مجله دانشگاه علوم پزشکی مازندران
پیاپی 151 (امرداد 1396)

Background and Cyclophosphamide (CP) is used as an anti-cancer and immunosuppressive agent and it is accompanied with severe cardiotoxicity and anemia. Atorvastatin (ATV) is a widely used medication in hypercholesterolemia that has antioxidant and anti-inflammatory properties at low dose. The aim of this study was to investigate the protective effect of ATV on cyclophosphamide-induced cardiotoxicity and hematotoxicity in rats.
Thirty two rats were randomly divided into four groups as following: control group that received normal saline; CP group that received CP intraperitonealy single dose (150 mg/kg); the ATV group that were treated through gavage (10 mg/kg) for 10 days; and ATV CP that received ATV five days before and five days after CP treatment. The animals were killed three days after the last treatment.
Administration of CP caused heart damage through increased activity of cardiac marker enzymes, such as CK-MB and LDH. Histological evaluation of heart tissue showed interstitial edema, necrosis, hemorrhage, congestion, and vacuole around the nucleus. The number of red and white blood cells, platelets, hemoglobin and hematocrit significantly decreased in the group that received CP. ATV significantly reduced the amount of oxidative stress enzymatic activity and heart tissue damage and preserved blood cell counts induced by CP.
These findings prove the protective role of ATV on CP-induced cardiotoxicity and hematotoxicity in mice.

Background and Exosome as drug delivery system is a novel and smart methodology enabling delivery of exosome cargo into specific tissue. This aim could be accessed by manipulation of exosome producer cells for expression of specific transmembrane-anchored ligand on exosomes surface. Accordingly, Lysosomal Associated Membrane Protein (LAMP) is one of the best choices for anchoring and chimerization with any ligand for this propose. In current study we designed a lentiviral vector which carries a chimeric gene for expression of LAMP2-DARPin in exosome to attach to HER2 on cancer cell surfaces.
RNA was extracted from mouse skeletal muscle, then, cDNA was produced by RT-PCR and CDS of LAMP2b gene was amplified by specific primers. Two restriction sites were introduced between signal and mature peptide sequence by SOEing PCR. This fragment was inserted into pLEX-MCS lentiviral vector and cloned in E.coli. DARPin gene was designed, optimized and synthesized, then cloned between signal and mature peptide. Positive clone was confirmed by colony PCR and DNA sequencing.
Electrophoresis of SOEing PCR product showed 1290 bp DNA fragment of LAMP2B CDS. Insertion of LAMP2 in pLEX vector was confirmed by electrophoresis and sequencing. Accordingly, DARPins was synthesized and inserted into pLEX-LAMP vector, electrophoresis and sequencing of purified plasmid from positive clone confirmed the insertion of DARPins into pLEX-LAMP vector.
We generated two lentiviral vectors, pLEX-LAMP for expression of any ligands in exosome surface and pLEX-LAMP DARPin for expression of DARPin on exosome surface for HER2 targeting.

Background and Tumors are one of the most important threats to human life and improving the drugs used in their treatment is always necessary. Isatin is found in many plants and also synthesized through different methods. Many studies have been done on Isatin ring, including the construction of Dibromoisatin derivatives that exhibit anti-cancer effects. The aim of this study was to determine the cytotoxic effects of Dibromoisatin derivatives on cervical and liver cancer cells.
In this study, 10 Dibromoisatin derivative made at concentrations of 1, 50, 100, 200, and 400 µg/mL were tested against cervical (HeLa) and liver cancer cell lines (HepG2). The cell viability was assessed by MTT assay and the IC50 value was calculated in PRISM software.
Comparing the cytotoxic effects of Dibromoisatin derivatives showed that the highest cytotoxic effects in both cell lines was detected in composition No. 9 with IC50 value of HepG2= 1.194 and IC50 value of HeLa= 0.025.
These derivatives were more effective against liver cancer cells and some Dibromoisatin derivatives were found to have high toxicity against cancer cells, therefore, they could be of great benefit in improving the drugs used in chemotherapy.

