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Background: Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties., Objective: To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations., Methods: In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis., Results: Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis., Conclusions: Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory findings, reference intervals must be determined in every population., Objective: To establish a normal reference range for CD3+, CD4+, CD8+, CD19+ and CD56+ lymphocytes in a healthy Iranian adult population using flowcytometry., Method: Blood samples were collected from 221 HIV seronegative individuals, including 112 females and 109 males, with ages ranging from 20 to 40 years old. The percentage of lymphocytes expressing either of CD3, CD4, CD8, CD19 and CD56 surface markers were determined by flowcytometry assay., Result: Total mean percentage and absolute count of lymphocyte subsets were as follows: CD3+: 70.90 ± 7.54%, 1800.87 ± 471.09 cells/µl; CD4+: 41.04 ± 7.86%, 1039.99 ± 338.02 cells/µl; CD8+: 31.11 ± 6.60%, 783.95 ± 234.87 cells/µl; CD19+: 12.77 ± 4.56%, 328.37 ± 153.17 cells/µl; CD56+: 15.53 ± 6.34%, 388.62 ± 176.17 cells/µl, respectively. The ratio of CD4+/CD8+ lymphocytes for the studied population was 1.39 ± 0.48. Significant differences were observed between male and female subjects indicating that the average percentage of CD3+ cells (p=0.017) and CD4+ T cells (p=0.003) were higher in the female population, whereas the average percentage of CD19+ cells (p=0.02) tended to be higher among males. However, investigations on the CD56+ NK cell and CD8+ T cell sub-populations did not show any statistical differences between the two genders. In comparison with reports of other populations, we were confronted with different results., Conclusion: Establishing reference values of lymphocyte subsets for each population is helpful in achieving standard criteria for the prognosis of HIV infection. Therefore, normal ranges established by this survey can be used as a reference for decisions made in clinical practice.

Background: Dyslipidemia is an established feature of metabolic syndrome (MS) that is associated with an increased risk of atherosclerotic cardiovascular disease. Curcuminoids are natural products with anti-atherosclerotic and lipid-modifying effects but their efficacy in patients with MS has not yet been tested., Objective: To investigate the effects of bioavailability-enhanced curcuminoids, as adjunctive to standard of care, on serum lipid concentrations in patients with MS., Methods: Patients diagnosed with MS according to the NCEP-ATPIII criteria who were receiving standard of care were assigned to either curcuminoids (C3 complex(®); 1000 mg/day; n=50) or placebo (n=50; matched with drug capsules in shape and color) for 8 weeks. In order to improve the oral bioavailability, curcuminoids were co-administered with piperine (bioperine(®)) in a ratio of 100:1. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, small dense LDL (sdLDL), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of 8-week treatment period., Results: Curcuminoids were more effective than placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides and Lp(a), and elevating HDL-C concentrations. However, changes in serum sdLDL levels were found to be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C, total cholesterol and Lp(a) remained significant after adjustment for baseline values of lipids and body mass index., Conclusion: Curcuminoids-piperine combination is an efficacious adjunctive therapy in patients with MS and can modify serum lipid concentrations beyond what is achieved with standard of care., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To report the results of endoscopic correction of vesicoureteral reflux (VUR) with concomitant injection of pure calcium hydroxyapatite (CaHA) and autologous blood., Patients and Methods: Records of patients who underwent endoscopic correction of VUR using concomitant injection of CaHA and autologous blood from 2008 through 2010 were retrospectively reviewed. Data regarding patients' demographics, preoperative VUR grades, febrile urinary tract infections, complications of procedure, postoperative VUR grades and cure rates were collected. Voiding cystourethrography was performed 3 months postoperatively., Results: Total number of 23 children (9 girls and 14 boys) with 40 refluxing ureters were included. The mean age of children was 1.9 ± 0.97 (SD) years. Reflux grades were II to IV in 14, 11 and 15 renal refluxing units (RRUs), respectively. The mean follow-up period was 44 months. VUR was successfully treated in 87.5% of RRUs after three injections. Significant statistical difference was found between VUR grades before and after the first, second and third injections (p < 0.001, p = 0.001 and p = 0.011, respectively). Moreover, there was a significant difference between primary reflux grade and treatment success (p = 0.031). Febrile UTI was resolved in 85% of patients (17 of 20 patients with febrile UTI) after endoscopic treatment which shows significant improvement (p < 0.001). The procedure was uneventful in all patients, and no obstruction was reported during the follow-up period., Conclusion: Concomitant injection of pure CaHA without any additives (hyaluronic acid, etc.) and autologous blood can be an effective, repeatable and cost-benefit approach for the management of children suffering VUR with a success rate of 87.5% after three injections.

