Nitric oxide and the control of renin secretion

Summary— Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituitary and other endocrine glands, and evidence is accumulating that it contributes to the regulation of the secretion of renin by the kidneys. The enzyme nitric oxide synthetase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa , a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney and is responsive to changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro , suggesting a stimulatory role for the L-arginine-nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa and beta adrenoceptor mechanisms that regulate renin secretion. Future research should clarify the mechanisms by which nitric oxide regulates the secretion of renin and establish the physiological significance of this regulation.     

神经调节素对阿尔茨海默病大鼠模型海马细胞凋亡和核转录因子κB表达的影响

目的 研究神经调节素1β( neuregulin 1β,NRG1β)对β-淀粉样蛋白1-40(beta-amyloid protein,Aβ1-40)所致的模拟阿尔茨海默病模型大鼠空间学习记忆能力、神经元凋亡、核转录因子κB( nuclear factor kappa B,NFκB)表达的影响,探讨NRG改善学习记忆能力的作用机制.方法 成年健康雄性Wistar 大鼠30只,随机数字表法分为对照组、模型组和治疗组,每组10只,经侧脑室微量注射Aβ1-40建立实验性阿尔茨海默病模型大鼠,经侧脑室注射NRG1β(0.3μg·kg-1)干预治疗.各组大鼠实验前及造模7d后、治疗14d后均用Y型迷宫检测大鼠学习和记忆功能,利用HE染色观察海马神经细胞的结构变化,原位TUNEL法检测海马神经细胞凋亡,免疫组织化学法检测海马神经细胞NFκB的表达.结果 模型组大鼠学习能力[ (57.50±1.58)次]和记忆能力[(7.20±1.03)次]较对照组学习[(59.50±2.79)次]和记忆能力[(7.50±1.08)次]明显下降(=20.36,5.28,P＜0.05),海马区神经细胞排列稀疏、紊乱,有明显神经元脱失,TUNEL阳性细胞数明显增多、NFκB表达增加(P＜0.05).NRG1β治疗组大鼠学习记忆能力[ (67.70±4.90)次,(5.80±0.63)次]及细胞结构较模型组[(79.10±4.12)次,(4.40±0.69)次]显著改善( t=5.63,4.69,P＜0.05).相对于模型组[(41.10±7.95)次,(29.30±7.24)个],NRG1β治疗组NFκB表达(25.90±6.67)明显减弱、细胞凋亡数量[(23.50±3.89)个]明显减少(t=4.63,2.23,P＜0.05).结论 NRG1β能抑制海马神经细胞NFκB表达,减少细胞凋亡,从而改善阿尔茨海默病大鼠的学习和记忆能力.     

The Epidemiology of Dependence in Older People in Nigeria: Prevalence, Determinants, Informal Care, and Health Service Utilization. A 10/66 Dementia Research Group Cross-Sectional Survey

OBJECTIVES: To describe the prevalence and determinants of dependence in older Nigerians and associations with informal care and health service utilization. DESIGN: A single‐phase cross‐sectional catchment area survey. SETTING: Dunukofia, a rural community in southeastern Nigeria. PARTICIPANTS: One thousand two hundred thirty‐eight adults aged 65 and older, for whom full data were available on 914. MEASUREMENTS: The full 10/66 Dementia Research Group survey protocol was applied, including ascertainment of depression, cognitive impairment, physical impairments, and self‐reported diagnoses. The interviewer rated dependence as not needing care, needing some care, or needing much care. The prevalence of dependence and the independent contribution of underlying health conditions were estimated. Sources of income, care arrangements, caregiver strain, and health service use are described according to level of dependence. RESULTS: The prevalence of dependence was 24.3% (95% confidence interval=22.1–26.5%), with a concentration in participants aged 80 and older. Only 1% of participants received a pension, and fewer than 7% had paid work. Those who were dependent were less likely than others to receive income from their family. Cognitive impairment, physical impairments, stroke, and depression were each independently associated with dependence. Depression made the largest contribution. Dependence was strongly associated with health service use (particularly private doctor and traditional healer services) and with high levels of out‐of‐pocket expenditure. CONCLUSION: In Nigeria, dependence is an important outcome given rapid demographic aging and increases in chronic disease prevalence in all developing regions. Enhancing the social protection of dependent older adults should be a policy priority. Cognitive and mental disorders are important contributors to disability and dependence; more attention should be given to their prevention, detection, and treatment.     

糖皮质激素反应性与急性淋巴细胞白血病患儿预后的关系

目的评价糖皮质激素反应性与急性淋巴细胞白血病患儿持续缓解、复发、死亡等预后的关系。方法收集中山大学附属第一医院2008年6月至2011年12月146例住院急性淋巴细胞白血病患儿,通过泼尼松诱导试验初步判断激素的反应性,根据激素反应性不同分组并结合相应的实验室指标:初始外周血白细胞数,初始外周血幼稚淋巴细胞数,外周血幼稚淋巴细胞百分比,融合基因MLL及BCR/ABL,化疗后第8、26天骨髓象,从而评价急性淋巴细胞白血病患儿糖皮质激素反应性与预后的关系。结果 146例患儿中,糖皮质激素反应性敏感(PR+)者为121例(82.88%),其中107例(88.43%)处于持续缓解状态,复发11例,死亡2例,放弃治疗1例。糖皮质激素反应性不敏感(PR-)者为25例(17.12%),其中持续缓解13例,复发6例,死亡5例,放弃治疗1例。PR+组复发死亡率明显低于PR-组,其中两组患儿的初始外周血白细胞数、初始外周血幼稚淋巴细胞数、外周血幼稚淋巴细胞百分比、化疗后第8、26天骨髓象、危险度的分级差异有统计学意义,且复发组的初始幼稚淋巴细胞百分比明显高于未复发组。结论通过泼尼松诱导试验结合一系列实验室指标可判断糖皮质激素的反应性,从而指导疾病的治疗和预测疾病转归。     

Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective

While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors.

Methods

Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children''s Hospital of Bern, Switzerland 1999-2006.

Results

Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score.

Conclusions

Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.