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61.
62.
Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia. 相似文献
63.
Allen Cato III Linda E. Gustavson Jiang Qian Tawakol El-Shourbagy Edward A. Kelly 《Epilepsia》1998,39(1):43-47
Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment. 相似文献
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment. 相似文献
64.
Grimbizis G.; Tarlatzis B.C.; Bontis J.; Miliaras D.; Lagos S.; Pournaropoulos F.; Mantalenakis S. 《Human reproduction (Oxford, England)》1995,10(3):520-523
Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one. 相似文献
65.
The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (–)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects. 相似文献
66.
Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose. 相似文献
67.
A. Perio J. P. Terranova P. Worms R. M. Bluthe R. Dantzer K. Biziere 《Psychopharmacology》1989,97(2):262-268
The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. In this study the effect of various psychotropic drugs on this investigatory behaviour was examined. The procedure was as follows: an unfamiliar juvenile rat was placed in the home cage of an adult rat for 5 min. The time spent by the adult rat in investigating the juvenile was recorded. The adult rat was then immediately treated with vehicle or test compounds, and was again exposed for 5 min to the same juvenile 2 h later. At this time point vehicle-treated rats no longer recognized the juvenile rat, i.e. the time of investigation was similar to that observed during the first presentation. Arecoline (1 and 3 mg/kg IP), physostigmine (0.05 and 0.1 mg/kg SC), RS86 (0.5 mg/IP) and nicotine (0.125 and 0.5 mg/kg IP) reduced in a dose-dependent fashion the time spent in investigating the juvenile during the second exposure. This result cannot be attributed to nonspecific effects, since it was not observed when a different juvenile was used for the second exposure. The effect of arecoline was reversed by scopolamine, but not by methylscopolamine. Aniracetam reduced investigatory behaviour at the dose of 50 mg/kg IP. FG 7142 (5 mg/kg IP) and -CCM (0.4 mg/kg IP) were also active and their effect was reversed by Ro 15-1788. dl-Amphetamine (0.5 and 1 mg/kg IP), nomifensine (1.25–10 mg/kg IP) and strychnine (0.25 and 0.5 mg/kg IP) were ineffective or reduced this behaviour unspecifically. Social recognition may therefore represent a useful and simple test to detect compounds which enhance short-term, olfactory, memory and to assess in the same animals the specificity of this activity. 相似文献
68.
Jun Ishigooka Mitsukuni Murasaki Hirobumi Wakatabe Sadanori Miura Kozo Hikida Masahiro Shibata 《Psychopharmacology》1989,97(3):303-308
The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16±0.01 (mean ± SD, n=3) for CCP and 0.29±0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43±0.07 and 0.79±0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63±0.05 and 0.63±0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa. When CCP and Y-516 were given orally to man, the plasma concentrations of both parent drugs increased in a dose-dependent manner. The t1/2 of CCP at a dose of 50 mg was 46±6 h (n=3) while that of Y-516 at a dose of 25 mg was 15±2 h (n=5), so that elimination from the circulation was slower than in the dog in both cases. As in the dog, Y-516 was detected in the plasma following administration of CCP, but its concentration was approximately one fifth that of CCP and lower than that found in the dog. From the ratios of Y-516 produced upon oral administration of CCP in dog and man, we concluded that Y-516 is involved to a considerable degree in the pharmacological action of CCP in the dog and, though to a lesser degree, in man as well. 相似文献
69.
Otagiri Masaki Yamamichi Ryuji Marayama Toru Imai Teruko Suenaga Ayaka Imamura Yorishige Kimachi Kazuhiko 《Pharmaceutical research》1989,6(2):156-159
The interactions of acidic and basic drugs with 1-acid glycoprotein (1-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to 1-AGP. The CD data suggested the presence of a single binding site on the 1-AGP molecule. The induced ellipticities of the acidic drug–1-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to 1-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with 1-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs. 相似文献
70.
Gilbert TH Corley SM Teskey GC 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,146(3):336-344
This study addressed the anticonvulsant effects of phenobarbital, valproate, and ethosuximide in the amygdala of kindled guinea pigs to further validate this model for the screening of anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using quantitative locomotor tests, as well as scores on a sedation and muscle relaxation rating index. The anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioral seizure severity (SS) during early and late phases of kindling acquisition, and in kindled guinea pigs. ADD and SS were also measured in response to both threshold and suprathreshold kindling stimulation. All drugs exerted slight to moderate sedative effects in guinea pigs on both the behavioral tests and rating index. We found that phenobarbital exhibited effective anticonvulsant properties in guinea pigs by consistently reducing ADD and SS in response to both threshold and suprathreshold kindling stimulation. Valproate exhibited effective anticonvulsant properties at threshold stimulation and less effective properties at suprathreshold stimulation. Lastly, we found that ethosuximide lacked effective anticonvulsant action at either threshold or suprathreshold kindling stimulation. Our results indicate that the guinea pig kindling model correctly predicted the actions of phenobarbital, valproate, and ethosuximide in the treatment of partial seizures. Guinea pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy. 相似文献