Effect of Vitamin D Supplementation on the Regulation of Blood Pressure in Iranian Patients with Essential Hypertension: A Clinical Trial.

BACKGROUND: Low serum vitamin D level is associated with both high blood pressure and incidence of primary hypertension. Experimental studies suggest that vitamin D supplements may reduce blood pressure. OBJECTIVE: The aim of this study was to investigate whether vitamin D supplementation reduces systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Iranian patients with essential hypertension. METHOD: A total of 173 patients with essential hypertension participated in this open-label clinical trial. SBP, DBP, and serum vitamin D levels were measured at baseline and at the end of the study. Vitamin D was administered at a dose of 50,000 IU/week, and 1000 IU/day in patients with serum vitamin D levels <20 ng/mL and 20-30 ng/mL, respectively, for 8 weeks. RESULTS: Based on serum vitamin D levels, 45.1%, 17.3%, and 29.5% of patients were deficient, insufficient, and sufficient for vitamin D intake, respectively. Baseline serum levels of vitamin D were not correlated with SBP, DBP, and MAP at the beginning of the study (p = ns). Multiple logistic regression analysis revealed that the risk of vitamin D deficiency was 2.5-fold times higher in women than in men (p = 0.03). After 8 weeks of supplementation with vitamin D, mean SBP and MAP were significantly reduced by 5.5 ± 16.16 (p = 0.01) and 3.7 ± 9.24 (p = 0.004) mmHg, respectively. Neither sex nor age could significantly predict BP response to vitamin D supplementation. CONCLUSION: Vitamin D supplementation may significantly reduce SBP and MAP but not DBP in patients with essential hypertension.

Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals. METHODS: In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period. RESULTS: Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin). CONCLUSION: The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

Effect of angiotensin receptor blockade on prevention and reversion of tamoxifen-resistant phenotype in MCF-7 cells.

Tamoxifen (TAM) is a standard adjuvant endocrine therapy in postmenopausal breast cancer patients, but innate or acquired TAM resistance has remained to be a therapeutic challenge for clinicians. The aim of this study was to explore the possible participation of renin-angiotensin system (RAS) in the acquisition of TAM resistance and try to prevent and regress the resistance using an angiotensin II receptor type-1 (AGTR1) blocker, losartan. Establishment of TAM-resistant (TAM-R) cells was accomplished by continuous exposure of MCF-7 cells to 1 µmol/L TAM. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed to determine cell growth. Moreover, messenger RNA (mRNA) expression levels of AGTR1 and angiotensin II receptor type-2 (AGTR2) were measured by quantitative real-time polymerase chain reaction. A significant increase of AGTR1 and AGTR2 transcripts was observed in TAM-R cells compared to MCF-7 cells. Interestingly, losartan-TAM combination effectively resensitized TAM-R cells to tamoxifen treatment by inducing cell death. Therefore, our findings suggest an important role of RAS in acquired TAM resistance and targeting of RAS by losartan may overcome TAM resistance phenomenon and provide a novel avenue for treatment of resistant breast cancers.

Association of ABCB1 Gene Polymorphisms and Clopidogrel Responsiveness in Iranian Patients undergoing Percutaneous Coronary Intervention.

Clopidogrel is an antiplatelet agent currently used for preventing stent thrombosis. Despite certain clinical benefits of clopidogrel in patients undergoing percutaneous coronary intervention (PCI), adequate antiplatelet effect has not been obtained in some patients. The present study was designed to investigate the potential association of ABCB1 (ATP-Binding Cassette, Subfamily B, member1) gene polymorphism, and clopidogrel responsiveness in Iranian patients after PCI. Sixty-seven patients were included in the study. Blood samples were taken from patients at baseline, 2 h after administration of 600-mg loading dose of clopidogrel, 24 h and 30 days after PCI. Platelet aggregation was measured by light transmittance aggregometry (LTA) with two levels of adenosine diphosphate (ADP) concentrations (5 and 20 µM). ABCB1 genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). The allelic frequencies of wild type, heterozygote, and homozygote genotypes of ABCB1 were 20.9%, 74.6%, and 4.5%, respectively. There was no significant association between polymorphism of ABCB1 and clopidogrel non-responsiveness (P > 0.05) in various situations. No significant difference was observed for demographic characteristics. Genetic and demographic factors had no significant effect on the platelet activity of clopidogrel in an Iranian population.

Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial.

INTRODUCTION: Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients. METHODS: T2D patients aged 18-65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions. RESULTS: A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (-9±16 mg/dL vs. -3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (-0.9±1.1% vs. -0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (-2±6 vs. -1±5; p=0.032) and aspartate aminotransferase (-3±5 vs. -0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05). CONCLUSION: The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.

