DARU, Journal of Pharmaceutical Sciences
Volume:20 Issue: 4, 2012

Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis. In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2. A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn’t change significantly between the two groups (P>0.05). Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.

Background and the purpose of the Study: Complementary medicine received high attention during last decades. We aimed to assess the efficacy of Green tea mouthwash on plaque-induced gingivitis as the most common form of periodontal disease.We designed a single blinded placebo controlled clinical trial. High school female students with chronic generalized plaque-induced gingivitis were distributed to receive either 5 ml of Green tea 5% two times/day or normal saline with the same dosage. Gingival index (Sillness & Loe), plaque index (Sillness & Loe) and bleeding index (Barnett) were recorded at baseline and five consecutive weeks. Comparisons were made by a general linear model, repeated measure ANOVA and a Bonferroni test applied for multiple comparisons.Twenty five students were recruited in each arm of the study. A significant improvement was observed in all periodontal indices during the study (P < 0.001). Two groups were contrasted by changing patterns of alteration of indices (P < 0.05). Although total amount of improvement was higher in mouthwash group, the differences did not reach a statistically significant level (P > 0.05, observed power for GI: 0.09, PI: 0.11 and BI: 0.07). Green tea mouthwash may be a safe and feasible adjunct treatment for inflammatory periodontal diseases. A future larger scale study is warranted for better evaluating the effect of green tea.

Background and purpose of the study: Glimepiride (GLM) was chosen as a model substrate in order to determine the kinetic parameters for in vitro metabolism via human liver micrososmes (HLM). We aimed to optimize the turnover of the substrate by the test system in relation to incubation time and HLM concentration in such a way that it was linearly dependent on time and less than 20% of the substrate was consumed which utilized the lowest amount of the HLM. Further we aimed to report Km and Vmax values for GLM. Linearity of enzyme reactions in microsomal incubations was assessed by monitoring the effect of incubation time (from 5 to 60 min) and HLM concentration (from 0.2 to 0.75 mg/ml) on metabolite formation of GLM. The ideal conditions for turnover of GLM were justified using 3x3 factorial design. F value was calculated to confirm the omission of insignificant terms from the full-model to derive a reduced- model polynomial equation. The regression equation was used to develop a contour plot that showed turnover rate within the limits of this design. The optimized reaction velocity data was extrapolated to carry out the kinetic studies in vitro to generate a saturation curve for the determination of Km and Vmax values. The reaction was found to be linear with respect to both incubation time between 24 and 50 min and HLM concentration between 0.3 to 0.65 mg/ml. The Km and Vmax values obtained by nonlinear least squares regression method was found to be 28.9 ± 2.97 μMole and 0.559 ± 0.017 μMole respectively. Lineweaver-Burk plot was also used to estimate Km and Vmax which yield value of 29.411 ± 1.25 μMole and 0.571 ± 0.020 μMole/min/mg protein respectively. Major The statistical approach successfully allows for the optimization of reaction time course experiments. The results obtained with linear as well as the nonlinear transformation were found to be in close agreement with each other which shows the best precision for estimates of Km and Vmax.

Background and the purpose of the study: The early stage of diabetes mellitus type 2 is associated with postprandial hyperglycemia. Hyperglycemia is believed to increase the production of free radicals and reactive oxygen species, leading to oxidative tissue damage. In an effort of identifying herbal drugs which may become useful in the prevention or mitigation of diabetes, biochemical activities of Polygonum hyrcanicum and its constituents were studied. Hexane, ethylacetate and methanol extracts of P. hyrcanicum were tested for α-glucosidase inhibitory, antioxidant and radical scavenging properties. Active constituents were isolated and identified from the methanolic extract in an activity guided approach. A methanolic extract from flowering aerial parts of the plant showed notable α-glucosidase inhibitory activity (IC50 = 15 μg/ml). Thirteen phenolic compounds involving a cinnamoylphenethyl amide, two flavans, and ten flavonols and flavonol 3-O-glycosides were subsequently isolated from the extract. All constituents showed inhibitory activities while compounds 3, 8 and 11 (IC50 = 0.3, 1.0, and 0.6 μM, respectively) were the most potent ones. The methanol extract also showed antioxidant activities in DPPH (IC50 = 76 μg/ml) and FRAP assays (1.4 mmol ferrous ion equivalent/g extract). A total phenol content of 130 mg/g of the extract was determined by Folin-Ciocalteu reagent. This study shows that P. hyrcanicum contains phenolic compounds with in vitro activity that can be useful in the context of preventing or mitigating cellular damages linked to diabetic conditions.

Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetate)that indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE) measurements to achieve the normal values of BE (−5 to +5 mEq/L). In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15). Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

To monitor the adverse drug reactions (ADRs) caused by antihypertensive medicines prescribed in a university teaching hospital. The present work was an open, non-comparative, observational study conducted on hypertensive patients attending the Medicine OPD of Majeedia Hospital, Jamia Hamdard, New Delhi, India by conducting patient interviews and recording the data on ADR monitoring form as recommended by Central Drugs Standard Control Organization (CDSCO), Government of India. A total of 21 adverse drug reactions were observed in 192 hypertensive patients. Incidence of adverse drug reactions was found to be higher in patients more than 40 years in age, and females experienced more ADRs (n = 14, 7.29%) than males, 7 (3.64%). Combination therapy was associated with more number of adverse drug reactions (66.7%) as against monotherapy (33.3%). Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions (n = 7), followed by diuretics (n = 5), and β-blockers (n = 4). Among individual drugs, amlodipine was found to be the commonest drug associated with adverse drug reactions (n = 7), followed by torasemide (n = 3). Adverse drug reactions associated with central nervous system were found to be the most frequent (42.8%) followed by musculo-skeletal complaints (23.8%) and gastro-intestinal disorders (14.3%). The present pharmacovigilance study represents the adverse drug reaction profile of the antihypertensive medicines prescribed in our university teaching hospital. The above findings would be useful for physicians in rational prescribing. Calcium channel blockers were found to be the most frequently associated drugs with adverse drug reactions.

Herbal combination of Itrifal Saghir (triphala) has been widely used in traditional medicine. And brings health benefits such as antioxidant effect and scavenger of hydroxyl radicals and nitric oxide radicals activity and substantiated in traditional medicine a anti-obesity. In this study we aimed to assess the efficacy of this herbal medicinal on reduction of weight and body mass index (BMI) of simple obese subjects in comparison with placebo. Obese subjects aged between 16 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial using a parallel design. Subjects were randomly assigned to take 5 grams of either the Itrifal Saghir (n = 31) or placebo (n = 31), 2 times daily for 12 weeks. Measures of body weight, BMI, waist circumference (WC), hip circumference (HC), were assessed at baseline and once every four weeks during the 12 week treatment period. The safety was evaluated by means of measuring the liver and kidney function. Homeostasis model of insulin resistance (HOMA-IR) was calculated as [fasting insulin (muU/mL) x fasting glucose (mmol/L)/22.5]. Compared to placebo group, in treatment group the mean difference of effective weight loss was 4.82Kg (CI95% 3.52 - 6.11, rho < 0.001), the mean of decrease in waist circumference was 4.01 cm (CI 95% 2.13 - 5.90, rho < 0.001), and the mean decrease in hip circumference was 3. 21 cm (CI 95% 1.96 - 4.45, rho < 0.001) in treated subjects. No adverse effects or significant changes in liver and kidney function tests were observed in both placebo and treated groups.

Herbal combination of Itrifal Saghir (triphala) has been widely used in traditional medicine. And brings health benefits such as antioxidant effect and scavenger of hydroxyl radicals and nitric oxide radicals activity and substantiated in traditional medicine a anti-obesity. In this study we aimed to assess the efficacy of this herbal medicinal on reduction of weight and body mass index (BMI) of simple obese subjects in comparison with placebo. Obese subjects aged between 16 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial using a parallel design. Subjects were randomly assigned to take 5 grams of either the Itrifal Saghir (n = 31) or placebo (n = 31), 2 times daily for 12 weeks. Measures of body weight, BMI, waist circumference (WC), hip circumference (HC), were assessed at baseline and once every four weeks during the 12 week treatment period. The safety was evaluated by means of measuring the liver and kidney function. Homeostasis model of insulin resistance (HOMA-IR) was calculated as [fasting insulin (muU/mL) x fasting glucose (mmol/L)/22.5]. Compared to placebo group, in treatment group the mean difference of effective weight loss was 4.82Kg (CI95% 3.52 - 6.11, rho < 0.001), the mean of decrease in waist circumference was 4.01 cm (CI 95% 2.13 - 5.90, rho < 0.001), and the mean decrease in hip circumference was 3. 21 cm (CI 95% 1.96 - 4.45, rho < 0.001) in treated subjects. No adverse effects or significant changes in liver and kidney function tests were observed in both placebo and treated groups. Itrifal Saghir appears to produce a positive effect on weight loss in obese subjects.

