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101.
Hit, Lead & Candidate Discovery
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   
102.
目的 探讨N-乙酰半胱氨酸(N-acetyl-L-cysteine,NAC)对糖氧剥夺(oxygen and glucose deprivation,OGD)诱导的星形胶质细胞损伤过程中AKT信号通路的影响及其意义。方法 以原代培养的星形胶质细胞建立OGD模型,并分为4组:对照组,OGD组,NAC组和NAC+AKT特异性抑制剂MK-2206组(NAC+MK-2206组);细胞培养24 h后,采用噻唑蓝(MTT)法检测细胞存活率、流式细胞仪技术分析细胞凋亡比例,试剂盒检测细胞内SOD活性和丙二醛(MDA)含量,蛋白免疫印迹法检测细胞内AKT、磷酸化AKT(p-AKT)、mTORC1、磷酸化mTORC1(p-mTORC1)、胞浆型磷脂酶A2(cLPA2)、caspase3及Bcl-2的表达水平。结果 与OGD组相比,NAC组的细胞存活率,p-AKT、p-mTORC1及Bcl-2表达和SOD活性增加,细胞凋亡比例,cPLA2、caspase3表达,MDA含量降低。与NAC组相比,NAC+MK-2206组的细胞存活率,p-AKT、p-mTORC1及Bcl-2表达和SOD活性降低,细胞凋亡比例、cPLA2、MDA含量、caspase3表达增加。结论 NAC缓解OGD诱导AKT信号通路抑制作用,降低cPLA2诱导细胞凋亡作用。  相似文献   
103.
章容  戴武  叶军  曹永红  刘燕  汪运生  张苏皖  匡蕾  邹玲玲 《安徽医药》2018,39(12):1462-1465
目的 动态血糖监测(CGM)评估血糖波动,探讨糖化血红蛋白(HbA1c)<7.0%的2型糖尿病患者视网膜病变(DR)与血糖波动的关系。方法 选择2014年5月至2018年1月在合肥市第二人民医院内分泌科住院的168例HbA1c<7.0%的2型糖尿病患者为研究对象,根据DR病变程度,将108例无DR的患者纳为NDR组,60例DR患者纳为DR组。对受试者进行连续72 h的CGM,计算平均血糖(MBG)、血糖水平标准差(SDBG)、有效波动平均幅度(MAGE),同时检测HbAlc、血压、体质指数,评估HbA1c控制理想的2型糖尿病视网膜病变与血糖波动之间的相关性。结果 DR组患者病程(8.33±0.82)年、收缩压(138.20±11.84)mmHg、舒张压(86.53±8.57)mmHg、SDBG(2.73±0.54)、MAGE(3.98±0.70)mmol/L,均高于NDR组,差异有统计学意义(P<0.05)。logistic回归分析显示,病程、MAGE是2型糖尿病患者发生DR的危险因素(P<0.05)。结论 HbAlc<7.0%的2型糖尿病患者DR与糖尿病病程、血糖波动及血压有关。  相似文献   
104.
廖晓现  成力  朱洪斌 《安徽医药》2018,22(10):1962-1964
目的 研究血糖水平与慢性心力衰竭合并2型糖尿病患者预后的相关性。 方法 选取2014年4月至2016年3月重庆市开州区人民医院收治的90例慢性心力衰竭合并2型糖尿病患者为研究对象,并将患者按照随访中测定的糖化血红蛋白(HbA1c)值划分为血糖达标组(HbA1c<7.0%)与血糖未达标组(HbA1c≥7.0%),对比两组患者联合主要心血管事件的发生率,并分析无联合主要心血管事件患者的生存率。 结果 与血糖达标组相比,血糖未达标组的空腹血糖及餐后2 h血糖水平差异有统计学意义,而且心力衰竭程度越重,糖化血红蛋白水平越高(P<0.05),联合主要心血管事件的发生率较高(3.77%比18.92%,P=0.018);两组患者的N末端B型利钠肽原与左室射血分数水平差异无统计学意义(P=0.721,P=0.117)。 结论 将HbA1c控制在7.0%以下,可有效改善慢性心力衰竭合并2型糖尿病患者的预后水平。  相似文献   
105.

Background

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   
106.
目的 分析宁波市2型糖尿病患者空腹血糖及其控制情况的影响因素,为糖尿病的社区防控提供依据。 方法 2015年12月从宁波市江东区5个街道招募600名2型糖尿病患者,进行集中问卷调查、体格检查和实验室检测,采用linear线性回归对空腹血糖的影响因素进行分析,采用logistic回归对空腹血糖控制情况的相关因素进行分析。 结果 本次调查检测600名2型糖尿病患者,平均空腹血糖为(6.94±2.25)mmol/L,空腹血糖控制良好的患者有345人(57.50%)。Linear一元线性回归分析显示空腹血糖与腰围、舒张压、吸烟、糖尿病病程及高脂饮食呈正相关(P<0.05),与行为转变阶段、按照糖尿病要求饮食、运动及饮食信心2(与非糖尿病患者共同进食坚持按要求进食信心)呈负相关(P<0.05)。Linear多元线性回归分析显示空腹血糖与腰围(标化回归系数β=0.113,P=0.007)、舒张压(β=0.096,P=0.023)、糖尿病病程(β=0.087,P=0.030)呈正相关,与行为转变阶段(β=- 0.111,P=0.006)呈负相关。单因素logistic回归分析显示按照糖尿病饮食要求进食、饮食信心2得分高、运动多能够提高空腹血糖控制率(P<0.05);而腰围大、糖尿病病程长会降低空腹血糖控制率(P<0.05)。多因素logistic回归分析显示糖尿病病程长(OR=0.90, 95%CI:0.81~0.99)会降低空腹血糖控制率,按照糖尿病饮食要求进食(OR=1.46, 95%CI:1.12~1.88)能够提高空腹血糖控制率。 结论 本次研究2型糖尿病患者空腹血糖控制良好,空腹血糖及其控制率的危险因素是病程、腰围及舒张压,保护因素是按照糖尿病要求进食、适度运动及较高的行为转变阶段。  相似文献   
107.
108.
109.
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   

110.
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   
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