Caffeine modulates apoptosis, oxidative stress, and inflammation damage induced by tramadol in cerebellum of male rats.

Tramadol, an opioid used as analgesic, can induce neurotoxic effects associated to cognitive dysfunction. Moreover, caffeine has been reported to have neuroprotective effects. In this regard, we hypothesized that administration of caffeine can modulate tramadol-induced damages in cerebellum. For this study, forty male Wistar rats were divided into four groups: the control group, the tramadol group (50 mg/kg), the caffeine group (37.5 mg/kg), and the tramadol+caffeine group (50 mg/kg tramadol+37.5 mg/kg caffeine). At the end of study (day 21), after performing rotarod behavioral test, cerebellum tissue samples were removed and prepared for further evaluations including biochemical profile markers (MDA, GPx, and SOD), immunohistochemistry for Caspase-3, as well as the expression of genes involved in cellular processes such as inflammation markers (IL-1ß, HMGB1, IL-6, and TNF), apoptosis markers (Caspase-3, Caspase-8, Bax, and P21), and autophagy markers (LAMP2, ATG5, BECN1, and ATG12). Stereological evaluations were performed to determine the total volume of granular and molecular layers and white matter of cerebellum tissue and numerical density of the Purkinje cells. Our results showed that the stereological parameters, biochemical profiles (except MDA) and behavioral function were significantly higher in the tramadol+caffeine group compared to the tramadol group. Autophagy-related genes were significantly upregulated in tramadol+caffeine group compared to the tramadol group. While the expression of inflammatory and apoptosis genes, MDA level, as well as density of apoptosis cells were significantly lower in the tramadol+caffeine group compared to the tramadol group. Briefly, it can be concluded that administration of caffeine has neuroprotective effects in cerebellar damages induced by tramadol.

Report of a Novel Bilateral Variation of Sciatic and Inferior Gluteal Nerve: A Case Study.

INTRODUCTION: The sciatic nerve is the thickest nerve of the sacral plexus which innervates many muscles and vast areas of the skin of the lower limb. It leaves the pelvis via the greater sciatic foramen, emerges into the gluteal region by passing under the piriformis muscle, and descends beneath the gluteus maximus to divide into its terminal branches; the tibial and common peroneal nerve at the superior angle of the popliteal fossa. In some cases, the sciatic nerve divides into the tibial and common peroneal nerves at a higher level and one of them or both passes through or over the piriformis muscle. CASE PRESENTATION: We find an interesting bilateral variation of sciatic nerve accompanying a very thick inferior gluteal nerve on the right side and unusual route and branching of tibial and common peroneal nerves on the left side. CONCLUSION: As in conditions like intramuscular injections, gluteal surgeries, and piriformis syndrome such variations may increase the risk of injury, it is important for the medical team to be aware of them. In this paper, by reporting many variations in a cadaver, we emphasize the importance of anatomical variations, especially for surgeons and nurses.

Evaluation of Glutathione Bioactivity on Toxoplasma Gondii in BALB/c Mice Post Impact of Selenium and Calcium Supplementation.

BACKGROUND: Studies have shown that selenium is an essential component of glutathione as an important antioxidant to reduce oxidative stress and inhibit intracellular parasites' growth. In contrast, calcium in the cytosol of such parasites plays a key role in the entry of the parasite into the host cell and its primary motility. AIMS AND OBJECTIVES: The present study was designed to evaluate and compare glutathione peroxidase bioactivity effects post administration of selenium and calcium in BALB/c mice infected by Toxoplasma gondii. METHODS: Sixty BALB/c mice susceptible to T. gondii were randomly divided into twelve groups of case and control groups. There were six control groups including two positive controls infected only with the parasites either 104 or 5×104, non-infected and untreated groups. Treated controls received only calcium, selenium, or both respectively. Case groups were infected with 104 or 5×104 parasites. While each set of three case groups separately received minerals alone or together. Mice were orally fed with 200 µg selenium, 50 µg calcium or their combination for 7 days. Mice were infected by parasite's tachyzoites. Sera of mice were kept and the peritoneal macrophages were isolated for counting tachyzoites during infection. RESULTS: The results showed that selenium unlike calcium was significantly effective in reducing Toxoplasma tachyzoites compared to control groups. Moreover, glutathione peroxidase [GPX] activity was elevated in mice treated with selenium and vice versa decreased in mice treated with calcium. CONCLUSION: Administration of selenium unlike calcium reduced Toxoplasma tachyzoites proliferation by elevating bioactivity of selenium-dependent detoxification enzyme, GPX.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

