Iranian Journal of Basic Medical Sciences
Volume:17 Issue: 10, Oct 2014

Preclinical studies show that iron plays a key role in mediating neuronal injury. This study was performedin order to identify the relationship between the serum level of ferritin and severity of the brain injury which occur after an Intracerebral hemorrhage (ICH). This was a cross sectional descriptive – analytic study, which was conducted on those patients who had suffered from an ICH and had attended Poursina Hospital. The Serum levels of ferritin were measured at admittance. A Cranial CT scan was performed at admission and also 72 hr afterward. Hematoma and edema surrounding the hematoma volumes were also measured at entrance and 72 hr afterward. Data analysis was carried out by a descriptive - analytic statistics approach and calculated later on by the Spss-20 software. In this investigation, 63 patients were studied, from which 34 (54%) were male and 29 (46%) female. The average age of the patients was 69.7± 11.9 (Min 43 and Max 94 years old). A significant relationship was observed between the level of ferritin and the edema volume surrounding the hematoma at first and next 72 hr after the patients were admitted. These results delineated the effective role of iron on the edema volume elevation. More studies are essentially urged to ascertain the clinical evaluation of the curing effect of iron chelators in those patients who suffer from ICH.

Amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disorder, is the most common motor neuron disease in European populations. Approximately 10% of ALS cases are familial (FALS) and the other patients are considered as sporadic ALS (SALS). Among many ALS causing genes that have been identified, mutations in SOD1 and C9orf72 are the most common genetic causes of the disease. In Iranian patients, it has been shown that SOD1, as compared to C9orf72, plays a much more prominent role. To date, more than 170 mutations have been reported in SOD1. Genotype/phenotype correlation with respect to either different causative genes or different mutations of a specific gene has not been well established. Five exons of SOD1 and flanking intronic sequences of an Iranian FALS proband were screened for mutations by direct sequencing. Also, the clinical features of the proband were described. Heterozygous p.Val48Phe causing mutation was identified in SOD1. Age at onset was 29 years and site of the first presentation was the lower extremity in the proband. The p.Val48Phe causing mutation appears to cause early onset of ALS.

One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

The purpose of the present study was to investigate the protective effect of oxytocin on cisplatin (CP)-induced renal damage in rats. Fourteen adult Sprague Dawley rats, weighing 200 to 210, were administered by cisplatin (CP, 2 mg/kg/day) twice a week for five weeks. Then, they were randomly divided into two groups and treated with either saline (1 ml/kg/day) or OT (200 µg/kg/day) for five weeks. Seven rats served as control group. At the end of the treatment period, animals were sacrificed and their kidneys were assessed histologically. In addition, C-reactive protein (CRP), TGF-β and Akt expression were evaluated immunohistochemically. Both tubules and glomeruli were found to be severely damaged with marked medullary tubulo-interstitial inflammation due to chronic cisplatin exposure, particularly in the saline-treated group (Group 1) compared to control group. Oxytocin treatment spared renal tissue significantly by suppressing CRP and TGF-β, and enhancing Akt expression. We conclude that renal damage due to cisplatin toxicity was prevented to a great extent by the anti-inflammatory effect of oxytocin.

Neuropathic pain is caused by lesions or diseases affecting the somatosensory system and often responds poorly to typical medications. In this study, we evaluated anti-nociceptive effects of morphine, gabapentin and their combination on heat hyperalgesia, cold and mechanical allodynia in chronic constriction injury (CCI) model of neuropathic pain in rats. Morphine (2, 4 and 8 mg/kg) and gabapentin (5, 10 and 20 mg/kg) were administered either alone or in combination (morphine 2 mg/kg and gabapentin 5 mg/kg). Our results showed that morphine and gabapentin alone produce anti-nociceptive effects at higher doses (morphine 4 and 8 mg/kg and gabapentin 10 and 20 mg/kg) whereas their combination resulted in better analgesia at lower doses as compared to other treatment groups (morphine 2 mg/kg or gabapentin 5 mg/kg). These findings suggest that gabapentin potentiates the analgesic effects of morphine in the chronic constriction injury (CCI) model of neuropathic pain and combination of these drugs may be considered as a beneficial treatment for neuropathic pain.

