摘要:

Abstract:Actions and interactions of two antidepressants and diazepam on human skilled performance and mood were studied in a randomized double‐blind cross‐over trial with single oral doses of 50 mg amitriptyline (AMI), 15 mg Org 3770 (ORG) and placebo, given alone and in combination with 15 mg diazepam (DZ) to 12 young healthy subjects at one‐week intervals. Objective tests (digit substitution, tapping, flicker fusion, Maddox wing, tracking, choice reactions, body sway, memory) and subjective assessments (visual analogue scale) were performed at baseline and 1.5, 3, 4.5 and 6 hours after drug administration. Side‐effects were reported, blood pressure and heart rate measured and blood samples taken after each testing run. Placebo was nearly inert on performance and mood. DZ impaired some objective skills and showed sedative effects in the subjective tests. AMI produced sedation and impaired coordination as well as cognitive performance (digit substitution), most clearly at 3 to 4.5 hr. ORG resembled AMI in impairing objective and subjective performance, however, not necessarily in the same tests. Their combined effects with DZ were additive in objective tests but less additive in subjective tests. The drug combinations, but not any single drug, impaired learning acquisition. Plasma concentrations of the drugs given alone were about as expected, without important interactions. We conclude that the combinations of benzodiazepines with the antidepressants used impair skilled performance but may not cause major

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01132.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effect of two decongestive substances and two preservatives used in nasal drops on phagocytosis by human granulocytes was studied. The vasoactive substances oxymetazoline chloride and zylometazoline chloride incubated with human granulocytes during 20 min. gave a reduction of phagocytosis to almost zero when using concentrations found in commercially used nasal drops (500 mg/l respectively 1000 mg/l). However, a dilution of 1:100 was consistent with an almost normal phagocytic function. The preservatives benzalkonium chloride and thiomersal gave a dose related reduction of phagocytosis down to zero. A dilution of 1:100 of the benzalkonium chloride solution used commercially (200 mg/l) and a dilution of 1:10 of the thiomersal solution used commercially (24 mg/l) were needed to get an almost normal phagocytic function. These results together with previous studies indicate that the addition of preservatives in nasal drops should be questioned, excluded or replaced with other less harmful substances.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01133.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The degradation of the vasopressin analogue dDAVP was studied by reversed phase high‐performance liquid chromatography (HPLC) after incubations in pancreatic juice and intestinal mucosa homogenates. dDAVP remained stable in pancreatic juice for a period of 60 min. while the parent hormone arginine vasopressin (AVP) was completely degraded within 5 min. In intestinal mucosa homogenates dDAVP was degraded with half‐lives of 9 min. (fast phase) and 161 min. (slow phase), about four times slower than AVP. By amino‐acid analysis it was confirmed that the metabolite [Mpa1, Des‐D‐Arg8‐Gly9NH2]‐vasopressin was gradually produced. No other breakdown products were observed. These findings may be of value for the further development of more stable peptide analogues which may be effective upon oral a

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01134.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:We have evaluated the pharmacokinetics, reliability and patient tolerability of a newly developed injection pen for cartridged growth hormone (GH). The cartridge contains 25 IU GH in 2 ml solvents. The pen, which is basically a needle, syringe and vial in one piece, is operated by a turning movement and allows doses from 0.25‐4 IU. Nine GH deficient patients were hospitalized twice for overnight bloodsampling following subcutaneous injections (at 8 p.m.) of GH: i.e. when using traditional syringe and vial and after 6 weeks of use of the pen. Serum GH antibodies were measured immediately prior to, and 3 and 6 months following pen treatment. GH containers were collected regularly from the patients for chemical analysis. A questionnaire was completed during and at the end of the study. The absorption rate and bioavailability of GH tended to be higher with syringe and vial (2 P = 0.07) but there were no differences in the profiles of IGF‐I, insulin, glucagon or pertinent metabolic parameters following the 2 injection modes. No GH antibodies occurred during 6 months of pen treatment. The content of polymeric GH was lower in the cartridges (2 P<0.001). Seven of the patients reported less injection pain when using the injection pen, which they all strongly preferred and wished to continue using. We conclude that the GH injection pen is a reliable tool which seems to be more convenient for the patie

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01135.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The binding of3H‐prostaglandin F2αto bovine iris and synthetic melanin was studiedin vitrousing a ligand binding assay. Prostaglandin F2αwas reversibly bound to both types of melanin. The binding was saturable and the Scatchard analysis revealed the existence of at least two binding sites with the corresponding KDvalues of 3.71 nM and 1.99 μM for natural and 4.99 nM and 0.19 μM for synthetic melanin, respectively. The high affinity Bmaxvalues were 3.4 nM/g for natural and 2.5 nM/g for synthetic melanin. The dissociation of prostaglandin F2αfrom melanin after dilution of the complex was rapid and u

