Effect of oral naltrexone on pruritus in cholestatic patients

AIM:To determine the efficacy and potential complica-tions of oral naltrexone used in the treatment of pruritusin cholestatic patients and to compare them with otherstudies.METHODS:Thirty-four enrolled cholestatic patientscomplaining of pruritus were studied.In the initial phase,pruritus scores during day and night were evaluated.Sub-sequently,patients were given a placebo for one weekfollowed by naltrexone for one week.In each therapeuticcourse(placebo or naltrexone)day and night pruritusscores were distinguished by a visual analogue scale(VAS)system and recorded in patients'questionnaires.RESULTS:Both naltrexone and placebo decreased VASscores significantly.Naltrexone was more effective thanplacebo in decreasing VAS scores.Both day and nightscores of pruritus decreased by half of the value priorto therapy in thirteen patients(38%).Daytime pruritusimproved completely in two patients(5.9%),but no im-provement in the nighttime values was observed in anypatient.Sixteen patients(47%)suffered from naltrexonecomplications,eleven(32%)of them were related to itswithdrawal.Complications were often mild.In the caseof withdrawal,the complication was transient(withinthe first 24-28 h of therapy)and self-limited.We had tocease the drug in two cases(5.9%)because of severewithdrawal symptoms. CONCLUSION:Naltrexone can be used in the treatmentof pruritus in cholestatic patients and is a safe drugshowing few,mild and self-limited complications.     

In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers

Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis. Cytotoxic effects of six compounds of 4H-chromene-3-carbonitrile were evaluated against five tumor cell lines, with the help of colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Compound 4 showed significant cytotoxic activity and was selected for conjugation with the synthesized gold nanoparticles by aspartic acid. Also, we evaluated apoptosis induction capacity of the selected compound with the help of fluorescent dyes and DNA fragmentation. The result showed that the conjugated and non-conjugated forms of compound 4 were effective in inducing apoptosis and conjugated one had more efficiency and reduced the effective dose. Also, molecular modeling experiments involving compound 4 and colchicine binding site of tubulin dimer showed several strong hydrogen bonds and hydrophobic interactions to many important amino acid residues and GTP.     

Mg2+ protects adult beating cardiomyocytes against ischaemia

Although Mg2+ reduces infarct size in whole heart models of ischaemia/reperfusion, the cardioprotective effect of Mg2+ at the cellular level is still a controversial issue. Therefore, we tested whether Mg2+ protects cardiomyocytes against ischaemia. To accomplish this aim we used an experimental model of ischaemia that utilises single beating adult cardiomyocytes in which oxygen tension is tightly regulated without the use of oxygen scavengers or metabolic inhibitors. Taking all these into consideration, this model is probably closer to in vivo conditions than the majority of previously published cellular models of ischaemia. We found that the addition of extracellular Mg2+ (8 mM) increased the survival of cells exposed to ischaemia. As sarcolemma and mitochondria are end-effectors of cardioprotective signalling, we examined whether Mg2+ regulates sarcolemmal and mitochondrial events. Mg2+ (8 mM) did not affect the whole cell K+ current as revealed by patch clamp electrophysiology. Experiments with laser confocal microscopy and the mitochondrial membrane potential-sensitive dye, JC-1, showed that Mg2+ (8 mM) did not affect ischaemia-induced mitochondrial membrane depolarisation. However, a significantly lower JC-1 ratio was required to kill cells under control conditions than cells treated with Mg2+ (8 mM). Based on the obtained data, we conclude that Mg2+ protects single beating cardiomyocytes against ischaemia by increasing cellular resistance to the consequences of mitochondrial membrane depolarisation in the cytosol.     

