The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys

Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3 receptor, one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats. In order to test if these findings can be generalized to primates we investigated the role of the tachykinin NK3 receptor in the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with the tachykinin NK3 receptor antagonist, (R)-(N)-[1-[3-[1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N-methylacetamide (SR142801; 0, 0.02, 0.2, 2.0 mg/kg, i.p.), and received either a treatment with cocaine (10 mg/kg, i.p) or saline (i.p.). Cocaine increased locomotor activity and aerial glance behavior, but reduced exploratory and bodycare activities, scent marking and terrestrial scanning behavior. A sensitivity analysis revealed that two responder types can be differentiated in relation to the occurrence of a hyperlocomotor response to cocaine. SR142801 blocked the actions of cocaine on several behaviors dose-dependently for each responder type, respectively. There was no effect of SR142801 alone on any behavior measured. These data suggest that the tachykinin NK3 receptor contributes to the individual behavioral response to cocaine in marmoset monkeys. Having no behavioral effects on its own, but blocking the cocaine effects, might suggest the tachykinin NK3 receptor antagonist, SR142801, as a potential treatment of cocaine addiction in humans.     

Determining the region-specific contributions of 5-HT receptors to the psychostimulant effects of cocaine

Cocaine is a drug of abuse that has complex neurochemical and behavioural profiles. When it became evident that models that involve only dopamine do not fully explain the complex effects of cocaine on behaviour, the focus of research expanded to include the 5-hydroxytryptamine (5-HT) system in the brain. The 5-HT system comprises several subtypes of 5-HT receptors, which contribute differentially to the various behavioural effects of cocaine. In this article, we describe which subtypes regulate behaviours that are related to cocaine addiction and how they might provide new therapeutic approaches. Numerous subpopulations of each 5-HT receptor can be distinguished according to their location in the brain. We also discuss how these subpopulations relate to the effects of 5-HT-receptor stimulation at the systemic level. These insights provide a new receptor-based approach for understanding the 5-HT mechanisms that subserve the actions of cocaine and possible pharmacotherapies against cocaine addiction.     

Correlations between hypothalamus-pituitary-adrenal axis parameters depend on age and learning capacity

Glucocorticoid hormones are released after activation of the hypothalamus-pituitary-adrenal (HPA) axis and in the brain can modulate synaptic plasticity and memory formation. Clear individual differences in spatial learning and memory in the water maze allowed classification of groups of young (3 months) and aged (24 months) male Wistar rats as superior and inferior learners. We tested 1) whether measures of HPA activity are associated with cognitive functions and aging and 2) whether correlations of these measures depend on age and learning performance. Basal ACTH, but not corticosterone, was increased in aged rats, with the stress-induced ACTH response exaggerated in aged-inferior learners. Aged-superior learners had lower expression of glucocorticoid receptor and CRH mRNA in the parvocellular paraventricular nucleus of the hypothalamus compared with all other groups. Hippocampal mineralocorticoid receptor and glucocorticoid receptor mRNAs differed modestly between groups, but steroid receptor coactivator and heat-shock-protein 90 mRNAs were not different. Strikingly, correlations between HPA axis markers were dependent on grouping animals according to learning performance or age. CRH mRNA correlated with ACTH only in aged animals. Parvocellular arginine vasopressin mRNA was negatively correlated to basal corticosterone, except in aged-inferior learners. Corticosteroid receptor mRNA expression showed a number of correlations with other HPA axis regulators specifically in superior learners. In summary, the relationships between HPA axis markers differ for subgroups of animals. These distinct interdependencies may reflect adjusted set-points of the HPA axis, resulting in adaptation (or maladaptation) to the environment and, possibly, an age-independent determination of learning ability.     

Inflammatory local recurrence after breast-conservation therapy for noninflammatory breast cancer

Inflammatory local recurrence after breast-conserving therapy for noninflammatory breast cancer is uncommon and carries a poor prognosis. Over a 5-year period, 7 such cases were treated at the New York-Presbyterian Hospital/Weill-Cornell Medical Center. The characteristics of these 7 patients were compiled and are reviewed along with a discussion of inflammatory recurrence. Tumor size, location, histologic type, grade, stage, margin status, lymphovascular invasion (LVI), estrogen receptor (ER) status, progesterone receptor (PgR) status, adjuvant therapy, and/or radiation therapy at the time of primary treatment and at recurrence were analyzed. The median survival time was 79 months (range, 26-130 months) for patients initially ER-positive, compared with 23 months (range, 0-67 months) for initially ER-negative patients. The median survival for patients without lymph node involvement was 78 months (range, 26-130 months) compared with 41 months (range, 0-79 months) for those with nodal metastases. Survival time in this series of inflammatory local recurrences correlated with the ER status and lymph node involvement of the primary lesion. The optimal management for inflammatory local recurrence is a multimodality approach combining preoperative chemotherapy and surgery.     

Anatomical basis of a new naso-labial island flap

Summary We describe a nasolabial island flap with a proximal base. This anatomical study confirms the interest of a proximal base especially with regard to venous return. As opposed to classical naso-labial flaps with subcutaneous pedicle, it has a vascularization of musculo-cutaneous type which allows a greater degree of mobility and reliability. This flap is an effective therapeutic option in surgery for skin defects of the face.

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Bases anatomiques d'un nouveau lambeau musculo-cutané nasolabial en îlôt

Résumé Nous décrivons un lambeau nasolabial en îlot à pédicule supérieur. Cette étude anatomique confirme l'intérêt d'un lambeau à pédicule supérieur, en particulier sur le plan du retour veineux. Contrairement aux lambeaux nasolabiaux classiques à pédicule sous dermique, il possède une vascularisation de type musculo-cutanée qui lui confère une grande mobilité et une excellente fiabilité. Ce lambeau représente une arme thérapeutique supplémentaire pour la chirurgie réparatrice des pertes de substance de la face.

     

Anatomic basis of laparoscopic surgery in the male pelvis

Summary Laparoscopic surgery of the male pelvis remains a risky procedure, with around 15% of perioperative complications, as compared to 0.03% in laparoscopic surgery for gynecologic and obstetric conditions. Many of these complications are due to the surgeon's being faced with an unfamiliar anatomic situation in his approach through the laparoscopic operative field. We have added to the data of the literature our anatomic and clinical experience in order to define the anatomic basis of surgical risk in this type of procedure. While dissection lateral to the iliac vessels (surgery of the spermatic cord) is safe, dissection medial to these vessels is more risky because of the confined anatomic relationships and their variations (particularly vascular anomalies and variable relations of the ureter).

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Bases anatomiques de la chirurgie coelioscopique dans le pelvis masculin

Résumé La chirurgie laparoscopique du pelvis masculin reste une chirurgie à risque, environ 15 % de complications péri-opératoires, si on la compare aux 0,03 % de la chirurgie laparoscopique en milieu gyné-co-obstétrical. Bon nombre de ces complications sont liées à la confrontation de l'opérateur à une situation anatomique nouvelle par son approche à travers un champ opératoire laparoscopique. Nous avons confronté aux données de la littérature notre expérience anatomique et clinique afin de préciser les bases anatomiques du risque chirurigical pour ce type d'interventions. Si la dissection en dehors des vaisseaux iliaques (chirurgie du cordon spermatique) est sûre, par contre les rapports anatomiques étroits et leurs variations rendent la dissection sur le bord médial des vaisseaux iliaques plus risquée (anomalies vasculaires et rapports variables de l'uretère en particulier).

     

Behavioral and neuronal reorganization after unilateral substantia nigra lesions: Evidence for increased interhemispheric nigrostriatal projections

This study was intended to investigate the possibility of a relationship between compensation of sensory-motor asymmetries induced by unilateral substantia nigra lesions and changes in inter-hemispheric nigrostriatal projections. Adult male rats were used in two experiments:Experiment I. Animals received an injection of either 6-OH-dopamine or kainic acid into the substantia nigra. They were observed for intervals of 7, 21 or 90 days with respect to spontaneous turning, d-amphetamine-induced turning and other sensory-motor asymmetries. Interhemispheric nigrostriatal projections were examined by injecting horseradish peroxidase into the striatum homolateral to the nigral lesion. Labeled perikarya were counted in the contralateral substantia nigra. A significant increase in number of labeled neurons was observed 7 and 21 days, but not 90 days after the nigral lesion in comparison to control animals. Spontaneous lesion-induced turning behavior ceased within the first postoperative week. After 21 and 90 days it was still possible to elicit turning by injection of amphetamine.Experiment II. An increase in number of interhemispheric nigro striatal projections one week after the nigral lesion was also found when Nuclear Yellow was used as a tracer substance. Animals received a unilateral injection of Fast Blue into the caudate nucleus, followed by an injection of Nuclear Yellow at the identical locus one week later. An increase in number of Nuclear Yellow-labeled neurons was registered only if the injection of Fast Blue was followed by a 6-hydroxydopamine lesion in the homolateral substantia nigra within 24 h. Interhemispheric nigro striatal projections were of monoaminergic as well as of non-monoaminergic origin, as revealed by histofluorescent tracing for monoaminergic neurons.These results may reflect sprouting of interhemispheric fiber projections in response to, or as correlates of, behavioral compensation of the lesion-induced behavioral asymmetries.     

