Iranian Journal of Basic Medical Sciences
Volume:18 Issue: 1, Jan 2015

Helicobacter pylori (H. pylori) is a pathogenic bacterium that colonizes the stomachs of approximately 50% of the world’s population. Resistance of H. pylori to antibiotics is considered as the main reason for the failure to eradicate this bacterium. The aim of this study was to determine the rate of resistant H. pylori strains to various antimicrobial agents in different areas of Iran. A systematic review of literatures on H. pylori antibiotic resistance in Iran was performed within the time span of 1997 to 2013. Data obtained from various studies were tabulated as following, 1) year of research and number strains tested, 2) number of H. pylori positive patients, 3) study place, 4) resistance of H. pylori to various antibiotics as percentage, and 5) methods used for evaluation of antibiotic resistance. Over the period, a total of 21 studies on H. pylori antibiotic resistance have been conducted in different parts of Iran. In these studies, H. pylori resistance to various antibiotics, including metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin, levofloxacin and furazolidone were 61.6%, 22.4%, 16.0%, 12.2%, 21.0%, 5.3% and 21.6%, respectively. We found no study on H. pylori resistance to rifabutin in Iran. Compared to the global average, we noted that the prevalence of H. pylori resistance to metronidazole, clarithromycin, amoxicillin, and tetracycline has been rapidly growing in Iran. This study showed that in order to determine an appropriate drug regimen against H. pylori, information on antibiotic susceptibility of the bacterium within different geographical areas of Iran is required.

Fumonisins are a group of toxic and carcinogenic mycotoxins, which contaminate the grains and their products. The aim of this study was to examine the apoptotic and proliferative activity of mouse gastric mucosa following administration of fumonisin B1 (FB1). Twenty-nine female mice divided into treatment (n=15) and control (n=14) groups. The treatment group received FB1 (150 mg/kg diet) for 16 weeks. The gastric atrophy was allocated using grading criteria modeled on the updated Sydney System. Immunohistochemistry studies were performed for evaluation of apoptosis and proliferative activity in gastric mucosa. Mild to moderate gastric atrophy were observed in microscopic findings of the gastric mucosa in treated animals (P<0.05). Number of parietal cells significantly decreased in the treatment group in comparison with the control (P<0.05). Treatment with FB1 for 16 weeks significantly reduced both gastric mucosa height and mitotic index in the gastric glands (P<0.05). TUNEL- and Bax-labeled positive cell numbers significantly increased in the FB1-treated group compared to the control (P<0.05). In addition, proliferative activity of gastric glands in the treated group was significantly lower than the control (P<0.05). Oral administration of FB1 caused atrophy in gastric mucosa both via increasing of apoptosis and suppressing the mitotic activity of these cells.

Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1[F1] [M2] region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection.

The present day challenge is how to obtain germ cells from stem cells to treat patients with cancer and infertility. Much more efforts have been made to develop a procedure for attaining germ cells in vitro. Recently, human umbilical cord-derived mesenchymal stem cells (HUMSCs) have been introduced with higher efficacy for differentiation. In this work, we tried to explore the efficacy of HUMSCs and some effective products of placental cells such as transforming growth factors. This study is aimed to optimize a co-culture condition for HUMSCs with placental cells to obtain primordial germ cells (PGCs) and reach into oocyte-like cells in vitro. In this experimental study, HUMSCs and placental cells were co-cultured for 14 days without any external inducer in vitro. Then HUMSCs were assessed for expression of PGC markers; Octamer-binding transcription factor 4(OCT4),Tyrosine-protein kinase Kit (CKIT), Stage specific embryonic antigen 4 (SSEA4), DEAD (Asp-Glu-Ala-Asp) box polypeptide 4(DDX4) and oocyte specific markers; Growth differentiation factor-9(GDF9), Zona pellucida glycoprotein 3(ZP3). The pertinent markers were assessed by immunocytochemistry and Q-PCR. Co-cultured HUMSCs with placental cells (including amniotic and chorionic cells) presented Oct4 and DDX4, primordial germ cells specific markers significantly, but increment in expression of oocyte-like cell specific markers, GDF9 and ZP3 did not reach to statistically significant threshold. Placental cell supplementsTransforming growth factor (TGF α, β) and basic fibroblast growth factor (bFGF) in a co-culture model can provide proper environment for induction of HUMSCs into PGCs and expression of oocyte-like markers.

