Platelet activation status decreases after menopause

Objective.?The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation.

Background.?Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women.

Methods.?By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb–IIIa complex (GPIIb–IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets?×?mean fluorescence of positive platelets). Also, thromboxane A₂ was quantified by means of its main plasma metabolite, thromboxane B₂, by enzyme immunoassay.

Results.?P-selectin and GPIIb–IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin^?+? platelets and of GPIIb–IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3?±?3, n?=?10) and Group B (6.2?±?2.9, n?=?27; mean?±?standard deviation (SD), p?<?0.001). GPIIb–IIIa binding index also differed significantly between both groups (Group A: 18.8?±?2.3, n?=?10 vs. Group B: 16.2?±?3.1, n?=?27; mean?±?SD, p?<?0.0018). Plasma concentration of thromboxane B₂ was 1.07?±?0.5?pg/well before menopause (Group A, n?=?10) and 1.9?±?4.1?pg/well after menopause (Group B, n?=?27), not significantly different (mean?±?SD, baseline?×?therapy, p?=?0.85).

Conclusions.?After the menopause, climacteric women – whose estradiol status is low – have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.     

Plasma adenosine levels and P-selectin expression on platelets in preeclampsia

OBJECTIVE: To measure the correlation of plasma adenosine levels with platelet activation in women with preeclampsia. METHODS: Plasma adenosine concentration and expression of P-selectin, a marker for platelet activation, were measured in 18 normal pregnant women and 18 preeclamptic women. The effect of 8-sulfophenyltheophylline, an adenosine receptor blocker, on expression of P-selectin on platelets also was measured. RESULTS: Plasma adenosine level averaged 0.77 +/- 0.11 microM (standard error of the mean [SEM]) in women with preeclampsia, significantly higher than the mean level of 0.47 +/- 0.08 microM in women with normal pregnancies (P <.05). Expression of P-selectin on platelets averaged 7.8 +/- 1.2% in women with preeclampsia, also significantly higher than the mean level of 4.7 +/- 0.7% in normal pregnancy (P <.05). Adenosine receptor blockade significantly increased expression of P-selectin on platelets in women with preeclampsia by 26% (P <.05), which was significantly higher than the 13% increase of activation in those with normal pregnancies (P <.05). CONCLUSION: Adenosine is an established platelet activation suppressor. Increased plasma levels of adenosine in preeclampsia might partially compensate and tend to prevent further excessive platelet activation in women with preeclampsia.     

Effect of nicotine on fetal prostacyclin and thromboxane in humans

To study the effect of nicotine on fetal prostacyclin and thromboxane A2, specimens from the umbilical arteries of infants born to healthy nonsmoking mothers were superfused in the absence or presence of nicotine (50 to 10,000 micrograms/mL), and the releases of 6-keto-prostaglandin F1alpha (a break-down product of prostacyclin) and thromboxane B2 (a metabolite of thromboxane A2) were measured. The baseline production of 6-keto-prostaglandin F1alpha (63.9 +/- 8.8 ng/minute per gram of dry weight tissue, mean +/- SE, N = 10) or that of thromboxane B2 (1.3 +/- 0.2 ng/minute per gram, N = 10) were unaffected by nicotine. To study the effect of nicotine on thromboxane A2 synthesis by the fetal platelets, thrombin-induced platelet aggregation and consequent thromboxane A2 synthesis were allowed to occur in the whole cord blood in the absence or presence of nicotine (10 to 500 micrograms/mL). Nicotine inhibited concentration dependently platelet thromboxane A2 synthesis from the baseline level (107.3 +/- 7.1 ng/mL) by 15 to 93%. This inhibition was also seen in thromboxane A2 synthesis starting from exogenous arachidonic acid, suggesting that nicotine inhibits either cyclooxygenase and/or thromboxane A2 synthetase in the fetal platelets. Thus, nicotine is hardly responsible for maternal smoking-induced changes in fetal prostacyclin formation.     

