PubMed Health⌕ Search

Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 19 recordsLinked to original sources
PubMed1995

Oxygen release kinetics in healthy subjects and diabetic patients. II: Effects of HbCO.

Glycosylated hemoglobin (HbA1c) and carboxyhemoglobin (HbCO) are elevated in diabetic smokers. Both increase the oxygen affinity of hemoglobin and lower the velocity of oxygen release. We have, therefore, measured the influence of HbCO on the oxygen dissociation kinetics of hemoglobin in blood from healthy subjects (HbA1c = 5.3 +/- 0.3%, n = 12) and diabetic patients (HbA1c = 8.4 +/- 1.6%, n = 12) using the stopped flow technique. In addition, the effect of 2,3-DPG on the oxygen dissociation rate of hemoglobin containing high concentrations of HbCO was examined. Neither statistically nor clinically significant differences in the oxygen dissociation rate between blood from healthy subjects and diabetic patients were found. Increasing the HbCO concentration up to 20% of total hemoglobin produced an approximately 20% decrease (p < 0.001) in the dissociation rate constant in blood samples from both groups of subjects. Addition of 20 mmol 2,3-DPG per 10 mmol hemoglobin had little effect on the magnitude of these changes. It is concluded that HbCO values similar to those present in smokers cause a significant decrease of oxygen release in healthy subjects and diabetic patients. Elevated HbA1c concentrations do not potentiate the effects of HbCO on oxygen release in either group of subjects.

2,3-Diphosphoglycerate↗
PubMed1994

Reactions of human keratinocytes in vitro after application of nicotine.

Nicotine is rapidly taken up by human keratinocytes (HaCaT cells) and after 3 h the uptake is approximately 50% of maximum. Cotinine, a metabolite of nicotine, was detected, thus demonstrating the metabolism of nicotine in HaCaT cells. Low nicotine concentrations (0.1-200 micrograms/ml) did not influence the incorporation rate of thymidine into DNA or amino acids into proteins. Inhibition of DNA and protein synthesis was only observed at concentrations > 200 micrograms/ml. After application of 400 micrograms/ml nicotine, the cells were vacuolated. This process was reversed after nicotine withdrawal. At low nicotine concentrations, no changes in microtubules and actin filaments could be detected. However, in the presence of nicotine (1-10 micrograms/ml), keratin filaments showed a more orderly pattern that controls, and the expression of the suprabasal keratins 1 and 10/11 was induced and increased according to the concentration of nicotine. The number of cornified envelopes also increased markedly. Nicotine concentrations > 100 micrograms/ml led to a disarrangement of keratin filaments and to a decrease in keratin expression and cornified envelope formation. Our results suggest that nicotine at concentrations up to 100 micrograms/ml is not an irritant but may induce cornification of the skin.

Cell Differentiation↗
PubMed1993

Effect of free fatty acids on the binding kinetics at the benzodiazepine binding site of glycated human serum albumin.

The effect of free fatty acids (FFA) and non-enzymatic glycation on the binding kinetics of dansylsarcosine (DS) to human serum albumin (HSA) was studied using the stopped-flow technique. The influence of FFA on the binding parameters of 25% glycated HSA depended on the type of fatty acid. The addition of stearic, oleic and linoleic acids in a concentration of 0.3 mmol/l showed no inhibitory effects on the association rate constant (k2) value for DS binding to 25% glycated HSA (k2 without FFA: 385 +/- 10 s-1, k2 with FFA > or = 385 +/- 10 s-1). In contrast, shorter chain fatty acids (hexanoic, octanoic, decanoic, lauric and myristic acids) showed marked inhibitory effects for 0.3 mmol/l FFA (k2 range: 233 +/- 32 to 69 +/- 5 s-1) and for 0.6 mmol/l FFA (k2 range: 125 +/- 3 to 20 +/- 4 s-1). The association rate constant (k2) as well as the affinity constant (KA) of DS were markedly affected by glycation: k2 was 686 +/- 61 s-1 for 7% glycated HSA, 385 +/- 10 s-1 for 25% glycated HSA and 209 +/- 12 s-1 for 50% glycated HSA. KA decreased from 6.1 +/- 2.9 x 10(5) M-1 for 7% glycated HSA, to 5.1 +/- 0.1 x 10(5) M-1 for 25% glycated HSA and to 1.3 +/- 0.6 x 10(5) M-1 for 50% glycated HSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzodiazepines↗
PubMed1992

Oxygen-dissociation kinetics in the blood of smokers and non-smokers: interaction between oxygen and carbon monoxide at the hemoglobin molecule.

