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Biomedical subjects

T Koschinsky

Publications and source records attributed to T Koschinsky.

At least 37 records · Page 2Linked to original sources
PubMed1985

Sera from type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells.

Diabetic angiopathy may be due, in part, to increased growth in vascular cells. We have investigated serum growth factors in Type 2 (non-insulin-dependent) diabetic and healthy subjects and their effect on cultured human arterial smooth muscle cells and fibroblasts. Removal of the dialyzable serum fraction (mol. wt. less than 12,000) reduced the growth effect of the diabetic sera by 37% (2p less than 0.005) and of the non-diabetic sera by only 8% (2p less than 0.01). In contrast, there was no difference in growth stimulation between the dialyzed diabetic or non-diabetic sera. Complete recovery of the dialyzable serum growth fraction was also obtained at a mol. wt. below 3,500. Ten times the concentration of the low molecular weight growth factor (mol. wt. less than 3,500) from diabetic sera stimulated growth of fibroblasts or arterial smooth muscle cells by a mean of 243% or 174% and from non-diabetic sera by a mean of 146% or 137%, respectively (2p less than 0.01). The growth stimulating potency of this serum fraction (mol. wt. less than 3,500) contained in 10% diabetic sera, was two to ten times higher than that of human growth hormone or insulin, added in amounts equivalent to 10% or physiological serum concentrations. This diabetic serum growth factor was further characterized by: (1) linear dependence of growth stimulation over a concentration range of twenty times and by (2) reduction of the growth stimulating activity to control levels by pretreatment: (a) at 95 degrees C for 30 min, or (b) with two different proteases: Serva pronase E (Streptomyceus griseus) or Calbiochem protease (Subtilisin calsberg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Vascular growth factors and the development of macrovascular disease in diabetes mellitus.

There are two different classes of humoral growth factors for arterial smooth muscle and endothelial cells that age of potential relevance for the development of macrovascular disease inn diabetes mellitus: hormones (growth hormone, insulin like growth factor I and II, insulin) and locally released growth factors of platelet origin. The following hormones have to be considered: Increased growth hormone plasma levels might contribute to macrovascular disease, but its actual relevance remains to be determined. Insulin like growth factor I and II are present in vivo and stimulate growth of vascular cells in vitro but their relevance for macrovascular disease in diabetes is unproven. To insulin, see Dr. Stout's paper. Human platelets contain at least six growth peptides or proteins that all stimulate in vitro growth of arterial wall cells: platelet derived growth factor, epidermal growth factor, platelet derived endothelial cell mitogen, endothelial growth factor, diabetic serum growth factor (DSGF), transforming growth factor-beta. As their plasma concentrations have not been shown to be increased in diabetes increased local availability at sites of stimulated platelet aggregation has been postulated. Therefore, their relevance for macrovascular disease i diabetics is based mainly on circumstantial evidence. The concentration of DSGF of platelet origin depends on the metabolic control: it increases in vivo in poorly controlled diabetics and is normalized after 2-3 weeks of good metabolic control in the same diabetic patient. The growth potency of DSGF from poorly controlled diabetics is greater than that of physiological amounts of insulin or growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1984

[Reflolux--a new test system for the self control of blood glucose for diabetics].

Correctness and accuracy of Reflolux, a new microprocessor-controlled minireflectometer for measuring blood-glucose concentrations, were tested in ten instruments. There was good agreement between the Reflolux values and those obtained in the laboratory with the hexokinase method, over the entire range of 40-350 mg/dl with a relatively small margin of error. Thus the Reflolux provides even in the hypoglycaemic range values accurate enough for everyday use by a diabetic. An important advantage of this test system lies in the use of Haemo-Glukotest 20-800 test strips which, in conjunction with the Reflolux, provide a visual color comparison for blood-glucose levels in the range of 20-800 mg/dl.

Blood Glucose↗
PubMed1984

[Improved metabolic state in insulin-tested diabetes. Self-testing of blood or urine glucose on 2 days per week].

Randomized serial tests of their metabolic state over four weeks, without self-testing and during daily urinary glucose-profile testing (4 tests) with the Diabur-Test or blood-glucose levels with the Haemo-Gluco-test 20-800 (5 tests daily) on two days weekly were undertaken on 27 unselected insulin-treated outpatient diabetes. HbA1, blood glucose, serum cholesterol, triglycerides and VLDL, LDL and HDL cholesterol were the target values. The following metabolic values were significantly reduced (P less than 0.05) during blood-glucose self-testing, compared with the results during the non-testing phase: HbA1 on average by 11%, blood-glucose (starving) by 20%, serum cholesterol by 9%, serum triglycerides by 13%. Self-testing of urinary glucose (compared with the test-free phase) brought little improvement in the metabolic state. The results of self-testing were the more impressive the worse the metabolic state during the phase without self-testing. Except for VLDL and HDL cholesterol, changes in HbA1 correlated well during all phases with changes in the other metabolic values (P less than 0.05).