Time since menopause does not affect plasma viscosity, plasma thromboxane levels and Doppler findings.

OBJECTIVES: To evaluate whether the use of transdermal hormone replacement therapy (HRT), in women within 5 years of menopause compared with women who were postmenopausal for > 5 years, would significantly influence thromboxane B2 levels, plasma viscosity and Doppler flow parameters at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries. METHODS: Thirty-five normal-weight (body mass index > 19 and < 25 kg/m(2)) postmenopausal women (age 54.6 +/- 3.9 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 19, time since menopause < 5 years; and Group II: n = 16, time since menopause > 5 years). Patients were treated with a continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle). RESULTS: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Baseline plasma viscosity was similar in both groups, and decreased significantly after therapy in both Group I (-17.5%) and Group II (-15.6%). Plasma levels of thromboxane B(2) were similar at baseline and diminished equally in Group I and Group II (-85.6% and -85.2%, respectively) after treatment. Doppler assessment of the pulsatility index at the level of uterine, internal carotid, ophthalmic and bladder wall arteries showed no differences between groups at baseline and revealed a significant reduction of vascular impedance at the end of the treatment in both groups. CONCLUSIONS: Time since menopause does not affect the potential hemodynamic benefits of HRT in normal-weight women.     

Increased thromboxane biosynthesis in normal pregnancy is mainly derived from platelets

Thromboxane biosynthesis was determined in normal pregnant subjects by measurement of its major urinary and plasma metabolites, 2,3-dinor-thromboxane B2 and 11-dehydro-thromboxane B2. Urinary 2,3-dinor-thromboxane B2 increased early in pregnancy (731 +/- 124 pg/mg creatinine) compared with nonpregnancy (less than 350 pg/mg creatinine; p less than 0.001) and the postpartum period (155 +/- 42 pg/mg creatinine, p = 0.015) and remained elevated throughout gestation. Similarly, plasma and urinary 11-dehydro-thromboxane B2 were increased in pregnancy. To determine the cellular origin of the increase in thromboxane biosynthesis in pregnancy, platelet cyclooxygenase was selectively inhibited with aspirin in a dose of 120 mg orally followed by 20 mg twice daily for 7 days (n = 4). Selectivity was confirmed by measurement of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha, an index of prostacyclin biosynthesis. Coincident with a 97% inhibition of serum thromboxane B2, urinary 2,3-dinor-thromboxane B2 was almost completely inhibited and paralleled the recovery of platelet cyclooxygenase after withdrawal of aspirin. This study demonstrates that thromboxane biosynthesis is increased in pregnancy. The increase is mainly platelet derived and is consistent with increased platelet activation throughout pregnancy.     

Low-dose aspirin. I. Effect on angiotensin II pressor responses and blood prostaglandin concentrations in pregnant women sensitive to angiotensin II

Decreased incidence of proteinuric hypertension after low-dose aspirin therapy is hypothesized to be a consequence of selective thromboxane A2 inhibition and sparing of prostacyclin. This study was designed to ascertain if low-dose aspirin therapy (81 mg/day for 1 week) alters vascular refractoriness to angiotensin II and the prostacyclin/thromboxane A2 ratio in pregnant women sensitive to angiotensin II (n = 17). Low-dose aspirin increased the effective pressor dose of angiotensin II from 5.9 +/- 2.4 to 10.2 +/- 5.5 ng/kg/min (p less than 0.01, mean +/- SD). Platelet-derived serum thromboxane B2 (a metabolite of thromboxane A2), a measure of therapy compliance, decreased from 1804 +/- 1771 to 132 +/- 206 pg/ml (p less than 0.01). Plasma thromboxane B2 decreased from 130 +/- 107 to 19 +/- 12 pg/ml (p less than 0.01). Inhibition was not selective because 6-keto-prostaglandin F1 alpha (a metabolite of prostacyclin) also decreased from 243 +/- 90 to 163 +/- 90 pg/ml (p = 0.039) and prostaglandin E2 was reduced from 155 +/- 67 to 95 +/- 40 pg/ml (p = 0.014). Decreases in thromboxane B2, however, were significantly greater (75% +/- 19%) than decreases in 6-keto-prostaglandin F1 alpha (21% +/- 33%) or prostaglandin E2 (29% +/- 36%); thus the 6-keto-prostaglandin F1 alpha/thromboxane B2 ratio increased from 3.1 +/- 2.0 to 12.4 +/- 9.9 (p less than 0.01). Although low-dose aspirin increases the effective pressor dose of angiotensin II, it does not return to normal pregnancy values. This observation is consistent with the hypothesis that this represents only a partial selective prostaglandin inhibition.     

