فصلنامه علوم پزشکی دانشگاه آزاد اسلامی
سال بیست و نهم شماره 2 (پیاپی 96، تابستان 1398)

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that is caused through loss of function mutations of a tumor suppressor gene termed neurofibromin 1. Therapeutic decisions are presently restricted for NF1-associated tumors, where treatment is often restricted to thorough surgical resection with perfect margins. In this review article, the multifunctional role of neurofibromin in tumor suppression has been discussed. While neurofibromin inhibits proliferative growth through blockade RAS-mediated signal transduction, neurofibromin should also be considered as a modulator of cell motility and cell adhesion. Through interfacing with the cytoskeleton and membrane structures, neurofibromin acts as a negative regulator of RHO/ROCK signaling pathways involved in cytoskeletal dynamics that are involved in proper neuronal expansion.
The loss of function of neurofibromin through genetic mutation results in heightened cell proliferation and migration, predisposing NF1 patients to cancer. Malignant peripheral nerve sheath tumors (MPNSTs) can be developed from benign neurofibromas and are the main cause of death amongst NF1 patients. Recent researchers in MPNSTs have been attempting to reveal key molecular events that lead MPNSTs to malignancy. Advances regarding malignant drivers involved in cell migration, cell invasion and angiogenic signaling are discussed in this review, where these findings will likely influence future therapies for both NF1 and related sporadic cancers.

Over the past years, orally disintegrating films (ODFs) have been a suitable alternative to conventional oral dosage forms such as tablets and capsules, especially for patients with dysphagia. ODF is relatively a new dosage form which is prepared using hydrophilic polymers, which rapidly dissolve on tongue or buccal cavity and has other advantages of rapid onset of action and improved bioavailability. The aim of this study was formulation of ODF dosage forms containing alprazolam, which is a short-acting anxiolytic of the benzodiazepines class of psychoactive drugs. Various polymers like hydroxy propyl methyl cellulose (HPMC6cps), sodium carboxy methyl cellulose (Na CMC), polyvinyl alcohol (PVA72000), and different plasticizers like propylene glycol (PG), polyethylene glycol (PEG400) with different percentage using solvent casting technique were used to prepare ODF formulations. Physicochemical tests including weight and thickness determination, disintegration time, assay and dissolution time were performed to find the optimum formulation. The optimized formulation contained PVA72000 and PEG400 with disintegration time less than 60 seconds and acceptable dissolution rate. ODT dosage form of alprazolam with acceptable dissolution behavior and proper disintegration time was successfully formulated in this study.

Hepatoprotective effects of Fumaria parviflora have been approved in pharmaceutical and chemical toxicity models. Given the importance of the vincristine- induced hepatotoxicity during chemotherapy, the aim of this study was to investigate the potential hepatoprotective effects of F. parviflora extract on vincristine induced toxicity in adult male rats. In this experimental study, the rats (n=42) were divided into 7 groups: 1) Sham group, 2) vehicle group, 3) vincristine group (VCR) (0.5 mg/kg, i.p.), 4) F. parviflora extract (300 mg/kg, p.o.), 5) F. parviflora extract (500 mg/kg, p.o.), 6) Pretreatment group: F. parviflora extract (300mg/kg for 10 days, p.o.) + VCR (0.5 mg/kg, i.p.) on 9th and 10th days of the experiment, and 7) Pretreatment group: F. parviflora extract (500mg/kg for 10 days, p.o.) +VCR (0.5 mg/kg, i.p.) on 9th and 10th days of the experiment. Serum values of AST, ALT, ALP and malondialdehyde (MDA) were measured. Data were analyzed by one way ANOVA using prism software. F. parviflora extract with dose of 500 mg/kg markedly decreased ALT hepatic enzyme level caused by vincristine (P<0.01). In addition, the dose of 300 mg/kg could not decrease the elevated liver enzymes, including ALP, ALT and AST and also MDA levels. Hepatoprotective effects of F. parviflora extract were not considerable in pretreatment groups.

