Histological changes in the vulva and vagina from ovariectomised rats undergoing oestrogen treatment.

BACKGROUND: The purpose of this study was to assess the histological changes occurring in the vagina and vulva in ovariectomised female rats, as well as the response to the administration of injectable oestrogens. MATERIAL AND METHODS: We used 30 female Wistar white rats, distributed as follows: group 1 - the control group, group 2 - the operated but untreated rats, and groups 3, 4 and 5 - operated rats, to which oestrogenic treatment was administered (Estradiol, Estradurin, Sintofolin) at a dosage of 0.2 mg/rat/day. After 14 days of treatment, all animals were sacrificed and vaginal and vulvar biopsies were taken from all groups. RESULTS: In group 2, we encountered structural changes of the vaginal mucosa, with severe atrophy and alterations in the thickness of the vagina and vulva. In groups 3, 4 and 5 we found marked hyperplasia of the vaginal and vulvar epithelium, eosinophilic and mast cell infiltration in the chorion. CONCLUSIONS: Our study proves that the histopathological changes during anoestrus after administration of oestrogens are cell hyperplasia, thickening of the superficial mucosal layer, eosinophilic and mast cells infiltrations, and chorionic congestion. Furthermore, we demonstrated that Estradiol therapy induces the most evident histological changes when compared to synthetic oestrogens such as Estradurin or Sintofolin.

Apolipoproteins A1 and B levels and serum cholinesterase activity in hyperlipidemic subjects.

Serum apolipoprotein B (apo B) levels were found to be significantly (p < 0.001) higher in the 27 patients with combined hyperlipidemia (144 m./dl +/- 27.6) than in the 17 normal weight normolipidemic control subjects (92 mg/dl +/- 20.6; X +/- SD). When compared to apolipoprotein A1 (apo A1) levels obtained in controls (168.5 mg/dl +/- 28.4), hyperlipidemic subjects displayed a moderate yet significant (p < 0.02) decrease of this apolipoprotein (140 mg/dl +/- 24.2). Serum apo B levels were significantly (p < 0.001) correlated with serum cholesterol concentrations and also, to a lesser degree (p < 0.01), with serum cholinesterase activity. A highly significant correlation (p < 0.001) between apo A1 and HDL cholesterol levels was also noted. The decrease ofHDL cholesterol occurring in hyperlipidemic men (-30%) was however more accentuated than the decrease of apo A1 (-18%) suggesting an enhanced transfer of cholesterol esters from HDL to VLDL and LDL. It is considered that the determination of apolipoproteins may be useful not only for the detection of risk factors for atherosclerosis, but also for a better insight concerning the mechanisms involved in the development of an atherogenic dyslipidemia.

Serum lactate dehydrogenase and alkaline phosphatase activities and serum cholesterol level in bone marrow blood.

Serum cholesterol level as well as serum lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were measured in 65 samples of bone marrow blood and in matched peripheral blood taken from patients with various hematological diseases. As expected, serum LDH activities were higher and serum total cholesterol levels were lower in the bone marrow blood than in the blood taken from the cubital vein. More interestingly, an important increase of heat-labile ALP, but not of serum GGT, was found in the bone marrow blood obtained from patients characterized by a proliferating bone marrow. Actually, both LDH and ALP activities were obviously higher in the bone marrow blood of patients with megaloblastic anemia, myelodysplastic syndrome and chronic myeloid leukemia than in samples taken from patients with chronic lymphocytic leukemia, a disease characterized by a slower proliferation rate. While the expected increased LDH activity is the result of an accelerated turnover of bone marrow cells implying the release of this enzyme from the dividing and/or decaying cells, the much higher activity of the heat-labile alkaline phosphatase found in the bone marrow blood would reflect an enhanced local remodeling of bone structures, probably related to an expanded proliferating bone marrow. The lower serum cholesterol level in the bone marrow blood could be subsequent to an enhanced uptake of low density lipoproteins by specific receptors on the bone marrow cells.

Clinical studies on plasma protein C. Correlation with serum cholinesterase.

