Iranian Journal of Basic Medical Sciences
Volume:15 Issue: 5, Sep-Oct 2012

Ethical misconduct is not a new issue in the history of science and literature. However, ethical misconducts in science have grown considerably in the modern era which is due to emphasis on the scientific proliferation in research institutes and gauging scientists according to their publications. In the current case series, several misconducts occurring over the previous years in Mashhad University of Medical Sciences (Mashhad, Iran) either for Journals or Faculty members were gathered and specific recommendations were provided to avoid similar events in the future. All recommendations are according to Committee on Publication Ethics (COPE).

In a recent published paper in IJBMS, Kazeem A, et al evaluated the changes of acute phase proteins after moderate and prolonged exercise (1). They found that prolonged exercise increased plasma C-reactive protein (CRP); however, moderate exercise did not change plasma CRP level. They concluded that moderate exercise, and not prolonged exercise, should be encouraged.Chronic low-grade inflammation may contribute to pathogenesis of some diseases including cardiovascular disease, diabetes and metabolic syndrome (2). Among inflammatory markers, CRP is the most clinically useful and the best markers of inflammation and is considered as valuable predictors of cardiovascular risk (3). The beneficial effects of exercise on cardiovascular system have been documented in experimental and clinical studies by modification of numerous known risk factors (4), however, the exact mechanisms of these protective effects are not fully understood. One of the suggested mechanisms for beneficial effects of exercise in coronary artery disease (CAD) patients is the impact of exercise on vascular inflammation; however, the results are contrary. Some studies reported that exercise is not associated with reduced inflammatory markers (5, 6), while, other studies supported that exercise reduces (7, 8) or even increases those markers (1). This discrepancy depends on some variables including: 1- Acute vs. chronic exercise: Inflammatory cytokines including IL-6 are produced and released by skeletal muscles. IL-6 is the first inflammatory cytokines released from exercising muscles (9). Therefore, it is clear that acute bout or short-term exercise elevates plasma IL-6 and CRP concentrations and it is related to duration, intensity and muscle mass involved during exercise. A single session of exercise not only increases inflammatory cytokines, but also, elevates oxidative stress and leukocytosis. However, after regular exercise, reduced inflammatory markers and simultaneously increased anti-inflammatory substances are reported (7, 8). 2- Exercise with or without weight loss: One of the suggested mechanisms for reduced plasma levels of CRP is the decrease in level of adipocyte tissue. Adipocytes are the major sources of inflammatory cytokines such as TNFα and IL-6 (10). It is indicated that exercise training reduced plasma CRP levels in CAD patients regardless of being with or without metabolic syndrome, drug therapy or weight gain or loss (2, 11) and they showed that effect of exercise on CRP is independent of weight loss and statin therapy.3- Coexistence of chronic diseases: baseline inflammatory markers are important in the effect of exercise. In a large study, 20 weeks of training could not significantly reduce markers in control subjects; however, they showed that in basal high-level CRP, training significantly reduced CRP level (3). On the other hand, although, acute bout of exercise increases serum inflammatory and endothelial dysfunction markers, however, in patients with chronic heart failure who have increased level of inflammatory markers, these effects were not observed (12). It is indicated that short-term exercise (2 weeks) in control mice increased plasma levels of CRP, however, in db/db mice that had higher baseline CRP levels it reduced plasma CRP level (13). Thus, it seems that exercise has more benefits in those with high basal CRP level. 4- Age and gender effects: In children, acute and chronic exercise increases some plasma inflammatory markers such as IL-1 and TNFα which may be related to developmental changes (14). On the other hand, since female cycle has an important role in immunological response of exercise (14), in clinical studies, the age and gender of population should be considered (for example, OCP usage and menstrual stage).5- Diet supplementation: Diet supplementation plus exercise is more effective in reducing inflammatory markers than exercise alone. Diet supplementation by omega-3 fatty acids after eccentric exercise reduced much more plasma TNFα level (15).

