D-glucose uptake by a rat liver plasma membrane preparation.

1. Plasma membranes isolated from rat liver according to a modification of the method of Neville, D.M. ((1960) J. Biophys. Biochem. Cytol. 8, 413-422) were used as model to test current hypotheses on the mode of glucose uptake into the liver cell. Glucose uptake studies were performed by a filtration technique using labeled glucose analogues. 2. D-glucose Uptake by rat liver plasma membranes is characterized by features of simple diffusion, i.e. linearity of uptake, lack of stereospecificity, and by facilitated diffusion, i.e. temperature dependence, counterflow phenomenon and inhibition by phloretin. These findings confirm earlier studies on liver slices and perfused liver. 3. Binding studies on sonicated membranes provide evidence for a specific binding site or protein for D-glucose at the plasma membrane by isolating Tris-soluble membrane proteins which reveal a higher binding capacity than the unsonicated membrane. 4. These findings are interpreted as showing the presence of a "carrier" mediated transport system for D-glucose superimposed by free diffusion due to artificial disruption of the plasma membranes.

Human insulin (recombinant DNA) in the treatment of patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM).

Human insulin (recombinant DNA) was administered subcutaneously to 16 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), whereas a control group of 11 patients received highly purified pork insulin (PPI). The control group was only available for the inpatient period, while the HI-treated patients could be observed monthly afterward. For metabolic control, basal and post-prandial blood glucose, plasma C-peptide, and HbA1 were measured. During the outpatient period, blood glucose self-monitoring was also performed. Within 6 days of therapy, blood glucose levels were lowered to normal without any statistical differences between the HI and PPI groups. Mean insulin requirement was 35 U/day in both groups. Plasma C-peptide levels were not different at any time. In the human insulin group, HbA1 values were continuously lowered from the initial 13% to the normal range within 2-3 mo and remained normal after 6 mo of therapy. No allergic reaction and no other side effects could be seen. The results suggest that in the first period of treatment, the metabolic situation of patients with IDDM could be well controlled by human insulin as well as by PPI. Human insulin has been proven to be an effective and safe insulin.

Intradermal desensitization with human insulin (recombinant DNA) in a patient with severe allergic skin reaction due to insulin.

This is a case report of a 70-yr-old female patient with a severe allergic skin reaction (necroses) due to insulin injections. Because of insulin dependency, desensitization to insulin was mandatory. For desensitization, a schedule with intradermal injections of increasing insulin concentrations (from 0.02 to 2 U per injection) at time intervals of 3 h was used. With highly purified pork insulin, the concentration limit of 0.04 U was reached in spite of 75 injections. After changing to human insulin (recombinant DNA), a rapid desensitization could be performed at the same concentration. Desensitization resulted not only to human insulin but also to highly purified pork insulin, as shown by intradermal testing 6 mo later.

Efficiency of human insulin (recombinant DNA) in the treatment of diabetic ketoacidosis and severe nonketoacidotic hyperglycemia.

Human insulin (recombinant DNA) was compared with pork insulin in the treatment of diabetic ketoacidosis and severe nonketoacidotic hyperglycemia using a continuous, intravenous, low-dose regimen. Seven patients (age range 48 +/- 26 yr, mean +/- SD) with diabetic ketoacidosis and three (52, 65, and 70 yr) with nonketoacidotic hyperglycemia were studied. In the ketoacidotic group the initial values of blood glucose, pH, and base excess were 808 +/- 353 mg/dl, 7.06 +/- 0.1, and -22.8 +/- 5.9 mmol/L, respectively. The mean initial values of blood glucose and osmolality of the three patients with nonketoacidotic hyperglycemia were 731 +/- 127 mg/dl and 355 +/- 49 mosmol/kg, respectively. Within 24 h insulin therapy led to continuous improvement in blood glucose to 187 +/- 90 (ketoacidotic patients) and 172 +/- 28 mg/dl (nonketoacidotic group) and normalization of pH, base excess, and osmolality. The mean insulin requirement was 84 +/- 45 U/24 h in ketoacidotic and 86 +/- 18 U/24 h in nonketoacidotic patients, respectively. The comparison groups receiving pork insulin did not differ significantly in either clinical or initial and subsequent biochemical data or in insulin requirement.

Binding of biosynthetic human insulin to erythrocytes of normal and insulin-dependent diabetic subjects: comparison with pork and human pancreatic insulin.

Biosynthetic human insulin (BHI) was compared with highly purified human pancreatic and pork insulin with regard to its ability to bind to erythrocytes of normal and insulin-dependent diabetic subjects (type I diabetes). The binding affinity or capacity of erythrocyte from both normal and diabetic subjects were comparable for biosynthetic and pancreatic human insulin. In contrast, binding of pork insulin to erythrocytes was significantly decreased at low insulin concentrations in normal as well as in diabetic subjects due to a reduced receptor affinity. The affinity of the "empty sites" was 5.25 x 10(-8) M-1 with pork insulin in normal subjects and 6.1 x 10(-8) M-1 in diabetic subjects; with both human insulins, the affinities were 6.9 x 10(-8) M-1 in normal subjects and 8.6 x 10(-8) M-1 in diabetic subjects. The number of insulin receptors per erythrocyte was calculated as being 30 in normal subjects and 35 in diabetic patients.

Treatment with human insulin (recombinant DNA) in diabetic subjects pretreated with pork or beef insulin: first results of a multicenter study.

