Association of bilateral oophorectomy and menopause hormone therapy with mild cognitive impairment: the REDLINC X study.

BACKGROUND: Dementia is a major public health problem. Estrogen is a regulator of the central nervous system and its deficit could be involved in cognitive decline in older women. OBJECTIVE: This study aimed to evaluate the association of bilateral oophorectomy, menopause hormone therapy (MHT) and other factors on mild cognitive impairment (MCI). METHOD: The case-control study included 941 otherwise healthy postmenopausal women aged 60 years and over from six Latin American countries. Personal and family data were recorded and MCI was assessed using the Montreal Cognitive Assessment test (MoCA). RESULTS: Average age, years of education and body mass index were 66.1 ± 5.8 years, 12.4 ± 5.0 years and 26.0 ± 4.3 kg/m2, respectively. A total of 30.2% had undergone bilateral oophorectomy and 40.3% had used MHT. A total of 232 women (24.7%) had MCI. The prevalence of MCI was higher in women with intact ovaries and non-MHT users as compared to MHT users (29.3% vs. 11.7% [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.20-0.51]). Among oophorectomized women, MCI prevalence was higher among non-MHT users as compared to MHT users (45.2% vs. 12.8% [OR 0.18; 95% CI 0.10-0.32]). Logistic regression analysis determined that the variables associated with MCI were age >65 years (OR 1.69; 95% CI 1.20-2.38), parity (having >2 children; OR 1.69; 95% CI 1.21-2.37), bilateral oophorectomy (OR 1.56; 95% CI 1.09-2.24), hypertension (OR 1.41; 95% CI 1.01-1.96), being sexually active (OR 0.56; 95% CI 0.40-0.79), education >12 years (OR 0.46; 95% CI 0.32-0.65) and MHT use (OR 0.31; 95% CI 0.21-0.46). CONCLUSION: Age, parity, bilateral oophorectomy and hypertension are independent factors associated with MCI; contrary to this, higher educational level, maintaining sexual activity and using MHT are protective factors.

Muscle health in Hispanic women. REDLINC VIII.

Objectives: This study aimed to evaluate muscle strength and related factors in Hispanic women.Methods: We studied 593 women between 40 and 89 years old. The women were asked about personal and clinical information. The following instruments were applied: dynamometer (strength), Short Physical Performance Battery (physical performance), SARC-F (sarcopenia), International Physical Activity Questionnaire (physical activity), Menopause Rating Scale (quality of life), 36-item Short Form (general health), and Frailty (Fried's criteria).Results: Low muscle strength rises from 7.1% of women in their 40s to 79.4% in their 80s. Physical performance is low in 0.5% of the first group and rises to 60.5% in the second. The risk of sarcopenia increases significantly from 6.7% in younger women to 58.1% in older women. Frailty, which affects less than 1% of women under age 60 years, increases to 39.5% in their 80s. Sedentary lifestyle rises from 26% to 68.3%. Fragility impairs the quality of life and the perception of health (p < 0.0001). The deterioration of different tests of muscle function is significantly associated with age >70 years (OR 5-20) and with osteoarthritis (OR 4-9). Menopause before the age of 45 years increases the risk of sarcopenia (odds ratio 2.2; 95% confidence interval 1.2-4.0).Conclusion: With aging there is a decrease in muscle strength and an increase in frailty. This entails a decrease in the quality of life.

Gender differences in the prevalence of vitamin D deficiency in a southern Latin American country: a pilot study.

