Biomedical subjects

N Rietbrock

Publications and source records attributed to N Rietbrock.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effect of 2,3-diphosphoglycerate on O2-dissociation kinetics of hemoglobin and glycosylated hemoglobin using the stopped flow technique and an improved in vitro method for hemoglobin glycosylation.

Studies under equilibrium conditions have shown that the oxygen affinity of hemoglobin (Hb) is lowered by 2,3-diphosphoglycerate (2,3-DPG), the physiological allosteric effector in erythrocytes, and enhanced by glycosylation of Hb. The kinetics of oxygen release, as a function of 2,3-DPG and the degree of glycosylation have been determined using the stopped flow method and a new in vitro glycosylation procedure allowing adequate amounts of functionally intact hemoglobin to be obtained. The rate constant k of O2-dissociation in glycosylated Hb (8% HbA1c) was approximately 10% lower than in native Hb (4% HbA1c). The addition of 2,3-DPG in concentrations up to 20 mmol/l resulted in a progressive increase of k from 61.5 +/- 3.3 s-1 to 65.3 ae 4.1 s-1 for native Hb and from 56.8 +/- 5.2 s-1 to 59.4 +/- 4.1 s-1 for glycosylated Hb. We conclude that (a) the degree of glycosylation similar to that found in diabetic patients is responsible for a significant decrease of the oxygen dissociation velocity and (b) 2,3-DPG concentration similar to those occurring in vivo have only a weak effect on the oxygen dissociation velocity.

2,3-Diphosphoglycerate↗

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↗

PubMed1993

Supermolecular inclusion of piroxicam with beta-cyclodextrin: pharmacokinetic properties in man.

Piroxicam beta-cyclodextrin is a novel inclusion complex in which the piroxicam molecule has higher wettability and faster dissolution characteristics than plain piroxicam. Pharmacokinetic studies comparing piroxicam beta-cyclodextrin with plain piroxicam have been carried out in both patients and healthy subjects. The absorption rate of piroxicam from the complex, determined using tmax, absorption rate constant (Ka) and plasma concentrations at 15 min and 30 min post-dose, is considerably faster than that for plain piroxicam. This difference, that can be demonstrated with both tablet and sachet formulations, is still present during repeated dose administration and when the drugs are administered after food. After absorption from piroxicam beta-cyclodextrin formulations, the kinetic disposition of piroxicam and bioavailability parameters are identical to those for plain piroxicam. The more rapid rise in piroxicam plasma concentrations and the reduced contact time of piroxicam in the upper gastrointestinal-tract may be reasons for the reduced incidence of gastrointestinal complaints and gastrointestinal bleeding and the rapid attainment of pain relief with piroxicam beta-cyclodextrin. The most rapid relief of pain will be achieved using piroxicam beta-cyclodextrin sachets administered in the fasting state, since piroxicam is immediately bioavailable in this formulation and the onset of action is similar to that for injectable piroxicam.

Absorption↗

PubMed1993

Transdermal nicotine substitution: pharmacokinetics of nicotine and cotinine.

The use of tobacco has resulted in major health related problems worldwide. Nicotine replacement is one of the most promising strategies in smoking cessation. The in vivo delivery rate and the pharmacokinetic properties of a recently developed transdermal nicotine system (TNS) was investigated in three separate studies. Two sizes (16 cm2 and 24 cm2) of the patches were tested. Mean daily nicotine delivery, expressed by a first order kinetic, varied between 0.9 and 1.0 mg/cm2 patch. The different sizes of the patches led to linearly dose-related nicotine plasma Cmax- and AUC-values. The nicotine levels achieved were in the same range with those of other nicotine patches and the chewing gum. As a result of multiple dose kinetic, no significant accumulation of nicotine was observed. Mean elimination half-life of nicotine after removal of the patches (3.5 +/- 1.8 h for the larger patch and 4.5 +/- 1.9 h for the smaller patch) was longer than reported values after i.v. administration, which was reported to vary between 40 and 120 min.

