Eyebrow anomalies as a diagnostic sign of genomic disorders

Silengo M, Belligni E, Molinatto C, Baldassare G, Biamino E, Chiesa N, Zuffardi O, Girirajan S, Eichler EE, Ferrero GB. Eyebrow anomalies as a diagnostic sign of genomic disorders. Microdeletions and microduplications in the human genome, termed genomic disorders, contribute to a high proportion of human multisystemic neurodevelopmental diseases and are detected by array‐based comparative genomic hybridization (aCGH). In general, most genomic disorders are associated with craniofacial and skeletal features and behavioural abnormalities, in addition to learning disability and developmental delay (LD/DD). Specifically, recognition of a characteristic ‘acial gestalt’ has been the key to distinguish one genomic disorder from the other. Here, we report our experience concerning the relevance of abnormal eyebrow pattern as a diagnostic indicator of specific genomic disorders.     

LEARN 2 MOVE 0-2 years: effects of a new intervention program in infants at very high risk for cerebral palsy; a randomized controlled trial

Background

Bronchiolitis is the most common reason for admission of infants to hospital in developed countries. Fluid replacement therapy is required in about 30% of children admitted with bronchiolitis. There are currently two techniques of fluid replacement therapy that are used with the same frequency-intravenous (IV) or nasogastric (NG). The evidence to determine the optimum route of hydration therapy for infants with bronchiolitis is inadequate. This randomised trial will be the first to provide good quality evidence of whether nasogastric rehydration (NGR) offers benefits over intravenous rehydration (IVR) using the clinically relevant continuous outcome measure of duration of hospital admission.

Methods/Design

A prospective randomised multi-centre trial in Australia and New Zealand where children between 2 and 12 months of age with bronchiolitis, needing non oral fluid replacement, are randomised to receive either intravenous (IV) or nasogastric (NG) rehydration. 750 patients admitted to participating hospitals will be recruited, and will be followed daily during the admission and by telephone 1 week after discharge. Patients with chronic respiratory, cardiac, or neurological disease; choanal atresia; needing IV fluid resuscitation; needing an IV for other reasons, and those requiring CPAP or ventilation are excluded. The primary endpoint is duration of hospital admission. Secondary outcomes are complications, need for ICU admission, parental satisfaction, and an economic evaluation. Results will be analysed using t-test for continuous data, and chi squared for categorical data. Non parametric data will be log transformed.

Discussion

This trial will define the role of NGR and IVR in bronchiolitis

Trail registration

The trial is registered with the Australian and New Zealand Clinical Trials Registry - ACTRN12605000033640     

电磁辐射后小胶质细胞活化状态和分泌功能的变化

目的:一定量的电磁辐射可引起中枢神经系统神经元的损伤,但其对小胶质细胞的影响尚不清楚。实验观察电磁辐射对小胶质细胞活化状态以及分泌功能的影响,揭示电磁辐射对小胶质细胞及中枢神经损伤的效应关系。方法:实验于2006-08/2007-05在解放军第三军医大学电磁辐射医学防护教育部重点实验室完成。取体外培养的N9小胶质细胞接受X波段脉冲波,平均功率密度为90mW/cm2的电磁波,一次性照射20min,在辐照后0,1,3,6,12,24h等6个时相点观察活化的N9细胞形态学,采用免疫组化的方法观察OX-42的表达情况,用酶联兔疫吸附测定方法检测N9细胞培养上清液中肿瘤坏死因子α的水平,采用硝酸还原酶法检测培养上清液中NO浓度。以未接受电磁波辐照的N9小胶质细胞为假辐照组进行对照。结果:①电磁辐射后3hN9小胶质细胞OX-42表达开始明显增强,并一直持续到辐照后24h,细胞形态由静息状态转变为激活状态;②NO的浓度在辐照后1h开始升高(P<0.05),到辐照后6h达到峰值(P<0.01),12h后趋于恢复,24h后再次明显升高(P<0.05)。③肿瘤坏死因子α水平辐照3h后显著升高(P<0.01),并一直持续到12h,到辐射后24h又再次升高,并达到峰值(P<0.01)。结论:电磁辐射辐照可明显诱导小胶质细胞激活,活化后的小胶质细胞分泌NO、肿瘤坏死因子α等细胞因子的功能增强,分泌大量细胞因子反馈调节引起辐射后期的小胶质细胞激活。     

Pituitary adenomas in patients with Cushing disease: initial experience with Gd-DTPA-enhanced MR imaging

To assess the role of magnetic resonance imaging in the evaluation of adrenocorticotropic-hormone (ACTH)-producing pituitary adenomas, and the effect of intravenously administered gadolinium-diethylenetriaminepentaacetic acid (DTPA) on lesion/pituitary contrast, imaging was performed in 13 patients with clinical and chemical evidence of Cushing disease. Images were obtained at 0.5 T before and after the injection of Gd-DTPA (0.1 mmol/kg). Lesions were identified in eight of 12 precontrast and ten of 12 postcontrast studies. In these 12 patients adenomas were found at transsphenoidal surgery. The other patient, with normal images, was found to have an ectopic source of ACTH. Coronal images corresponded remarkably well with the neurosurgeon's intraoperative findings. Serial T1-weighted images disclosed early enhancement of the pituitary gland and delayed enhancement of the cystic adenomas. The discrepancy in times to peak enhancement accounted for improved lesion/pituitary contrast in some early images and for reversal or diminution of lesion/pituitary contrast in later images.     