Background and Breast cancer is the most common cancer in woman. About one million new cases are diagnosed every year worldwide. Many researchers are interested in anti-cancer effects of natural products. In this research, cytotoxic effects of Crocus caspius extract against breast cancer and normal cell lines were investigated and total phenols and flavonoids were also determined.
Flowers of Crocus caspius were collected from Neka in Mazandaran province, Iran, in autumn 2014. The powder of dried flowers were macerated with 80% methanol, three times every 48 hr. The methanol extract was concentrated under reduced pressure. Cell viability was determined using MTT and trypan blue assay was done on breast carcinoma cell lines (MCF7, 4T1, and SKBR3) and Swiss mouse embryo fibroblast (NIH/3T3) as normal cell lines. Various concentrations (1, 50, 100, 500, and 1000 µg/ml) of the extract and positive control were examined for determination of IC50.
Crocus caspius extract showed no considerable cytotoxic effects against breast cancer and normal cell lines. Total phenolic and flavonoid contents of the extract were quite high; 238.25±4.35 mg GAE/g and 85.41±6.24 mg quercetin/g of dry extract, respectively.
These results indicated non toxicity of Crocus caspius extract. Further studies are needed to investigate the preventive effect of C.caspius extract against cancer according to its total phenolic and flavonoid contents.

Background and Plasmid-medicated quinolone resistance (PMQR) genes play an important role in resistance to quinolones. The aim of this study was to determine the frequency of PMQR genes in extended-spectrum β-lactamase-producing (ESBL) Escherichia coli.
This study was done on 240 isolates of E.­coli from urine samples of patients in Kermanshah, Iran. The susceptibility of isolates to selected antibiotics was tested using disc diffusion and broth microdilution methods. The isolates were screened for ESBL-producing phenotype by combined disc diffusion test. The qnrA, qnrB, qnrS, aac (6­')­-­Ib, and qepA genes were detected by PCR. All PCR products for aac­(6')­-Ib gene were digested by BtsCI for detection of aac­(6')­-Ib-cr variant. Data analysis was done using statistical methods.
Of 66 ESBL-producing isolates, 45 (68.1%) were resistant to ciprofloxacin and levofloxacin and 56 (84.8%) were found to be resistant to nalidixic acid. The qnrA, qnrB, qnrS, and qepA genes were detected in 28.7%, 40.9%, 4.5%, and 3% of the isolates, respectively. The aac­(6')­-Ib gene was found in 65.1% of the isolates amongst which 88.4% were aac­(6')­-Ib-cr variant.
Our results indicate a high prevalence of PMQR genes in ESBL-producing E.coli isolates in Kermanshah. A correlation was observed between resistance to beta-lactams and quinolones which may indicate the cotransfer of quinolone genes by plasmids carrying the ESBL. As a result, identifying E. coli strains with ESBL may indicate a high resistance to quinolones. So, before using quinolones, the screening test for ESBL is recommended to prevent the increasing resistance to this class of drugs.

Background and The main purpose of this study was determination of different genotypes and phenotypes of N-acetyltransferase 2 gene and its relationship with drug-induced liver injury among patients in Mazandaran province, Iran, which was done for the first time.
A total of 65 newly diagnosed unrelated pulmonary tuberculosis patients (47 men, 18 women) was enrolled in the study. A combination of polymerase chain reaction -restriction fragment length polymorphism method was used to investigate different allels of N-acetyltransferase-2. The patients were followed for occurrence of antituberculosis induced hepatotoxicity during the course of treatment. Relationship between N-acetyltransferase-2 phenotypes and antituberculosis induced hepatotoxicity was evaluated.
Frequency of slow, intermediate and fast acetylator genotypes in patients were 34%, 60% and 6%, respectively. Hepatotoxicity was diagnosed in 13.64% of slow acetylators, in 2.56% of intermediate acetylators and interestingly in none of the fast acetylators. The Chi-Square Test showed no significant difference between different acetylation phenotypes and risk of hepatotoxicity (P = 0.1086).
These results could improve treatment profile, prevent from drug-related adverse effects such as hepatotoxicty and lead to better outcomes in tuberculosis patients.

