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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is associated with a hypercoagulable state. Eighty percent of patients with diabetes mellitus die due to various thrombotic vascular complications. Disorder of coagulation and fibrynolysis is associated with diabetic retinopathy and nephropathy. Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells. Various serine proteases play important role in this process. The homeostatic system is also the source of endogenous inhibitors of angiogenesis. Human serum contains various factors able to induce or suppress formation of new blood vessels. The aim of the present study was to evaluate the activity of some angiogenesis inhibitors, anti-proteases, anti-thrombin III, a1 anti-trypsin and a2 anti-plasmin in sera of patients with diabetes mellitus type 1 and 2 and non-proliferative retinopathy, and to correlate this activity to total angiogenic potential of these sera, measured by mice cutaneous test. Sera of 22 persons with DM1, aged 33-70 years, 35 persons with DM2, aged 37-79 years, and 51 healthy people, aged 22-80 years (as control group) were studied. Direct serum-induced cutaneous angiogenesis test in mice (SIA) was applied. Berichrom (ade Behring) tests and immunoturbidimetric method were used for evaluation of anti-proteases activity. Angiogenic activity of DM1 patients sera was statistically lower than this parameter in DM2 patients and in control group. Levels of anti-proteases were similar in DM1, DM2 and control group, with one exception: anti-thrombin level was lower in DM2 patients' sera than this in the control group. Analysis of correlation revealed important difference in behaviour of DM1 sera, as compared to other groups. Significant negative correlation was observed between angiogenic activity and anti-thrombin, as well as anti-trypsin level of DM1 patients' sera. On the other hand, correlation analysis performed for the sera of control group revealed significant positive correlation between their angiogenic activity and anti-thrombin level. No other correlations were found.
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PMID:[Proteinases inhibitors in sera of diabetic patients with non-proliferative retinopathy]. 1563 23

Tissue plasminogen activator (tPA) is the predominant plasminogen activator present in the vascular and nervous systems. Prior studies of the two have emphasized different tPA sources; respectively, endothelium and neurons. A closer relationship is now suggested by evidence that the peripheral sympathetic nervous system synthesizes and infuses enzymatically active tPA into small artery walls and the microcirculation. TPA may thus be the only known neural product able to effect degradation of the artery wall extracellular matrix. This brief review considers historical and current indications for the existence of such an autonomically controlled system and some physiologic implications. Immunohistochemical tPA expression in small arteries and arterioles is more prominent in the outer wall sympathetic axon plexus than in endothelium. Its presence in nerve filaments beneath the seldom-studied adventitia was obscured in earlier localizations. The systemic impact of a neural distribution is suggested by a 60% reduction of blood tPA activity after chemical sympathectomy. TPA-bearing axons extend outward from ganglion neuron cell bodies to reach even thin-walled vasa vasora and uveal microvessels. Ganglion cell bodies synthesize and package tPA in vesicles for the long axoplasmic transport. Densely innervated intact vessels release much greater amounts of tPA in vitro than do larger vessels, indicating a high neuron tPA production capacity and a large storage reservoir available within axon networks. The influence of an autonomically controlled plasmin production within small artery walls on regulation of blood pressure and capillary perfusion awaits further investigation. Its possible role in the pathogenesis of vessel wall matrix degradations in aging, hypertension, and diabetes may also merit further consideration.
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PMID:Distribution of sympathetic tissue plasminogen activator (tPA) to a distant microvasculature. 1567 11

The aim of the paper was to determine concentrations of plasmin-alpha2 antiplasmin complexes (PAP) and D-dimers in blood of patients suffering from acute coronary syndromes without ST segment elevation. 78 patients, including 37 females and 41 males, aged 41-79 years (mean age 63.2) were included in the study. Concentrations of PAP were determined by immmunoenzymatic method using Enzygnost PAP micro kit and concentrations of D-dimers using Dade Berling Enzygnost D-Dimer micro kit. Statistically significant, higher concentrations of PAP and D-dimers, indicating increased fibrinolytic activity of blood, were observed in patients with acute coronary syndrome than in the control group. Significantly higher concentrations of D-dimers were found in the group of patients above the age of 50, when compared with younger patients. Lower D-dimers levels were observed in smokers. Gender, coexisting hypercholesterolaemia, arterial hypertension and diabetes had no impact on concentrations of PAP and D-dimers in blood of patients suffering from acute coronary syndrome without ST segment elevation.
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PMID:[Fibrinolysis parameters: plasmin-alpha2 antiplasmin complexes (PAP) and D-dimers in acute coronary syndromes without ST segment elevation]. 1577 Nov 20

