A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19.

Context: COVID-19 may cause respiratory distress syndrome and death. Treatment of COVID-19 to prevent complications remains a priority. Objective: Our investigation sought to determine whether combination of spironolactone and sitagliptin could reduce mortality for inpatients with SARS-CoV-2 infection. Methods: This single-blind, 4-arm, prospective randomized clinical trial was conducted at Shiraz and Bushehr University of Medical Sciences hospitals between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into 4 groups: control, combination therapy, sitagliptin add-on, or spironolactone add-on. The primary outcome was the clinical improvement of the patients in the hospital as measured on an 8-point numerical scale. The secondary outcomes included intubation, ICU admission, end organ damages, CT findings, and paraclinical information. Results: A total of 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), sitagliptin group (66 patients), and spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes (clinical score on fifth day of admission: 3.11 ± 2.45 for controls, 1.33 ± 0.50 for combination, 1.68 ± 1.02 for sitagliptin, and 1.64 ± 0.81 for spironolactone; P = 0.004). However, the mortality rate was lower in patients who received spironolactone (21.84% control, 13.33% combination, 13.64% sitagliptin, 10.00% spironolactone; P = 0.275). Our intervention reduced lung infiltration but not the area of involvement in lungs. Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients.

Bitter Melon (Momordica charantia L.) Supplementation Has No Effect on Hypercholesterolemia and Atherosclerosis in Mice.

Bitter melon (BM; Momordica charantia L.) has been reported to ameliorate diet-induced obesity and dyslipidemia. However, the effects of BM on atherosclerosis have not been determined. This study investigated the effects of BM diet-induced atherosclerosis in LDL receptor-deficient mice. A total of 30 female mice (aged 6-8 wk) were fed a saturated fat-enriched diet. In group 1 (n = 10), mice were fed this diet alone, whereas mice in groups 2 and 3 (n = 10/group) were fed the diet supplemented with BM either 0.1% or 1% by weight. After 12 wk, body weight, plasma cholesterol, and atherosclerotic plaque areas were analyzed. No significant differences in body weight and plasma cholesterol concentrations were observed among the groups. Also, BM supplementation did not affect atherosclerosis development. In conclusion, dietary BM has no effect on plasma cholesterol concentration and atherogenesis in hypercholesterolemic mice.

Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice.

Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. Calpain inhibition showed a transient improvement in glucose tolerance at 5 weeks of HFD whereas it lost this effect on glucose and insulin tolerance at 16 weeks HFD in obese mice. However, CAST overexpression significantly reduced adipocyte apoptosis, adipose tissue collagen and macrophage accumulation as detected by TUNEL, Picro Sirius and F4/80 immunostaining, respectively. CAST overexpression significantly attenuated obesity-induced inflammatory responses in adipose tissue. Furthermore, calpain inhibition suppressed macrophage migration to adipose tissue in vitro. The present study demonstrates a pivotal role for calpains in mediating HFD-induced adipose tissue remodeling by influencing multiple functions including apoptosis, fibrosis and inflammation.

Role of vitamin E and D3 supplementation in Intra-Cytoplasmic Sperm Injection outcomes of women with polycystic ovarian syndrome: A double blinded randomized placebo-controlled trial.

BACKGROUND & AIMS: Ovulation induction has been proven to impose oxidative stress during ICSI treatment cycle. Also, data indicates that PCOS women show higher oxidative markers. Available data are not convincing about which antioxidant supplements have the potential to overcome oxidative stress in PCOS subjects. The aim of this trial was to investigate the possible role of combined vitamin E and D supplementation in the ICSI outcomes (oocyte number and quality, embryo number and quality, pregnancy rate) of PCOS subjects. METHODS: A total of 105 PCOS infertile women scheduled for ICSI were enrolled in a double-blinded RCT to treatment group (vitamin E, 400 mg/day - and vitamin D3, 50,000 IU/one in two weeks, n = 52) or placebo group (n = 53) for 8 weeks. The primary outcomes were implantation rate, pregnancy and clinical pregnancy rate. Secondary outcomes included oocyte quality, embryo quality, fertilization rate, alteration in serum MDA, TAC and vitamin D3 after treatment. Further, association between serum and follicular fluid Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), and serum vitamin D3 level were assessed. RESULTS: Pregnancy, clinical pregnancy and implantation rate were significantly higher in treatment group (P < 0.001). Data analysis in both groups revealed a significant increase in serum MDA compared to baseline and a significant decrease in serum TAC compared to baseline after treatment. Further analysis showed that there is a positive weak association between vitamin D level, implantation rate (P = 0.015) and increased clinical pregnancy (P = 0.037). No significant association was detected between either follicular fluid or serum MDA and TAC and ICSI outcomes. CONCLUSIONS: In conclusion, the findings of this trial do not add clinical support to the evidence that vitamins E and D3 may play a role in the success rate of IVF via an antioxidant mechanism. REGISTRY CODE: IRCT2014081018662N1.

Nutritional modifications in male infertility: a systematic review covering 2 decades.

CONTEXT: Studies suggest that appropriate nutritional modifications can improve the natural conception rate of infertile couples. OBJECTIVES: The purpose of this study was to review the human trials that investigated the relation between nutrition and male infertility. DATA SOURCES: A comprehensive systematic review of published human studies was carried out by searching scientific databases. Article selection was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The American Dietetic Association Research Design and Implementation Checklist was also used for quality assessment. DATA EXTRACTION: A total of 502 articles were identified, of which 23 studies met the inclusion criteria. DATA SYNTHESIS: Results indicated that a healthy diet improves at least one measure of semen quality, while diets high in lipophilic foods, soy isoflavones, and sweets lower semen quality. CONCLUSION: The role of daily nutrient exposure and dietary quality needs to be highlighted in male infertility. Mechanistic studies addressing the responsible underlying mechanisms of action of dietary modifications are highly warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2013: CRD42013005953. Available at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013005953.

Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice.

Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.

Impact of an individualized type 2 diabetes education program on clinical outcomes during Ramadan.

OBJECTIVE: To determine if individualized education before Ramadan results in a safer fast for people with type 2 diabetes. METHODS: Patients with type 2 diabetes who received care from participating clinics in Egypt, Iran, Jordan and Saudi Arabia and intended to fast during Ramadan 2014 were prospectively studied. Twelve clinics participated. Individualized education addressed meal planning, physical activity, blood glucose monitoring and acute metabolic complications and when deemed necessary, provided an individualized diabetes treatment plan. RESULTS: 774 people met study criteria, 515 received individualized education and 259 received usual care. Those who received individualized education were more likely to modify their diabetes treatment plan during Ramadan (97% vs 88%, p<0.0001), to perform self-monitoring of blood glucose at least twice daily during Ramadan (70% vs 51%, p<0.0001), and to have improved knowledge about hypoglycemic signs and symptoms (p=0.0007). Those who received individualized education also reduced their body mass index (-1.1±2.4 kg/m(2) vs -0.2±1.7 kg/m(2), p<0.0001) and glycated haemoglobin (-0.7±1.1% vs -0.1±1.3%, p<0.0001) during Ramadan compared those who received usual care. There were more mild (77% vs 67%, p=0.0031) and moderate (38% vs 19%, p<0.0001) hypoglycemic events reported by participants who received individualized education than those who received usual care, but fewer reported severe hypoglycemic events during Ramadan (23% vs 34%, p=0.0017). CONCLUSIONS: This individualized education and diabetes treatment program helped patients with type 2 diabetes lose weight, improve glycemic control and achieve a safer fast during Ramadan.