Investigations of the lymphokine system in elderly individuals.

Elderly people are at risk from an increased incidence of infections. Therefore we have studied the correlation between the production of several immunological parameters such as interferon-gamma (IFN-gamma), interferon-alpha-2 (IFN-alpha-2), interleukin-2 (IL-2), soluble interleukin-2 receptors (sIL-2R) and interleukin-6 (IL-6) in young controls of 25-34 years old and old individuals with a minimum age of 65 years. All persons were selected according to the basic concept of the 'Senieur protocol'. Heparinized blood was taken and cultured in the whole-blood assay. The determination of all cytokines in the supernatants of stimulated cultures was done by the ELISA technique. We found significantly decreased levels of sIL-2R and IFN-alpha-2 after stimulation, whereas the values of IFN-gamma and IL-2 showed no significant difference between elderly and young persons. The values of IL-6 showed a distinct trend towards an increased synthesis for the elderly. We also studied the lymphocyte subpopulations T4 and T8 by flow cytometry. Elderly individuals showed a significantly increased T4/T8 ratio, caused by a slightly but not significantly decreased level of T8 cells. These results show that the elderly have decreased values of some immunological parameters such as IFN-alpha-2 and sIL-2R, which might explain an increased susceptibility of elderly individuals to bacterial and viral infections.

[Vascular diseases in the elderly]. / Gefässerkrankungen im Alter.

Obliterary artery diseases are not confined to the elderly but on the other hand a higher rate of acute symptoms in old age is observed because of multiple influences of the hemodynamics. Furthermore in old age only rarely a reversal of these symptoms takes place. In the underlying paper the several regions of the body which may be changed by the obliteration of the arteries are discussed. In addition the question of therapy will be taken into consideration. In general the therapeutic regimes will be the same as in younger age: muscle training of the legs, local lysis by catheter, late fibrinolysis, hemodilution, rheologically acting substances, along with an active interval training or a transluminal dilatation by catheter or a surgical intervention. Relevant concomitant diseases such as diabetes mellitus or hypertension and their relevance for obliterative vessel diseases will especially be stressed.

Investigation of the bioequivalence of two carbamazepine sustained-release formulations in healthy subjects.

A bioavailability study of two commercial carbamazepine sustained-release formulations was carried out in 14 healthy male subjects in order to compare plasma concentration/time profiles and to determine the relative bioavailability of carbamazepine (CBZ). This randomized study had a single-dose, crossover design and consisted of two trial periods separated by a three-week wash-out period. A sensitive, validated HPLC method was used to analyze plasma carbamazepine levels. Bioequivalence was only accepted for the test (Timonil 600 retard from Desitin Arzneimittel GmbH) and reference preparations (T and R) if the 90% confidence interval (parametric or non-parametric) for the ratios of the median values of the target variables was completely within the bioequivalence range. The following values were found for relative bioavailability: T/R: AUC = 109.6 (101.5-116.5)%, MRT = 96.4 (92.0-100.4)%, HVD = 92.4 (85.0-97.8)%. Applied to these pharmacokinetic data, the requirements for bioequivalence are met when the inclusion rule is used.

Glibenclamide steady state plasma levels during concomitant vinpocetine administration in type II diabetic patients.

The influence of vinpocetine on glibenclamide steady state plasma levels was investigated in 18 patients suffering from type II diabetes and symptoms of dementia. During the study patients continued to follow their individual scheme of glibenclamide intake and 10 mg vinpocetine were given t.i.d. from day 2 to 5. Glibenclamid as well as glucose plasma levels were repeatedly determined on the first day of the trial and compared to those on the fifth day where patients had received additional vinpocetine medication for four days. Time point comparisons were employed to exclude clinically relevant changes of glibenclamide bioavailability and kinetics. The data of this trial show that vinpocetine does not interfere with the kinetics of glibenclamide. Thus, it can be concluded that the comedication with vinpocetine does not represent a potential risk for a possible drug interaction in case of antidiabetics treatment with glibenclamide.

Plasma protein binding of furosemide in the elderly.

The protein binding of furosemide was investigated in plasma from 22 old and 11 young subjects by equilibrium dialysis. The unbound fraction of furosemide was 3.16% in plasma from the elderly and 1.7% in plasma from the young. A significant correlation was found between the unbound fraction of furosemide and the plasma concentration of albumin. The average number of binding sites was 3.8 (elderly) and 2.7 (young) 10(-6) mol/g albumin. The average association constant (K) was 4.3 (elderly) and 4.2 (young) 10(5) M-1. By increasing the concentration of furosemide up to 200 micrograms/ml buffer the unbound fraction of the drug rose to 5.2% (elderly) and 3.5% (young).