Because most bacteria responsible for hospital infections are resistant to common antibiotics, the tendency to produce effective and nontoxic anti-microbial drugs have increased. Therefore, it is attempted to substitute antibiotics with natural products, such as nanoparticles and plant extracts. The aim of this study was to investigate the synergistic antibacterial effects of silver nanoparticles with extracts of nettle and shallot plants against multi drug resistant (MDR) kebsiella. Of 360 clinical samples, 112 kebsiella were isolated from ICU hospitalized patients. The klebsiella isolates were identified by biochemical tests. The antibiotic susceptibility of isolates was determined using disc diffusion method. Minimum inhibitory concentration of silver nanoparticles, nettle and shallot extracts against resistant isolates was assessed by broth microdilution method and their synergitic effects were determined using checkerboard method. Also the fractional inhibition concentration (FIC) was calculated. The silver nanoparticles were more effective than plant extracts against MDR isolates. The use of silver nanoparticles and shallot extract together led to synergistic effect on both MDR klebsiella isolate and Klebsiella pneumoniae ATCC 1290. In addition, the use of the silver nanoparticles and nettel extract led to synergistic effect on MDR isolate of klebsiella and additive effect ATCC isolate. Due to good antibacterial effect of AgNPs, shallot and nettle extracts on resistant klebsiella isolates and their affordable production, they can be exploited in addition to antibiotic treatments.

Ulcerative colitis is a multifactorial disease in which the environmental and genetics factor are being involved together. Interleukins are a group of cytokine which are produced through T cells, monocytes, macrophages, and endothelial cells. Interleukin-10 is an important multitasking cytokine that has a key role in inflammatory responses. The promoter of interlekin-10 is highly polymorphic and many of its polymorphisms were identified. The purpose of this study was to investigate and detect the A1082G and T819C polymorphisms of interleukin-10 promoter in ulcerative colitis patients. In this case- control study, DNA from 150 individuals with ulcerative colitis and 150 controls were determined by PCR technique. Data were analyzed by Chi-square test using SPSS software. Also, odds ratios and 95% confidence interval were calculated. The results showed that distribution of GG and CC genotypes and frequency of G and C alleles (related to A1082C and T819C polymorphisms, respectively) was significantly different between patient and control groups. According to the results, both polymorphisms of IL-10 gene promoter (A1082G and T819C), including G allel and C allel, respectively, are likely to be considered as risk factors for ulcerative colitis. Moreover, both genotype of GG and CC can increase the incidence of ulcerative colitis.

Viral hepatitis is one of common infectious diseases and known as health problem around the world. Present cross-sectional study was performed to determine the association between HBeAg and HBV-DNA in patients who referred to Royan Institute for Reproductive Biomedicine and Amiralmomenin Hospital (Islamic Azad University) between 2012 and 2015. In this cross-sectional study, 222 patients were assessed and their HBe-Ag and HBV-DNA were analyzed by serological and molecular assays to determine the association between HBeAg and HBV-DNA for infectivity of infection. The results were gathered and recorded in the study checklist. 222 chronic HBsAg positive carriers, including 74 (33.2%) female and 148 (66.8%) male were studied. Of studied population, 10(6.8%) HBeAg positive, 108 (75.5%) HBeAb positive and 94 (42.34%) HBV DNA were detected. Level of detectable HBV-DNA was significantly higher in patients with HBeAg positive in compare with patients with negative HBe Ag (, P<0.001). According to study findings, there is clinical association between HBe Ag positive and HBV-DNA level and we can use HBeAg for assessing the infectivity of HBV infection.

Ischemic heart diseases (IHD) cause most deaths worldwide in a way that they are the cause of more than 30 percent of the deaths. After the discovery of miRNA in 1990 and the discovery of more than 2500 types of miRNA, gradually the importance of these mechanism regulators and molecular signals and gene routes were identified in the processes and the cellular mechanisms, especially in cardiovascular system. The goal of this research was to investigate miR-499 dominating the apoptosis of heart cellules in serums of the patients with MI (myocardial infarction). In this case-control study, miR-499 were investigated by real time PCR among 70 MI patients in Shahid Madani Hospital in Tabriz in 2017 and the data were compared with healthy persons. The statistical analyses were carried out using SPSS (version19) by t-test method. P<0.05 were considered as significant. The expression levels of miR-499 significantly increased among MI patients compared to control group (P=0.007). The miR-499 expression has no significant difference between overweight and normal weight people (P=0.06). The present study showed that the expression of miR-499 among individuals suffering from MI has been greater than healthy people and it can be utilized as a diagnostic and also prognostic factor of MI patients.