Plasma nitric oxide levels and the expression of P-selectin on platelets in preeclampsia

OBJECTIVE: The purpose of this study was to investigate the correlation of plasma nitric oxide levels with the expression of P-selectin on platelets in preeclampsia. STUDY DESIGN: Plasma levels of nitrite and nitrate (the stable nitric oxide metabolites) and the expression of P-selectin on platelets (a platelet activation marker) were measured in 25 normal pregnant women and 25 women with preeclampsia. The effects of the inhibition of nitric oxide synthesis on the expression of P-selectin also was measured in vitro. RESULTS: Plasma nitrate levels and the expression of P-selectin averaged 30.5 +/- 2.2 micromol/L and 8.9% +/- 1.1% (SEM), respectively, in preeclampsia, which was significantly higher than in normal pregnancy (P <.05). Nitric oxide synthesis inhibition in vitro significantly increased the expression of P-selectin in normal pregnancy by 284% (P <.05), which was significantly higher than in preeclampsia (156%, P <.05). CONCLUSION: The inhibitory effects of increased nitric oxide on the expression of P-selectin is attenuated in preeclampsia, which may contribute partly to the pathogenesis of preeclampsia.     

Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors

The clinical and biochemical effects of a prostaglandin synthesis precursor (Efamol) containing linoleic acid and its metabolite, gamma-linolenic acid, were studied in 30 women with severe, incapacitating premenstrual syndrome. Efamol treatment alleviated the premenstrual symptoms in general and depression especially better than did a placebo. The capacity of platelets to release thromboxane B2 during spontaneous clotting was decreased in patients undergoing Efamol treatment (141 +/- 59 ng/ml, mean +/- SD) as compared to those undergoing placebo treatment (186 +/- 44 ng/ml, p less than 0.01) and control subjects (176 +/- 40 ng/ml, n = 25, p less than 0.05). No changes were found in plasma 6-keto-prostaglandin F1alpha or in FSH, LH, prolactin, progesterone, estradiol and testosterone. The data suggest that prostaglandins might play a role in the pathophysiology of the premenstrual syndrome.     

Low-dose aspirin in pregnancy

In a prospective study, we evaluated the effects of low-dose aspirin on maternal and neonatal plasma 6-keto-prostaglandin (PG) F1 alpha concentration, platelet aggregation, platelet thromboxane production, and neonatal transitional circulation. Forty women, at a mean (+/- SD) of 37 +/- 2 weeks' gestation, were randomized to receive (N = 10 each) placebo or 20, 60, or 80 mg of aspirin per day until delivery. Maternal serum 6-keto-PGF1 alpha levels were not affected by these doses of aspirin, whereas thromboxane B2 generated during clotting of maternal blood was decreased significantly by 60 and 80 mg of aspirin by 1 week of therapy. Maternal platelet thromboxane B2 production in response to adenosine diphosphate or collagen was reduced 98% by the 80-mg dose after 1 week of aspirin therapy. The 60-mg dose reduced maternal platelet thromboxane B2 production in response to adenosine diphosphate (50% decrease) or collagen (60% decrease) after 1 week of treatment, a nonsignificant difference. After 2 weeks of treatment with 60 mg of aspirin, platelet thromboxane B2 production induced by both collagen and adenosine diphosphate was inhibited significantly (P less than .01). Neonatal serum levels of 6-keto-PGF1 alpha and thromboxane B2 were not affected by any doses of aspirin. Further, neonatal platelet aggregation in response to platelet stimulation by collagen and adenosine diphosphate was not inhibited. All neonates had echocardiographic evidence of a patent ductus arteriosus, and noninvasive estimates of pulmonary arterial pressure were similar among the groups of infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental thromboxane and prostacyclin in the regulation of placental blood flow