Aim: This study aimed to study the prevalence of vitamin D deficiency, assessing the influence of sex, age, and season of the year.Methods: A cross-sectional study was conducted with 1329 healthy subjects (668 women and 661 men) aged 18-89 years in Santiago, Chile. Age (years), body mass index, medical history, working status, sex, and date of blood sample were collected.Results: Men were slightly older than women (53.1 ± 18.2 vs. 50.0 ± 15.6 years; p < 0.01) and a higher percentage worked outside the home (73.1% vs. 51.9%, p < 0.001). The mean serum concentration of 25-hydroxyvitamin D (25(OH)-D) was 23.3 ± 9.3 ng/ml in women and 20.9 ± 9.5 ng/ml in men (p < 0.001). The levels of 25(OH)-D by season were 26.7 ± 9.0, 23.6 ± 9.7, 19.4 ± 8.5, and 19.1 ± 9.5 ng/ml (for summer, fall, winter, and spring, respectively; p < 0.05). The prevalence of vitamin D deficiency increases with age, rising from 36.5% under 40 years to 48.0% over 60 years (p < 0.004). Male sex, winter and spring, and age showed negative correlation with levels of 25(OH)-D (p < 0.05). Multivariate linear regression showed a final model that incorporates: age (coefficient: -0.06; 95% confidence interval [CI]: -0.09 to -0.03; p < 0.001), male sex (coefficient: -2.00; 95% CI: -2.96 to -1.05; p < 0.001), summer (coefficient: 7.30; 95% CI: 6.17 to 8.43; p < 0.001), and fall (coefficient: 4.27; 95% CI: 3.04 to 5.50; p < 0.001).Conclusions: Vitamin D deficiency is more prevalent in men than in women, in the elderly, and during the winter and spring seasons.

Postmenopausal androgen-secreting ovarian tumors: challenging differential diagnosis in two cases.

Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido. The laboratory tests showed high levels of testosterone (>100 ng/ml). A normal value of dehydroepiandrosterone sulfate and a normal cortisol level at 9 am after 1 mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands. A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.

Risk factors of long-term mortality in middle-aged women: a 27-year follow-up cohort.

OBJECTIVE: This study aimed to evaluate the impact of different risk factors on long-term mortality in middle-aged women. METHODS: Women who received preventive health care control between 1990 and 1993 were recruited. Anamnesis and physical examination were recorded. Blood samples for the measurement of glycemia and lipids were taken. Data are reported as of December 2017. RESULTS: We studied 1197 women aged between 40 and 60 years. We observed 183 deaths (survival 84.0%; 95% confidence interval [CI], 81.7-86.1, Kaplan-Meier survival analysis). The main causes of death were cancer (39.9%; 95% CI, 32.7-47.1), cardiovascular disease (22.9%; 95% CI, 16.8-29.1), infectious disease (13.7%; 95% CI, 8.6-18.7), other causes (7.1%, 95% CI, 3.4-10.9), and unspecified cause (6.6%; 95% CI, 2.9-10.2). The final Cox regression model showed the following hazard ratios for mortality: diabetes mellitus 2.51 (95% CI, 1.40-4.51), history of fracture 2.47 (95% CI, 1.15-5.30), history of heart illness 2.06 (95% CI, 1.15-3.72), arterial hypertension 1.51 (95% CI, 1.08-2.11), age 1.07 (95% CI, 1.04-1.10), body mass index 1.06 (95% CI, 1.02-1.09), and sexual intercourse 0.94 (95% CI, 0.89-0.98). Lipid disorders did not reach statistical significance as a risk factor. CONCLUSION: Diabetes, a history of fractures, and cardiovascular risk factors, except lipids, are markers of long-term mortality in middle-aged women. Physicians should pay special attention to these risk factors.

Does the menopausal status of female gynecologists affect their prescription of menopausal hormone therapy?

OBJECTIVE: To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT). METHODS: Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use. RESULTS: A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%). CONCLUSION: Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.

Life cycle sustainability assessment of short chain carboxylic acid produced from municipal bio-wastes.