Health literacy among Iranian patients with type 2 diabetes: A systematic review and meta-analysis

Health literacy is one of the most important determinants of health. Limited health literacy can leads to reduced adherence to treatment, repeated hospitalizations, and increased diseases complications. Several studies on health literacy among Iranian patients with type 2 diabetes have reported different prevalences of health literacy. The present study is aimed to determine through a systematic review and meta-analysis the prevalence of adequate health literacy in the Iranian population. A total of 8 articles that met the inclusion criteria, published from inception until December 2018, were collected. Articles were searched using the following keywords and their possible combinations: Health Literacy, Illiteracy, Functional Health Literacy, Diabetes, Diabetes Mellitus, and Iran. The data were analyzed using meta-analysis and the random-effects model was used to obtain a pooled prevalence estimate along with its 95% confidence interval. Heterogeneity among the studies was assessed using the I² statistic. Analyses were performed using STATA software, version 12. The overall prevalences of inadequate and borderline health literacy among Iranian patients with type 2 diabetes were 43.47% (95% CI: 31–55.95) and 26.34% (95% CI: 19.49–33.19), respectively. In addition, the prevalence of adequate health literacy among patients with type 2 diabetes was 29.72% (95% CI: 22.79–36.64). There was no significant relationship between health literacy with year of publication, sample size, and patients’ age. Inadequate health literacy is high (43.5%) among Iranian patients with type 2 diabetes. This makes it necessary to provide interventions aimed at improving their heath literacy which will reduce hospitalizations and diseases complications.     

Preconditioning with acute and chronic lithium administration reduces ischemia/reperfusion injury mediated by cyclooxygenase not nitric oxide synthase pathway in isolated rat heart

The aim of the present study was to determine whether various glutamate receptor antagonists could affect ethanol withdrawal-induced anxiety-like behavior measured in the elevated plus-maze test in rats. In our study, memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, did not show any effect on ethanol withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate5 (mGlu5) receptor antagonist), at a dose of 400 mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and open arms entries. Antagonists of group I mGlu receptors, such as MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, mGlu5 receptor) or EMQMCM (3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate, mGlu1 receptor), caused similar effects to acamprosate. In contrast to acamprosate and MTEP, EMQMCM (5 mg/kg) elevated the ethanol withdrawal-induced decrease in locomotion. When given alone to the saline-treated group, EMQMCM indicated anxiolytic-like effect. Our results imply a crucial role of mGlu5 receptor in an anxiety-like effect of ethanol withdrawal because MTEP (a selective mGlu5 receptor antagonist) and acamprosate (which also indirectly inhibits mGlu5 receptor) attenuated ethanol withdrawal anxiety-like behavior without influence on ethanol withdrawal hypolocomotion and did not show any effect in the saline-treated groups. However, difference in anxiolytic-like potency between both these group I mGlu receptors antagonists may be due to the recent experimental design. Therefore, taking into account a positive correlation between ethanol withdrawal-induced anxiety and relapse to ethanol drinking, our results suggest that mGlu receptor antagonists of group I (similarly to acamprosate) could prevent relapse to drinking and, therefore they might be useful in therapy of alcoholism.     

The response of circulating omentin-1 concentration to 16-week exercise training in male children with obesity

Objectives: The purpose of the present study was to investigate the effects of the 16-week exercise training program on serum omentin-1 in relation to change in insulin resistance in obese male children.

Methods: Thirty-two obese male children, aged 9–12 years, were randomly assigned into Exercise Group (ExG; n = 16) and Control Group (CG; n = 16). ExG participated in a 16-week exercise training program which combined various forms of aerobic activities and resistance training. Body composition, body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment estimate of insulin resistance (HOMA2-IR), blood lipids and serum omentin-1 were assessed before and after 16 weeks of training.

Results: Exercise training significantly decreased body mass (7.5%), BMI (7.6%), WC (4.3%), body fat % (15%), fasting insulin (18.5%), total cholesterol (TC) (5.4%), low-density lipoprotein cholesterol (LDL-C) (17%) and triglyceride (TG) (7.4%) compared to CG. Between-groups comparison showed a considerable exercise-induced upregulation in omentin-1 (ES = 89; P < 0.05) levels. Furthermore, in ExG serum omentin-1 levels were significantly increased from 24.5 ± 8.4 to 35.9 ± 9.3 ng/ml (45%; P < 0.001) after the training program, which was accompanied with significantly decreased fasting insulin (P < 0.001). The changes in omentin-1 concentrations correlated with the changes in BMI (r = ?0.67, P < 0.001), WC (r = ?0.62, P = 0.002), body fat % (r = ?0.50, P = 0.004), insulin (r = ?0.65, P = 0.001), HOMA2-IR (r = ?0.60, P = 0.004), TC (r = ?0.53, P = 0.004) and LDL-C (r = ?0.51, P = 0.004) in ExG. BMI (β = ?0.50, P = 0.009) and fasting insulin (β = ?0.54, P = 0.006) changes were found to be independent predictors of omentin-1 increment in multiple regression analysis.