The effect of regulatory aerobic exercise on lipoproteins index of plasma in epileptic male rat

There is no report on the evaluation aerobic exercise on lipoproteins and Atherogenic Index of Plasma (AIP) in epileptic male rats. In the present study our purpose was to elucidate the effect of regulatory aerobic exercise on Lipoproteins and (AIP) in epileptic male rat by pentylentetrazol. In this experimental study, 40 male rats randomly divided into 2 main different epileptic (kindling) and non-epileptic groups (n = 20). The epileptic groups were kindled by intraperitoneal injection of 40 mg/kg pentylentetrazol (PTZ), then divided into two epileptic subgroups, including the aerobic exercise and without exercise. The non-epileptic groups were divided into two subgroups including aerobic exercise and without exercise. After 6-week exercise rats were deep anesthetized by ketamine, and then blood was taken. Data were analyzed by t-test and ANOVA. The epileptic male rats that received aerobic exercise increased significantly the seizure of parameters S2L and S4L, compared with the epileptic group that did not receive regular exercise P < 0.05. Also, in the aerobic exercise groups decreased the parameters S5D and SD compared with the control group P < 0.001. The exercise significantly de-creased total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDLP) as compared with the epileptic group without exercise P < 0.001. The present study indicates that the aerobic regularly exercise not only decreased the duration of seizures, but also reduce the vascular risk factor in epileptic group rats

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The effects of two types of renin-angiotensin system inhibitors on the hypertension induced by new pressor protein associated with beta-factor XIIa in rats.

BACKGROUND AND PURPOSE: New pressor protein (NPP) is a human plasma enzyme, which is structurally related to the beta-fragment of activated factor XII. The present study aimed to compare the effects of angiotensin converting enzyme inhibitors (captopril) and angiotensin type 1 receptor blocker (losartan) on the hypertension induced by NPP injection in normal (sham-2NX) and bilaterally nephrectomized rats (2NX). EXPERIMENTAL APPROACH: In total, 60 male Wistar rats were sham operated or bilaterally nephrectomized under anesthesia. After 24 h of anesthesia with Inactin® (100 mg/kg), their systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before and after the intravenous administration of captopril, losartan, and NPP. FINDINGS / RESULTS: In the sham-2NX group, after NPP injection, changes were observed in SBP (145.99 ± 3.6 mmHg), DBP (93.9 ± 3.87 mmHg), and HR (400.29 ± 12.78 bpm). In the captopril group, SBP and DBP had no significant changes, while HR increased significantly (P = 0.001). In the losartan group, SBP and DBP decreased (P = 0.001 and P = 0.000, respectively), while HR had no significant changes. In the 2NX group, after NPP injection, changes were denoted in SBP (127.89 ± 9.03 mmHg), DBP (65.86 ± 5.69 mmHg), and HR (333.35 ± 11.47 bpm). In addition, captopril injection increased DBP (P = 0.016) and HR (P = 0.036) in response to NPP injection, while losartan injection had no significant effects in this regard. CONCLUSION AND IMPLICATIONS: It could be concluded that losartan could improve hypertension in normal rats, while captopril deteriorated hypertension in bilaterally nephrectomized rats in this hypertension model.

Protective impacts of erythropoietin on myelinization of oligodendrocytes and schwann cells in CNS and PNS following cuprizone-induced multiple sclerosis- histology, molecular, and functional studies.

