Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway

Noradrenergic systems are integrally involved in the release of growth hormone (GH) from the anterior pituitary gland and in regulating the activity of hypothalamic growth hormone-releasing hormone (GHRH) neurones. GH secretagogues act at both the pituitary and the hypothalamus to facilitate the release of GH. In male rats, using the induction of Fos protein as an indicator of neuronal activation, we examined whether neurones in the brainstem, the main noradrenergic input to the hypothalamus, were activated by systemic administration of peptide and non-peptide GH secretagogues. In addition, we examined the effects of chronic central noradrenaline depletion upon GH secretagogue-induced activation of the arcuate nucleus. Systemic injection of the GH secretagogues, GHRP-6 and MK-0677 induced Fos protein expression in a population of area postrema cells, but less than 10% of these cells were noradrenergic. Depletion of hypothalamic noradrenaline by the specific neurotoxin, 5-ADMP, did not alter GH secretagogue-induced activation of Fos protein in the arcuate nucleus compared to vehicle-treated controls. We conclude that the central actions of GH secretagogues involve the activation of non-noradrenergic cells in the area postrema and that GH secretagogue-induced activation of the arcuate nucleus occurs independently of noradrenergic tone.     

Variation of Nasal Respiratory Pattern With Age During Growth and Development

The purpose of this study was to determine changes in nasal respiratory pattern with growth and development, particularly to determine the age where upper airway growth ceases. The results on 361 healthy subjects, aged 7 to 24 years, based on aerodynamic measurements during rest breathing, showed clear differences between inspiratory and expiratory phases. Nasal airflow rate and cross-sectional area increased and oral-nasal pressure and nasal resistance decreased with age up to the age of 16, levelling by the age of 20 years. The body size and gender had effect only on nasal airflow rate. This study suggests that the measurements of the nasal respiratory pattern, determining impaired nasal airway, should be done during inspiration and using age-related assesment from a healthy population until the age of 16 years. From then on, guidelines for adults are applicable.     

Tyrosine kinase effects on adrenoceptor-stimulated cyclic AMP accumulation in preoptic area and hypothalamus of female rats: modulation by estradiol

These studies examined the functional interactions between adrenergic G-protein coupled receptors and protein tyrosine kinases in the preoptic area and hypothalamus, brain regions that regulate reproductive function in female rats, and evaluated whether in vivo treatment with estradiol for 2 days modulates the cross-talk between these two signaling pathways. In hypothalamic slices genistein, a general tyrosine kinase inhibitor, enhances norepinephrine-stimulated cAMP synthesis independent of estradiol treatment. Genistein appears to act by increasing beta-adrenoceptor signaling. At high norepinephrine concentrations, estradiol potentiates genistein enhancement of the cAMP response in hypothalamic slices. This interaction between estradiol and genistein appears to involve modification of alpha(2)-adrenoceptor signaling mechanisms. In preoptic area slices, genistein enhancement of norepinephrine-stimulated cAMP synthesis is only observed in estradiol-treated rats. In this brain region, genistein enhances cAMP accumulation by modifying alpha(1)- and/or alpha(2)-adrenoceptor rather than beta-adrenoceptor signaling. Genistein amplification of norepinephrine-stimulated cAMP synthesis is not mediated by interactions with estrogen receptors, or by regulation of adenylyl cyclase or phosphodiesterase activities. At the concentration used, genistein inhibits tyrosine phosphorylation in slices from both brain regions. Daidzein, an inactive analogue of genistein, fails to enhance the norepinephrine-stimulated cAMP response in either brain region independent of hormone treatment. These results suggest that protein tyrosine kinases regulate adrenergic responses in the hypothalamus and preoptic area. Moreover, the functional interaction between adrenergic G-protein coupled receptor signaling and protein tyrosine kinases is modified in a brain region and receptor subtype specific manner by estradiol.     

NMDA receptor antagonist-induced dopamine release in the ventral pallidum does not correlate with motor activation

The ventral pallidum is the output structure of the nucleus accumbens in the ventral corticostriato-thalamocortical loop. Information processing in this loop is critically involved in motor behavior and reinforcement. The ventral pallidum receives a direct dopaminergic input from the ventral tegmental area, but also glutamatergic input from cortical and limbic areas. It has been assumed that dopamine release in the VP is indeed modulated by glutamate. The present study investigated the effects of NMDA receptor blockade on motor behavior and dopamine release in the ventral pallidum. In a first experiment, rats were implanted with microdialysis probes in the ventral pallidum and were systemically injected or locally perfused via the microdialysis probe with dizocilpine (0.32 mg/kg, 10 and 100 microM, respectively). Effects on dopamine and on locomotion were simultaneously monitored. In a second experiment, ventral pallidum was lesioned by quinolinic acid and the effects of systemic dizocilpine (0.08 and 0.16 mg/kg) on locomotion and stereotyped sniffing behavior were determined. It was found that systemic and local dizocilpine administration increased dopamine release in the ventral pallidum to a similar extent whereas only systemic treatment was accompanied by locomotor stimulation. Lesion of the ventral pallidum did not affect locomotion and stereotyped sniffing behavior induced by systemic dizocilpine treatment. Thus, DA release in the ventral pallidum that is elevated by blockade of NMDA receptors is not relevant for activation of motor behavior.     

