The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement.

AIMS: Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement. MAIN METHODS: In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period. KEY FINDINGS: The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 µg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups. SIGNIFICANCE: Previous studies have shown that tramadol-induced CPP occurs through µ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R.

Vitamin D Status in Women with Pelvic Floor Disorders: A Meta-Analysis of Observational Studies.

The current evidence regarding the association between vitamin D status and pelvic floor disorder (PFD) are inconclusive. This meta-analysis was aimed to summarize existing data demonstrating the association between Vitamin D status and PFD using published observational studies. All national and international databases including Web of Science, PubMed, Google Scholar, and Scopus were searched up until January 30, 2018, and related published studies retrieved for meta-analysis. The effect sizes of Vitamin D status were presented as standardized mean difference (SMD) with 95% confidence interval (CI), using random-effect models and inverse variance method. The Cochran Q statistic and I 2 tests were used to evaluate the heterogeneity across included studies. Seven studies with 3219 women were included our meta-analysis. There was heterogeneity existing among included studies (I 2 = 96.4%, P < 0.001), so a random-effect model was used. The findings of this meta-analysis revealed that the mean serum Vitamin D levels in women with PFD were significantly lower than healthy women (SMD -0.60; 95% CI, -1.06, -0.13; P = 0.01). This meta-analysis demonstrates lower levels of serum Vitamin D in women with PFD rather than healthy women. Additional prospective studies regarding the association between Vitamin D status and PFD are required to confirm our findings.

Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD). METHODS: The study is randomized, double-blind, placebo-controlled clinical trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 109 CFU/day probiotic or placebo (n = 30 each group) that lasted 12 weeks. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was recorded at pre- and post-intervention. RESULTS: Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P < 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3 µmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7 µmol/L, P = 0.03) in comparison with the placebo. Additionally, probiotic consumption resulted in a statistically significant reduction in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1 µIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles. CONCLUSIONS: Our study evidenced that 12 weeks of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.

The effects of fatty acids consumption on OPG/RANKL/RANK system in cardiovascular diseases: Current status and future perspectives for the impact of diet-gene interaction.

Cardiovascular disease (CVD) is an overall term that comprises a number of related pathologies, these include peripheral arterial disease, cerebrovascular disease, coronary heart disease (CHD), venous thromboembolism, and rheumatic and congenital heart diseases. Fatty acids in the diet have been reported to affect CVD. The OPG/RANKL/RANK system appears to have a role in CVD outcomes. However, there have been few studies on the impact of diet-gene interaction for effects of fatty acids consumption on the OPG/RANKL/RANK system in CVD. This review focuses on the effects of fatty acids on OPG/RANKL/RANK in CVD.

The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin and Lipid in Patients with Parkinson's Disease: A Randomized, Double-blind, PlaceboControlled Trial.

BACKGROUND: This study was conducted to evaluate the effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted in 50 patients with PD as a pilot study. Participants were randomly allocated into two groups to take either 8×109 CFU/day probiotic supplements or placebo (n = 25 each group, one capsule daily) for 12 weeks. Gene expression related to inflammation, insulin, and lipid was quantified in peripheral blood mononuclear cells (PBMC) of PD patients, with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, probiotic intake downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), IL-8 (P < 0.001) and tumor necrosis factor alpha (TNF-α) (P=0.04) in PBMC of subjects with PD. In addition, probiotic supplementation upregulated transforming growth factor beta (TGF-ß) (P = 0.02) and peroxisome proliferatoractivated receptor gamma (PPAR-γ) (P = 0.03) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of probiotic intake on gene expression of low-density lipoprotein receptor (LDLR) and vascular endothelial growth factor (VEGF) in PBMC of patients with PD. CONCLUSION: Overall, probiotics supplementation for 12 weeks in PD patients significantly improved gene expression of IL-1, IL-8, TNF-α, TGF-ß and PPAR-γ, but did not affect gene expression of VEGF and LDLR, and biomarkers of inflammation and oxidative stress.

The effects of probiotic supplementation on metabolic status in type 2 diabetic patients with coronary heart disease.

BACKGROUND: This study was conducted to evaluate the effects of probiotic supplementation on metabolic profiles in diabetic patients with coronary heart disease (CHD). METHODS: This randomized, double-blind, placebo-controlled trial was performed among 60 diabetic patients with CHD, aged 40-85 years at a cardiology clinic in Kashan, Iran, from October 2017 through January 2018. Patients were randomly divided into two groups to take either probiotic supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at the beginning of the study and after the 12-week intervention to determine related markers. RESULTS: After 12-week intervention, probiotic supplementation significantly decreased fasting plasma glucose (ß - 20.02 mg/dL; 95% CI - 33.86, - 6.17; P = 0.005), insulin (ß - 2.09 µIU/mL; 95% CI - 3.77, - 0.41; P = 0.01), insulin resistance (ß - 0.50; 95% CI - 0.96, - 0.03; P = 0.03) and total-/HDL-cholesterol ratio (ß - 0.27; 95% CI - 0.52, - 0.03; P = 0.02), and significantly increased insulin sensitivity (ß 0.008; 95% CI 0.001, 0.01; P = 0.02) and HDL-cholesterol levels (ß 2.52 mg/dL; 95% CI 0.04, 5.00; P = 0.04) compared with the placebo. Moreover, probiotic supplementation led to a significant reduction in serum high sensitivity C-reactive protein (ß - 0.88 mg/L; 95% CI - 1.39, - 0.38; P = 0.001), and a significant elevation in total antioxidant capacity (ß 108.44 mmol/L; 95% CI 47.61, 169.27; P = 0.001) and total glutathione levels (ß 45.15 µmol/L; 95% CI 5.82, 84.47; P = 0.02) compared with the placebo. Probiotic supplementation did not affect other metabolic profiles. CONCLUSIONS: Overall, we found that probiotic supplementation for 12 weeks had beneficial effects on glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, biomarkers of inflammation and oxidative stress in diabetic patients with CHD.Trial registration Clinical trial registration number http://www.irct.ir: IRCT2017082733941N5.