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N R Contel

Publications and source records attributed to N R Contel.

5 recordsLinked to original sources

Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II.

Prostaglandins have wide-ranging effects in the body and are thought to be important mediators of inflammation. Cyclooxygenase (COX) plays a key regulatory role in prostaglandin synthesis, and occurs in both constitutive (COX-1) and inducible (COX-2) isoforms. COX-1 is thought to provide cytoprotective effects, whereas COX-2 is both inducible and the major isoform of inflammatory cells. Reduction of prostaglandin production by inhibition of cyclooxygenases appears to be the main mechanism of action of most non-steroidal anti-inflammatory drugs (NSAIDS). Here we present an animal model of COX-2 deficiency that was generated by gene targeting. Defects in null mice correlating with reduced viability included renal alterations, characteristic of renal dysplasia (100% penetrance), and cardiac fibrosis (50% penetrance). Female Cox-2-/- mice were infertile. COX-2 deficiency failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed.

Animals↗

Electroconvulsive seizures inhibit amygdala kindling: implications for mechanisms of action in affective illness.

Amygdala kindling, the progressive development of seizures following repeated electrical stimulation, has been used as a model of epileptogenesis, neural memory, and the development of behavioral alterations. In an attempt to interfere with the kindling process, electroconvulsive seizures (ECS) were administered 6 h prior to or immediately after once-daily amygdala stimulation. ECS compared with sham ECS 6 h prior to kindling profoundly inhibited the development of amygdala-kindled seizures, while ECS immediately after the afterdischarge (AD) were not effective. In a second study, seven daily ECS, but not a single ECS followed by a 6-day delay, markedly suppressed established amygdala-kindled seizures compared with sham ECS controls. The generalized seizures of ECS thus appear to be paradoxically anticonvulsant to limbic seizures. Carbamazepine, a potent anticonvulsant for temporal lobe and limbic seizures in animals and man, inhibits amygdala-kindled seizures and is effective in the treatment of manic-depressive illness. The current findings suggest the possibility that the efficacy of ECS in affective illness may be, in part, related to its limbic antikindling and anticonvulsant effects.

Amygdala↗

Impaired behavioral sensitization to cocaine in vasopressin deficient rats.

Behavioral sensitization to cocaine involves progressive and long-lasting increases in hyperactivity and stereotypy in response to the same daily dose. In order to test whether vasopressin, a neuro-hormone implicated in drug tolerance and in other models of learning and memory, affected behavioral sensitization, cocaine was administered daily to animals with hereditary absence of vasopressin. Brattleboro homozygotes which lack vasopressin show deficient onset and persistence of cocaine-induced behavioral sensitization compared to heterozygote, litter-mate controls. These data extend previous reports of vasopressin's role in memory and long-term coding of behavior to the model of pharmacologically-induced behavioral sensitization.

Animals↗