Metformin protects PC12 cells against oxygen-glucose deprivation/reperfusion injury

Oxidative stress has a causative role in ischemic reperfusion-induced cell death. Evidence has shown that metformin is capable to reduce ischemic reperfusion injuries. The current study investigated the effect of metformin on ischemia/reperfusion-induced apoptosis in PC12 cells by evaluation of Bcl-2 family proteins expression. Cells were exposed to a time-dependent in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) injury and then treated with metformin. The intracellular reactive oxygen species (ROS) levels were measured. Western blotting was used to examine the expression of anti- and pro-apoptotic proteins. Moreover, the number of apoptotic cell death was evaluated by TUNEL assay. Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells. Moreover, metformin reduced cell death under OGD/R condition which was confirmed by lower apoptotic cell death in the TUNEL assay. These findings suggest that neuroprotective effect of metformin on OGD/R-induced cell death is possibly mediated by inhibition of ROS-induced apoptosis pathway.     

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.     

Repeated administration of nicotine attenuates the development of morphine tolerance and dependence in mice

Clinical use of morphine in pain management is a controversial issue. Both nicotine and morphine are widely abused. So, investigating the interaction between nicotinic and opioid receptors is of great interest to both basic mechanistic and clinical view. We investigated the influence of repeated administration of nicotine on the development of morphine tolerance and dependence. Adult male albino mice were rendered dependent on morphine by subcutaneous (s.c.) injections three times daily for 3 days. Repeated intraperitoneal (i.p.) injection of nicotine (0.001-2 mg/kg) or saline (1 ml/kg) was performed 15 min prior to each morphine injection. Maximal possible effect (MPE%) of morphine (50 mg/kg; s.c.) was used on the fourth day as an index for the development of tolerance. Likewise, to assess the occurrence of dependence in drug-treated mice, naloxone (5 mg/kg; i.p.) was injected 2 h after the last dose of morphine. Repeated nicotine administration significantly attenuated the development of tolerance in a dose-dependent manner whereas it significantly decreased withdrawal jumping behavior in a biphasic profile (V-shape) manner. Furthermore, the central nicotinic receptor antagonist mecamylamine (0.01-0.1 mg/kg; i.p.) neither the peripheral nicotinic receptor antagonist hexamethonium (0.01 and 0.1 mg/kg; i.p.) nor the muscarinic receptor antagonist atropine (2.5-10 mg/kg; i.p.), dose-dependently antagonized both the inhibition of withdrawal jumping as well as increase in MPE% which was produced by repeated nicotine administration (0.1 mg/kg; i.p.). On the other hand, 3 days of solely nicotine treatment resulted in significant jumping behavior precipitated by naloxone after single morphine injection on the test day. The data suggests that the inhibitory effect of nicotine on the morphine tolerance and dependence is mediated by central nicotinic receptors and there is a cross-dependence between nicotine and morphine.     

Using quadratic inference functions to determine the factors associated with obesity: findings from the STEPS Survey in Iran

PurposeThe last study that had a representative sample of the Iranian population and examined the association between sociodemographic and lifestyle factors with obesity used data from the 1999 to 2000 National Health Survey in Iran. Concern about the increased prevalence of obesity has heightened interest in the association between varieties of these factors with obesity among Iranian households.MethodsData (20,917 adults) were taken from the 2009 STEPwise approach to Surveillance survey in Iran that was conducted under the supervision of World Health Organization. Using quadratic inference function, we evaluated the relation of age, sex, physical activity, serving of fruit and vegetable, employment status, smoking, and place of residence with obesity.ResultsUsing 20–30 years as the reference group, the obesity odds ratios (ORs) were 2.48, 3.79, 3.52, and 3.15 for ages 30–40, 40–50, 50–60, and 60+ years, respectively. Obesity OR for female was 2.63, compared with male. Obesity ORs for smokers and ex-smokers were 0.64 and 1.18, respectively, compared with nonsmokers. Among Iranian adult, obesity ORs for the moderate and vigorous physical activity were 0.99 and 0.90, respectively, compared with low level. The estimated odds of obesity were 46% higher for rural adults. Obesity ORs for public and private employed were 0.79 and 0.76, respectively, compared with unemployed.ConclusionsOur results may provide better insights of the factors associated with obesity and can be used as a basis to reinforce health programs to prevent obesity in Iran.     

Determination of heavy metals in albumen of hen eggs from the Markazi Province (Iran) using ICP-OES technique

Increase of distribution of environmental contaminants such as heavy metals have been caused the knowledge of the safety and hygiene of food is very important, especially eggs, because of its role in the daily diet. There are very few studies about the investigation of the heavy metal contents in egg-white. In this study, six heavy metals include Aluminium (Al), Arsenic (As), Lead (Pb), Cadmium (Cd), Mercury (Hg), Antimony (Sb) in egg-white from 32 industrial poultry farms were investigated, by ICP-OES. All the samples were collected in all area of Markazi Province, Iran in autumn 2013. The mean concentrations of heavy metals in egg-white as follows: 0.119 for Al, 0.785 for As, 0.750 for Pb, 0.249 for Cd, 0.270 for Hg and 0.186?mg/kg for Sb. Also, the concentration of the some heavy metals were higher than maximum allowable concentration that probably it is associated to use pesticides and activities of industrial factories around the poultry farms.     

