Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids

Production of prostaglandins involved in renal salt and water homeostasis is modulated by regulated expression of the inducible form of cyclooxygenase-2 (COX-2) at restricted sites in the rat renal cortex. Because inflammatory COX-2 is suppressed by glucocorticoids, and prostaglandin levels in the kidney are sensitive to steroids, the sensitivity of COX expression to adrenalectomy (ADX) was investigated. By 2 weeks after ADX in mature rats, cortical COX-2 immunoreactivity increased 10-fold in the cortical thick ascending limb and macula densa. The constitutive isoform, COX-1, was unchanged. The magnitude of the changes and specificity of COX-2 immunoreactivity were validated by in situ hybridization histochemistry of COX-2 mRNA and Western blot analysis. Increased COX-2 activity (>5-fold) was documented by using a specific COX-2 inhibitor. The COX-2 up-regulation in ADX rats was reversed by replacement therapy with either corticosterone or deoxycorticosterone acetate. In normal rats, inhibition of glucocorticoid receptors with RU486 or mineralocorticoid receptors with spironolactone caused up-regulation of renal cortical COX-2. These results indicate that COX-2 expression in situ is tonically inhibited by adrenal steroids, and COX-2 is regulated by mineralocorticoids as well as glucocorticoids.

Índice del perfil del donante renal (KDPI) como factor pronóstico del trasplante

La enfermedad renal crónica ha aumentado a nivel mundial y nacional, mientras que el número de donantes viene en descenso, y los pacientes en lista de espera aumentan. Los donantes cadavéricos son una opción para estos pacientes, y han sido utilizados en últimos años para aumentar los órganos disponibles. La evaluación de la calidad de estos es importante para optimizar su uso. Estudio analítico tipo cohorte retrospectiva, cálculo de KDPI en donantes cadavéricos, seguimiento función renal creatinina sérica 1 mes, 3 meses, 6 meses y un año. Correlación supervivencia del injerto, función renal, KDPI y EPTS. Análisis de supervivencia y regresión logística con variables del donante, receptor y acto quirúrgico.

Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study

Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study

Design Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 mu g estradiol plus 170 mu g norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. Results No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. Conclusions There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women

Objective To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. Methods Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n=29) received one tablet of equine estrogens (CEE) 0.625mg plus medroxyprogesterone acetate (MPA) 2.5mg and one capsule of placebo; EP+A (n=31) received one tablet of CEE 0.625mg plus MPA 2.5mg and one capsule of methyltestosterone 2.0mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. Results There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p=0.021). No significant effect on orgasmic capacity was noted after the treatment period. Conclusion Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.

Exercise training associated with estrogen therapy induced cardiovascular benefits after ovarian hormones deprivation

Menopause is recognized as a period of increased risk for coronary heart disease. Although the benefits of exercise training in lowering cardiovascular risk factors are well established, the risks and benefits of hormone therapy have been questioned. The purpose of the present study was to investigate the effects of estrogen therapy (HT) associated or not with exercise training (ET) in autonomic cardiovascular control in ovariectomized (OVX) rats. Female rats were divided into: control, OVX, OVX+HT, OVX+ET and OVX+HT+ET. HT was performed using a 0.25 mg 8-weeks sustained release pellet. Trained groups were submitted to an 8-week exercise training protocol on treadmill. Baroreflex sensitivity (BRS) was evaluated by heart rate responses to arterial pressure (AP) changes, and vagal and sympathetic tonus by pharmacological blockade. Ovariectomy induced an AP increase (123 +/- 2 mmHg vs. 108 +/- 2 mmHg), BRS impairment (similar to 69%), sympathetic activation (similar to 100%) and vagal tonus reduction (similar to 77%) compared to controls. HT or ET normalized the changes in parasympathetic tonus. However, only the association HT + ET was able to promote normalization of AP, BRS and sympathetic tonus, as compared to controls. These results indicate that ET induces cardiovascular and autonomic benefits in OVX rats under HT, suggesting a positive role of this association in the management of cardiovascular risk factor in postmenopausal women. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Aerobic training abolishes ambulatory blood pressure increase induced by estrogen therapy: A double blind randomized clinical trial