Background and Chitin is one of the main components of crustaceans’ exoskeleton. Chitosan is produced by deacetylation of chitin. Molecular weight and degree of deacetylation play important roles in biological activity of chitin, chitosan, and their derivatives. So far, various derivatives of chitin and chitosan are obtained. The purpose of this study was to prepare derivatives of chitin and chitosan derived from the shells of shrimp (Metapenaeus affinis) to compare their antibacterial properties.
By investigating different factors, the best condition was determined for extracting chitin and chitosan from the shell of Metapenaeus affinis. N-acetyl chitooligosaccharides and chitooligosaccharides oligomers were prepared through chemical hydrolysis of chitin and chitosan, respectively. The antimicrobial properties of four polymers obtained were investigated on four bacterial strains and compared with an emphasis on molecular weight and percentage of deacetylation
The amounts of ash, moisture, protein, and molecular weight of chitin was found to be more than those of chitosan. But, the degree of deacetylation of chitosan was much higher than that of chitin. The highest and lowest antibacterial activity was seen in chitooligomers and chitin, respectively. Chitin (somewhat) and chitosan showed bacteriostatic properties against most strains. But, the oligomers revealed bactericidal activity against most of the strains.
This study showed that a product with higher purity can be obtained by manipulating the extraction method (demineralization and deproteinization). Moreover, antibacterial activity is directly related to reduced molecular weight and increased percentage of deacetylation, so, oligomers showed more antibacterial properties.

Background and Medicinal plants have gained much interest in today’s world because they have fewer adverse effects compared to chemical drugs. Urtica dioica L could be used in treatment of some chronic diseases. This study aimed at investigating its treatment properties in vitro.
Different parts of the plant were collected and the extract was prepared using maceration and percolation. The antibacterial effects of the plant were identified using disk diffusion method. The MIC and MBC values were determined using dilution method against Listeria Monocytogenes (PTCC 1294), Staphylococcus aureus (ATCC 25923), Proteus vulgaris (ATCC 13315), Kellebsiella pneumoniae (PTCC 1053), and Candida albicans (ATCC 10231). The major components in the extract were identified by Gas Chromatography (GC). The extract consisted of 20 different combinations, including Neophytadiene (21.25%), Phthaleic acid (15.8%), phthalate Dibutyl (37.7%), maleate Bis (2-ethyl hexyl 32.6%), and 1,2 - Benzenedicarboxylic acid (62.7%). The amount of these compounds were higher in leaves.
The aqueous extract obtained from different organs of Urtica dioica L was found to have more antibacterial effect (the leaf and root at dilution of 5 mg /ml) compared to those of the alcoholic extract. In different dilutions, it also exhibited more antifungal effect on Candida albicans.
According to this study, Urtica dioica has antibacterial and antifungal properties, therefore, it could be used against a broad spectrum of microorganisms.

Background and Lung cancer is a public health problem worldwide. Identifying the epidemiological characteristics of involved patients can play an important role in designing analytical studies. The aim of this study was to identify the epidemiology of patients with lung cancer attending Tooba clinic and Imam Khomeini Hospital in Sari, Iran.
In this descriptive study, a sample size of 229 patients with lung cancer were chosen using census sampling. SPSS V22 was used for data analysis applying descriptive and analytic tests.
Of 229 patients, 74.2% were males. The mean ages of male and female patients were 63.4±12.6 and 64.6±12.01, respectively, indicating no significant difference between the two groups (P=0.534). The majority of samples (78.6%) had non-small-cell-lung cancer and the method of diagnosis was biopsy in 88.9%. The most and least common sites of involvement were the upper edge of the right lung (22.3%) and the upper lobe of the left lung (18.8%), respectively. Among the patients, 85.1% were in stage IV and chemotherapy was the main treatment in most of the patients (57%).
This study showed that men were more infected with lung cancer. We found that the average age of female patients was slightly more than that of male patients. Most of the patients were diagnosed with non-small cell lung carcinoma. The majority of patients were diagnosed at higher stages that were made at advanced and metastatic stages.

