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BACKGROUND: Acute cholecystitis is defined as gallbladder inflammation caused by obstruction of the cystic duct. The pro-inflammatory cytokine, high mobility group box-1 (HMGB1), has been found to hold critical roles in the pathogenesis of several different inflammatory diseases. This study aimed to determine the relationship between HMGB1 and acute cholecystitis, and examine the potential for this cytokine as a biomarker for clinical diagnosis. METHODS: The serum of 23 patients with severe acute cholecystitis, 45 patients with mild acute cholecystitis and 35 healthy subjects was collected and isolated from peripheral blood. The serum levels of HMGB1, CRP, amylase, lipase and the number of white blood cells were measured prior to the patient’s cholecystectomy and 48 hours following the procedure. RESULTS: A significant increase in the levels of HMGB1 were observed in both patient groups with mild or severe acute cholecystitis compared with normal group. ROC analysis determined a cut-off point of 2.34 for HMGB1 serum levels to discriminate between the normal group and acute cholecystitis patients with a sensitivity of 79.41% and a specificity of 54.3%. The area under the ROC curve was 0.71. Furthermore, a positive correlation was observed between CRP and HMGB1 levels and no significant difference in the levels of amylase and lipase was observed between groups. CONCLUSION: These findings suggest a potential role for HMGB1 as an effective biomarker in improving the diagnostic accuracy of acute cholecystitis when used in conjunction with the standard diagnostic tests.

Background: Prediabetes is strongly associated with high blood pressure; however, a little is known about prediabetes and high blood pressure comorbidity in the high-risk individuals. This is the first study in the world to assess the long-term effects of risk factors associated with high blood pressure and prediabetes comorbidity in the first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients. Materials and Methods: The longitudinal data obtained from 1388 nondiabetic FDRs of T2DM patients with at least two visits between 2003 and 2011. We used univariate and bivariate mixed-effects logistic regressions with a Bayesian approach to identify longitudinal predictors of high blood pressure and prediabetes separately and simultaneously. Results: The baseline prevalence of high blood pressure, prediabetes, and the coexistence of both was 27.4%, 19.1%, and 29.8%, respectively. The risks of high blood pressure and prediabetes were increased by one-unit raise in the age (odds ratio [OR] of high blood pressure: 1.419 (95% credible intervals [CI], 1.077–1.877), prediabetes: 1.055 (95% CI: 1.040–1.068)) and one-unit raise in remnant-cholesterol (OR of high blood pressure: 1.093 (95%CI, 1.067–1.121), and prediabetes: 1.086 (95% CI, 1.043–1.119)). Obese participants were more likely to have high blood pressure (OR: 2.443 [95% CI, 1.978–3.031]) and prediabetes (OR: 1.399 [95% CI, 1.129–1.730]) than other participants. Conclusion: We have introduced remnant-cholesterol, along with obesity and age, as a significant predictor of prediabetes, high blood pressure, and the coexistence of both in the FDRs of diabetic patients. Obesity index and remnant-cholesterol showed the stronger effects on high blood pressure and prediabetes comorbidity than on each condition separately.

Background: The prevalence of prediabetes in the world continues to increase. These patients have elevated the risk of atherosclerosis. The current study was designed to assess the prevalence of peripheral arterial disease (PAD) and its related risk factors in prediabetes patients. Methods: This was the case-control study in which 135 adults in three groups: Diabetes, prediabetes, and normal were studied. We evaluated the prevalence of PAD through the measurement of ankle-brachial index (ABI). All the patients were interviewed about demographic and medical data, including age, sex, disease duration, body mass index, hypertension (HTN), fasting blood glucose, hemoglobin A1C (HbA1C), lipid profile, and medication use. Results: The prevalence of PAD in diabetes patients was higher than the normal group (8.5%vs. 0.0%) (P < 0.05), but the differences between prediabetes compared with diabetes and normal group were not significant. The mean level of ABI in normal, prediabetes, and diabetes group was (1.11 ± 0.11), (1.09 ± 0.12), and (1.05 ± 0.03) respectively (P < 0.1). There were marginally significant differences of ABI observed between the normal group and the diabetes group. The observed differences between groups in the ABI were significant after adjusting the effects of age and sex (P < 0.05). There was an association observed between ABI and HbA1C in diabetes patients (r = 0.249, P < 0.01) and a significant association seen between PAD and HTN in the prediabetes group (P < 0.01). Conclusions: Peripheral arterial disease is common in asymptomatic diabetes and prediabetes patients. Management of hypertensive prediabetes patients and early detection of PAD in this group as well as in asymptomatic patients is important.

Background: The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. Materials and Methods: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. Results: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01). Conclusion: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.