Impact of Premorbid Malnutrition and Dysphagia on Ischemic Stroke Outcome in Elderly Patients: A Community-Based Study

Objective: The present study was performed to assess nutritional status and its relationship with clinical outcomes in elderly stroke patients.

Method: In this cross-sectional study, 253 stroke patients were studied. Mini Nutritional Assessment (MNA) was used to assign patients to three groups: malnourished, at risk of malnutrition, and well nourished. Northwestern Dysphagia Patient Check Sheet was administered to all patients. Anthropometric measures, including body mass index (BMI), calf circumferences (CC), mid-arm circumferences (MAC), and triceps skinfold thickness were brought out. In addition, National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and biochemical tests were performed.

Results: Of 253 patients, 34.4% were malnourished, 42.3% were at risk of malnutrition, and 23.3% were well nourished. The malnourished patients had significantly lower BMI, CC, and MAC (p?<?0.05). The levels of albumin and high-sensitivity C-reactive protein were significantly different among the groups (p?<?0.001). The admission and 3-month follow-up mRS scores, as well as dysphagia, were significantly higher in the malnourished patients and those at risk of malnutrition (p?<?0.001). In addition, mRS scores at admission and 3-month follow-up scores, as well as the length of hospital stay (LOS), were significantly correlated with MNA score, dysphagia, BMI, CC, MAC, albumin, and high-sensitivity C-reactive protein (p?<?0.05). Significant unadjusted associations were observed among MNA scores, BMI, CC, MAC, dysphagia scores, NIHSS scores, length of hospital stay (LOS), albumin, hs-C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) with a poor outcome. With a multivariate logistic regression analysis, NIHSS scores and MNA scores remained significantly associated with the poor outcome in patients with ischemic stroke.

Conclusions: The findings of the present study underline the importance of nutritional status in elderly stroke patients.     

Topical antiglaucoma medications and lacrimal drainage system obstruction

PURPOSE: To evaluate the effect of topical antiglaucoma medications on the lacrimal drainage system. METHODS: In a prospective controlled blind observational case series, 627 eyes of 384 patients (219 males, 165 females) were screened. Data recording (demographics and history taking), allocation in case (on topical antiglaucoma medications) and control (no glaucoma) groups, and examinations (eye examination and dye disappearance test) were performed by a senior ophthalmology resident. Exclusion criteria were epiphora prior to onset of treatment with topical antiglaucoma medication (only for case group), history of long-term use of topical medications (other than antiglaucoma medications in the case group), and previous ocular and periocular disorders. Diagnostic probing and irrigation of the lacrimal drainage system were performed by an oculoplastic surgeon masked to a patient's status as case or control. RESULTS: After exclusion, there were 130 eyes from 98 patients and 280 eyes from 178 patients in the case and control groups, respectively. Case and control groups were matched. There was significantly more lacrimal drainage system obstruction in the case group (26 of 130, 20%) than in the control group (24 of 280, 8.57%) (p = 0.002). Upper lacrimal drainage system obstruction was significantly more in the case group (p = 0.018). Increasing age was associated with significantly more obstruction in the control group only (p = 0.029). Statistically significant obstruction was found in the patients taking timolol + dorzolamide (p = 0.021) and timolol + dorzolamide + pilocarpine (p = 0.017) with a duration of 2 weeks to 156 months. CONCLUSION: Patients taking a combination of topical antiglaucoma medications showed significantly increased risk of developing lacrimal drainage system obstruction. Both total and upper obstruction was significantly more frequent in patients on topical antiglaucoma medications.     

Synthesis with improved yield and study on the analgesic effect of 2-hydroxyphencyclidine

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of its derivatives have been synthesized and their biological properties were studied. Since a hydroxyl group has been added to the position 2 of the cyclohexane ring of PCP, this compound would be more hydrophilic than PCP. This compound was synthesized using a different and improved method with a higher yield. Its analgesic effect was studied using the tail-flick test on rats and was compared with that of ketamine (CAS 1867-66-9). The results showed that 2-hydroxyphencyclidine can increase tail-flick latencies as compared to the control group and indicate that the maximum analgesic effect of this compound occurs 2-5 min after its injection while the effect of ketamine is observed 10-25 min after injection.     

Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty

In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2–4 times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.     

The effects of fenugreek seed extract supplementation in patients with Alzheimer's disease: A randomized,double-blind,placebo-controlled trial

The aim of the current randomized control trial (RCT) study was to investigate the effects of fenugreek seed extract on memory, depression, quality of life, blood pressure, and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in adult AD patients. This randomized clinical trial was conducted in geriatric homes in Iran. The study participants included 82 AD patients with mild-to-moderate memory deficit. Patients in the intervention group received 5 cc of fenugreek seed extract for 4 months and subjects in the control group received a placebo. Memory, depression, quality of life, and BP levels, as well as serum MDA and TAC, were assessed before and after the intervention. There was a significant increase in serum levels of TAC (p < 0.001) and a reduction in serum MDA status (p < 0.001) after 4 months of fenugreek seed extract supplementation. In addition, increasing levels of memory (p < 0.001) and quality of life (p < 0.001), as well as reduction of depression (p = 0.002), systolic BP (p < 0.001), and diastolic BP (p < 0.001) levels were detected in the intervention group compared with baseline. Fenugreek seed extract supplementation in AD patients shows promising positive effects on memory, quality of life, BP, and selective oxidative indices levels.