Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine whether exercise training produces a myocardium intrinsically more tolerant to ischemic-reperfusion injury. Male Fischer 344 rats were treadmill trained for 11-16 wk at one of the following intensities: LOW (20 m/min, 0% grade, 60 min/day), moderate (MOD; 30 m/min, 5% grade, 60 min/day) or intensive (INT; 10 bouts of alternating 2-min runs at 16 and 60 m/min, 5% grade). Cardiac function was evaluated both before and after 25 min of global, zero-flow ischemia in the isolated, working heart model. Compared to hearts from sedentary (SED) rats, postischemic cardiac output (CO) and work were significantly higher in all trained groups. Percent recovery of CO (relative to preischemia) was 36.0 +/- 7.1 in SED and 61.2 +/- 6.5, 68.1 +/- 9.3, and 73.2 +/- 5.0 in LOW, MOD, and INT, respectively. Postischemic increases in stroke volume with increased preload and cardiac work at high work load were significantly higher in INT compared with SED. Coronary flow during initial retrograde reperfusion was significantly enhanced with training and correlated with subsequent recovery of CO (R2 = 0.613). Furthermore, trained hearts had higher phosphocreatine (P less than 0.05) and ATP (P less than 0.01) contents after 45 min reperfusion. It is concluded that exercise training results in an intrinsic myocardial adaptation, allowing greater recovery of cardiac pump function after global ischemia in the isolated rat heart.
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PMID:Exercise training improves cardiac function after ischemia in the isolated, working rat heart. 141 6

On the basis of vascular involvement, an open clinical trial was performed to determine whether or not the antithrombotic drug cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone, OPC-13013, Pletaal, CAS 73963-72-1) applied as a single 100 mg tablet increases peripheral blood flow and prevents diabetic neuropathy in 30 patients with non-insulin dependent diabetes mellitus. The hemodynamic effects of this drug on the a. dorsalis pedis were examined using a new real-time two-dimensional Doppler echography. 1 h after oral administration of cilostazol, the cross-sectional area of the a. dorsalis pedis significantly increased from 2.2 +/- 0.2 to 2.9 +/- 0.3 mm2 (p less than 0.05). Also, the a. dorsalis pedis blood flow index significantly increased from 16 +/- 1 to 31 +/- 4 (p less than 0.05). Cilostazol did not affect plasma glucose level (from 213 +/- 14 to 198 +/- 15 mg/dl), but slightly plasma ratio of 6-keto PGF1a to TXB2 (from 0.71 +/- 0.09 to 0.83 +/- 0.12). These effects of cilostazol might ameliorate diabetic neuropathy by improving blood flow and preventing nerve tissue ischemia.
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PMID:Hemodynamic effects of cilostazol on peripheral artery in patients with diabetic neuropathy. 164 79

The chronic effects of tolbutamide on myocardial contractility of the diabetic heart during ischemia and reperfusion were evaluated in perfused, isolated rat hearts. Five experimental groups were used: (1) control rats (C), (2) insulin dependent diabetic rats (IDDM, single intravenous injection of 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley rats), (3) non insulin dependent diabetic rats (NIDDM; single subcutaneous injection of 90 mg/kg STZ in 5 day neonates), (4) tolbutamide-treated IDDM and (5) NIDDM (T-IDDM, T-NIDDM; giving tolbutamide 100 mg/kg/day for 6 weeks via an orogastric tube every day, respectively). At 14 weeks of age, experiments were performed using a Langendorff perfused heart preparation. After equilibration, T (myocardial developed tension), +dT/dt (contraction velocity), -dT/dt (relaxation velocity) and RT (resting tension) were measured during a 15 min period of global ischemia, followed by reperfusion for 20 min. Basal values of T increased in both T-IDDM and T-NIDDM, compared to IDDM and NIDDM, respectively. The percent recovery rate of +dT/dt in T-IDDM increased significantly during both ischemia and reperfusion, but the change in T-NIDDM was not significant. The recovery rates of -dT/dt in T-IDDM and T-NIDDM were significantly higher throughout reperfusion than in IDDM and NIDDM, respectively. On the other hand, that of T in T-IDDM and T-NIDDM were significantly higher than IDDM and NIDDM throughout ischemia and reperfusion, respectively. The RT was significantly higher in IDDM than in C and NIDDM throughout ischemia and reperfusion. The RT was significantly lower during ischemia in IDDM, but it did not differ significantly from IDDM during reperfusion. These results indicate that chronic oral administration of tolbutamide directly improved myocardial contractility throughout ischemia and reperfusion regardless of the improvement of glycemia. The improvement was also greater in IDDM than in NIDDM.
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PMID:Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats. 192 Aug 21