Background: It is believed that paraoxonase-2 gene polymorphism is associated with type 2 diabetes. This study is aimed to investigate the association between paraoxonase-2 gene polymorphism and type 2 diabetes in an Iranian population. Methods: This study was performed on 200 individuals including 100 diabetics and 100 healthy subjects. Genomic DNA was extracted from peripheral blood leukocytes, and PCR-RFLP was carried out. Palindromic sequence in PON2 gene was recognized by Dde1 restriction endonuclease. In order to visualize restriction products, electrophoresis was carried out using polyacrylamide gel (8%) and ethidium bromide staining. Results : The expected PCR product of 331 bp was obtained. Digestion of this product with DdeI showed four Ser homozygotes, three Cys homozygotes, and five Ser311 Cys heterozygotes. The gene frequency of Cys (C) in diabetic subjects was significantly higher than in healthy subjects. Conclusions : This study suggests that an association exists between Ser311 Cys polymorphism and type 2 diabetes mellitus.

Background: This study aimed to investigate the beneficial effects of angiotensin receptor blockers (ARBs) on markers of endothelial function in patients with early stage of diabetic nephropathy (DN). Methods: This cross-sectional study was conducted on 32 participants with IDDM from January 2010 until May 2011 in Isfahan, Iran. The participants were candidate for receiving ARBs or angiotensin-converting enzyme inhibitors (ACEIs) to decrease microalbuminuria. The inclusion criteria were as follows: the age of onset of insulin-dependent diabetes mellitus (IDDM)less than 15 years; normal glomerular filtration rate (GFR); normal blood pressure; normal cardiovascular examination; negative urine culture, receiving no medications except insulin. Microalbuminuria was measured in two fasting urine samples with a sampling interval of at least 1–2 months by ELISA method. Patients with two abnormal results were included. Microalbumin to creatinin ratio equal to or more than 30 mg/gm was considered abnormal. The fasting blood samples to determine serum nitric oxide (NO) and vascular cell adhesion molecule (VCAM) were obtained at the time 0 (before starting the study), and after 2 months of receiving ARBmedication. Valsartan tablet (Diovan, Novartis Company) with a dose of 1 mg/kg/day up to 80 mg/day in a single dose was administered. Results: Urine microalbumin to creatinin ratio after valsartan consumption was lower than microalbumin level before the medication, P < 0.05. After valsartan consumption, serum VCAM-1 level reduced and NO level increased significantly, P < 0.05. Conclusion: Angiotensin receptor blockers may reduce VCAM-1 and microalbuminuria and may increase NO levels in early stages of DN. Thus administration of ARBs might be considered even in early stages of DN.

Objective: Low testosterone, with or without symptoms, reported in diabetic men in some studies. We investigated the prevalence of hypogonadism in Iranian type 2 diabetic men. Materials and Methods: Total testosterone (TT) and sex hormone binding globulin (SHBG) concentrations were measured in 247 diabetic men >30 years who had symptoms of androgen deficiency, according to ADAMs questionnaire. The correlation between some parameters and total, free and bioavailable testosterone levels was determined using Pearson correlation coefficient. Free and bioavailable testosterone were calculated by electronic calculator. Four patients were excluded because of high testosterone level, due to unreported androgen use. Overt hypogonadism was defined as total testosterone ≤8 nmol/l or calculated bioavailable testosterone (cBT)≤2.5 nmol/l and borderline hypogonadism was considered as TT 8-12 nmol/l or cBT 2.5-4nmol/l. Results: The mean and SD of age was 59 (9.3) years. The mean TT, calculated free testosterone (cFT), and cBT and SHBG levels were 4.81 (1.7) nmol/l, 0.11 (0.06) nmol/l, 2.42 (1.17) nmol/l and 36.15 (18.3) nmol/l, respectively. According to TT and cBT, overt hypogonadism observed in 7.4% and 61.6% of men, respectively, and the prevalence of borderline hypogonadism was 9.9% and 36%, respectively. cFT ≤0.16 nmol/l found in 227 diabetic men (96%). Hypogonadism (TT ≤12 nmol/l) was not correlated with obesity, smoking, age, duration of diabetes, blood pressure, and HbA1c. Conclusion: Hypogonadism is highly prevalent in type 2 diabetes men.

Background: This study aimed to compare different body mass index (BMI) categories in individuals with diabetes, prediabetes and normal glucose tolerance among the first degree relatives of type 2 diabetic patients. Materials and Methods: A cross-sectional study was conducted during 2005-2007 in Isfahan, Iran. It evaluated 3323 first-degree relatives of diabetic patients selected by consecutive convenient sampling method. Participants were classified as diabetic, prediabetic, and normal glucose tolerance test groups according to the results of 75 g oral glucose tolerance test (OGTT). The analysis of variance (ANOVA) was used for comparison of quantitative variables, and chi square test for comparison of categorical parameters. Results: The study population consisted of 3323 individuals including 306 diabetics (98 males and 208 females), 1309 prediabetics (337 males and 972 females), and 1708 normal subjects (430 males and 1278 females). Among diabetic patients, the prevalence of obesity was 48.5% in women and 27.6% in men. Among prediabetics, the corresponding figures were 45.6% and 27.3%, respectively. Conclusions: Our findings suggest that men are diagnosed with T2DM at lower BMI than women. Moreover, the alarming high prevalence of overweight and obesity among females necessitates preventing and controlling this underlying problem among females.

