Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test

This study investigated the involvement of the opioid system in the antidepressant-like effect of agmatine in the mouse forced swimming test (FST). The antidepressant-like effects of agmatine (10 mg/kg, i.p.), as well as those of fluoxetine (32 mg/kg, i.p, a selective serotonin reuptake inhibitor, SSRI) or morphine (5 mg/kg, s.c., a nonselective opioid receptor agonist) in the FST was completely blocked by pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Pretreatment of mice with naltrindole (3 mg/kg, i.p., a selective delta-opioid receptor antagonist), clocinnamox (1 mg/kg, i.p., an irreversible mu-opioid receptor antagonist), but not with 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (DIPPA; 1 mg/kg, i.p., a selective kappa-opioid receptor antagonist) completely blocked the anti-immobility effect of agmatine (10 mg/kg, i.p.) in the FST. These results firstly demonstrate that the antidepressant-like effects of agmatine in the FST seem to be mediated, at least in part, by an interaction with the opioid system, that involves an activation of delta- and mu-opioid receptors.     

Tourette's syndrome. Tics, jerks, and quirks

Over the past 20 years, public and physician awareness of tic disorders, including Tourette's syndrome, has increased remarkably. In fact, Tourette's syndrome is now "diagnosed" by many families before they consult a physician. Patients seek help not only for the involuntary movements and noises that characterize the illness but also for the accompanying learning, behavioral, and social problems. The authors of this article define the various tic disorders and discuss diagnosis and treatment of the most severe type, Tourette's syndrome.     

Public, animal, and environmental health implications of aquaculture.

Aquaculture is important to the United States and the world''s fishery system. Both import and export markets for aquaculture products will expand and increase as research begins to remove physiologic and other animal husbandry barriers. Overfishing of wild stock will necessitate supplementation and replenishment through aquaculture. The aquaculture industry must have a better understanding of the impact of the "shrouded" public and animal health issues: technology ignorance, abuse, and neglect. Cross-pollination and cross-training of public health and aquaculture personnel in the effect of public health, animal health, and environmental health on aquaculture are also needed. Future aquaculture development programs require an integrated Gestalt public health approach to ensure that aquaculture does not cause unacceptable risks to public or environmental health and negate the potential economic and nutritional benefits of aquaculture.     

The contribution of treatment outcome research to the reform of children's mental health services: multisystemic therapy as an example

Service system reforms of the past decade have yielded innovations in type, accessibility, and cost of services provided for some children and families with serious problems, but few of the treatments delivered have been empirically evaluated. Rigorous tests of well-conceived treatments are needed to provide a solid foundation for continued reform. Multisystemic therapy has demonstrated efficacy in treating serious clinical problems in adolescents and their multineed families and is an example of the successful blending of rigorous treatment outcome research and service system innovation.     

Curative surgery for gastric cancer: Study of 166 consecutive patients

From January 1980 to December 1991 we operated on 295 patients with a gastric carcinoma. In 166 cases (56.3%) surgery was performed with curative intent. In 93 patients (56%) a subtotal gastrectomy was performed, and in 73 cases (44%) a total gastrectomy. In all the cases a D-2 type lymphadenectomy was used. The global morbidity rate was 23%, and in-hospital mortality was 3.6%. The morbidity and mortality rates of these two operations were statistically different. Global 5-year survival estimate for the whole series is 61.3%. Univariate and multivariate analysis according to T and N (TNM classification), the number of positive nodes resected, and the relation of positive per resected nodes, revealed statistically different outcomes. This kind of quantitative classification allowed identification of high risk groups irrespective of site of nodal involvement. Tumors classified as intestinal or diffuse type by the Lauren classification had similar survival curves and 5-year survival estimates (p=0.834). By univariate and multivariate analysis this classification did not reveal a prognostic value in this group of patients. In our opinion, tumor penetration and lymph node involvement are at present the most reliable prognostic factors available.

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Resumen En el período enero 1980 a diciembre 1991 se operaron 295 pacientes con carcinoma gástrico. En 166 (56.3%), la cirugía fue realizada con intención curativa; en 93 (56%) se realizó gastrectomía subtotal y en 73 (44%) gastrectomía total. En la totalidad de los casos se realizó linfadenectomía D-2. La mortalidad global fue 23% y la mortalidad hospitalaria 3.6%. Las tasas de mortalidad y morbilidad de estas dos operaciones aparecieron significativamente diferentes. La sobrevida global a cinco años estimada para la totalidad de la serie es de 61.3%. Los análisis uni y multivariables de acuerdo con la clasificación TNM, el número de ganglios positivos resecados y la relación positivos/resecados revelaron resultados estadísticamente diferentes. Este tipo de clasificación cuantitativa permitió la identificación de Grupos de alto riesgo independientes del lugar de la invasión ganglionar. Los tumores clasificados como intestinales o difusos (clasificación de Lauren), registraron similares curvas de sobrevida y de sobrevida estimada a cinco años (P=0.834). Mediante el análisis univariable y multivariable esta clasificación no demostró tener valor pronóstico en nuestro Grupo de pacientes. En nuestra opinión, el grado de penetración del tumor y la invasión ganglionar son los factores de pronóstico más confiables.