The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 μg/cm2/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

Previous studies demonstrate that changes in pre-mRNA splicing play a significant role in human disease development. Furthermore, many cancer-associated genes are regulated by alternative splicing. There are mounting evidences that splice variants which express predominantly in tumors, have clear diagnostic value and may provide potential drug targets. Located on the X chromosome, ZFX gene functions as a transcription regulator for self-renewal of stem cells. This gene has 5 splice variants that encode 3 isoforms. In the present study, we evaluated the clinicopathological relevance of the expression of ZFX isoform 3/variant 5 gene in gastric carcinoma. A total of 60 tumoral and non-tumoral gastric specimens were evaluated for ZFX isoform 3/variant 5 gene expression using quantitative real-time PCR. Our results showed that the expression of ZFX isoform 3/variant 5 transcript was heterogeneous in gastric specimens. We further showed that there was a positive correlation between the variant expression and tumor size, but not with other clinicopathological features of gastric tumors. This report shows that the expression of ZFX isoform 3/variant 5 transcript was heterogeneous in gastric specimens. Furthermore, there was no significant association between ZFX isoform 3/variant 5 expression and most of clinicopathological features of gastric tumors except for a positive correlation with tumor size. The elucidation of the precise molecular mechanisms governed by the ZFX isoforms/variants needs further investigation.

One of the major challenges in the field of vaccine design is choosing immunogenic antigens which can induce a proper immune response against complex targets like malignant cells or recondite diseases caused by protozoan parasites such as leishmaniasis. The aim of this study was to find a way to construct artificial liposome-based cells containing fragments of target’s cell membrane. This structure not only mimics the real biological properties of proteins in the cell membrane of target cells, but also may induce the required immune responses, which culminate in eradication of target cells. Five different techniques have been investigated to engraft the plasma membrane’s vesicles (PMVs) derived from a characterized Leishmania parasite into liposomes. The most efficient method was tested again on the PMVs derived from well-known breast cancer cell line SK-BR-3. The percentage of engraftment was determined by two-color flowcytometry after staining the engrafted dioctadecyl-3,3,3''3''-tetramethylindocarbocyanine DiI[FA1] -labeled liposomes with FITC-labeled PMVs. Among the investigated techniques, freeze-drying method with 91±2% and 90±3% of engraftment for Leishmania and SK-BR-3 derived PMVs, respectively, showed superiority over the other methods. In addition, after 9 weeks storage in refrigerator, freeze-dried fused particles kept their original size (660±350 nm) and fusion efficiency (94±3%). Among five different engraftment techniques, freeze-drying is preferred over the other methods due to its simplicity, more fusion efficiency and stability of produced particles during storage.

In developing countries and worldwide cervical cancer is an important cause of female mortality. Reports describing the frequency and pattern of abnormal Pap smears in Saudi Arabia, using the revised Bethesda system (RBS) are very few. The current study was conducted to explore the changing pattern of epithelial cell abnormalities (ECA) detected in Pap smears (PS) in females of the Western region of Saudi Arabia at King Abdulaziz University Hospital, Jeddah using the RBS. A retrospective study was designed to review all the PSs from the archives of Cytopathology Department at King Abdulaziz University Hospital, starting from January 2000 to October 2012 using RBS. Cytological aspects of PSs were reviewed with age distribution. Of the 15805 PS, 84 (0.53%) unsatisfactory smears were excluded. There were 2295 cases (14.52%) with ECA. In the abnormal squamous cell category the distribution of lesions was as follows: Atypical squamous cells of indeterminate significance (ASC-US) were 7.1%; atypical squamous cells, cannot exclude high squamous intraepithelial lesion (ASC-H) were 1.08%; low grade squamous intraepithelial lesion (LSIL) including human papillomavirus was 2.2%, high grade squamous intraepithelial lesion (HSIL) was 0.8% and high grade squamous intraepithelial lesion with suspicious invasion was 0.06% smears. The mean age (MA) incidence was 39,43,45,46 and 45 years respectively. The percentage of abnormal PS is increasing (14.52%) over the last decade. This increase is evident by different studies conducted across Saudi Arabia. Under present circumstances the need for mass screening.