Bio-based products are a fast-growing market due to increasing consumer consciousness for sustainability. Although this is per se a positive trend, it leads to a higher demand for organic feedstocks which normally comes from primary agricultural sources and can lead to undesired deforestation or other land use changes to farmland. At the same time, Europe is facing another challenge related with the treatment of organic wastes. In this context, the project CAFIPLA developed an integrated process to convert heterogeneous organic materials to building blocks for the bio-based economy. This study performs a life cycle sustainability assessment (life cycle assessment, life cycle costing and social life cycle assessment) of the production of short chain carboxylic acids (SCCA) employing municipal bio-wastes as a feedstock. In addition to a hot-spot identification to detect the main sources of impact, a comparison of the novel technology with the current benchmark is carried out applying a cradle-to-gate approach and using 1 kg of SCCA as a functional unit. Results show the great performance of CAFIPLA in all the environmental categories analysed. Furthermore, the profitability of the plant is also verified, reaching a payback period below 6 years as long as the product is sold above 0.49 €/kg. Finally, the potential social risk associated to the supply chain is also improved with CAFIPLA technology.

Melatonin exerts direct inhibitory actions on ACTH responses in the human adrenal gland.

In nonhuman primates and rodents, melatonin acting directly on the adrenal gland, inhibits glucocorticoid response to ACTH. In these species, an intrinsic adrenal circadian clock is involved in ACTH-stimulated glucocorticoid production. We investigated whether these findings apply to the human adrenal gland by determining i) expression of clock genes in vivo and ii) direct effects of melatonin in ACTH-stimulated adrenal explants over a) expression of the clock genes PER1 (Period 1) mRNA and BMAL1 [Brain-Muscle (ARNT)-like] protein, ACTH-induced steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and b) over cortisol and progesterone production. Adrenal tissue was obtained from 6 renal cancer patients undergoing unilateral nephrectomy-adrenalectomy. Expression of the clock genes PER1, PER2, CRY2 (Cryptochrome 2), CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1, was investigated by RT-PCR in a normal adrenal and in an adenoma. In independent experiments, explants from 4 normal adrenals were preincubated in culture medium (6 h) followed by 12 h in: medium alone; ACTH (100 nM); ACTH plus melatonin (100 nM); and melatonin alone. The explants' content of PER1 mRNA (real-time PCR) and StAR, 3ß-HSD, BMAL1 (immuno slot-blot), and their cortisol and progesterone production (RIA) were measured. The human adrenal gland expresses the clock genes PER1, PER2, CRY2, CLOCK, and BMAL1. ACTH increased PER1 mRNA, BMAL1, StAR, and 3ß-HSD protein levels, and cortisol and progesterone production. Melatonin inhibited these ACTH effects. Our study demonstrates, for the first time, direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland.

Ovarian thecoma: A very unusual cause of postmenopausal bleeding.

We describe a 67-year-old woman with postmenopausal bleeding having ceased estrogen plus progestogen therapy nine months before. Transvaginal ultrasonography showed endometrial thickening with normal ovarian appearance. Hormonal studies revealed high estradiol and inhibin B levels but normal androgens and adrenal hormones. Magnetic resonance image demonstrated a 13-mm left ovarian tumour. Hysterectomy and bilateral salpingo-oophorectomy were performed, and the pathological study revealed an 8 mm ovarian thecoma. This case illustrates a very unusual cause of postmenopausal bleeding. We suggest a study protocol and discuss the differential diagnosis of this case.

New splicing mutation of MEN1 gene affecting the translocation of menin to the nucleus.