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Résumé Entre Janvier 1980 et Décembre 1991, nous avons opéré 295 patients ayant un cancer gastrique. Chez 166 (56.3%), l'exérèse a été jugée curative. Chez 93 (56%) des cas, il s'agissait d'une gastrectomie subtotale alors que dans 73 (44%) cas, une gastrectomie totale a été pratiquée. Dans tous les cas une lymphadénectomie du type D-2 lui a été associée. La morbidité globale a été de 23% et la mortalité hospitalière de 3.6%. La morbidité et la mortalité des deux types d'intervention différaient de façon statistiquement significative. La survie à 5 ans de la série en entier a été de 61.3%. Une analyse uni et multifactorielle a pu mettre en évidence une différence statistiquement significative en ce qui concerne la survie par rapport à la classification T-N (TNM), le nombre de ganglions réséqués et le nombre de ganglions envahis/nombre de ganglions enlevés. Cette analyse a permis d'identifier les malades à haut risque, indépendamment du site de l'envahissement lymphatique. La courbe de survie et la survie estimée à 5 ans étaient identiques selon que la tumeur a été classée intestinale ou diffuse selon Lauren. Cette classification n'a pas, pourtant, de valeur pronostique d'après les analyses uni et multifactorielle. A notre avis, la pénétration tumorale et le degré d'envahissement lymphatique sont les deux facteurs pronostiques les plus constants.

     

Immunophenotyping of acute leukemia by flow cytometry: closing the black holes of morphology

The heterogeneity of disease conditions in acute leukemia (AL) requires the most discriminative procedures for a differential diagnostic classification. Selected cases of AL, representative of lineage fidelity, multilineage phenotype and phenotypic switch, are reviewed to document that the diversity of the leukemic cells (lineage involved, maturation stage, aberrant markers), although not always characterizable by morphological differences, is reflected by a variety of immunophenotypes which may be efficiently characterized by flow cytometry to obtain a precise diagnosis.     

Methylmercury neurotoxicity in Amazonian children downstream from gold mining.

In widespread informal gold mining in the Amazon Basin, mercury is used to capture the gold particles as amalgam. Releases of mercury to the environment have resulted in the contamination of freshwater fish with methylmercury. In four comparable Amazonian communities, we examined 351 of 420 eligible children between 7 and 12 years of age. In three Tapajós villages with the highest exposures, more than 80% of 246 children had hair-mercury concentrations above 10 microg/g, a limit above which adverse effects on brain development are likely to occur. Neuropsychological tests of motor function, attention, and visuospatial performance showed decrements associated with the hair-mercury concentrations. Especially on the Santa Ana form board and the Stanford-Binet copying tests, similar associations were also apparent in the 105 children from the village with the lowest exposures, where all but two children had hair-mercury concentrations below 10 microg/g. Although average exposure levels may not have changed during recent years, prenatal exposure levels are unknown, and exact dose relationships cannot be generated from this cross-sectional study. However, the current mercury pollution seems sufficiently severe to cause adverse effects on brain development.     

Identification of a homologue of CD59 in a cyclostome: implications for the evolutionary development of the complement system

We have employed a COS cell expression cloning procedure to isolate a full length cDNA clone encoding a hagfish leukocyte-associated membrane protein (HLMP1). The protein, which is identified by a monoclonal antibody (JB3) generated in our laboratory, is present on the majority of hagfish leukocytes and is also expressed on erythrocytes. The cDNA clone contained an open reading frame encoding a 120 residue polypeptide which exhibits 33% amino acid sequence identity with the precursor protein of human CD59, a leukocyte-associated membrane protein which regulates the action of the complement membrane attack complex on homologous cells. CD59 belongs to a family of structurally related glycoproteins which includes the Ly-6 proteins expressed on mouse lymphocytes. In addition to significant overall sequence homology HLMP1 shows conservation of 8 key cysteine residues with members of the CD59/Ly-6 family. Comparison of the hagfish sequence with that of the mature human CD59 protein suggested a processed protein consisting of 74 amino acids associated with the cell membrane via a GPI anchor. The latter was confirmed by immuno-flow cytometry following treatment of transfected COS cells with phospholipase. Phylogenetic analysis and tissue distribution of this protein in the hagfish are consistent with HLMP1 being a homologue of CD59. A three-dimensional model of HLMP1, constructed using the NMR-determined structure for human CD59 as a template, indicated conservation of a core structure of five strands of beta-sheet and a short helix stabilised by four disulfide bonds. These findings, when taken together with our previous identification of C5a-like chemotactic activity in LPS-activated serum, provide indirect evidence for the existence of the terminal lytic complement pathway (C5 to C9) in these primitive vertebrates.     

A capture enzyme-linked immunosorbent assay for species-specific detection of Bothrops venoms

A direct sandwich enzyme-linked immunosorbent assay (ELISA), employing affinity purified antivenom antibodies specifically recognizing the homologous venom, was developed for species-specific detection of bothropic venom. The method is based on a two-step affinity purification of the specific antibodies. A species monovalent antivenom is adsorbed onto a venom adsorbent containing heterologous venoms from the Bothrops, Crotalus and Lachesis genera. The species-specific antibodies obtained, are then adsorbed onto a second venom adsorbent containing only the homologous venom for the removal of non antivenom antibodies. Venom concentrations of 0.1 and 1,000 ng/ml were specifically identified for Bothrops jararacussu and B. alternatus venom respectively.