Free fatty acids and platelet prostacyclin binding.
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Blood Platelets↗
Biomedical subjects
W Renn
Publications and source records attributed to W Renn.
The binding of 6-oxo-prostaglandin E1 to platelet prostanoid receptors.
6-oxo-PGE1 has been shown to cause a dose dependent stimulation of platelet adenylate cyclase (Km 1.6 X 10(-7)M). Since this compound also displaced specifically bound 9-3H-PGI2 from intact washed platelets (Ki 1.6 X 10(-6)M), the coupling to platelet PGI2 receptors has been suggested to account for the observed platelet cyclase stimulation. However, the Ki/Km-ratio of 6-oxo-PGE1 appears to be high (10.3) as compared to PGI2, ZK 36 374, and PGE1 (1.9, 2.4 and 3.1, resp.). Thus, one might expect that 6-oxo-PGE1 interacts with a heterogeneous population of platelet receptors mediating the same biological response, eg cyclase activation. In this study, we present evidence supporting this concept and report that 6-oxo-PGE1 also displaces specifically bound 3H-PGD2 from its platelet receptor (Ki 1.6 X 10(-5)M).
Adenylyl Cyclases↗
Platelet prostacyclin binding in coronary artery disease.
Reduced responsiveness of platelets to prostacyclin, reported in vitro in patients with coronary artery disease, has been thought to be a factor predisposing toward coronary thrombosis and vasospasm as a result of enhanced in vivo release of cyclic endoperoxides and thromboxane A2 by the platelets. In this study, specific binding of prostacyclin to intact platelets was determined in patients with coronary artery disease by direct binding studies using 9-3H-prostacyclin sodium salt. In addition, the inhibitory effect of prostacyclin on primary aggregation induced by adenosine diphosphate and cyclic adenosine monophosphate (cyclic AMP) accumulation stimulated by prostacyclin was examined. Twenty patients with angiographically documented coronary artery disease and stable angina, 8 patients with acute myocardial infarction, 14 healthy volunteers and 10 patients with normal angiograms were studied. In patients with stable angina, binding capacity and affinity of platelet prostacyclin binding sites and prostacyclin-induced cyclic AMP accumulation were not different from those of control subjects. In patients with acute myocardial infarction, however, binding capacity of platelet prostacyclin receptors was significantly reduced (0.69 +/- 0.45 versus 1.35 +/- 0.37 pmol/10(9) platelets, p = 0.001) and the postreceptor response, represented by platelet responsiveness to prostacyclin and prostacyclin-induced cyclic AMP synthesis, was impaired. Because all patients with myocardial infarction were receiving intravenous heparin and nitroglycerin, which might interfere with platelet prostacyclin binding, competition experiments were performed in vitro. Neither heparin (3 to 250 IU/ml) nor nitroglycerin (0.8 to 22 microM) displaced specifically bound 9-3H-prostacyclin. L-Epinephrine in concentrations up to 10 microM also exhibited no competition with specific platelet prostacyclin binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
Platelet prostacyclin binding in smokers.
Binding capacity (Bmax) and dissociation constant (KD) of platelet prostacyclin (PGI2) receptors in 23 male smokers and 14 nonsmokers have been determined by direct binding studies to investigate whether platelet prostacyclin binding is altered in smokers. In addition, the inhibitory effect of PGI2 (IC50) on adenosine diphosphate (ADP)-induced platelet aggregation was measured. As confirmed by discriminant analysis, 69% of the smokers had significantly different Bmax and KD. Binding capacity was increased in 12 smokers (Bmax + 74%), with a concomitant decrease in affinity (KD + 94%). In these volunteers, the postreceptor responses (PGI2-induced cyclic adenosine monophosphate [AMP] accumulation in platelet-rich plasma as well as IC50) did not differ from those of controls. In contrast, four smokers with considerably reduced PGI2 binding capacity (Bmax - 65%) exhibited a lower antiaggregatory effect (IC50 + 74%), although the affinity was slightly increased (KD - 61%). Nicotine, L-epinephrine, and prostaglandin E2 did not significantly compete with the binding of 9-3H-PGI2 sodium salt. The antiaggregatory effect of PGI2 on ADP-induced platelet aggregation, however, was inhibited by L-epinephrine (Ki 26 nmol/L) and prostaglandin E2 (Ki 230 nmol/L). Our data suggest that with respect to platelet PGI2 binding and in vitro responsiveness to PGI2, smokers are a heterogeneous population. Although increased binding capacity was observed in 50% of the smokers investigated, our data provide no evidence that a biologically relevant upregulation, for example with concomitant enhanced postreceptor reaction, occurs in smokers.