UNLABELLED: Multiple endocrine neoplasia type 1 (MEN1) is a syndrome inherited in an autosomal dominant trait caused by the inactivation of the tumor suppressor gene MEN1. OBJECTIVE: To communicate a family with a new heterozygous germ line mutation in the intronic region of MEN1 gene and to study its influence in the menin expression. PATIENTS AND METHODS: We studied 5 members of a family with symptomatic hyperparathyroidism (HPT). One of them had also a neuroendocrine pancreatic tumor, and 2 had non-functional multinodular cortical adrenal hyperplasia compatible with the diagnosis of MEN1. After the mutation was identified, HSP92II restriction enzyme was used to determine both zygosity and segregation of the mutation. RT-PCR from leukocyte's isolated mRNA and western blot from pancreatic tumor tissue were performed. In vitro studies were done in Chinese hamster ovary (CHO) cells transfected with reporter minigenes carrying the coding regions spanning exon (EX)-intron 9 and EX10 with the mutant and the wild type sequences. RESULTS: We identified a heterozygous G-to-T substitution in the intron-EX junction (IVS9-1 G>T) of MEN1 gene in the index case and the family members. The mRNA from patient's leukocytes was larger (934 bp) in comparison to the normal transcript (717 bp). Immunoblot analysis demonstrated that wild type (67 kDa) and two additional mutant proteins (approximately 55 and approximately 90 kDa) were expressed in the pancreatic tissue. The in vitro study showed a 45% nuclear localization of the mutated menin signal and a 95% in the wild type protein. CONCLUSIONS: We identified a new intronic heterozygous germ line mutation (IVS9-1G>T) of MEN1 gene in a family affected by MEN1 syndrome. This mutation alters the splice acceptor site of intron 9 that promotes an incorrect splicing, generating aberrant proteins without the nuclear localization signals necessary for the normal menin translocation to the nucleus.

Studies of impaired aldosterone response to spironolactone-induced renin and potassium elevations in adenomatous but not hyperplastic primary aldosteronism.

Spironolactone (SPL) corrects hypertension, hypokalemia, and hyporeninemia in patients with primary hyperaldosteronism (PHA) by blocking mineralocorticoid (MCH) receptors. We evaluated the effect of continuous SPL treatment (100 to 300 mg/day for 7 days to 9 years) on plasma renin (PRC), potassium, aldosterone (PA), 18-hydroxycorticosterone (18-OHB), deoxycorticosterone (DOC), and corticosterone (B) concentrations and 24-hour urinary excretion of aldosterone (UA) in 24 patients with PHA (15 with an aldosterone-producing adenoma [APA] and nine with idiopathic PHA [IHA]). Despite the normalization of PRC and K in both APA and IHA patients by SPL, UA and PA failed to increase in APA (55.8 +/- 8.8 to 51.4 +/- 7.3 micrograms/24 hr and 54.0 +/- 9.4 to 44.6 +/- 6.2 ng/dl, respectively) in contrast to rises in IHA patients (22.3 +/- 2.5 to 69.3 +/- 10.3 micrograms/24 hr and 16.0 +/- 1.0 to 49.9 +/- 9.9 ng/dl). Similar corrections with amiloride (20-40 mg/day for 2 months) in one patient with APA produced a three- to fourfold increase in UA and PA. In addition, while on SPL the characteristic fall or no change in PA and 18-OHB during upright posture persisted in all APA patients despite further increases in PRC (4.48 +/- 1.15 to 7.86 +/- 1.89) and K (4.0 +/- 0.1 to 4.3 +/- 0.1). The patterns of the aldosterone precursors, DOC, B, and 18-OHB, and their ratios to acute stimulation with cosyntropin were not altered by SPL. Thus, SPL treatment causes a sustained impairment of the aldosterone secretory response to normalized PRC and K, but not to ACTH stimulation, only in patients with APA.

A prepubertal surge of thyrotropin precedes an increase in thyroxine and 3,5,3'-triiodothyronine in normal children.

The variations in plasma levels of TSH, T4, T3, and rT3, during the pubertal period, were studied in 647 school students from the urban area of Santiago in Chile (47% males and 53% females) with ages ranging between 7.5 and 15 yr. The subjects were grouped by age in consecutive intervals of 6 months each, and pubertal development was determined in every subject. TSH showed a significant increase, reaching a peak in the 9- to 9.5-yr interval. The same was found for T3 and T4, which reached a peak by 10 and 11 yr. The T4/T3 ratio did not show any significant variation with age. After 9.5 yr, a decrease in rT3 and increase in the T4/rT3 ratio was found. The TSH peak preceded the onset of clinical pubertal development, while the T3 and T4 peaks coincided with this onset. The variations in rT3 suggest an increase of peripheral conversion of T4 to T3. These transient events, not described until now, could be termed thyroidarche and could have a significant effect on pubertal growth and development.