Background and Mindfulness is defined as particular targeted attention in present time that is free from prejudice and judgment. Diabetes mellitus is a chronic disease accompanied by different complications and persistent disabilities. The aim of this study was to determine the effectiveness of mindfulness on happiness, and level of blood sugar in diabetic patients.
A pretest-posttest design was used including an intervention group and a control group. The participants were 50 patients with type-2 diabetes attending Touba Endocrine Clinic in Sari, Iran. The training program consisted of 10 weekly sessions. Happiness was investigated in participants using the Oxford Happiness Inventory. The levels of glycosylated hemoglobin was recorded before and after the intervention.
There was a significant increase (r= 0.240, P= 0.002) in happiness in posttest (62.60 ± 8.40) compared to that in pretest (46.08 ± 7.16) in the experimental group. But no significant difference was found in the scores of the control group (P= 0.708). The mean blood glucose level showed a significant reduction in case group (r= 0.126, P= 0.000) but it was not significantly different in control group (P= 0.510). The mean glycosylated hemoglobin level in the control group did not change significantly, but it decreased significantly in experimental group (6.52±1.20) compared to pretest (7.57 ± 1.26) (r= 0.104, P= 0.005).
In current study, improvement in average of happiness score and the average of blood sugar level occurred due to mindfulness training.

Background and Increasing spread of dementia is one the consequences of aging. Due to the nature of the disease and dependence of involved patients, their caregivers might face mental health problems. Hence, evaluating family functioning can be a suitable tool for predicting family’s mental health. This research aimed at investigating the level of depression in caregivers and their relationship with family function.
In this correlational study, 150 family caregivers of the elderly suffering from dementia were recruited. They were selected from those attending the Iran Alzheimer's Association who met the study inclusion criteria, by sampling in 2015-2016. Depression in caregivers and their family function was measured through the Beck Depression Inventory II and family functioning McMaster. Data was analyzed using Pearson Correlation Coefficient, Analysis of Variance and Stepwise Multiple Linear Regression.
In current study about 22%, 21.3%, and 14.7% of the family caregivers had mild, moderate, and severe depression, respectively. Family function was poor in all aspects except for problem solving. Also, there was a significant negative relationship between all subscales of family functioning and depression (P According to the prevalence of depression syndrome in caregivers of patients with dementia and their relation to family functioning with depression, evaluating the dimensions of family functioning as one of the important indicators of Family Therapy and Education can improve such caregivers’ health.

Background and Family background is effective in incidence of unhealthy personality traits such as pathological narcissism. The aim of this study was to predict pathological narcissism according to family system and the mediating role of narcissistic wounds and perfectionism.
In a cross-sectional descriptive study, 477 high school girls in Qom, Iran were selected by convenience sampling in 2015-2016 academic year. Data was obtained by Family Dynamic Environment Scale (FDES), Childhood Recollection Scale (CRS), Narcissistic Injury Scale (NIS), Clinical Perfectionism Questionnaire (CPQ), and Maladaptive Covert Narcissism Scale (MCNS). Data was then analyzed using structural equation modeling by LISREL-8.53 Software. Moreover, descriptive statistics were analyzed using SPSS-22 Software.
Fit indices in final model indicate good model fit with data (RMSEA=0.066, GFI=0.98, IFI=0.98, x2=18.60, P The family system affects pathological narcissism directly and indirectly via reinforced narcissism wounds and negative perfectionism. In preventing the pathological narcissism, any appropriate intervention on family status and family-related unhealthy personality traits could be of great benefit.

Background and H1N1 influenza circulate worldwide and affects the world population in case of pandemic. The aim of this study was to evaluate the awareness of urban family physicians in Mazandaran province, Iran about H1N1 influenza.
In a descriptive study, 373 urban family physicians were questioned. A standard questionnaire including different items were completed by participants. The items included epidemiology (7 questions), treatment (5 questions), virology and diagnosis (5 questions), clinical manifestations (6 questions), and prevention (4 questions) of H1N1 influenza. Data was then coded and analyzed in SPSS V18 applying Chi-square, t-test, and Fisher's exact test.
The participants were 47.5% females and 52.5% males. The levels of knowledge about H1N1 influenza were poor in 0.8%, fair in 11.3% and good in 60.3%. Also, 27.6% of the participants had excellent levels of knowledge on this type of influenza. The average scores of participants for epidemiology, virology and diagnostics, clinical manifestations, prevention, and treatment were 4.30, 3.38, 4.59, 2.79, and 3.67, respectively. The mean scores for knowledge in epidemiology and treatment were found to be higher in female physicians compared to those of their male counterparts. Our results indicated a direct correlation between experience and knowledge on virology, diagnosis, clinical symptoms, and prevention and treatment, while it was inversely related with knowledge on epidemiology of H1N1 influenza.
This study showed a relatively high level of knowledge among urban family physicians in Mazandaran province about H1N1 influenza. But they are strongly recommended to participate in continues education programs that increase their awareness and enhance their knowledge.