Staphylococcus aureus is a prevalent pathogen worldwide. Methicillin resistant S. aureus (MRSA), which is usually multi-resistant in hospitals, has been a daunting challenge for clinicians for more than half a century. The aim of this systematic review and meta-analysis is to determine the relative frequency (RF) of MRSA in different regions of Iran. Search terms “Staphylococcus aureus”, “Methicillin”, “mecA” and “Iran” were used in PubMed, Scirus and Google Scholar. Two Persian scientific search engines and ten recent national congresses were also explored. Articles/abstracts, which used clinical specimens and had done PCR to detect the mecA gene, were included in this review. Comprehensive Meta-Analysis and Meta-Analyst software were used for statistical analysis.Out of 2690 results found in the mentioned databases, 48 articles were included in the final analysis. These studies were done in Ahvaz, Falavarjan, Fasa, Gorgan, Hamedan, Isfahan, Kashan, Mashhad, Sanandaj, Shahrekord, Shiraz, Tabriz, Tehran and Tonekabon. Pooled estimation of 7464 S. aureus samples showed that 52.7%±4.7 (95% confidence interval [CI]) of strains were mecA positive. MRSA RF in different studies varied from 20.48% to 90% in Isfahan and Tehran, respectively. We found a moderate heterogeneity (I2= 48.5%) of MRSA RF among studies conducted in Tehran (ranging from 28.88% to 90%, mean 52.7% [95% CI: 46.6%±58.8%]).According to the results of this study, MRSA RF in Iran is in the high range. Thus, measures should be taken to keep the emergence and transmission of these strains to a minimum.

Marfan syndrome (MFS) is a severe connective tissue disorder withan autosomal dominant inheritance pattern. Early diagnosis is critical in MFS. Because of the large size of fibrillin-1 gene (FBN1), the uniqueness of mutations, and the absence of genotype-to-phenotype correlations linkage analysis can be very helpful for early diagnosis of MFS. In this study, eight polymorphic markers were evaluated among families related to an affected pedigree.An extended family in Birjand, Iran, with numerous cases of Marfan Syndrome in three consecutive generations, is being reported. From all consented members of these families, peripheral blood samples were collected in tubes containing EDTA. DNA extraction was performed by the conventional salting-out method. Eight STR markers were selected for linkage analysis, including four intragenic markers (MTS1, MTS2, MTS3, and MTS4) and another four flanking FBN1 markers (D15S119, D15S126, D15S1028, and D15S143). PCR-amplified fragments were evaluated on 15% polyacrylamide gel.MTS1, MTS2, and MTS3 were informative in the extended pedigree. D5S1028 was the only non-MTS marker which showed an informative diagnostic capability.MTS markers were informative and useful in the molecular diagnosis of Marfan Syndrome in an extended pedigree. MTS1, MTS2, and MTS3 can be used as a prenatal or presymptomatic diagnosis for all members of the extended pedigree.

The aim of this study was to investigate the radioprotective effect of green tea against genotoxicity induced by gamma irradiation in cultured blood lymphocytes from 5 human volunteers.Peripheral blood samples were collected from volunteers before and 1, 3 and 5 hr after drinking a decoction 4 g green tea in 280 ml boiling water for 5 constitutive days with the same quantity. At each time point, the whole blood samples were exposed to 200 cGy of 60 Co gamma irradiation and then were cultured with mitogenic stimulation to determine the chromosomal aberration in micronucleus assay on cytokinesis-blocked binucleated cells.As expected, for each volunteer, the results showed a significant increase in the incidence of micronuclei after exposure to gamma irradiation as compared to non-irradiated control samples. Only lymphocytes blood sample collected 3 hr after drinking green tea exhibited a significant decrease in incidence of micronuclei compared to non-treated irradiated samples.These results suggest the radioprotective ability of green tea against ionizing radiation in human lymphocytes, at specified time after consumptior.