Paraplegia is a fearful and not uncommon complication of aortic clamping in surgical procedures involving thoracic and abdominal aorta. We report a case of transient spinal cord ischemia during the early postoperative period of aortobifemoral bypass in a 69-year-old male with arteriosclerosis obliterans, hypertension, type II diabetes mellitus and COLD. The anesthetic procedure was combined (peridural + intubation and mechanical ventilation + isofluorane). Two hypotensive episodes of about 80 mmHg developed, one after induction and another in the Reanimation area. The first one had a short duration, whereas the second one required the administration of colloids, crystalloids and blood. The infrarenal aortic clamping time was 35 minutes. In the early postoperative period the patient had clinical features consistent with spinal ischemia, which progressively recovered. To prevent spinal ischemia during surgery a shorter duration than 30 minutes of aortic clamping, a higher distal perfusion pressures higher than 60 mmHg during clamping, and the attempt to exclude the least possible number of intercostal and/or lumbar vessels are recommended. Drugs (corticosteroids, naloxone) and hypothermia can be useful.
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PMID:[Spinal cord ischemia in the postoperative period of aortic surgery]. 207 98

Published "normal" values of some hormones have an excessively wide range and unequal mean values because the material on which these values are based is from subjects suffering from different diseases which only apparently are not associated with the investigated hormone, or else the specimens are obtained under non-standard conditions (malnutrition, stress, alcohol etc.). This wide range of normal values may hide incipient pathological processes and is not suitable even as control group. The investigation is based on the assessment of insulin, growth hormone (GH), cortisol, thyroxine (T4) and triiodothyronine (T3) in a group of blood donors. The assembled results were compared with two other groups of blood donors and a group of obese subjects. The following findings were assembled: We recommend to lower the upper borderline of "normal" insulinaemia from the recommended value of 26 to 20 i.u./l, as the original range may comprise milder forms of hyperinsulinism which is recently assumed to participate in the genesis of type 2 diabetes, hypertension, coronary ischemia and polycystic ovaries. Elevated normal values of serum insulin may be obtained also from blood donors who usually have breakfast before the blood is collected. The wide range of cortisolaemia is due to the diurnal rhythm. The basal value is raised by a declining blood sugar level, alcohol, obesity and of course, varying forms of stress. The upper range of cortisolaemia at 8 a.m. should not be beyond the range of 140-690 nmol/l. GH secretion is governed by an individual 3.5-hour cycle as well as changes of the blood sugar level, e. g. during the OGTT: the declining blood sugar level raises the GH level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Factors affecting normal levels of insulin, cortisol, STH, thyroxine and triiodothyronine]. 226 67

