New indolinone 1, 2, 3-triazole derivatives: Design, synthesis and anti-Alzheimer activity evaluation

Novel 1,2,3-triazole indolinone derivatives have been synthesized. All the titled compounds were characterized by 1H NMR, 13C NMR, MS and IR spectral data. The in vitro AChE and BChE inhibitory activity of all the compounds were evaluated.  Introduction: Alzheimer disease is the most frequent cause of dementia, which is very common in elder population with high morbidity. Treatment of this disease is one of the most promising targets in medicinal chemistry researches. Design and synthesis of novel 1,2,3 diazole indolinone derivatives as cholinesterase inhibitor (ChEI), are investigated in this study. Indolinone derivatives with 1,2,3-triazole moiety have been recently reported as potential AChE and BuChE inhibitors. There is also, a growing interest in evaluating the biological activity of these compounds and their derivatives to investigate their role in the prevention of neurodegenerative diseases. Methods and Results: The target compounds were prepared via the 1-methyl-3-((prop-2-yn-1-yloxy)imino)indolin-2-one as an intermediate in click reaction with substituted benzyl halides in water and DMF as solvent in room temperature. All the synthesized compounds were characterized by 1H NMR, 13C NMR, MS and IR spectral data. The in vitro AChE and BuChE inhibitory activity of all the compounds were evaluated. Conclusions: In conclusion, various novel 1,2,3-triazole indolinone derivatives were designed, synthesized, and evaluated against AChE and BChE. All these results clearly confirmed the efficacy of the corresponding compounds for further drug discovery developments

Cytotoxicity of Two Gypsophila Species to Human Breast Adenocarcinoma (MCF-7)

Introduction: Cancer is known as the second cause of death worldwide which results in serious problems in human life. It is developed by uncontrolled growth of a cell or a group of cells. Caryophyllaceae is a large family which has been reported to possess cytotoxic species and in the present study, the cytotoxic activity of two plants from this family has been evaluated. Methods and Results: Dried powder of Gypsophila bicolor (Freyn & Sint.) Grossh and Gypsophila ruscifolia Boiss. aerial parts were extracted with methanol 80% by maceration method (10 g). For fractionation, 30 g of the dried powder of both species was macerated with petroleum ether at room temperature. After 24 hours, the mixture was filtered and the plant residues were extracted with chloroform and methanol successively through the same process. Then they were concentrated using a rotary evaporator apparatus. The cytotoxic activity was evaluated against MCF-7 (human breast adenocarcinoma), A-549 (non-small cell lung carcinoma) and AGO-1522 (human fibroblast) cell lines using MTT assay. The chloroform fractions of both Gypsophila species showed cytotoxic effects against MCF-7 cells with IC50 value <100 μg/mL. None of the extracts or fractions demonstrated cytotoxicity to A-549 or AGO-1522 cells up to the tested concentrations. Conclusions: The selective toxicity of the chloroform fractions of the species only to the MCF-7 cell line suggested that Gypsophila bicolor and G. ruscifolia could be proper candidates for further studies in the field of cancer researches

Public awareness, education and participation in solid waste management in Tehran

Background and objectives: Public participation in is vital in optimal management of municipal solid waste. Thepublic awareness, education and empowerment are the pre-requisites for the use of this potential. In this study, public awareness, education and participation in solid waste management were studied among a community samplein Tehran-2012. Materials and methods: The overall situation of solid waste management in Tehran was firstly assessed. Study participants were, thereafter, sampled from households from the 22 urban districts in the city of Tehran. A questionnaire was prepared and applied to 500 householders to estimate the public awareness, education and participation in solid waste management.Results: The results of this study showed that only about one-third of people had appropriate awareness in the field of solid waste management. The overall status of public education in solid waste management was also insufficient, so that 86% of people were trained at level of poor or very poor. Public participation in solid waste management was variable in different fields. Public participation in simple activities such as avoiding waste spillage and splurge in public places and scheduled transfer of collected waste to public containers was relatively good; and in waste reduction and separation of recyclable components was moderate. Furthermore, separation of hazardous waste and household composting were not done due to lack of required facilities and training.Conclusion: The present study revealed that public education and required facilities should be supplied and expanded in order to increase public participation in solid waste management. Repetition and continuity of education programs, face to face training, and greater use of television and Internet media are emphasized.Keywords: Public education, Public participation, Municipal solid waste, Tehran Cit