CpG oligodeoxynucleotides (CpG ODNs) have been shown to have potent immunostimulatory adjuvant activity for a wide range of antigens. Due to susceptibility of phosphodiester CpG ODNs (PO CpG) to nuclease degradation, nuclease-resistant phosphorothioate CpG ODNs (PS CpG) were currently utilized in an in vivo model. In this study, according to some recently reported drawbacks with PS CpG, the adjuvant potential of liposomal PO CpG as a substitute for PS CpG was evaluated. Soluble Leishmania antigens (SLA) as a model antigen and distearoylphosphatidylcoline (DSPC) as a neutral lipid were employed to prepare liposomes. Susceptible BALB/c mice received buffer, SLA, Lip-SLA, Lip-SLA-PS CpG, Lip-SLA-PO CpG, SLA+PS CpG, or SLA+PO CpG subcutaneously 3 times with 3 weeks intervals and then were challenged with Leishmania major’s live promastigotes. Blood and spleen samples were analyzed to determine the level and type of antibodies and cytokines. The number of live parasites in the spleen of immunized mice was determined. Moreover, the lesion size progress was assessed weekly by footpad swelling measurement.The results showed that mice immunized with Lip-SLA-PS CpG or Lip-SLA-PO CpG developed a significantly smaller footpad swelling, higher level of anti SLA IgG antibodies before and after challenge, and lower spleen parasite burden compared with the control groups. However, there was no significant difference between mice received Lip-SLA-PS CpG and those received Lip-SLA-PO CpG. The results demonstrated that liposomal PO CpG ODN could be used instead of PS CpG ODN to overcome the possible drawbacks.

Progesterone is a steroid hormone whose biology has been greatly studied within the confines of reproductive function. In recent years, the neuroprotective effects of progesterone have attracted growing interest. Glial cell line-derived neurotrophic factor (GDNF), is a neurotrophic factor which plays a crucial role in the development and maintenance of distinct sets of central and peripheral neurons. In the present study, we investigated the potential implication of GDNF in the neuroprotective action of progesterone. Cultured rat C6 glioma cells were treated with progesterone (100 nm, 1 µM, and 10 µM) or its vehicle. After 24, 36, 48 and 72 hr, GDNF protein levels were measured in the cell-conditioned media and cell lysates using a GDNF ELISA kit. Cell numbers were determined by a cell-counting assay kit.Forty-eight hr treatment with progesterone (10 µM) resulted in a significant elevation of GDNF secretion from C6 glioma cells that remained elevated up to 72 hr. The intracellular content of GDNF and cell numbers were not affected by progesterone treatment. Stimulation of GDNF release from glial cells appears as a potential mechanism through which progesterone exerts its neuroprotective effects.

Definite diagnosis of Hirschsprung’s disease (HD) is based on histopathological study, but there are limitations associated with standard histology and histochemistry in this regard. The aim of this study was to investigate calretinin immunostaining patterns in both ganglionic and aganglionic HD intestinal specimens and to compare them with control specimens.Specimens included 30 patients with histopathologic diagnosis of HD and 20 patients that underwent colectomy for other reasons (as control group). Eighty paraffin wax blocks of full thickness intestinal specimens (30 blocks of ganglionic segments, 30 blocks of aganglionic segments and 20 blocks of control group) were studied. Calretinin immunoreactivity and pattern of staining for ganglion cells (nuclear and cytoplasmic) and also nerve fibers in different layers of bowel were evaluated in IHC stained slides. There were positive immunostaining of nerve fibers in the lamina propria, submucosa and muscularis propria in control and patient group. There were also nuclear and cytoplasmic staining of ganglion cells in submucosa and muscularis propria in all specimens of both control group (100%) and ganglionic segments (100%). Calretinin immunoexpression of nerve fibers in muscularis propria of the aganglionic segments was negative in all but two cases (6.7%). This method had sensitivity of 93.3% and specificity of 100% for diagnosis of HD in full thickness specimens of intestinal wall. The positive predictive value was 100% and negative predictive value was 93.8%. Calretinin immunohistochemistry can be used on suction rectal biopsies as a reliable and adjunctive method to diagnose HD.

