摘要:

We have examined the ability of the nitroso derivative of chloramphenicol (NO-CAP) to inhibit subsequent growth of logarithmically growing or plateau phase cell cultures after short-term drug exposure. Raji cells taken from log growth cultures exhibited complete inhibition after 6-hour preincubation with 2–3 ×10–5 M NO-CAP, while similarly treated cells taken from plateau populations demonstrated 90–100% of expected growth on replating. Flow-cytometric studies indicate that the irreversible effects of NO-CAP are greatest as cells proceed into and through the DNA synthetic portion (S phase) of the cell

ISSN:0031-7012    

DOI:10.1159/000137577

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Three carcinogens with different requirements for activation were used to generate sister chromatid exchange (SCE) in cultured lymphocytes from 22 untreated patients with solid tumors. These data were compared to SCEs produced by incubating lymphocytes, from 44 normal persons, with the same carcinogens. In vitro treatments with butadiene epoxide (0.125 µg/ml) show no significant differences in the SCEs generated. However, in vitro treatment with mitomycin-C (0.04 µg/ml) did induce significant differences (p < 0.05) in the distribution of the SCE scores. Treatment of the cultured cells with benzo(a)pyrene (10 µg/ml), a carcinogen requiring extensive metabolic activation, significantly (p < 0.001) altered the distribution of the SCEs generated in vitro. The SCE data suggest that metabolic activities play an important role in the processing of carcinogens in solid tumor patien

ISSN:0031-7012    

DOI:10.1159/000137578

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Extracts of calf thymus have been shown to contain a number of inhibitors of lymphocyte transformation. A low molecular weight (600 daltons) anionic inhibitor of lymphocyte transformation has been identified and separated from contaminating polyamines and nucleotides. The active fraction inhibited the DNA synthetic response of murine or human T cells to alloantigens in mixed lymphocyte culture and to T-cell-specific mitogens. It was inactive against stimulation of B lymphocytes and several cultured tumor cell lines.

ISSN:0031-7012    

DOI:10.1159/000137579

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Nanogram quantities of flunitrazepam and its major metabolite, desmethylflunitrazepam, can be reliably quantitated in human plasma using electron-capture gas-liquid chromatography. After addition of methylnitrazepam as the internal standard, plasma samples are extracted with an organic solvent (benzene:isoamyl alcohol). The organic extract is separated, evaporated to dryness, reconstituted, and injected onto the chromatograph using an automatic sampling system which allows up to 100 analyses/24 h. The sensitivity limits are 0.5 ng/ml for flunitrazepam and 1–2 ng/ml for desmethylflunitrazepam. Use of the method is illustrated in a study of the pharmacokinetic properties of flunitrazepam following a single 1.0-mg intravenous dos

ISSN:0031-7012    

DOI:10.1159/000137580

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Iproniazid (25–100 mg/kg) produced a marked, dose-related reduction in antipyrine elimination in the rabbit, whereas reductions produced by nitrazepam (32 mg/kg) or SKF 525 A (25 and 40 mg/kg) were small. Phenobarbitone, 10 mg/kg chronically, increased antipyrine elimination. The small inhibitory effect of SKF 525A on antipyrine metabolism in the rabbit was unexpected compared to the marked effect in the ra

ISSN:0031-7012    

DOI:10.1159/000137581

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The single and combined effects of acute phencyclidine (PCP) and propranolol, each given intraperitoneally, were studied on rat behavior. PCP (5, 10, 25, 50, and 100 mg/kg) produced dose-related stereotypy and increases in (photocell) hyperactivity over 4 h observation. Propranolol (10 and 25 mg/kg) neither caused any stereotypy nor had any effect on activity relative to vehicle control. Additionally, propranolol (10 and 25 mg/kg), given 30 min after PCP (10, 25 and 50 mg/kg), reduced or completely blocked the stereotypy and hyperactivity caused by PCP. These data provide the first experimental verification of a clinical observation that propranolol may be an effective antagonist of the behavioral toxicity produced by PCP.

ISSN:0031-7012    

DOI:10.1159/000137582

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Bethanechol chloride, administered intracerebroventricularly, induces a characteristic wet dog shake (WDS) response in rats in a dose-related manner. WDS induced by bethanechol at the dose of 100 µg was antagonized by atropine, scopolamine and spiperone (muscarinic cholinergic and dopaminergic antagonists, respectively), whilst metergoline, methysergide, phentolamine, propranolol and bicuculline (serotonergic, alpha-adrenergic, beta-adrenergic and GABA-ergic antagonists) fail to inhibit this effect. The present experiments show that the shaking response may be produced by bethanechol, a potent muscarinic agent administered by the intracerebral route, and suggest that bethanechol-induced shaking behavior in rats may be a useful animal model for delineating agents with antimuscarinic activity

ISSN:0031-7012    

DOI:10.1159/000137583

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The amount of ouabain necessary to produce ventricular fibrillation (VF) was significantly decreased by 2-hour pretreatment with 50, 100 or 200 mg/kg tolbutamide in anesthetized rabbits. The two higher doses also decreased the dose of ouabain needed to produce ventricular ectopic (VE) beats. Only the 200 mg/kg dose decreased blood glucose. In unanesthetized rabbits, 30-min pretreatment with tolbutamide (200 mg/kg i.v.) significantly decreased the doses of ouabain that produced VE beats and VF. A similar effect was noted when the same dose (200 mg/kg) was given subcutaneously 30 min, 2 or 4 h before ouabain. In these experiments blood glucose decreased after 2 h. Pretreatment for 30 min with subcutaneous administration of 50, 100 or 200 mg/kg tolbutamide significantly reduced the doses of ouabain needed to produce VE beats and VF. Blood glucose was unaltered by any tolbutamide dose after 30 min. Insulin (1 unit) decreased blood glucose but did not alter the amount of ouabain that produced VE beats and VF. The mechanism for enhancement of ouabain cardiotoxicity by tolbutamide appears to be independent of alterations in blood glucose and may be related to some direct myocardial effect.

ISSN:0031-7012    

DOI:10.1159/000137584

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The effects of hydrogen peroxide on the normal and ischaemic myocardium were investigated using the isolated ‘working’ rat heart preparation. In the range 0–3 µM no changes in heart rate, aortic flow, coronary flow, or aortic pressure were observed. Between 3 and 30 µM, however, there was a dose-dependent fall in aortic flow and an accompanying increase in coronary flow, the total cardiac output remaining unchanged. At concentrations above 30 µM functional failure occurred. Following a 25-min ischaemic period during which time 6 µM hydrogen peroxide was infused via the aorta at a constant rate to remove any vasodilatory effect, all hearts failed to recover. In contrast, 50% of control hearts recovered pump function. In conclusion, therefore, hydrogen peroxide can reduce function in the aerobic working rat heart and may exert a vasodilatory effect. When this effect is eliminated hydrogen peroxide affords no protection during ischaemia and appears to exacerbate tiss

ISSN:0031-7012    

DOI:10.1159/000137585

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Hyponatremia was induced by intraperitoneal administration of 5.5% glucose followed by treatment with cabamazepine. Serum determinations of carbamazepine were also performed. Carbamazepine decreased serum Na+ and increased blood glucose concentration in the hyponatremic rats.

ISSN:0031-7012    

DOI:10.1159/000137586

出版商:S. Karger AG    

年代:1982

数据来源: Karger