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991.
992.
Summary The excitatory amino acid antagonists 2-amino-5-phosphonovalerate and -D-glutamylglycine have been applied focally to the ventral tegmental area and both the pars compacta and pars reticulata of the substantia nigra of the rat. The injections were performed under halothane anaesthesia so that behavioural effects could be observed 5 min afterwards. Bilateral application of either antagonist to the ventral tegmental area and the pars compacta of the substantia nigra induced enhanced locomotor activity in an open field. This effect was blocked by pretreatment of the animals with a low dose of the dopamine receptor antagonist fluphenazine. Bilateral application of either antagonist to the pars reticulata of the substantia nigra produced sedation and a reduction in locomotor activity. Unilateral injection of either of the excitatory amino acid antagonists into the pars reticulata or pars compacta of the substantia nigra both resulted in contraversive circling behaviour The effect of intranigral (both pars compacta and reticulata) 2-APV and -DGG was accompanied by a significant increase in concentrations of both 3,4-dihydroxyphenylacetic acid (to 158–160% of control following injection into pars compacta, and 134–146% of control injected into pars reticulata) and homovanillic acid (to 161–166% of control following injection into pars compacta, and 186–210% of control injected into pars reticulata) in the ipsilateral, striatum. Pretreatment of these animals with fluphenazine (0.3 mg/kg) antagonized this circling behaviour.These results indicate that antagonism, of excitatory amino acid receptors in the region of the midbrain of the rat leads to specific behavioural effects, which may in part be mediated through the ascending dopaminergic projections.Abbreviations used 2-APV
2-amino-5-phosphonovaleric acid
- -DGG
-D-glutamylglycine
- SN
substantia nigra
- VTA
ventral tegmental area
- HVA
homovanillic acid
- DOPAC
3,4-dihydroxyphenylacetic acid
A preliminary communication of this work was presented to the British Pharmacological Society in Bradford, April 1981 相似文献
993.
Summary Six patients with recently ruptured intracranial aneurysms were treated preoperatively with tranexamic acid (AMCA). Two patients received 6 g daily in i.v. infusion, two had 6 g daily by i.v. injection, and two patients were given AMCA 9 g daily by mouth during the first week after bleeding. Serial assays of AMCA and fibrin/fibrinogen degradation products (FDP) in cerebrospinal fluid (CSF) were performed during 6–13 days after the initial subarachnoid haemorrhage (SAH). Judged from the decline in CSF-FDP, an assumed therapeutic level of 1 mg/l of AMCA in CSF was reached within 24–36 hours after the first dose when the drug was administered intravenously and within 48 hours when the drug was given orally. 相似文献
994.
D. Athen H. Beckmann M. Ackenheil M. Markianos 《European archives of psychiatry and clinical neuroscience》1977,224(2):129-140
Summary In eight male patients with alcoholic delirium concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovannilic acid (HVA) in CSF, activity of dopamine--hydroxylase (DBH), and urinary excretion of noradrenaline (NA), adrenaline (A), and dopamine (DA) were measured during the delirium and a drug-free control period.MHPG concentration in CSF, excretion of NA and A as well as activity of serum DBH were significantly elevated during the delirium phase as compared to the control period. Urinary DA excretion and HVA in CSF did not show any constant changes. There was a positive correlation (r=0.64) between DBH activity and the intensity of the delirium (as measured on the delirium rating scale).It is hypothesized that there is a relationship between alcoholic delirium and increased central noradrenergic activity.Parts of this study were presented at the Sixth International Institute on the Prevention and treatment of Drug Dependence (Hamburg, June 28–July 2, 1976) 相似文献
995.
Antero Aitio Sinikka Valkonen Helena Kivistö Erkki Yrjänheikki 《International archives of occupational and environmental health》1983,53(2):139-147
Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day. 相似文献
996.
Recent researches on the rickettsial group microorganisms are summarized in their comparative aspects of morphology, cultivation and multiplication, susceptibility to chemotherapeutics, chemical structure of envelopes, nucleic acid, protein constitution, and gene structures. From this overview, Rickettsia tsutsugamushi seems to have different properties from the others and should be reclassified into a new genus, and a new species name as Orientia tsutsugamushi is proposed.Presented at the 4th International Symposium on Rickettsiae and Rickettsial Diseases, Pietany, C.S.F.R., 1–6 October, 1990. 相似文献
997.
Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid,urinary metabolites of the fungicide captan,in rats and humans 总被引:1,自引:0,他引:1
R. T. H. van Welie P. van Duyn E. K. Lamme P. Jager B. L. M. van Baar N. P. E. Vermeulen 《International archives of occupational and environmental health》1991,63(3):181-186
Summary Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 g/l for THPI and 110 g/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%–2% and 3%–9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan. 相似文献
998.