The urinary tract infection is the secondary most common human infection. Colon bacteria, including Klebsiella pneumonia, are the main cause of urinary tract infections. The occurrence of the antibiotic resistance is a major problem in the treatment of infections. Beta- lactamases and efflux pumps constitute the major defense mechanisms of antibiotic resistance of Klebsiella pneumoniae. The aim of present study was to detect oqxA and oqxB genes that encoding oqxAB efflux pumps, in the resistant strains of Klebsiella pneumoniae. Among 430 urine samples gathered from Mofoid and Modares Hospitals and Farabi Tajrish Laboratory, 100 strains of Klebsiella pneumoniae has been isolated. Antibiotic sensitivity tests have been accomplished by disc diffusion method based on CLSI standard. The ESBL strains have been identified by Roscoe's compound discs. Finally, the presences of oqxAB efflux pumps have been detected by PCR method through finding the genes encoding these pumps. Among 100 Klebsiella pneumoniae strains, 43% were ESBL positive. Imipenem, piperacillin tazobactam and morphenem were identified more effective than other antibiotics. The prevalence of oqxA and oqxB genes among resistant isolates was 69.76% and 72.1%, respectively. Regarding our findings, the urinary tract infections caused by Klebsiella pneumoniae were more prevalent in hospitalized patients. As well as, it was shown a higher percentage of resistance in compare with strains isolated from outpatients. Since the high resistance of Klebsiella pneumoniae strains is very worrying, antibiotics prescribing especially carbapenems need to be strongly supervised.

Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder. Deficit of executive functions is the main feature of ADHD which has negative outcomes on the affected children. The purpose of the current study was to determine the effectiveness of computerized motion-based cognitive rehabilitation on improvement of executive function, and working memory of children with ADHD. The research method was semi-experimental with pre-test and post-test design with control group which was done on 28 ADHD children with age of 8-12 years old in Karaj city using a purposeful sampling method. The samples were allocated randomly into two control and intervention groups. N-Back test was used to assess the working memory. Data were analyzed with repeated mixing variance analysis and using SPSS.ver20. The result of the study showed that working memory improved with cognitive rehabilitation through exercise (CORTEX) (P<0.01). This study showed that computerized motion-based cognitive rehabilitation can improve working memory of children with ADHD.

The aim of the present study was to compare effectiveness of metacognitive therapy (MCT) and acceptance commitment therapy (ACT) on reducing syndromes, psychological capital and quality of life of patients suffering from irritable bowel syndrome (IBS). Research method was quasi-experimental with pre-test, post- test, three-month follow-up and control group. Statistical population was all 20-40 years old females suffering from IBS who applied to Counseling Center of Pharmaceutical Sciences University located in Tehran City. Through available sampling, 45 patients were selected and assigned randomly in experimental group 1 (MCT), experimental group 2 (ACT) and control group (15 in each group). The Psychological Capital Inventory (Luthans, 1992) and Quality of Life Inventory (Ware & Sherbourne, 1992) were administered pre-test, post-test and follow-up period. The therapeutic packages of acceptance, commitment therapy and metacognitive therapy applied on experimental groups for eight 90- minute sessions once a week. Control group was placed in a waiting list. Both therapeutic methods equally increased psychological capital and quality of life in patients suffering from IBS. According to physicians’ report and own patients themselves, the symptoms of the disease were significantly reduced. Three- month follow-up confirmed these results. Since psychosocial factors, in addition to biological elements, influence on severity of IBS symptoms, improving healthy quality of life and psychological capital indicators should be paid attention to prevent and treat this disorder.