Aim our study is to compare the effects of repaglinide vs glimepiride administration on cardiovascular risk factors after meal test. Thus, after 2 weeks washout period, a 3-month randomised, cross-over parallel group trial of repaglinide (1 mg x 2/day) vs glimepiride (2 mg/day) in 14 patients with type 2 diabetes "naive" on diet treatment was made. Both treatments significantly declined plasma glucose, total-cholesterol, LDL-cholesterol, triglycerides, PAI-1, PAP levels and increased HDL-cholesterol. Lowering in plasma PAI-1 and PAP levels was significantly greater in repaglinide group. Furthermore, repaglinide administration resulted in a significant decrease in fasting plasma free fatty acids, fibrinogen, thrombin-antithrombin complex and reaction product of malondialdehyde with thiobarbituric acid (TBARS) levels, in absence of significant difference in fasting plasma insulin levels. Decrease in plasma TBARS levels correlated with the decrease in Plasminogen Activator Inhibitor-1 (r = 0.72; P < 0.003) and free fatty acids concentrations (r = 0.62; P < 0.01). Analysis of the insulin and glucose concentrations throughout the meal test revealed that AUC for glucose (758 +/- 19 vs 780 +/- 28 mg/Lxmin; P = 0.02) was significantly lower after repaglinide than glimepiride administration despite similar AUC for insulin (2327 +/- 269 vs 2148 +/- 292 mU/Lxmin; P = 0.105). At time 120' of meal test, repaglinide vs glimepiride administration was associated with a significant decline in plasma triglycerides, free fatty acids, fibrinogen, Plasminogen Activator Inhibitor-1, plasmin-alpha(2)-antiplasmin complex, thrombin-antithrombin complex, TBARS levels and increase in plasma HDL-cholesterol levels. In repaglinide group a negative correlation between insulin secretion during 1st phase of meal-test and plasma TBARS levels (r = -0.55; P < 0.03) at time 120' was found. Such correlation was lost after adjusting for changes in postprandial hyperglycaemia (r = -0.48; P < 0.09). In conclusion, our results support the hypothesis that repaglinide is more efficient than glimepiride on controlling for postprandial glucose excursion and may have beneficial effect on reducing cardiovascular risk factors.
Diabetes Metab 2005 Jun
PMID:Repaglinide has more beneficial effect on cardiovascular risk factors than glimepiride: data from meal-test study. 1614 16

Despite many years of study, clinical trials of new drugs to prevent thrombosis have often been disappointing. Part of the problem lies in our incomplete understanding of the regulation of plasminogen activation and/or inhibition in vivo. We have previously shown that in vitro nitration of plasminogen in plasma by peroxynitrite resulted in decreased plasmin activity. We hypothesized that macrophages may be agents of plasminogen nitration and designed this study to prove this hypothesis. We first better characterized our previous observations using purified plasminogen instead of whole plasma, studied the time and concentration dependence of these reactions, and co-incubated plasminogen with macrophages, as well as with non-inflammatory cells as controls, to assess nitration and impaired activity. When plasminogen (10 micromol/L) is incubated in the presence of SIN-1 (0.01-2 mmol/L), plasmin activity (generated by streptokinase) is reduced in a time- and concentration-dependent fashion. We performed experiments incubating human plasminogen in the presence of murine RAW264.7 macrophages, allowing for free diffusion of reactive oxygen species, while preventing the action of proteases. In this way we show that incubation of plasminogen with macrophages also decreases plasmin activity, while increasing nitration of the molecule, an effect that is already apparent after 2 h and reaches a plateau of 60% inhibition after 24 h of incubation. This effect appears specific for macrophages, since 31EG4 murine mammary cells used in parallel and under the same conditions failed to produce any deleterious changes in plasminogen. Our data on quick functional inactivation of plasminogen by nitration, mediated by macrophages, adds a new pathophysiological dimension to our previous work showing plasminogen as a target for peroxynitrite damage. Nitrosative stress may be implicated in impaired fibrinolysis. New therapeutic approaches for nitrosative stress in atherosclerosis and diabetes should limit the formation of superoxides and peroxynitrite.
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PMID:Nitration of human plasminogen by RAW 264.7 macrophages reduces streptokinase-induced plasmin activity. 1647 10

