黄芩苷、二甲双胍和氨基胍对D-半乳糖诱导大鼠体内蛋白非酶糖基化-氧化应激、醛糖还原酶活性及胰岛素抵抗作用

目的：观察黄芩苷、二甲双胍和氨基胍对D-半乳糖诱导大鼠体内蛋白非酶糖基化-氧化应激、醛糖还原酶活性及胰岛素抵抗作用。方法：清洁级健康SD大鼠90只,完全随机分为6组正常对照组、模型对照组、氨基胍组、二甲双胍组、黄芩苷高剂量和黄芩苷低剂量组,每组各15只。除空白对照组外,其余组大鼠均采用腹腔注射D-gal,灌胃;结束时观察各组大鼠晚期糖基化终末产物、糖化血红蛋白、胰岛素等,并计算胰岛素敏感指数,醛糖还原酶和超氧化物歧化酶的活性。结果：D-gal处理大鼠出现血糖升高、糖耐量减退、糖基化产物及胰岛素含量增高,SOD活性降低及红细胞内AR活性增强;Met,AG以及Bai高和低剂量均能改善D-gal诱导大鼠IGT和降低糖基化产物和胰岛素含量。结论：D-gal诱导能使大鼠体内糖基化反应、胰岛素抵抗和醛糖还原酶活性增强;Bai,Met和AG能抑制蛋白非酶糖基化反应和醛糖还原酶活性,改善高胰岛素血症。     

Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia

Abstract

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. Method: Forty SD rats were randomly divided into normal diet group (NN, n?=?8) and high cholesterol supplemented dietary group (HN, n?=?32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10?mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3?mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p?<?0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p?<?0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p?<?0.01). The renal injuries induced by contrast media (CM) were alleviated. Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.     

Theoretical and Experimental Evaluation of Flow Pattern of Pharmaceutical Powder Blends Discharged From Intermediate Bulk Containers (IBCs)

The purpose of this study is to assess the prevalence of funnel flow pattern for common pharmaceutical powder blends, upon discharging from modern intermediate bulk containers (IBCs) in drug product manufacturing. The estimation was built upon Jenike’s original radial stress field theory. It was modified to account for the stress-dependence of wall friction angle commonly observed in pharmaceutical powders. A total of 260 flow pattern estimations, based on 20 real-life IBCs and 13 investigational powder blends, were made. The estimated results showed that the mass flow pattern is present in less than 5% of all cases. Funnel flow pattern is clearly prevalent among pharmaceutical powder blends. The prevalence of funnel flow stems from several factors: 1) relatively shallow hopper section shared by all IBCs, 2) the common transition-type geometry, leading to even shallower hopper inclination at the edge of the hopper section, and 3) relatively high wall friction angles resulting from low wall normal stresses. This conclusion was verified through at-scale experiments, by discharging multiple pharmaceutical powder blends from a representative IBC. In general, our study suggests that, unless the powder wall friction can be substantially reduced, pharmaceutical powders are likely to discharge under funnel flow from modern IBCs.     

Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [11C]-(+)-PHNO

A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [¹¹C]-(+)-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BP_ND) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in [¹¹C]-(+)-PHNO BP _ND) between CU and HV was tested with analysis of variance. SMCT BP_ND was significantly higher in CU compared with HV in the AST (F=10.38, p=0.003), LST (F=4.95, p=0.036), SMST (F=4.33, p=0.048), and whole striatum (F=9.02, p=0.006). Percentage of displacement (change in BP_ND between SMCT and MIST PET scans) was not significantly different across groups in any brain region, except in the GP (−5.03±14.6 in CU, compared with 6.15±12.1 in HV; F=4.39, p=0.049). Duration of cannabis use was significantly associated with stress-induced [¹¹C]-(+)-PHNO displacement by endogenous DA in the LST (r=0.566, p=0.044), with no effect in any other brain region. In conclusion, despite an increase in striatal BP_ND observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release.     

Aggregate-Level Predictors of the Prevalence of Selected Drinking Patterns in Multiple Studies: A Research Synthesis from the Collaborative Alcohol-Related Longitudinal Project

This paper examines the prevalence of two “at-risk” alcohol drinking patterns (infrequent heavy drinking and frequent heavy drinking) within age/gender groups in multiple general population studies. When heterogeneity in findings across studies is found, we test the hypotheses that suicide, divorce, unemployment rates, and the per capita consumption of alcohol in each country are associated with the prevalence of these drinking patterns. These analyses should inform the literature on the relationships between societal factors and the prevalence of persons in different societies and periods in history that drink at these levels. [Translations are provided in the International Abstracts Section of this issue.]     

A single session of hatha yoga improves stress reactivity and recovery after an acute psychological stress task—A counterbalanced,randomized-crossover trial in healthy individuals

ObjectivesYoga is promoted as an anti-stress activity, however, little is known about the mechanisms through which it acts. The present study investigated the acute effects of a hatha yoga session, displayed on a video, on the response to and recovery from an acute psychological stressor.MethodsTwenty-four healthy young adults took part in a counterbalanced, randomized-crossover trial, with a yoga and a control condition (watching TV). Participants attended the laboratory in the afternoon on two days and each session comprised a baseline, control or yoga task, stress task and recovery. Blood pressure (BP), heart rate (HR) and salivary cortisol responses were measured. State cognitive- and somatic-anxiety along with self-confidence were assessed before and after the stressor.ResultsAlthough no difference in the BP or HR responses to stress were found between conditions, systolic BP (p = 0.047) and diastolic BP (p = 0.018) recovery from stress were significantly accelerated and salivary cortisol reactivity was significantly lower (p = 0.01) in the yoga condition. A yoga session also increased self-confidence (p = 0.006) in preparation for the task and after completion. Moreover, self-confidence reported after the stress task was considered debilitative towards performance in the control condition, but remained facilitative in the yoga condition.ConclusionOur results show that a single video-instructed session of hatha yoga was able to improve stress reactivity and recovery from an acute stress task in healthy individuals. These positive preliminary findings encourage further investigation in at-risk populations in which the magnitude of effects may be greater, and support the use of yoga for stress reactivity and recovery.