Background: Sleep apnea is associated with increased risk of diabetes mellitus. However, no studies have compared sleep apnea symptoms in diabetic patients and their first degree relatives. The purpose of our study was to investigate high risk for sleep apnea syndrome, in diabetics and their first degree relatives for prevention of diabetes in family. Methods: As a part of a cohort study, all of diabetic and their first degree relatives who came for glucose control in diabetes clinic were invited to take part in the survey. Two thousand, four hundred and sixty-two individuals (82% of invited) agreed to fill out the Berlin and Epworth sleep questionnaire. Participants consisted of 2462 subjects of 15-70 years of age, both males and females with diabetes and family history of type 2 diabetes mellitus. A total of 1234 participants had diabetes and 11,231 were relatives of diabetic patients. High risk for sleep apnea regarding Berlin questionnaire and Epworth sleepiness scale, diabetic and relative were analyzed. Results: Prevalences of high risk for sleep apnea were higher among diabetics than relatives (P-value

Background Her2/neu is one of the epidermal growth factor receptors families and seems to have prognostic significance of some solid tumors. The objective of this study is to evaluate the possibility of Her2 expression in gastric cancers and the possible relationship of Her2 with tumor’s clinicopathologic parameters and also its prognostic role. Methods This study was performed on 100 cases of gastric carcinoma with stage I b to III (according to TNM staging). Survival, recurrence date of patients, grade and lymph nodes involvement were assessed. Her2/neu expression was determined by immunohistochemical method on received sample blocks. Survival of patients with or without Her2-neu expression were evaluated by Kaplan- Meier method and compared with the log-rank test followed by multivariate analysis using Cox regression. Results Seven cases were 3+ membranous Her2 reactivity, 5 cases were 2+ and13 cases were 1+; also 75% of cases demonstrated no reactivity. Regardingrelationship between tumor grade and membranous Her2 , all patients with poorly differentiated tumors were Her2 negative but patients with moderate and well differentiated tumor had 18.1% and 19.6% Her2 reactivity respectively; there were no significant difference between groups statistically(P>0.05). Median overall survival was 27.25 and 46 months in Her2 negative and her2 positive cases respectively; there were no significant difference between groups statistically as well (P>0.05). Conclusion Her2 reactivity has not relationship with tumor grade and lymph node involvement as well as tumor stage. From the other point of view no significant correlation is found between Her2 expression and disease free survival or overall survival of gastric cancer patients.

Background: The aim of this study is to investigate the need for diabetes primary prevention program in isolated impaired fasting glucose (i-IFG) of the first degree relatives of type 2 diabetics. Methods: In a cross sectional study, 793 individuals with prediabetes [543 with i-IFG and 250 with isolated impaired glucose tolerance (i-IGT)] who were the first degree relatives of type 2 diabetic patients, were enrolled. Isolated IFG was considered as fasting plasma glucose between 100-125 mg/dl and 2 hour plasma glucose < 140 mg/dl and isolated IGT as FPG < 100 mg/dl and 2 hour plasma glucose between 140-199 mg/dl during an overnight fasting 75 g oral glucose tolerance test. Mean of the age, weight, waist circumference, body mass index, systolic and diastolic blood pressure, plasma glucose, HbA1C, and lipid profile were compared between two groups (i-IFG and i-IGT). The prevalence of cardiometabolic risk factors (BMI ≥ 25 kg/m2, hypertension, cholesterol ≥ 200 mg/dl, LDL-C ≥ 100 mg/dl, HDL-C ≤ 40 mg/dl, and triglyceride ≥ 150 mg/dl) adjusted by age, sex and BMI were compared. Results: The prevalence of cardiometabolic risk factors is higher in i-IFG group than i-IGT. The mean level of LDL-C is significantly higher in i-IFG than i-IGT group. Conclusions: First degree relatives of T2DM with isolated impaired fasting glucose should probably be included in the primary preventive program for diabetes. However, longitudinal cohort study is required to show high progression of i-IFG to T2DM.

Background: In this study, we evaluated the quality of care and control of cardiovascular risk factors in newly diagnosed diabetic patients, identified during diabetes screening program, 1 year after diagnosis. Methods: In this prospective study, 83 newly diagnosed diabetic patients identified at screening in Isfahan, were studied. Height, weight, blood pressure, plasma glucose, lipids, and hemoglobin A1c (HbA1c) of these patients were measured 2 times, first at the time of diagnosis and then 1 year later, and the results were compared between two groups, with and without regular course of treatment. Results: Nearly 46.99% and 53.1% of the studied patients have regular and irregular course of treatment. After 1 year, significant improvement in the mean of plasma glucose, cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein and HbA1c was seen in patients with regular course of treatment except for blood pressure (P < 0.05). Frequency of controlled cardiovascular risk factors including fasting plasma glucose, HbA1c, cholesterol and LDL was significantly improved in patients with regular course of treatment (P < 0.05). Mentioned changes were not seen in patients with irregular course of treatment. Conclusions: The findings of the current study demonstrated that though diabetes screening program result in earlier diagnosis of patients with type 2 diabetes, but it seems that regular follow-up and proper management of newly diagnosed patients is crucial for appropriate glycemic and metabolic control and preventing its related micro and macrovascular complication.