Given the increased prevalence of HIV infection in older individuals, we evaluated the adequacy of HIV-specific health maintenance, age-appropriate cancer screening, and diabetes management in an urban HIV clinic. We randomly selected 222 HIV-positive patients 40 years or older followed at the Johns Hopkins University Moore Clinic between 1999 and 2002. Demographic, clinical, and pharmaceutical data were abstracted from clinic charts. Outcomes of interest were vaccinations, annual rapid plasmin reagin (RPR) testing, and Papanicoloau smears and mammography in women. Logistic regression analyses were performed to identify variables significantly associated with being up to date on vaccinations. The sample was 56% female and 82% African American with a mean age of 50.9 years. Sixty-five percent used tobacco, 10% used alcohol, and 13% used illicit drugs daily. At the time of evaluation, 87% had received the pneumococcal vaccine. Of nonimmune patients, 66% were vaccinated for hepatitis B and 28% for hepatitis A. Eighty-two percent of women were referred for Papanicoloau smears and 56% for mammography. Only 59% completed the Papanicoloau smear, and 31% had mammography. Forty-two percent of patients with diabetes underwent quarterly foot examinations, and 33% had microalbuminuria screening. Risk factors for missed vaccinations include prior AIDS diagnosis (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.55, 3.13), CD4+ cell count less than 50 cells/mm(3) at the time of visit (OR 6.31, 95% CI 1.74, 22.9), and a history of chronic obstructive pulmonary disease (COPD) or asthma (OR 2.54, 95% CI 1.03, 6.28). In summary, HIV-positive patients are more likely to receive HIV-specific primary care interventions, especially vaccinations that can be given in clinic, than routine health maintenance screening that required referral and evaluation elsewhere. This suggests that if health maintenance screening can be delivered in the same clinic, usage rates are likely to increase.
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PMID:Provision of general and HIV-specific health maintenance in middle aged and older patients in an urban HIV clinic. 1670 6

Obesity is a common disorder and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Western-type societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems in the development of obesity. These studies support a role of both systems in adipogenesis and obesity; the role of specific members of these families, however, remains to be determined.
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PMID:Role of the fibrinolytic and matrix metalloproteinase systems in development of adipose tissue. 1717 99

Inflammatory processes, such as phagocytosis, coagulation, and vascular dilation, promote the release of serine proteases by neutrophils, macrophages, mast cells, lymphocytes, and the epithelial or endothelial cells. These proteases further facilitate the release of inflammatory cytokines and growth factors as well as take part in signal-cell proliferation through protease-activated receptors (PARs). Controlling the action of this cascade is necessary to prevent further damage to the normal tissues. One of the main anti-inflammatory response mediators is bikunin (Bik) that is responsible for inhibiting the activity of many serine proteases such as trypsin, thrombin, chymotrypsin, kallikrein, plasmin, elastase, cathepsin, Factors IXa, Xa, XIa, and XlIa. During the acute-phase response, Bik is released into plasma from proinhibitors primarily due to increased elastase activity. Bik is a glycoprotein, also referred to as urinary trypsin inhibitor, which in plasma inhibits the trypsin family of serine proteases by binding to either of the two Kunitz-binding domains. Bik also accumulates in urine. In conditions such as infection, cancer, tissue injury during surgery, kidney disease, vascular disease, coagulation, and diabetes, the concentrations of Bik in plasma and urine are increased. Several trypsin inhibitory assays for urine and immunoassays for both blood and urine have been described for measuring Bik. In addition to presenting the synthesis, structure, and pathophysiology of Bik, we will summarize various diagnostic approaches for measuring Bik. Analysis of Bik may provide a rapid approach in assessing various conditions involving the inflammatory processes.
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PMID:Bikunin (urinary trypsin inhibitor): structure, biological relevance, and measurement. 1768 44

Obesity is a common disorder, and related diseases such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer are a major cause of mortality and morbidity in Western-type societies. Development of obesity is associated with extensive modifications in adipose tissue involving adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in these processes. A nutritionally induced obesity model in transgenic mice has been used extensively to study the role of the fibrinolytic and MMP systems in the development of obesity. These studies support a role of both systems in adipogenesis and obesity, and suggest that modulation of proteolytic activity may affect development of adipose tissue.
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PMID:Role of proteolysis in development of murine adipose tissue. 1827 77

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.
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PMID:Abeta-degrading enzymes in Alzheimer's disease. 1836 35


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