BACKGROUND: Multiple sclerosis (MS) is known as one of the chronic inflammatory diseases characterized by lesions in the central nervous system (CNS) and peripheral nervous system(PNS) resulting in serious cognitive or physical disabilities as well as neurological disorders. Thus, protective effects of erythropoietin(EPO) on myelinization of oligodendrocytes and schwann cells respectively in CNS and PNS following MS induced by cuprizone (CPZ) administration in young female mice. METHODOLOGY: To meet the objectives of this study; a chow with 0.2 % CPZ was used to feed young female C57BL/6 J mice for six weeks. After three weeks, EPO (5000 IU/kg body weight) was administered via daily intra-peritoneal injection for simultaneous treatment of the mice. Measurement of latency and amplitude of the compound muscle action potential (CMAP) of gastrocnemius muscle was also performed every week during a six-week demyelination interval, and then examinations were fulfilled on the histological sections of the brain and sciatic nerve. Therefore, we focused on the removal of the sciatic and sciatic nerve specimens and analysis of the use of the stereological procedures, western blot, immuno-histochemistry, and gene expression. RESULTS: According to the results of this study, MBP levels increased in oligodendrocytes (OLs) in the treated mice. Moreover, EPO could concurrently enhance motor coordination and muscle activity. Analysis showed the significant enhancement of the gene expression of MBP, MAG, and S100, as well as stereological variables in the treatment group in comparison with the cuprizone (CPZ) group. CONCLUSION: Findings could help further understand the alleviation of the detrimental impacts of CPZ using the OLs that would be capable of increasing the level of S100, MAG, and MBP.

A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.

Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.

Prognostic Role of PTEN Gene Expression in Breast Cancer Patients from North-East Iran

Background: PTEN protein is one of the most important tumour suppressor factors which is detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression in breast cancer patients. Materials and Methods: This descriptive-analytical study was conducted on 100 breast cancer patients referred to Sabzevar hospitals in the north-east of Iran between 2010 and 2011, who were followed up to 2015. PTEN gene expression in tissue samples was determined using specific monoclonal antibodies and data were analyzed using Chi-square test and Fisher's exact test. Patient survival was analyzed after 4 years of follow-up using the Cox regression model. Results: PTEN gene expression was evident in 70 of 100 cnacer samples but was found at high levels in all non-cancer samples. There was an inverse significant relationship between PTEN gene expression and tumour stage or tumour grade (p<0.001). The expression of PTEN in invasive ductal tumours was lower than in non-invasive tumours. There was also an inverse significant relationship between the hazard of death and PTEN gene expression (p<0.001). In addition, there was an inverse significant relationship between tumour stage and hazard of death (p<0.001). Conclusion: These findings indicate that lack of PTEN gene expression can be a sign of a worse prognosis and poor survival in breast cancer cases.

Effect of hydroalcoholic extract of Anethum graveolens leaves on the dentate gyrus of the hippocampus in the epileptic mice: a histopathological and immunohistochemical study.

Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae (Umbelliferae) and is used traditionally for the treatment of convulsion and diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic extract of A. graveolens leaves on the histology of the dentate gyrus of the hippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this experimental study, the epileptic BALB/c mice kindled by PTZ were randomly divided into four groups of 10 animals each. Three experimental groups received 250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control group received phosphate-buffered saline (PBS). After the treatment period, the mice were anesthetized, and their hippocampi were dissected for the histopathological analysis, and immunohistochemical analysis for caspase-3 activity. Histopathological examinations showed that the mean numbers of the healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of A. graveolens extracts were significantly higher than those of the mice received 250 and 750 mg/kg/day of the extracts as well as the control group (P < 0.05 and P < 0.001, respectively). In addition, the results of immunohistochemical analysis revealed that in mice treated with 500 mg/kg/day of A. graveolens; the numbers of caspase-3-positive cells in the dentate gyrus were significantly lower than those of the two other test and the control groups. The findings of this study suggest that 500 mg/kg/day of the A. graveolens extract could have protective effect on the dentate gyrus of the hippocampus in the epileptic mice.

