No description available.

No description available.

No description available.

No description available.

Recently, models of aggressive behavior have begun to appreciate the influence of both psychological and biological predictors of maladaptive behavior. The aim of the current project was to clarify the roles that the noradrenergic system (i.e., norepinephrine metabolite, 3-methoxy-4-hydroxyphenyglycol [MHPG]) and characteristics of the rearing environment play in different expressions of aggression (i.e., hostile and instrumental). It was predicted that higher concentrations of MHPG would be related to increased self-reports of aggressive behavior, especially hostile forms, while expressing aggression during an analog aggression task would lead to decreases in MHPG. It was also predicted that concentrations of MHPG would interact with childhood environment characteristics to predict aggressive behavior in youth. A sample of 68 male youth, aged 7 to 17, were recruited from two agencies in southwest Virginia serving disadvantaged youth. They completed self-report measures on their childhood environment, aggressive and delinquent behaviors, as well as exposure to community violence and negative life events. In addition, youth played a challenging computer game with an alleged "opponent" and lost. Half of the participants were able to retaliate after the game against their "opponent." Salivary MHPG was measured once before and three times after the game. A series of ANOVAs and hierarchical regressions were conducted in order to test the main and interactive effects of punitive childhood experiences and baseline MHPG on aggressive behavior. Findings failed to support the primary predictions; however, results of supplemental analyses showed significant associations of aggression with negative mood, negative family atmosphere, and increased baseline MHPG after controlling for negative family atmosphere. Also, parental punishment and rejection significantly predicted delinquency, and a significant interaction effect indicated that higher recovery concentrations of MHPG placed rejected youth more at risk for engaging in delinquent behavior. Results of the present study help to enhance understanding of the differences in biological and psychological correlates of aggression and delinquency in at-risk youth, and inform prevention and intervention efforts. / Ph. D.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 7 uppsatser.

Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [ H]NE uptake capacity, an effect characterized by a robust decrease in the V of the transport of [ H]NE. As expected, reserpine did not displace the binding of [ H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [ H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [ H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca /Ca -calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [ H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, α-methyl-p-tyrosine, increased [ H]NE uptake and eliminated the inhibitory effects of reserpine on [ H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca -independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors.

Recent approaches in depression therapeutics include triple reuptake inhibitors, drugs that target three monoamine systems. Using in vivo electrophysiological and microdialysis techniques, the effects of 2- and 14-day treatments of escitalopram, nomifensine and the co-administration of these two drugs (TRI) were examined in male Sprague-Dawley rats. Short- and long-term TRI administration decreased NE firing and had no effect on DA neurons. Normal 5-HT firing rates were maintained after 2-day TRI administration compared to the robust inhibitory action of selective serotonin reuptake inhibitors (SSRIs). Escitalopram treatment enhanced the tonic activation of the 5-HT1A receptors given the increase in firing observed following WAY100635 administration. Nomifensine treatment enhanced tonic activation of the α2–adrenoceptors following idazoxan administration. TRI treatment caused a robust increase in extracellular DA levels that was in part mediated by a serotonergic contribution. Therapeutic effects of the drugs examined in this study may be due to the enhancement of 5-HT, NE and/or DA neurotransmission.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Sanjeev K. Narayanan / Antibiotics are substances produced by bacteria or fungi that are inhibitory to other bacteria and fungi. Antimicrobial compounds include substances that are naturally produced, chemically modified or completely synthetic (chemically designed or synthesized). The chemical modification of naturally produced antibiotic generally results in increase stability, solubility, increased spectrum of activity, or efficacy. Antimicrobial compounds are used in animals to treat and control infectious diseases, and also for growth promotion. Bacteria may gain resistance to antibacterial agents via a variety of mechanisms. There is growing evidence that antimicrobial resistance has significant public health consequences. Rationale use of antimicrobial drugs using appropriate medication at the proper dosage and for duration is one of the important means to reduce selective pressure that helps reduce life of resistant organism. It is also vital to reduce the spread of multi drug resistant organisms in the environment especially in health care facilities. Bacteria evolve rapidly not only by mutation, but also by horizontal gene transfer through the transformation, transduction, and conjugation. Conjugation involves a close contact between two bacteria and transfer of the plasmid that carry many genetic elements. The pathogenic bacteria have the ability to sense as well as respond to the stress in the recipient. The epinephrine and norepinephrine play a key role in stress situations in animals. A previous study showed that norepinephrine (NE), a catecholamine at physiological concentrations promoted the conjugation efficiencies of a conjugative plasmid from a clinical strain of Salmonella typhimurium to an E. coli recipient in vitro. The objective of this study was to determine the effect of norepinephrine on conjugation of two E. coli strains. Both filter mating and liquid mating assays were used. The results revealed that there was no significance difference between the presence and the absence of norepinephrine on conjugative transfer of RP4 plasmid between E. coli strains (FS1290 and C600N) either in filter mating or liquid mating. Further studies are needed to determine whether higher concentration of (more than 20 mM) has any effects on conjugation in E. coli.

