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Biomedical subjects

B Schulz

Publications and source records attributed to B Schulz.

At least 91 records · Page 5Linked to original sources

Semisynthetic human insulin: pharmacokinetics and biological potency in healthy subjects in comparison with highly purified porcine insulin.

Pharmacokinetics and the biological activity of a new semisynthetic human insulin (VEB Berlin-Chemie) were investigated in 5 healthy men. Following an overnight fast, 0.2 IU per kg body weight of human and pork insulins (SNC insulin; VEB Berlin-Chemie) were injected subcutaneously into thigh of each individual at a time interval of 8 days. To assess biological potency of both insulins all subjects were twice connected to the BIOSTATOR. A very similar pattern of serum insulin levels (IRI) was observed following subcutaneous injection of human and pork insulin, marked by a sharp initial increase and maximum values reached after 2.5 hours. 8 hours after the insulin administration the original fasting concentrations were nearly attained. According to C-peptide levels, both insulins inhibited endogenous insulin secretion. Evaluation of insulin action was determined by euglycemic clamp technique, provided by the BIOSTATOR, whose function was transformed into a glucose-controlled dextrose infusion system. The amount of glucose delivered by the system in order to keep the blood glucose steady state concentrations at the fasting level was utilized as the measure of biological activity of the injected insulin on glucose metabolism. Maximum values of glucose infusion were achieved between 3 and 4 hr after injection of human and pork insulins. At the end of the study (8 hr) the glucose administration did not return to its initial rate. After administration of both the human and porcine insulins, a marked but similar decrease of FFA concentrations was observed. This indicated a clear-cut inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

[Visualization of multiple neurofibromas using gadolinium-DTPA assisted MRT: a case report].

Although magnetic resonance imaging has a high sensitivity for cerebral and spinal tumors, demonstration of small lesions can be difficult. In a patient with multiple extra- and intraspinal tumors due to neurofibromatosis generalisata, the use of the MRI contrast agent Gadolinium-DTPA resulted in a better differentiation especially of small lesions. High tumor contrast facilitated a safe localisation of the widespread disease using a fast imaging sequence (FLASH).

Adult↗

[Problems of metabolic control in type I diabetic patients with chronic renal failure].

The aetiopathogenesis of the diabetic nephropathy today is still unknown. Uncontested is the contribution of chronic hyperglycemia in the pathogenesis of diabetic nephropathy. For this, there are convincing evidences from clinical and experimental experiences including transplantation surgery. The quality of the metabolic adjustment of the diabetics from the first time of diabetes manifestation is important to prevent the development of diabetic nephropathy. For this, an almost normoglycemic compensation of the glucose metabolism is mandatory. More problematically is the management of the diabetic metabolism during chronic renal insufficiency. Considerable fluctuations of the blood glucose concentration are predominately in the daily profile. The intensive conventional metabolic therapy by multiple insuline injections under self control of the blood glucose level are indicated absolutely in those patients. The therapeutic aim is a smoothing of the blood glucose fluctuation. With that it is possible--together with the elimination of hemodynamic risk factors--to delay effectively a progradient decline of the glomerulo-filtration rate and to improve the assumption to an invasive therapy.

Blood Glucose↗

Structure-release relationships of physically based polymer-biocide combinations. Part 3: Effect of the environment on the release of 3(5)-methylpyrazole from monolithic matrix systems.

The release behaviour of the antimicrobially active 3(5)-methylpyrazole from matrix systems prepared from maleic anhydride copolymers as well as from copolymers of maleic esters and maleic amides was studied. Under alkaline conditions erosion is the predominant release mechanism compared to the release of the agent by diffusion into neutral or acid media. The presence of potassium and calcium salts influences the release rate under aquatic conditions in a different way. The diffusion rate of the active ingredient through membranes of maleic anhydride copolymers also depends on interactions with the surrounding media as well as on the hydrophilicity of the matrix.

Anti-Infective Agents↗

Nucleocytoplasmic protein traffic in single mammalian cells studied by fluorescence microphotolysis.

