In recent studies, we have shown that pyrrolo[3,4‐f]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives act as good potency in vitro inhibitors of the monoamine oxidase (MAO) enzymes. To expand on these series and to further derive structure‐activity relationships (SARs) for MAO inhibition, in the present study we synthesized additional homologs and related analogs of these chemical classes. Analyzes of the MAO inhibition properties of the synthesized compounds show that among the pyrrolo[3,4‐f]indole‐5,7‐dione derivatives good potency MAO inhibitors exist as exemplified by 10 , which possesses IC50 values for the inhibition of MAO‐A and MAO‐B of 0.023 and 0.178 µM, respectively. Among thirteen pyrrolo[3,4‐f]indole‐5,7‐diones, nine compounds exhibit IC50 values for the inhibition of an MAO isoform in the submicromolar range. It may be concluded that active MAO inhibitors, such as 10 represent suitable leads for the development of drugs for neurodegenerative and neuropsychiatric disorders such as Parkinson's disease and depression. MAO inhibitors are also of interest for the treatment of prostate cancer, certain types of cardiomyopathies and Alzheimer's disease. 相似文献
Patients with uncontrolled type 1 diabetes mellitus (T1DM) are at a high risk for Ramadan fasting and are exempt from fasting; however, most still insist on fasting. The aim of this study was to examine glucose level fluctuations in those patients during Ramadan fasting using a real-time continuous glucose monitoring system (RT-CGMS).
Methods
This pilot study involved adult patients with uncontrolled T1DM (HbA1c?>?7%) who insisted on fasting during Ramadan in 2014 from Maternity and Children’s Hospital, Medina, Saudi Arabia. A Medtronic RT-CGMS was used to monitor the participants’ glucose levels for 3 consecutive days during fasting.
Results
The study included 22 patients (mean age 22?±?6?years, duration of diabetes 10.9?±?7.2?years, HbA1c level 9.3?±?1.2). All participants were using the basal-bolus insulin regimen, except for one patient who was on an insulin pump. Sensor glucose (SG) profiles typically followed a pattern that was characterized by an exaggerated increase after iftar, which was sustained overnight, and a second rapid rise after suhoor, with a prolonged glucose decay over the daylight hours. The average SG was 199?±?104.1?mg/dl, which was lower during fasting 188.4?±?103.41?mg/dl than during the eating hours 212.5?±?103.51?mg/dl (P?=?0.00). There was a higher rate of hyperglycemia (48%) than hypoglycemia (10%).
Conclusions
Patients with uncontrolled T1DM who fasted during Ramadan experienced a wide fluctuation of glucose levels between fasting and eating hours, exhibiting a greater tendency toward hyperglycemia. The long-term effects for this finding are not known and warrant further investigation. 相似文献
Objective: Individuals looking to improve their health or weight status often use nonnutritive sweeteners (NNS), yet NNS consumption has been associated with increased risk factors for metabolic syndrome (MetS). Most studies examining NNS only assess total intake using diet soda as a proxy for NNS consumption, without distinguishing potential risks associated with individual sweeteners. The objective of this cross-sectional investigation was to identify whether there were associations between NNS consumption (total or individual) and risk factors for MetS in adults (n = 125) from Southwest Virginia.
Methods: Participants provided three 24-hour dietary recalls and blood pressure, waist circumference, fasting glucose, triglycerides, and high-density lipoprotein cholesterol were assessed. Linear regression models, adjusted for age, sex, caloric intake, dietary quality, and physical activity, examined associations between total and individual types of NNS with MetS and MetS risk factors.
Results: Sixty-three participants were classified as NNS consumers and eighteen met the criteria for MetS. While no significant associations between MetS and NNS consumption were found, waist circumference was positively associated with total NNS, saccharin, sucralose, and acesulfame potassium, and both fasting glucose and triglyceride values were positively associated with total NNS and aspartame consumption.
Conclusion: While these cross-sectional data are consistent with previous work implicating NNS in development of MetS, additional research using randomized controlled trials is needed to clarify whether and how NNS in general or specific NNS might contribute to risk factors for MetS. This trial was registered at clinicaltrials.gov (NCT03364452). 相似文献
Objective: Data on the effects of coenzyme Q10 (CoQ10) supplementation on glucose metabolism, lipid profiles, inflammation, and oxidative stress in subjects with diabetic nephropathy (DN) are scarce. This research was done to determine the effects of CoQ10 supplementation on metabolic status in subjects with DN.Methods: This randomized double-blind placebo-controlled clinical trial was done in 50 subjects with DN. Participants were randomly assigned into two groups to intake either 100 mg/day CoQ10 supplements (n = 25) or placebo (n = 25) for 12 weeks. Fasting blood samples were obtained at first and after 12-week intervention to quantify metabolic profiles.Results: After 12 weeks of treatment, compared with the placebo, CoQ10 supplementation resulted in significant decreases in serum insulin levels (?3.4 ± 6.8 vs +0.8 ± 6.4 µIU/mL, p = 0.02), homeostasis model of assessment-estimated insulin resistance (?1.0 ± 2.0 vs +0.2 ± 1.8, p = 0.03), homeostasis model of assessment-estimated B cell function (?12.3 ± 26.3 vs +3.5 ± 23.1, p = 0.02) and HbA1c (?1.1 ± 1.0 vs ?0.1 ± 0.2%, p < 0.001), and a significant improvement in quantitative insulin sensitivity check index (+0.009 ± 0.01 vs ?0.006 ± 0.01, p = 0.01). In addition, CoQ10 supplementation significantly decreased plasma malondialdehyde (MDA) (?0.6 ± 0.5 vs +0.5 ± 1.0 µmol/L, p < 0.001) and advanced glycation end products levels (AGEs) (?316.4 ± 380.9 vs +318.6 ± 732.0 AU, p < 0.001) compared with the placebo. Supplementation with CoQ10had no significant impacts on fasting plasma glucose (FPG), lipid profiles, and matrix metalloproteinase-2 (MMP-2) compared with the placebo.Conclusions: Taken together, our study demonstrated that CoQ10 supplementation for 12 weeks among DN patients had favorable effects on glucose metabolism, MDA, and AGEs levels, but unchanged FPG, lipid profiles, and MMP-2 concentrations. 相似文献