An anatomical and radiological study of the femoropatellar articulation

Summary An analytical study was made of 30 knees by dissection, 200 by conventional radiology, 120 by CT scans, and of 2,400 pathological knees by conventional radiology, and 900 by CT. The radiological and scanning methods most used for a study of the femoropatellar articulation are described and the normal values of each feature determined by a computer study. The femoral trochlea and its shape are very important for the stability of the patella. The normal and pathological types of trochlea are described. This study established a number of anatomical factors which influence patellar stability, and form a basis for proposing the correction of anatomical anomalies in the treatment of instability of the joint.

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Etude radio-anatomique de l'articulation fémoro-patellaire

Résumé Les auteurs ont analysé 30 genoux par dissection, une série en radiologie conventionnelle de 200 genoux témoins, une série de 120 tomodensitométries de genoux témoins, une population pathologique de 2 400 genoux en radiologie conventionnelle et de 900 genoux en tomodensitométrie. Les méthodes radiologiques et scannographiques les plus utiles pour analyser l'articulation fémoro-patellaire sont décrites et les valeurs normales de chaque facteur précisées à partir d'une étude informatique. la trochlée fémorale et sa morphologie sont très importantes pour stabiliser la rotule. Des types de trochlées normales et pathologiques sont décrits. Cette étude permet d'établir un certain nombre de facteurs anatomiques influençant la stabilité patellaire et, en s'appuyant sur une étude parallèle, de proposer la correction des anomalies anatomiques dans le traitement des instabilités patellaires.

     

Anatomic basis of venous drainage in gastric tubular esophagoplasty

Summary This study was made with the aim of specifying the general architecture of the venous system of the stomach and its mode of drainage under normal conditions, and also of investigating the role of the venous drainage in the origin of disunion, anastomotic fistula and structure after tubular esophagoplasty pedicled on the right gastroepiploic vessels. Sixty stomachs removed from fresh cadavers were studied by injection-corrosion, using colored Altufix P₁₀ as the injection mass. 35 specimens were injected globally via the superior mesenteric v., 15 by the same route but after clamping of the splenic, left gastric and right gastric vv., which corresponds to the technique of gastrolysis performed in esophagoplasty, and 10 were injected simultaneously with media of four different colors via the left gastric, right gastric, superior mesenteric and splenic vv. to define their respective territories. Also studied were the origin, course, termination, territory and caliber of the main gastric veins. Analysis of the results confirmed the richness of the venous anastomoses of the stomach, effected on the one hand between the two extraparietal arches at the greater and lesser curvatures, and on the other by intraperitoneal communications arranged perpendicular to these two arches. It emerges that the right gastroepiploic v. cannot always ensure drainage of the entire stomach. The factors involved are discussed. The risk of venous stasis in gastric esophagoplasty must always be borne in mind.

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Bases anatomiques du drainage veineux dans l'oesophagoplastie gastrique tubulée

Résumé Ce travail a été effectué dans le but de préciser l'architecture générale du système veineux de l'estomac et son mode de drainage dans des conditions normales. Il est aussi motivé par la recherche du rôle du drainage veineux dans la genèse des désunions, des fistules anastomotiques, des sténoses après oesophagoplastie tubulée pédiculisée sur les vaisseaux gastro-épiploïques droits. 60 estomacs prélevés sur des cadavres frais ont été étudiés par la méthode d'injection-corrosion. Le produit utilisé est l'Altufix P₁₀ coloré. 35 pièces ont été injectées globalement par la veine mésentérique supérieure, 15 pièces par la même voie mais après clampage de la veine splénique, de la veine gastrique gauche et de la veine gastrique droite, ce qui correspond a la technique de gastrolyse effectuée pour oesophagoplastie, et 10 ont été injectées simultanément par les produits colorés en quatre couleurs par les veines gastrique gauche, gastrique droite, mésentérique supérieure et splénique (ou liénale) pour préciser leur territories correspondants. L'origine, le trajet, la terminaison, le territoire et le calibre des principales veines de l'estomac ont été étudiés. L'analyse des résultats permet de confirmer la richesse des anastomoses veineuses de l'estomac qui s'effectuent d'une part, entre deux arcades extrapariétales au niveau de la grande et de la petite courbure, et d'autre part au niveau de communications intrapariétales disposées perpendiculairement à ces deux arcades. Il apparaît que la veine gastro-épiploïque droite ne peut pas toujours assurer le drainage de la totalité de l'estomac. Les facteurs influençants sont discutés. Le risque de stase veineuse dans l'oesophagoplastie gastrique doit toujours être pris en compte.