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01136.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Etomidate, metomidate and metyrapone, all potent inhibitors of steroid metabolizing monooxygenases, inhibit preferentially coumarin 7‐hydroxylase (COH) amongst several liver microsomal monooxygenase activities from control and pyrazole‐treated D2 micein vitro.SKF‐525A, an inhibitor of phenobarbital‐inducible monooxygenase activities has a much weaker effect on COH than the other three drugs, even though COH is a phenobarbital‐inducible enzyme. Treatment of mice with eto‐ and metomidate decreases the microsomal COH alsoin vivowhile the other activities remained unchanged (with the exception of 7‐ethoxycoumarin O‐deethylase (ECDE) in case of metomidate). Despite of the decrease in COH no parallel decrease in the amount of microsomal P450Coh (P450 isoenzyme highly active in the 7‐hydroxylation of coumarin) could be found in dot immuno‐binding analysis. These data suggest that among several liver microsomal P450 isoenzymes, metyrapone, eto‐ and metomidate interact preferentially with the P450Coh and that eto‐ and metomidate may alter selectively the catalytic properties of P450Coh leading to decreased enzyme activity. Two different Ks‐values could be found for all three drug in their binding to microsomal cytochrome(s) P450. Based on substrate binding spectra, potassium ferricyanide treatment does not dissociate the complex between reduced P450 and metomidate and does it only partly for etomidate. Furthermore potassium ferricyanide treatment of microsomes does not increase COH afterin vivotreatment of mice with eto‐ and metomidate. These data further suggest that the complex between P450Coh and eto‐ and metomidate may be particularly strong and independent from the

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01137.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics (radioreceptor assay, RRA) and some clinical effects of atropine were studied in 7 elderly gynaecological surgery patients. The RRA measures only the pharmacologically active isomer of atropine, 1‐hyoscyamine. Following a single 0.01 mg/kg intramuscular (M. deltoideus) injection, a very fast rate of absorption was found with mean peak serum concentration occurring after only 13 min. The reason for this could be either a preferential tissue uptake of the 1‐form or the injection site or both. The elimination half‐life was 2.27 hr. Only 23.1% of the given drug was excreted in urine in 24 hr as a pharmacologically active form. The clinical effects (heart rate rise, subjective sedation and antisialogogue effect) were seen after only 30 min. This somewhat faster appearance of clinical effects than in previous studies can be due to the injection site. The sedative effect of the drug is clear and long lasting in elderly p

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01138.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effects of (‐)15‐deoxyspergualin (15‐DS), a newly described immunosuppressive drug, have been investigated on diabetes induced in mice treated with multiple low‐dose streptozotocin (multiple SZ). Male C3D2F1 mice were treated with either intraperitoneal injections of saline or 15‐DS (2.5 mg/kg body weight) for a total of 10 days, starting during the first day of SZ administration (5 days; 40 mg/kg body weight). On day 14, 15‐DS‐treated animals were still normoglycaemic, whilst on day 21 there was only a partial reduction in the hyperglycaemia compared to that found in the saline treated animals receiving SZ. 15‐DS did not prevent hyperglycaemia in the long run (day 35‐63). Furthermore, morphological examinations of pancreatic glands suggested that the insulitis in the pancreatic islets was delayed in the 15‐DS‐treated animals. In control experiments mice were treated with 15‐DS+ the vehicle for SZ. This regimen did not hamper the glucose homeostasis of the animals.In vitroeffects of 15‐DS were also examined. Isolated islets from C3D2F1 mice were cultured at different concentrations of 15‐DS (0.1‐10.0 mg/l). After one week in culture, islet insulin release, islet insulin and DNA content were measured. The islets looked fluffy after culture at the higher 15‐DS concentrations (4.0‐10.0 mg/l) and at 10 mM almost all of the islets disappeared. A dose‐dependent reduction of glucose‐stimulated insulin release could also be seen. In other experiments islets were exposed to SZ and subsequently cultured in the presence of 0.5 mM 15‐DS, however, 15‐DS could not prevent the reduction in insulin release due to SZ exposure. Since 15‐DS influences macrophage functions, the presently observed protective effects against the multiple SZ‐treatment could reflect a reduced local interleukin‐1 production in the islet vicinity. Alternatively, a lowered interleukin‐1 secretion could prevent the activation of other im

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01139.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The constancy of rat EEG during surgical anaesthesia induced by phenobarbital, cholorose, paraldehyde, and inactin was investigated. The results showed that intraindividual variations and spontaneity of EEG were not abolished in the anaestheized animals. However, at the higher of the two doses used, the EEG was less variable. Our findings thus indicate that in the study of drug actions on the EEG of anaesthetized animals, the results obtained not only represent the interaction of the anaesthetic and the drug on the animal EEG but is also a reflection of the dosage of the anaesthetic employed.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01140.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The inhibitory effects of sulfasalazine, some sulfasalazine‐related compounds and indomethacin on superoxide production by human polymorphonuclear (PMN) leukocytes were studied. The inhibition of the chemotactic peptide (FMLP)‐induced superoxide production, which is membrane receptor‐mediated, was strongly dependent on the concentration both of the secretory stimulus and of the test compounds, indicating an interaction between the receptor and the test compound. Furthermore, a positive correlation was found between the lipophilicity of the compound and the degree of inhibition. However, when the receptor was by‐passed by direct activation of the receptor‐linked G protein by the use of fluoride ions as secretory stimuli, the test compounds still inhibited superoxide production. On the other hand, superoxide production by cells stimulated with phorbol ester was not inhibited by the test compounds. Furthermore, the production of phosphatidic acid was decreased in the presence of sulfasalazine, indicating impaired phosphoinositide metabolism. The inhibition of this metabolism was not due to increased intracellular concentrations of cyclic AMP, although sulfasalazine did inhibit cyclic nucleotide phosphodiesterase. We conclude that sulfasalazine attenuates superoxide production by PMN leukocytes at a post‐receptor site of action at a step before the activation of protein kinase C, possibly by interfering with the phosphoinositide metabolism but independent of

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01141.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY