Purification of the NADH reductase component of the steroid 9α-hydroxylase fromMycobacterium fortuitum

The NADH reductase component of the steroid 9α-hydroxylase fromMycobacterium fortuitum was purified to homogeneity. Recovery of the enzyme from the 50≈60% ammonium sulfate saturated fraction was 49%, with a purification factor of 100-fold. The NADH reductase has a relative molecular mass of 60 KDa as determined by SDS-PAGE. The absorption maxima at 410 and 450 nm indicate the presence of iron-sulfur group and flavin. These prosthetic groups seemed to function as redox groups that transfer electrons from NADH to the following protein. The K_M value for NADH as substrate was 68 μM. The NH₂-terminal amino acid sequence of the reductase was determined as Met-Asp-Ala-Ile-Thr-Asn-Val-Pro-Leu-Pro-Ala-Asn-Glu-Pro-Val-His-Asp-Tyr-Ala-Thr. This sequence does not show a homology with the NH₂-terminal sequences reported for the reductase component of other monooxygenases, suggesting that the NADH reductase component of the steroid 9α-hydroxylase system is novel.     

Synthesis and biological evaluation of 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds as open-chain analogues of neplanocin A

Novel 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds were designed and synthesized as open-chain analogues of neplanocin A. Alkylation of adenine or pyrimidine bases with the mesylate4 was chosen as a simple approach to the synthesis of 2-fluoro-2-butenylated nucleosides. Mesylate4 was prepared from dihydroxyacetone dimervia four steps in 58% overall yield. The synthesized compounds were evaluated their antiviral activity against HSV, HIV and Polio viruses.     

Melatonin in humans: a biochemical marker of the circadian clock and an endogenous synchronizer

Melatonin (MLT) is a methoxyindole secreted principally by the pineal gland. It is synthesized at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and activated by the light/dark cycle. Light is able to both suppress or activate melatonin production on the light schedule. The nycthohemeral rhythm of this hormone can be determined by repeated measurements of plasma or saliva MLT or urine sulfatoxy-MLT, the main hepatic metabolite. Melatonin can be considered as the output (the hand) of the endogenous clock. Since the regulating system follows a central and sympathetic nervous pathway, an abnormality at any level could unspecifically modify the MLT secretion, especially in patients with sympathalgia or dysautonomia. Melatonin plays the role of an endogenous Zeitgeber on core temperature or sleep-wake cycle. Exogenous MLT is able to influence the endogenous secretion of the hormone according to a phase response curve. There are practical implications for this property in situations when biological rhythms are disturbed (jet-lag syndrome, delayed sleep phase syndrome, insomnia in blind people, shift-work, insomnia in elderly people). Improvement of pharmaceutical forms (controlled release preparations) or development of MLT analogs could lead to decisive progress.

Résumé

La mélatonine est une hormone de structure indolique produite par la glande pinéale. Elle est sécrétée préférentiellement pendant la nuit avec un pic vers 3 h du matin dans des conditions d'environnement normal. Le rythme endogène de sécrétion est généré par les noyaux suprachiasmatiques et entraîné par l'alternance jour/nuit. La lumière peut à la fois supprimer ou entraîner la production de mélatonine selon la plage horaire d'éclairement. Le rythme nycthéméral de cette hormone peut être appréhendé par sa mesure répétée dans le plasma ou la salive, ou la détermination de la sulfatoxymélatonine (le principal metabolite hépatique) dans l'urine. La mélatonine peut être considérée comme l'aiguille de l'horloge interne. Le système de régulation de sa sécrétion est complexe, empruntant le système nerveux central puis le système sympathique (ganglion cervical supérieur). Toute anomalie à un quelconque niveau de cet axe altère non spécifiquement la sécrétion de mélatonine, en particulier chez les patients présentant une dysautonomie. Le rôle de la mélatonine est de synchroniser les rythmes biologiques, en particulier le rythme de température ou le rythme veille-sommeil. De plus la mélatonine exogène est capable d'influencer la sécrétion endogène de cette hormone selon une courbe de réponse de phase. Cette donnée constitue la justification théorique du traitement de troubles des rythmes biologiques (syndrome de franchissement rapide des fuseaux horaires, insomnie par retard de phase, désynchronisation chez les aveugles ou les travailleurs postés, insomnie des personnes âgées). D'autres indications thérapeutiques sont envisageables (troubles de l'immunité). L'amélioration des formes galéniques (préparations à libération contrôlée de la mélatonine) ou le développement d'analogues pourrait constituer un progrès décisif.     