Self-Monitoring of Blood Glucose (SMBG) is considered as a key factor in management of people with diabetes which is a growing and cost demanding health problem. The purpose of this study was to investigate the effect of comprehensive patient management using structured SMBG on metabolic control as well as its cost consequence analysis. Sixty subjects were recruited in an observational study for a period of 6 months. They were provided with the ACCU-CHEK 360° View tool to fill in the values of the 7-point blood glucose profiles in three consecutive days during the study on a monthly basis. Changes in metabolic control were assessed by HbA1c and lipid profile measurement at the beginning and at the end of the study. In addition, cost consequence analysis was done considering different level of health care professionals with or without insurance coverage. The Average Cost Effectiveness Ratio (ACER) as well as Cost saving analysis were calculated and compared. The analysis showed significant reduction in HbA1c during the 6-month period in all subjects (P = 0.000). Furthermore, a positive effect was observed on lipid profile. The cost of endocrinologist’s visit in private sector was estimated to be 265.76 USD while this figure was149.15 USD for general practitioner in public sector with insurance coverage. Total complications and mortality cost saving was 154.8 USD. The lowest ACER was calculated for intervention with general practitioner in public sector with insurance coverage. Structured SMBG results in significant improvement of glycemic status. Moreover, it is more cost saving in public sector with insurance coverage. It seems that general practitioner visits with insurance coverage is the most affordable option for people with type 2 diabetes.

Background and of the study Multimodal distribution of descriptors makes it more difficult to fit a single global model to model the entire data set in quantitative structure activity relationship (QSAR) studies. The linear (Multiple linear regression; MLR), non-linear (Artificial neural network; ANN), and an approach based on «Extended Classifier System in Function approximation» (XCSF) were applied herein to model the biological activity of 658 caspase-3 inhibitors. Various kinds of molecular descriptors were calculated to represent the molecular structures of the compounds. The original data set was partitioned into the training and test sets by the K-means classification method. Prediction error on the test data set indicated that the XCSF as a local model estimates caspase-3 inhibition activity, better than the global models such as MLR and ANN. The atom-centered fragment type CR2X2, electronegativity, polarizability, and atomic radius and also the lipophilicity of the molecule, were the main independent factors contributing to the caspase-3 inhibition activity. The results of this study may be exploited for further design of novel caspase-3 inhibitors.

Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive–microbial disturbances. To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC) on the levels of tumor necrosis factor alpha (TNF- α), interleukin- 6(IL-6) and IL-17 and post-treatment pain level in chronic periapical lesions. Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg), ibuprofen tablets (400 mg), NAC (400 mg)/ibuprofen (200 mg) combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- α, IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale (VAS). There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019). Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043). Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017). Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033). After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049). The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain.

The purpose of the study. Along with research on development of more efficient gene delivery systems, it is necessary to search on stabilization processes to extend their active life span. Chitosan is a nontoxic, biocompatible and available gene delivery carrier. The aim of this study was to assess the ability of this polymer to preserve transfection efficiency during spray-drying and a modified freeze-drying process in the presence of commonly used excipients. Molecular weight of chitosan was reduced by a chemical reaction and achieved low molecular weight chitosan (LMWC) was complexed with pDNA. Obtained nanocomplex suspensions were diluted by solutions of lactose and leucine, and these formulations were spray dried or freeze dried using a modified technique. Size, polydispersity index, zeta potential, intensity of supercoiled DNA band on gel electrophoresis, and transfection efficiency of reconstituted nanocomplexes were compared with freshly prepared ones. Results and major Size distribution profiles of both freeze dried, and 13 out of 16 spray-dried nanocomplexes remained identical to freshly prepared ones. LMWC protected up to 100% of supercoiled structure of pDNA in both processes, although DNA degradation was higher in spray-drying of the nanocomplexes prepared with low N/P ratios. Both techniques preserved transfection efficiency similarly even in lower N/P ratios, where supercoiled DNA content of spray dried formulations was lower than freeze-dried ones. Leucine did not show a significant effect on properties of the processed nanocomplexes. It can be concluded that LMWC can protect DNA structure and transfection efficiency in both processes even in the presence of leucine.