Background: The aim of this study was to compare the usefulness of ultrasonography and scintigraphy in diagnosing the etiology of primary congenital hypothyroidism (CH). Methods: The newborns that were examined by both thyroid scintigraphy and ultrasonography during CH screening program in Isfahan were included in this study. The ultrasonographic findings were compared with the scintigraphic findings and the sensitivity and specificity of the ultrasonography was determined. Results: During this study, 102 CH newborns were studied. According to the ultrasonographic results, 61.8%, 26.5%, 2.9% and 8.8% of them had normal thyroid gland, agenesia, ectopia and hypoplasia, respectively, and according to scintigraphic results, 55.9%, 35.3% and 8.8% of them had normal thyroid gland, agenesia and ectopia, respectively. Ultrasound detected sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 77%, 92%, 89%, 84%, 9.6 and 0.25, respectively. The sensitivity and specificity of ultrasonography compared with thyroid scintigraphy in diagnosis of thyroid gland ectopia was 33% and 100%, respectively. Conclusions: Though thyroid ultrasonography failed to diagnose 67% of ectopic cases and nonfunctioning thyroid gland, it had the ability to determine the anatomy of thyroid gland. So, considering some limitations of scintigraphy, we concluded that ultrasonography is a relatively appropriate imaging tool for diagnosing CH etiologies, especially in the initial phase of CH screening.

Introduction: The application of organizational ethics in hospitals is one of the novel ways to improve medical ethics. Nowadays achieving efficient and sufficient ethical hospital indicators seems to be inevitable. In this connection, the present study aims to determine the best indicators in hospital accreditation. Methods: 69 indicators in 11 fields to evaluate hospital ethics were achieved through a five-step qualitative and quantitative study including literature review, expert focus group, Likert scale survey, 3 rounded Delphi, and content validity measurement. Expert focus group meeting was conducted, employing Nominal Group Technique (NGT). After running NGT, a three rounded Delphi and parallel to Delphi and a Likert scale survey were performed to obtain objective indicators for each domain. The experts were all healthcare professionals who were also medical ethics researchers, teachers, or Ph.D students. Content validity measurements were computed, using the viewpoints of two different expert groups, some ethicists, and some health care professionals (n=46). Results: After conducting NGT, Delphi, Likert survey, 11 main domains were listed including: Informed consent, Medical confidentiality, Physician-patient economic relations, Ethics consultation policy in the hospital, Ethical charter of hospital, Breaking bad medical news protocol, Respect for the patients’ rights, Clinical ethics committee, Spiritual and palliative care unit programs in the hospitals, Healthcare professionals’ communication skills, and Equitable access to the healthcare. Also 71 objective indicators for these 11 domains were listed in 11 tables with 5 to 8 indicators per table. Content Validity Ratio (CVR) measurements were done and 69 indicators were highlighted. Conclusion: The domains listed in this study seem to be the most important ones for evaluating hospital ethics programs and services. Healthcare organizations’ accreditation and ranking are crucial for the improvement of healthcare services. Ethics programs would also motivate hospitals to improve their services and move towards patients’ satisfaction. In this regard, more involvement of bioethicists can help healthcare organizations to develop ethics programs and ensure ethicsbased practice in hospitals.

Due to the antitumor activity of Gallium MAL complex, as well as recent findings on new targeted biomolecules in malignant cells through this complex, the development of radiolabeled gallium complex for future imaging studies was targeted. Ga-67 labeled 3-hydroxy-2-methyl-4H-pyran-4-onate (Ga-67 MAL) was prepared using freshly prepared Ga-67 chloride and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 40° C. The stability of the complex was checked in final formulation and human serum for 24 h followed by the administration in Swiss mice for biodistribution studies. The complex was prepared in high radiochemical purity (> 97% ITLC, > 98% HPLC) and specific activity of 13-14 GBq/mmol and was stable in the presence of serum for 48 h. The partition coefficient was calculated for the compound (log p = 0.40). A detailed comparative pharmacokinetic study was performed for Ga-67 cation and Ga-67-MAL. The complex is more rapidly washed out from the circulation through kidneys and liver compared to Ga-67 cation and can be an interesting tumor imaging agent due to the fact that the cold compound is undergoing clinical trials as a safe and potential therapeutic agent for cancer.