Zona glomerulosa function after life-long suppression in two siblings with the hypertensive virilizing form of congenital adrenal hyperplasia.

The function of the adrenal zona glomerulosa was studied in two pubertal siblings with the hypertensive virilizing form of congenital adrenal hyperplasia who had never been treated. Initially, their plasma 11-deoxycortisol and 11-deoxycorticosterone (DOC) levels were very high, PRA was suppressed, and plasma aldosterone and 18-hydroxycorticosterone (18-OHB) were undetectable. To selectively study zona glomerulosa function, the patients and five normal subjects were given dexamethasone (2 mg/day; thus suppressing zona fasciculata function), and their sodium intake was restricted to 10 mmol/day. After 3-5 days, the zona glomerulosa was stimulated with either angiotensin II or potassium chloride. The same protocol was repeated in the patients at various intervals up to 39 months after beginning maintenance therapy with dexamethasone (0.25 mg twice daily). PRA, plasma aldosterone, and 18-OHB remained low during the first 6 months of treatment. After the first year, PRA recovered, and the zona glomerulosa began to respond. Plasma aldosterone and 18-OHB levels reached normal basal and stimulated values in one of the patients after 2 yr of treatment, but remained subnormal after 39 months of treatment in the other patient. Both patients, however, had persistently elevated plasma DOC concentrations, suggesting slight but definite impairment of 11 beta-hydroxylation in the zona glomerulosa. We conclude that in spite of a severe and persistent 11 beta-/18-hydroxylation deficiency in the zona fasciculata, the zona glomerulosa can recover almost completely after prolonged treatment. Appropriate stimulation, however, discloses a minor 11 beta-hydroxylation impairment also in the zona glomerulosa. In addition, the lack of parallelism in zona glomerulosa 11 beta- and 18-hydroxylation of DOC provides evidence for the concept of different 18-hydroxylating systems in the adrenal cortex.

Use of the saline infusion test to diagnose the cause of primary aldosteronism.

Angiotensin II has a major effect on mineralocorticoid hormone synthesis in patients with idiopathic hyperaldosteronism; it has little or no effect in those with an aldosterone-producing adenoma. To determine if this difference could be of use in clinically separating these two forms of primary aldosteronism, saline infusion tests were performed in 20 patients--14 with surgically proved aldosterone-producing adenoma and six with idiopathic hyperaldosteronism. With the patients receiving a balanced diet containing 120 meq of sodium, 1,250 ml of isotonic saline was infused intravenously between 8 A.M. and 10 A.M. after overnight recumbency. Plasma samples were obtained immediately before and after the infusion. Plasma cortisol level decreased appropriately in both groups, but plasma renin concentration decreased only in those patients with idiopathic hyperaldosteronism (p less than 0.05). Aldosterone and 18-hydroxycorticosterone levels decreased in both groups. To account for the circadian variation in adrenocorticotropin levels during the course of saline infusion, 18-hydroxycorticosterone/cortisol and aldosterone/cortisol ratios were examined. Both ratios increased in every patient with aldosterone-producing adenoma (p less than 0.01 and p less than 0.001, respectively), but these ratios remained unchanged or decreased in the patients with idiopathic hyperaldosteronism. This divergent variation in ratios after saline infusion allows for the differentiation of patients with an aldosterone-producing adenoma from those with idiopathic hyperaldosteronism. In patients with primary aldosteronism, an 18-hydroxycorticosterone/cortisol ratio of less than 3.0 or an aldosterone/cortisol ratio of less than 2.2 after saline infusion is diagnostic of idiopathic hyperaldosteronism.

Relation between interstitial myocardial collagen and the degree of clinical impairment in Chagas' disease.

Cardiac performance is negatively associated with interstitial collagen in Chagas' cardiomyopathy. The magnitude of dysfunction is related to the degree of collagen, and this association seems to exhibit a threshold above it if definite cardiac deterioration occurs.

