BACKGROUND & AIMS: :Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates. Key findings include exercise/housing arrangement's contribution to significant differences in bodyweight, levels of fasting plasma glucose, total cholesterol, and high- and low-density lipoproteins. Age also had profound effects on glucose, triglyceride and high-density lipoproteins, particularly in single-caged animals. Moreover, females had higher fasting glucose, total cholesterol and triglyceride levels than male counterparts within the same housing situations. These factors may be critical to identifying preventive measures that could eventually be used to minimize obesity and diabetes in humans.

背景与目标： : 2型糖尿病是人类和非人类灵长类动物中最常见的糖尿病形式。尽管自发性糖尿病的非人类灵长类动物在糖尿病相关研究中被广泛使用，并且是研究糖尿病自然史的公认有价值的工具，但对于导致这种代谢紊乱的关键因素以及可以采取的预防措施知之甚少。最大程度地减少糖尿病的后果。本研究使用一种发展中的糖尿病和未治疗的模型，描述了住房安排 (社会群体与单独单独居住)，运动，饮食，年龄和性别对空腹血糖，与糖尿病相关的关键脂质和体重的影响在两个大型非人类灵长类动物队列中。主要发现包括运动/住房安排对体重，空腹血糖水平，总胆固醇以及高密度和低密度脂蛋白的显着差异的贡献。年龄对葡萄糖，甘油三酸酯和高密度脂蛋白也有深远影响，尤其是在单笼动物中。此外，在相同住房条件下，女性的空腹血糖，总胆固醇和甘油三酸酯水平高于男性。这些因素对于确定最终可用于减少人类肥胖和糖尿病的预防措施可能至关重要。

BACKGROUND & AIMS: :The sensorimotor cortical system undergoes structural and functional changes across its lifespan. Some of these changes are physiological and parallel the normal aging process, while others might represent pathophysiological mechanisms underlying neurodegenerative disorders. In the last years, the study of possible age-related modifications in brain sensorimotor functional characteristics has been the focus of several research projects. Here we have used the transcranial magnetic stimulation (TMS)-electroencephalography (EEG) navigated co-registration to investigate the influence of physiological aging on the excitability and connectivity of the human sensorimotor cortical system. To this end, we compared the TMS-evoked EEG potentials (TEPs) collected after stimulating the dominant primary motor cortex (M1) in healthy young subjects (mean age 24.5years) with those collected in healthy older adults (mean age 67.6years). We have shown that, after stimulation of the left motor cortex, TEPs are significantly affected by physiological aging. This phenomenon has a clear spatio-temporal specificity and we speculate that normal aging per se leads to some changes in the excitability of specific cortical neural assemblies whereas other alterations could reflect compensatory mechanisms to such changes.

背景与目标： : 感觉运动皮层系统在其整个生命周期内经历结构和功能变化。其中一些变化是生理性的，与正常的衰老过程平行，而另一些变化可能代表神经退行性疾病的病理生理机制。在过去的几年中，对大脑感觉运动功能特征中可能与年龄相关的修饰的研究一直是一些研究项目的重点。在这里，我们使用经颅磁刺激 (TMS)-脑电图 (EEG) 导航的共同配准来研究生理衰老对人感觉运动皮层系统的兴奋性和连通性的影响。为此，我们比较了在健康的年轻受试者 (平均年龄24.5岁) 中刺激显性初级运动皮层 (M1) 后收集的TMS诱发EEG电位 (TEPs) 与在健康的老年人 (平均年龄67.6岁) 中收集的TMS诱发EEG电位 (TEPs)。我们已经表明，在刺激左运动皮层后，tep受到生理衰老的显着影响。这种现象具有明显的时空特异性，我们推测正常衰老本身会导致特定皮质神经组件的兴奋性发生某些变化，而其他变化可能反映出这种变化的补偿机制。

BACKGROUND & AIMS: PURPOSE:Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS:A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS:Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS:These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.