Background: Some studies have shown the possible role of protein-energy malnutrition (PEM) in persistence of endemic goiter in iodine replenished areas. The present study was conducted to assess the association between PEM and goiter in schoolchildren of Isfahan, Iran., Methods: In a cross-sectional study using multistage cluster random-sampling, 2331 schoolchildren with age ranged from 6-13 years old with a female to male ratio of 1.60 were enrolled. Thyroid size was examined by two endocrinologists for goiter detection. Children were considered goitrous if they had palpable or visible goiters according to World Health Organization (WHO)/United Nations children's Fund/International Council for the Control of Iodine Deficiency criteria. Weight and standing height were measured using the standard tools and anthropometric indices were calculated using the WHO AnthroPlus software developed by the World Health Organization. Height-for-age Z-scores (HAZ), weight-for-age Z-scores (WAZ) and body mass index (BMI) for age were calculated for each child. Children with a HAZ, WAZ or BMI-for-age of Z-score < -2.0 were classified as stunted, underweight or thin, respectively. Blood samples were drowned to measure serum thyroid hormones., Results: Overall, 32.9% of subjects were classified as goitrous. Weight, height, BMI, WAZ and BMI-for-age Z-score were significantly lower in children with goiter than in children who did not have goiter (P < 0.05). The prevalence of goiter in thin children was higher than that in non-thin ones (48.4 vs. 31.6%, odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.52-2.69, P < 0.001). Although 33.4% of non-stunted children were goitrous, 31% of stunted ones had goiter (P = 0.5). According to the logistic regression model taking sex and age as covariates, the only significant parameter affecting palpable goiter detection was thinness (OR = 2.13, 95% CI: 1.22-3.69, P < 0.001)., Conclusions: In the present study, we found a high prevalence of goiter in children who were malnourished. It seems that PEM may play a role in the still high prevalence of goiter in this region.

Background: The beneficial effect of using nonacetylated salicylates such as salsalate on decreasing the speed of diabetes progression is a controversial issue. The aim of this study was to evaluate the effect of salsalate on metabolic-syndrome-associated parameters as well as the endothelial function of diabetic and impaired glucose tolerance patients., Materials and Methods: Patients were collected from Isfahan endocrinology research center referrals. Patients with impaired glucose tolerance diagnosis or newly diagnosed diabetes were enrolled in the study. Patients were randomized to receive 1.5 g salsalate (2 × 750 mg) BID or placebo twice a day for 3 months. After the mentioned period, all patients were recalled and complete examination was done; blood samples for biochemistry measurements were drawn (for measuring FBS, post prandial glucose, HbA1C, Total cholesterol, HDL, TG, LDL) and forearm flow-mediated dilation (FMD) was performed., Results: Forty patients were enrolled, 32 patients (80%) were female. Mean age of patients was 47.15 ± 6.67 years. FBS (fasting blood sugar) was shown to be significantly different between intervention and control subjects before or after treatment. FMD increased significantly in the intervention group (P = 0.004)., Conclusion: The study showed that salsalate decreased FBS levels of patients. It may also improve endothelial function as FMD increased significantly in the intervention group.

Background: Asthma is a common condition in general medical practice, and it accounts for about 1% of all ambulatory hospital visits. Nowadays, hospitalization rates for asthma have actually been increased in some demographic subgroups despite recent advances in treatment. Understanding the underlying factors that contribute to hospitalization and especially duration of the hospitalization of asthmatics could help elucidate the recent rise in morbidity and also reduce the high demand on health care systems of the disease. The aim of this study was to evaluate factors affecting the duration of hospitalization for Iranian patients with asthma., Methods: This study was conducted on 55 asthmatic patients (diagnosis of asthma was in accordance with the criteria of the American Thoracic Society). The study was performed on patients hospitalized in Rasoul-e-Akram hospital in Tehran, Iran during the period 2005-2006. During hospitalization, the patients' most common complaints were recorded as the symptoms and signs of the medical condition, results of physical examinations, spirometry, arterial blood gas analysis (ABG), and ICU admission., Results: There were 18(32.7%) male and 37(67.3%) female patients with a mean age of 54.96 (SD=17.54) years. The mean duration of hospitalization was 8.31(SD=4.69) days that ranged between 2 and 23 days. The mean baseline arterial PH (p=0.039, RPearso = -0.362), baseline arterial [HCO3] (p=0.042, RPearson = 0.361), changes of FEV1 after bronchodilator (p=0.041, RPearson= -0.363) and patient's age (p=0.002, RPearson=0.0433) were determined as factors affecting duration of hospitalization., Conclusion: Our results showed that more attention needs to be given to the findings of arterial blood gas and spirometry which can potentially affect the duration of hospitalization of asthmatic patients.