Conclusion: Exercise training resulted in a significant increase in serum omentin-1 concentrations in children with obesity. The ?ndings suggest that exercise-induced changes in omentin-1 may be associated with the bene?cial effects of exercise on reduced insulin and weight lost.     

“Evaluation of a Very Low-Cost and Simple Teleradiology Technique”

This paper describes and analyzes a proposed solution of fundamental limitative factor of teleradiology to overcome the teleradiology usages problems in underdeveloped and developing countries. The goal is to achieve a very simple and cost-efficient way to take advantage of teleradiology in anywhere even in remote and rural areas. To meet the goal of this study, the following methodology which is consists of two main procedures was done: (1) Using a digital camera in order to provide a digital image from radiographs. (2) Using an image compression tool in order to compress digital images. The results showed that there is no significant difference between digital images (non-compress and compress images) and radiographic films. Also, there was a logic relationship between the diagnostic quality and diagnostic accuracy. Since the maximum percent of diagnostic accuracy can be seen among “Good” quality images and the minimum to was related “Poor”. The results of our study indicate that a digital camera could be utilized to capture digital images from radiographic films of chest x-ray. To reduce the size of digital images, a lossy compression technique could be applied at compression percent of 50 or less without any significant differences. The compressed images can be sent easily by email to other places for consultation and also they can be stored with a smaller size.     

“Finding a Space for Me Outside the Stereotypes”: Community Engagement in Policy and Research to Foster Canadian Racialised Immigrant Women’s Mental Health and Well-Being

Racialised immigrant women face many challenges with resettlement with potential impacts on their mental health and well-being. Recent community-based research (CBR) and associated knowledge translation/exchange (KTE) activities with racialised immigrant women in Toronto, Canada, suggest that activism can promote their mental health and well-being. In this paper, the researchers describe community engagement processes in the CBR that included a stakeholder Think Tank with communities, researchers and service providers in settlement and mental health sectors to create an action plan based on the research. Using a feminist post-colonial lens to analyse the Think Tank data yielded research, policy and program strategies aligned with principles such as building on individuals’ and communities’ strengths and foregrounding gender and racialisation in strategies that can enhance racialised immigrant women’s capacities to take action and overcome barriers. Research, policy and program implications for comprehensive strategies that support health equity, thereby promoting their mental health and well-being, are considered.     

Expression pattern of ATM and cyclin D1 in ductal carcinoma, normal adjacent and normal breast tissues of Iranian breast cancer patients

ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. Cyclin D1 acts in regulating the G1 phase of the cell cycle. Experimental and clinical studies suggest them to be involved in transformation and tumour progression. To elucidate the role of ATM and cyclin D1 expression in sporadic breast cancer, we investigated the possible link between their RNA expression levels in ductal carcinoma and normal adjacent versus normal breast tissues measured by Taqman real-time PCR in 119 breast tissues. Results showed that cyclin D1 over-expressed in 51.4% of breast tumours, whereas ATM expression was down regulated in 55% of breast tumours compared to both normal adjacent and normal controls (P ≤ 0.01). Cyclin D1 expression in adjacent normal and normal tissues was not significantly differed, whereas ATM expression in normal adjacent was lower than normal control (P ≤ 0.01). Over-expression of cyclin D1 correlated with ER(+) and/or PR(+) (oestrogen/progesterone receptor) status, whereas it mostly under-expressed in HER2(+) (human epidermal growth factor 2) tumours. ATM under-expression was more observed in triple-negative tumours (ER(-), PR(-) and HER2(-)). Our results indicated that reduced expression of the ATM and aberrant cyclin D1 expressions may contribute to the development and/or malignant progression of breast carcinomas also the latter could be involved in the regulation of hormone sensitivity associated with ER and PR.     

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using β-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases.Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment.