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A Korn

Publications and source records attributed to A Korn.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pharmacokinetics and pharmacodynamics of the hydroxymetabolite of glimepiride (Amaryl) after intravenous administration.

Glimepiride is a new sulphonylurea which is eliminated by the formation of a hydroxy-metabolite (hydroxy-gli) and a carboxymetabolite (carboxy-gli). Animal studies have shown hydroxy-gli to exhibit some hypoglycaemic effects while carboxy-gli does not appear to have any pharmacological activity. Pharmacokinetic and pharmacodynamic effects of hydroxy-gli were assessed in humans. 12 healthy male volunteers received an intravenous injection of hydroxy-gli (1.5 mg) or placebo in a single blind, randomised, cross-over study. Samples were collected for up to 24 hours (blood) or 48 hours (urine) following administration of hydroxy-gli or placebo. Hydroxy-gli significantly decreased the minimum serum concentration (Cmin) of glucose by 12% and the average serum glucose concentration over the first four hours of treatment (Cavg0-4) by 9% compared with placebo (P < or = 0.05). In addition, maximum serum C-peptide concentration (Cmax) and Cavg0-4 were both increased by 7% after hydroxy-gli (p < or = 0.05). Serum insulin concentrations (Cmax and Cavg0-4) increased by 4% but the differences from placebo were not statistically significant. No adverse events were reported during the study. In conclusion, the hydroxymetabolite of glimepiride shows pharmacological activity in human subjects.

Adolescent↗
PubMed1996

Tyramine pharmacodynamics during combined administration of lazabemide and moclobemide.

The objective of this study was to assess the tyramine pressor sensitivity during combined administration of selective and reversible inhibitors of monoamine oxidase A and B, viz. moclobemide (300 mg b.i.d.) and lazabemide (100 mg b.i.d.), respectively. In part A, 5 healthy male subjects underwent i.v. tyramine pressor tests before (baseline) and during (day 7) combined treatment with both drugs. The tyramine dose was titrated until an increase in systolic blood pressure of 30 mmHg was attained. Subsequently, lazabemide treatment was discontinued and i.v. tyramine pressor tests were again conducted after 2 - 3 days of moclobemide monotreatment. The tyramine pressor sensitivity factor (mean + or - SD) during combined moclobemide and lazabemide treatment was 4.2 + or - 0.9 and during moclobemide monotreatment 3.1 + or - 1.1. In part B, a separate panel of 8 subjects received combined treatment with moclobemide and lazabemide for up to 10 days. Ascending oral doses of tyramine were administered on days 7 - 10 to determine the threshold dose eliciting a 30 mmHg increase in systolic blood pressure. In comparison to baseline the effects of oral tyramine were potentiated by a factor of 13.5 + or - 6.9. The low amount of oral tyramine needed (51 + or - 20 mg) to induce relevant increases in blood pressure indicates that dietary precautions are needed when both MAO-A and B are inhibited by 2 reversible inhibitors.

Administration, Oral↗
PubMed1995

Enhancement of uptake of lipopolysaccharide in macrophages by the major outer membrane protein OmpA of gram-negative bacteria.

Monoclonal antibodies (MAb) to lipopolysaccharide (LPS) and to the major outer membrane protein OmpA from Proteus mirabilis were generated and used to monitor the kinetics of uptake in macrophages of LPS as well as LPS bound to OmpA. Uptake was measured by a modified enzyme-linked immunosorbent assay (ELISA) in a microtiter culture system. The MAb were of various immunoglobulin G subclasses and showed strong reactivities with their antigens. Four hybridoma clones recognizing LPS and three recognizing OmpA from P. mirabilis 19 were selected for the present study on the basis of reactions in ELISA and Western blot (immunoblot) analyses. In the uptake assay, it was possible to differentiate between antigen on the cell surface and antigen which had been internalized. Uptake of LPS by macrophages was relatively rapid during the first 4 h of culture and then progressed more slowly over the remaining 24-h observation period. The level of detection of LPS in this assay system was in the nanogram range. When macrophages were pulsed with LPS for 30 min and subsequently washed to remove antigen not bound to the cells, the amount of LPS detectable on the macrophage surface decreased progressively for 3 h after the pulse, which indicated internalization of the antigen. Thereafter, LPS rose to an increased level on the cell surface. The rate of uptake of LPS was more rapid when it was in complex with OmpA. When the fate of OmpA was monitored in the same LPS-protein complexes by use of MAb to OmpA in a pulse experiment, the level of protein measured on the cell surface decreased after an initial rise, which again indicated internalization, but the protein did not reappear on the cell surface in a form detectable with the MAb. Compared with the LPS monitoring system, detection of OmpA associated with macrophages was weak, although the MAb to OmpA reacted strongly with the protein in the ELISA and Western blot analyses.

Acute-Phase Proteins↗
PubMed1995

Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function.

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 +/- 6 vs. 13 +/- 5%, P < 0.05) and a lower PFR (5.9 +/- 0.8 vs. 7.3 +/- 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

3-Iodobenzylguanidine↗
PubMed1994

Absolute bioavailability of glimepiride (Amaryl) after oral administration.

