Glycemic spikes may negatively affect the long-term prognosis of patients with diabetes. Extracellular signal-regulated kinases (ERKs) are intracellular mediators of cell proliferation, and they can ...be activated in response to high glucose levels. However, the modifications of their activity in response to hyperglycemia have been poorly investigated, in vivo, in humans. Thus, we sought to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs activity and phosphorylation, and 2) whether hyperglycemia affects mitogen-activated protein kinase kinase (MEK) activity and mitogen-activated protein phosphatase-1 (MKP-1) expression. These goals were performed in five normal subjects. Baseline monocyte ERKs activity was 60 +/- 5 pmol/min.mg protein; when exogenous hyperglycemia was induced, both monocyte ERKs activity (81 +/- 11 pmol/min.mg protein; P < 0.05) and phosphorylation significantly increased (P < 0.01). MEK activity was significantly increased by hyperglycemia (1251 +/- 136 vs. 2000 +/- 42 cpm; P = 0.0017), whereas no changes were observed in MKP-1 expression. We conclude that hyperglycemia acutely stimulates ERKs activity and phosphorylation in human monocytes by the MEK pathway in vivo. These findings may be relevant in understanding the negative role of acute hyperglycemia on monocyte pathophysiology.
the correlation between primary antiphospholipid syndrome (APS) and cardiovascular events is well known, but the correlation between APS and sudden death is not clear; it probably correlates with ...sympathetic alterations of the autonomic system.
To compare the autonomic nervous system (ANS) in a group of subjects suffering from APS against that of a control group with no cardiovascular risk factors, matched for age, sex, and body mass index.
An equal number (n = 31) of subjects with APS, and healthy controls, underwent autonomic evaluation: tilt test, deep breath, Valsalva maneuver, hand grip, lying-to-standing, Stroop, and sweat tests.
Cases in the APS group were positive for the tilt test, relating to changes in respiratory rate intervals, by comparison with controls. Results of other tests were also altered significantly in APS cases, by comparison with controls. (The sweat and Stroop tests were only performed in 14 cases). Autonomic disease did not correlate with age, sex, history of disease, arterial or venous thrombosis, or antibody positivity; only their coagulation parameters correlated with autonomic dysfunction.
Autonomic dysfunction in APS seems to correlate with coagulation parameters. APS patients should receive autonomic evaluation, to minimize the risks of fatal arrhythmias and sudden death.
Summary
We investigated a family with prekallikrein deficiency, using both standard coagulation tests and molecular biology techniques. The propositus was found to be a compound heterozygote for a ...Trp383 stop codon and a Cys529Tyr point mutation. The former mutation was located in exon 11, the latter in exon 14. The propositus inherited the first defect from his father and the second from his mother. Both parents had slightly low prekallikrein levels, but the combination of the two genetic defects produced a phenotype characterized by an extremely low prekallikrein activity and antigen. The propositus’ plasma showed a progressive reduction in APTT when incubated for a long time. Conversely, plasma deficient in factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show shortening of the APTT. No circulating anticoagulant was found because the patient’s APTT was fully corrected by pooled normal and factor XII-, factor XI- or HMWK deficient plasma. No associated abnormality was apparent in the propositus or his parents. As expected, no tendency for bleeding was noted even after tonsillectomy.
The coinheritance of hypoplasminogenemia and heterozygous factor V deficiency in a relative with thrombotic disease and no hemorrhagic tendency is described. The proposita, a 28-year-old woman, ...suffered from neurologic dis turbances due to two ischemic cerebral lesions confirmed by nuclear magnetic resonance scan. She was found to be affected with heterozygous plasminogen deficiency in a coagulation study for inherited thrombophilia. Moreover, she disclosed a prolongation of prothrombin time and activated partial throm boplastin time, which was compatible with heterozygous factor V deficiency. Her father, with a history of deep vein thrombo sis, was also affected with plasminogen deficiency, as well as three brothers and one sister who were asymptomatic. The mother of the proposita showed borderline or slightly decreased factor V levels and normal plasminogen levels; she was there fore considered to be heterozygous for factor V deficiency. Heterozygous factor V deficiency was also found in one brother and one sister of the proposita, and they were both asymptomatic. Among the other available family members, one brother and one sister of the proposita, all asymptomatic for either thrombotic or bleeding events, showed a normal clotting and fibrinolytic profile. To our knowledge, this is the first case of combined heterozygous plasminogen and factor V defi ciency in the same family. Two of six patients with hypoplas minogenemia showed thrombotic events, and in one of these symptomatic cases the coexistence of factor V deficiency did not prevent the occurrence of thrombosis. As expected, no hemorrhagic tendency was observed in patients with heterozy gous factor V deficiency, who may be mildly symptomatic only in 10% of cases.
Systemic lupus erythematosus is an autoimmune disease that often involves the cardiovascular system. Coronary artery narrowing in patients with lupus erythematosus is severe, progressive, and related ...to the duration of the disease rather than to the age of the patient. Steroid use in such patients has improved their life expectancy but seems to be increasing the incidence of coronary involvement. Consequently, a larger number of systemic lupus erythematosus patients may be candidates for myocardial revascularization in the future. We report our experience with myocardial revascularization in 2 women with severe systemic lupus erythematosus, incapacitating angina, and severe obstructive coronary artery disease. One of the women required balloon angioplasty 19 months after coronary artery bypass grafting and remains asymptomatic nearly 3 years later. The other patient is free of symptoms 9 months after surgery. Our results with these 2 patients are encouraging. Long-term follow-up should yield further information regarding the benefits of myocardial revascularization and coronary angioplasty in patients with systemic lupus erythematosus.
Hypertension is a common early finding after an acute ischemic stroke, even in previously normotensive patients. But its significance and proper management are a matter of debate, because of the lack ...of adequately powered randomized clinical trials. A close analysis of observational and interventional trials, published so far, fails to convince that an early antihypertensive therapy is needed and beneficial. During the first 24-48 hr after ischemic stroke, only blood pressure values repeatedly higher than 220/120 mmHg require antihypertensive treatment to keep blood pressure levels in the range of 180-220 mmHg systolic and 100-120 diastolic. Blood pressure reduction should be cautious with the aim of keeping the pressure at relatively high values (180/100-105 in previously hypertensive patients and 160-180/90-100 in previously normotensive patients). The usefulness of increasing blood pressure with vasopressive agents in selected patients with ischemic stroke deserves adequate testing with randomized clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Defibrotide is a polydeoxyribonucleotide salt that shows antithrombotic activity through a suggested profibrinolytic mechanism. To study the effectiveness of defibrotide in atherosclerosis, we ...evaluated the fibrinolytic and coagulation behavior in normal subjects and patients with atherosclerotic disease, before and after single or repeated intravenous defibrotide infusion. A significant shortening of the ELT was found in all subjects. However, since neither t-PA increase nor PAI decrease was observed, we suggest that the profibrinolytic response to defibrotide may be due to mechanisms other than t-PA stimulation. Our results provide further evidence for the usefulness of defibrotide antithrombotic prophylaxis in atherosclerosis.
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