Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated.
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PMID:Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. 1 Jul 36

Ten maturity-onset diabetics with chronic vascular disease were treated with 400 mg pentoxifylline 3-times daily for 14 days. Erythrocyte deformability (using a filtration technique for whole blood) and phosphatide fatty acid distribution in the erythrocyte membrane were measured before and after the treatment period. Statistical analysis of the data showed that the erythrocyte filtration rate had increased significantly by the end of treatment (2alpha = 0.02), and that there were only slight changes in erythrocyte membrane phosphatide fatty acid levels. The drug was well tolerated, and there were no adverse laboratory findings in the parameters measured. On the basis of results described by other investigators, theimprovement in erythrocyte deformability was attributed to an increase in erythrocyte ATP levels. The authors discuss the importance of red cell fluidity for capillary perfusion.
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PMID:The effect of pentoxifylline on erythrocyte deformability and on phosphatide fatty acid distribution in the erythrocyte membrane. 59 22

Positron scintigrams were obtained in normal subjects and in patients with intracranial tumors and cerebral vascular disease, using a multicrystal positron camera. The radiopharmaceuticals were 68Ga complexed with adenosine triphosphate (68Ga-ATP), 13N-ammonia (13NH3), and 15O2. Six clinical cases are described to illustrate the different cerebral distributions of intravenously administered 68Ga-ATP, 13NH3, and inhaled 15O2. The possible value of these agents in the study of cerebral metabolism and in differential diagnosis of intracranial disease is discussed.
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PMID:Techniques for positron scintigraphy of the brain. 126 65

Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.
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PMID:Plasma metabolic disturbances and reperfusion injury following partial limb ischaemia in man. 271 61

The relationship between erythrocyte nucleotide profiles and the presence of atherosclerotic peripheral occlusive vascular disease was investigated. In elderly male patients with severe vascular insufficiency the mean red cell content of NAD, GDP, GTP, AMP, ADP and ATP and the cellular adenylate energy charge were not significantly different from those observed in young healthy males. It has been claimed that drugs such as oxpentifylline improve peripheral tissue oxygenation in vascular disease by reversing the fall in red cell ATP content which has been reported to accompany vascular insufficiency resulting in a restoration of normal cell deformability and hence whole blood viscosity. We have carried out in vitro studies using erythrocytes from normal adults to assess the effect of oxpentifylline on erythrocyte ATP content and glycolytic rate. The drug failed to significantly affect the rates of glucose consumption and lactate production or the ATP content of the erythrocytes compared with controls. Furthermore the drug did not influence the rate of ATP utilisation by erythrocytes. We conclude that red cell ATP and total adenylate content is not different from normal in patients with peripheral vascular disease. If oxpentifylline alters red cell deformability it does so by some mechanism not related to the cellular ATP concentration, the cellular adenylate energy charge or the glycolytic rate.
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PMID:Adenine nucleotides in erythrocytes from patients with peripheral vascular disease and the effects of oxpentifylline. 350 68

The relationship between erythrocyte ATP content and the presence of atherosclerotic peripheral occlusive vascular disease was investigated. In 20 elderly patients with severe peripheral vascular insufficiency (10 male, 10 female; age 68.8 +/- 12.5 years; Mean +/- SD) the mean erythrocyte ATP content was 1.57 +/- 0.16 mmol/litre. In a sex and age matched group (69.1 +/- 9.6 years) with no signs or symptoms of peripheral or myocardial ischaemia, erythrocyte ATP content did not differ significantly (1.49 +/- 0.29 mmol/litre). In young healthy volunteers, there was no difference in erythrocyte ATP content between males and females or between cigarette smokers and non-smokers, nor were the values for the young group different from those obtained from the elderly patients. The effect of oxpentifylline administration on erythrocyte ATP levels in patients with peripheral vascular disease was also studied. Administration of oxpentifylline (1.6 g per day in divided doses) over 7 days had no effect on erythrocyte ATP content in 10 patients (5 male, 5 female) with ischaemic lower limbs. These results suggest that measurement of erythrocyte ATP content is unlikely to be a useful index in the assessment of peripheral vascular disease.
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PMID:Whole blood and red cell ATP content in patients with peripheral vascular disease: the effect of cigarette smoking and oxpentifylline. 649 47