From the ancient era, emergence of Agriculture in the connecting region of Mesopotamia and the Iranian plateau at the foothills of the Zagros Mountains, made Iranian gene pool as an important source of populating the region. It has differentiated the population spread and different language groups. In order to trace the maternal genetic affinity between Iranians and other populations of the area and to establish the place of Iranians in a broad framework of ethnically and linguistically diverse groups of Middle Eastern and South Asian populations, a comparative study of territorial groups was designed and used in the population statistical analysis. Mix of 616 samples was sequenced for complete mtDNA or hyper variable regions in this study. A published dataset of neighboring populations was used as a comparison in the Iranian matrilineal lineage study based on mtDNA haplogroups. Statistical analyses data, demonstrate a close genetic structure of all Iranian populations, thus suggesting their origin from a common maternal ancestral gene pool and show that the diverse maternal genetic structure does not reflect population differentiation in the region in their language. In the aggregate of the eastward spreads of proto-Elamo-Dravidian language from the Southwest region of Iran, the Elam province, a reasonable degree of homogeneity has been observed among Iranians in this study. The approach will facilitate our perception of the more detailed relationship of the ethnic groups living in Iran with the other ancient peoples of the area, testing linguistic hypothesis and population movements.

Parkinson's disease (PD) is known for motor impairments. But often, there are non-motor symptoms such as cognitive deficiency and pain misperception, owing to possible role of nigrostriatal pathway. Antioxidants have protective effect on free radical-induced neuronal damage in PD. To further address, we examined the effects of ellagic acid (EA) in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). Right medial forebrain bundle (MFB) was lesioned by injecting 6-OHDA (16 µg/2 µl), in PD–animals.Sham operated animals received vehicle instead of 6-OHDA. PD was approved by apomorphine-induced contralateral rotation. EA (50 mg/kg/2 ml, PO, for 10 days) was administered to PD-EA group. Some PD-animals received pramipexole (PPX; 2 mg/kg/2 ml, PO) as a positive control group. Analgesia was measured by tail-flick and hot-plate tests. Passive avoidance task was measured by shuttle box apparatus to record the initial and step-through latency. Spatial cognition task was evaluated by Morris water maze test, measuring the escape latency time, path length, swimming speed and time spent in target quadrant. MFB-lesioned rats showed hyperalgesic responses to the stimulus in tail-flick and hot-plate tests. Also they showed memory and learning deficit in cognitive tests. These effects reversed by EA treatment. 6-OHDA can induce oxidative stress and can disrupt the neural mechanisms underlying proper integration of painful stimuli and cognitive processes in MFB-lesioned rats. Consequently, nigrostriatal pathway can play possible role in nociception and cognition. EA, a natural antioxidant, has neuroprotective effect on this pathway and can ameliorate this defect and be considered in PD management.

This study aims at exploring cytotoxic activity of different peptides derived from VSVG protein against MCF-7 and MDA-MB-231 breast cancer cell lines and human embryonic kidney normal cell (HEK 293). The ANTICP web server was used to predict anticancer peptides. The cytotoxic activity of peptides with high score (P26, P7) and low score (P19) was examined by MTT and DNA fragmentation assays. The results obtained from ANTICP web serverdemonstrated that 4 out of 48 peptides (P26, P7, P10, and P16) had anticancer activity. P26 and P7 peptides of these 4 peptides were detected to have high cytotoxic activity against MCF-7 cells with CC50 values of 98,280 µg/ml and MDA-MB231 cells with CC50 100,550 µg/ml, respectively. In addition, the results showedthat amino acid residues of these 4 peptides were located near fusion domain. The results confirmed that P26 and P7 peptides might induce membrane damage and initiate apoptosis. The present study suggested that P26 and P7 peptides could be appropriate candidates for further studies as cytotoxic agents and modifications in the residue at positions 70-280 might potentially produce a more efficient VSVG protein in gene therapy.