Oxytocin in Brattleboro Rats: Increased Synthesis is Contrasted by Blunted Intrahypothalamic Release From Supraoptic Nucleus Neurones

Adult male Brattleboro rats were used to investigate the impact of the congenital absence of vasopressin on the release pattern of oxytocin (OXT) within the hypothalamic supraoptic nucleus (SON) in response to a 10-min forced swimming session and osmotic stimulation. Both immunohistochemical and in situ hybridisation data suggest that vasopressin-deficient animals have more oxytocin-synthesising neurones in the SON than homozygous wild-type controls. Unexpectedly, both forced swimming and peripheral osmotic stimulation resulted in a blunted release profile of oxytocin within the SON of vasopressin-deficient rats compared to controls. A similar intranuclear OXT response to direct osmotic stimulation of the SON by retrodialysis with hypertonic Ringer's solution in both genotypes confirmed the capability of SON neurones to locally release oxytocin in vasopressin-deficient rats, indicating an altered processing of information originating from multisynaptic inputs rather than a deficit in release capacity. Taken together with data obtained in previous studies, the present findings provide evidence suggesting that autocrine and paracrine signalling of magnocellular neurones differs within the paraventricular nucleus and the SON. Thus, significant alterations in intra-SON oxytocin mRNA levels cannot easily be extrapolated to intranuclear release profiles and the local signal intensity of this neuropeptide after physiological stimulation.     

巴曲酶对急性心肌缺血犬冠脉节段阻力和流量的影响

犬冠状动脉定量狭窄造成急性心肌缺血,观察巴曲酶(batroxobin)对冠脉循环及血流动力学的影响。结果显示,batroxobin可剂量依赖性地增加缺血心脏冠脉血流量,2BU·kg^-1(0.1BU·kg^-1·min^-1)iv后40min,缺血犬冠脉流量比盐水对照组增加12%,此时小冠脉阻力由4.1±0.5降至3.2±0.5mmHg·min·ml^-1,而大冠脉阻力无明显变化;给药后120min,上述作用仍然持续,且冠脉总阻力降低13%,左室压上升及下降最大速率与盐水对照组相比分别增大14%和16%。结果表明,batroXobin在冠脉低灌流状态下仍可降低小冠脉阻力,增加冠脉流量,这可能是其改善缺血犬冠状循环及心脏功能的机理之一。     

Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa

Mitogen-activated protein kinases (MAPK), also known as extracellular signal-regulated kinases (ERKs) are cytoplasmic and nuclear serine/threonine kinases involved in signal transduction of several extracellular effectors. Recently, we have demonstrated that ERKs are present in spermatozoa and are involved in the regulation of the process of capacitation. We report here the effect of progesterone, a well-known inducer of the acrosome reaction in mammalian spermatozoa, on the immunolocalization, phosphorylation and activity of ERKs in capacitated human spermatozoa. We demonstrated that short-term incubation of spermatozoa with progesterone induces phosphorylation and activation of ERKs, resulting in redistribution of the proteins from the post-acrosomal region to the equatorial segment within the sperm head. To investigate the role of ERKs on the biological effects of progesterone, we used the MAPK cascade inhibitor PD098059, which strongly inhibited progesterone-induced activation of ERK-2. This compound did not inhibit progesterone-induced acrosome reaction, although it prevented redistribution of the enzyme to the equatorial region of the sperm head. These results suggest that the two processes, although temporally related, are independent. In conclusion, we provide new insight into the signal transduction pathways involved in the non- genomic action of progesterone in spermatozoa and suggest a possible involvement of ERKs in the process of fertilization.      

Postnatal development in vasopressin deficient Brattleboro rats with special attention to the hypothalamo-pituitary–adrenal axis function: the role of maternal genotype

Anomalies in hormonal and neurotransmitter status during perinatal period can lead to lifespan alterations in the central nervous system. Vasopressin is present early in the brain and has various mitogenic, metabolic and physiological actions, e.g. in water homeostasis or in the regulation of the hypothalamo-pituitary–adrenal (HPA) axis. Therefore we examine the possible role of vasopressin in perinatal development with special attention to the influence of maternal genotype and to the HPA axis regulation. We compared homozygous vasopressin deficient (di/di) Brattleboro rats to their heterozygous (di/+) littermates both from di/+ and di/di mother. Higher locomotion due to reduced adaptation was present at preweaning. During the first 10 days of life the di/di pups from di/di mother were the smallest, while in the later perinatal period the genotype of the pups became the more important determinant of the somatic development, namely the di/di pups from both mothers had reduced weight gain. Generally the lack of vasopressin in the pups fastened the somatic development (pinna detachment, eye and ear opening, incisor eruption) however the neurobehavioral development (palmar grasp reflex, righting reflex, negative geotaxis, etc.) was not influenced profoundly by either the mother's or the pup's genotype. The lack of vasopressin in pups abolished the 24 h maternal separation induced adrenocorticotrop hormone (ACTH) elevation while the accompanying corticosterone rises were even higher. The vasopressin deficiency of the mother reduced the resting ACTH and all corticosterone levels in all pups. So we can conclude that the lack of vasopressin speeds up the development, probably there is a greater drive for self-sufficiency in these animals. The mother's vasopressin deficiency reduced the HPA axis reactivity of the pups. The role of vasopressin in the HPA axis regulation is important during the perinatal period independently from the mother's genotype. The large discrepancy between ACTH and corticosterone regulation requires further studies.