Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2–51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP

Zum biochemischen Wirkungsmechanismus des adrenocorticotropen Hormons

Es wird eine Übersicht über zwei Hypothesen und die dazugehörigen Befunde zum Wirkungsmechanismus des adrenocorticotropen Hormons gegeben: 1. Der Gehalt der Nebenniere an cyclischem Adenosinmonophosphat wird durch ACTH erhöht, die stimulierende Wirkung des Hormons auf die Corticoidsynthese wird durch cyclisches Adenosinmonophosphat imitiert. Die Beschleunigung der Corticoidsynthese dürfte allerdings nicht durch eine Aktivierung der Phosphorylase in der Nebenniere erfolgen. 2. Befunde zum biochemischen Mechanismus der Stimulation der Proteinsynthese in der Nebenniere durch ACTH werden referiert. Die Intaktheit der Proteinsynthese der Nebenniere scheint für den steroidogenen Effekt des ACTH Voraussetzung zu sein.Two current hypotheses on the mechanism of action of ACTH are reviewed: 1. The content of cyclic 3,5-adenosine monophosphate of the adrenals is increased by ACTH, and cyclic AMP or ACTH enhance corticoid synthesis. However, stimulation of corticoid synthesis presumably is not mediated by activation of adrenal phosphorylase. 2. Experiments dealing with the biochemical mechanism of the stimulation of adrenal protein synthesis are reviewed. The integrity of the adrenal protein synthesis appears to be necessary for the enhancement of corticoid synthesis by ACTH

A Single Sex Pheromone Receptor Determines Chemical Response Specificity of Sexual Behavior in the Silkmoth Bombyx mori

In insects and other animals, intraspecific communication between individuals of the opposite sex is mediated in part by chemical signals called sex pheromones. In most moth species, male moths rely heavily on species-specific sex pheromones emitted by female moths to identify and orient towards an appropriate mating partner among a large number of sympatric insect species. The silkmoth, Bombyx mori, utilizes the simplest possible pheromone system, in which a single pheromone component, (E, Z)-10,12-hexadecadienol (bombykol), is sufficient to elicit full sexual behavior. We have previously shown that the sex pheromone receptor BmOR1 mediates specific detection of bombykol in the antennae of male silkmoths. However, it is unclear whether the sex pheromone receptor is the minimally sufficient determination factor that triggers initiation of orientation behavior towards a potential mate. Using transgenic silkmoths expressing the sex pheromone receptor PxOR1 of the diamondback moth Plutella xylostella in BmOR1-expressing neurons, we show that the selectivity of the sex pheromone receptor determines the chemical response specificity of sexual behavior in the silkmoth. Bombykol receptor neurons expressing PxOR1 responded to its specific ligand, (Z)-11-hexadecenal (Z11-16:Ald), in a dose-dependent manner. Male moths expressing PxOR1 exhibited typical pheromone orientation behavior and copulation attempts in response to Z11-16:Ald and to females of P. xylostella. Transformation of the bombykol receptor neurons had no effect on their projections in the antennal lobe. These results indicate that activation of bombykol receptor neurons alone is sufficient to trigger full sexual behavior. Thus, a single gene defines behavioral selectivity in sex pheromone communication in the silkmoth. Our findings show that a single molecular determinant can not only function as a modulator of behavior but also as an all-or-nothing initiator of a complex species-specific behavioral sequence

Pheromones and Other Semiochemicals for Monitoring Rare and Endangered Species

As global biodiversity declines, biodiversity and conservation have become ever more important research topics. Research in chemical ecology for conservation purposes has not adapted to address this need. During the last 10-15 years, only a few insect pheromones have been developed for biodiversity and conservation studies, including the identification and application of pheromones specifically for population monitoring. These investigations, supplemented with our knowledge from decades of studying pest insects, demonstrate that monitoring with pheromones and other semiochemicals can be applied widely for conservation of rare and threatened insects. Here, I summarize ongoing conservation research, and outline potential applications of chemical ecology and pheromone-based monitoring to studies of insect biodiversity and conservation research. Such applications include monitoring of insect population dynamics and distribution changes, including delineation of current ranges, the tracking of range expansions and contractions, and determination of their underlying causes. Sensitive and selective monitoring systems can further elucidate the importance of insect dispersal and landscape movements for conservation. Pheromone-based monitoring of indicator species will also be useful in identifying biodiversity hotspots, and in characterizing general changes in biodiversity in response to landscape, climatic, or other environmental changes

Growth And The Growth Hormone-Insulin Like Growth Factor 1 Axis In Children With Chronic Inflammation:Current Evidence, Gaps In Knowledge And Future Directions

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the growth hormone-insulin like growth factor axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate studies further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biologic therapy may lead to improvement of growth in some of these children but approximately one third continue to grow slowly. There is increasing evidence that the use of relatively high dose recombinant human growth hormone may lead to partial catch up growth in chronic inflammatory conditions, although long term follow-up data is currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis, systemic abnormalities of the growth hormone-insulin like growth factor axis and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human growth hormone in these conditions and discuss the role of recombinant human insulin like growth factor-1