Background: Excess serum uric acid (UA) accumulation can lead to various diseases. Increasing evidences reveal that UA may have a key role in the pathogenesis of metabolic syndrome. Little is known about the associations of UA levels with cardiometabolic risk factors in prediabetic individuals. This study was designed to evaluate the association between UA and cardiometabolic risk factors in prediabetic subjects with family history of diabetes compared with those with normal glucose tolerance (NGT). Materials and Methods: In a cross-sectional setting, a sample containing 643 (302 prediabetic subjects and 341 normal) of the first-degree relatives of diabetic patients aged 35-55-years old were investigated. Samples were assessed in prediabetic and normal groups using glucose tolerance categories. Prediabetes was defined based on American Diabetes Association (ADA) criteria. Body weight and height, systolic and diastolic blood pressure (SBP and DBP), UA, creatinine (Cr), albumin (Alb), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and lipid profiles were measured and compared between two groups. Results: Prediabetic persons were older and obese than normal persons. Also, prediabetic persons (5.2 ± 1.3 mg/dl) had significantly higher UA than normal persons (4.9 ± 1.4 mg/dl) (P < 0.05). FBG after 0, 30, 60, and 120 min in prediabetic were higher than normal persons (P < 0.001). With respect to metabolic parameters, the patients in the higher UA quartiles exhibited higher levels of body mass index (BMI), SBP, FBG and triglycerides (TG). The higher quartiles of UA tended to be associated with higher BMI and higher total cholesterol (TC) in females prediabetic persons. Based on logistic regression analysis in different models, UA was positively (odds ratio (OR) >1, P < 0.05) associated with glucose tolerance categories. This association remained statistically significant after adjusting the effects of age and BMI. Also, the association between glucose tolerance categories and UA were positively significant in both genders. Conclusion: High UA level was associated with some cardiometabolic risk factors in prediabetic individuals compared with normal person. UA level was also a significant predictor for prediabetes condition.

The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully was applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys (OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.

Background: The goal of this study was to examine the construct validity of the diagnostic and statistical manual of mental disorder-5 (DSM-5) conceptual model of antisocial and borderline personality disorders (PDs). More specifically, the aim was to determine whether the DSM-5 five-factor structure of pathological personality trait domains replicated in an independently collected sample that differs culturally from the derivation sample. Methods: This study was on a sample of 346 individuals with antisocial (n = 122) and borderline PD (n = 130), and nonclinical subjects (n = 94). Participants randomly selected from prisoners, out-patient, and in-patient clients . Participants were recruited from Tehran prisoners, and clinical psychology and psychiatry clinics of Razi and Taleghani Hospital, Tehran, Iran. The SCID-II-PQ, SCID-II, DSM-5 Personality Trait Rating Form (Clinician′s PTRF) were used to diagnosis of PD and to assessment of pathological traits. The data were analyzed by exploratory factor analysis. Results: Factor analysis revealed a 5-factor solution for DSM-5 personality traits. Results showed that DSM-5 has adequate construct validity in Iranian sample with antisocial and borderline PDs. Factors similar in number with the other studies, but different in the content. Conclusions: Exploratory factor analysis revealed five homogeneous components of antisocial and borderline PDs. That may represent personality, behavioral, and affective features central to the disorder. Furthermore, the present study helps understand the adequacy of DSM-5 dimensional approach to evaluation of personality pathology, specifically on Iranian sample.

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetrazole and maximal electroshock induced seizures tests. Nifedipine was used as reference drug. Our pharmacological results revealing the compounds 2, 4, 5, and 6 can be effective in both absence and grandmal seizures in human. These pharmacological studies have displayed that these new dihydropyridine derivatives are capable to inhibiting seizures induced by pentylenetetrazole and maximal electroshock in mice efficiently.

The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect.

A rapid, simple and reproducible HPLC method was developed and validated for the analysis of nimodipine (NM) and/or its metabolite, oxidized nimodipine (OX-NM) in rat cerebrospinal fluid (CSF) and artificial CSF. The NM and OX-NM were eluted in less than 10 min with no interferences from the endogenous CSF peaks. Analysis was carried out on a Eurospher Performance (RP-C18, 250 × 4.6 mm) column and UV detection at 236 nm. The mobile phase consisted of acetonitrile and water (70:30 v/v, respectively) with a flow rate of 1 mL/min. Limit of detection was 0.1 μg/mL for OX-NM. The calibration curve was linear over the concentration range of 0.5-10 µg/mL and analytical recovery was more than 95%. The coefficients of variation for intra-day and inter-day assays were less than 5%.

The uses of non-steroidal anti-inflammatory drugs (NSAIDs) are limited by a variety of side effects. So research on preparing new analgesic agents is important. According to some reports about the analgesic activity of hydrazide and hydrazine derivatives a new series of these compounds were synthesized in order to obtain new analgesic compounds. The final compounds 10a-10e and 15a-15d were prepared by condensation of corresponding hydrazides 7,8 and 11-14 with different aldehydes 9a-9e. The structures of all synthesized compounds were confirmed by means of FT-IR, 1H-NMR and Mass spectra. All compounds were evaluated for their analgesic activities by abdominal constriction test (writhing test). Most of the synthesized compounds induced significant reduction in the writhing response when compared to control and compound 15 was more potent than mefenamic acid in the writhing test.