背景与目标：

BACKGROUND & AIMS: :A study was conducted to determine the changes that occur to proteolysis and related genes due to age, protein, and energy intake in high-yield broiler breeder hens (Gallus gallus). Cobb 700 broiler breeders were randomly assigned to one of six diets in a 2×3 factorial fashion. Two levels of energy (390 and 450 kcal/day) and three levels of protein (22, 24, and 26 g CP/day) were utilized. Protein turnover was determined in the left pectoralis at 22, 26, 31 and 44 weeks. Relative mRNA expression of calpain 2 (CAPN2), proteasome C2 subunit (PSMA1), and F box protein 32 (FBXO32) were determined via RT-PCR at 20, 25, and 44 weeks. Contrasts indicate fractional synthesis rate (FSR) and FBXO32 increase to a maximum at 25-26 weeks and a decrease thereafter. A significant drop in PSMA1 and FBXO32 was observed between 25 and 44 weeks and matched the decrease observed in FBR. No differences were detected in the levels of fractional synthesis and degradation, or the expression of CAPN2, PSMA1, and FBXO32, due to protein or energy intake. In summary, protein turnover was upregulated during the transition into sexual maturity and decreased thereafter. The observed changes in degradation appeared to be mediated by the ubiquitin-proteasome pathway.

背景与目标： : 进行了一项研究，以确定由于年龄，蛋白质和能量摄入而导致的蛋白水解和相关基因发生的变化。高产肉鸡种鸡 (Gallus gallus)。将Cobb 700肉鸡饲养者以2 × 3因子的方式随机分配到六种饮食中的一种。利用两个水平的能量 (390和450 kcal/天) 和三个水平的蛋白质 (22、24和26g CP/天)。在22、26、31和44周时确定左胸肌的蛋白质更新。在第20、25和44周通过rt-pcr测定calpain 2 (CAPN2)，蛋白酶体C2亚基 (PSMA1) 和F box蛋白32 (FBXO32) 的相对mRNA表达。对比表明分数合成速率 (FSR) 和FBXO32在25-26周时增加到最大值，此后降低。在25到44周之间观察到PSMA1和FBXO32的显着下降，并且与FBR的下降相匹配。由于蛋白质或能量摄入，在分数合成和降解水平或CAPN2，PSMA1和FBXO32的表达中未检测到差异。总而言之，在过渡到性成熟期间，蛋白质更新上调，此后降低。观察到的降解变化似乎是由泛素-蛋白酶体途径介导的。

BACKGROUND & AIMS: :Anxiety and depression for 399 survivors of a 1,102-member heart disease cohort were assessed 8 to 9 years post-hospitalization. Approximately one-third reported symptoms of emotional distress and one-fourth were on anti-anxiety drugs. Predictors of anxiety and depression were analyzed through logistic regression. Subjects age 65 and over were less likely than younger patients to report anxiety or depression and also reported less heart-associated disability, the strongest predictor of distress for both age groups. Other significant predictors included a previous history of distress, low income, female sex, and beta blocker use.

背景与目标： : 住院后8至9年评估了一个由1,102名成员组成的心脏病队列的399幸存者的焦虑和抑郁。大约3分之1个报告的情绪困扰和4分之1症状是使用抗焦虑药物。通过logistic回归分析焦虑和抑郁的预测因子。与年轻患者相比，65岁及以上的受试者报告焦虑或抑郁的可能性较小，并且与心脏相关的残疾也较少，这是两个年龄组中困扰的最强预测指标。其他重要的预测因素包括以前的困扰史，低收入，女性性别和使用 β 受体阻滞剂。

