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91.
The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons. 相似文献
92.
ANDREW A. AMOSCATO GEORGE F. BABCOCK R. MICHAEL SRAMKOSKI BARBARA A. HYND J. WESLEY ALEXANDER 《Chemical biology & drug design》1987,29(2):177-186
This study reports on the synthesis of two fluorescent analogues of thymopentin (TP-5; Arg-Lys-Asp-Val-Tyr). A fluorescein isothiocyanate labeled analogue (FITC-TP-5) and a stilbene isothiocyanate labeled analogue (SITS-TP-5) were extensively purified by ion-exchange and gel filtration chromatography. Characterization of the coupling site through amino acid analysis, dansylation and N-terminal cleavage of the fluorescent amino acid yielded results which indicated that both were mono-labeled analogues derivatized at the N-terminal. These analogues were shown to be TP-5-like in nature by their ability to induce the expression of the Thy 1.2 surface marker on nude mouse prothymocytes in both in vivo and in vitro assays. In addition, these analogues were able to inhibit the specific binding of radiolabeled TP-5 to human lymphocytes. Initial studies describing the interaction of FITC-TP-5 with human lymphocytes are shown. 相似文献
93.
ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5,N^10—METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION 总被引:5,自引:1,他引:4
OBJECTIVE: To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level. METHODS: The plasma Hcy level was measured by capillary electrophoresis-ultraviolet detection and the gene polymorphism of N5,N10-methylenetetrahydrofolate reductase (MTHFR) was studied with PCR-RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy control. RESULTS: The plasma Hcy level of the patients (19.3 +/- 6.0 micromol/L) was markedly higher than that of the controls (13.7 +/- 5.4 micromol/L) (t = 4.16, P < 0.001). There are 3 genotypes, C/C, C/T and T/T, about base-variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls. CONCLUSIONS: The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C-->T mutation at locus 677 of MTHFR gene. 相似文献
94.
T B Vree Y A Hekster M W Tijhuis E F Termond J F Nouws 《Biopharmaceutics & drug disposition》1986,7(3):239-252
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
95.
Annemieke Smit-van Oosten Winston W. Bakker Harry van Goor 《Transplant international》2002,15(12):602-609
Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF. 相似文献
96.
Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene. 相似文献
97.
Rupert R Lanzenberger Markus Mitterhauser Christoph Spindelegger Wolfgang Wadsak Nikolas Klein Leonhard-Key Mien Alexander Holik Trawat Attarbaschi Nilufar Mossaheb Julia Sacher Thomas Geiss-Granadia Kurt Kletter Siegfried Kasper Johannes Tauscher 《Neuropsychopharmacology》2007,61(9):1081-1089
BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders. 相似文献
98.
作者用同位数前体参入法及透射与扫描电镜研究了平阳霉素(博莱霉素A_5)对HeLa细胞大分子生物合成及超微结构的影响。结果显示:平阳霉素能抑制HeLa细胞DNA,RNA和蛋白质的生物合成,对DNA的抑制作用强,ID_(50DNA)为42.77μg/ml。表现为:染色质减少,核内电子密度低,核仁分离及“核仁帽”形成,细胞表面微绒毛消失或变形,最终导致质膜破裂等。作者认为,细胞膜是否为此类药物作用的靶位值得进一步研究。 相似文献
99.
Lars von Knorring Béla G. L. Almay Jan Häggendal Folke Johansson Lars Oreland Lennart Wetterberg 《European archives of psychiatry and clinical neuroscience》1986,236(3):131-138
Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet 相似文献
100.
Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon-Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently. 相似文献