Background and Antibiotics are non-biodegradable and wastewater treatment processes are not fully effective in their removal. Therefore, presence of some antibiotics such as erythromycin and metronidazole in environment has become a major concern in recent years. The aim of this study was to evaluate TiO2 nano-particles for removal of these two antibiotics from aqueous solution based on the response surface methodology (RSM).
Effect of independent variables including pH, catalyst dose, contact time, and initial concentrations of erythromycin and metronidazole on the removal efficiency of these antibiotics were evaluated using RSM based on Box-Behnken design. All experiments were performed under ultrasonic irradiation in ultrasonic bath at a frequency of 35 kHz.
According to ANOVA analysis and the model proposed, the optimum condition of pH, nano-particle concentration, reaction time and initial concentration of antibiotics for removal of erythromycin and metronidazole were 3, 0.4 g/l, 89.8 min, and 50.0 mg/l for erythromycin and 3, 0.4 g/l, 85.5 min, and 50.0mg/l for metronidazole. Under these conditions, efficiency of COD removal in erythromycin and metronidazole was 98.5% and 99.4 %, respectively.
In current study, sono-catalytic process was accelerated in the presence of TiO2 nano-particle and enhanced the removal of erythromycin and metronidazole.

Background and Waste stabilization pond is one of the conventional wastewater treatment processes especially in warm climate regions. This study investigated the effect of baffle and attached growth on improvement of coliform removal efficiency.
This research was carried out in pilot scale adjacent to wastewater treatment plant in Ahvaz, Iran. The pilot composed of a control system and three other systems. In control system two ponds were serially connected. Dimension and configuration of other three systems were similar to those of the control system. However, the ponds in these systems were equipped with various baffles and fixed bed media. Within four months, the capability of each system in coliform removal was evaluated in various detention times and coliform die-off coefficient (Kb) of each pond was determined.
During sampling with average detention time of 8.7 day, the average of coliform removal was 69% in control system, while it in two, three and four baffles system these values were 80, 84 and 86%, respectively. Also, Kb20 average in the first pond of control system was 0.11 d-1 and in other systems with increasing of baffles and media packages number to two, three and four it increased to 0.16, 0.17 and 0.18 d-1, respectively. Furthermore, Kb20 in second pond was higher than first pond of each system.
Use of baffles and fixed bed media improved coliform removal efficiency. The efficiency of two and three baffles system was more than that of the control system and was found to be better than four baffles system technically and economically

Background and Particulate matter is one of the main pollutants in underground transport systems. Increase in its concentration leads to health problems in passengers and metro staff. Current research aimed at studying the concentration of particulate matter with aerodynamic diameter less than 10 micron (PM10) in Tehran underground transport system.
In this study, concentrations of PM10 were measured in 18 over ground stations and two underground stations during one month in autumn. Sampling was done three times a day (morning, afternoon, and evening) at the beginning, middle, and end of the platforms and the ticket hall. A portable Real-Time Direct Reading Particulate Monitor (HAZ DUST EPAM 5000) with a flow of 4 liters per minute was used. We studied the effect of depth of stations, number of passengers in stations and, number of trains on the emission of PM10 concentration.
The results showed that average concentrations of PM10 in underground and over ground stations were 17.23±33.64 and 14.41±21.60 µg/m3, respectively. The concentration of pollutant were found to be higher at noon (8.25±32.01µg/m3), beginning of the platforms, and ticket halls (3.28±29.8 and 12.82±39.91 µg/m3, respectively).
This study indicated that the average concentration of particulate matter in Tehran underground transport system was lower than the standard levels accepted by the Environmental Protection Agency and the Department of Energy.

