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Biomedical subjects

M Cucuianu

Publications and source records attributed to M Cucuianu.

At least 19 recordsLinked to original sources

Plasma phospholipase A2 in children with malignant disorders.

Forty nine children with various malignant disorders showed plasma phospholipase A2 catalytic activity concentrations in the range 0-48 U/l, and in 19 (39%) cases the values significantly exceeded 10 U/l. In 16 healthy children the catalytic concentration never exceeded 10 U/l. Of the 18 children with malignant lymphoma and 16 with acute leukaemia (14 of these with lymphoblastic leukaemia), 44% had plasma phospholipase A2 activities greater than 10 U/l. In 9 patients, an associated infection was either documented or could not be excluded. Of the remaining 40 patients, 33% had enzyme activities above 10 U/l. Although the determination of phospholipase A2 may not be relevant for the diagnosis of a malignancy, it may give an indication of the patient's reaction to the malignant process.

Child

Alpha 2-antiplasmin, plasminogen activator inhibitor (PAI) and dilute blood clot lysis time in selected disease states.

This paper is an attempt to assess the relevance of the inhibitors of fibrinolysis for clot lysis in selected disease states and to discuss the mechanisms leading to acquired abnormal levels of such inhibitors. When compared to 20 control subjects the 30 hypertriglyceridemic patients (14 with type IIb and 16 with type IV) displayed significantly (p less than 0.001) increased plasma plasminogen activator inhibitor (PAI) activity (221 +/- 88% and 290 +/- 104% respectively; mean +/- SD), moderately (p less than 0.01) increased alpha 2 antiplasmin (alpha 2AP) level (112 +/- 11% and 115 +/- 16%) and accordingly an obviously prolonged dilute blood clot lysis time (DBCLT). Neither PAI activity and alpha 2AP level nor DBCLT were significantly different from controls in the 10 patients with hyperlipoproteinemia type IIa. The 18 patients with severe hepatic cirrhosis had low alpha 2AP level (59 +/- 19.7%) and accelerated clot lysis, while mean PAI activity (160 +/- 87%) was slightly (p less than 0.05) increased. In the 17 nephrotic patients alpha 2AP was increased (115 +/- 12%) while PAI activity was similar to controls and DBCLT rather shorter. Two liver secretion enzymes, namely serum cholinesterase and plasma protein C, were found to be decreased in cirrhotic patients, similar to control values in hyperlipoproteinemia type IIa and obviously increased in nephrotic patients as well as in hypertriglyceridemic subjects. The relevance of PAI and alpha 2AP for clot lysis was considered in relation to data in the literature concerning the behaviour of t-PA and factor XIII.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Similar behaviour of lecithin:cholesterol acyltransferase and pseudocholinesterase in liver disease and hyperlipoproteinemia.

Using exogenous substrate for its assay, lecithin:cholesterol acyltransferase (LCAT) was found to be decreased in liver disease and higher than normal in endogenous hypertriglyceridemia. LCAT activity was positively correlated with serum cholesterol and triglyceride. However in the six patients with excessive hypertriglyceridemia (type V), LCAT activity was lower than in type IV hyperlipoproteinemia. LCAT activity was not changed significantly in type II-a hyperlipoproteinemia. A striking parallel was noted between plasma LCAT and serum pseudocholinesterase activity. It suggested that both these liver secretion enzymes might be induced by an accelerated turnover of serum lipids and lipoproteins. Pathogenical implications of these findings are briefly discussed.

Adult

Pseudocholinesterase changes in anesthesia using pancuronium.

Pseudocholinesterase activity was investigated in three groups of unselected patients. A slight rise of the enzyme was found during surgery under local anesthesia with lidocaine. In general anesthesia with thiopentone and halothane, the pseudocholinesterase activity diminished. The inhibition was more pronounced when pancuronium had been injected. From these data one may conclude that pancuronium must be carefully given in patients with low level of pseudocholinesterase when other drugs inhibiting the enzyme activity, like succinylcholine, procaine and propanidid, are used.

Anesthesia, Inhalation

Increased serum gamma-glutamyltransferase in hypertriglyceridemia: comparison with serum pseudocholinesterase.