To study the significance of placental thromboxane A2 and prostacyclin in the regulation of placental blood flow, intervillous blood flow was measured using a 133Xenon method from 39 women zero to two days before delivery and compared it with the placental production of thromboxane A2 and prostacyclin as measured with a superfusion method postpartum. The placental production of thromboxane B2 (a metabolite of thromboxane A2; 4.5 +/- 1.3 ng/minute per gram dry weight of tissue; mean +/- SD) and that of 6-keto-prostaglandin F1 alpha (a metabolite of prostacyclin; 0.64 +/- 0.27 ng/minute per gram) did not correlate significantly with intervillous blood flow (153.1 +/- 108.0 mL/minute per 100 mL; r = -0.308 and 0.245, respectively), whereas the thromboxane B2/6-keto-prostaglandin F1 alpha ratio (8.53 +/- 4.3) was inversely related to intervillous blood flow (r = -0.419; P less than .01). In the women with intervillous blood flow below the normal mean (less than 130 mL/minute per 100 mL; N = 20) placental thromboxane B2 production (5.1 + 1.2 ng/minute per gram) was higher (P less than .005) and that of 6-keto-prostaglandin F1 alpha (0.54 +/- 0.23 ng/minute per gram) lower (P less than .02) than those in women with intervillous blood flow above 130 mL/minute per 100 mL (thromboxane B2 4.01 +/- 1.0 and 6-keto-prostaglandin F1 alpha 0.75 +/- 0.27 ng/minute per gram; N = 19). These results suggest that placental thromboxane A2 and prostacyclin may be factors in the regulation of intervillous blood flow and that their balance of production is more important than the presence of either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostacyclin and thromboxane levels in women with severe preeclampsia undergoing magnesium sulfate therapy during antepartum and postpartum periods.

OBJECTIVE: To study effects of magnesium sulfate (MgSO(4)) on prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)) levels in women with severe preeclampsia during antepartum and postpartum periods. METHODS: Women with severe preeclampsia were randomized into two groups. Patients in Group A were continuously infused with MgSO(4) for 24 hours postpartum. In Group B, MgSO(4) administration was discontinued when urinary output was of > or =100 ml/hr for 2 consecutive hours. Patient demographic data were collected. Venous blood was drawn at time of MgSO(4) administration and 24 hours after delivery. Plasma levels of 6-keto-PGF1alpha and TXB(2), stable metabolites of PGI(2) and TXA(2), were measured by enzyme-linked immunosorbent assay (ELISA). Data are presented as mean +/- SE, and analyzed by paired t-test. RESULTS: A total of 50 patients were recruited, with 27 in Group A and 23 in Group B. There were no statistical differences for demographic data between the two groups with regards to maternal age; gestational age; systolic and diastolic blood pressures at admission, 12 hours postpartum, and 24 hours postpartum; and mode of delivery. Platelet counts were all within the normal range at the time of enrollment. MgSO(4) was administered for an average of 10 hours postpartum in Group B. Maternal blood pressures returned to normal or close to normal levels in both groups at 24 hours postpartum. 6-keto PGF1alpha levels were significantly decreased 24 hours after delivery compared with the levels at enrollment in both groups, (Group A: 98 +/- 13 vs. 180 +/- 28 pg/mL; Group B: 142 + 17 vs. 194 +/- 31 pg/mL, p < 0.05, respectively). However, there was no difference detected between the two groups. TXB(2) levels were not different between group A and Group B at the time of enrollment, 38 +/- 9 vs. 33 +/- 8 pg/mL, and 24 hours postpartum, 26 +/- 5 vs. 25 +/- 3 pg/mL, respectively. CONCLUSIONS: Administration of MgSO(4) does not affect prostacyclin and thromboxane levels in the maternal circulation in women with preeclampsia during antepartum and postpartum periods. We speculate that a higher level of prostacyclin before delivery may reflect compensatory effects of this vasodilator to offset increased maternal blood pressure during pregnancy.     

Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.     

Evaluation of a rat model of preeclampsia for HELLP syndrome characteristics

OBJECTIVE: To determine whether a rat model of preeclampsia includes features consistent with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. METHODS: Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats using the reduced uterine perfusion pressure (RUPP) model. On day 14 of gestation, silver clips were placed around the aorta below the renal arteries and on the left and right uterine arcade at the ovarian artery. All animals were chronically instrumented to determine conscious blood pressure and to obtain blood samples for analysis of complete blood count, platelet count, liver function tests, uric acid, creatinine, and albumin. Blood samples were collected and animals sacrificed on day 19 of gestation, at which time placental and pup weight were obtained. A control group was analyzed similarly. Statistical analysis was performed with the Student t test. RESULTS: The RUPP model animals (n = 8), when compared with the normotensive controls (n = 9), did not show a statistically significant difference in hemoglobin, platelets, liver function tests, uric acid, creatinine, or albumin, although the mean arterial pressure was higher (mean +/- SD 131.9 +/- 17.1 mmHg versus 104.0 +/- 14.0 mmHg, respectively; P = .003) and pup number was lower (RUPP 6.6 +/- 2.4 versus control 13.8 +/- 2.3, P < .001). CONCLUSION: Although decreased uteroplacental perfusion induces changes similar to symptoms of preeclampsia, the RUPP rat model does not appear to express features of HELLP syndrome.     

Placental umbilical cord blood transfusion: a new method of treatment of patients with diabetes and microalbuminuria in the background of anemia

Diabetes mellitus is the commonest endocrine disease in all populations and all age groups. It is a syndrome of disturbed intermediary metabolism caused by inadequate insulin secretion or impaired insulin action, or both. Anemia is a common accompaniment of diabetes, particularly in those with albuminuria justifying tubulointestitial injury or reduced renal function. There are other additional factors present in diabetes, which may contribute to the development of an increased risk of anemia. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, hypo-antigenic nature, altered metabolic profile and high affinity for oxygen, may be an ideal choice for cases of diabetes with severe anemia necessitating blood transfusion. This article presents my team's experience with 78 units of placental umbilical cord whole blood (from 1 April 1999 to April 2005), collected after lower uterine cesarean section (LUCS) from consenting mothers (56 ml-138, ml mean 82 ml +/- 5.6 ml SD, median 84 ml, mean packed cell volume 49.7 +/- 4.2 SD, mean percent hemoglobin concentration 16.6 g/dl +/- 1.5 g/dl SD) and transfused to diabetes patients with microalbuminuria and severe anemia necessitating transfusion. After collection, the blood was transfused, in most cases immediately after completion of the essential norms of transfusion. In rare cases, it was kept in the refrigerator and transfused within 72 hours of collection to a suitable recipient. For inclusion in this study, the patient's percent plasma hemoglobin had to be 8 g/dl or less (the pretransfusion hemoglobin in this series varied from 5.2 g/dl to 7.8 g/dl) in the background of type two diabetes (fasting sugar 200 mg or more), along with features of microalbuminuria (albumin excretion 30-299 mg/g creatinine). This study included 39 informed consenting patients (22 males + 17 females, aged 48-74 yrs, mean 59.6 yrs). The patients were randomized into two groups: Group A (control cases N = 15, males = 8 and females = 7) and Group B (study group N = 24, males = 14 and females = 10). In Group A the rise of hemoglobin (Hgb) after two units of adult blood transfusion was 1.5 to 1.8 g/dl, as seen after a 72-hour blood sample assessment. The rise of Hgb as noted after 72 hours of two units of freshly collected cord blood transfusion was .6 g/dl to 1.5 g/dl. Each patient received two of four units of freshly collected cord blood transfusion (two units at a time), depending on availability and compatibility. Microalbuminuria was assessed in both groups after one month of treatment with transfusion and other identical support. The mean result was 152 +/- 18 m SD of albumin per gram of creatinine excreted through 24-hour urine (pre-transfusion mean excretion was 189 +/- 16 mg) in Group A and 103 +/- 16 mg SD of albumin excretion per gram of creatinine in 24-hour excretion of urine in Group B (pretransfusion mean excretion was 193 +/- 21 mg). Univariate analysis using Fisher's exact test was performed for the results of Groups A and B. The difference between Group A and B values and its comparison with the pre-transfusion microalbuminuria appeared to be statistically significant (p < less than .003). We have not encountered any clinical, immunological or non-immunological reaction so far in either group. Fetomaternal cell traffic has been implicated as the cause of scleroderma in mothers delivering male babies. In the present series, we did not see any such rare and unusual complication due to neonatal blood transfusion in the adult system in Group B patients in the six years from the initiation of the study.     

