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111.
M. B. Murphy M. A. Orchard E. L. Conway S. E. Barrow 《European journal of clinical pharmacology》1985,29(4):413-416
Summary Pre-incubation of human platelets with nifedipine in vitro or treatment of normal volunteers with nifedipine, 30 mg daily for one week, did not alter ADP induced aggregation measured by whole blood aggregometry. 6-oxo-Prostaglandin F1 remained undetectable in plasma following oral administration of nifedipine to normal volunteers. The hypotensive response to intravenous nifedipine administration was similar in spontaneously hypertensive rats pretreated with indomethacin or placebo. These results conflict with previous reports that nifedipine alters platelet aggregation and prostaglandin metabolism. 相似文献
112.
Eric N. Juberg Kenneth P. Minneman Peter W. Abel 《Naunyn-Schmiedeberg's archives of pharmacology》1985,330(3):193-202
Summary The properties of
1- and
2-adrenoceptors in right and left atria of rat heart, and their roles in mediating chronotropic and inotropic responses to-adrenoceptor agonists were examined. [125I](-)-pindolol (125IPIN) bound saturably and specifically to a single class of high affinity sites in homogenates of both right and left atria. Thek
1's for association in right and left atria were 6.5×109 l/mol-min and 2.3×109 l/mol-min respectively, while thek
–1's for dissociation were 0.20 min–1 and 0.17 min–1. The kinetically determinedK
D's were 75 pmol/l in right and 30 pmol/l in left atria and were similar to the equilibriumK
D's determined from Scatchard analysis of saturation isotherms of specific125IPIN binding. Inhibition of125IPIN binding by-adrenoceptor antagonists was stereoselective and the order of potency was timolol > 1-propranolol > d-propranolol > sotalol. Inhibition by
1- and
2-adrenoceptor subtype selective antagonists yielded flat displacement curves with low Hill coefficients. Nonlinear regression analysis of displacement by
1-selective (practolol, atenolol and metoprolol) and
2-selective (ICI 118,551) antagonists gave estimates of the proportion of
1- and
2-adrenoceptors present in rat atria. Right atria contained 67±4.2%
2-adrenoceptors and 33±4.2%
2-adrenoceptor, while left atria contained 67±2.8%
1- and 33±2.8%
2-adrenoceptors. Increases in the rate of spontaneously beating right atria and the force of electrically driven left atria caused by-adrenoceptor agonists were also measured. pA2 values for non-subtype selective-adrenoceptor antagonists in inhibiting isoprenaline-induced increases in rate and force were highly correlated withK
D values determined for specific125IPIN binding. pA2 values for
1- and
2-selective antagonists in inhibiting isoprenaline-induced increases in rate and force correlated well with the pK
D values of these drugs in binding to
1-adrenoceptors, but not with the pK
D values in binding to
2-adrenoceptors. Dose-response curves for stimulation of both rate and force by the
2-selective agonists procaterol and zinterol were shifted to a much greater extent by selective blockade of
1-adrenoceptors with metoprolol than by selective blockade of
2-adrenoceptors with ICI 118,551, suggesting that these compounds caused their effects by activating
1-adrenoceptors. These results suggest that
1- and
2-adrenoceptors coexist in both left and right atria of rat heart in approximately a 21 ratio, however only
1-adrenoceptors mediate the chronotropic and inotropic effects of-adrenoceptor agonists.Supported by a grant from the American Heart Association — Georgia Affiliate 相似文献
113.
Summary Ultrastructural changes in central nervous system (CNS) white matter of three goats affected with-mannosidosis were analyzed to further define characteristics and pathogenesis of axonal and myelin abnormalities. The variations in myelin association and contents of axonal spheroids were delineated. The occurrence of spheroids in a 96/150-day fetus documented the early development of these axonal lesions. In regions of severe myelin deficits, the presence of apparently normal axons and a reduction in the number of oligodendrocytes were confirmed. Many remaining cells in myelin-deficient regions were characterized by dark, vacuolated cytoplasm. The occurrence of internodes with myelin sheaths adjacent to internodes without myelin sheaths suggested that an axonal defect is not primarily responsible for the absence of myelin sheaths. A mild myelin deficit in the spinal cord was indicated by the presence of unmyelinated axons. Except for occasional mild cytoplasmic vacuolation, the spinal cord glial cells appeared relatively normal. The findings presented here are consistent with the hypothesis that an oligodendrocyte defect, expressed by regional differences, is a major factor in the pathogenesis of myelin deficiency in-mannosidosis.Supported by NIH grant NS-16886 to MZJ and BRSG funds from the College of Osteopathic Medicine, Michigan State University, to KLL 相似文献
114.