In two double-blind studies 66 insulin-dependent diabetic subjects pretreated with pork insulin were changed to human insulin (recombinant DNA) or a purified pork insulin preparation (regular and NPH insulin). Sixty-five patients previously pretreated with beef insulin were transferred, in a randomized, double-blind fashion, to human insulin and purified beef insulin of the same preparations (regular and NPH insulin). Patients' metabolic control, as demonstrated by fasting and 1-h postprandial blood glucose, HbA1c, and daily insulin dosage, over 4 mo was unchanged in our four groups compared with the values before changing insulin preparation. No severe hypoglycemic attacks or skin reactions were reported.

Ciglitazone reverses cAMP-induced post-insulin receptor resistance in rat adipocytes in vitro.

Ciglitazone (cig), a thiazolidine-dione, lowers glucose and insulin levels in animal models of diabetes type II but not in controls. Since catecholamines given to rat adipocytes in vitro induce insulin resistance similar to that seen in type II diabetes in vivo, we measured the effect of cig on mono-A14-[125I]insulin binding and 3-O-methyl-D-glucose transport (GT) in isolated rat adipocytes treated with isoprenaline (iso, 10 microM). Cig (less than or equal to 5 microM) reversed (ED50 10 nM) the inhibitory effect of iso on insulin stimulation of GT. It had no effect on either basal or insulin stimulated GT. Furthermore, cig did not influence insulin binding either in the presence or absence of iso, which indicates that cig acts only on a post-insulin receptor level. Cig also reversed the inhibition of GT by both forskolin, a cyclase activator and RO20-1724, an imidazolidine phosphodiesterase inhibitor but not that of db-cAMP. It thus seems that cig does not act within the cAMP system but only neutralizes its inhibitory effect on the insulin stimulation of GT.

Protein kinase activity of the insulin receptor from muscle.

The insulin receptor is associated with a protein kinase activity. This has been shown for the receptor of liver, fat, and some other tissues which are not primary targets of insulin action. Here kinase activity is demonstrated for the insulin receptor of rat skeletal and cardiac muscle with similar characteristics. Insulin (10(-7) mol/l) stimulates phosphorylation of the 95-kDa receptor subunit 3- to 18-fold. The effect is detectable at 10(-10) mol/l insulin; the ED50 is approx. 3 X 10(-9) mol/l. The kinase phosphorylates exogenous substrate as well, and it is recovered after immunoprecipitation of the receptor with antireceptor antibody suggesting that kinase activity is intrinsic to the muscle receptor.

ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.

PURPOSE: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. PATIENTS AND METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. RESULTS: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). CONCLUSION: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Strategy for the primary and secondary prevention of occupational diseases in the German Democratic Republic.

This review explains the German Democratic Republic's strategy for preventing occupational diseases, which is considered one of the primary purposes of public health. It is a complex challenge that is being tackled through close cooperation between enterprise-linked occupational health services, the inspectorates of industrial hygiene, public health centers, and trade unions. In primary prevention, planning is based on results obtained in thorough analyses of all the relevant parameters, such as work conditions, industrial accidents, occupational diseases, morbidity records, and the quality of social services, and a complex work analysis has been developed to provide comprehensive and measurable information on health hazards due to harmful physical and chemical factors, dust, and job-related physical and neuropsychic stresses. Primary prevention is realized mainly through the elimination of health hazards and the improvement of work conditions, both based on a comprehensive framework of legislation. At the level of secondary prevention, company-linked occupational health services are a part of the national health services. A nationwide information system consists of compatible components for primary and secondary prevention, thus enabling control of exposure-effect relationships and the optimization of health policy.

The present status of rhinomanometry.

Rhinomanometry is today a routine method that may be used in private specialist practice, if X-Y recording is used. The results become clinical statements only when directly compared with mirror findings, i.e. by functional analysis of structure or when physiological variance is taken into account by reagibility tests. In those cases this elegant technique becomes indeed indispensable.

[Silicone impression procedure. Principles for determining ablation and healing parameters in vitro and in vivo]. / Silikonabgussverfahren. Grundlage zur Bestimmung von Ablations- und Heilungsparametern in vitro und in vivo.

Topometry and measurement of photoablation patterns are key questions for keratorefractive photoablation. So far, ablation rates have been determined either by tissue perforation or histological micrometry. A cast of irradiated cornea was made by using a 2-component silicon that polymerizes within minutes, thus preserving the corneal topography immediately after photoablation. The silicon surface is extremely smooth and the accuracy of the cast better than 1 micron. Reproducibility and long-term stability were proven for casts of photoablated PMMA. Thus ablation rates and profile, volumetry and topometry can be determined at any time. The method was applied for 193 nm excimer and 2.94 microns Er:YAG laser in vitro irradiation of the human cornea. Ablation rates in Bowman's layer and stroma were observed for various radiant energies and distinct pulse numbers. The average ablation rates are in agreement with published data. It could be demonstrated that there was an incubation effect for the first pulses. The method feasibility for in vivo measurement was also proven in an animal model. After excimer photoablation in rabbit eyes (beam diameter 3.5 mm, radiant energy 185 mJ/cm3, ablation rate 0.3 micron/pulse), wound healing was recorded: for the right eye silicon casts were molded at three different moments. For the left eye only photographs were taken. There was no difference in the time course of wound healing, so the silicon does not seem to interfere with repair mechanisms of the corneal epithelium. No side effects were observed.

A two-axis goniometer for low-temperature nuclear magnetic resonance measurements on single crystals.

We report on the construction of a two-axis goniometer intended for low-temperature, single-crystal nuclear magnetic resonance (NMR) measurements. With the use of home-made and commercially available parts, our simple probe-head design achieves good sensitivity, while maintaining a high angular precision and the ability to orient samples also when cooled to liquid helium temperatures. The probe with the goniometer is adapted to be inserted into a commercial (4)He-flow cryostat, which fits into a wide-bore superconducting solenoid magnet. Selected examples of NMR measurements illustrate the operation of the device.