Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cross-sectional studies elevations in growth hormone (GH), factor VIII related antigen (VIIIR:Ag), and plasminogen activator activity (PAA) have been connected with diabetic retinopathy. To evaluate the importance of these factors for the development of retinopathy, we have carried out a prospective study. In a primary study GH, VIIIR:Ag, and PAA were evaluated during a 25 min exercise test in 22 insulin dependent diabetes mellitus (IDDM) patients. After 5-7 years, the patients were re-evaluated and the presence of retinopathy in the follow-up study was correlated to the findings in the primary study. Patients with retinopathy in the primary or the second study (n = 14) showed a significant increase in GH (p less than 0.05) during the first 5 min of exercise compared with patients without retinopathy. Moreover, the 14 retinopathy patients showed further significant elevations in GH (p less than 0.001), VIIIR:Ag (p less than 0.01) and PAA (p less than 0.001) during the remaining 20 min of exercise. In contrast, patients without retinopathy (n = 8) in the follow-up study, did not show significant elevations in GH, VIIIR:Ag, and PAA during exercise. A lack of rise in GH, VIIIR:Ag, and PAA during exercise seems to indicate a resistance to retinopathy in IDDM patients.
Diabetes Res 1988 Jan
PMID:Absent elevations in growth hormone, factor VIII related antigen, and plasminogen activator activity during exercise in diabetic patients resistant to retinopathy. 313 76

The fibrinolytic response to venous occlusion was assessed in 29 women with normal or complicated pregnancy, by measurements of total t-PA and free t-PA with specific ELISAs. The release of t-PA from the vessel wall was 11 +/- 9 ng/ml in non-pregnant women (mean +/- SD, n = 6) but was markedly reduced throughout pregnancy. Following venous occlusion, free t-PA increased by 12 +/- 11 ng/ml in non-pregnant women but remained below the detection limit of 2 ng/ml towards the end of pregnancy. A markedly reduced t-PA release with absence of free t-PA was also observed during late pregnancy in patients with insulin-dependent diabetes mellitus, intra-uterine growth retardation and pre-eclampsia. Plasma levels of fragment D-dimer of cross-linked fibrin were measured with a specific ELISA in 79 pregnant women. D-dimer levels were 129 +/- 36 ng/ml (mean +/- SD, n = 8) in non-pregnant women and increased to 400 +/- 170 ng/ml (n = 25) and 440 +/- 220 ng/ml (n = 22) during the second and third trimester of pregnancy respectively. Significantly higher levels than observed in uncomplicated third trimester pregnancies were found in 3 out of 6 diabetic and in 2 out of 7 pre-eclamptic women. It is concluded that the t-PA release after venous occlusion is significantly reduced during pregnancy. In addition, released t-PA is rapidly inhibited. The levels of fragment D-dimer increase during pregnancy, suggesting that, notwithstanding the marked impairment of the fibrinolytic response to venous occlusion, the fibrinolytic system remains functionally active.
...
PMID:Fibrinolytic response to venous occlusion and fibrin fragment D-dimer levels in normal and complicated pregnancy. 344 23

Hypernatraemic states are associated with an increased risk of thrombosis. To examine the relative contributions of sodium and vasopressin, we infused hypertonic saline in 11 male volunteers and measured the effect on factor VIII (FVIII), euglobulin clot lysis time (ELT) and fibrinopeptide A (FPA) generation. Samples were taken pre-infusion, hourly during a 3h infusion of 450 ml 6M saline and one hour after the infusion had stopped. Mean plasma osmolality (SEM) rose from 287(0.7) to 302(10) mOsm after 3h (p less than 0.01). Plasma vasopressin concentrations rose from 1.0(0.3) to 4(0.94) pg/ml over 3 hr (p 0.01). Plasminogen activator activity (10(6)/ELT2) rose from 65(10) to 372(55) units (p less than 0.001). There was a highly significant correlation between plasma osmolality and plasminogen activator activity (r = 0.5 p less than 0.0001). FPA generation time shortened from 7.2(0.4) to 5.4(0.6) min after 2h and 5.3(0.6) after 4h (n = 6). Values for FPA after 4 min incubation steadily increased from 5.8(1.2) to 14.3(4.6) pmol/ml during the infusion but differences failed to achieve statistical significance. FVIIIC (1 stage) remained constant at 75(5.5%) during the infusion. There was a small and statistically insignificant increase in FVIII RiCof after 3h and FVIII RAg decreased slightly. The results suggest that hypernatraemia and increasing plasma aVP concentrations produce changes in haemostatic function consistent with a hypercoaguable state. The mechanisms for the effect are unclear. These changes in haemostatic function might contribute to the thrombo-embolic complications of conditions such as hyperosmolar coma in diabetes mellitus or severe heatstroke in which degrees of hypernatraemia occur.
...
PMID:Does hypernatraemia promote thrombosis? 393 26