This paper reports the determination of blood flow of the lower leg in 50 cases of non-insulin dependent diabetes mellitus (NIDDM) using an XLJ-2 Bipolar Rheoencephalometry Impedance Rheogram. In patients with leg pain (but without obvious vascular pathological changes, 85 legs) the blood flow was decreased. In male patients the blood flow of the left leg (9 legs) was 3.28 +/- 0.47 ml/100ml.tissue.min (mean +/- S), while that in the right leg (11 legs) was 3.88 +/- 0.80; in females, the blood flow of the left leg (32 legs) was 2.72 +/- 0.8; while that in the right leg (33 legs) was 2.94 +/- 0.66. These figures were significantly (P less than 0.01-0.001) lower than those obtained from normals. In diabetic feet (15 painful legs) the decrease of blood flow of the lower leg was more apparent: it averaged 1.87 +/- 0.79 for the left leg (7 legs) and 2.66 +/- 0.87 for the right leg (5 legs) in male patients. The values were significantly different when compared with those of normals (P less than 0.001) or with those of the diabetic patients with leg pain (P less than 0.05). These results demonstrated that determination of the blood flow of the lower leg of diabetic patients might aid in early discovery of the abnormal changes of blood supply to the lower legs in diabetes mellitus and judge the degree of ischemia. Of the 50 cases of diabetics 32 were Qi-Yin deficiency with blood stasis while the remaining 18 cases were deficiency of both Yin and Yang with blood stasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Determination of blood flow of the lower leg in patients with diabetes mellitus and the effects of treatment with the principle of vitalizing blood and solubilizing thrombus]. 226 28

To evaluate the frequency of painless myocardial ischemia, all patients with positive exercise tolerance test responses (at least 2 mm of ST depression) from 1983 to 1985 were examined. Of the 211 patients with exercise-induced ischemia, 101 (48%) did not have pain during the ischemic period; 26 (12%) had diabetes mellitus, 24 of whom (92%) had type II diabetes mellitus. Lack of pain was not correlated with age, gender, history of cigarette smoking, systemic hypertension, past acute myocardial infarction, coronary artery bypass grafting, use of beta-blocking or calcium-channel blocking drugs, number of narrowed coronary arteries or average calculated ejection fraction at cardiac catheterization. Patients with painless myocardial ischemia were less often taking nitrates (39% vs 55%, p less than 0.05) and reported prior episodes of chest pain less often (50% vs 82%, p less than 0.01) than control subjects. There was no difference in the frequency of painless myocardial ischemia between patients with and without diabetes mellitus (54% vs 47%). Duration of exercise was shorter in patients with diabetes mellitus and in patients who had pain with myocardial ischemia. No significant difference in age, gender, use of nitrates, beta-blocking or calcium-channel blocking drugs, history of myocardial infarction, angina pectoris or cigarette smoking was found between diabetic and nondiabetic patients. Systemic hypertension was more common in diabetic patients. Thus, painless myocardial ischemia is common in our patients with positive exercise tolerance test responses, but its frequency is similar in diabetic and nondiabetic patients.
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PMID:Frequency of painless myocardial ischemia during exercise tolerance testing in patients with and without diabetes mellitus. 381 54

Cardiovascular risk factors such as hypertension, diabetes, and dyslipemia are associated with an impaired endothelium-dependent vasodilation. In patients with type 2 diabetes mellitus, these risk factors are frequently clustered. We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril can improve endothelium-dependent vasodilation in this particular group of patients. We selected 10 patients with type 2 diabetes and hypertension (age 59.4 +/- 3.2 years, body mass-index 29.7 +/- 1.5 kg.m-2, blood pressure 169 +/- 6/92 +/- 1 mm Hg, total cholesterol 6.6 +/- 0.3 mM). Using venous occlusion plethysmography, we recorded the increases in forearm blood flow (FBF) in response to three vasodilator stimuli: (a) 5 min of forearm ischemia, (b) infusion of the endothelium-dependent vasodilator methacholine (Mch) into the brachial artery (0.03, 0.3, and 1.0 micrograms/min/100 ml), and (c) intraarterial infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP 0.06, 0.2, 0.6 microgram/min/100 ml). This procedure was repeated after 6 months of treatment with perindopril 4-8 mg/day. Forearm vascular resistance (FVR) was calculated by the quotient of the mean arterial pressure (MAP) and the FBF. Perindopril reduced blood pressure (BP) by 19/10 mm Hg (p < 0.05) and increased baseline FVR, but improved neither the maximal percentage decrease in vascular resistance induced by Mch (from -80 +/- 2 to -82 +/- 2%) nor that induced by SNP (from -73 +/- 3 to -72 +/- 3%). Perindopril decreased the FVR reached after the ischemic stimulus from 6.5 +/- 1.2 to 4.8 +/- 0.6 U (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of long-term angiotensin-converting enzyme inhibition on endothelial function in patients with the insulin-resistance syndrome. 759 36