Objectives: To evaluate quetiapine XR in patients with anxious depression, as defined by HAM-A total and HAM-D anxiety/somatisation factor scores., Methods: Post hoc analyses of pooled data from two 6-week, double-blind, randomised, placebo-controlled studies of adjunctive quetiapine XR (150 or 300 mg/day) in patients with MDD and inadequate response to antidepressants. Patients were stratified in a primary analysis using HAM-A (HAM-A total score at baseline ≥ 20 ["high"] or < 20 ["low"]) and a secondary analysis using HAM-D (anxious depression defined as HAM-D anxiety/somatisation factor score ≥ 7). Outcomes included change in MADRS total score., Results: In patients with high anxiety levels (HAM-A total score ≥ 20), reductions in MADRS total score were -15.20 (P = 0.122) and -15.92 (P < 0.05) for quetiapine XR 150 and 300 mg/day, respectively, vs. placebo (-13.49). In patients with low levels of anxiety (HAM-A total score < 20), both quetiapine XR doses (P < 0.001) improved MADRS total scores vs. placebo. In the secondary analysis, quetiapine XR 150 (P < 0.01) and 300 mg/day (P < 0.001) improved MADRS total score vs. placebo in patients with HAM-D anxiety/somatisation factor score ≥ 7., Conclusions: Adjunct quetiapine XR demonstrates efficacy in patients with anxious and non-anxious depression, assessed using HAM-A total score, and anxious depression assessed using HAM-D anxiety/somatisation factor score.

This pooled analysis evaluated the efficacy of extended-release quetiapine fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups.

Introduction: Fetuin-A (A2-HS-glycoprotein) is a protein that plays several functions in human physiology and pathophysiology. The role of fetuin-A in type 1 diabetes mellitus (DM) has been less studied. We investigated the serum levels of fetuin-A in type 1 diabetic patients with microalbuminuria. Furthermore, the blocking effect of renin-angiotensin-aldosteron system on serum levels of fetuin-A was assessed., Materials and Methods: From January 2010 to May 2011, 32 patients with type 1 DM with confirmed microalbuminuria were included in this study in Isfahan, Iran. Serum fetuin-A levels before and 8 weeks after valsartan administration were measured. In addition, serum lipid profile, creatinine, hemoglobin A1c, and urine microalbuminuria were determined., Results: The mean age of participants was 21.65 +/- 0.38 years. Before valsartan administration, the mean values of fetuin-A were not significantly different between males and females (64.22 +/- 1.77 ng/mL versus 61.39 +/- 3.35 ng/mL, respectively). After valsartan administration, serum levels of fetuin-A and urine albumin-creatinine significantly decreased. A negative correlation was observed between serum fetuin-A level after valsartan administration and serum low-density lipoprotein cholesterol level (P = .007, r = -0.507)., Conclusions: Administration angiotensin receptor blockers concomitantly decreases fetuin-A levels and urine albumin levels.

Introduction: Kidney transplantation and its conventional treatment can lead to increased risk of diabetes mellitus outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may increase allograft loss and decrease patient survival. We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors., Materials and Methods: A retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were collected. All laboratory tests were done in a one laboratory, and hyperglycemia was defined as a fasting plasma glucose level greater than 125 mg/dL. Univariable and multivariable logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation., Results: There were 2120 men (63.4%) and 1212 women (36.3%) included in the study. The prevalence of hyperglycemia was 22.5%. Hyperglycemia was significantly higher in patients with cytomegalovirus infection (P = .001), elevated serum creatinine (P < .001), low high-density lipoprotein cholesterol (P = .01), and increased blood levels of cyclosporine (P < .001). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with a cyclosporine trough level greater than 250 ng/mL (P < .001), a serum creatinine level greater than 1.5 mg/dL (P < .001), and a high-density lipoprotein cholesterol less than 45 mg/dL (P = .03)., Conclusions: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher cyclosporine level, impaired kidney function, and reduced high-density lipoprotein cholesterol values.

Background: Chronic renal failure is an important and common complication of diabetes mellitus; hence, renal transplantation is a frequent and the acceptable treatment in patients with diabetic nephropathy requiring renal replacement therapy. On the other hand, renal transplantation and its conventional treatment can lead to increased diabetes outbreak in normoglycemic recipients. Also, uncontrolled hyperglycemia may be increased and allograft lost thus decreasing patient survival., Objectives: We aimed to assess the frequency of hyperglycemia in transplant patients and its risk factors., Patients and Methods: A large retrospective study was performed on 3342 adult kidney transplant recipients between 2008 and 2010. Demographic and laboratory data were gathered for each patient. All tests were done in a single laboratory and hyperglycemia was defined as a fasting plasma glucose of > 125 mg/dL. Univariate and multivariate logistic regression analyses were used to determine the risk factors of hyperglycemia following kidney transplantation., Results: There were 2120 (63.4%) males and 1212 (36.3%) females. Prevalence of hyperglycemia was 22.5%. By univariate linear regression, hyperglycemia was significantly higher in patients with CMV infection (P = 0.001), elevated serum creatinine (P = 0.000), low HDL (P = 0.01), and increased blood levels of cyclosporine (P = 0.000). After adjusting for covariates by multivariate logistic regression, the hyperglycemia rate was significantly higher for patients with Cyclosporine trough level > 250 (P = 0.000), serum creatinine > 1.5 (P = 0.000) and HDL < 45 (P = 0.03)., Conclusions: This study indicated that hyperglycemia is a common metabolic disorder in Iranian kidney transplant patients. Risk factors for hyperglycemia were higher Cyclosporine level, impaired renal function, and reduced HDL value.