Evaluating the antiemetic administration consistency to prevent chemotherapy-induced nausea and vomiting with the standard guidelines: a prospective observational study.

Nausea and vomiting (NV) are the most prevalent adverse effects of chemotherapy (CT). This study was conducted to evaluate adherence of the health care team to standard guidelines for antiemetics usage to prevent acute chemotherapy-induced nausea and vomiting (CINV) in a large CT center. A prospective study was performed during an 11-month period on patients receiving CT. A form was designed to collect patients' demographic information and their chemotherapeutic and antiemetic regimen data. The Likert scale was used to measure the effectiveness of the antiemetics in patients. In this study, the effect of patient-related risk factors on the incidence rate of CINV was examined. Based on the results, CINV events were reported by 74.4% of patients. The antiemetic regimen of 71.2% of the patients complied with the guidelines. The complete response, complete protection, and complete control end points did not differ significantly between patients undergoing guidelines-consistent prophylaxis or guidelines-inconsistent prophylaxis. The females clearly showed a higher incidence rate of CINV (P=0.001) during the first course of CT (P=0.006). A history of motion sickness did not affect the incidence of NV. The maximum compliance error occurred for the use of aprepitant, as 16.16% of the patients who were receiving aprepitant did not comply with its instructions. The results of this study highlight how CINV was controlled in this center, which was significantly lower than that of the global standard. Perhaps, factors such as noncompliance to antiemetic regimens with standard guidelines and the failure to adhere to the administration instructions of the antiemetics were involved in the incomplete control of CINV.

Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. OBJECTIVE: To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. METHODS: In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. RESULTS: Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). CONCLUSION: Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Curcuminoids Plus Piperine Modulate Adipokines in Type 2 Diabetes Mellitus.

OBJECTIVE: Curcumin is a naturally occurring polyphenol derived from tumeric that has been reported to have anti-inflammatory properties with effects on adipokine and ghrelin levels. Adiponectin, leptin and ghrelin modulate energy homeostasis but each has modulatory effects on inflammatory cytokines and the immune system. Therefore, this analysis was performed to investigate the effect of curcumin on adiponectin, leptin and ghrelin. METHOD: A double blind randomised control trial comparing curcumin 1000mg with 10mg of piperine daily to placebo over a 12 week period. 118 patients with type 2 diabetes were recruited out of which 50 control and 50 active subjects completed the trial. Adiponectin, leptin, ghrelin and tumor necrosis factor-α (TNF-α) were measured at baseline and 12 weeks. RESULTS: Between group comparison of the magnitude of changes showed serum levels of leptin (p<0.001), TNF-α (p<0.001) and leptin:adiponectin ratio (p<0.001) to be significantly reduced while serum adiponectin levels were elevated in the curcuminoids versus placebo group (p=0.032). Changes in serum ghrelin levels did not differ between the study groups (p=0.135). CONCLUSION: Curcumin supplementation increased adiponectin, whilst the the leptin:adiponectin ratio (a measure of atherosclerosis) and leptin levels were decreased independent of weight change and reflected a decrease in the inflammatory TNF-α levels.

The role of captopril and losartan in prevention and regression of tamoxifen-induced resistance of breast cancer cell line MCF-7: an in vitro study.

Innate and acquired tamoxifen (TAM) resistance in estrogen receptor positive (ER+) breast cancer is an important problem in adjuvant endocrine therapy. The underlying mechanisms of TAM resistance is yet unknown. In the present study, we evaluated the role of renin-angiotensin system (RAS) in the acquisition of TAM resistance in human breast cancer cell line MCF-7, and the potential role of captopril and captopril+losartan combination in the prevention and reversion of the TAM resistant phenotype. MCF-7 cells were continuously exposed to 1 µmol/L TAM to develop TAM resistant cells (TAM-R). MTT cell viability assay was used to determine the growth response of MCF-7 and TAM-R cells, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess angiotensin I converting enzyme (ACE), angiotensin II receptor type-1 and type-2 (AGTR1 and AGTR2) mRNA expressions. Preventive and therapeutic effects of RAS blockers - captopril and losartan - were examined on MCF-7 and TAM-R cells. Based on qRT-PCR, TAM-R cells compared to MCF-7 cells, had a mean ± SD fold increase of 319.1 ± 204.1 (P = 0.002) in production of ACE mRNA level, 2211.8 ± 777.9 (P = 0.002) in AGTR1 mRNA level, and 265.9 ± 143.9 (P = 0.037) in production of AGTR2 mRNA level. The combination of either captopril or captopril+losartan with TAM led to the prevention and even reversion of TAM resistant phenotype.