Ischemia of the limb stimulates thromboxane production and myocardial depression

Thromboxane A2 is thought to be an important mediator of cardiopulmonary dysfunction, hence stimuli that effect synthesis of this prostanoid are of major interest. In this study, the thesis that ischemia of the limb is a significant stimulus to thromboxane A2 synthesis and the generation of a circulating negative inotrope is tested. Twelve healthy volunteers, taking no medications and ranging in age from 21 to 29 years, underwent inflation of an arm cuff to either 70 or 220 millimeters of mercury for ten minutes. Immediately after deflation of the cuff from 220 millimeters of mercury, the stable degradation product of thromboxane A2, thromboxane B2, rose from a base line plasma level of 34 +/- 6 picograms per milliliter (mean +/- SEM) to 70 +/- 18 picograms per milliliter. In contrast, deflation from a cuff pressure of 70 millimeters of mercury resulted in a lower thromboxane B2 level of 26 +/- 9 picograms per milliliter (p less than 0.05). Plasma obtained before and after inflation of the cuff to 220 millimeters of mercury was used to bathe a rat papillary muscle. Developed tension fell from a base line of 2.80 +/- 0.19 to 2.44 +/- 0.17 grams (p less than 0.01). There was no significant change in developed tension induced by plasma harvested after the cuff was inflated to 70 millimeters of mercury. The base line plasma level of 6-keto-prostaglandin F1 alpha, the hydrolysis product of prostacyclin, was 46 picograms per milliliter; the plasma serotonin, 51 nanograms per milliliter; the platelet serotonin, 1.02 micrograms per 10(9) platelets; platelet count, 220,000 per cubic millimeter, and white blood count, 6,094 per cubic millimeter. These values did not change significantly with cuff inflation to either 220 or 70 millimeters of mercury. The results show that ischemia of the limb leads to thromboxane A2 production. Possible adverse cardiac effects related to this event are suggested by the bioassay demonstrating that circulating plasma with high levels of thromboxane B2 is associated with the depression of tension of an isolated rat papillary muscle.     

Effects of hormone replacement therapy on plasma viscosity and Doppler variations in postmenopausal non-smokers and heavy smokers.