Familial Mediterranean Fever (FMF) is an autosomal recessive disorder characterized by recurrent episodes of fever accompanied by peritonitis, pleurisy, and arthritis. FMF affects mainly Mediterranean populations and is caused by mutations in the familial Mediterranean fever (MEFV) gene. The aim of this study was to identify the frequency and distribution of MEFV mutations in Iranian Azerbaijanis with FMF. Medical records of 1330 Iranian Azerbaijanis who were diagnosed with FMF according to Tel-Hashomer criteria from May 2006 to April 2013 were reviewed and 10 MEFV mutations were found in affected individuals. 243 patients (18.27%) were homozygous, 370 (27.82%) were compound heterozygous and 717 (53.91%) were identified as heterozygous for one of the studied mutations. Of the studied mutations, M694V, E148Q, V726A, M680I, and M694I accounted for 42%, 21%, 19%, 14% and 2% of mutations respectively. In our study, M694V was found to be the most prevalent mutation. M694I, the most common mutation among Arabs, is rare in this cohort. Allele frequencies of the common mutations in our studied population have some similarities to those of the Turkish population reported previously. However, M680I is less common in our cohort.

In the current study, sunscreen and moisturizing properties of solid lipid nanoparticle (SLN)-safranal formulations were evaluated. Series of SLN were prepared using glyceryl monostearate, Tween 80 and different amounts of safranal by high shear homogenization, and ultrasound and high-pressure homogenization (HPH) methods. SLN formulations were characterized for size, zeta potential, morphology, thermal properties, and encapsulation efficacy. The Sun Protection Factor (SPF) of the products was determined in vitro using transpore tape. The moisturizing activity of the products was also evaluated by corneometer. The SPF of SLN-safranal formulations was increased when the amount of safranal increased. Mean particle size for all formulas was approximately 106 nm by probe sonication and 233 nm using HPH method. The encapsulation efficiency of safranal was around 70% for all SLN-safranal formulations. The results conclude that SLN-safranal formulations were found to be effective for topical delivery of safranal and succeeded in providing appropriate sunscreen properties.

Solanum acueastrum Dunal.has been shown to have some chemotherapeutic value. Leaf and berry water and methanol compounds of S. acueastrum were evaluated for possible antileishmanial activity In vivo on BALB/c mice and in vitro against Leishmania major promastigotes, amastigotes and vero cells. Dry S. aculeastrum berry and leaf material were extracted in methanol and water. L. major parasites were exposed to different concentrations of S. aculeastrum fruit and leaf compounds and the IC50 on the promastigotes, percentage of infection rate of macrophages by amastigotes and the toxicological effect on vero cells were determined. BALB/c mice were infected subcutaneously with 1×106 promastigotes and kept for four weeks to allow for disease establishment. Infected mice were treated with fruit and leaf methanolic and water compounds, amphotericin B (AmB), and sterile phosphate buffered saline (PBS). Fruit methanol compound was most effective in inhibiting the growth of promastigotes with IC5078.62 μg/ml. Fruit water compound showed the best activity in inhibiting infection of macrophages by amastigotes. Fruit methanol compound was more toxic at Ld50=8.06 mg/ml to vero cells than amphotericin B. Analysis of variance computation indicated statistically significant difference in lesion sizes between experimental and control mice groups (P=0.0001). Splenic impression smears ANOVA indicated a highly significant difference in parasitic numbers between the experimental and the control groups (P=0.0001). The results demonstrate that compounds from S. aculeastrum have potential anti-leishmanial activities and the medicinal use of the plant poses considerable toxicity against dividing vero cells.