Improved yeast delivery of fluconazole with a nanostructured lipid carrier system

Despite the growing trends in the number of patients at risk for invasive fungal infections, management with current antifungal agents results in complications due to changes in the epidemiology and drug susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the optimal formulation on a large number of Candida species. The morphology of the obtained nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 126.4 ± 15.2 nm, −35.1 ± 3.0 mV, and 93.6 ± 3.5%, respectively. The drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at the initial stage followed by sustained release over 24 h. Using a new formulation of fluconazole led to a significant decrease in MICs for all Candida groups (P < 0.05). Furthermore, C. albicans isolates showed more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis (P < 0.05). The MIC50 drug concentration was obtained as 0.0625, 0.031 and 0.25 μg/ml for fluconazole-resistant strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery system which can be used as part of a strategy to improve the antifungal activity of fluconazole against various Candida strains with different susceptibilities to conventional formulations of fluconazole was evaluated

Burden of Drug and Alcohol Use Disorders in Iran: Findings from the Global Burden of Disease Study 2010

Background: Due to its specific socio-cultural and geographical situation, Iran has a major public health problem in terms of drug and alcohol use. The aim of this study is to report and critique the burden of drug and alcohol use disorders in Iran, and to compare these measurements with similar findings. Methods: This study used data for Iran for the years 1990, 2005, and 2010 derived from the Global Burden of Disease study conducted by the Institute for Health Metrics and Evaluation (IHME) in 2010. The burden of drug and alcohol use disorders was evaluated in terms of disability adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Results: All rates were reported per 100,000 individuals. Death rates attributed to drug and alcohol use disorders were 7.7 and 0.16 for men, and 0.62 and 0.02 for women, respectively. YLL rates regarding drug use disorders were 351.8 and 24.8 for men and women, while these figures were 5.8 and 1.0 for alcohol use disorders for men and women, respectively. YLD rates of drug use disorders were 452.6 for men and 202.1 for women, and 105.8 for men and 23.7 for women for alcohol use disorders. DALY rates attributed to drug use disorders were 804.5 for men and 227 for women, while these rates were 111.7 for men and 24.7 for women, related to alcohol use disorders. Conclusions: Similar to the cases in many other countries, the burden of both drug and alcohol use disorders is higher for men than women in Iran. Although prevention policies and programs for drug and alcohol use are required for both genders, the need for drug and alcohol use intervention seems more urgent for men in Iran

National and sub-national HIV/AIDS-related mortality in Iran, 1990–2015: a population-based modeling study

Surveillance of HIV/AIDS mortality is crucial to evaluate a country’s response to the disease. With a modified estimation approach, this study aimed to provide more accurate estimates on deaths due to HIV/AIDS in Iran from 1990 to 2015 at national and sub-national levels. Using a comprehensive data set, death registration incompleteness and misclassification were addressed by demographical and statistical methods. Trends of mortality due to HIV/AIDS at national and sub-national levels were estimated by applying a set of models. A total of 474 men (95% uncertainty interval [UI]: 175–1332) and 256 women (95% UI: 36–1871) died due to HIV/AIDS in 2015 in Iran. Peaked in 1995, HIV/AIDS-related mortality has steadily declined among both genders. Mortality rates were remarkably higher among men than women during the period studied. At the sub-national level, the highest and the lowest annual percent change were found at 10.97 and −1.36% for women, and 4.04 and −3.47% for men, respectively. The findings of our study (731 deaths) were remarkably lower than the Joint United Nations Programme on HIV and AIDS (4000) but higher than Global Burden of Disease (339) estimates in 2015. The overall decrease in mortality due to HIV/AIDS may be attributed to the increasing burden of noncommunicable diseases; however, the role of the national and international organizations to fight HIV/AIDS should not be overlooked. To decrease HIV/AIDS mortality and to achieve international goals, evidence-based action is required. To fast-track targets, the priority must be to prevent infection, promote early diagnosis, provide access to treatment, and to ensure treatment adherence among patients. Keywords HIV, AIDS, mortality, estimation, modeling, Ira

The study of chromosomal abnormalities and heteromorphism in couples with 2 or 3 recurrent abortions in Shahid Beheshti Hospital of Hamedan

