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The effects of denervation of central noradrenergic system on the interpartner relationships of adult cats were examined in a predatory test in the competitive situation for paired animals. Direct administration of the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4 12 microg) into the medial forebrain bundle (MFB) of submissive cats changed previously established dominant-submissive relationship. Biochemical analysis demonstrated a significant reduction of noradrenaline (NA) concentration in the hypothalamus (AH), amygdala (AM), hippocampus (HC), and frontal cortex (CTX), and elevation of NA content in the midbrain central gray matter (CG) in MFB-lesioned cats. Simultaneously, DSP-4-induced lesions exerted significant decrease of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) content in AH, CG, HC and CTX, and increased GABA level in AH, CG, AM, and HC. These results suggest that a coincident decrease of NA metabolism and increase of GABA metabolism led to fear drive reduction.  相似文献   
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Human hair was collected from the occipital crown region of the head from several subjects; these hair samples were presumptively positive for amphetamines by a previously evaluated immunoassay. Hair was washed briefly with methanol to remove external contamination, then extracted with hot methanol for 2 h to recover the drugs. The extracts were evaporated to dryness, reconstituted in buffer, and analyzed using a new enzyme-linked immunosorbent assay (ELISA) technique adapted for the detection of amphetamines in hair. Gas chromatography-mass spectrometry was used as the reference technique. Cross-reactivity of several related compounds was evaluated by equating the inverse of the ligand concentration at 50% antibody binding to the affinity constant for each compound. The ratio of a compound's affinity constant to that for d-methamphetamine was used to derive percent crossreactivity. These experiments yielded values of 30.8% for d-amphetamine, 7.4% for I-methamphetamine, 4.3% for phentermine, 2.9% for I-amphetamine, and <1% for ephedrine, methylenedioxyamphetamine, and methylenedioxymethamphetamine. Cross-reactivity of unrelated compounds was found to be non-existent. The optimum cutoff concentration was determined by receiver operating characteristic curve analysis to be 300 pg/mg and the observed limit of detection was 60 pg/mg. Intra-assay precision at 300 pg/mg was 3.3% (coefficient of variation, CV), and the interassay CV was 10.5%. The sensitivity and specificity of the method were 83% and 92%, respectively.  相似文献   
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There continues to be considerable effort towards the construction of compound libraries targeted for the inhibition of protease enzymes. New tag-encoding methods for library deconvolution have been applied to this problem and there has been particular interest in novel solid-phase linkers for the introduction of key pharmacophore groups required for protease inhibition. Recent reports have tended to focus on nonpeptidic libraries, and, notably, structure-based design methods are now being applied to direct library design.  相似文献   
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Impaired pulmonary function is a frequent but poorly understood complication of acute head injury (HI). A potential early contributor to the pulmonary dysfunction seen in HI patients is neurogenic pulmonary edema (NPE). We hypothesized that NPE would occur early after HI and that it would have a continuum of clinical severity depending on the severity of the HI and associated intracranial hypertension. A large autopsy data base and inpatient HI data base were used to search for cases of NPE. Patients in the autopsy data base were stratified according to injury type and whether they died at the scene or within 96 hours of injury. There were significant (p < 0.0001, analysis of variance) elevations in lung weights in patients dying at the scene and within 96 hours from HI, compared with those dying from other noncentral nervous system injuries. No other organs studied showed significant weight increases. The incidence of NPE in isolated HI patients dying at the scene was 32%. In patients with isolated HI dying within 96 hours, the incidence of NPE was 50%. We found an inverse correlation (r = 0.62; p < 0.0014) between the initial cerebral perfusion pressure and the PaO2/FIO2 ratio despite a normal-appearing chest x-ray film. We conclude that NPE occurs frequently in HI patients. The process of edema formation begins early in the clinical course and is isolated to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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