Expression of immunoregulatory cytokines in neurons of the lateral hypothalamic area and amygdaloid nuclear complex of rats immunized against human IgG

Present results showed that interleukin-1 (IL-1), IL-6 and transforming growth factor-beta (TGF-beta) were constitutively expressed in the supraoptic and paraventricular nuclei of the rat hypothalamus. Immunoreactive cells were also detected, but to a lesser extent, in other parts of hypothalamus as well as in the cerebral cortex. In rats immunized with IgG, there was moderate increase in immunoreactivities of the cytokines. A notable feature, however, was the induction of the cytokine expression in the lateral hypothalamic area and the amygdaloid nuclear complex, suggesting that the neurons in these two areas are involved in possible immune regulation.     

发达地区新型农村合作医疗模式的探索--广州市番禺区新型农村合作医疗的实践

广州市番禺区农村合作医疗坚持了30多年从未间断,2003年,被列为全国新型农村合作医疗试点县以来,建立了发达地区新型农村合作医疗模式。探讨沿海经济发达地区新型农村合作医疗的成功经验、主要特点和存在问题。     

Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r ²×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSV_D: RSV_D= TSV − FSV) and regurgitant fraction (RF: RF = RSV_D/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSV_D (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m²) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.     

Central neurotensin receptor activation produces differential behavioral responses in Fischer and Lewis rats

Rationale Lewis (LEW) and Fischer (F344) rats exhibit marked differences in appetitive and consummatory responses to numerous drugs, including psychostimulants. Neurotensin (NT) produces psychostimulant-like actions, which sensitize with repeated exposure, and neuroleptic-like actions; effects that are dependent on the site of microinjection. The aim of the present experiments was to assess the behavioral sensitivity of these two strains of rats to NT receptor activation. Methods In expt 1, locomotor activity was assessed on alternate days following an ICV injection of NT, [d-Tyr¹¹]neurotensin (d-NT; 18 nmol/10 μl), or vehicle (days 1, 3, 5, and 7) in independent groups of LEW and F344 rats. On day 14, locomotor activity was assessed in all rats following an injection of d-amphetamine (1 mg/kg, IP). In expt 2, activity was assessed following injection into the ventral tegmental area of NT, or d-NT, (2.5 μg/hemisphere) or into the nucleus accumbens (2.5 and 5.0 μg/hemisphere). Results Repeated ICV injections of NT, or d-NT, produced differential behavioral effects in the two strains of rats on days 1–7; activity was initially suppressed in LEW, but less so in F344 rats, following NT. In F344, but not in LEW rats, d-NT produced a significant increase in activity. Neurotensin and d-NT sensitized LEW rats to amphetamine-induced ambulatory and non-ambulatory activity. Except for vertical activity, this effect was weaker or in the opposite direction in F344 rats. When injected into the ventral tegmental area, NT produced an increase in locomotor activity in both strains, an effect that was greater in F344 than LEW rats with d-NT. In the nucleus accumbens, NT marginally decreased activity in both strains, while d-NT produced a significant increase in F344 but not in LEW rats. Conclusions These results provide empirical evidence that endogenous NT neurotransmission within limbic circuitry differs in F344 and LEW rats.     

基于人工智能的骨龄辅助评价系统对四川地区完全性生长激素缺乏症患儿骨龄研究

目的 探讨采用基于“人工智能(AI)的骨龄辅助评价系统(上海初云医疗科技有限公司与四川大学华西第二医院合作开发)”(以下简称为AI系统)对完全性生长激素缺乏症(CGHD)患儿诊断及骨龄评价准确性。方法 选择2014年7月至2019年11月,于四川大学华西第二医院确诊的66例来自四川地区CGHD患儿为研究对象,纳入研究组。选择同期于病例收集医院儿童保健科进行骨龄测定的67例来自四川地区身高达标儿童作为对照,纳入对照组。对每例受试儿进行左手腕关节正位X射线摄片骨龄测定,由2位医师采用《TW₂骨龄评分法中国未成年人南方标准》(以下简称为TW₂CHN)》与《TW₃骨龄评分法标准》(以下简称为TW₃),盲法评价受试儿TW₂CHN-桡、尺、掌指骨(RUS)与TW₂CHN-腕骨(carpal)、TW₂CHN-20、TW₃-RUS及TW₃-carpal骨龄(以下简称为5种传统骨龄),以及以同性别、年龄身高达...