OBJECTIVES: To evaluate the effects of transdermal hormone replacement therapy (HRT) on some biological cardiovascular risk factors, specifically thromboxane B2 level and plasma viscosity. Furthermore, we investigated Doppler flow modifications at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries, and evaluated whether there were significant differences, in the examined parameters, between postmenopausal women who were non-smokers and heavy smokers. METHODS: Forty-three postmenopausal women (age 53.6 +/- 3.3 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 21, normal controls; and Group II: n = 22, heavy smokers). Patients were treated with continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle). RESULTS: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Plasma viscosity decreased significantly after 6 months of therapy both in non-smokers and heavy smokers (-18% and -14%, respectively). Plasma levels of thromboxane B2, which were similar at baseline, underwent a dramatic reduction in both Group I and Group II (-93% and -88%, respectively). Doppler assessment of pulsatility index at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries showed a significant reduction in vascular impedance at the end of treatment in both groups. However, the treatment was significantly less beneficial, in terms of the analyzed factors, in heavy smokers. CONCLUSIONS: Cigarette smoking represents a cardiovascular risk factor that can only partially be modified by the administration of transdermal HRT.     

Plasma immunoreactive beta-endorphin, ACTH and cortisol concentrations in mothers and their neonates immediately after delivery--their relationship to the duration of labor

In 29 cases of vaginal delivery with normal outcome and 4 cases of cesarean section, the concentrations of beta-endorphin, ACTH and cortisol were determined in maternal venous and umbilical venous plasma immediately postpartum. According to duration of labor and mode of delivery the cases examined were classified into three groups: Group A (18 cases) = vaginal delivery of less than 10 hours' duration, Group B (11 cases) = vaginal delivery of more than 10 hours' duration of labor, Group C (4 cases) = cesarean section under general anesthesia. With the exception of one, the deliveries took place at term. The 33 neonates were in a very good clinical state 5 minutes after parturition (11 Saling points as median value). For measurement of the hormone concentrations radioimmunoassays were used. In Group a the mean beta-endorphin concentration in maternal plasma amounted to 150.9 +/- 16.3 pg/ml, that in neonatal plasma to 239.2 +/- 23.5 pg/ml (means +/- SEM). In Group B plasma beta-endorphin, both maternal and neonatal, was slightly higher than in Group A: 153.0 +/- 12.0 pg/ml (maternal) and 260.9 +/- 37.1 pg/ml (neonatal). The differences between maternal and neonatal beta-endorphin levels were statistically significant: Group A p less than 0.01, Group B p less than 0.05; chi 2-test. The mean ACTH concentrations in the plasma of the newborn infants were also found to be considerably higher compared with those in the plasma of their mothers: Group A 78.2 +/- 16.5 pg/ml (maternal) and 98.0 +/- 23.3 pg/ml (neonatal); Group B 98.0 +/- 20.1 pg/ml (maternal) and 165.8 +/- 39.6 pg/ml (neonatal).(ABSTRACT TRUNCATED AT 250 WORDS)     

Perinatal outcome of very low birthweight infants by mode of delivery.

In order to evaluate the influence of mode of delivery on perinatal morbidity and mortality in vertex infants weighing less than 1500 g (VLBW), we made a retrospective study of 152 singleton newborns, in vertex presentation, with a birthweight of less than 1500 g, delivered in the Cruces Hospital (Vizcaya, Spain), a major perinatal referral center, between 1 January 1987 and 31 December 1989. Twins and infants with lethal congenital anomalies or gross intrauterine growth deviations were excluded from the study (n = 71). Of the infants studied (n = 81), 37 were delivered by cesarean section (mean weight 1120 +/- 206 g, range: 680-1495 g) and 44 were delivered vaginally (mean weight 1029 +/- 283 g, range: 530-1475 g). The patients were divided into four groups: Group A: 500-749 g (n = 10); Group B: 750-999 g (n = 21); Group C: 1000-1249 g (n = 27); and Group D: 1250-1499 g (n = 23). The percentages of cesarean sections in each group were 10%, 42%, 66% and 39%, respectively. A comparison within each group of immediate perinatal outcome (Apgar score and umbilical vein cord pH), as well as mortality and sequelae up to 1 year of age did not yield any significant differences between cesarean and vaginal birth. We conclude that cesarean delivery does not appear to offer improved outcome over vaginal delivery in live births without congenital anomalies. For this reason, we believe that fetal weight should not be the only obstetrical variable considered when deciding whether or not to perform a cesarean section in these circumstances.     