Background: Breast cancer is the most common malignancy among Iranian women and is a significant stressor in women's life that may affect their coping strategies and quality of life. This study aimed to investigate coping strategies, quality of life and pain of women with breast cancer., Materials and Methods: This was a cross-sectional study which held in Seyed-AL shohada hospital and two private offices in Isfahan, Iran. Target population was women with confirmed diagnosis of breast cancer in a recent year and between 18 and 60 years old. Data were collected via3 questionnaires (Brief cope, EORTC QLQ-C30 and Brief pain Inventory). The reliability and validity of these questionnaires were confirmed in different studies. Sixty-two patients completed the questionnaires. Analysis included descriptive statistics and Pearson correlation coefficient and t-test where necessary. All analysis were conducted using the SPSS version 16.0 and P-value of less than 0.05 considered as statistically significant., Results: Sixty-two women with breast cancer completed questionnaires. The mean age of respondents was 45/81±6/78 years; most married (93/5%), high school-educated (41/97%), house wife (82/3%) and stage II (46/8%). The most common coping strategies were religion, acceptance, self-distraction, planning, active coping, positive reframing and denial. Mean score for the worst pain during the past 24 hours was 6/24 ± 2/55 and for the least pain was 3/19 ± 2/17. The global health scale was 60.34 ± 21.10. Emotion-focused coping strategies were positively and significantly related to symptom aspect of quality of life (r = 0/43 P ≤ 0/01) and affective interference of pain (r = 0/36 P = 0/004) and also was inversely correlated to functional health status (r = -0/38 P = 0/002). There was no significant correlation between problem-focused coping strategies and dimensions of quality of life and also different aspects of pain., Conclusions: The findings of this study indicated that the care of breast cancer should address physical, psychological and social wellbeing and the findings point to the importance of taking individual coping strategies into account when evaluating the impact of breast cancer on psychosocial wellbeing. Description of coping strategies might be useful for identifying patients in need to particular counseling and support.

Objective: Our purpose was to investigate the effects of acupressure on sleep quality in hemodialysis patients., Design: Randomized clinical trial., Setting: The setting of the study was dialysis wards located in two university hospitals (Imam and Golestan) in Ahvaz, Iran., Interventions: 48 end-stage renal disease patients on hemodialysis who scored 5 points or higher on the Pittsburgh Sleep Quality Index (PSQI) were enrolled to the study. Acupressure group received acupressure intervention on the Shenmen (He7) and He Gu (Li4) points in the hands and Sanyingjao (sp6) point in the feet for 4 weeks beside routine care and control group received only routine care., Main Outcome Measures: subjective sleep quality, latency and duration, habitual sleep efficiency; sleep disturbances, daytime functional status, and use of sleeping medications., Results: The result indicated significant differences between the acupressure group and the control group after intervention in PSQI global scores (p<0.001) and all sleep quality indices between two groups after intervention: subjective sleep quality (p<0.001), sleep latency (p<0.001), sleep duration (p<0.001), sleep efficiency (p=0.006), sleep disturbance (p<0.001), the use of sleeping medication (p=0.028), and daytime dysfunction (p<0.001)., Conclusion: This study supports the effectiveness of acupressure in improving sleep quality of end-stage renal disease patients as a noninvasive therapy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Methadone is currently the most frequently used substance in the treatment of short-term and particularly long-term opiate dependence. Patients' beliefs about the adverse effects of methadone on function of organs, especially liver, have widely affected the use of this substance. This study aimed to determine the effects of methadone on liver enzyme levels in patients on methadone maintenance treatment., Methods: In a retrospective study, a total of 94 patients undergoing methadone maintenance therapy were recruited from Shahid Beheshti Hospital (Kerman, Iran). Liver enzyme levels in all patients were tested every six months from the onset of treatment until 24 months. The relations between test results and age, gender, and methadone dose were then evaluated. Data was analyzed using logistic regression with random data plan., Findings: At the 24th month, alanine aminotransferase (ALT) levels in 4 patients (4.3%) and aspartate aminotransferase (AST) levels in 3 patients (3.2%) were above normal. Among 46 patients (50%) who had normal alkaline phosphatase (ALP) levels after 24 months, 26 subjects were younger than 40 and 20 subjects were over 40 years of age. The mean age of subjects with abnormal ALP levels and the mean methadone dose were 39.9 years and 19.55 cc, respectively., Conclusion: The results of this study indicated the significant effect of methadone on ALP levels. These effects can account for cholestatic pattern liver injury (obstruction). Further prospective studies including greater samples of patients with heart and liver complications and encompassing other drugs are required to confirm our findings.

Objectives: The purpose of the present study was to use the solid dispersion (SD) technique to improve the dissolution rates of indomethacin (IMC)., Materials and Methods: IMC solid dispersions in PVP K30 and isomalt (GALEN IQ 990) were prepared using the solvent evaporation technique and a hot melt method in weight ratios of 2, 10 and 30% (IMC:PVP). Solid dispersions and physical mixtures were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution test. Physical stability tests were also performed at different temperatures and humidity conditions., Results: The dissolution rates of all solid dispersions were faster than those of their physical mixtures. In samples containing 2% or 10% of IMC, there were no significant differences between the dissolution rates of IMC in PVP and isomalt solid dispersions, but in samples containing 30% of IMC, the dissolution rates were higher in isomalt dispersions. The XRPD analysis showed no crystalline peaks in solid dispersions, indicating that IMC was amorphous within the carrier. The DSC results showed that an interaction occurred between the drug and the carrier in PVP and isomalt dispersions. Physical stability tests at severe storage conditions showed that the dissolution rate of IMC in PVP solid dispersions decreased, while the dissolution profile of IMC in isomalt solid dispersions did not change significantly., Conclusion: It was shown that the dissolution rates of IMC in PVP and isomalt solid dispersions were substantially increased compared with their physical mixtures and pure IMC.

Adult cats with a complete spinal cord transection at T12-T13 can relearn over a period of days-to-weeks how to generate full weight-bearing stepping on a treadmill or standing ability if trained specifically for that task. In the present study, we assessed short-term (milliseconds to minutes) adaptations by repetitively imposing a mechanical perturbation on the hindlimb of chronic spinal cats by placing a rod in the path of the leg during the swing phase to trigger a tripping response. The kinematics and EMG were recorded during control (10 steps), trip (1-60 steps with various patterns), and then release (without any tripping stimulus, 10-20 steps) sequences. Our data show that the muscle activation patterns and kinematics of the hindlimb in the step cycle immediately following the initial trip (mechanosensory stimulation of the dorsal surface of the paw) was modified in a way that increased the probability of avoiding the obstacle in the subsequent step. This indicates that the spinal sensorimotor circuitry reprogrammed the trajectory of the swing following a perturbation prior to the initiation of the swing phase of the subsequent step, in effect "attempting" to avoid the re-occurrence of the perturbation. The average height of the release steps was elevated compared to control regardless of the pattern and the length of the trip sequences. In addition, the average impact force on the tripping rod tended to be lower with repeated exposure to the tripping stimulus. EMG recordings suggest that the semitendinosus, a primary knee flexor, was a major contributor to the adaptive tripping response. These results demonstrate that the lumbosacral locomotor circuitry can modulate the activation patterns of the hindlimb motor pools within the time frame of single step in a manner that tends to minimize repeated perturbations. Furthermore, these adaptations remained evident for a number of steps after removal of the mechanosensory stimulation.

The aim of this study was to report hypomanic symptoms after opioid withdrawal. In this case series, nine opioid-dependent patients with hypomanic profile on opioid withdrawal were selected from outpatients in a private psychiatric clinic. Opium dependency was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Substance history, clinical features, temperament, and family history were retrospectively probed. Patients displayed pure or mixed hypomanic symptoms on opioid withdrawal. In nearly all subjects, the symptoms continued until individuals started taking the opioid again. Features of hyperthymic temperament and family history of bipolarity were traced in most of the individuals.

Introduction: It is accepted that preventing hyperglycaemia during critical illness while assuring adequate caloric intake can reduce mortality and morbidity. The aim of this study was to compare the metabolic effects of metformin and insulin on hyperglycaemia in ICU patients., Methods: This double-blind randomised clinical trial was performed on 24 patients who were admitted to the intensive care unit (ICU) from 20 March to 20 September 2007. All patients with serious injuries or with major non-abdominal surgeries were included if they met the inclusion criteria, and were assigned randomly to one of the study groups. Patients in Group 1 received intensive insulin therapy, and patients in Group 2 were treated with metformin. Moreover, the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system was used to grade disease severity., Results: Both glycaemic management protocols led to significantly improved glucose levels without any report of hypoglycaemia. The mean initial glucose levels for the insulin group decreased significantly after the intravenous infusion of insulin (p < 0.001). Additionally, the blood glucose concentration was significantly lower after two weeks of metformin administration compared to baseline measurements (p < 0.001). Moreover, the blood glucose concentration decrease during these two weeks was significantly higher in the insulin group (p = 0.01). Besides, APACHE II score was lower than baseline at the end of the study for both therapeutic groups (score of 10 vs. 15 [insulin] and 16 [metformin]). Finally, new renal dysfunction (maximum serum creatinine level at least double the initial value) was observed in three of the patients (two patients from the metformin group and one from the insulin group) in the last days of the protocol, although none of the patients showed lactic acidosis after ICU admission., Conclusions: Both metformin and intensive insulin therapy significantly decreased hyperglycaemia in ICU patients. Insulin caused a greater reduction in blood glucose concentration but required more attention and trained personnel.

The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR) and as an extended release (XR) formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse), the treatment of bipolar disorder (manic and depressive episodes), and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D(2) receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT)(2A) receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS). The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily) dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability) also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation. Overall, evidence from clinical trials suggests that quetiapine XR is an effective and generally well-tolerated treatment option in patients with schizophrenia and bipolar disorder.