As espécies reativas de oxigênio (EROs) são intermediários de vias de sinalização que regulam eventos celulares relevantes na função de células musculares lisas vasculares como migração, proliferação e contração. A NADPH oxidase é a principal fonte enzimática de EROs com finalidade sinalizadora no sistema cardiovascular. Estudos do nosso grupo demonstraram que a proteína dissulfeto isomerase (PDI), uma chaperona redox do retículo endoplasmåtico é capaz de modular a geração de EROs e a ativação de vias de sinalização redox dependentes pela Ang II. Apesar dos recentes avanços na compreensão dos mecanismos que regulam a interação entre a PDI e NADPH oxidase, o papel desta chaperona nos efeitos biológicos relacionados a EROs, como a contração vascular, não estão esclarecidos. A inibição da resposta contrátil pelo DTNB, um oxidante de tióis sugere o envolvimento de proteínas contendo tióis como a PDI e a NADPH oxidase na contração de aortas isoladas estimuladas com Ang II. Estes resultados foram confirmados por experimentos que demonstraram a expressão de PDI em todas as camadas vasculares da aorta de ratos Wistar e uma co-localização desta proteína com a isoforma NOX-1. A inibição da PDI diminuiu a geração de EROs e a reatividade vascular induzida por Ang II e NOR independente da presença do endotélio. A investigação dos mecanismos envolvidos sugere um papel da PDI na mobilização de cálcio dos estoques intracelulares via NADPH oxidase. A ativação de MAP quinases contribuiu para aumentar a mobilização de cálcio intracelular em aortas estimuladas com Ang II e NOR. No entanto, a inibição da PDI reduziu a fosforilação da ERK 1/2 em aortas estimuladas com Ang II, mas não com NOR. A análise conjunta dos nossos resultados sugere que mecanismos redox dependentes e independentes estariam envolvidos na regulação da resposta contrátil à Ang II e NOR pela PDI. / The reactive oxygen species (ROS) are intermediates of signaling pathways which regulates cellular events relevant for the vascular smooth cells function as migration, proliferation and contraction.The NADPH oxidase is the main enzimatic source of ROS with the signaling purpose on the cardiovascular system. We previously demonstrated that the protein disulfide isomerase (PDI), a redox chaperone of endoplasmic reticulum, is able to modulate the ROS generation and the activation of signaling redox ways dependent of Ang II. Although the recent advances in the understanding of mechanisms that regulate the interaction of PDI and NADPH oxidase, the role of this chaperone in the biological effects related to ROS, as vascular contraction, are not well clarified. The inhibition of the contractile response by DTNB, an oxidant thiol, suggest the involvement of proteins containing thiols as the PDI and NADPH oxidase in the contraction of isolated aortas stimulated with Ang II. These results were confirmed by experiments that demonstrated the PDI expression in Wistar rats vascular layers and a co-localization of this protein with the NOX-1 isoform. The PDI inhibition decreased ROS generation and the Ang II and NOR induced vascular reactivity endothelium independent. The investigation of involved mechanisms suggest that one PDI role is the calcium mobilization from the intracellular storage by NADPH oxidase way. The MAPkinases activation contributed to increase de intracellualar calcium in stimulated aortas with AngII and NOR. However, the PDI inhibition reduced the ERK ½ fosforilation in AngII- stimulated aorta, but not with NOR. The analyses of all of our results suggests that dependent and independent redox mechanims were involved in the regulation of contractile response to Ang II and NOR by PDI.