Emerging data reveal that oral estrogen therapy can increase clinic blood pressure (BP) in postmenopausal women; however, it is important to establish its effects on ambulatory BP, which is a better predictor for target-organ damage. Besides estrogen therapy, aerobic training is widely recommended for post-menopausal women, and it can decrease ambulatory BP levels. This study was designed to evaluate the effect of aerobic training and estrogen therapy on the ambulatory BP of post-menopausal women. Forty seven healthy hysterectomized women were randomly divided (in a double-blind manner) into 4 groups: placebo-control (PLA-CO = 12), estrogen therapy-control (ET-CO = 14), placebo-aerobic training (PLA-AT = 12), and estrogen therapy-aerobic training (ET-AT = 09). The ET groups received estradiol valerate (1 mg/day) and the AT groups performed cycle ergometer, 3x/week at moderate intensity. Hormonal status (blood analysis), maximal cardiopulmonary exercise test (VO(2) peak) and ambulatory BP (24-h, daytime and nighttime) was evaluated before and 6 months after interventions. A significant increase in VO(2) peak was observed only in women who participated in aerobic training groups (+4.6 +/- 1.0 ml kg(-1) min(-1), P=0.00). Follicle-stimulating hormone was a significant decreased in the ET groups (-18.65 +/- 5.19 pg/ml, P=0.00), and it was accompanied by an increase in circulating estrogen (56.1 +/- 6.6 pg/ml). A significant increase was observed in the ET groups for daytime (P=0.01) and nighttime systolic BP (P=0.01), as well as nighttime diastolic BP (P = 0.02). However, daytime diastolic BP was increased only in the ET-CO group (+3.4 +/- 1.2 mmHg, P=0.04), and did not change in any other groups. No significant effect was found in ambulatory heart rate. In conclusion, aerobic training abolished the increase of daytime ambulatory BP induced by estrogen therapy in hysterectomized, healthy, normotensive and postmenopausal women. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n = 9, 1 mg/day) or placebo (n = 9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59 +/- 2 vs. 71 +/- 2 beats/min, P < 0.01). In both groups, exercise produced significant decreases in systolic BP (145 +/- 3 vs. 154 +/- 3 mmHg, P = 0.01), diastolic BP (71 +/- 3 vs. 75 +/- 2 mmHg, P = 0.04), mean BP (89 +/- 2 vs. 93 +/- 2 mmHg, P = 0.02), MSNA (29 +/- 2 vs. 35 +/- 1 bursts/min, P < 0.01), and FVR (33 +/- 4 vs. 55 +/- 10 units, P = 0.01), whereas it increased FBF (2.7 +/- 0.4 vs. 1.6 +/- 0.2 ml (.) min(-1) (.) 100 ml(-1), P = 0.02) and did not change HR (64 +/- 2 vs. 65 +/- 2 beats/min, P = 0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.

A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women

Objective: The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy. Design: A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Forrn Health Survey and symptoms by Kupperman Index at baseline and after 6 months. Results: There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL. Conclusions: Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken.

Low-dose transdermal hormone therapy does not interfere with the blood pressure of hypertensive menopausal women: a pilot study