The importance of smoking as a possible factor in coronary heart disease (CHD) may be related to the effect of carbon monoxide (CO) on oxygen exchange at the hemoglobin molecule (Hb). We examined the kinetics of this process in vitro and ex vivo using a fast-reaction technique (stopped-flow) whereby the dissociation-rate constant of oxygen was determined in the blood of smokers and non-smokers and at fixed HbCO-concentrations in non-smokers blood. In non-smokers, carbon monoxide saturated blood was obtained by gassing with carbon monoxide and mixing the samples with appropriate carbon monoxide free blood to achieve HbCO-concentration in the range of 10-60%. The reaction time course for the oxygen-dissociation was divided into a non-linear-initial phase (loss of the first oxygen molecule) and a subsequent linear phase. The oxygen-dissociation velocity decreased from 96.5 x 10(3) ms-1 to 42.7 x 10(3) ms-1 in the linear phase at pH 7.4 and decreased from 29.2 x 10(3) ms-1 to 20.9 x 10(3) ms-1 at pH 9.2 when the HbCO-concentration was increased to 63%. For the initial phase at pH 7.4, the dissociation velocity decreased depending on the HbCO-concentration. In non-smokers 50% of the bound oxygen was released in 17.5 +/- 2.3 ms (n = 13) whereas in smokers 19.4 +/- 1.8 ms (n = 14) (p less than 0.05) was required.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Current concepts: converting enzyme inhibitors in coronary artery disease.

Studies investigating the antiischemic action of converting enzyme inhibitors (CEIs) in patients with coronary artery disease (CAD) have, after single dosing, provided evidence for mechanisms of action such as coronary vasodilation and reduction of myocardial oxygen-consumption due to pre- and afterload reduction. Measurements of exercise-induced ST-segment depression and exercise duration as criteria for clinical efficacy have revealed contradictory findings. Patient characteristics, which may be important for a satisfactory response to CEI treatment, have yet to be identified. Patients with ischemic left ventricular dysfunction may benefit from CEI therapy. Neurohumoral factors, e.g., plasma renin activity and atrial natriuretic peptide, may also be relevant. The anti-ischemic efficacy of CEIs given as monotherapy has not yet been convincingly demonstrated. The protective effect of CEI treatment with regard to ventricular enlargement after myocardial infarction seems to be established; however, data on mortality are still outstanding.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Drug-protein binding kinetics in patients with type I diabetes.

Sera from 17 patients with Type I diabetes and 19 healthy volunteers have been examined to evaluate whether the kinetics of the binding of drugs to Site II of serum albumin is altered in diabetes. Stopped-flow measurements showed that the association velocity and the affinity constants of the fluorescent marker dansylsarcosine were significantly lower in diabetes (160 s-1 and 2.0 x 10(5) l.mol-1) than in non-diabetics (196 s-1 and 4.0 x 10(5) l.mol-1). The dissociation velocity was not different [20.3 s-1 vs. 19.4 s-1]. Although patients with a reduced albumin concentration were excluded the diabetics had significantly lower concentrations than the healthy volunteers. There was a significant correlation between decreased glycosylation of albumin and increased association velocity. The dissociation velocity constants were correlated with the molar concentration ratio of free fatty acids/human serum albumin. Thus, the extent of glycosylation and the amount of fatty acids bound per mole albumin can both affect the kinetics of drug binding to Site II. The lower affinity in patients with Type I diabetes is due to the increased in the glycoalbumin concentration.

Adult↗
PubMed1992

Concentration/effect relationship and enantioselective analysis of verapamil in hypertensive patients.

The concentration/effect relationship of verapamil was analyzed in 9 hypertensive patients using concentrations of racemic verapamil and the corresponding decrease in mean arterial blood pressure (MBP) in a sigmoidal Emax model. Concentration/effect data were obtained after a first dose (240 mg sustained release preparation) and at steady state after stepwise dose adjustment to obtain satisfactory BP control (less than 90/150 mm Hg). Emax (MBP) ranged from 15 to 40 mm Hg, and EC50 averaged 81 +/- 40 ng/ml (mean +/- SD). The fraction of S-verapamil in the overall racemic verapamil concentrations was measured in two patients by chiral high-performance liquid chromatography (HPLC) and showed a slight increase at steady state from 12.2 +/- 1.5 to 14.4 +/- 1.4% and from 14.0 +/- 1.3 to 16.3 +/- 0.6%. Concentration/effect curves for S-verapamil concentrations were similar to those obtained with racemic verapamil concentrations.

Administration, Oral↗
PubMed1992

[Pharmacokinetics of low-dose isosorbide dinitrate and metabolites after buccal or oral administration].

