N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not conditioned taste aversion, in rats

Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the relevant brain regions and activates the hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric oxide (NO) in the central nervous system may play a role not only in the activation of HPA axis but also in CTA learning, and that LiCl may activate the brain NO system. To determine the role of NO in lithium-induced CTA, we examined the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium-induced c-Fos expression in the brain regions implicated in CTA learning, such as the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA acquisition or the increase in plasma corticosterone was not attenuated by l-NAME pretreatment. These results suggest that NO may be involved in lithium-induced neuronal activation of the brain regions, but not in the CTA acquisition or the HPA axis activation.     

Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis

Summary The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by barbecuespit (yaw) rotations, vertical eye movements by head-over-heels (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.Supported by Grants NS 01330 from the National Institutes of Health and NGR-14-001-225 from the National Aeronautics and Space Administration     

寰枢椎后路二种内固定技术的三维稳定性评价

目的:对比寰枢椎椎弓根螺钉固定系统与枢椎椎弓根螺钉联合寰椎椎板钩固定系统的生物力学稳定性,为临床应用提供实验依据。方法:新鲜颈椎标本6例,损伤齿突基底部,建立寰枢椎失稳模型,在脊柱三维运动实验机上先测量失稳寰枢椎的三维运动范围,再在失稳模型上对每具标本进行两种内固定:C1椎弓根螺钉 C2椎弓根螺钉的钉棒内固定系统,C1椎板钩 C2椎弓根螺钉的钉棒钩内固定系统,测量二种不同固定方法的寰枢椎三维运动范围,比较两种状态下的寰枢椎稳定状况。结果:C1椎弓根螺钉 C2椎弓根螺钉的钉棒内固定与C1椎板钩 C2椎弓根螺钉的前屈、后伸、左右侧屈无显著性差异,左右旋转C1椎弓根螺钉组优于C1椎板钩组。结论:两种寰枢固定方法:C1椎弓根螺钉 C2椎弓根螺钉固定系统在抗左右旋转方面较C1椎板钩 C2椎弓根螺钉固定系统的稳定性优越,临床上应优先选择C1、C2椎弓根螺钉固定方法,当C1椎弓根过于细小时可选用C1椎板钩 C2椎弓根螺钉的固定技术。     

Adolescent cocaine and injection stress effects on the estrous cycle

Chronic cocaine exposure during critical periods of development induces short- and long-term effects. During the pubertal period, the hypothalamic–pituitary–gonadal (HPG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive maturity in the rat. Sixty female Long–Evans hooded rats were randomly assigned to one of three conditions (20 mg cocaine/kg/day, saline injected and uninjected), for dosing from postnatal day 21 (P21) through P60. Several indicators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus–estrus transitions was significantly lower in cocaine-exposed females compared to uninjected females, but not compared to saline-injected controls. This reduction was observed during exposure to cocaine, as well as after the cessation of injections. During the dosing period, cocaine-exposed rats also exhibited a greater number of cycles that had no clear P–E transition than did UN subjects; this effect disappeared once injections stopped. These alterations suggest immediate, and possibly persisting, alterations in the control of ovulation after chronic cocaine exposure throughout adolescence. Interestingly, during the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. These differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by cocaine and recoverable after exposure. The present findings indicate that the HPG axis is susceptible to short-term, and possibly to long-term, alterations induced by cocaine exposure throughout the adolescent period.     

计算机辅助全膝置换中股骨力线定位精度的实验研究

摘要利用光学定位追踪仪确定全膝置换中患者的股骨头中心从而确定其股骨力线，在力线的定位精度分析中，首次采用股骨的三维重建模型进行精度校验。实验结果表明通过追踪固定于股骨末端的刚性定位器即能确定精确的股骨力线，与传统的髓内定位相比，不仅可重复性好，而且大大地提高了术中股骨力线的位置精度，将其位置偏差减小到10以内。     

Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal and dynamic measures of hypothalamic–pituitary–adrenal-axis activity in healthy volunteers

BACKGROUND : Most published studies show that intranasal corticosteroids have no effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been isolated reports to the contrary, contradicting accumulated knowledge on pharmacokinetics. OBJECTIVE : To re-evaluate the effect of fluticasone propionate aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray on the HPA axis using an improved study design. METHODS : Twenty-three healthy volunteers were randomized in a double-blind, three-way crossover study. The study comprised a 4-day placebo run-in phase followed by three 4-day treatment periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220 microg once daily)), separated by 7-14 days washout intervals. Before the first, and on the last day of each treatment period, 12-h overnight urine was collected to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h after the last administration of study medication, volunteers underwent stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol concentrations were measured before and 20 and 30 min after injection. Blood and urine samples were analysed for cortisol by liquid chromatography tandem mass spectrometry. RESULTS : Compared with placebo, EP or TAA had no significant effect on mean overnight (12 h) urinary cortisol excretion, and did not significantly suppress the overnight geometric mean urinary cortisol/creatinine excretion ratio. Values for serum cortisol before and after ACTH simulation showed no significant suppression, although there was a slight blunting of the HPA-axis response following TAA treatment. CONCLUSION : This study confirms that there are no detectable effects on the HPA axis following short-term intranasal FP or TAA at their recommended dosages.     

High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety

In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.     

Relationship between REM sleep latency and nocturnal cortisol concentrations in depressed patients

SUMMARY  Due to conflicting reports on the possible association between shortening of rapid eye movement (REM) latency and increased cortisol secretion in patients with severe depression, this study examined the relationship between REM sleep latency and nocturnal cortisol concentration in 12 outpatients with major depression. The results showed a significant inverse correlation ( r = —0.71, P <0.01) between REM sleep latency and mean (23.00 hours-03.00 hours) plasma cortisol concentration. Age and severity of depression did not contribute to the inverse relationship. REM activity and density during the first REM period showed no significant correlations with the cortisol measures. A review of the literature suggests that this relationship might be unique to subjects with major depression, and again raises the possibility that these biological disruptions may have a common neurochemical basis.     

The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.     

The Gut‒Breast Axis: Programming Health for Life

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.