K. Racké M. Sommer F. Burns B. Hering 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(4):337-343
Summary Isolated rat pineal glands were incubated in vitro and the release of endogenous noradrenaline or 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was determined by HPLC with electrochemical detection. In the absence of test drugs, the spontaneous outflow of noradrenaline was about 10 fmol/10 min and electrical stimulation (5 Hz, 1500 pulses) evoked the release of about 70 fmol noradrenaline. Nomifensine enhanced the spontaneous outflow of noradrenaline about threefold and the electrically evoked release of noradrenaline about sixfold. In the presence of nomifensine, the 2-adrenoceptor antagonist yohimbine markedly increased the electrically evoked release of noradrenaline, whereas the 1-adrenoceptor antagonist prazosin had no effect. Clonidine inhibited the electrically evoked release of noradrenaline by about 65%, and this was antagonized by yohimbine in a competitive manner. In the absence of drugs, the initial spontaneous outflow of 5-HT was (compared with noradrenaline) very high 64 mol/10 min. It declined by 80% within 1 h of incubation in vitro. The outflow of 5-HIAA amounted initially to 38 mol/10 min and declined by 40% within 1 h of incubation. Addition of l-tryptophan (10 mol/1) after 1 h of incubation in vitro largely enhanced the outflow of 5-HT and 5-HIAA within 30 min of incubation (about ten- and fourfold, respectively). When l-tryptophan was present from the onset of incubation the initial outflow of 5-HT and 5-HIAA was only slightly elevated, but the decline was largely attenuated. Neither omission of calcium nor addition of nomifensine, clonidine or yohimbine significantly affected the spontaneous outflow of 5-HT or 5-HIAA. Likewise, neither electrical stimulation in the absence or presence of nomifensine and yohimbine nor stimulation by high potassium (45 mmol/1) significantly affected the outflow of 5-HT or 5-HIAA.In conclusion, the release of endogenous noradrenaline from the sympathetic nerves terminating in the pin eal gland is inhibited by presynaptic 2-adrenoceptors. The outflow of 5-HT from the pineal gland originates almost exclusively from non-neuronal cells, most probably the pinealocytes, and depends largely on a continuous de novo synthesis. Catabolism of 5-HT to 5-HIAA in the pineal gland occurs mainly in an extraneuronal compartment, probably the pinealocytes and/or the interstitial cells of the pineal gland.
Send offprint requests to K. Racké at the above address 相似文献
999.
L. Bertin E. Rey G. Pons J. L. Mathiot M. O. Richard P. Chrétien C. Saint-Maurice C. Moran D. Ginisty G. Olive 《European journal of clinical pharmacology》1991,41(3):251-253
Summary. Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg · kg–1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC.No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age; tmax=2.12h, Cmax=8.78mg · l–1, AUC(08 h) 33.9mg · h · l–1, AUC=39.3 mg · h · l–1, t1/2=2.35 h, Vz=0.319 l · kg–1, CL=0.094 l · h–1 · kg–1. Renal clearance was 14 ml · h–1. kg–1. 33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates.The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg · kg–1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3–11 year-old children from that in adults. 相似文献
1000.
Suhonen Pekka Järvinen Tomi Rytkönen Päivi Peura Pekka Urtti Arto 《Pharmaceutical research》1991,8(12):1539-1542
0,0-(l,4-Xylylene) bispilocarpic acid esters are pilocarpine pro-drugs containing two pilocarpic acid monoesters linked with one pro-moiety. Each mole of prodrug forms two pilocarpine moles in the presence of esterases. Corneal uptake and permeability of various bispilocarpic acid diesters were investigated in vitro using isolated albino rabbit corneas. The permeability coefficient of pilocarpine was 2.8 × 10 –6 cm/sec, whereas for bispilocarpic acid diesters, despite their large molecular weights (between 638 and 722), permeability coefficients were 6.5–20.2 × 10 –6 cm/sec. Only pilocarpine, and no intact prodrug, was observed at the endothelial side. Corneal uptake was increased with increasing lipophilicity, but a parabolic relationship between the logarithm of the apparent partition coefficient (1-octanol–pH 7.4 phosphate buffer) (log PC) and the corneal permeability was noticed. Corneal permeability and the rate of enzymatic hydrolysis of the compounds correlated well. The corneal permeability of pilocarpine given as lipophilic bispilocarpic acid diester (log PC 3) prodrugs seems to be controlled by the formation of pilocarpine in the corneal epithelium rather than by the absorption of prodrugs into the epithelium or their epithelium–stroma transport rate. 相似文献