D. Ratge W. Bauersfeld H. Wisser 《Journal of neural transmission (Vienna, Austria : 1996)》1985,62(3-4):267-284
Summary The concentration of free and conjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) were measured by a modified radioenzymatic assay in the plasma and in the cerebrospinal fluid (CSF) of 45 patients with normal and in 21 patients with disturbed blood-CSF barriers. In patients with an undisturbed blood-CSF barrier the free NE and E in CSF were 128±45 ng/l and 27±20 ng/l (mean values±S.E.), respectively, and represented about 50 % of the average plasma values. Mean DA was not different in plasma (47±22 ng/l) and in CSF (41±19 ng/l). Both in plasma and in CSF, considerable higher free catecholamine (CA) levels were measured in patients with dysfunction of the blood-CSF barrier. In one patient with bacterial meningitis twofold higher concentrations of free NE and DA in CSF as compared with plasma were detectable. Sulfate conjugates of catecholamines are predominant in plasma and CSF.The contribution of conjugated CA to total CA in plasma from patients with normal blood-CSF barrier averaged 69.7 %, 63.1 % and 98.1 % for NE, E and DA, respectively and was significantly lower in the CSF (p<0.001). In patients with disturbed blood-CSF barrier, the increases of conjugated CA were more pronounced in CSF than in plasma. Further, the contribution of conjugated NE and E to total NE and E in CSF was not only increased in patients with bacterial meningitis, but also in patients with renal insufficiency compared to the control patients (p<0.02 and p<0.001 resp.). Free and conjugated NE, E and DA in the plasma and CSF were related significantly (p<0.01 resp.) with stronger correlation for conjugated CA (p<0.001 resp.). These results together with findings in the literature, suggest that there is little or no rostral-caudal gradient in CSF CA conjugate concentrations and that even in patients with intact blood-CSF barrier plasma conjugated CA concentrations influence those in CSF. Thus only free CA levels in CSF may reflect the central adrenergic activity. 相似文献
115.
A. Marczell H. Rosen H. Spoula 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》1987,371(3):177-181
Zusammenfassung Es wird anhand einer konsekutiven Serie über eine modifizierte fortlaufende Nahttechnik am Colon berichtet, die gerade bei älteren Patienten eine sichere und rasche Methode der Anastomosierung darstellt. Die klinisch relevante Insuffizienzrate sowie auch die Letalitätsrate betrugen in dieser Serie je 2%, wobei die Ursachen für die Letalität aber keine Folge der Insuffizienz waren. Die Komplikationsrate betrug 11%, die urologischen Komplikationen mit 6% standen hierbei im Vordergrund.
A consecutive series of 100 resections of the colon using a modified technique of continuous (running away) suture
Summary Based on a consecutive series it is reported about a modified type of continuous suture on the colon, used especially in elderly patients for being a secure and prompt method of anastomosing. The rate of insufficiency and mortality, as far as the clinical relevance is concerned, turns out to be 2% each and there was no relation between mortality and insufficient anastomosis. The complication rate was 11%, whereby the urological complications predominated with 6% of the total.相似文献
116.
Two Mannich-base prodrugs of 5-iodo-2-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/ propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself. 相似文献
117.
Long Evans rats were trained to discriminate 0.2 mg/kg IP (±)-rolipram from vehicle injection in a food-motivated two-lever operant task. Eight out of nine rats acquired the discrimination after an average of 91 sessions (min 65, max 137). The ED50 of (±)-rolipram was 0.06 mg/kg IP. Generalization tests with (–)- and (+)-rolipram showed that the (–)-isomer was 8 times more active than (+)-rolipram with an ED50 of 0.06 and 0.4 mg/kg IP respectively. The phosphodiesterase inhibitor RO 20-1724 partially (83%) generalized to (±)-rolipram in doses of 0.6 and 1.0 mg/kg IP. IBMX 5 mg/kg IP showed 63% generalization. Tests with imipramine and the (+)- and (–)-isomer of the noradrenaline uptake inhibitor oxaprotiline suggest that NA-uptake inhibiting drugs do not form an interoceptive cue which is (±)-rolipram-like. dbcAMP 12.5 mg/kg SC and 100 mg/kg SC dbcGMP did not generalize to the training drug. The nature of the discriminative stimulus produced by this dose of (±)-rolipram in rats remains to be elucidated.
Offprint requests to: R. Ortman 相似文献
118.
Summary The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to 1-acid glycoprotein and for total binding in serum. For 1-acid glycoprotein, the k-values ranged from 1·105 to 8·105 M–1, and for pooled serum from 0.4·105 to 8·105 M–1. The determined number of binding sites on the 1-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of 1-acid glycoprotein. 相似文献
119.
Jeffrey M. Liebman Nancy R. Hall James Prowse Susan Gerhardt Linda Noreika Howard M. Fenton 《Psychopharmacology》1984,84(3):336-341
The effects of -adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on leverpressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS leverpressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although -adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance. 相似文献
120.
Using the "canine model of the completely ischemic brain regulated with a perfusion method," the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia. 相似文献