[Show abstract][Hide abstract] ABSTRACT: Haemostasis is a complexly controlled process which takes place in two stages. The first initial stage leads to the formation of a small amount of thrombin. The crucial step of initiation is the bond between the activated factor VIIa and the tissue factor. It is regulated by interaction between factors promoting and inhibiting the process of thrombogenesis. The initiation of haemostasis must be associated with the formation of the thrombus and for effective fibrinogenesis the second stage, amplification of haemostasis, is necessary. A new two-stage model of coagulation imitates the process of haemostasis in vivo as the classical MacFarlan cascade model and makes it possible to explain the pathogenesis of prothrombotic conditions.
No preview · Article · Dec 1998 · Vnitr̆ní lékar̆ství
[Show abstract][Hide abstract] ABSTRACT: We examined 34 non-insulin-dependent diabetes mellitus (NIDDM) patients treated with sulfonylurea regimens, 24 NIDDM patients with 2-3 months long- acting insulin treatment and 19 age-matched normoinsulinemic healthy controls. NIDDM patients were divided into two subgroups, with and without endothelial dysfunction according to von Willebrand factor level 0.14 IU/mL. There were significant differences in PAI-1 levels among patients without endothelial dysfunction treated by sulfonylurea agents (median 48.1, range 14-108 ng/mL) or insulin (27.9, 2-53 ng/mL) and patients with endothelial dysfunction treated by sulfonylurea regimens (80.7, 43-217 ng/mL) or insulin, respectively, (16.7, 7-34 ng/mL) (analysis of variance p < .001). NIDDM subgroups were not different in metabolic parameters (C-peptide and triglyceride levels, body mass index) and platelet activation marker (platelet factor 4 values). von Willebrand Factor and thrombomodulin levels were elevated in groups with endothelial dysfunction (analysis of variance p < .001, p = .025, respectively). Insulin treatment was accompanied by decreased PAI-1 levels especially in patients with endothelial dysfunction. Insulin is the inhibitor of endothelial PAI-1 production induced by cytokines. Therefore, we suggest that long-term insulin application may decrease PAI-1 levels by direct inhibitive action on the endothelial PAI-1 compartment. This hypothesis requires further research.
No preview · Article · Oct 1998 · Clinical and Applied Thrombosis/Hemostasis
[Show abstract][Hide abstract] ABSTRACT: To assess the prevalence of markers of autoimmune destruction of pancreatic beta-cells in patients with non-insulin dependent diabetes mellitus (NIDDM).
127 hospitalized NIDDM patients subdivided to the following subgroups: non-obese with C-peptide < 0.3 nmol/l (NIDDM-(-)), non-obese with C-peptide > 0.3 nmol/l (NIDDM-(+)), obese with C-peptide < 0.3 nmol/l (NIDDM+(-)) and obese with C-peptide > 0.3 nmol/l (NIDDM2+). METHODS AND MEASURED PARAMETERS: Age, BMI, C-peptide, autoantibodies to glutamic acid decarboxylase (antiGAD-Ab), autoantibodies to islet cells (ICA), markers of specific cellular immunity CD4, CD8, CD19, CD4/CD8, CD4/CD45/RA+, CD4/CD45/RA-, NK (CD16+56), CD3/HLADR, organ specific/non-specific autoantibodies.
AntiGAD-Ab were positive in 5/15 (33.3%) NIDDM-(-), 1/32 (3.1%) NIDDM-(+), 2/9 (22.2%) NIDDM+(-) and in 3/71 (4.2%) NIDDM2+. The positivity of antiGAD-Ab in NIDDM-(-) and NIDDM+(-) was significantly higher (p < 0.05) than in NIDDM-(+) and NIDDM2+.
Some patients with manifestation of diabetes in older age initially classified and treated as having NIDDM may have in fact slowly evolving autoimmune insulin-dependent diabetes mellitus (LADA). These patients can be identified by measurement of antiGAD-Ab or other markers (ICA, IA-2) of autoimmune destruction of pancreatic beta-cells (AID). Moreover, in some patients both AID and insulin resistance may coexist in parallel.
No preview · Article · Feb 1998 · Vnitr̆ní lékar̆ství
[Show abstract][Hide abstract] ABSTRACT: The authors examined 25 patients with diabetes mellitus type 2 (NIDDM) without vascular complications, treated by sulphonyl urea preparations, 12 hyperinsulinaemic (HI) non-diabetic subjects and 11 normoinsulinaemic healthy subject s. Patients with NIDDM and HI non-diabetics had significantly elevated PAI-1 levels which correlated with the C-peptide level (r = 0.519, p < 0.001), triacylglycerols (TG) (r = 0.685, p < 0.001), BMI (r = 0.607, p < 0.001) and levels of endothelial markers such as von Willebrand s factor and thrombomodulin (TM). In the group of patients with NIDDM no relationship of PAI-1 and C-peptide was found and a significant correlation was found with TM levels (r = 0.609, p = 0.001) and TG levels (r = 0.476, p = 0.046). The results suggest that the endothelial department has an effect on the regulation of PAI-1 levels in patients with NIDDM.
No preview · Article · Nov 1997 · Vnitr̆ní lékar̆ství
[Show abstract][Hide abstract] ABSTRACT: Digoxin-like immunoactivity (DLIA) reflects the presence of endogenous substances which are close to cardiac glycosides. These substances via inhibition of Na(+)-K(+)-ATPase increase intracellular calcium stores (Ca2+i) and may modulate various Ca(2+)-dependent mechanisms. Although DLIA are known primarily as hypertension and natriuresis promoting factors, several recent works have suggested that DLIA relates also to diabetes mellitus. The main stimulus for DLIA secretion represents volume-expansion.
To assess relation of DLIA to glucose tolerance and insulin levels in pregnant women (PW).
1) 67 PW (DLIA measured by RIA-kit HUMA-LAB Kosice), 2) 53 PW (DLIA measured by RIA-kit ORION). PW were subdivided according to the glucose tolerance and insulin concentrations.
1. DLIA in hyperinsulinemic PW were significantly higher than in those with normal insulin levels. 2. DLIA significantly correlated with insulin levels as well as with insulinogenic index. 3. The increase in plasma glucose and insulinemia during OGTT was accompanied by a decrease in DLIA. These findings were independent of other measured parameters (age, body mass index, pregnancy induced weight gain, blood pressure and steroid hormones).
These findings suggest that DLIA does not respond only to changes regarding sodium-retention and volume-expansion, but also to changes in glucose and insulin metabolism. Thus, DLIA could represent one of the markers of "specific" neurohumoral activation. However, the question of whether an elevation in DLIA may consequently modulate mechanisms of insulin secretion, insulin sensitivity, vascular reactivity and other Ca2+i-dependent mechanisms remains speculative. (Tab. 4, Fig. 4, Ref. 41).
No preview · Article · Nov 1997 · Bratislavske lekarske listy