BACKGROUND & AIMS: :Age-related changes in brain function are complex. Although ageing is associated with a reduction in cerebral blood flow and neuronal activity, task-related processing is often correlated with an enlargement of the corresponding and additionally recruited brain areas. This supplemental employment is considered an attempt to compensate for deficits in the ageing brain. Although there are contradictory reports regarding the role of the primary somatosensory cortex (SI), currently, there is little knowledge about age-related functional changes in other brain areas in the somatosensory network (secondary somatosensory cortex (SII), and insular, anterior (ACC) and posterior cingulate cortices (PCC)). We investigated 16 elderly (age range, 62-71 years) and 18 young subjects (age range, 21-28 years) by determining the current perception threshold (CPT) and applying functional magnetic resonance imaging (fMRI) using a 3.0 Tesla scanner under tactile stimulation of the right hand. CPT was positively correlated with age. fMRI analysis revealed significantly increased activation in the contralateral SI and ipsilateral motor cortex in elderly subjects. Furthermore, we demonstrated age-related reductions in the activity in the SII, ACC, PCC, and dorsal parts of the corpus callosum. Our study revealed dramatic age-related differences in the processing of a simple tactile stimulus in the somatosensory network. Specifically, we detected enhanced activation in the contralateral SI and ipsilateral motor cortex assumingly caused by deficient inhibition and decreased activation in later stages of somatosensory processing (SII, cingulate cortex) in elderly subjects. These results indicate that, in addition to over-activation to compensate for impaired brain functions, there are complex mechanisms of modified inhibition and excitability involved in somatosensory processing in the ageing brain.

背景与目标： : 与年龄相关的脑功能变化是复杂的。尽管衰老与脑血流量和神经元活动减少有关，但与任务相关的处理通常与相应和额外招募的大脑区域的扩大有关。这种补充就业被认为是弥补大脑老化缺陷的一种尝试。尽管关于初级体感皮层 (SI) 的作用有相互矛盾的报道，但目前，关于体感网络中其他大脑区域 (次级体感皮层 (SII) 和岛状，前部 (ACC) 和后部扣带回 (PCC))。我们通过确定当前感知阈值 (CPT) 并使用3.0特斯拉扫描仪在右手的触觉刺激下应用功能磁共振成像 (fMRI)，调查了16位老年人 (年龄范围，62-71岁) 和18位年轻受试者 (年龄范围，21-28岁)。CPT与年龄呈正相关。fMRI分析显示，老年受试者对侧SI和同侧运动皮层的激活显着增加。此外，我们证明了与年龄相关的SII，ACC，PCC和call体背侧活动的减少。我们的研究揭示了体感网络中简单触觉刺激处理过程中与年龄相关的显着差异。具体来说，我们检测到对侧SI和同侧运动皮层的激活增强，假定是由于老年受试者的体感加工 (SII，扣带回皮层) 后期的抑制不足和激活减少所致。这些结果表明，除了过度激活以补偿大脑功能受损外，衰老大脑的体感过程还涉及改良的抑制和兴奋性的复杂机制。

BACKGROUND & AIMS: BACKGROUND:in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE:the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS:this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS:at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION:the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries. METHODS:In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently. RESULTS:There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis. CONCLUSION:Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

背景与目标：

BACKGROUND & AIMS: PURPOSE:To identify the relationship between epidermal growth factor (EGF) concentration in human tears and clinical tear-flow parameters and how these vary with age and gender.

METHODS:Tear samples were collected with minimal stimulation from 68 healthy and asymptomatic adults (33 men, 35 women), aged 21-88 years. EGF concentrations were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 65 cases. Schirmer tests were performed without anesthesia, and the clearance of fluorescein from the tear film assessed. The Tear Function Index (TFI) was calculated from these values.

RESULTS:There were approximately equal numbers of male and female subjects with a similar age distribution for each gender (48 +/- 3 and 51 +/- 3 years, mean +/- SEM, respectively). Ninety percent of tear EGF concentrations were between 0.75 and 7.1 ng/ml. Tear EGF level correlated significantly with Schirmer I value, but not with age. Schirmer I value correlated with tear clearance [LN(TCR)] but not with age. Tear EGF concentrations were significantly higher for men (3.4 +/- 0.3 ng/ml) than for women (2.4 +/- 0.3 ng/ml; p = 0.043).