Multiple Sclerosis (MS) is known as a progressive inflammatory CNS disease. Cytokines belong to Th1 or Th2 family and inflammatory cells, play significant role in pathophysiology of MS. Thus, any treatment supposed to influence the relation between Th1 to Th2 cytokines expression. Although vitamin D has been prescribed as a therapeutic supplement of MS for a long time, it is not clear how much it may affect the Th1/Th2 ratio. To answer this question the present research was designed. Thirty C57BL/6 adult female mice were used. The animals were randomly divided into trial and control groups. Experimental Autoimmune Encephalomyelitis (EAE) modeling for MS and clinical scoring as cited by others was used. Based on scoring and step of the disease vitamin D3 prescription (5 mg/kg) started and continued for three weeks. By using ELISA and RT-PCR the brain level of TNF-α, IL-10, IL-4 and IL-12 determined. Significant decrease of clinical symptoms in trial group which received vitamin D was seen comparing to control animals (P<0.05). The level of TNF-α but not IL-10 significantly decreased following vitamin D3 administration. By comparing the level of Th1 and Th2 Interleukins and counting the ratio of them we found that in treated animals the ratio was significantly less than non-treated (P =0.01). According to the results, vitamin D3 may be able to suppress the inflammatory ways that lead to progression of MS. Whether this ability is clinically valuable in human subjects is not clear and needs more clinical research.

Cone snails are estimated to consist of up to 700 species. The venom of these snails has yielded a rich source of novel peptides. This study was aimed to study the analgesic effect of Persian Gulf Conus textile and its comparison with morphine in mouse model. Samples were collected in Larak Island. The venom ducts were Isolated and kept on ice then homogenized. The mixture centrifuged at 10000 × g for 20 min. Supernatant was considered as extracted venom. The protein profile of venom determined using 15% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Venom was administered intraperitoneally (IP) to evaluate the LD50 in Swiss albino mice. Different concentrations of Conus textile venom were injected intrathecally to mice to evaluate their analgesic effect in comparison to morphine. Injection was carried out between the L5 and L6 vertebrae. Differences between groups in the first and second phase were tested with Two-Way analysis of variance (ANOVA). SDS-PAGE indicated 12 bands ranged between 6 and 180 KDa. Finally, ten ng of Conus crude venom showed the best analgesic activity in formalin test. No death observed up to 100 mg/kg. Analgesic activity of crude venom was more significant (P<0.05) in acute pain than inflammatory pain. The analgesic effect of 10 ng Conus venom was the same as morphine for reduction of inflammatory pain (P=0.27). The venom of Persian Gulf Conus textile contains an analgesic component for reliving of acute pain which can lead to find an analgesic drug.

HTLVI-1 is the first human retrovirus with limited endemic regions in the world. The epidemiological studies have shown that the genetic background and immune response to the virus have a significant role in HTLV-I-associated diseases. Among the genes are involved in HTLV-I infection, the role of human leukocytes antigen (HLA) have been studied in different population. In the present study we examined the association between HLA-DQB1 alleles and HTLV-I infection in HAM/TSP patients, HTLV-I carriers and healthy controls in north east of Iran, Mashhad. The blood samples of 16 patients with HAM/TSP, 20 HTLV-1 carriers, and 30 healthy individuals were taken and DNA was extracted by salting out method. HLA-DQB1 typing was performed using PCR-SSP method and the frequency of HLA-DQB1 alleles were compared by Fischer Exact Test. There was a significant difference between HAM/TSP patients and healthy controls in the frequency of HLA-DQB1*07 (P=0.004, RR=7). Furthermore, we found that possession of HLA- DQB1*02 or HLA-DQB1*05 increased the risk of disease 1.5 times. The data presented here suggest that both HLA-DQB1*07 and HLA-DQB1*06 are associated with disease development.