31P NMR is used to determine the relationship between work output in the exercising human forearm and the steady-state capability of oxidative phosphorylation as measured by the phosphocreatine/inorganic phosphate ratio (PCr/Pi). Exercise intensities (one contraction per 5 sec) permitting comfortable continuation of activity for greater than 1 hr produced PCr/Pi of about 1 for a subject of moderate training. Linear relationships between work rate per unit volume of muscle and the 5-min mean PCr/Pi were found for the subject's left and right arms. The protocol affords sensitive criteria of muscle performance in normal subjects and of biochemical or vascular disease in abnormal subjects. The Pi, PCr, and ATP levels found by 31P NMR represent the initial values in the cycle of contraction and relaxation which permit restitution of resting state 4 prior to the next contraction and the continuation of steady-state work performance.
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PMID:Mitochondrial regulation of phosphocreatine/inorganic phosphate ratios in exercising human muscle: a gated 31P NMR study. 694 47

Plasma fron some diabetic patients, particularly those with advanced retinopathy and nephropathy, will potentiate ADP-induced platelet aggregation. Partial purification of plasma from a diabetic patient with nephropathy has yielded a fraction with this activity. A linea dose response curve relating plasma factor (6.25-50 ng protein) and platelet aggregation or ATP release at 4 minutes after adding ADP has been found. The effect is blocked by exposure of platelets to aspirin, prostaglandin or eicosapentaenoic acid. Soluble immune complexes are found in many diabetics and are known to be platelet-active. We have isolated immune complexes from sera of six diabetics and have shown enhancement of the second phase of platelet aggregation and of ATP release by these immune complexes from platelets sensitized to ADP. We conclude that plasma proteins from diabetics may accentuate ADP-induced platelet aggregation and ATP release, possibly by acting through prostaglandin pathways. Immune complexes appear to be one group of plasma proteins with such platelet active behavior. Further studies are indicated to characterize these plasma factors and to assess their in vivo significance regarding platelet function and vascular disease in diabetes mellitus.
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PMID:Plasma factors and platelet aggregation in diabetes mellitus. 697

Using guinea pigs, a study was conducted on the effects of KBT-3022, a new anti-platelet agent, on hemorheological properties in various tests including blood filterability, blood viscosity, shear stress-induced red blood cell (RBC) deformability and contents of ATP and 2,3-diphosphoglycerate (2,3-DPG). Oral administration of KBT-3022 at 1 and 10 mg/kg significantly increased blood filterability, and significantly reduced blood viscosity at 10 mg/kg without changing the hematocrit, plasma fibrinogen concentration or plasma viscosity. KBT-3022 (10 mg/kg, p.o.) improved RBC deformability in response to shear stress, which was evoked by passing the blood through a thin tube. This dose of KBT-3022 also increased the contents of ATP and 2,3-DPG in RBC. These findings indicate that KBT-3022 may reduce blood viscosity as a sequel to improvement of RBC deformability through direct action on RBC. The increase in the intracellular levels of ATP and 2,3-DPG was considered to be involved in this improvement of hemorheological properties. These hemorheological effects of KBT-3022 appear to be promising for the treatment of patients with ischemic vascular disease.
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PMID:The effects of KBT-3022, a new anti-platelet agent, on hemorheological properties in guinea pigs. 774 Apr 82

Patients with polycythaemia and normal controls have been studied to establish and subsequently test non-conventional criteria for the diagnosis of primary polycythaemia (primary proliferative polycythaemia, polycythaemia vera) as compared with conventional Polycythaemia Vera Study Group (PVSG) assessment. One criterion was erythroid colony formation from peripheral blood in a serum-free system, assayed alone and with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha interferon (alpha-IFN) (Dudley et al. 1990). The remaining criteria were non-culture associated and comprised platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), serum erythropoietin and clinical evidence of ischaemic vascular disease. The combination of culture associated and non-culture associated variables, by use of a simple additive scoring system, gave no false positive and only 6% false negative results in distinguishing primary polycythaemia from other polycythaemias and normal controls in those (34 patients Group A) used in its derivation. Testing the scoring system in a newly presenting group (25 patients Group B) was highly satisfactory with no false positives and only a few false negative results (14%). Use of these non-conventional criteria should allow more confident diagnosis of primary polycythaemia, where conventional clinical and laboratory assessment is inconclusive.
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PMID:Primary polycythaemia: diagnosis by non-conventional positive criteria. 824 12


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