Fluorescence microphotolysis was employed to measure in single living cells the kinetics of nucleocytoplasmic transport and the coefficients of intracellular diffusional mobility for the nuclear non-chromosomal protein nucleoplasmin. Nucleoplasmin was isolated from Xenopus ovary and labeled fluorescently. By injection into Xenopus oocytes it was ascertained that fluorescent labeling did not interfere with normal nuclear accumulation. Upon injection into the cytoplasm of various mammalian cell types nucleoplasmin was rapidly taken up by the nucleus. In rat hepatoma cells the half-time of nuclear uptake was approx. 5 min at 37 degrees C; the nucleocytoplasmic equilibrium concentration ratio had a maximum of 6.5 +/- 1.4 and depended on the injected amount. Upon co-injection of ATPases or reduction of temperature to 10 degrees C a nucleocytoplasmic equilization but no nuclear accumulation was observed. Equilization was fast (time constant 65 s at 23 degrees C), similar to that of 10-kDa dextran permeating the nuclear envelope by simple diffusion through functional pores. Nucleoplasmin (160 kDa), however, is too large to permeate passively the nuclear envelope, which is apparent from the fact that its tryptic 'core' fragment (100 kDa) could not permeate the nuclear envelope. On the other hand, a large fluorescent protein, phycoerythrin (240 kDa), was targeted to the nucleus by conjugation with nucleoplasmin. In the nucleus-to-cytoplasm direction the nuclear envelope was completely impermeable to nucleoplasmin, independently of temperature or ATP depletion. Nucleoplasmin, its core fragment, phycoerythrin and the phycoerythrin-nucleoplasmin conjugate were mobile in both cytoplasm and nucleus.

Animals↗

Islet cell surface antibodies (ICSA) in subjects with a previous mumps infection--a prospective study over a 4 year period.

It has been suggested that the mumps virus may be involved in the etiopathogenesis of Type-I diabetes mellitus. Most studies have analyzed this relationship retrospectively. We, however, carried out a prospective study over a 4 year period after a mumps infection in two age groups (16 years and under [group A no = 32] and over 16 years [group B no = 18]). These subjects with "diabetic risk factors" (impaired glucose tolerance, low insulin response, ICSA and/or HLA-DR3/DR4) were selected from 1581 registered cases, in whom an antecedent mumps infection had occurred in 1980 and 1981. Glucose tolerance and insulin secretion did not change significantly during 4 years after a mumps infection. Overt diabetes was not observed in any of the cases. One year after a mumps infection 35% of children and 63% of adolescents/adults exhibited ICSA (control subjects = 5%; a serum was considered ICSA-positive if more than 25% of the intact rat islet cells showed distinct cell surface immunofluorescence). After 4 years the percentage of subjects with ICSA decreased significantly to 13% and 14%, resp. Only 21% of ICSA-positive sera were found to be cytotoxic on rat islet cells (51Cr-release assay). No relationship could be evaluated between complications resulting from a mumps infection and the appearance of ICSA. There was no correlation between ICSA, glucose tolerance, and insulin secretion. In fact, our prospective study did not reveal any relationship between a mumps infection and Type-I diabetes. ICSA would seem to be of no predictive value.

Adolescent↗

Measurement of insulin in human sera using a new RIA kit. 1. Insulin determination in the absence of insulin antibodies--conventional assay and micro modification.

A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 +/- 2.0% (n = 38) and 100.1 +/- 1.9% (n = 42), respectively. In addition to human insulin, porcine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40% on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated.

Humans↗

Pharmacokinetics and biological activity of the new intermediate-acting insulin L-SNC).

To assess pharmacokinetics and biological activity of the new L-SNC insulin (Berlin-Chemie, a low immunogenic pork insulin in neutral solution purified by chromatography) ten healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.4 U of L-SNC insulin per kg body weight were injected subcutaneously in the thigh of each individual. Plasma insulin concentrations rose gradually reaching their maximum values after 8 hours. According to C-peptide levels there was some inhibition of endogenous insulin secretion. For the evaluation of insulin action we used the closed loop system (BIOSTATOR) which was transformed in its function into a glucose controlled dextrose infusion system. The amount of glucose delivered by the BIOSTATOR in order to maintain blood glucose steady state concentrations at the "basal" level was taken as a measure of biological activity of the injected insulin. The glucose infusion rate increased after insulin administration, reaching statistical significance after 3 hr. The maximum effect of L-SNC insulin was observed between 5 and 12 hours after injection. The overall duration of action of more than 16 hours meets the increasing need for insulin in the early morning in many diabetic patients. Therefore, L-SNC insulin should be recommended for intensified conventional insulin therapy to cover the night and to prevent dawn phenomenon in insulin dependent diabetics.

Adult↗

[Significance of drug prevention of thromboembolism in urologic risk patients].