Maternal-neonatal 8-hydroxy-deoxyguanosine serum concentrations as an index of DNA oxidation in association with the mode of labour and delivery

AIM: To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS), and the biomarker of DNA oxidation, 8-hydroxy-deoxyguanosine (8-OHdG) serum levels, in mothers and their newborns. SUBJECTS AND METHODS: Some 106 women with normal pregnancy and normal blood biochemical parameters were divided into 4 groups: Group A (n=28) with normal labour and vaginal delivery (VG), Group B (n=25) with scheduled cesarean section (CS), Group C (n=26) with 'emergency' CS, and Group D (n=27) with prolonged labour+VG. Blood was obtained from the mothers at the beginning of labour, and immediately after delivery (pre- and post-delivery), as well as from the umbilical cord (CB). TAS, 8-OHdG and creatine kinase (CK) were measured in the sera with appropriate methodology. RESULTS: TAS levels were almost similar in all the groups pre-delivery, and in CB irrespective of the mode of labour and delivery, and remarkably decreased in Groups C and D post-delivery. 8-OHdG levels in Group C (0.94+/-0.08 ng/ml) and Group D (0.98+/-0.08 ng/ml) were significantly higher than those in Group A (0.26+/-0.01 ng/ml, p<0.001) and Group B (0.28+/-0.07 ng/ml, p<0.001) post-delivery. 8-OHdG levels were low in CB, independent of the mode of labour. CK positively correlated with 8-OHdG (r=0.48, p<0.001), the latter negatively correlated with TAS (r=-0.53, p<0.01). CONCLUSIONS: The lowest TAS and the highest 8-OHdG levels were found in Groups C and D post-delivery, probably due to the long-term participation of the mothers' skeletal and uterus muscles, whereas 8-OHdG levels were low in CB irrespective of the mode of delivery, possibly as a consequence of the antioxidant action of the placenta and/or the low lipid levels in the serum of the umbilical cord.     

Long-acting gonadotropin hormone-releasing hormone analog used to treat uteri

Because the size of leiomyomata uteri often decreases significantly after menopause, the authors elected to employ a long-acting gonadotropin hormone-releasing hormone analog (GnRH-alpha) (imbzl-D-His6-Pro9-Net-GnRH) to create a state of pseudomenopause in six patients with leiomyomata uteri diagnosed on the basis of pelvic examination and confirmed by pelvic ultrasonography. Patients received daily, subcutaneous injections of GnRH-alpha (4 micrograms X kg-1 X 24 hour-1) for 6 months. Uterine size (13.8 +/- 4 weeks [mean +/- standard deviation (SD), n = 6]) was determined by pelvic examination and uterine volume (533.9 +/- 394 ml [mean +/- SD, n = 6]) was determined by pelvic ultrasonography before medical therapy was begun. They observed a decrease in uterine size by pelvic examination within 4 weeks of the initiation of therapy, and all patients experienced a decrease in uterine size (9.5 +/- 4 weeks [mean +/- SD, n = 6]) (P less than 0.05) within 8 weeks of initiation of therapy. After 6 months of therapy, uterine size was 229.5 +/- 145 ml (mean +/- SD, n = 6). During treatment, plasma estrogen concentrations were assessed intermittently (every 1 to 4 weeks) and remained less than 4 pg X ml-1 throughout the period of therapy. All six patients have discontinued therapy. There has been no increase in uterine size in these patients for a period from 3 to 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)