CONCLUSIONS:EGF concentrations is tear samples from normal humans were found to correlate with gender and Schirmer I value but not with tear clearance.

背景与目标： 目的 : 确定人眼泪中表皮生长因子 (EGF) 浓度与临床泪液流量参数之间的关系，以及这些参数随年龄和性别的变化。
方法 : 在最小的刺激下，从68名健康和无症状的成年人 (33名男性，35名女性) 收集了眼泪样本，年龄在21-88岁之间。用夹心酶联免疫吸附法 (ELISA) 测定65例患者的EGF浓度。在没有麻醉的情况下进行Schirmer测试，并评估了泪膜中荧光素的清除率。泪液功能指数 (TFI) 是根据这些值计算得出的。
结果 : 每个性别年龄分布相似的男性和女性受试者数量大致相等 (48/- 3岁和51/- 3岁，分别为平均值 +/- SEM)。90% 的泪液EGF浓度在0.75至7.1 ng/ml之间。泪液EGF水平与Schirmer I值显着相关，但与年龄无关。Schirmer I值与泪液清除率 [LN(TCR)] 相关，但与年龄无关。男性的泪液EGF浓度 (3.4/- 0.3 ng/ml) 显着高于女性 (2.4/- 0.3 ng/ml; p = 0.043)。
结论 :EGF浓度是正常人的泪液样本与性别和Schirmer I值相关，但与泪液清除率无关。

BACKGROUND & AIMS: This report describes a 91-year-old patient with patent ductus arteriosus (PDA) complicated by combined valvular disease (CVD) (aortic and mitral stenosis, and aortic, mitral, pulmonic and tricuspid regurgitation). This patient seems to be the oldest living female with PDA and CVD hitherto reported in the medical literature. The patient developed several bouts of congestive heart failure which were treated medically. She not only has survived without surgical management, but is still enjoying her life at age 91. The features of PDA in the elderly are reviewed.

背景与目标： 该报告描述了一名91岁的动脉导管未闭 (PDA) 合并合并瓣膜疾病 (CVD) (主动脉和二尖瓣狭窄以及主动脉，二尖瓣，肺动脉和三尖瓣反流) 的患者。该患者似乎是迄今为止医学文献中报道的患有PDA和CVD的最年长的女性。该患者出现了几次充血性心力衰竭，并接受了医学治疗。她不仅在没有手术治疗的情况下幸存下来，而且还在享受91岁的生活。回顾了老年人PDA的功能。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the relative influence of age and edentulousness upon mandibular bone mineral density (BMD) in a sample of dentate and edentulous female subjects. STUDY DESIGN:Seventy-two patients (43-79 years of age; mean age, 62.5 years), of whom 49 were edentulous and 23 dentate, underwent dual x-ray energy absorptiometry (DXA) to determine the BMD of the body of mandible. Mandibular BMD was measured using DXA. The investigators independently determined rectangular regions of interest (ROIs) on the mandibular images, and the computer calculated the BMD of these specified regions. For the dentate patients, the ROIs were placed to exclude the roots of teeth. RESULTS:A linear multiple regression model was fitted to the dependent variable, mandibular body BMD, with age and whether the patient was edentulous or dentate being explanatory factors in the statistical model. The variable describing the dentate/edentulous state was not significant in the statistical model (P = .91). The model showed that age was significantly related negatively to the BMD of the mandibular body (P = .01). CONCLUSION:Age was a predictor of mandibular BMD but edentulousness was not.

