05 was considered statistically significant. Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8) was found to be sustained well compared to the most satisfactory formulation (F7) of 7 runs. The n value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian) diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24h.Study showed these eco-friendly natural gums can be considered as promising SR polymers.

Cuscuta species known as dodder, have been used in traditional medicine of eastern and southern Asian countries as liver and kidney tonic. Flavonoids are considered as the main biologically active constituents in Cuscuta plants especially in C. chinensis Lam. In the present study, a fast, simple and reliable method for the simultaneous determination and quantization of C. chinensis flavonols including hyperoside, rutin, isorhamnetin and kaempferol has been developed. The chromatographic separation was carried out on a reversed phase ACE 5 C18 with eluting at a flow rate of 1 ml/min using a gradient with O-phosphoric acid 0.25%: acetonitrile for 42 min. UV spectra were collected across the range of 200–900 nm, extracting 360 nm for the chromatograms. The method was validated according to linearity, selectivity, precision, recovery, LOD and LOQ. The method was selective for determination of rutin, hyperoside, isorhamnetin and kampferol. The calibration graphs of flavonols were linear with r2 > 0.999. RSDs% of intra- and inter-day precisions were found 1.3&3.4 for rutin, 1.5&2.8 for hyperoside, 1.3&3.3 for isorhamnetin and 1.7 & 2.9 for kaempferol which were satisfactory. LODs and LOQs were calculated as 1.73 & 8.19 for rutin, 0.09 & 4.19 for hyperoside, 2.09 & 6.3 for isorhamnetin and 0.18 & 0.56 for kaempferol. The recovery averages of above-mentioned flavonols were 90.3%, 97.4%, 98.7% and 90.0%, respectively. The simplicity of the method makes it highly valuable for quality control of C. chinensis according to quantization of flavonols.

Background and purpose of the study: The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT) and blood biochemical indices of experimentally-induced hyperglycemic rats. Late stage and early stage of Type 2 diabetes mellitus (T2DM) were induced in rats by streptozotocin (STZ) and a combination of STZ and niacinamide (NIA/STZ), respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days). Body weight and fasting blood sugar (FBS) were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c) and sera for alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), triacylglycerol (TG), total cholesterol (TC), total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT) along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days. During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05). Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated earlystage diabetic rats. Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned) and longterm (28 days, in this study) effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.

Priapism is defined as an unwanted, prolonged, and painful erection which is unrelated to sexual stimulation. Some case studies suggest that priapism is an adverse effect of antipsychotic medications. In our case study a 30 year-old Iranian male with schizophrenia was experiencing recurrent priapism associated with quetiapine use. There are three interesting facts about this case: Firstly, the patient suffered priapism after even low dose consumption of quetiapine. Secondly, this case had experienced priapism with risperidone, olanzapine, and even clozapine in the past, suggesting a possible pharmacodynamic interaction of antipsychotics and inner biological traits in this particular case. Thirdly, priapism induced by low dose quetiapine was resolved after cigarette smoking.

Background and purpose of the study: Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale. We investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing. The yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1) and 10-deacetyl baccatin III (4.2 mgl-1) were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1) in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1), Baccatin III (5.0 mgl-1), and 10-deacetyl baccatin III (1.45 mgl-1) were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media.

Background and purpose of the study: Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale. We investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing. The yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1) and 10-deacetyl baccatin III (4.2 mgl-1) were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1) in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1), Baccatin III (5.0 mgl-1), and 10-deacetyl baccatin III (1.45 mgl-1) were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media.

Acute poisoning with organophosphorus compounds (OPs) is a major global clinical problem in the developing countries. There have been many animal studies and few human surveys on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation. The aim of this prospective study was to document the pattern of tympanic temperature changes among OP poisoned patients throughout the length of their hospital stay. 60 patients with diagnose of organophosphate poisoning were included in this study. Questioner was filled out by trained nurses including demographic, clinical and paraclinical data. Tympanic temperature and Pulse rate data of the cases were collected on five- occasions after admission. There were 41 (68.3%) male and 19 (31.7%) female, with a mean age of 34.4 ±19.4 years (range 13–89 years). Forty five patients had intentional poisoning for suicidal attempt. At the time of entry, the mean tympanic temperature, pulse rate, respiratory rate and blood pressure (systolic and diastolic) of the OP poisoned patients were respectively 37.1+/−0.6°C (36.0- 39.5), 91+/−18 (55–145), 18+/−5.6 (8–44), 116+/−20 mm Hg (70–170) and 75+/−11.6 mm Hg (40–110). 41.7% of the cases had serum butyryl cholinesterase activities (BChE) ≥ 50% normal (≥1600 mU/ml). Our patients had normal temperature at the time entry (mean = 37.1). Tympanic temperature decreasing below 36°C was not detected among the patients during the study period. A rise in mean tympanic temperature was found after atropine administration. Our study showed hypothermia was not considerable factor among organophosphate poisoned patients, although more studies with similar situations in tropical countries are needed.