Drug effects on response duration differentiation I: differential effects of drugs of abuse

Rats were trained to respond under a response duration differentiation schedule in which responses on a lever were reinforced if lever press durations were greater than or equal to 1.00 s but were also less than 1.30 s. Dose-effect curves were generated for cocaine, methamphetamine, pentobarbital, phencyclidine, delta-9-tetrahydrocanninabol (⁹-THC), and morphine. All drugs produced dose-dependent decreases in accuracy (the percentage of total response durations that were reinforced); however, the degree to which changes in accuracy were accompanied by changes in response rates varied among drugs. Pentobarbital and morphine affected primarily longer (> 1.3 s) response durations, phencyclidine and ⁹-THC affected primarily shorter response durations, whereas cocaine and methamphetamine affected both shorter and longer response durations. High doses of methamphetamine and cocaine increased the dispersion of response duration distributions with increasing dose, whereas higher doses of pentobarbital, ⁹-THC and morphine did not increase dispersion of response duration distributions as much. These data show that behavior under this novel schedule is differentially sensitive to a number of pharmacologic manipulations, and that the schedule can provide a useful addition to the analysis of drug effects upon behavior.     

Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats

The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of ⁹-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED₅₀=0.13 mg/kg). ⁹-THC and WIN-55,212-2 disrupted mazechoice accuracy at equipotent doses (ED₅₀ values =2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of ⁹-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED₅₀=8 µg/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.     

长效避孕栓剂对家兔的抗生育作用

目的和方法:是观察NP-9长效避孕栓(100mg/栓)于家兔阴道给药后15分钟和3.5小时的抗生育作用和连续7天给药的阴道刺激试验。结果:长效避孕栓无论在给药15分钟还是3.5小时交配避孕率均为100％。而生理盐水和赋型剂对照组避孕率分别为0％和40％。家兔阴道刺激试验结果表明:该栓剂阴道刺激炎症总分值为6.9,在可接受范围内。     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.     

Exercice physique, carence estrogénique, monoxyde d'azote et remodelage osseux

Summary

Objectives

The aim of this paper is to emphasize the possible relationships established between estrogens and physical exercise and concerning bone metabolism. Nitric oxide (NO) might play an important role in such relationships.

Topics

Cellular metabolism of NO, as well as NO effects upon osteoblasts and osteoclasts have been summarized. Several studies indicate that NO deficiency might be implicated in various vascular diseases observed in post-menopausal women. Other works also indicate that NO deficiency induced by cessation of ovarian activity might be responsible for osteopenia associated with this condition. Thus, decreased production of NO would be responsible both for post-menopausal osteoporosis as well as for osteopenia sometimes observed in amenorrheic athletes. Moreover osteoblastic response to mechanical stimulation might implicate estrogenic receptor(s). The role of these receptors in the regulation of NO synthesis is still unknown.     

A case of small cerebral cyst and pericentric inversion of chromosome 9 that developed schizophrenia-like psychosis

A case of schizophrenia-like psychosis (psychotic disorder not otherwise specified according to the DSM-IV criteria) with pericentric inversion on chromosome 9 [inv.(9) (p11; q13)] is reported. In this case, a minor brain anomaly, a small cyst in the left subcortex, was observed on magnetic resonance imaging of the brain. In the clinical course, prominent chronic hallucinations were observed; however, there was no evidence of the disorganization of personality, delusion, and deterioration in level of functioning that are usually seen in schizophrenia. This case and a review of the literature indicate that the pericentric region of chromosome 9 might be a potential areas of interest for the aetiology of psychiatric disorders. The phenotype-karyotype relationship of pericentric inversion on chromosome 9 and its relationship to psychosis are discussed.