Oliveria decumbens is an aromatic plant traditionally used for treatment of infections and gastrointestinal diseases. In the present study, the volatile oil of the plant was obtained by hydrodistillation and analyzed by GC-MS. In addition, antibacterial and anti-Helicobacter pylori activities of this essential oil were determined using disc diffusion and agar dilution methods, respectively. Insecticidal activity was assessed through topical and fumigation application of the essential oil to cabbage looper larvae. Acetylcholinesterase (AChE) inhibition by the essential oil was examined using Ellman’s method. Furthermore, its cytotoxic potential against three different cancer cell lines was assessed using the MTT assay. The phenolic monoterpenoids, thymol (38.79%), and carvacrol (36.30%) were identified as major constituents of the essential oil. We observed significant antibacterial activity of the essential oil against H. pylori (MIC=20.4 µg /mL) as well as other tested bacteria, except for Pseudomonas aeruginosa. O. decumbens essential oil showed significant toxicity to cabbage looper larvae with LD50 value of 52.1 µg /larva following topical and fumigant administration. O. decumbens essential oil was considerably inhibitory to acetylcholinesterase activity (IC50 = 0.117 µg/mL). Cytotoxic assay of the volatile oil resulted in IC50 = 0.065, 0.104, and 0.141 μg/mL for MCF-7, T47D and MDA- MB-231 cell lines, respectively. According to our data, this species with high concentrations of thymol and carvacrol could be considered as a natural source for pharmaceutical products.

PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of peptides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bis-thiol alkylating reagent (V) was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and (1)H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, (1)H-NMR analysis showed a 7.44% degree of PEG substitution.

Background: We investigated the effect of acute hypothyroidism on lipid concentrations especially on high density lipoprotein (HDL-cholesterol) level in athyroatic patients. Materials and Methods: Thirty-one patients, with a history of differentiated thyroid carcinoma and total thyroidectomy, who were candidates of radioiodine therapy, enrolled in the study. Their lipid profiles and serum thyrotropin stimulating hormone (TSH) levels were measured before and two-to-six weeks after thyroid hormone withdrawal. The lipid concentrations were compared with the paired t test and serum TSH using the Wilcoxon singed rank test. P values < 0.05 were considered statistically significant. Results: The median of TSH concentration was 0.06 mU / liter on thyroid hormone suppressive therapy and 102 mU / liter at the thyroid hormone withdrawal phase (P < 0.0001). The serum concentrations of all lipids were significantly increased after withdrawal (P < 0.0001). The mean (SD) of the HDL-cholesterol concentration rose from 44 ± 9 mg / dL to 58 ± 17 mg / dL. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride increased by 58, 75, 30, and 59%, respectively, during acute hypothyroidism. Conclusion: The present study showed that thyroid hormone withdrawal altered the lipid concentrations significantly, in a short period of time. The levels of both atherogenic (LDL-cholesterol) and cardioprotective (HDL-cholesterol) particles increased concurrently. Their clinical importance should be investigated in future.

Background: There are some evidences that control the blood sugar decreasing the risk of diabetes complications, and even fatal. There are so many studies, but they are mostly cross-sectional and ignore the trend and hence it is necessary to implement a longitudinal study. The aim of this prospective study is to find the trend of glycosylated hemoglobin (HbA1c) over time and the associative factors on it. Methods: Participants of this longitudinal study were 3440 eligible diabetes patients referred to Isfahan Endocrine and Metabolism Research Center during 2000-2012 who are measured 2-40 times. A linear mixed model was applied to determine the association between HbA1c and variables, including lipids, systolic, diastolic blood pressure and complications such as nephropathy, and retinopathy. Furthermore, the effect of mentioned variables on trend of HbA1c was determined. Results: The fitted model showed total cholesterol, retinopathy, and the method of therapy including oral antidiabetic drugs (OADs) plus insulin and insulin therapy decreased the trend of HbA1c and high-density lipoprotein, weight, hyperlipidemia and the method of therapy including diet, and OADs increased the trend of HbA1c. Conclusions: The present study shows that regular visits of diabetic patients as well as controlling blood pressure, lipid profile, and weight loss can improve the trend of HbA1c levels during the time.

