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991.
The metabolism of nomifensine was studied after single oral and intravenous administration and after 2 weeks of oral dosing. The three principal metabolites reached maximum plasma concentrations rapidly (in 1 to 1.5 hours) after nomifensine administration. Less than 10% was detected as a free, unconjugated form. All three metabolites were eliminated rapidly (elimination t1/2 values between 6.8 and 9.0 hours). Only very low concentrations of free metabolites were found in plasma after 24 hours of nomifensine administration. AUC values for free metabolites were between 0.27 to 0.46 hr X mumol/L after all nomifensine schedules. Two weeks of dosing had no significant influence on the elimination t1/2 or AUC values of the metabolites, indicating no change in the hydroxylation and methylation reactions. In addition, there were no changes in the conjugation reactions during prolonged nomifensine dosing. Nomifensine has a very short t1/2 and no tendency for accumulation after repeated doses. We conclude that nomifensine's clinical pharmacokinetic profile is not significantly changed by the kinetic behavior of its three main metabolites after the usual maintenance doses. 相似文献
992.
A R Young H S?veland J D Pickard S Perry L Brandt B Ljunggren 《Journal of cerebral blood flow and metabolism》1987,7(2):237-247
The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries. Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE). The greater magnitude of the contractions was of the following order: [K+] greater than 5-HT greater than TEA greater than NE. High concentrations of TEA alone (10(-2) M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent. Low concentrations of TEA (10(-8)-10(-6) M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10(-7) M) and NE (3 X 10(-6) M) and attenuated the contraction produced by 60 mM [K+]. An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10(-2) M), but not high [K+], the subsequent addition of 5-HT (10(-7) M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10(-8) or 10(-6) M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10(-4) M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10(-3) M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 +/- 9% and 149 +/- 14% of control values following the second and third applications, respectively). With TEA (10(-6) M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10(-2) M) or [K+] (60 mM) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10(-5) M) were less sensitive to withdrawal of calcium from the extracellular medium (31 +/- 6% relative to the maximal response at 4 mM calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity. 相似文献
993.
994.
Nadir Y?net?i Nevin Oru? A Omer Ozütemiz Kamil Kumanlioglu Gül Yüce Yücel Batur 《Experimental and toxicologic pathology》2002,54(3):197-201
BACKGROUND: Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats. METHODS: Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP. RESULTS: Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05). CONCLUSION: METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property. 相似文献
995.
大脑中动脉狭窄的TCD与DSA检查比较研究 总被引:1,自引:0,他引:1
目的 :通过大脑中动脉狭窄的TCD检查与DSA检查方法比较 ,为临床提供方便可靠的检查方法。方法 :对经TCD检查确诊为大脑中动脉狭窄 6 0例做DSA检查 ,对两种检查结果进行比较分析。结果 :经TCD确诊为大脑中动脉狭窄病例 ,病变侧狭窄处的血流速度(Vm)均明显高于健侧一倍以上 ,在动脉硬化性狭窄中多伴有“海鸥鸣”或“铁锅炒沙”样杂音 ,且频谱形态呈圆钝或脉动指数值增高的阻力波形。该 6 0例在DSA的检查中均出现不同部位的不同狭窄。结论 :TCD检查具有快速方便、安全、经济、确诊率高的优点 ,可作为脑血管病首选检查手段 相似文献
996.
997.
Polyamine metabolism in transient focal ischemia of rat brain. 总被引:4,自引:0,他引:4
Polyamine metabolism was studied in rat brains subjected to 30 min transient cerebral ischemia by measuring the activity of the key enzyme ornithine decarboxylase (ODC) and levels of the polyamines putrescine, spermidine and spermine. A transient increase in ODC activity was apparent after 4 h of recirculation in the ipsilateral cortex and striatum (P less than 0.05). Putrescine levels were significantly increased in the ipsilateral striatum after 4 h of recirculation, and after 24 h of recirculation in both the ipsilateral cortex and striatum. During ischemia spermidine levels were significantly reduced in the ipsilateral hemisphere and spermine levels in the ipsilateral cortex. It is suggested that during ischemia polyamines are released from neurons into the extracellular compartment and cleared into the blood. 相似文献
998.
C Joborn J Hetta F Niklasson J Rastad L Wide H Agren G Akerstr?m S Ljunghall 《Psychoneuroendocrinology》1991,16(4):311-322
Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines. 相似文献
999.
In subtypes of schizophrenia and unipolar depression, both increased and decreased levels of platelet serotonin were found. Hyperserotonemia was usually observed in patients with psychotic features (i.e., in paranoid schizophrenia and psychotic depression). Hyposerotonemia, although less common than hyperserotonemia, was present in nonparanoid schizophrenia and nonpsychotic depression (i.e., in patients without psychotic symptoms). A sex difference in platelet monoamine oxidase activity was observed among healthy subjects, but not among schizophrenic patients. The activity of platelet monoamine oxidase in paranoid and nonparanoid schizophrenic patients did not differ from that in healthy subjects. The findings in this study suggest that biological differences between subtypes of unipolar depression or schizophrenia might depend upon the presence of psychotic symptoms. 相似文献
1000.
目的:初步了解木樨草素对庆大霉素耳毒性的影响。方法:设庆大霉素组与庆大霉素加不同剂量木樨草素(10mg、20 mg)两组,并进行组间比较,观察听性脑干反应(ABR)阈值、眼震电图(ENG)的频率,了解其听功能及前庭功能的变化。结合耳蜗基底膜铺片琥珀酸脱氢酶(SDH)染色方法观察耳蜗形态学变化。结果:听功能检查结果显示,庆大霉素加不同剂量木樨草素组的ABR阈值明显低于庆大霉素组,经统计学处理,差异有显著性。形态学检查结果与听功能检查结果一致。前庭功能检查结果亦发现木樨草素对庆大霉素引起的前庭功能变化有拮抗作用。结论:本实验发现木樨草素对庆大霉素引起的耳蜗和前庭损伤有拮抗作用。 相似文献