Adolescent↗
PubMed1984

[New instrument for blood glucose determination. Results of a clinical trial of the Reflocheck].

Reflocheck, a new microprocessor-regulated apparatus determining blood sugar levels was tested in six laboratories. In the range of 20-450 mg/dl the apparatus gave precise results (co-efficient of variance 0.8%-6.4%), in good agreement with results by the hexokinase method. Reflocheck is an accurate and reliable instrument for the measuring of blood glucose levels.

Blood Chemical Analysis↗
PubMed1984

[Inborn and acquired metabolic disorders in human vascular cells in diabetes mellitus and hyperlipoproteinemia].

Fibroblast growth from diabetics with poor metabolic control is increased in vitro by 15-92% as compared to healthy age matched controls. In contrast, fibroblast growth from patients with different types of familial hyperlipoproteinemia is decreased by 9-83%. In these fibroblasts the activity of lysosomal cathepsin D, the key enzyme for LDL-apo B degradation, was decreased by 12-31% too. These cell associated alterations could be related to different stages of premature aging. Serum from type II diabetics with poor metabolic control (DS) and from hypercholesterolemics (HS) stimulated growth of human arterial smooth muscle cells and fibroblasts in vitro by 6-64% as compared to serum from healthy controls or to serum from diabetics with good metabolic control. DS increased in these vascular cells LDL- and HDL-binding up to 260%, but decreased LDL-apo B degradation by cathepsin D by 16-39% similar to HS that decreased it by 29-42%. These serum effects depend on the metabolic control and could stimulate the cell turnover. This growth effect of DS is mainly related to at least two new peptides of very low molecular weight (less than 2000 daltons), which might easily penetrate the arterial wall and could contribute to the increased angiopathic risk in diabetes.

Diabetes Mellitus↗
PubMed1982

[Small reflectometers, independent of the electric current, for home blood glucose monitoring. Testing for correctness and precision].

Thirty small reflectometers not requiring mains electricity (23 Glucosemeter and 7 individual appliances of various makes) were tested under standardised laboratory conditions as to their relative and absolute accuracy in the measurement of blood glucose. The hexokinase method delivered the reference values. The investigation demonstrated systematic deviations of 1 to 97%, coincidental deviations of 8 to 24% and total deviations of between 25 and 153%. If one accepts a value of up to 50% for the total deviation only 13 out of 30 reflectometers are acceptable. The results show that each individual meter must be assessed by the doctor before it can be given to the patient for glucose monitoring at home.

Blood Chemical Analysis↗
PubMed1982

Effect of neomycin sulphate alone and in combination with D-thyroxine on serum lipoproteins in hypercholesterolaemic subjects.

Treatment with neomycin sulphate 1.5 g/d for 8 weeks significantly lowered total serum cholesterol by an average of 19% in 15 out of 19 patients with primary hypercholesterolaemia and LDL-cholesterol by 21%, without significantly changing the corresponding triglyceride and HDL-cholesterol concentrations. Combined treatment with neomycin sulphate 1.5 g/d and d-thyroxine 6 mg/d for 8 weeks lowered total serum cholesterol in the same patients by an average of 30%, LDL-cholesterol by 27% and serum triglycerides by 18%, without significantly changing the HDL-cholesterol concentration. Continued treatment for 10 patients with neomycin sulphate 1.5 g/d for up to 13 months did not further change the reduced serum cholesterol level. 10 of 19 patients complained of side effects after 4-8 weeks of treatment with neomycin: 8 of recurrent diarrhoea, abdominal pain or poor appetite, and 4 of acute attacks of vertigo with nystagmus. All side effects were reversed a few days after stopping the neomycin treatment. No additional serious side effects due to d-thyroxine were observed. These serious side effects of neomycin sulphate limit its use to selected high risk patients with hypercholesterolaemia, who have failed to respond successfully to other LDL-cholesterol-lowering drugs. They stress the necessity for frequent monitoring for the side effects described.

Adult↗
PubMed1982

Studies on inherited and acquired metabolic disorders in cultured arterial smooth muscle cells and fibroblasts.

Cultured mesenchymal cells from insulin- and non-insulin-dependent diabetics with poor long-term control showed an increased growth rate as compared to age matched normal cells independent of the serum type used. These growth changes occurred independent of the genetic background as mesenchymal cells, (a) from four pancreatectomized diabetics with poor long-term metabolic control showed similar increased growth rates and (b) from two diabetics with good metabolic long-term control showed no growth changes as compared to age matched controls. There is no evidence (a) for the specific impact of obesity on these cell associated growth changes, and (b) for cell associated differences between cultured mesenchymal cells from diabetics and normal controls as far as protein and lipoprotein metabolism are concerned. The metabolic control of diabetes is of primary importance for the regulation of growth, protein synthesis and for lipoprotein binding and degradation in cultured mesenchymal cells independent of their origin, as serum from diabetics with poor metabolic control increased in these cells growth, protein synthesis and lipoprotein metabolism. Serum from well controlled diabetics did not differ from normal serum in its growth stimulating effects. As far as obesity could effect the metabolic control of diabetes, probably this could also affect indirectly the metabolism of mesenchymal cells. The interaction of cell associated and serum factors can further increase the observed growth and metabolic changes of mesenchymal cells. As far as these cell and serum related changes also occur in vivo they could contribute to the accelerated atherogenic development in diabetics as well as to an increased basal lamina layering in different tissues.

Adolescent↗
PubMed1981

Regulation of diabetic serum growth factors for human vascular cells by the metabolic control of diabetes mellitus.

Serum factors from non-ketotic poorly controlled non-insulin-dependent diabetic patients stimulated growth and protein synthesis of human arterial smooth muscle cells and fibroblasts by 15-42%, compared to serum factors from well controlled diabetics. In contrast, the growth stimulating effect of pooled sera from well controlled diabetics did not differ from the effect of normal sera. Single sera from the same diabetics before and after improvement of the metabolic control stimulated cell growth to a similar degree as the respective pooled sera from different diabetic populations. As far as increased growth stimulation of vascular cells is related to increased angiopathic risk in diabetics, this metabolic regulation of growth factors supports the demand for a continuous optimal control of diabetic metabolism.

Cells, Cultured↗
PubMed1980

Increased growth stimulation of fibroblasts from diabetics by diabetic serum factors of low molecular weight.

Serum factors from non-ketotic poorly controlled diabetic patients when compared to serum factors from normal subjects, stimulate growth and protein synthesis of cultured fibroblasts from diabetic patients by 25-50%. This increased growth stimulating effect of diabetic serum is mainly related to low molecular weight components (mol. wt. < 12,000 daltons), but not to insulin or glucose. These low molecular weight components of diabetic serum are effective only in combination with serum factors of a molecular weight > 12,000 daltons which are essential for initiation and continuous stimulation of cellular growth. As the growth stimulation by diabetic serum factors with a molecular weight < 12,000 daltons does not differ from comparable normal serum factors, the relevance of these serum factors (e.g. growth hormone, lipoproteins) for the increased growth stimulation of mesenchymal cells in diabetes mellitus seems to be only of limited importance. In as much as these in vitro results represent the in vivo situation, chronic exposure of vascular cells from diabetics to these serum factors could be related to the increased angiopathic risk in diabetes mellitus.

Cell Division↗
PubMed1979

Increased growth of human fibroblasts and arterial smooth muscle cells from diabetic patients related to diabetic serum factors and cell origin.

Fibroblasts from 3 diabetic patients (DF) grew faster, resulting in higher cell counts in the stationary phase than fibroblasts from 3 age-matched healthy volunteers (NF). This difference was apparent when DF or NF were cultured in either diabetic (DS) or normal serum (NS). Diabetic serum increased growth of both DF and NF compared with normal serum. Total protein content per plate paralleled the increase of cell number per plate in relation to cell origin and serum type. DS increased growth and total protein per plate in the arterial smooth muscle cell line from a non-diabetic patient in a way similar to in DF and NF. It is concluded that increased growth of DF in vivo could result in an increased turnover of vascular cells with a shortened replicative lifespan, leading to an accumulation of basal lamina. This effect would be even further accentuated by exposure of DF to DS. Taken together with the increased protein synthesis the accelerated development of diabetic angiopathy could be the final consequence.

Adolescent↗
PubMed1977

[Treatment of primary hyperlipoproteinemia type IIb and IV. Comparison of the lipid lowering effect of phenformin, clofibrate, and a combination of both (author's transl)].

22 outpatients with primary hyperlipoproteinemia type IIb and IV were treated in periods of eight weeks as follows: placebo; 0,15 g phenformin/day; 0,15 g phenformin + 1,5 g clofibrate/day; 1,5 g clofibrate/day; placebo. Compared to the first placeboperiode the serumtriglycerides were significantly lowered by phenformin (about 26%), by the combined treatment with phenformin + clofibrate (60%) and by clofibrate (51%) after eight weeks of treatment. The serumcholesterol was significantly lowered by phenformin (10%) and by the combined treatment with phenformin and clofibrate (14%), but not significantly by clofibrate (8%). After eight weeks of treatment with phenformin alone or in combination with clofibrate the body weight decreased significantly (1,9% or 1,4%). These changes in body weight were not related to changes in blood lipids. In conclusion, the combined treatment with 0,15 g clofibrate/day was more effective in lowering increased serum lipids than the treatment with phenformin or clofibrate alone.

Adult↗