背景与目标：

BACKGROUND & AIMS: :Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis with a very poor prognosis. We aimed at assessing risk factors related to the prognosis of patients with TBM.Forty-five inpatients with TBM in our institution from January 2013 to December 2015 were enrolled retrospectively. The good or poor prognosis in the patients was defined, based on Glasgow Outcome Scale System at discharge. Patients with a GOS score less than 5 were defined as "poor prognosis." Univariate and multivariate logistic regression analyses were performed to assess the predictors for TBM outcome.Among 45 TBM patients, 35 (77.8%) and 10 (22.2%) were in good, poor prognoses, respectively. Old age, disturbance of consciousness, moderate to severe electroencephalogram abnormality, hydrocephalus, remarkable increase of protein (≥ 236 mg/dL) and white blood cell counts (≥ 243 /μL) in cerebral spinal fluid were associated with poor prognosis. Multivariate analysis indicated that old age (odds ratio (OR) = 18.395, P = .036) and hydrocephalus (OR = 32.995, P = .049) were independent factors for a poor outcome of TBM.In conclusion, old age and hydrocephalus are the predictors for poor prognosis of TBM. Patients with these risk factors should be treated promptly with a special care paid to improve their outcomes.

背景与目标： 结核性脑膜炎 (TBM) 是中枢神经系统结核病的最常见形式，预后很差。我们旨在评估与TBM患者预后相关的危险因素。我们机构从2013年1月到2015年12月的45例TBM住院患者被回顾性纳入。根据出院时格拉斯哥结局量表系统，确定了患者的良好或不良预后。GOS评分小于5的患者被定义为 “不良预后”。进行单因素和多因素logistic回归分析以评估TBM结果的预测因素。在45例TBM患者中，分别有35例 (77.8% 例) 和10例 (22.2% 例) 预后良好。年龄大、意识障碍、中重度脑电图异常、脑积水、脑脊液中蛋白质 (≥ 236  mg/dL) 和白细胞计数 (≥ 243  /μ l) 均与预后不良相关。多因素分析显示，高龄 (优势比 (OR)  =   18.395，p   =  .036) 和脑积水 (OR   =   32.995，p   =  .049) 是TBM预后不良的独立因素。老年和脑积水是TBM预后不良的预测因素。具有这些危险因素的患者应及时接受特殊护理治疗，以改善其预后。

BACKGROUND & AIMS: INTRODUCTION:New diagnostic tools such as the retinal thickness analyzer (RTA), optical coherence tomography (OCT), and topographic angiography (TAG) were introduced into clinical ophthalmology during the last years giving the examiner new insights into anatomical and functional aspects of macular disease. In this study, advantages and disadvantages of the new imaging methods have been evaluated in patients with serous (sPED) and fibrovascular pigment epithelial detachments (fPED) secondary to age-related macular degeneration (AMD). METHODS:TAG, using fluorescein angiography (FA), provides a three-dimensional profile of the fluorescein pattern based on the analysis of a set of 32 confocal images over a depth of 4 mm. RTA and OCT provide cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex as well as retinal thickness data encoded in a false color map. We compared and evaluated these modalities in 15 patients with fPED and 15 patients with sPED secondary to AMD. RESULTS:In patients with classic fPED, TAG detected neovascular structures and delineated their configuration. In sPEDs, pooling of extravascular fluid was detected in a dome-shaped configuration. OCT provided detailed information on the neurosensory retina's structures but failed to detect the neovascular membrane in fPED. Mapping the retinal thickness, RTA and OCT both failed to detect the PED and showed typical algorithm error-based patterns. CONCLUSION:TAG OCT and RTA are useful imaging modalities in the evaluation of AMD cases. TAG visualizes the vascular configuration, dynamic perfusion, and leakage changes. OCT and RTA are able to complementarily document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. However, OCT seems to be more efficient in imaging AMD-related pathologies than RTA, as this modality is often compromised by intra- or subretinal structural abnormalities. Nevertheless, all modalities may provide further valuable insight into AMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The incidence of rectal cancer in patients ≤ 50 years of age is increasing. The response to neoadjuvant treatment in patients ≤ 50 years of age is not known. Factors affecting the response to neoadjuvant therapy in this age group have not been evaluated. OBJECTIVE:This study aims to evaluate the rate and identify factors that affect pathologic response to neoadjuvant therapy in patients with early age-of-onset rectal cancer. DESIGN:This study is a retrospective review. SETTING:The investigation was conducted at a tertiary-care cancer referral center. PATIENTS:Included were 193 consecutive patients ≤ 50 years of age with rectal cancer who underwent neoadjuvant therapy followed by surgical resection. INTERVENTIONS:No interventions were performed. MAIN OUTCOME MEASURES:The primary outcome measured was the pathologic response to neoadjuvant treatment. RESULTS:The median age was 44 years, and 34% of the patients were female. The median distance from the anal verge was 7 cm. The median percentage of lumen occupied by tumor was 50%. The median CEA level was 3.5 ng/mL. The median treatment response was 80%. The mean number of lymph nodes examined was 15 per patient. Twenty-two percent of patients had a complete or near-complete (≥ 95%) response to neoadjuvant treatment. Seventy-seven percent of evaluable patients experienced tumor or lymph node downstaging on pathologic examination. The presence of adverse histologic features, percentage of lumen occupied by tumor, and CEA level differed between those with <95% response and those with ≥ 95% response to neoadjuvant therapy, although CEA level was not significant when stage IV patients were excluded. LIMITATIONS:This is a retrospective review with heterogeneity in workup, treatment regimens, and interval to surgery. Long-term oncologic outcomes are not available. CONCLUSIONS:The rate of response to neoadjuvant treatment appears similar in patients with early age-of-onset rectal cancer to non-age-based cohorts in the literature. Adverse histologic features and bulky circumferential tumors may be suggestive of a decreased response to neoadjuvant therapy.