The phlebothrombosis and pulmonary embolism are severe postoperative complications. Urological patients are particularly at risk with thrombosis. Therefore it becomes necessary for urology to perform a consequent prophylaxis of thromboembolism which, when an increased risk is present, must contain medicamentous measures. As it is confirmed by evident studies, the low-dose heparin prophylaxis proved as optimum method. A still more effective thrombosis protection can be achieved by the combination of small heparin doses with dihydroergotamine. Retrospectively, 2 comparable groups of urological risk patients with and without heparin prophylaxis were examined. In the adenomectomies under heparin prophylaxis a trend to the reduction of the events of postoperative thromboembolism is revealed. The heparin prophylaxis does not lead to an increase of complications of haemorrhages which need therapy. The prophylaxis of thromboembolism with heparin and a heparin-DHE-combination, respectively, is recommended for the application in urological risk patients.

Dose-Response Relationship, Drug↗

[Structure-release relationship of physical polymer/drug combinations. 2. Diffusion of 3-methylpyrazole through a synthetic polymer matrix].

The diffusion of 3-methylpyrazole through a synthetic polymer matrix and the effect of the solubility of the bioactive agent in polymers on the release behaviour of polymer combinations were studied. With increasing hydrophilicity of the polymer both the diffusion and the diffusion coefficient of 3-methylpyrazole increased and the solubility of the agent in the polymer decreased. The hydrophilicity of various polymers is discussed on the basis of a parameter determined by turbidimetric titrations.

Chemical Phenomena↗

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Cross-correlation analysis of discharge patterns of neighbouring neurones.

Temporal relations of discharges of 73 pairs of neurones located in the medial parts of the reticular formation of the lower brainstem were studied by cross correlation analyses in chloralose-urethane anaesthetized dogs. The action potentials of 2 or 3 neighbouring neurones were recorded with one electrode simultaneously. Uncorrelated discharges of neurones and 4 different types of correlated discharges were observed in cross correlation histograms: they were: (1) rhythmic couplings with frequencies between 2 and 5 Hz related to the same rhythm in the EEG; (2) strong, non-rhythmic couplings with short latencies up to 5 ms; (3) a combination of strong and rhythmic couplings, and (4) high-frequency oscillation couplings. Most pairs of neurones showed different types of correlation during the recordings. The different forms of correlated discharge behaviour could be related to different types of functional organization of the neuronal network in the reticular formation.

Afferent Pathways↗

Further support for inhibition of endogenous insulin secretion by exogenous insulin.

In order to investigate whether or not insulin exerts any influence on endogenous insulin secretion, 6 non-obese healthy volunteers were connected to the artificial beta-cell (BIOSTATOR) for 16 hours. After an overnight fast 0.4 U of intermediate acting insulin (Monotard MC/NOVO INDUSTRIES) per kg body weight were injected subcutaneously. The computer program was set to maintain steady-state plasma glucose concentrations at fasting levels by a variable glucose infusion. This approach is able to prevent completely hypoglycemic episodes. Endogenous insulin secretion was evaluated by measuring plasma C-peptide concentrations. Whereas plasma insulin levels increased markedly in response to insulin injection at the same time C-peptide levels declined correspondingly, indicating an inhibition of insulin secretion. Thus, our results provided further support for a negative feedback regulation of insulin secretion by insulin itself.

Adult↗

Muscular exercise in type I-diabetics. II. Hormonal and metabolic responses to moderate exercise.

In Type I-diabetics metabolic response to exercise is largely determined by the availability of exogenous insulin. The aim of the present study was to assess the metabolic response to moderate exercise of 24 insulin-dependent (Type I-) diabetics treated by multiple subcutaneous injections of short acting insulin. Differences in insulin availability (hypo- [trial A] or hyperinsulinemia [trial B]) resulted from the different periods of time that had elapsed since the previous insulin injection, i.e., after 3 hours (trial A), and 1 hour (trial B). Bicycle ergometer tests at intensities up to 75% VO2max, were carried out with patients and controls. Plasma glucose, FFA, glycerol, alanine, growth hormone and glucagon levels were measured during a period of 85 min. In both trials, physical exertion did not have a significant statistical effect on the glucose concentration in the blood of hypo- and hyperinsulinemics. Surprisingly, despite the different insulin availabilities FFA, glycerol, alanine and glucagon concentrations were not statistically different in either trial and appear similar to those of healthy controls. A normal metabolic response to exercise can thus also be expected in Type I-diabetics, provided adequate insulin is available. When compared to controls, growth hormone concentrations were found to have increased during exercise. These experimental data strongly suggest the great necessity of adequate insulin availability in order to obtain normal metabolic responses to exercise in insulin-dependent diabetics. Despite certain degrees of hypo- or hyperinsulinemia, moderate exercise did not cause any marked metabolic derangements. This type of moderate exercise is therefore recommended for improving metabolic control in such patients.

Adult↗