Background: Different studies show that chromosomal balance translocation in the parents can cause recurrent spontaneous abortions. Incidence of chromosomal translocation abnormalities in couples with repeated abortions is from 0% to 31%. Objective: The purpose of this research was studying the presence or absence of chromosomal abnormalities and heteromorphism in couples with recurrent abortions and also the role of this anomaly in the abortions. Materials and Methods: This study is a cross sectional descriptive study which have investigated 75 couples who had three abortions or more, and 65 couples who had two abortions that referred by gynecologist to the lab of Beheshti Hospital in Hamedan for cytogenetical investigation. Also 40 healthy individuals without history of abortion investigated as control group.GTG bonding technique (staining banding with gymsa and trypsin) is used in this study. Results: Frequency of chromosomal abnormalities and heteromorphism among couples with three or more abortions were reported respectively 5.3% and 9.3%. This frequency in couples with two abortions was respectively 3.07%and 6.15%. The frequency of chromosomal heteromorphism in control group was 7.5% and no chromosomal abnormalities were observed in them. Conclusion: This study shows that chromosomal abnormality can be one reason of recurrent spontaneous abortions and more abortion increases the probability of this anomaly. Also, existence of chromosomal heteromorphism in the general population without clinical abortion symptoms shows that chromosomal heteromorphism cannot be the reason of these spontaneous abortions

In silico prediction and in vitro validation of the effect of pH on adhesive behaviour of the fused CsgA-MFP3 protein

Abstract Recombinant production of mussel foot proteins among marine-inspired proteinaceous adhesive materials has been attracted high attention for medical applications, due to their exceptional versatility potential of hierarchically arranged nanostructures. Various biochemical and proteinous factors such as amyloid CsgA curli protein have been used as a synergistic factor to enhance the constancy of obtained bio-adhesion but their mechanistic interactions have not yet been deeply investigated widely in different pH conditions. To this end, the present study has first sought to assess molecular simulation and prediction by using RosettaFold to predict the 3-dimensional structure of the fused CsgA subunit and the MFP3 protein followed by in vitro verification. It was developed an ensemble of quantitative structure-activity relationship models relying on simulations according to the surface area and molecular weight values of the fused proteins in acidic to basic situations using PlayMolecule (protein preparation app for MD simulations) online databases followed by molecular dynamic simulation at different pHs. It was found that acidic conditions positively affect adhesive strength throughout the chimeric structure based on comparative structure-based analyses along with those obtained in prevailing literature. Atomic force microscopy analysis was confirmed obtained in silico data which showed enhanced adhesive properties of fused protein after self-assembly in low pH conditions. In conclusion, the augmented model for reactivity predictions not only unravels the performance and explain ability of the adhesive proteins but in turn paves the way for the decision-making process for chimeric subunits modifications needed for future industrial production

Time to overcome fluconazole resistant Candida isolates: solid lipid nanoparticles as a novel antifungal drug delivery system

Antifungal therapy results in complications in management due to changes in the patterns of epidemiology and drug susceptibility of invasive fungal infections. In this study, we prepared fluconazole-loaded solid lipid nanoparticles (FLZ-SLNs) and investigated the efficacy of the optimal formulation on fluconazole (FLZ)-resistant strains of several Candida species. FLZ-SLN was produced using probe ultrasonication techniques. The morphology of the obtained SLNs was characterized by field emission scanning electron microscopy. The minimum inhibitory concentrations for the new formulations against fluconazole-resistant strains of Candida were investigated using CLSI document M27-A3. The FLZ-SLNs presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 84.8 nm, -25 mV and 89.6%, respectively. The drug release from FLZ-SLNs exhibited burst release behaviour at the initial stage (the first 30 min) followed by a sustained release over 24 h FLZ-resistant yeast strains behaved as susceptible strains after treatment with FLZ-SLNs (≤8 μg/ml). The MIC50 drug concentrations were 2 μg/ml, 1 μg/ml and 2 μg/ml for FLZ-resistant strains of Candida albicans, Candida parapsilosis and Candida glabrata, respectively. In this study, we evaluated novel delivery systems for combating Candida strains that exhibit low susceptibility against the conventional formulation of FLZ as a first-line treatmen