Background: Unexplained infertility is still a challenging issue as to its causes, appropriate management and treatment. Evidence implicates early embryopathy or implantation failure as likely causes. Objective: This study aims to investigate the effect of local endometrial injury on pregnancy rate in selected unexplained infertile patients. Materials and Methods: This was a randomized clinical trial conducted in Shiraz University Infertility Clinic of Ghadir Hospital. A total of 217 women with unexplained infertility aged 23-35 years old were randomly divided into two study groups through block randomization. After superovulation by clomiphene-citrate and gonadotropins and when the dominant follicles reached 18-20 mm, patients were randomly assigned to undergo endometrial local injury at posterior uterine wall by piplle endometrial sampling (n=114) or mock pipette biopsy (n=103) during pre-ovulatory days (when spontaneous urinary LH surge was detected). Then all the patients were instructed to follow a regularly timed intercourse. Results: The pregnancy rate was significantly higher in the endometrial injury group compared to the control group [17/114 (14.9%) vs. 6/103 (5.8%) (OR: 2.83 95% CI: 1.07-7.49, p=0.03]. The abortion rate was comparable between two groups (17.64% vs. 14.28%; p=0.701). Conclusion: Local mechanical injury of the endometrium can enhance the uterine receptivity and facilitates the embryo implantation. This simple, easy, and cost effective procedure is worth considering in selective unexplained infertility patients who implantation failure is the likely causes of infertility before complex treatments. This procedure may help reduce psychological tensions and high expenses imposed through such interventions. Registration ID in IRCT: IRCT2012082510657N1

Background: To determine whether uric acid levels are associated with the components of metabolic syndrome and whether uric acid is a significant factor for development of metabolic syndrome in the first-degree relatives of type 2 diabetic patients as high risk group. Materials and Methods: A total of 694 (182 male and 512 female, aged 30-69 years) first-degree relatives of type 2 diabetic patients during 2007-2011 were enrolled. The height, weight, waist circumference, blood pressure, fasting plasma glucose, lipid profile and uric acid concentrations were measured. Metabolic syndrome was defined by NCEP-ATP III. Results: Uric acid was associated with waist circumference, blood pressure, triglyceride and HDL-cholesterol level in both sexes (r = 0.1-0.3, P < 0.05). The prevalence of metabolic syndrome in the fourth quartile of uric acid (64.4% of male and 60.2% of female population) was significantly more than those in the first (25.5% of male and 31.2% of female population) and second quartiles (33.3% of male and 32.0% of female population). The mean of uric acid in people with metabolic syndrome was significantly higher than in those without (6.6 ± 1.2 mg/dL vs. 5.8 ± 1.2 mg/dL; P = 0.0001). The age-adjusted odds ratios (95% confidence interval) of uric acid for metabolic syndrome in univariate analysis were [1.60 (1.23-2.07); P = 0.008] for men and [1.61 (1.34-1.92); P = 0.0001] for women but the effect of uric acid in multivariate logistic regression was not significant. Conclusions: Uric acid is associated with majority of the metabolic syndrome components. People with metabolic syndrome have higher uric acid levels. However, uric acid probably is not an independent factor to predict the metabolic syndrome.

Background: Some epidemiological and interventional studies have shown the role of vitamin D on insulin secretion and resistance. A previous study in our center showed that intramuscular vitamin D decreases insulin sensitivity in pre-diabetic patients. We investigated the role of oral vitamin D on the insulin sensitivity index and insulin resistance in pre-diabetic patients. Materials and Methods: In a randomized clinical trial, we divided 45 people with pre-diabetes aged 47.4 ± 6.6 (range 33-61) years into three groups: group A subjects treated with 50,000 IU oral vitamin D and 500 mg calcium carbonate (n = 21), group B subjects treated with a single 300,000 IU intramuscular vitamin D and 500 mg calcium carbonate (n = 9), and group C subjects treated with 500 mg calcium carbonate alone (n = 15). Serum 25-hydroxyvitamin D [25(OH) D] was measured at baseline. If it was less than 75 nmol/l, 50,000 IU vitamin D was given weekly, and if serum 25(OH) D was more than that, vitamin D was administered every 2 weeks. Before and after 12 weeks of treatment, a 75-g glucose tolerance test was performed. We used paired t-test and analysis of variance (ANOVA) to analyze the data. P values less than 0.05 were considered significant. Results: Mean (SD) of serum vitamin D increased from 77.5 ± 39.2 to 118.8 ± 56.3 nmol/l (P = 0.009) in group A and from 80 ± 36 to 102.8 ± 43.3 nmol/l (P = 0.053) in group B, and decreased from 44.8 ± 18.3 to 34.6 ± 13.9 nmol/l (P = 0.06) in group C. Insulin sensitivity index (Matsuda) decreased from 11.4 ± 3 to 9.9 ± 3.2 (P = 0.046) in group A, but in comparison with other groups, it was not significant. Conclusion: Oral vitamin D had no effect on insulin sensitivity in pre-diabetes patients in 12 weeks treatment. A randomized double-blind study with a longer duration of treatment is suggested to investigate the effect of vitamin D on insulin resistance.