Both gamma-glutamyltransferase (gammaGT) and pseudocholinesterase (PCE) were found to be increased in hypertriglyceridemic subjects. High values of gammaGT were noted in alcoholic subjects and especially in those with either increased serum triglyceride or alanine aminotransferase higher than 16 mU/ml, while PCE was not significantly changed in alcoholic subjects. Although both enzymes were strongly correlated with the logarithm of serum triglyceride and the prebeta electrophoretic fraction, there were striking differences concerning their behavior in various hypertriglyceridemic subjects. PCE activity was high even in moderate hypertriglyceridemias but its correlation with serum triglyceride had a tendency to flatten with increasing concentration of triglyceride. However, increase of gammaGT was rather characteristic for gross hypetriglyceridemia. Short-term, triglyceride-lowering therapy was accompanied by a tendency to normalization of gammaGT, while PCE values were not influenced. An attempt was made to interpret these changes of serum-enzyme activity in hypertriglyceridemia in connection with mechanisms of lipoprotein synthesis and with the pathogeny of hyperlipemic conditions.

Adult

Serum pseudocholinesterase and ceruloplasmin in various types of hyperlipoproteinemia.

Starting from previous observations emphasizing an increased pseudocholinesterase (PCE) activity in obese and hyperlipemic subjects, the behaviour of this enzyme and of ceruloplasmin was studied in connection with changes of serum lipids and lipoproteins in various types of hyperlipoproteinemia. When compared to values detected in 67 middle-aged normal weight normolipemic subjects, PCE activity was found to be significantly greater (smaller than 0.001) in the 49 overweight subjects without obvious hyperlipemia but presenting a moderate increase of the prebeta electrophoretic fraction. PCE activity was much higher in lean or overweight subjects with endogenous hypertriglyceridemia (68 patients with type IV and 86 patients with mixed hyperlipemia). The slight increase of mean values of PCE activity in the 53 subjects with type II-a was due mainly to overweight subjects, while this enzyme's activity was not significantly changed in lean subjects with pure hypercholesterolemia. PCE activity was positively correlated with serum triglyceride (r equals 0.540; p smaller than 0.001) and the prebeta electrophoretic fraction (r equals 610; p smaller than 0.001). The correlation with beta-lipoproteins was not significant. Ceruloplasmin levels were not significantly changed. It is suggested that elevation of PCE activity could be connected to mechanisms leading to an increased secretion rate of lipoproteins.

Adolescent

Effects of some benzodiazepine derivatives on Triton WR-1339-Induced hyperlipidaemia in rats.

Oral administration of the benzodiazepines (diazepam, lorazepam, chlordiazepoxide, bipotassium chlorazepate) in Triton WR-1339-induced (200 mg/kg, blood collection 18 h later) hyperlipidaemia in rats elicited marked decrease of serum total lipids, total cholesterol and triglyceride levels, and alterations in free fatty acid and free glycerol content. The optimal doses for diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were estimated to be 5 mg/kg. Other benzodiazepines, namely oxazepam, medazepam and nitrazepam, elicited only minor changes in serum lipids levels, while with grandaxin no change was observed. The optimal doses of diazepam and lorazepam brought about the same changes in serum lipid content as did clofibrate (90 mg/kg, p. o.). If diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were administered in doses of 5 mg/kg in Triton WR-1339-treated rats (blood collection taken 3 h later), a significant decrease of total lipids and triglyceride levels was observed. The free glycerol level only altered after the administration of chlordiazepoxide, which brought about a significant reduction.

Animals

Serum cholesterol and apoprotein B levels and serum cholinesterase activity in selected hematologic malignancies.

As compared to values recorded in 10 healthy normal-weight normolipidemic control subjects, serum cholesterol and apoprotein B levels as well as serum cholinesterase activity were found to be obviously decreased in the 28 patients with acute leukemia, the lowest levels being associated with the worst prognosis. The values of the above-mentioned biochemical variables in the 21 patients with chronic disorders (13 with chronic myeloproliferative disease and 8 with chronic lymphocytic leukemia) were not as low as in patients with acute leukemia. It should however be mentioned that in patients with chronic myelogenous leukemia, the lowest levels of serum cholesterol were correlated with a large tumor burden as assessed by a score taking into account for clinical and hematologic parameters. It is concluded that hypocholesterolemia could be regarded as a factor of adverse prognosis in hematologic malignancies, being probably the result of both enhanced catabolism of low density lipoproteins and impaired hepatic lipoprotein synthesis.