Background and Surveillance studies evaluating antimicrobial susceptibilities are of great value in preventing the spread of resistant pathogens by elucidating the trend of resistance in commonly used antibiotics and as a consequence providing information for prescribing the most appropriate agent. This study is a longitudinal antimicrobial resistance surveillance study designed to evaluate the trend in antimicrobial resistance to gram negative microorganisms from 2007 to 2010. During a four-year period (2007–2010) isolates derived from all patients admitted to infectious diseases ward of Imam Khomeini Hospital, the major referral center for infectious disease in Iran with the highest admission rates, were evaluated. Based on disk diffusion method and zone of inhibition size, the microorganism was regarded as to be sensitive, resistant or has intermediate susceptibility to the antimicrobial agents. The widest spread Gram-negative microorganism in all of isolates taken together in our study was E.coli (30%) followed by Stenotrophomonas maltophilia in 28.6% and Enterobacter spp. in 11.9%, respectively. The susceptibility to amikacin, imipenem, piperacillin/tazobactam, and nitrofurantoin was equal or above 50% for all microorganisms over four years. However, the susceptibility to ampicillin, ampicillin/sulbactam, cefotaxim, and ceftriaxone was less than 50% in derived isolates during the study period. In conclusion, the finding of the present study revealed that resistance rate to common antimicrobial agents in Iran is growing and isolates were susceptible mostly to broad-spectrum antibiotics including imipenem and piperacillin/tazobactam.

Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

The application of emerging nanotechnology to the practice of medicine represents a frontier of nanomedicine. Nanomedicine has been defined as a science which emphasizes the use of nanoscale tools in conjunction with background knowledge of the human body for medical diagnosis and treatment. Application of nanomedicine in EM may give EM providers the opportunity to diagnose and treat life-threatening diseases in a shorter period of time. These applications include diagnostic utilities, preventive medicine, targeted pharmacotherapy, and tissue regeneration.

Aluminum phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide which is commonly used for grain preservation. In Iran it is known as the “rice tablet”. AlP has currently aroused interest with increasing number of cases in the past four decades due to increased use in agricultural and non-agricultural purposesand also its easy availability in the markets has increased its misuse to commit suicide. Upon contact with moisture in the environment, AlP undergoes a chemical reaction yielding phosphine gas, which is the active pesticidal component. Phosphine inhibits cellular oxygen utilization and can induce lipid peroxidation. It was reported that AlP has a mortality rate more than 50% of intoxication cases. Poisoning with AlP has usually occurred in attempts to suicide. It is a more common case in adults rather than teen agers. In some eastern countries it is a very common agent with rapid action for suicide. Up to date, there is no effective antidote or treatment for its intoxication. Also, some experimental results suggest that magnesium sulfate, N-acetyl cysteine (NAC), glutathione, vitamin C and E, beta-carotenes, coconut oil and melatonin may play an important role in reducing the oxidative outcomes of phosphine. This article reviews the experimental and clinical features of AlP intoxication and tries to suggest a way to encounter its poisoning.

The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics.

Along with research on development of more efficient gene delivery systems, it is necessary to search on stabilization processes to extend their active life span. Chitosan is a nontoxic, biocompatible and available gene delivery carrier. The aim of this study was to assess the ability of this polymer to preserve transfection efficiency during spray-drying and a modified freeze-drying process in the presence of commonly used excipients. Molecular weight of chitosan was reduced by a chemical reaction and achieved low molecular weight chitosan (LMWC) was complexed with pDNA. Obtained nanocomplex suspensions were diluted by solutions of lactose and leucine, and these formulations were spray dried or freeze dried using a modified technique. Size, polydispersity index, zeta potential, intensity of supercoiled DNA band on gel electrophoresis, and transfection efficiency of reconstituted nanocomplexes were compared with freshly prepared ones. Results and Size distribution profiles of both freeze dried, and 13 out of 16 spray-dried nanocomplexes remained identical to freshly prepared ones. LMWC protected up to 100% of supercoiled structure of pDNA in both processes, although DNA degradation was higher in spray-drying of the nanocomplexes prepared with low N/P ratios. Both techniques preserved transfection efficiency similarly even in lower N/P ratios, where supercoiled DNA content of spray dried formulations was lower than freeze-dried ones. Leucine did not show a significant effect on properties of the processed nanocomplexes. It can be concluded that LMWC can protect DNA structure and transfection efficiency in both processes even in the presence of leucine.