Adenosine Diphosphate↗
Macro creatine kinase type 2: results of a prospective study in hospitalized patients.
We determined total CK activity with the N-acetylcysteine-activated method and residual activity after immunoinhibition of the CK-M subunits in the sera of 2018 patients consecutively admitted to our university hospital for internal diseases, and of 936 outpatients, regardless of the patients' diagnoses. We could detect not more than two types of macro CK: macro CK type 2, which we observed in the sera of 85 patients (prevalence, 3.7% for hospitalized patients), and macro CK type 1. Most patients showing macro CK type 2 were older than 50 years, but we additionally observed a second peak at 20-30 years of age. We saw no preponderance by sex. We detected macro CK type 2 predominantly in severely ill patients of all ages, mainly those with malignant tumors or cirrhosis of the liver. Our findings support the assumption that macro CK type 2 is the manifestation of mitochondrial CK in serum. Occasionally, macro CK type 2 disappeared from the circulation after amelioration of the associated disease. Its occurrence in serum nevertheless is a sign of a serious illness with high mortality but not inevitably a sign of impending death.
Adult↗
Stability of macro creatine kinases and creatine kinase isoenzymes compared: heat inactivation test for determination of thermostable creatine kinases.
Creatine kinase isoenzymes showed decreasing thermal stability and increasing lability towards pH changes in the order: MM, MB, and BB. The three isoenzymes exhibited their highest stability between pH 6.5 and 7.0. At 37 degrees C and an almost physiological pH of 7.5 the decay constants were 0.025, 0.164 and 0.580 h-1 (MM, MB, and BB isoenzyme), respectively. In contrast to free creatine kinase BB, immunoglobulin-linked creatine kinase BB (macro creatine kinase BB, type 1 macro creatine kinase) showed a markedly higher stability; this accounts for the persistence of creatine kinase BB activity in macro creatine kinasaemia. In addition we identified a second type of macro creatine kinase in patients' sera, which is also thermostable. A simple heat inactivation test (20 minutes, 45 degrees C, immunoinhibition of the M-subunits) differentiates thermostable macro creatine kinases from thermolabile creatine kinases and thus completes isoenzyme diagnosis.
Creatine Kinase↗
Influence of cardiovascular diseases upon the results of the cardiovascular reflex tests in diabetic and nondiabetic subjects.
Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (less than or equal to 45 years) and older (greater than 45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.
Blood Pressure↗
Cognitive and psychomotor function during hypoglycemia: a comparison between porcine and human insulin.
After an overnight euglycemic clamp, blood glucose levels were precisely lowered on two nonconsecutive mornings via a glucose-controlled insulin infusion system (GCIIS, Biostator) using either purified porcine insulin (PPI) or human insulin (HI). Two cognitive and psychomotor tests were significantly different in 8 type-I diabetic subjects and 8 healthy volunteers at four timepoints, when mean blood glucose concentrations (BGCs) were 100, 65, 50, and 40 mg/dl. Also, a significant difference (p = 0.005) could be found between the mean of all reaction time testing (RTT) values under HI as compared with the mean of all RTT values under PPI. Lowering the BGC resulted in a significant increase in the reaction time (p = 0.012). These effects were not dependent on the type of insulin being used nor were they typical of a particular study group.
Adolescent↗