BACKGROUND: Cardiovascular diseases (CVD) are a set of metabolic disorders affecting heart and blood vessels. Green tea and sour tea (Hibiscus sabdariffa L.) have attracted significant attention recently due to their high popularity, nutrient profile and therapeutic effects. The aim of the present study was to compare the effects of green tea and sour tea supplementation on blood pressure and lipid profile in healthy adult men. METHODS: This randomized, double-blind, placebo-controlled trial included 54 healthy adult men. The participants were randomly assigned to two intervention groups receiving 450 mg green tea or sour tea and one placebo group which consumed 450 mg placebo (maltodextrin) for 6 weeks. Blood pressure, lipid profile, dietary intake and physical activity were measured pre- and post-intervention and compared. RESULTS: After 6 weeks of intervention, sour tea supplementation led to a significant decrease in systolic blood pressure (SBP) compared with the placebo group. However, we faild to find any significant difference in SBP between green tea and control groups. Also, no significant changes were observed in diastolic blood pressure (DBP) and lipid profile between the three groups. In comparison with baseline, there was a significant increase in the mean level of serum high-density lipoprotein cholesterol (HDL-C) in green tea and sour tea groups. Also, the interventions resulted in significant decrease in the mean levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and DBP in the sour tea group compared with the pre-intervention value. CONCLUSION: On the basis of our findings, sour tea supplementation led to decreased SBP in healthy men compared with the placebo, but there was no significant difference between their effects on DBP and lipid profile.&nbsp

Background: Diabetes Education by Peer Coaching is a strategy which helps the patients with diabetes in the field of behavioral and emotional problems. However, the results of studies in this field in other countries could not be generalized in our context. So, the current study aimed to examine the effectiveness of Diabetes Education by Peer Coaching on Diabetes Management. Methods: Outcome variables for patients and peer coaches are measured at baseline and in3,6 and 12 months. The primary outcome consisted of Fasting Blood Sugar (FBS) and HbA1c. Secondary outcomes included Blood Pressure (BP), Body Mass Index (BMI,) Waist-Hip Ratio (WHR), Lipid Profile, diabetes self-care activities, diabetes-related quality of life, depression, and Social Capital levels.Initial analyses compared the frequency of baseline levels of outcome and other variables using a simple Chi-square test, t-test and the Mann-Whitney- U test. Sequential measurements in each group were evaluated by two-way analysis of variance. If significant differences in baseline characteristics were found, analyses were repeated adjusting for these differences using ANOVA and logistic regression for multivariate analyses. Additional analyses were conducted to look for the evidence of effect modification by pre-specified subgroups. Conclusion: The fact is that self-control and self-efficacy in diabetes management and treatment of diabetes could be important components. It seems that this research in this special setting with cultural differences would provide more evidence about peer-coaching model. It seems that if the peer-coaching model improves learning situations between patients with diabetes by offering one-on-one Diabetes Self Management Education, it could be an interactive approach to diabetic education. Trial Registration Number: IRCT201501128175N3

Carbon nanotubes have unique properties like high stability, high surface to mass ratio and so on which make them suitable for medicinal purpose applications. Treatment of cancer by organoplatinum agents like Cisplatin has become unresponsive in most cases due to low distribution of drug in biological fluids, inability of drug to cross cellular membranes and low stability in biological environments. Recently, carbon nanotubes (CNT) have stimulated much interest to overcome these limitations. ‎‎ Herein, we report the preparation of single-wall carbon nanotube functionalized by diaminedicarboxyplatinum (II) as an analogy of SWCNT-based Carboplatin. Functionalization was started by cyclopropanation through Bingel reaction and by use of diethylmalonate to yield cyclopropane-1,1-dicarboxy ethyl ester. Final product was obtained by hydrolysis of ester group and then chelation of platinum (IV) by dicarboxylate groups on the surface of SWCNT. Raman and Fourier transform -Infrared ‎spectroscopy (IR), ‎Thermogravimetric ‎analysis ‎(TGA) and energy dispers‎ive X-ray‎spectroscopy ‎(EDAX) truly showed and confirmed the presence of the platinum (II) complex on the side wall of SWCNT. Cytotoxicity evaluation of the functionalized-SWCNTs on HeLa cells showed its higher anticancer ability than Cisplatin as indicated by IC50 value of 13 µg/mL.

Caffeic acid phenethyl ester (CAPE) suppresses the growth of transformed cells such as human breast cancer cells, hepatocarcinoma , myeloid leukemia, colorectal cancer cells, fibrosarcoma, glioma and melanoma. A group of heterocyclic esters of caffeic acid was synthesized using Mitsunobu reaction and the esters were subjected to further structural modification by electrooxidation of the catechol ring of caffeic acid esters in the presence of sodium benzenesulfinate and sodium toluensulfinate as nucleophiles. Both heterocyclic esters of caffeic acid and their arylsulfonyl derivatives were evaluated for their cytotoxic activity against HeLa, SK-OV-3, and HT-29 cancer cell lines. HeLa cells showed the highest sensitivity to the compounds and heterocyclic esters with no substituent on catechol ring showed better activity compared to their substituted counterparts. QSAR studies reemphasized the importance of molecular shape of the compounds for their cytotoxic activity.