Iranian Journal of Basic Medical Sciences
Volume:14 Issue: 2, Mar-Apr 2011

Objective(s)Carbamazepine (CBZ) is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects (NTDs), growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice.Materials and MethodsSixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal injection (IP) of 30 mg/kg (I) or 60 mg/kg (II) of CBZ on gestational days (GD) 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg (III) or 60 mg/kg (IV) of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X2 test using SPSS software.ResultsThe mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations.ConclusionThis study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research.

Objective(s)The aim of this study was to evaluate the effects of dexamethasone on striatal dopaminergic, glutamatergic and gamma amino butyric acid (GABA) ergic neurotransmission in normal and parkinsonian rats.Materials and MethodsDexamethasone (0.15, 0.30, 0.60 and 0.8 mg/kg) was administered to normal or parkinsonian rats (i.p.) followed by the analysis of the striatal neurotransmitters concentrations. Additionally, the effect of dexamethasone on the damaged Substantia nigra pars compata (SNc) neurons has been investigated. ResultsDexamethasone resulted in decreased level of striatum glutamatergic-GABAergic and enhanced dopaminergic neurotransmission in normal and parkinsonian rats. In addition, acute treatment with dexamethasone did not improve the lesion at all. ConclusionThese findings suggest the new therapeutic mechanism of action for dexamethasone in Parkinson’s disease animal model.

Objective(s)In the present study, the effects of aqueous-ethanolic extract from Rosa damascena on heart rate and contractility were examined. Materials and Methods Isolated guinea-pig hearts were perfused through aorta in a Langendorff mode. Heart rate (HR) and contractility were determined in the presence of four concentrations of the extract (0.1, 0.2, 0.4 and 1.0 mg %) and isoprenaline (1, 10, 100 nM and 1 µM) in comparison with baseline values in the presence and absence of propranolol (n= 10 for each group). ResultsBoth isoprenaline and the extract caused increase in heart rate and contractility (P< 0.05 to P< 0.001). The percent increased in HR due to the final concentration of isoprenaline in the absence of propranolol was significantly greater than that of the extract (P< 0.01). Propranolol caused significant reduction in both HR and contractility (P< 0.05 for both) but this effect was significantly reversed by isoprenaline and the extract (P< 0.05 to P< 0.001). The percent increased in heart contractility due to the final concentration of the extract in the absence and presence of propranolol was significantly greater than that of isoprenaline (P< 0.05 for both cases). There was significant correlation between both HR and heart contractility with concentration of isoprenaline and the extract (P< 0.05 to P< 0.001). ConclusionIn conclusion this study showed a relatively potent inotropic and chornotropic effect for Rosa damascena on isolated guinea-pig heart.

Objective(s)During recent years, there has been an increasing interest in contribution of environmental pollutants as heavy metals to human male infertility. Present study was aimed to investigate the effects of maternal lead acetate exposure during lactation on postnatal development of testis in offspring rats.Materials and MethodsA total of 60 female rats randomly divided into four equal groups; control and three treatment groups received 20, 100 and 300 mg/kg/day lead acetate via drinking water from day 2 to day 21 of lactation. At 7, 14, 21, 28, 60, 90 and 120 days after birth, the testis weight and volume of offspring were measured and their epididymal semen analyzed. Following tissue processing, 5 μm sections were stained with haematoxylin-eosin and evaluated with quantitative techniques. Testicular parameters in different groups were compared by one-way ANOVA.ResultsTestis weight and volume of offspring decreased significantly in a dose-related manner in moderate (P< 0.05) and high (P< 0.01) doses groups. Dose-dependent significant reductions were seen in seminiferous tubules diameter and germinal epithelium height during neonatal, prepubertal and postpubertal periods in moderate (P< 0.05) and high (P< 0.01) doses groups until 90 and 120 days after birth, respectively. Significant decreases were observed in mean sperm density of offspring at puberty in moderate and high doses groups until 90 and 120 days after birth, respectively. Testosterone levels decreased significantly in a dose-related manner at puberty in moderate and high doses groups. ConclusionPresent study showed maternal lead acetate exposure during lactation caused dose-related and long-term alterations of testicular parameters in offspring rats.

Objective(s)Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial and community infections. Biofilm formation, mediated by a polysaccharide intercellular adhesin (PIA) and encoded by the ica operon, is considered to be an important virulence factor in both S. epidermidis andS. aureus. However, the clinical impact of the ica locus and PIA production is less well described in S. aureus. We studied biofilm formation in clinical isolates of MRSA in relation to the presence of the icaoperon. Materials and MethodsForty five MRSA were studied for biofilm formation by colony morphology on Congo red agar (CRA) and the microtitre plate assay (MtP). Presence of the ica genes was detected by PCR and specific primers. ResultsThe results showed that 53.3% of the isolates had the potential to form biofilm by colony morphology of which, 75% carried the ica operon. Weak biofilm production was observed in the MtP assay by 57.8%, of which 53.8% harbored the ica operon. However, about 70% of biofilm non-producers also carried the icaoperon. ConclusionOverall, there was no agreement between the icaAB gene carriage and biofilm phenotype by either of the two phenotypic methods. However, 91% of biofilm formers on CRA also produced biofilm in the MtP assay.