背景与目标：

BACKGROUND & AIMS: :A rapid elevation in the level of endogenous corticosterone (CORT) functions in the stress response associated with the hypothalamus-pituitary-adrenal axis, and it has been well documented that high levels of CORT play neurotoxic roles in the hippocampus. Both aging and the circadian rhythm possibly affect the sensitivity to CORT, although their endogenous modifications in the CORT-mediated events remain unclear. To explore the influence of age or circadian time on hippocampal vulnerability to excess CORT, we examined the relative mRNA expression of bcl-2 and bax in the dentate gyrus (DG) and the CA1 subfield, compared with the CA3 as an internal standard, after acute CORT administration using in situ RT-PCR. Male rats aged 10 weeks (young) or 6 months (adult) were treated with CORT at 0800 or 2000 h. The bcl-2 to bax mRNA ratio in the dentate gyrus (DG) was significantly decreased 2h after CORT exposure in the young rats treated at 0800 or 2000 h. In the adult rats, the treatment with CORT at 0800 h significantly decreased the bcl-2 to bax ratio, whereas the treatment at 2000 h was ineffective; the discrepancy between the treatment time points was apparent in adult rats, but not in young rats. Our results emphasize the importance of circadian time as well as age as a factor influencing the stress paradigm.

背景与目标： : 与下丘脑-垂体-肾上腺轴相关的应激反应中内源性皮质酮 (CORT) 功能的水平迅速升高，并且已充分证明高水平的CORT在海马中起神经毒性作用。衰老和昼夜节律都可能影响对CORT的敏感性，尽管它们在CORT介导的事件中的内源性修饰仍不清楚。为了探讨年龄或昼夜节律时间对海马对过量CORT易感性的影响，我们检查了齿状回 (DG) 和CA1子场中bcl-2和bax的相对mRNA表达，与CA3作为内标进行比较。使用原位rt-pcr给药。在0800或2000小时用CORT治疗10周 (年轻) 或6个月 (成年) 的雄性大鼠。在0800或2000小时处理的幼鼠中，CORT暴露后2小时，齿状回 (DG) 中的bcl-2与bax mRNA比率显着降低。在成年大鼠中，在0800 h用CORT处理显着降低了bcl-2与bax的比率，而在2000 h处理无效; 在成年大鼠中，治疗时间点之间的差异很明显，但在幼鼠中却没有。我们的结果强调了昼夜节律时间以及年龄作为影响压力范式的因素的重要性。