Objective: Studies in different populations have shown great variation in the prevalence of thyroid diseases in patients with type 1 diabetes mellitus (T1DM). Our aim was to study the prevalence of thyroid disorders such as autoimmunity of thyroid (AIT), thyroid dysfunction, and goiter in children and adolescents with T1DM, compared with age- and sex-matched healthy controls in Isfahan., Methods: One hundred patients with T1DM who were referred to Isfahan Endocrine and Metabolism Research Center and 184 healthy schoolchildren matched for age and sex were included. They were examined for goiter by two endocrinologists. Thyroid function test and serum thyroid antibodies (anti-TPO Ab and anti-Tg Ab) were measured., Findings: The prevalence of subclinical hypothyroidism was high in both groups (18%). T1DM patients had lower frequency of goiter (21% vs. 38%, P=0.001), and higher prevalence of positive AIT (22% vs. 8%, P=0.001), anti-TPO Ab positivity (19.3% vs. 5.3%, P=0.000), and anti-Tg Ab (11.1% vs. 6.4%, P=0.1) in comparison with the control group. Being positive for AIT in diabetic patients meant an odds ratio of 5 (CI 95%: 1.5-15.6) for thyroid dysfunction. There was no association between age, sex, duration of diabetes and HbA(1C) with serum anti-TPO Ab and anti-Tg Ab concentrations in this group., Conclusion: Our results demonstrated the high prevalence of AIT and thyroid dysfunction in patients with T1DM. We suggest regular thyroid function and antibody testing in these patients.

MEN-1 is an autosomal dominant familial cancer syndrome characterized by involvement of parathyroid, enteropancreatic endocrine tissues and the anterior pituitary gland. Malignant insulinomas are rare, and therefore, there are few data regarding their clinical presentation and long-term prognosis. In this report we present a large family with malignant insulinoma and hyperparathyroidism with MEN-1 gene mutation analysis. A large family (three generations) with several members affected were evaluated for clinical and biochemical characteristic of MEN-1 syndrome. Genetic analysis for MEN1 gene was carried out in all family members using PCR amplification of coding regions followed by direct sequencing. In three brothers that presented with hypoglycemia, insulinoma was confirmed and two were malignant according to pathology and surgery report. Two of them had hyperparathyroidism too. Mutation screening revealed the presence of a two nucleotide deletion in the exon 2 (c199&#95;200del2). In the current study, the deletion happens early in the sequence, and obviously results in a non-functional gene product. However, it will be helpful to further examine somatic mutations and other genetic markers for a more precise study of genotype-phenotype correlation.

Background: Evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) once-daily monotherapy for patients with major depressive disorder (MDD)., Methods: In this 10-week, (8-week active treatment phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel-group, placebo-controlled, double-blind, randomized, Phase III study (D1448C00003: Opal), patients initially received quetiapine XR 150 mg/day or placebo. At Week 2, inadequate responders (<20% reduction in MADRS total score) were up-titrated to 300 mg/day quetiapine XR or matching placebo for the final 6 weeks. Primary endpoint: change from randomization to Week 8 in MADRS total score. Secondary endpoints included: MADRS response (≥50% reduction in total score from randomization) and changes from randomization to Week 8 in HAM-D and CGI-S., Results: 310 patients were randomized. At Week 8, quetiapine XR significantly reduced mean MADRS total score versus placebo (-16.49 vs -13.10, respectively; p<0.01). Mean MADRS score was significantly reduced by quetiapine XR versus placebo at Week 1 (p<0.05). MADRS response rates were significantly greater at Week 8 for quetiapine XR versus placebo (61.9% vs 48.0%, respectively; p<0.05). Significant changes in HAM-D total score and CGI-S were seen at Week 8 for quetiapine XR versus placebo. Withdrawal rates due to AEs were 9.9% and 2.6% for quetiapine XR and placebo, respectively. Common AEs (>10% any group during the randomized phase) for quetiapine XR and placebo, respectively were dry mouth (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and headache (10.5% and 10.3%)., Limitations: The study was not designed to compare quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose titration that might occur in clinical practice., Conclusions: Quetiapine XR monotherapy is effective in patients with MDD, with symptom improvement seen as early as Week 1, and tolerability results consistent with the known profile of quetiapine., (Copyright © 2010. Published by Elsevier B.V.)