The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin.

OBJECTIVE: Estrogens have a potent antioxidant effect on low-density lipoprotein (LDL) cholesterol in vitro and in vivo. A variety of compounds with antioxidant properties, such as vitamins and other hormones, also have been recommended in clinical practice to prevent several diseases related to oxidation. The aim of this study was to compare the antioxidant potency of estradiol (E2), the liposoluble vitamin E (both, alpha- and gamma-tocopherol), and melatonin. DESIGN: LDL was isolated by ultracentrifugation from the plasma of 11 healthy, untreated postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with 15 microM of CuSO4 to induce oxidative stress and with one of the four compounds studied: E2, alpha-tocopherol, gamma-tocopherol, or melatonin in doses of 0, 5, 15, 50, and 500 microM and 1 and 2 mM. Malondialdehyde (MDA) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration (nmol/mg protein). MDA values were significantly different as compared with baseline at 5 microM of E2 (F = 47.17; p < 0.0001). Alpha-tocopherol, gamma-tocopherol, and melatonin also showed a significant decrease in MDA concentration but to a lesser degree. The reduction of MDA reached statistical significance at 50 microM with alpha-tocopherol, 500 microM with melatonin, and 1 mM with gamma-tocopherol. The antioxidant effect also reached a plateau at concentrations of 50 microM of E2 and 1 mM of alpha-tocopherol; gamma-tocopherol and melatonin did not reach a plateau at any dose tested. CONCLUSIONS: The antioxidant potency of E2 in vitro is at least 10-100 times greater than alpha- and gamma-tocopherol and melatonin. Whether this finding implies a better performance of E2 as a protective agent against oxidation-related diseases remains to be determined.

In vitro effect of estradiol, progesterone, testosterone, and of combined estradiol/progestins on low density lipoprotein (LDL) oxidation in postmenopausal women.

OBJECTIVE: One of the mechanisms currently proposed to explain the cardioprotective effect of hormone replacement therapy (HRT) is the antioxidative property of estrogens. Considering that HRT involves the administration of an estrogen, usually combined with a progestin and sometimes with an androgen, we investigated the following in vitro: (1) the effect of estradiol, progesterone, and testosterone on the oxidation of low density lipoprotein; (2) the possible pro-oxidative effect of progesterone and testosterone on native low density lipoprotein; and (3) the possible modification of the antioxidant effect of estradiol on low density lipoprotein induced by progestins. DESIGN: Low density lipoprotein was isolated from blood samples obtained from 20 untreated postmenopausal women and divided in multiple aliquots, each containing 0.5 mg LDL protein. In Protocol 1 (n = 10) different doses of estradiol, progesterone, and testosterone ranging from 0 to 26 micrograms/ml were tested inducing oxidation with 15 microM copper sulfate. In Protocol 2 (n = 6) we studied the rate of oxidation of low density lipoprotein incubated with progesterone or testosterone without any oxidative induction. In Protocol 3 (n = 10) we studied the concomitant effect of 15 microM estradiol with four separate progestins (progesterone, medroxyprogesterone acetate, norethindrone, and norgestrel) in different doses (0, 5, 15, and 50 microM). After incubation for 4 h at 37 degrees C, malonaldehyde was measured as a marker of low density lipoprotein oxidation. The results were expressed in mean +/- SD. RESULTS: Protocol 1: Estradiol induced a dose-dependent decrease in malonaldehyde generation, from a baseline of 61.8 +/- 30.2 nmol/mg protein to 11.6 +/- 7.1 nmol/mg protein at the highest dose of estradiol tested (p < 0.0001). Progesterone or testosterone did not modify malonaldehyde generation. Protocol 2: Progesterone and testosterone did not show pro-oxidative action. Protocol 3: Estradiol 15 microM alone induced a 35% decrease in malonaldehyde generation, from a baseline of 75.4 +/- 25.4 to 49.3 +/- 18.8 nmol/mg protein (p < 0.0001). Norgestrel and norethindrone did not modify the antioxidant effect of estradiol (p > 0.05). Progesterone and medroxyprogesterone acetate induced a further reduction of malonaldehyde concentration to 37.2 +/- 20.8 and 38.6 +/- 18.2 nmol/mg protein, only at the highest dose tested (p < 0.02 and p < 0.01, respectively). CONCLUSIONS: Our results demonstrate that, in contrast with the potent antioxidant effect of estradiol, progesterone and testosterone did not show any pro- or antioxidant effect on low density lipoprotein in vitro. Furthermore, progestins did not counteract the antioxidant effect of estradiol in vitro.