Iranian soldiers were attacked with chemical bombs, rockets and artillery shells 387 times during the 8-years war by Iraq (1980–1988). More than 1,000 tons of sulfur mustard gas was used in the battlefields by the Iraqis against Iranian people. A high rate of morbidities occurred as the result of these attacks. This study aimed to evaluate the delayed toxic effects of sulfur mustard gas on Iranian victims. During a systematic search, a total of 193 (109 more relevant to the main aim) articles on sulfur mustard gas were reviewed using known international and national databases. No special evaluation was conducted on the quality of the articles and their publication in accredited journals was considered sufficient. High rate of morbidities as the result of chemical attacks by sulfur mustard among Iranian people occurred. Iranian researchers found a numerous late complications among the victims which we be listed as wide range of respiratory, ocular, dermatological, psychological, hematological, immunological, gastrointestinal and endocrine complications, all influenced the quality of life of exposed victims. The mortality rate due to this agent was 3%. Although, mortality rate induced by sulfur mustard among Iranian people was low, variety and chronicity of toxic effects and complications of this chemical agent were dramatic.

Background and the purpose of the study:Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. Results and major Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation.

The currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives. The 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2''-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents. The in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 μg/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score. The 3-azolyl-4-chromanone phenylhydrazones considered as analogs of 3-azolyl-4-chromanone oxime ethers basically designed as antifungal agents. The antifungal activity of title compounds was comparable to that of standard drug fluconazole. The drug-likeness data of synthesized compounds make them promising leads for future development of antifungal agents.

Active pharmaceutical ingredients (APIs) are most conveniently developed and delivered orally as solid dosage forms that contain a defined crystalline form of an API. Co-crystal is a crystalline entity formed by two different or more molecular entities where the intermolecular interactions are weak forces like hydrogen bonding and π-π stacking. Co-crystals are an enabling technology that is used in new or existing drug delivery systems by majority of pharmaceutical companies in formulation and drug development. The concept of modifying the properties of a drug molecule by forming a pharmaceutical co-crystal containing a single APIs and a pharmaceutical relevant co-former with improved properties compared with the pure drug crystal has generated immense interest [1]. Physicians prescribe combination therapy frequently to treat and manage a plethora of medical conditions. Multi-API co-crystals, relatively unexplored solid forms of APIs, have potential relevance in the context of combination drugs for pharmaceutical drug development (Figure 1).

Background and the purpose of the study: Adverse drug reactions (ADRs) are important public health problem with significant morbidity, mortality and financial burden on the society. Nurses play important role in medication safety surveillance through the spontaneous reporting of ADRs. Nurses’ knowledge, attitude and practice towards ADR reporting and factors affecting reporting was assessed in the study. All nurses working in a tertiary care hospital, Ajman, UAE participated in this cross-sectional survey. A self administered questionnaire of four domains (knowledge, attitude, practice, factors affecting reporting) was distributed among nurses after obtaining informed consent. The knowledge and attitude components were assigned score of one for correct response. Data was analyzed using SPSS (version 19). Mann–Whitney U test was used to compare knowledge and attitude scores between subgroups; Spearman’s correlation for any relationship between knowledge and attitude. Of the total participants, females constituted 92.3%; average duration of clinical experience 6.5 ± 3.3 years; mean age 28.9 ± 4.1 years. Median score for knowledge components of ADR reporting was 11(total score: 17) and for attitude components was 4(total score: 8). No difference noted in knowledge and attitude scores between gender, age group, educational qualification. A positive correlation between knowledge and attitude components was observed (r = 0.38). ADRs are important cause for morbidity and mortality was reported by (54.9%). 49.5% were aware of Pharmacovigilance centers’ whereas, only (8.8%) reported. Uncertainty of ADRs (49.5%); concern that the report may be wrong (46.2%) and inadequate knowledge of ADR reporting procedure were the major barriers to reporting. Training in ADR reporting as the key measure to improve reporting was suggested by (86.8%). Major The results of the study strongly point out the need for interventional program among nurses focusing on the importance of ADR reporting and reporting procedure to encourage their active, voluntary participation in drug safety surveillance.

Metabolic and cardiovascular side effects have been noted with the use of second generation antipsychotics (SGAs) and mood stabilizers. Since Omega-3 fatty acids have been known to prevent some cardiovascular risks, this preliminary study was designed to evaluate the cardiovascular benefits of omega-3 when added to the combinations of olanzapine with mood stabilizers. This study was a randomized, double-blind, placebo-controlled, within-subject trial in adult psychiatric patients who were receiving olanzapine combined with lithium (Li) or valproate sodium (VPA). Omega-3 as fish oil with less than 1 g/day of EPA/DHA or its placebo was added to patients’ olanzapine and mood stabilizer regimens for 6 weeks. Metabolic parameters including anthropometric variables, lipid profile, metabolic syndrome indices, C-reactive protein, fibrinogen and lipoprotein (a) [(Lp) (a)] were assessed for participants. Forty one participants completed this study; 20 patients received omega-3 and 21 patients received placebo, added to their regimen of SGA and mood stabilizer. Omega-3 addition did not modulate anthropometric, metabolic syndrome and lipid parameter changes in 6 weeks. However, fibrinogen levels significantly decreased, Lp (a) did not increase and non-high-density lipoprotein cholesterol (non-HDL-C) did not go beyond its target level after omega-3 supplementation. Additionally, a significant inter-group effect was noted for Lp(a). This study suggests that use of short-term omega-3 supplementation added to a combined regimen of olanzapine and mood stabilizer may have a small modulating effect on some cardiovascular risk factors. Trials in longer periods of time and with larger number of patients are needed to further evaluate the effects of omega-3 supplements on preventing cardiovascular risk factors. This trial is registered at irct.ir and its Identifier is as following: IRCT138712231764N1