Objective(s)Matrix metalloproteinases comprise a family of enzyme that is able to degrade components of extra cellular matrix. There are single nucleotide polymorphisms in the promoter regions of several genes with ability to influence cancer susceptibility. The aim of this study was to analyses association between MMP2 and MMP9 promoter polymorphisms and head and neck squamous cell carcinoma occurrence and progression.Materials and MethodsAcase- control study was performed including 80 head and neck squamous cell carcinoma patients and healthy controls for MMP2 and 86 head and neck squamous cell carcinoma patients and 72 healthy controls for MMP9. Blood samples were genotyped for MMP2 and MMP9 using polymerization chain reaction– restriction fragment length polymorphism method (PCR-RFLP). Statistical analysis was performed using SPSS 12.0 software. Results Our results showed that distribution of MMP2 genotype between controls and patients was significantly different (χ2= 10.3, P= 0.005). Comparison between CC genotype in HNSCC patients and controls showed that C allele modified the risk of HNSCC progression (OR= 2.6, 95% CI, 1.0046–6.729). The MMP9 genotype distribution among HNSCC patients was significantly different (χ2= 14.56, P= 0.0007). The frequency of TT genotype in HNSCC patients was different from healthy controls and was more common genotype in HNSCC cases (OR= 2.18, 95% CI, 0.7052–6.7854).ConclusionOur results suggested an association of the MMP2 and MMP9 SNP with the development of HNSCC. Also, our results showed that MMP, MMP9 genotypes and smoking were related to HNSCC progression.

Objective(s)Studies have described immunomedulatory effects of sun exposure and ultraviolet radiation on infectious and neoplastic diseases. Here the effect of exposure to low potency radiation of sun on the course of leishmaniasis in mice was studied. Materials and MethodsFifteen BALB/c mice were exposed to suberythemogenic doses of sun (mean 180 mJ/cm2/day of UVB) 2 months before and 4 months after Leishmania major inoculation to food pad. Control group was kept in the sun protected environment. From 2nd to 17th week after inoculation, size of the lesion was recorded in each group weekly and at last week the parasite burden in spleen was detected. Results were compared between two groups. ResultsSeven mice from case group and 9 mice from control group survived up to last week. The mean lesion size was 0.90±0.59 cm in exposed and 4.01±3.59 cm in unexposed mice (P= 0.037). Parasite burden in spleen of case and control groups were 5.5±4.61 and 106.94±279.76 respectively (P= 0.006).ConclusionChronic exposure of BALB/c mice to suberythemogenic doses of sun suppressed skin lesion and decreased the extension of L. major to spleen.

Objective(s)Achillea genius is widely used in traditional medicine for gastrointestinal disorders. The aim of this study was to investigate the effects of aqueous-ethanol extract of Achillea wilhelmsii on rat’s gastric motility in basal and vagal stimulated conditions. Materials and MethodsTwenty four Wistar rats were randomly divided into two groups: control and test. The extract was prepared by maceration which was used to prepare three 0.5 ml samples of three doses (0.5, 1 and 2 mg/kg) in the test group. The same volume of saline was used in the control group. Gastric motility was measured by inserting a small balloon in the stomach which was connected to a pressure transducer. The data were recorded for 25 min duration after each dose and these data were analyzed for 3 intermittent five min intervals (t1= 0-5, t2= 10-15 and t3= 20-25 min).ResultsThe extract at basal condition decreased intragastric pressure (IGP) by 1 mg/kg dose in the t3 and 2 mg/kg in the t2 and t3 intervals. The extract at vagal stimulated condition decreased IGP by 1 and 2 mg/kg doses in the t2 and t3 intervals. The extract reduced contraction amplitude at basal condition by 2 mg/kg dose in the t2 and t3 intervals. At vagal stimulated condition contraction amplitude was reduced by 1 mg/kg dose in the t2 and t3 by 2 mg/kg in all three intervals. The extract showed no effect on frequency of gastric contraction in either basal or vagal stimulated conditions. ConclusionThe extract showed an inhibitory effect on gastric motility in both basal and vagal stimulated condition. This inhibitory effect may be exerted by an antagonistic effect on acetylcholine dependent calcium influx or release of calcium from intracellular storage in gastric smooth muscle.