Background and Inhalation is one of the main ways of exposure to occupational pollutants that can cause acute and chronic respiratory complications in workers. This study aimed to identify the predictors of using respiratory protection masks among workers based on the theory of planned behavior.
An analytical cross-sectional design was employed. Cluster sampling was used by which 120 workers exposed to occupational dust were recruited from four sanitary ware companies in Yazd, Iran. A self-administered questionnaire was applied. The validity and reliability of the scale was previously confirmed in an exploratory study. Statistical analyses of the data included bivariate correlation and linear regression.
The workers used respiratory mask in 19 days of the past month and intended to use that for 22 days in the next month. The relationship between intention and behavior was the strongest. Totally, perceived behavioral control, subjective norms, and attitude variables accounted for 20.8% of the variation in behavior with subjective norms being the strongest significant predictor.
Our results demonstrated the importance of subjective norms on using respiratory protection masks among workers. According to the relatively good identification of predictors of using respiratory protection masks, application of this theory is suggested in predicting safety related behaviors.

Background and Playing games is essential in children’s lives. Children convey their thoughts through games, unlike adults that express their feelings through words. The purpose of this study was to evaluate the effectiveness of Child Parent Relationship Therapy (CPRT) on distress, anxiety, and depression in mothers of children with mild intellectual disabilities.
In a quasi-experimental study, 30 mothers with children with mild intellectual disabilities were selected by convenience sampling. They were divided into experimental and control groups. Both groups completed the DASS inventory. The participants in experimental group attended 8 sessions of group play therapy.
Covariance analysis showed that CPRT led to significant reduction in stress, anxiety, and depression in mothers with intellectually disabled children (P Child Parent Relationship Therapy reduces anxiety, stress, and depression in mothers of children with mental and physical disabilities.

Background and Asthma is a chronic inflammatory disease of the airways that is caused by hypersensitivity to environmental allergens. Symptoms of asthma include shortness of breath, airway hyper-responsiveness, wheezing, and cough. The disease might vary from a mild to severe and intermittent to chronic disease. Asthma is known as a multifactorial disease due to the interaction of genetic and environmental factors in its development. Identifying the environmental and genetic factors are of great benefit for prevention, diagnosis and treatment of allergic asthma. The aim of this review was to investigate the factors that increase the risk of asthma.
Electronic databases including Scopus, PubMed, Google Scholar, Scientific Information Database (SID), Magiran, and Irandoc were searched for relevant articles published between 1990 and 2016. The search keywords were asthma, atopy, genetic factors, polymorphisms, environmental factors, and gene-environment interaction.
This review showed that asthma is a complex and multifactorial disease and the combination and interaction of environmental and genetic factors have a role in its development and progression. Therefore, each of these factors cannot be considered as an absolute cause of asthma, but a set of factors such as genes influencing inflammatory pathways, airway rebuilding, and environmental factors should be considered as risk factors.
Asthma is a complex and multifactorial disease and interaction of several genetic and environmental factors are involved in its clinical presentation. A major step in determining the genetic causes of asthma is identifying chromosomal regions and candidate genes associated with asthma.

Background and Scorpions have always received attention in Iran because of their frequency and venom. In the past 50 years many aspects of scorpion biology have been studied in Iran, including venom. Identifying the species of these predators are of great interest to researchers. This study presents the latest checklist of species of scorpions in Iran.
Electronic databases including Web of Science, Ovid, PubMed, Systematic Review, SID, Iran Medex, Scirus, Google Scholar, and Medline were searched using scorpion, species, family, systematic, and Iran as keywords. Articles published with emphasis on Iran and fauna of scorpion in 1985 to 2016 were investigated. A total of 150 studies was found from which 75 were selected that were mainly about different species of scorpion in Iran.
So far, 64 species of scorpions are reported in Iran belonging to Buthidae family (86%), Hemiscorpiidae family (9.5%), and Scorpionidae family (4.5%). These species were found most in tropical regions of Iran.
Scorpion species have considerably increased in last three decades, therefore, researchers are expected to provide latest checklist of species of scorpions regularly in Iran.

Regarding request of corresponding author article with entitled “Comparative Study of Direct Patient and Drug Costs before and after the Implication of Healthcare Reform Program in Sari, Iran.” that published in volume number 26 and issue 144 in this journal, there are mistake regarding affiliations of Shokoufeh Nikfar and Pardis Zaboli. The corrected affiliation of these authors are in below.