When compared to 32 healthy normal weight normolipidemic control subjects, plasma protein C antigen and serum cholinesterase activity were significantly decreased in 17 patients with decompensated cirrhosis of the liver and in 29 critically-ill surgical patients displaying the acute phase reaction, most of them without evidence of consumption coagulopathy. The low levels of these variables are considered to be subsequent to impaired and dysregulated hepatic protein synthesis. On the contrary, plasma protein C and serum cholinesterase were increased in 20 nephrotic patients and in 20 overweight hypertriglyceridemic subjects, a finding highly suggestive of enhanced hepatic synthesis probably related to an accelerated turnover of triglycerides. A discrepancy between low serum cholinesterase activity and normal or even high plasma protein C antigen was noted in 15 patients with cholestasis. This was particularly evident in 7 subjects with extrahepatic cholestasis and an abnormal pattern of hepatic protein synthesis or impaired clearance of plasma protein C would appear to develop in such pathological conditions.

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.

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.

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.

Plasma von Willebrand factor antigen and activity and platelet aggregability in patients with proteinuria.

Using a complex stimulating mixture containing ADP, epinephrine and collagen, a significantly (p less than 0.002) enhanced platelet aggregability, expressed as platelet sensitivity factor (PSF) was noted in platelet rich plasma of patients with proteinuria (PSF = 472 +/- 125), as against normal weight normolipidemic control subjects (PSF = 32.76 +/- 2.67). A significantly negative correlation (r. -0.579; p less than 0.001) was found between serum albumin concentration and the logarithmic values of platelet sensitivity factor. Plasma von Willebrand factor activity expressed as a percentage of normal was also significantly (p less than 0.001) higher in proteinuric patients (287% +/- 25.8) than in control subjects (99% +/- 5.02), but this hemostatic variable did not correlate with the logarithm of platelet sensitivity factor. Platelet aggregability was higher in hyperlipidemic nephrotic patients than in proteinuric patients with normal serum lipids, while renal failure led to a decrease of platelet function. The raised plasma levels of von Willebrand factor noted in proteinuric patients were not influenced by either hyperlipidemia or by chronic renal failure. It is concluded that changes affecting platelet function in the nephrotic syndrome are produced by other mechanisms than these leading to an increase of endothelia-derived von Willebrand factor. Both changes may, however, contribute to the thrombotic tendency of nephrotic patients.

Lupus anticoagulant and transient severe bleeding tendency in a girl aged nine years.

A 9-year old girl admitted in our clinic for severe hemorrhagic syndrome was found to display a high level of lupus anticoagulant (LA) leading to an important prolongation of phospholipid-dependent coagulation. Positive antinuclear and anti DNA antibodies, as well as very low levels of complement C3 and C4 proteins confirmed the diagnosis of systemic lupus erythematosus. Therapy with cortisone and cyclophosphamide led to normalization of the clotting tests but could not arrest the development of renal and hepatic lesions. The patient is one of the few cases with presence of lupus anticoagulant associated with severe hemorrhagic diathesis, in opposition to the more frequently reported thrombotic tendency connected with antiphospholipid antibodies.

Transient elevation of serum bile acids during acute pancreatitis.

An increase of serum bile acids was detected in patients with biliary acute pancreatitis who could be investigated during the first 24 hours after the onset of the acute phenomena. Serum bile acids levels, as well as alpha-amylase activity, however rapidly decreased and were found within normal limits after 48-72 h, while the increased serum gamma-glutamyltransferase activity persisted for at least 7 days. Changes affecting serum bile acids in patients with acute pancreatitis unassociated to biliary disease or in patients with acute biliary disease unaccompanied by a pancreatic reaction were less important. Mechanisms leading to these changes and their possible pathogenic relevance are briefly discussed.

Increased values of antipyrine clearance in type IV hyperlipoproteinemia.

When compared to values obtained in 17 normal weight normolipidemic control subjects (41.63 +/- 2.73 ml X min-1) antipyrine clearance determined in the saliva was found to be obviously decreased in the 10 patients with liver cirrhosis (21.88 +/- 0.79) and significantly increased in the 17 subjects with type IV hyperlipoproteinemia (59.91 +/- 4.59). Antipyrine clearance was positively correlated with both serum triglyceride concentration (r = 0.574; p less than 0.001) and serum cholinesterase activity (r = 0.705; p less than 0.001) and these correlations persisted even after the exclusion of cirrhotic patients. It is suggested that the accelerated hepatic secretion of very low density lipoproteins and of many export proteins and enzymes noted in most hypertriglyceridemic subjects is accompanied by an enhanced activity of liver microsomal enzymes involved in drug metabolism.