Administration, Cutaneous↗

PubMed1993

Transdermal nicotine in smoking cessation and involvement of non-specific influences.

The efficacy of a nicotine transdermal therapeutic system (TTS) (available size 10, 20 and 30 cm2; nicotine delivery rate = 0.7 mg/cm2/24 h) as an aid for smoking cessation, was evaluated in a randomized, single-blind, placebo-controlled, monocenter study using 160 heavy-smokers (> 20 cigarettes/day), male and female, who were divided into two matched parallel groups. The nicotine replacement treatment lasted for 3 months and was carried out according to the manufacturers recommendations. Abstinence was defined as smoking no cigarette during the last week of each month and COHb-levels < or = 1.2%. Efficacy was assessed using abstinence rates, withdrawal symptoms and cigarette consumption. Although at the commencement of the study all subjects expressed a high motivation to stop smoking, about a third were lost to follow-up at 4 weeks. This was attributed mainly to the lack of counselling and group dynamics. The greatest effect on smoking cessation and cigarette consumption was attributable to a non-specific aspect of treatment, i.e. the motivation to stop smoking on application of the first patch. On an intention-to-treat basis (all subjects), abstinence rates were 24% and 18% after 1 month, 24% and 14% after 2 months and 14% and 6% after 3 months for the nicotine-TTS and placebo-TTS, respectively. Nicotine-TTS was at least twice as effective as placebo in maintaining nicotine abstinence. The superiority of the nicotine-TTS was supported by the trend to a higher craving-for-cigarettes score and significantly higher blood COHb and cigarette consumption in the non-abstainers treated with placebo.

Administration, Cutaneous↗

PubMed1993

Selective determination of non-enzymatic glycosylated serum albumin as a medium term index of diabetic control.

Serum proteins are non-enzymatically glycosylated dependent on the concentration of free glucose and measurements of their concentration are used to control diabetic carbohydrate metabolism. Eight patients with insulin-dependent diabetes mellitus (IDDM) and 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) with glycosylated hemoglobin levels of at least 10.5% were studied during a 6-week period of antidiabetic therapy. Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP) were measured weekly using an affinity chromatography procedure. The fructosamine test (FA) and the measurement of mean blood glucose (MBG) were also carried out weekly. Glycosylated hemoglobin and its glucose adduct HbA1c were determined at 14-day intervals (HPLC-method). All measured parameters decreased during the period of the study. The correlation coefficients for the glycosylated proteins versus the MBG determined one week earlier were highest for GSA [IDDM: r(GSA/MBG-1) = 0.726, p < 0.001 for the single values and 0.984, p < 0.001 for the mean values; NIDDM: r (GSA/MBG-1) = 0.636, p < 0.001 for the single values and 0.986, p < 0.001 for the mean values]. The differences between the IDDM and NIDDM group probably occurred because 6 NIDDM patients were taking glibenclamide (7.0-10.5 mg/day) which is known to inhibit the glycosylation reaction of albumin. The fructosamine test is more prone to interferences than the selective determination of GSA. GSA determination therefore, gives precise data in medium term diabetic control.

Adult↗

PubMed1993

Plasma concentrations of S-verapamil after single doses of two different galenic formulations of racemic verapamil.

The results of enantioselective analysis of verapamil (CAS 52-53-9) in plasma samples obtained at tmax after single dose applications of a 80 mg fast dissoluting (IR) tablet, a controlled release (CR) formulation (240 mg) and an intravenous injection of 5 mg verapamil are reported. The mean fraction of S-verapamil obtained in samples containing the Cmax of racemic verapamil was somewhat smaller after application of the IR-form than observed with the CR formulation. (IR = 15.8 +/- 3.8%; CR = 18.8 +/- 2.0%; p < 0.01), after the intravenous application the mean S-fraction was 32.8 +/- 1.4%. In vitro dissolution tests of the two oral preparations prove that the isomers were released as racemate.

Administration, Oral↗

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