To study mechanisms underlying ischemia in hypertension and non-insulin dependent diabetes mellitus (NIDDM), 31P-magnetic resonance spectroscopy was used to evaluate adenosine triphosphate and 2,3 diphosphoglycerate (2,3 DPG) levels in erythrocytes of control (n = 21), hypertensive (n = 22), and NIDDM (n = 10) subjects. Compared to adenosine triphosphate levels in controls (2.22 +/- 0.10 mM), both hypertensive (1.89 +/- 0.10 mM, sig = 0.05 versus normal) and NIDDM subjects (1.57 +/- 0.13 mM, sig = 0.05 versus normal) exhibited lower values. NIDDM subjects also displayed suppressed levels of 2,3 DPG (6.84 +/- 0.48 mM, sig = 0.05 versus normal and EH), compared to hypertensives (8.34 +/- 0.27 mM). These data suggest cellular energy metabolism is disrupted in hypertension and NIDDM. Both conditions may thereby sensitize tissues to ischemic damage, lower adenosine triphosphate levels by decreasing energy reserves, and lower 2,3 DPG levels by inhibiting hemoglobin-oxygen dissociation.
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PMID:Is the higher incidence of ischemic disease in patients with hypertension and diabetes related to intracellular depletion of high energy metabolites? 814 Nov 68

Non-insulin-dependent diabetic (NIDDM) patients show a high incidence of cardiovascular disease, with greater risk of recurrent myocardial infarction and a less favourable clinical outcome than non-diabetic patients. The majority of NIDDM patients are treated with sulphonylurea (SU) derivatives. In the 1970's the University Group Diabetes Program concluded that tolbutamide treatment caused increased cardiovascular mortality; the study, which led to curtailment of oral antidiabetic treatment in the USA, was received with scepticism in Europe. Later criticism of its methodology reduced the impact of the study; however, the question of the safety of SU in NIDDM patients with cardiovascular disease has been re-opened in the face of new experimental data. The heart and vascular tissues do have prerequisites for SU action, i.e. SU receptors and ATP-dependent K+ (K+ATP) channels. These channels play an important role in the protection of the myocardium against ischaemia-reperfusion damage, and their closure by SU could lead to amplified ischaemic damage. Here we review evidence from animal and human studies for deleterious SU effects on ischaemia-induced myocardial damage, either by direct action or through diminished cardioprotective preconditioning. Closure of K+ATP channels by SU can lead to reduction of post-infarct arrhythmias; the drug has also been claimed to improve various atherosclerosis risk factors. The evidence for these beneficial effects of SU is also reviewed. We look at the major difficulties that hamper transfer of information from experimental studies to clinical decision-making: a) The affinity of SU for heart K+ATP channels is orders of magnitude lower than for beta-cell channels; is it reasonable to expect in vivo cardiac effects with therapeutic 'pancreatic' SU doses? b) Most studies utilized high doses of acutely administered SU; are effects similar in the chronic steady-state of the SU-treated diabetic patient? c) Convincing SU effects have been demonstrated in acutely induced ischaemia by acutely administering the drug; do such effects persist in the clinical situation of gradually progressive ischaemia? d) Ischaemia and modification of K+ATP channel activity induce complex events, some with opposing effects; what is the net result of SU action, and do different SU derivatives lead to different outcomes? e) In the chronic (and hence clinically relevant) situation, how can direct (deleterious or beneficial) SU effects be separated from beneficial effects mediated by the metabolic action of the drug? Only large prospective clinical studies, making use of advanced technology for assessment of cardiovascular function, can answer these questions. Millions of NIDDM patients are treated with SU derivatives; many are in the age group where cardiovascular risks are extremely high. The question of whether SU derivatives are beneficial or deleterious for these patients must finally be settle unequivocally.
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PMID:Sulphonylurea treatment of NIDDM patients with cardiovascular disease: a mixed blessing? 873 9


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