Detection and genetic relationship of dengue virus sequences in seventeen-year-old paraffin-embedded samples from Cuba.

This study describes the use of the reverse transcriptase-polymerase chain reaction (RT-PCR) to generate dengue 2 amplicons from paraffin-embedded autopsy tissues collected in Cuba 17 years ago. The presumptive diagnoses had been made only by clinical evolution without serologic confirmation. This study confirms once again that dengue 2 virus was directly associated with the fatal cases in children and illustrates the potential of the RT-PCR for retrospective diagnosis of dengue cases 17 years after death. A close similarity in the genomic sequences of the dengue 2 RNA detected in tissue samples from fatal cases and those dengue 2 Cuban strains that had been previously investigated confirms the appropriate genomic classification of the etiologic agent associated with the 1981 dengue hemorrhagic fever Cuban epidemic.

[Cardiovascular diseases observed during follow-up of a group of patients with undetermined form of Chagas' disease]. / Doenças cardiovasculares observadas durante o seguimento de um grupo de pacientes na forma indeterminada da doença de Chagas.

PURPOSE: The aim of this study was to evaluate the cardiovascular outcome in patients with the undetermined form of Chagas' disease and whether or not it is related to the infectious disease in the long-term. METHODS: One hundred and sixty patients were prospectively followed-up at three month intervals for up to 177 months. RESULTS: Twenty and three (14.4%) patients developed hypertension complicated by ischemic stroke in two (1.2%) and symptomatic heart failure in one (0.6%). Cardiac arrhythmias occurred in four (2.4%) patients corresponding to isolated ventricular ectopic beats in two (1.2%), isolated supraventricular ectopic beats in one (0.6%) and an isolated episode of acute atrial fibrillation in another (0.6%). Two (1.2%) patients developed symptoms of coronary artery disease, one of them had one episode of acute chest pain diagnosed as myocardial infarction and the other had chronic chest pain diagnosed as angina. CONCLUSION: Hypertension is the most common cardiovascular disease occurring in the long-term follow-up of patients with the undetermined form of Chagas' disease. Cardiac rhythm disturbances and coronary artery disease were not more frequent than those generally found in a healthy population. These data confirm a favorable long-term prognosis in patients with the undetermined form of Chagas' disease.

[Value of pericardial biopsy in the etiologic diagnosis of pericardial diseases]. / Valor da biópsia de pericárdio no diagnóstico etiológico das pericardiopatias.

PURPOSE: To determine the value of pericardial biopsy as a complementary exam in the etiology of pericardial effusion. METHODS: We analyzed retrospectively (from 1990 to 1997) 38 patients with pericardial effusion. The age ranged between 3 months and 79 years (mean 41.15 +/- 21.78 years). Pericardial biopsy was performed in all cases through a subxiphoid incision. RESULTS: In 4 patients (10.5%) the biopsy was able to define etiology, 2 had tuberculosis and 2 neoplasias (1 undetermined adenocarcinoma, 1 mesotelioma). In 34 patients the biopsy showed non-specific chronic pericarditis. CONCLUSION: Pericardial biopsy was not an effective method to determine the etiological diagnosis in pericardial effusion patients. We believe that we have to individualize the indication of pericardial biopsy especially if tuberculosis or neoplasia are suspected.