Effects of Different Dietary Interventions on Calcitriol, Parathyroid Hormone, Calcium, and Phosphorus: Results from the DASH Trial.

The "Dietary Approaches to Stop Hypertension" (DASH) diet, rich in fiber and low-fat dairy, effectively lowers blood pressure. DASH's effect on calcitriol and other markers of bone-mineral metabolism is unknown. This secondary analysis of the DASH trial aimed to determine the effect of dietary patterns on blood concentrations of calcitriol, parathyroid hormone (PTH), ionized calcium, and urinary excretion of calcium and phosphorus. Outcomes were available in 334 participants in the trial. After a 3-week run-in on the control diet, participants were randomized to control, fruits and vegetables (F&V), or DASH diets. Outcomes were assessed at the end of run-in, and during the last week of the intervention period. Mean age of participants was 45.7 ± 10.7 years, 46% female, and 57% African-American. Mean ± Standard Deviation(SD) baseline serum concentrations of calcitriol, PTH, and ionized calcium were 37.8 ± 9.2 pg/mL, 46.1 ± 18.5 pg/mL and 5.2 ± 0.23 mg/dL, respectively. Mean (±SD) urinary calcium and phosphorus excretions were 150.1 ± 77.8 and 708.0 ± 251.8 mg/24 h, respectively. Compared with control, DASH reduced calcitriol -3.32 pg/mL (p = 0.004). Otherwise, there was no significant effect on other biomarkers. DASH lowered serum calcitriol perhaps more among African-Americans. These results raise important questions about the interpretation and clinical significance of low calcitriol concentrations in the setting of recommended diets.

The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system.

The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells. Indole-exposed Salmonella colonized mice less effectively compared to solvent-treated controls, as evident by competitive index values less than 1 in multiple organs. Indole-exposed Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2-fold less invasion of J774A.1 macrophages compared to solvent-treated controls. However, indole did not affect Salmonella intracellular survival in J774A.1 macrophages suggesting that indole primarily affects Salmonella invasion. The decrease in invasion was corroborated by a decrease in expression of multiple Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the effect of indole was mediated by both PhoPQ-dependent and independent mechanisms. Indole also synergistically enhanced the inhibitory effect of a short chain fatty acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were 70% more resistant to Salmonella invasion suggesting that indole also increases resistance of epithelial cells to colonization. Our results demonstrate that indole is an important microbiota metabolite that has direct anti-infective effects on Salmonella and host cells, revealing novel mechanisms of pathogen colonization resistance.

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

OBJECTIVE: To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. STUDY DESIGN: Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. RESULTS: Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. CONCLUSION(S): Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation.