选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis

Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO₂ (EtCO₂; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO₂ and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Experiments with calculated therapeutic and toxic doses of digitalis: III. Effects on the coronary blood flow

Calculated therapeutic doses of digitalis did not produce a significant change in the coronary blood flow of the dog. This confirms the results of Essex, Herrick, Baldes, and Mann.²⁸Calculated toxic doses of digitalis decreased the coronary blood flow of dogs four to six hours after the drug had been administered. The diminution of flow persisted for several days after a single toxic dose of the drug.No myocardial lesions were observed after a therapeutic dose of digitalis, nor were they observed in one animal which received a toxic dose of digitalis. In the latter animal the coronary blood flow returned to the preinjection level within two days.Myocardial lesions were observed in one animal in which the coronary blood flow was kept well below the control level for twelve days by repeated injections of digitalis (toxic range).The diminution of coronary blood flow after the injection of toxic doses of digitalis could not be correlated consistently with changes in the pulse rate or systemic blood pressure.After the injection of toxic doses of digitalis the coronary blood flow returned to the control level in several experiments, and the animals recovered completely.     

Immunosuppression without liver induction by subchronic exposure to 2,7-dichlorodibenzo-p-dioxin in adult female B6C3F1 mice

The overall objective of this investigation was to begin to characterize the structure-activity relationship associated with dioxin-induced suppression of humoral immunity. Subchronic exposure (14 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototype of the class, produced a suppression of the antibody responses to both sheep erythrocytes, a T-dependent antigen, and dinitrophenyl-Ficoll, a T-independent antigen. Surprisingly, similar results were observed with 2,7-dichlorodibenzo-p-dioxin (DCDD), a dioxin congener lacking affinity for the Ah receptor. In contrast, subchronic exposure to octachlorodibenzo-p-dioxin (OCDD), another dioxin congener without affinity for the Ah receptor, was devoid of activity. Subchronic exposure to 2,3,7,8-TCDD, but not 2,7-DCDD, produced an induction of several liver parameters including: liver weight, amount of microsomal protein, amount of cytochrome P-450, activity of aminopyrine-N-demethylase and activity of aryl hydrocarbon hydroxylase. Subchronic exposure to 2,3,7,8-TCDD or 2,7-DCDD produced no marked changes in thymus weight. Acute exposure to 2,3,7,8-TCDD also produced suppression of the antibody response in the absence of effects on the thymus.     

Two novel loci,COBL and SLC10A2, for Alzheimer's disease in African Americans

Introduction

African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.