مجله دانشکده پزشکی اصفهان
پیاپی 218 (هفته چهارم بهمن 1391)

Anthracyclines are used to treat different types of cancer including hepatocellular carcinoma. However, they have various side effects such as cardiotoxicity. Designing a drug delivery system which targets retinoic acid receptors in hepatocellular carcinoma can reduce these side effects. Chitosan/retinoic acid/albumin nanoparticles were prepared using a coacervation method. Nanoparticles which were optimized according to their particle size, zeta potential, polydispersity index, loading efficiency and release of doxorubicin, were used for further tests of cytotoxicity on HepG2 cells [by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] and cellular uptake tests (by fluorescent microscopy). The optimum targeted nanoparticles (with particle size of 286 ± 50.0 nm, zeta potential of 30.5 ± 3.6 mv, polydispersity index of 0.50 ± 0.06, loading efficiency of 43.6 ± 13.5%, and drug release of 56.17 ± 6.00%) in a concentration of 0.5 mg/ml were two to three times more cytotoxic than non-targeted nanoparticles and free drug. Their cellular uptake was also more. Chitosan/retinoic acid/albumin targeted nanoparticles loaded with doxorubicin could affect HepG2 cells more effectively than non-targeted nanoparticles and free drug.

Breast cancer is the most common cancer among women. Genetic is a proven risk factor in this disease. As breast cancer genes (BRCA1 and BRCA2) affect the incidence of this type of cancer, identification of mutation carriers is important in reduction of the overall risk. The purpose of this study was to determine the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer using high resolution melting (HRM) analysis. Blood samples of 41 female patients with breast cancer and 20 healthy women were collected randomly. The studied mutations were 185delAG, 5382insC, 3889delAG and 1476delG in BRCA1 and 6174delT and 6033-34insGT in BRCA2. Genomic DNA was extracted from blood samples. Forward and reverse primers were designed for each mutation. DNA samples of healthy individuals were sequenced to make sure about the absence of the studied mutations. Real-time polymerase chain reaction (PCR) and HRM analysis were performed and HRM and melting curves were plotted for all samples. For each mutation, some random samples were sequenced. The curves in the case and control groups were compared for each mutation. The desired mutations were not observed in any samples of the case group. Sequenced samples confirmed the HRM results. Due to the low number of samples and lack of known native mutations, observation and identification of mutations seem to be impossible in studies such as the present one. However, this study can serve as a base for extensive and applied studies of native and non-native mutations in Iranian population.

Subconjunctival block (SCB) had been reported to be useful for strabismus surgery, laser cyclophotocoagulation, and glaucoma surgery. The aim of this study was to evaluate the efficacy of adding SCB to intravenous sedation and topical anesthesia for phacoemulsification surgery. After the approval from the institutional ethics committee and obtaining written consents from the patients, 64 adults scheduled for phacoemulsification were enrolled in this double-blind clinical trial. The subjects were randomly allocated to two equal groups of case and control. All patients received similar preoperative preparation, intravenous sedation (1.5 µg/kg fentanyl and 0.15 mg/kg ketamine), and topical anesthesia (0.05% tetracaine) before surgery. Intraoperative additional fentanyl and ketamine was administered as needed. The cases received SCB with 0.1 ml of bupivacaine 0.5% at the site of incision. The controls received equal volume of balanced salt solution. Patient cooperation and satisfaction, severity of intraoperative pain, additional drug requirement, postoperative nausea and vomiting, recovery time and surgeon satisfaction were determined and recorded. Data was analyzed using t-test, and chi-square, Fisher’s exact, and Mann-Whitney tests. P < 0.05 was considered significant. Demographic data was similar in the two groups. The frequency of excellent patient satisfaction was 28 (87.5%) in the case group and 15 (46.9%) in the control group. The corresponding values were 25 (78.1%) and 18 (56.3%) for patient cooperation and 24 (75.0%) and 19 (59.4%) for surgeon satisfaction (P < 0.05). Intraoperative additional fentanyl requirement, intra- and postoperative severity of pain, and recovery time were significantly lower in the case group than in the control group. This study showed that adding subconjunctival block to intravenous sedation and topical anesthesia in phacoemulsification surgery may enhance patients’ comfort and the conditions of the operation.

One of the most common postoperative complications is pain which is caused by tissue damage during surgeries. Many drugs, such as magnesium sulfate, are used to control postoperative pain. Magnesium sulfate has been reported to have analgesic effects. Pre-emptive analgesia is a treatment to control pain before a painful procedure. This study was conducted to understand the pre-emptive effects of magnesium sulfate. This double-blind clinical trial was conducted in Alzahra Hospital (Isfahan, Iran) in 2012. A total number of 92 candidates for lower abdominal surgeries were selected and randomly allocated to two groups of experimental and control (n = 46 each). One hour before the operation, the experimental group was infused with 50 mg/kg magnesium sulfate in 100 ml normal saline during 10 minutes. The control group received 100 ml normal saline through the same method. Vital signs, including pulse rate and blood pressure, were recorded in a checklist before, during, and 2, 12, and 24 hours after the operation. Postoperative pain was measured by a visual analogue scale (VAS) and a verbal rating scale (VRS). Patients with VAS scores of greater than 4 were injected with 0.1 mg/kg morphine or similar doses of other narcotics. The amount of injected narcotics during the first 24 hours and patient satisfaction were also recorded for all patients. The severity of pain at the second, 12th, and 24th postoperative hours was significantly lower in the experimental group than in the control group (P < 0.001). According to the results of the present study, magnesium sulfate can effectively decrease postoperative pain. It may thus be prescribed before operations when there are no contraindications.

Recently re-emerging infections occur due to antibiotic-resistant bacteria. The use of bacteriocins as a substitute for currently used antibiotics is promising. The isolated nitrogen-fixing Bacillus bacteria might be a potential candidate strain as an alternative source of peptide antibiotics in the future. A total of 15 nitrogen-fixing Bacillus strains with antibacterial activity were isolated from soil samples. Bacteriocin-producing strains against the indicator strains were co-cultured and isolated. The antibacterial activity of bacteriocin was detected by spot-on-the lawn method with different bacteria. Effects of proteolytic enzymes, pH, and heat treatment on bacteriocin activity were also determined. All isolated spore forming Bacillus strains had an inhibitory effect on Listeria monocytogenes and Staphylococcus aureus. Some of them had an inhibitory effect on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). None of them had an inhibitory effect on Gram-negative bacteria. The antimicrobial compounds produced by these novel strains were inactivated by the proteolytic enzymes which demonstrated their proteinaceous nature. These bacteriocins were also active in a wide range of pH and temperature. In the present study, new bacteriocin-producing nitrogen-fixing Bacillus strains with anti-MRSA and anti-VRE activity were isolated from the environment and their biochemical properties were determined.

The molecular mechanisms of aging are the subject of extensive research and have facilitated potential interventions to delay aging and age-related degenerative diseases in humans. The aging process is frequently affected by environmental factors. Caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic and molecular mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. The underlying molecular mechanisms for this effect include a lower rate of accrual of tissue oxidative damage that is associated with a significantly lower rate of mitochondrial free radical generation. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure and hence modify the expression of relevant genes. In this review, we assessed current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging, and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetic in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.