This study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms. Male Wistar rats were anesthetized by thiopental sodium (50 mg/kg, IP) followed by IV injection of heparin (250 IU). Remote ischemic preconditioning (RIPC) was induced by 3 cycles of 5 min liver ischemia followed by 5 min of reperfusion. The hearts were excised within 5 min after the final cycle of preconditioning and perfused using Langendorff’s system. The isolated perfused hearts were subjected to 30 min global ischemia followed by 90 min reperfusion. The myocardial arrhythmias induced by ischemia- reperfusion (I/R) were determined in accordance with the guidelines of Lambeth Conventions. The potential role of KATP channels on RIPC was assessed by injection of glibenclamide (nonselective KATP blocker) or 5-hydroxydecanoate (mitochondrial KATP blocker) on rats 30 and 15 min before induction of RIPC in the liver, respectively. Hepatic remote preconditioning of the heart significantly (P<0.0001) prevented the incidence of myocardial arrhythmias induced by I/R in the perfused hearts (5.33±1.54 vs. 32.33±6.44,). However, the protective effects of remote preconditioning was significantly (P<0.01) abolished by the KATP blocker, glibenclamide (25.5±4.9 vs. 5.33±1.54,). Hepatic RIPC may prevent the arrhythmias induced by I/R in the isolated perfused hearts via KATP channels.

Mesenchyme is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm. Recently, mesenchymal stem cells (MSCs), as adult stem cells (ASCs) able to divide into a variety of different cells, are of utmost importance for stem cell research. In this research, ability of the liver extract to induce differentiation of rat derived omentum tissue mesenchymal stem cells (rOT-MSCs) into hepatocyte cells (HCs) was investigated. After isolation and confirmation of rOT-MSCs they were co-cultured with liver extract and hepatogenic differentiation was monitored. Expressions of mesenchymal stem cell markers were also analyzed via flow cytometry. Moreover, expressions of octamer-binding transcription factor-4 (Oct-4), Wilm's tumor suppressor gene-1 (WT-1), albumin (ALB), alpha fetoprotein (AFP), cytokeratin-18 (CK-18), and mRNAs were analyzed using RT-PCR on days 16, 18 and 21. ALB production was analyzed by immunocytochemistry and western blot. Furthermore, glycogen and urea production were determined via periodic acid-Schiff (PAS) staining and colorimetric assays respectively. The phenotypic characterization revealed the positive expressions of CD90, CD44 and negative expression of CD45 inrOT-MSCs. These cells also expressed mRNA of Oct-4 and WT-1 as markers of omentum tissue. Differentiated rOT-MSCs in presence of 6 µg/ml liver extract expressed ALB, AFP, CK-18, glycogen and urea as specific markers of HCs. These observations suggest that liver extract is potentially able to induce differentiation of MSCs into hepatocyte lineage and can be considered an available source for imposing tissue healing on the damaged liver.

Therapies with high levels of oxygen are commonly used in the management of critical care. However, prolonged exposure to hyperoxia can cause acute lung injury. Although oxidative stress and inflammation are purported to play an important role in the pathogenesis of acute lung injury, the exact mechanisms are still less known in the hyperoxic acute lung injury (HALI). In this study, we investigated the time course changes of oxidative stress and inflammation in lung tissues of rats exposed to >95% oxygen for 12-60 hr. We found that at 12 hr after hyperoxia challenge, the activities of superoxide dismutase and glutathione peroxidase were significantly reduced with remarkably increased lipid peroxidation. At 12 hr, NF-κB p65 expression was also upregulated, but Iκ-Bα expression showed a remarkable decline. Significant production of inflammatory mediators, e.g, interleukin-1β, occurred 24 hr after hyperoxia exposure. In addition, the expression of intracellular adhesion molecule 1 expression and the activity of myeloperoxidase were significantly increased at 24 hr with a peak at 48 hr. Our data support that hyperoxia-induced oxidative damage and NF-κB pathway activation implicate in the early phase of HALI pathogenesis.

Melanocortin-4 receptor (MC4R) and agouti-related peptide (AgRP) are involved in energy homeostasis in the rat. The aim of the present study was to evaluate the expression of MC4R and AgRP mRNAs in arcuate nucleus (ARC) during long term malnutrition of female ovariectomized rats. Ten female ovariectomized rats were divided into two equal groups (n=6) of normal and restricted diet groups. Using real-time PCR, the relative expressions (compared to controls) of MC4R and AgRP mRNAs were compared between both diet groups. The relative expression of MC4R and AgRP mRNA in the ARC of female ovariectomized rats during long term malnutrition was higher than those with normal diet (P<0.05). Changes in the relative expression level of MC4R and AgRP mRNAs during long term malnutrition of rat indicated a stimulatory role of MC4R and AgRP in regulating energy balance in ARC of rat hypothalamus.