It is well known that prenatal stresses (PS) induce a variety of neurobiological and behavioral alterations, some of them involving the hippocampal formation. This study aimed to determine whether restraint stress influences the neuronal volume and number of granule cells in the hippocampus of adult rat offspring.Ten Wistar pregnant rats were randomly divided: stressed and control groups. Pregnant dams in the stressed group were placed in a Plexiglas restraint tube for 1 hr daily from days 15-21 of gestation. Neuroendocrinological consequences of prenatal stress exposure were evaluated in the male offspring on postnatal day 60. The total numbers and the individual volume of granule cells in the hippocampus were also estimated with the optical fractionator and the rotator methods, respectively. Prenatally stressed rats exhibited prolonged elevation in plasma glucocorticoid levels following acute exposure to restraint stress. Data also indicated that there is a decrease in neuronal volume of hippocampal granule cells in prenatally stressed compared with their controls (625±64.1 µm3 vs. 741±80.6 µm3). There was no significant difference in the total number of granule cells between prenatally stressed and control animals.The present study indicated that exposure of pregnant female during last week of pregnancy leads to a decline in neuronal size in hippocampus of adult male rats without neuronal loss. The present results may provide a basis for the understanding of the reported disturbances in behavior and learning of PS offspring.

Two new adjuvants from natural animal lipids (G2) and bacterial polysaccharide extracts (PC) were previously prepared by our group and showed a reduction in tracheal responsiveness. The aim of this study was to evaluate the preventive effect of recently introduced natural products (G2 and PC) on the development of asthma. Asthma was induced using a standard method in four groups of BALB/c mice. A non-sensitized control group was also included in order to be compared with treated groups. Three groups were premedicated with novel agents named G2, PC, and a combination of these two for 20 days before starting the induction of asthma. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells. Interferon-γ, and IL-4 and the histopathological of both lungs were also evaluated. In all pretreated groups, the inflammatory cells infiltration especially eosinophils and smooth muscle hyperplasia decreased significantly. BALF cytology also showed significant decrease in eosinophil count in all pretreated groups. There was a significant increase in the BALF and serum INF-γ in all pretreated groups but the combination of G2/PC was more effective. BALF IL-4 decreased significantly in the group pretreated with a combination of G2 and G2/PC (4.11±0.86 and 4.02±0.52 pg/ml in G2 and G2/PC, respectively). Serum IL-4 in the PC group was significantly higher than the sensitized control.G2 and PC may effectively prevent asthma development by activation of the type 1 T helper system.

Many studies have shown epidemiological links between strains isolated in tap water, and those isolated from patients. Molecular methods linked to PCR are more reliable and faster for identification of non- tuberculous mycobacteria (NTM). In this study molecular methods were used for identification and typing of NTM. Five hundred ml of 85 water samples was passed through 0.45 μm filters. The filters were transferred directly onto 7H10 Middle Brook solid media, containing 15% OADC. PCR for 16S rRNA was done and the PCR product (1500 bp) was sequenced. PRA of the hsp65 gene was investigated to identify the species of isolates. For evaluation of susceptibility of NTM to antimycobacterial agents, E-test method was used. The genus of 26 isolated NTM was confirmed by 16s rRNA sequence based method. Nineteen isolates of Mycobacteria were differentiated using hsp65genes PRA. The dominant isolates were M. fortuitum (26.7%), M. chelonae like organism(13.3%) and M. mucogenicum (13.3%). Seventy one percent of NTM species were resistant to isoniazid, 64% to rifampin, 57% to ethambutol, 35% to tetracycline, 14 % to azithromycin and 7.1 % to amikacin.The results showed that E-test method is not a proper technique for antimycobacterial assay because some NTM species are slow in growing and have no growth on Muller Hinton agar. Regarding the 16S rRNA sequence analysis, the identification of isolates was restricted to the genus level, because 99% similarity within 16S rRNA of two isolates may or may not determine the same species.

The brief interruption of cerebral blood flow causes permanent brain damage and behavioral dysfunction. The hippocampus is highly vulnerable to ischemic insults, particularly the CA1 pyramidal cell layer. There is no effective pharmacological strategy for improving brain tissue damage induced by cerebral ischemia. Previous studies reported that pentoxifylline (PTX) has a neuroprotective effect on brain trauma. The possible neuroprotector effects of PTX on behavioral deficit were studied in male Wistar rats subjected to a model of transient global brain ischemia. Animals (n= 32) were assigned to control, sham-operated, vehicle, and PTX- treated (200 mg/kg IP) groups. PTX administered at 1hr before and 3 hr after ischemia. Global cerebral ischemia was induced by bilateral common carotid artery occlusion, followed by reperfusion. Morris Water maze testing revealed that PTX administration in cerebral ischemia significantly improved hippocampal-dependent memory and cognitive spatial abilities after reperfusion as compared to sham-operated and vehicle-treated animals. After the behavioral test, the rats were sacrificed and brain sections were stained with Nissl staining. There were no significant differences between number of pyramidal cells in both control and PTX groups.Our study demonstrated that pentoxifylline had a protective effect on rats with transient global ischemia and could reduce cognitive impairment.