Background: Two positive studies evaluated adjunctive extended release quetiapine fumarate (quetiapine XR) in patients with major depressive disorder (MDD) showing inadequate response to antidepressant treatment. This preplanned, pooled analysis provides an opportunity for subgroup analyses investigating the influence of demographic and disease-related factors on observed responses. Additional post hoc analyses examined the efficacy of quetiapine XR against specific depressive symptoms including sleep., Methods: Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies, prospectively designed to be pooled. Patients received once-daily quetiapineXR 150mg/day (n=309), 300mg/day (n=307) or placebo (n=303) adjunctive to ongoing antidepressant therapy. The primary endpoint was change from randomisation to Week 6 in MADRS total score. Other assessments included MADRS response (≥50% decrease in total score) and remission (total score≤8), change from randomisation in HAM-D, HAM-A, PSQI global and CGI-S scores., Results: Quetiapine XR (150 and 300mg/day) reduced MADRS total scores vs placebo at every assessment including Week 6 (-14.5, -14.8, -12.0; p<0.001 each dose) and Week 1 (-7.8,-7.3,-5.1; p<0.001 each dose). For quetiapineXR 150 and 300mg/day and placebo, respectively at Week 6: MADRS response 53.7% (p=0.063), 58.3% (p<0.01) and 46.2%; MADRS remission 35.6% (p<0.01), 36.5% (p<0.001) and 24.1%. QuetiapineXR 150 and 300mg/day significantly improved HAM-D, HAM-A, PSQI and CGI-S scores at Week 6 vs placebo. Quetiapine XR demonstrated broad efficacy, independent of factors including concomitant antidepressant., Limitations: Fixed dosing; lack of active comparator., Conclusions: Adjunctive quetiapine XR is effective in patients with MDD and an inadequate response to antidepressant therapy, with improvement in depressive symptoms seen as early as Week 1., (Copyright © 2010 Elsevier B.V. All rights reserved.)

This study evaluated once-daily extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p<0.01). Quetiapine XR 300 mg/d showed significant improvements vs. placebo for: MADRS total score from week 1 onwards; MADRS response [(> or = 50% total score reduction) 58.9% vs. 46.2%, p<0.05] and remission [(total score < or = 8) 42.5% vs. 24.5%, p<0.01] rates; Hamilton Depression Rating Scale (HAMD) (-13.53 vs. -10.80, p<0.01) and Clinical Global Impression-Severity of illness (CGI-S) change (-1.52 vs. -1.23, p<0.05) at week 6. For quetiapine XR 150 mg/d, improvements were not significantly different vs. placebo, except for MADRS (weeks 1 and 2) and HAMD (week 6) total scores. Withdrawal rates due to adverse events (AEs) were: quetiapine XR 150 mg/d 11.5%, 300 mg/d 19.5%, and placebo 0.7%. The most common AEs (>10%) with quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated.

Background: Pseudomonas aeruginosa is an important cause of nosocomial infection and may lead to septicemia and death. We evaluated the immunogenicity of semi-purified exotoxin A from the bacterium in a mouse burn model., Methods: The toxoid was prepared from exotoxin A taken from toxigenic strains of P. aeruginosa (PA 103). 50 mice were immunized with the toxoid, burned with hot metal and infected with 1 x 10(8) CFU of toxigenic strains of P. aeruginosa (experimental group); 25 non-immunized mice were also burned and infected (control group). The mortality rate and presence of any exotoxin and P. aeruginosa in the sera, liver and spleen were determined., Results: In the experimental group, 2 mice died before the burns were administered and were excluded from the study. The remainder (48 mice) were challenged with a lethal dose of P. aeruginosa and followed for 70 days. 3 of these mice died. Neither P. aeruginosa nor exotoxin A was not detected in the liver, spleen or sera of the surviving mice. The protective efficacy of toxoid vaccination was therefore 93.8%. In the control group, all mice died from bacteremia and septicemia, most (80%) within 6 days, and P. aeruginosa and exotoxin A were isolated from sera, spleen and liver., Conclusion: Active immunization of mice using a semi-purified exotoxin A derived from P. aeruginosa was 93.8% effective at protecting mice from subsequent P. aeruginosa infections in a mouse burn model.

We describe the clinical, radiographic, and genetic features of a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait. Six affected members of the family had partial complex seizures often associated with behavioral abnormalities. On MRI, three patients had a thickened irregular cortex in the lateral occipital lobes with small gyri. A high-density genome-wide scan with 10,000 SNPs established linkage by homozygosity mapping to a 14-Mb region on chromosome 6q16-q22. Candidate genes by function (TUBE1, GRIK2, GPRC6A, GPR6, NR2E1, MICAL1, and MARCKS) in this locus were screened for mutations.

The objective of this study was to determine the influence of vehicles on the penetration of octyl methoxycinnamate (OMC), as a UV absorber, to the stratum corneum by the stripping method. The experimental formulations consisted of a conventional o/w emulsion and multilamellar and small unilamellar liposomes (MLVs and SUVs) containing OMC. MLVs containing OMC were prepared by the fusion method and then converted to SUVs by probe sonication. Various formulations were then applied onto the midvolar forearms of six volunteers at a dose of 2 mg/cm2. After determined timepoints, the stripping method was conducted whereby 22 tape strips were applied and subsequently divided into different stripping groups. The sunscreen agent was assessed by HPLC while the SPF (sun protection factor) of the formulations was determined in human volunteers in accordance with the Australian standard. Overall the results indicate that skin accumulation of OMC in MLVs was significantly greater than in the o/w emulsion and SUVs. Furthermore, SUV's penetration into the deeper skin layers was significantly greater than MLV's and that of a conventional o/w emulsion. Also, higher amounts of OMC were recovered from the upper layers of the stratum corneum than from the deeper layers in all the formulations tested. Finally, the SPF of the liposomes containing OMC was slightly greater than that of the control lotions at a similar concentration of OMC. In conclusion, the result of this study indicates that an MLV prepared by the fusion method could be a better vehicle for OMC as a sunscreen since it has a slightly better SPF compared to a conventional formulation and more remains in the stratum corneum, reducing its penetration to the deeper layers.