Acute Disease

The role of platelets and leukocytes in coagulation and fibrinolysis.

After briefly reviewing the literature concerning the role of leukocytes and platelets in coagulation and fibrinolysis, the authors present their own results on the effect of intact platelets and of platelet releasate on tissue plasminogen activator-induced lysis of plasma clots. At a final concentration of 7 IU/ml of tissue plasminogen activator in the clotted mixture, a suspension of intact platelets (110 x 10(6)/ml in final concentration) produced an acceleration of clot lysis, while the thrombin-induced platelet releasate obtained from the same platelet suspension caused an obvious inhibition of fibrinolysis. The respective mean lysis times obtained in 7 experiments were 91 min +/- 7.76 (mean +/- SEM) for the control clots, 65 min +/- 5.8 for the clots containing platelets and 114 min +/- 11.5 for the clots including platelet releasate. The statistical significance versus controls, calculated by paired difference analysis was p < 0.002 and p < 0.001, respectively. The results suggest that in the context of a potent activation of fibrinolysis the platelet surface would enhance the process by favouring the interaction between plasminogen and its activator, while the platelet releasate rich inhibitors would increase the resistance to lysis of the plasma clot.

Blood Coagulation

Heterozygous protein C deficiency and coumarin necrosis of the skin.

An obese female patient aged 47 with a personal and familial history of recurrent venous thrombosis, who developed a coumarin-induced skin necrosis is presented. Laboratory investigations, performed three months after the acute event and in absence of coumarin therapy, emphasized a decreased anticoagulant activity of her plasma protein C (50% of the normal). These results as well as the high incidence of thrombotic disease in her relatives point to a familial heterozygous protein C deficiency. The antithrombotic role of the protein C system and the mechanism of coumarin induced necrosis of the skin are briefly discussed.

Coumarins

Reduced passage of alpha 2-macroglobulin into malignant serous effusions and diminished antifibrinolytic potential of the fluid.

The ratio of the relative concentrations of large and small proteins between effusions and serum was measured in patients with benign and malignant effusions. The ratio of values for a large protein, alpha 2 macroglobulin (alpha 2 M) was significantly (p less than 0.0005) lower in the 22 patients with tumoral effusion (0.436 +/- 0.016) and in the 16 patients with transudates (0.388 +/- 0.017) than in the 21 cases with inflammatory exudates (0.838 +/- 0.036) while the ratios between relative concentrations of the lower molecular weight alpha 1 antitrypsin (alpha 1AT) in serous fluids and sera were similar (close to 1.0) in all the above mentioned conditions. Most inflammatory exudates inhibited fibrinolysis in a urokinase activated system, while the activity of the inhibitors of fibrinolysis was very weak in tumoral effusions and in transudates. These findings suggest a rather selective passage of plasma proteins into a tumoral effusion, a fact that might be relevant for a pathogenic diagnosis.

Adult

Hemostatic variables in nephrotic patients.

The paper reviews data in the literature as well as the authors' own investigations, performed during the last seven years, concerning the hemostatic balance in nephrotic patients. The obviously increased plasma levels of fibrinogen, fibronectin, fibrin-stabilizing factor XIII, clotting factors V and VIII, von Willebrand factor as well as the enhanced platelet aggregability of such patients, associated with a decreased plasma antithrombin III, are compatible with a thrombotic tendency. On the other hand the increased plasma protein C may provide a compensative antithrombotic mechanism. A rather complex behaviour of the fibrinolytic system was noted in the nephrotic syndrome. Actually the enhanced release of tissue plasminogen activator (t-PA) from the endothelia of nephrotic patients is accompanied by an accelerated lysis of dilute blood clots, although the inhibitors of fibrinolysis such as alpha 2-macroglobulin and alpha 2-antiplasmin are increased. Failure or exhaustion of the compensative antithrombotic mechanisms would accentuate the hemostatic imbalance and favour the occurrence of thrombotic events. It is considered that increased urinary loss of antithrombin III and the enhanced hepatic synthesis of clotting factors would represent the main mechanisms involved in the production of this precarious hemostatic balance of nephrotic patients.

Antithrombin III

Serum electrophoretic lipoprotein factors and pseudocholinesterase activity in thyroid disease.

Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.

Butyrylcholinesterase