Sildenafil citrate is a new drug and has special properties that bring about nitric oxide effects on vascular smooth muscle. The aim of this study was to assess the effects of ovarian stimulation and sildenafil citrate injection on pinopode expression in mice.Thirty adult female mice were randomly divided into three groups: control, hyperstimulated and hyperstimulated +sildenafil citrate injection. In experimental groups mice received 7.5 IU human menopausal gonadotropin (HMG) and then after 48 hr received 7.5 IU human chorionic gonadotropic (HCG) hormones. After that every two females were put with one male in one cage for mating. Hyperstimulated +sildenafil citrate group were injected with sildenafil citrate (3 mg/mouse) every 24 hr for three days, after HMG injection. The animals were sacrificed by cervical dislocation 96 hr after HMG injection, and their uterine specimens (the middle one-third) were prepared for transmission electron microscope studies. Electron microscopy observations showed that in the control group there were long and short microvilli while no developed pinopodes were observed, however, in the two other groups, well developed pinopodes were expressed 4 days after HMG injection.The results showed that hyperstimulation of mice with sildenafil citrate may be more helpful in formation of pinopodes and implantation.

In this study we investigated the expression of GABAA receptor subunits during brain development. These receptors may change in the embryonic chick forebrain.Materials and Methodes:The expression levels of four types of GABAA receptor gamma subunits (γ1, γ2, γ3 and γ4) were quantified in the embryonic chick forebrain at 32 hr, 3, 7, 14, and 20 days of incubation and day one after hatching. The expression level of mRNA in the forebrain of embryonic chicken was measured using real-time RT-PCR. The expression level of each subunit increased gradually with development and reached a plateau on 20th day of embryonic development. A reduction was observed on day one after hatching in all gamma subunits.This may explain the different physiological and pharmacological function of GABA receptor gamma subunits before and after hatching.

Cytokines such as IL-1β are involved in inflammatory responses. This study evaluated the role of two different kinds of drugs (ibuprofen and celecoxib) on brain IL-10 and IL-1β after traumatic brain injury (TBI) in male rats. Rats were assigned into 6 groups: intact, sham, TBI, and treated rats with vehicle, celecoxib or iboprophen. Cytokine concentrations were quantified by ELISA kits. Groups showed no significant difference in brain IL-10 either after TBI induction or after treatment with ibuprofen or celecoxib. Serum IL-10 in vehicle or ibuprofen treated animals was lower than in sham groups (P< 0.01). Brain IL-1β decreased after treatment by ibuprofen or celecoxib (P< 0.001). There was no statistical difference in serum IL-1β in TBI and intact. Serum IL-1β significantly decreased in rats that received celecoxib compared to TBI group (P< 0.01). Based on our study IL-1β can decrease through both cyclooxygenase 1 (COX-1) and COX-2 pathway but serum IL-1β can decrease only by COX-2 pathway.

Cannabinoids have been implicated in memory deficit. We examined the effect of AM281, cannabinoid antagonist/inverse agonist in prevention of scopolamine-induced cognitive deficit. Object recognition task was used to evaluate memory in mice. Exploration time in the first and the second trial was recorded. The differences in exploration between a previously seen object and a novel object in second trial were taken as an index of memory. Scopolamine and AM281 were administrated at the same time, 40 min before second trial in the treatment group.Object discrimination was impaired after scopolamine (2 mg/kg; IP) administration. AM281 (2.5, 5 mg/kg; IP) significantly restored object recognition ability in mice treated with scopolamine by 75%.This study extends earlier findings, suggesting the interaction of cannabinoid and cholinergic system in memory. Additionally cannabinoid antagonists seem to show variable pharmacological properties.