Twelve healthy fasting male volunteers received a single 1.0 mg dose of glimepiride either as an intravenous injection over one minute or as a tablet. Blood and urine samples were taken before drug administration and afterwards for up to 24 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2). There were no statistically significant differences between mean serum pharmacokinetic parameters for the oral and intravenous formulations either with glimepiride or M1. Mean urinary recovery of M1 plus M2 was 50% of the dose for the glimepiride tablet and 51% for the intravenous injection. The absolute bioavailability of the tablet formulation was 107% (AUDC(glimepiride)), 109% (AUDC(M1)) and 97% (urinary recovery). The tablet formulation of glimepiride is completely bioavailable and was safe and well tolerated in healthy volunteers.

Administration, Oral↗
PubMed1994

Dose linearity assessment of glimepiride (Amaryl) tablets in healthy volunteers.

Twelve healthy fasting male volunteers received glimepiride in 1, 2, 4 or 8 mg single oral doses. On the days when glimepiride was taken, the subjects were given a standardised carbohydrate diet (18 bread exchange units) and drank 125 ml of water hourly. Blood and urine samples were taken before drug administration and afterwards for up to 36 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2). The areas under the curve for glimepiride after oral doses of 1 to 8 mg and the urinary recovery of its metabolites M1 and M2 were dose linear. All confidence intervals were well contained within the bioequivalence range of 80-125%. There was a statistically significant difference for Cmax values of glimepiride between doses after dose normalisation. A dose-dependent increase for Cmax was nevertheless clearly observed with a correlation coefficient of r=0.90. The pharmacokinetics of glimepiride are dose linear in the dose range 1 to 8 mg, and glimepiride was safe and well tolerated in healthy volunteers.

Adolescent↗
PubMed1993

[Hepatitis C].

Explore the source record for details and available documents.

Adult↗
PubMed1993

Clinical evaluation of a new epidural pressure monitor.

Comparative measuring of epidural pressure using the Spiegelberg probe 1 and ventricular fluid pressure was carried out in 15 neurosurgical intensive-care patients. Deviations in both directions were established, with a trend toward overestimating ventricular pressure in epidural pressure measuring (r = 0.77). Individual pulsations, spontaneous wave courses and therapy-induced pressure changes were reflected without delays. There were no complications observed with probe implantation periods for up to 6 days. The system has been shown to be mechanically stable and easy to implant. We believe the device to be fit for trend monitoring of intracranial pressure. As with other epidural pressure monitoring systems, false assessments of ventricular pressure may lead to wrong decisions as to required therapy.

Adult↗
PubMed1993

Treatment of chronic hepatitis B with interferon alpha-2b and interleukin-2.

A total of 37 patients with histologically confirmed chronic viral hepatitis B and presence of HBV-DNA and HBsAg in the serum were treated in a randomized, prospectively controlled multicenter trial either with recombinant IFN alpha-2b alone or a combination of IFN alpha-2b and recombinant IL-2. Twenty-two patients from group A were treated with 3 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Starting at month 2 IL-2 was added: priming doses of 1.5 million CU were given s.c. on the first 2 days of each of the remaining 3 months, followed by maintenance doses of 0.3 million CU daily for 5 days per week. Fifteen patients from group B received 5 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Five patients from group A (24%) and 4 patients from group B (28%) cleared HBV-DNA and HBeAg from the serum, and normalized elevated serum aminotransferase activities. The response rate in both groups did not differ significantly. Since side effects were more pronounced during combination therapy than in IFN alpha-2b monotherapy, it is suggested that treatment with IFN alpha-2b alone is preferable to a regimen of IFN alpha-2b/IL-2 applied according to the above schedule.

Adult↗
PubMed1993

The 39-kilodalton outer membrane protein of Proteus mirabilis is an OmpA protein and mitogen for murine B lymphocytes.

Partial amino acid sequence analysis of a major outer membrane protein of Proteus mirabilis (39-kDa protein) indicates that it is an OmpA protein. The mitogenic activities of the 39-kDa protein for murine lymphocytes were also investigated with T lymphocytes isolated by passing spleen cells over columns of nylon wool fiber and B lymphocytes obtained by treating spleen cells with monoclonal antibodies to Thy1 plus complement. The 39-kDa protein showed little activity in stimulating T cells to proliferate but was strongly mitogenic for B cells.

Amino Acid Sequence↗
PubMed1993

Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man.

This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin-counterregulatory hormones secondary to induced hypoglycaemia.

Adult↗
PubMed1992

Absence of interaction between tenoxicam and warfarin.

The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.

Adult↗
PubMed1992

Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations.

The effects of high single doses of moclobemide (300, 450 and 600 mg given at the end of a standardized meal) on plasma levels of several catecholamines and their deaminated metabolites, and on plasma levels of pituitary hormones were determined in eight healthy young male volunteers in a randomized, double-blind, placebo-controlled study. Assessment of the i.v. tyramine potentiation and determination of the plasma levels of moclobemide were also performed. The tyramine sensitivity factor at 2 h after dosing was about 2.1, with no significant differences between the doses used. The inhibitory activity of moclobemide on MAO-A was reflected in significant reductions of plasma concentrations of DHPG and 5-HIAA. No clear differences were detected between the moclobemide doses. Prolactin plasma concentrations were only slightly increased after the two higher doses. The plasma concentrations of moclobemide were very much in agreement with those found in previous studies under similar experimental conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg induced a near-maximum effect.

Adult↗