Context and Aims: Diabetic burn patients comprise a significant population in burn centers. The purpose of this study was to determine the demographic characteristics of diabetic burn patients., Materials and Methods: Prospective data were collected on 94 diabetic burn patients between March 20, 2000 and March 20, 2006. Of 3062 burns patients, 94 (3.1%) had diabetes; these patients were compared with 2968 nondiabetic patients with burns. Statistical analysis was performed using the statistical analysis software SPSS 10.05. Differences between the two groups were evaluated using Student's t-test and the chi square test. P < 0.05 was considered as significant., Results: The major mechanism of injury for the diabetic patients was scalding and flame burns, as was also the case in the nondiabetic burn patients. The diabetic burn patients were significantly older, with a lower percentage of total burn surface area (TBSA) than the nondiabetic burn population. There was significant difference between the diabetic and nondiabetic patients in terms of frequency of infection. No difference in mortality rate between diabetic and nondiabetic burn patients was observed. The most common organism in diabetic and nondiabetic burn patients was methicillin-resistant staphylococcus. Increasing %TBSA burn and the presence of inhalation injury are significantly associated with increased mortality following burn injury., Conclusions: Diabetics have a higher propensity for infection. Education for diabetic patients must include caution about potential burn mishaps and the complications that may ensue from burns.

Characteristics and catalytic properties of a series of carbon-based catalysts (CBCs) produced from paper mill sludge were evaluated. The major processes involved in the production of the catalysts were chemical activation, impregnation, pyrolysis, and post pyrolysis rinsing. The porous structure, catalytic activity and thermostability of the catalysts were tailored during the production stage by introducing hetero-atoms (zinc chloride, and ferric nitrate) in the carbon structure. Characterization of the produced CBCs included determination of the surface area, pore size, and pore size distribution (PSD) from standard N2-adsorption isotherm data. The extent of graphitization and the presence of metal crystals were identified from X-ray diffraction (XRD). The limit of the catalyst gasification was estimated from thermogravimetric analysis (TGA) conducted in an oxidized environment. The NOx reduction capability of the produced catalysts was evaluated in the presence of carbon monoxide using a fixed bed reactor. The reaction temperature ranged from 300 to 500 degrees C. It was shown that paper mill sludge is an excellent precursor for the production of CBCs with NOx removal capability of 66-94%. The catalytic capability of the produced CBCs varied according to the method of production, catalyst surface properties (surface area, pore structure, PSD), metal composition and reaction temperature. The highest NOx removal capacity was observed for the catalytic reactions carried out at 400 degrees C. The mesoporous catalyst produced with a Zn:Fe molar ratio of 1:0.5 exhibited the maximum NOx removal catalytic activity of 94%.

The impact of the feed sludge (FS) concentration and addition of digested sludge (DS) to an aerobic digester was evaluated with respect to its capability for removal of the total suspended solids (TSS) and volatile suspended solids (VSS). The aerobic digesters, which operated in a batch mode at constant temperature and mixing rate, were initially filled with FS to 25%, 50%, 75%, and 100% of the reactor's volume. The remaining volume of the reactor was occupied by the DS, having DS/FS ratio of 3, 1, 1/3, and 0. Analysis of the experimental data showed that in the absence of DS, TSS, and VSS destruction rates are very small; however, increasing DS/FS ratio from 1/3 to 3 results in 74-77% increase in VSS and TSS destruction, respectively. The increase of the DS/FS ratio associated with increased ratio of the measured viable biomass (Cc) to VSS concentration (Xv) suggested that DS serves as the source of viable cell mass needed for degradation of organic solids. Assuming pseudo-first-order kinetics, it was shown that while organic solid destruction rate constants (k) are inversely related to initial concentrations of sludge, their values increase with increasing DS/FS ratios.

Training of medical staff on minimally invasive surgery (MIS) is an area where new effective training methods are needed. We have studied stent grafting, a type of MIS, which is used to treat abdominal aortic aneurysm. Our analysis revealed that this procedure requires a range of motor, perceptual and cognitive skills. In this paper, we present a training environment that could be used to acquire these skills. Our proposed solution differs from the usual VR solutions by operating within the World Wide Web as an environment for our system. This paper discusses how our solution covers the training skills and presents the results of an appraisal process, which we conducted to evaluate our solution.