Acute kidney injury (AKI), a syndrome characterized by decreased glomerular filtration, occurs in every 1 of 5 hospitalized patients. Renal ischemia-reperfusion, one of the main causes of AKI, is of particular importance in the setting of kidney transplantation. Sixty male rats were divided into four groups including control, nephrectomy, sham surgery and renal ischemia-reperfusion (IRI) group. The rats were anesthetized with intraperitonealketamin and xylazin. For making IRI group, right nephrectomywas performed, and after a week, the left kidney pedicle was occluded for 45 min for making ischemia that followed by 24 hr reperfusion. At the end of reperfusion phase, the lung tissues were isolated to be used in immunohistochemical and histological assays. Immunohistochemical assay was used to evaluate Bcl-2 and TNF-α, and hematoxylin-eosin staining assay was used to histopathology. lung tissues injury after renal ischemia-reperfusion was revealed by immunohistochemistry analysis to increase TNF-α level and decrease Bcl-2 (an anti-apoptotic protein) level. Lung injury and necrosis was discovered by hematoxylin-eosin staining to be more evident in IRI group than sham and control groups. The results demonstrated that increase in TNF-α and decrease in Bcl-2 levels in lungs induces the pulmonary inflammatory damage in renal IRI model.

The present study investigated the antidiabetic and hypolipidemic properties of Dorema aucheri leave hydroalcoholic extract in nicotinamide-streptozotocin induced type 2 diabetic rats. nicotinamide/streptozotocin-induced diabetic rats were supplemented orally with three different doses of D. aucheri (100, 200 and 400 mg/kg BW) or glibenclamide (0.25 mg/kg) for 4 weeks. Ultimately, blood of animals has taken and glucose, insulin, lipid profiles, SGPT, alkaline phosphatase, SGOT, leptin levels were assayed. D. aucheri has highly significant blood glucose lowering effect. Administration of the extract to diabetic rats resulted in a remarkable change in serum lipid profiles, insulin and leptin levels relative to diabetic group. Also the extract reversed back the serum levels of SGPT, alkaline phosphatase and SGOT to near normal in treated diabetic rats. D. aucheri could be useful in treatment of diabetes. Moderate dose of D. aucheri (200 mg/kg) was more effective than the others.

Several beneficial effects have been attributed to the probiotic lactic acid bacteria. It was determined that lactobacilli can exert antiproliferative effects on the various cancer cell lines including colon cancer. Effects of lactic acid bacteria on colon cancer may vary from strain to strain and there is a need to find the new probiotic strains with tumor suppressing properties through in vitro studies. Anti-proliferative activities of heat-killed cells and cell-free supernatants of a native strain of Lactobacillus plantarum A7 and a commercial strain of lactobacillus rhamnosus GG were assessed on human colon cancer cell lines (Caco-2 and HT-29) and normal cells (L-929), using MTT assay. Cells were seeded at 2×104 cells/mlin 96 well plates and incubated for 24 hr. Then heat-killed cells (OD620: 0.025, 0.0.05, 0.1) and cell-free supernatants of bacteria were added at concentration of 2.5, 5 and 10 mg/ml. After 48 hr incubation MTT (5 mg/ml) was added and the absorbance was measured at 540 nm using ELISA plate reader. Results showed that heat-killed cells and cell-free supernatants of both probiotic strains reduced the growth rate of cancer and normal cells. These results suggested that anti-proliferative effect may not be an exclusive characteris ticwhich is dedicated to officially approved probiotics. L. plantarum A7 could be considered as colon cancer biological product, most likely due to its advantages in significant organic acid production.