Objective(s) Bone is a dynamic tissue that is continuously renewed throughout life by the process of bone remodeling. Antioxidant system might be involved in the pathogenesis of bone loss, so the aim of this study was to evaluate the total antioxidant capacity (TAC), vitamin C and vitamin E levels of plasma besides measuring enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) enzymes activity in Iranian osteoporotic women comparing to the control group.Materials and MethodsBone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual x-ray absorptiometry. The participants were divided into groups: a) total participants (-3.9 ≤ T–score ≤ 3.6) including 192 women, b) the control group (T-score ≥ -1) including 76 women, c) the total patients (T-score < -1) including 76 women. Then, plasma TAC, vitamin C levels, SOD and GR activities, erythrocyte CAT were measured using spectrophotometrical methods separately, and for vitamin E by HPLC analysis.ResultsComparing the control group and osteoporotic women showed that: a) plasma levels for vitamin C and erythrocyte CAT were markedly lower in the patients than in the controls, but plasma activity of TAC, SOD and GR were significantly higher, respectively. b) the differences were higher between control and patients with severe disease (T-score <-1.7) comparing to patients in the group with milder disease (-1.7 ≤ T-score <-1). c) Femoral neck BMD adjusted with age and BMI showed a positive and significant correlation with plasma levels of vitamin C in all subjects, but this relation was reverse or negative for TAC, SOD and GR.ConclusionIt seems that a physiologic increase in the amount of some antioxidants occurs in osteoporosis; even though this amount may not be sufficient for the human body requirements.

Objective(s)Single injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence.Materials and MethodsConditioning to morphine (2.5-10 mg/kg, s.c.) was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing.ResultsThe results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p.) injections pre-testing of the response to morphine (7.5 mg/kg, s.c.) caused a significant aversion at the higher doses (0.4 mg/kg, i.p.). This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala) prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of NG-nitro-L-arginine methyl ester (L-NAME) (intra-central amygdala).ConclusionA single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.

Objective(s)The objective of this study was to determine the effect of aqueous extract of Origanum vulgare L. ssp. Viridis (ORG) on discrimination learning and long term potentiation (LTP) in CA1 region of the rat hippocampus. Materials and MethodsA group of adult male Wistar rats weighing 275±25 g received aqueous extract of ORG (150, 300, 450 mg/kg/day) by intraperitoneal injection for one week, and the other group received saline (n= 6). A wooden T-maze was used to evaluate the discrimination learning. In electrophysiological experiments, the effect of ORG leaves extract on induction and maintenance of long term potentiation (LTP) in CA1 hippocampus area was determined. LTP was evaluated in CA1 region after high-frequency stimulation (200 Hz) of the Schaffer collaterals. Also, serum antioxidant levels were analyzed in the two groups (n= 4).ResultsStatistical analysis showed significant decreases in the number of total (significantly at the dose of 300 and 450 mg/kg) and wrong (significantly at the dose of 300 mg/kg) entrance into opposite box of T-maze procedure in ORG-treated animals (P< 0.05). In electrophysiological study, the rats which had received ORG (150, 300, and 450 mg/kg) showed an increase in both population spike amplitude (59.7±14.1%, 85±14.7% and 49.3±8.7% respectively, compared to 39±9.2% increase in saline group) and maintenance of LTP in hippocampus CA1 after high frequency stimulation in Schaffer collateral pathway. In serum antioxidant assay, level of antioxidants in ORG groups (300 and 450 mg/kg) remarkably increased in comparison to saline group (P< 0.05 and P< 0.001, in turn).ConclusionOur results suggest that Origanum aqueous extract can improve the learning criteria in rats.

Objective(s) The aim of this study was to evaluate the expressions of two angiogenic immune-markers (CD-31 and VEGF), and one proliferative immune-marker (Ki-67) in oral pyogenic granulomas (PG), hemangiomas (Hem) and inflammatory gingivitis (IG).Materials and MethodsSixty cases of PG, Hem and IG (twenty cases each) were examined. Immunohistochemical (IHC) staining was performed based on routine techniques. The microvessel density (MVD) index was also evaluated. ResultsThe male to female ratio was 1:2. The mean age was 33.3 years old (±20.52). The reactivity percentages for all three markers (CD-31, VEGF and Ki-67) were significantly higher in PG compared to Hem (56.8%, 13.8% and 23.0% vs. 28.3%, 7.0% and 5.4%, respectively). The mean MVD in PG was also significantly higher than in Hem (26.1±0.11 vs. 13.6±0.08). There was no statistically significant difference between PG and IG.ConclusionThe current study supports the common nature of pyogenic granulomas and inflammatory gingivitis.