Prognostic Role of PTEN Gene Expression and Length of Survival of Breast Cancer Patients in the North East of Iran.

PTEN protein is an important tumour suppressor factor detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression focusing on length of survival in breast cancer patients. This descriptive-analytical study was conducted on 100 breast cancer cases referred to Sabzevar hospitals in the north east of Iran between 2010 and 2011, followed up to 2015. The PTEN gene expression of tumour tissue samples was determined using specific monoclonal antibodies. The data were analyzed using Chi-square test and Fisher's exact test. Patient length of survival was analyzed after 4 years of follow-up using the Cox regression model. The PTEN gene was expressed in 70 of 100 samples, while being found at a high level in all noncancerous samples. There was an inverse significant relationship between expression of PTEN and tumour stage and grade (p<0.001). In addition, expression of PTEN in invasive ductal tumours was less than in non-invasive tumours. There was also an inverse significant relationship between the likelihood of death and PTEN gene expression (p<0.01). These findings indicate that lack of PTEN gene expression can be sign for a poor prognosis in breast cancer.

Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran.

BACKGROUND/AIMS: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. METHODS: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. RESULTS: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). CONCLUSIONS: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease.

The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice.

There have been conflicting reports regarding the role of ethanol in seizure. Another effect of ethanol is vascular damage in cerebral tissue. This study investigates the influence of ethanol on antiepileptic efficacy of valproic acid (VPA) and cerebral microvascular structure. In this study, four groups of mice (25-30 g) received pentylenetetrazole (PTZ) i.p. (37 mg/kg) every other day. Different groups of animals received an injection of saline, ethanol (1 g/kg), VPA (100 mg/kg), or VPA and ethanol 30 min before PTZ. Animals in groups 5 and 6 received only ethanol and saline, respectively. After recording seizure parameters, the animals were sacrificed under deep anesthesia and the brains of the animals were removed and fixed, thereafter coronal sections were prepared from cerebral cortex. Then, the cerebral microvessels were counted in microscopic sections after hematoxylin-eosin staining. Ethanol injection (1 g/kg) for 7 days decreased stage 4 duration and increased latency to the onset of stage 1 and stage 4 of seizure (p < 0.001). Concomitant injection of VPA (5 min before ethanol) and ethanol had significantly stronger anticonvulsant effects than VPA alone (p < 0.001). Furthermore, the findings showed that not only the cerebral microvessels increased significantly in ethanol group compared with saline group (p < 0.05), but also there were morphological changes in vascular endothelium in ethanol group. The obtained results show that short-term ethanol administration has anticonvulsant effects along with VPA, and enhances the anticonvulsant effects of VPA. Furthermore, it is possible that VPA leads to decreased ethanol-induced vascular damage.

The prognostic value of the P53 protein and the Ki67 marker in breast cancer patients.

OBJECTIVE: To investigate and compare the prognostic value of P53 and Ki67 markers in patients with breast cancer in Sabzevar, north east of Iran. METHODS: A descriptive analytical study was conducted on 80 patients with breast cancer who were admitted to the hospitals in Sabzevar in 2006 and they were followed up to 2010. The expression of ki67 and stability of p53 genes were determined by immunohistochemistry. To assess the disease prognosis, patients were followed up to 48 months. Data were analyzed using SPSS software version 11.5. Chi-square, Fisher's exact test, Kaplan-Miere and Log Rank tests were used for statistical purposes. RESULTS: Eighty cancerous tissue samples were examined. The Ki67 marker was present in 37 (46.3%) cases and the P53 protein stability in 39 (48.8%) cases were observed. There was a significant relationship between ki67 gene expression and tumour stage (p = 0.001) or tumour type (P = 0.02). There was also a significant relationship between the survival rate and the tumor stage (P = 0.008). The Ki67 marker had significant relationship with the survival rate (P = 0.031), but over expression of P53 protein did not show such significance (P = 0.385). CONCLUSION: The results showed that the Ki67 marker was more important than P53 protein in prognosis of the breast cancer patients.