The kinetics of isosorbide dinitrate (ISDN; CAS 87-33-2) and its metabolites isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were examined after buccal and oral administration of 5 mg ISDN. Twelve healthy volunteers were included in a randomized cross-over study. The mean dose-corrected AUCs for total nitrate in serum after the two different preparations were in the same range. The relative bioavailability of ISDN applied buccally, however, was more than twice that after oral application. The metabolism of ISDN differed depending on the route of administration, where the AUC-ratios ISDN: IS-2-MN: IS-5-MN were 1:2.7:19.4 after buccal and 1:5.7:53.4 after oral application respectively. The absorption rate constants Ka for ISDN and the MRT after buccal and oral application did not differ significantly. The same holds for the mean residence time.

Administration, Buccal↗
PubMed1991

Prescription of drugs not listed in a clinic's pharmacopoeia: supervision by clinical pharmacologists.

The pharmaceutical market in the FRG offers about 11,000 different preparations and formulations. A restricted list (pharmacopoeia) containing approximately 1,000 drugs has been proved to cover the routine requirements of a university clinic and most of the additional drugs demanded by the physicians as 'exceptis excipiendis'. Restrictive control of requests for drugs not included in the internal pharmacopoeia by clinical pharmacologists has reduced the absolute number of requests by half, and about 60% of the remaining requests could be replaced by drugs listed in the pharmacopoeia. The majority of the special requests arose from the continuation of drugs presented to out-patients by the resident physicians after admission of the patient to the hospital. The supervision may lead to more critical revision of out-patient medication, but a substantial reduction of drug expenditure was not attained, as the drugs requested amounted only to a minor fraction of the overall drug expenditure by the hospital.

Drug Prescriptions↗
PubMed1991

Pharmacodynamic profile of verapamil in relation to absolute bioavailability: investigations with a conventional and a controlled-release formulation.

The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.

Administration, Oral↗
PubMed1991

Converting enzyme inhibition in coronary artery disease: a randomized, placebo-controlled trial with benazepril.

The antiischemic efficacy of the converting enzyme inhibitor (CEI) benazepril was investigated in a randomized, placebo-controlled double-blind study with intraindividual crossover in 11 normotensive patients with angiographically proven coronary artery disease. Bicycle ergometry and 24-h ambulatory ECG were performed before and after 2-week treatment with placebo and benazepril, respectively. Plasma concentrations of atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were measured before each exercise test. Maximal exercise-induced ST-segment depression was not significantly influenced by benazepril therapy (placebo 2.09 +/- 1.22 mm, benazepril 1.91 +/- 1.00 mm). Systolic blood pressure/heart rate (SBP/HR) product at maximum workload remained almost constant with 253 +/- 43 with placebo and 253 +/- 39 with benazepril treatment. The number of anginal attacks and ischemic episodes detected by ambulatory ECG were not significantly reduced. PRA increased significantly from 2.18 +/- 3.76 to 9.62 +/- 8.49 ng/ml/h after benazepril (p less than 0.005), whereas plasma concentrations of ANP remained unchanged (28.04 +/- 12.39 vs. 26.73 +/- 11.09 pg/ml). Therefore, measurement of ST-segment depression with exercise in 11 normotensive patients with coronary artery disease produced no evidence of an antiischemic action for the CEI benazepril 10 mg twice daily (b.i.d.) for 2 weeks, but an improvement was observed in six patients.

Adult↗
PubMed1990

Concentrations of isosorbide dinitrate, isosorbide-2-mononitrate and isosorbide-5-mononitrate in human vascular and muscle tissue under steady-state conditions.

The concentrations of isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were determined in plasma (PL), saphenous vein wall (SV) and pectoral muscle (PM) from 8 patients undergoing coronary bypass surgery. The patients were pretreated for 2 days with ISDN 240 mg per day (standard release formulation) in 4 doses of 40 mg and one dose of 80 mg. The plasma and tissue samples were obtained during the operation, 10-12 h after the last dose. Isosorbide-2-mononitrate and isosorbide-5-mononitrate were present in plasma and tissues in the same concentration ranges with molar concentration ratios of 0.88 (IS-2-MN: PM/PL), 0.85 (IS-5-MN: PM/PL), 0.99 (IS-2-MN: SV/PL) and 1.06 (IS-5-MN: SV/PL). Mean ISDN concentrations in tissue were considerably higher than in plasma; the molar concentration ratios were 4.9 (SM/PL) and 7.21 (SV/PL). The accumulation of ISDN in vessel walls may contribute to its greater vascular action compared to the mononitrates, but it may also facilitate the development of tolerance during long-term treatment.

Aged↗