In order to compare the metabolic and hemobiological properties of two sulfonylureas, thirty-five non-insulin-dependent diabetics were randomly assigned to two groups. Each group was given either gliclazide (n = 20) or glibenclamide (n = 15) for six months. Metabolic control was improved in both groups, as evidenced by the decrease in HbA1 concentrations. A significant fall in ADP (1 and 4 microM)--induced platelet aggregation was recorded in the gliclazide group, while antithrombin III levels remained normal throughout the trial and plasminogen activator levels increased. These hemobiologic changes may be effective in preventing the vascular complications of diabetes. In contrast, glibenclamide did not alter platelet aggregation. Furthermore, a significant decrease in both antithrombin III levels and basal and venostasis-stimulated plasminogen activator levels were seen in glibenclamide patients. The beneficial changes in hemostasis seen in gliclazide patients probably result from a direct effect of the drug since hemobiological parameters and metabolic control parameters were not correlated.
...
PMID:[Effects of gliclazide and glibenclamide on platelet function, fibrinolysis and metabolic control in diabetic patients with retinopathy (author's transl)]. 628 3

Changes in plasma growth hormone (GH), factor VIII related antigen (VIIIR:Ag), and plasminogen activator activity (PAA) during exercise were evaluated in 50 insulin-dependent diabetics. In patients with a short to moderately long duration of diabetes (5-19 years, mean 11), GH increased only in those with retinopathy. VIIIR:Ag and PAA increased most pronouncedly in retinopathy patients as well. In diabetics with long duration of the disease (21-49 years, mean 35), GH, VIIIR:Ag and PAA increased almost equally in those with and without retinopathy.
...
PMID:Growth hormone and endothelial function during exercise in diabetics with and without retinopathy. 642 Oct 91

The components of the fibrinolytic system were studied in patients with maturity onset diabetes, treated with chlorpropamide for three years or more. Half of the patients (7/15) were shown to have abnormally low plasminogen activator activity of the vascular walls. The patients were then shifted to gliclazide, a new sulfonylurea, and after six months all patients had a normal vascular plasminogen activator activity. At follow up after 24 and 48 months the results remained the same. The normalization of the vascular fibrinolytic defence system could not be explained by improvement of glucose control.
...
PMID:Effect of chlorpropamide and gliclazide on plasminogen activator activity in vascular walls in patients with maturity onset diabetes. 643 3

In diabetes mellitus the vascular endothelium often produces and releases abnormally low amounts of plasminogen activator, leading to an impaired fibrinolytic system, which might be of importance for the development of angiopathy. In this study tests of autonomic neuropathy (AN) were performed on diabetics without autonomic symptoms. It was discovered that diabetics without AN had a significantly lower mean fibrinolytic response to stimulation than nondiabetic controls, whereas this reduction was not found in those with AN. The suggestion that asymptomatic AN might induce a normalization of the impaired fibrinolytic system in diabetes, and thus have a modifying effect on the rate of development of angiopathy, requires further study to be properly evaluated.
Diabetes 1983 May
PMID:Fibrinolytic activity, autonomic neuropathy, and circulation in diabetes mellitus. 660 36

Biopsy specimens were obtained from 138 arteries and concomitant veins in different anatomic regions of both healthy subjects and patients undergoing surgery of various kinds. A fibrin slide technique was used to determine plasminogen activator (PA) activity, no significant difference being found between activity in arteries and that in veins, other than in epigastric veins where it was significantly greater. Arterial PA activity was similar in both healthy and uraemic subjects, and was unaffected by uraemia due to diabetes or other renal disorder, and by such factors as age and sex. Correlation between arterial activity and that in concomitant veins was found for all the anatomic regions studied.
...
PMID:Comparison of plasminogen activator activity in human arteries and veins. 668 29

A low plasminogen activator response to venous occlusion is frequently found in diabetes. The aims of this investigation were to study any relationships between plasminogen activator activity and autonomic neuropathy (AN), and between abnormal toe temperature reactions and AN. Asymptomatic AN is frequently found in insulin dependent diabetics. The results might be an abnormal balance between the parasympathetic and sympathetic innervation of the vessels, which in turn will lead to a change of the reaction to cooling of the feet followed by indirect heating. In this study 52 insulin dependent diabetics were examined with a combination of tests for AN and blood flow measurements as well as plasminogen activator activities of the blood and vascular walls. In patients with a short duration of diabetes (mean 11 years) the prevalence of AN was high in those with abnormally slow increase in toe temperature after cooling followed by indirect heating. The mechanism behind appeared to be a functional vasospasm. In diabetics of short as well as of long duration (mean 35 years), an abnormally low plasminogen activator activity of the blood during venous occlusion was found in those without AN, while those with AN showed a normal activity. Thus, AN might influence the deterioration of the circulation in diabetes.
...
PMID:Endothelial factors, toe temperature and leg circulation in diabetics with and without autonomic neuropathy. 681 Apr 94

Among endothelial secretogogues prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B2 kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI2 is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI2, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI2 analogues, whereas exogenous PGI2 or TXA2 synthase inhibitors (i.e. following increase in endogenous PGI2) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI2, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.
...
PMID:Interactions between endothelial secretogogues. 754 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>