Objectives To determine the effects of low-dose transdermal hormone therapy (HT) on systolic (SBP) and diastolic (DBP) blood pressure (BP) evaluated by 24-h ambulatory blood pressure monitoring (ABPM) in hypertensive postmenopausal women. Methods The study was conducted on 24 hypertensive postmenopausal women aged, on average, 54 years and under treatment with enalapril maleate (10-20 mg/day) combined or not with hydrochlorothiazide (25 mg/day). Thirteen women used a transdermal adhesive containing estradiol and norethisterone (25 and 125 mu g active substance/day, respectively) and 11 did not receive HT. ABPM, lipid profile, and climacteric symptoms were evaluated before and 3 and 6 months after treatment. Results After 3 and 6 months of follow-up, there was a statistically significant reduction of the Blatt-Kupperman menopausal index in the treated group (19.6 +/- 8.3 vs. 9.6 +/- 5.9 vs. 9.7 +/- 7.0; P=0.01). No significant difference in any of the ABPM variables (areas under the systolic and diastolic curves, mean SBP and DBP, SBP and DBP loads and wakefulness-sleep variation) or in the lipid profile was observed between or within groups at the three time points studied. Conclusion Low-dose transdermal HT administered for 6 months was effective in improving climacteric symptoms and did not change BP values or circadian pattern in postmenopausal women with mild-to-moderate arterial hypertension taking antihypertensive medications.

Predicting Hospital Mortality in Critically Ill Cancer Patients according to Acute Kidney Injury Severity

Background: Acute kidney injury (AKI) is a frequent complication in hospitalized patients, especially in those in intensive care units (ICU). The RIFLE classification might be a valid prognostic factor for critically ill cancer patients. The present study aims to evaluate the discriminatory capacity of RIFLE versus other general prognostic scores in predicting hospital mortality in critically ill cancer patients. Methods: This is a single-center study conducted in a cancer-specialized ICU in Brazil. All of the 288 patients hospitalized from May 2006 to June 2008 were included. RIFLE classification, APACHE II, SOFA, and SAPS II scores were calculated and the area under receiver operating characteristic (AROC) curves and logistic multiple regression were performed using hospital mortality as the outcome. Results: AKI, defined by RIFLE criteria, was observed in 156 (54.2%) patients. The distribution of patients with any degree of AKI was: risk, n = 96 (33.3%); injury, n = 30 (10.4%), and failure, n = 30 (10.4%). Mortality was 13.6% for non-AKI patients, 49% for RIFLE `R` patients, 62.3% for RIFLE `I` patients, and 86.8% for RIFLE `F` patients (p = 0.0006). Logistic regression analysis showed that RIFLE criteria, APACHE II, SOFA, and SAPS II were independent factors for mortality in this population. The discrimination of RIFLE was good (AROC 0.801, 95% CI 0.748-0.854) but inferior compared to those of APACHE II (AROC 0.940, 95% CI 0.915-0.966), SOFA (AROC 0.910, 95% CI 0.876-0.943), and SAPS II (AROC 0.869, 95% CI 0.827-0.912). Conclusion: AKI is a frequent complication in ICU patients with cancer. RIFLE was inferior to commonly used prognostic scores for predicting mortality in this cohort of patients. Copyright (C) 2011 S. Karger AG, Basel

Controversies regarding the effects of growth hormone on the heart

Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult patients with GH deficiency (GHD) and GH excess (acromegaly) provide important models in which to understand the effects of GH in adult cardiac physiology. An increasing body of clinical and experimental evidence illustrates the specific physiological abnormalities that are likely associated with the excess cardiovascular mortality observed in both acromegaly and GHD. Because human GH replacement is now available to treat adults with GHD, new questions emerge about the long-term cardiovascular effects of replacement therapy. In multiple trials, GH therapy for congestive heart failure has been proved ineffective in the absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH therapy can exert a potent beneficial effect on congestive heart failure. Long-term studies addressing cardiovascular morbidity and mortality are needed to assess the role of GH therapy for GHD.

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study

Objective To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. Methods Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 mug/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). Results No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotem cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p < 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p < 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. Conclusion Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.

Terapêutica Endovascular de Pseudoaneurisma e Fístula Arteriovenosa em Enxerto Renal

A 31 year old male Caucasian received a renal cadaveric allograft. Reconstruction of an inferior polar artery was corrected pre-implantation. Delayed graft function occurred leading to dialysis support for one month. Graft biopsies(days 7, 15) showed acute tubular necrosis(ATN) and no rejection. Serial ultrasound (US), performed on average weekly, were compatible with ATN. On day 31, Doppler US and a CAT scan suggested for the first time a pseudoaneurysm adjacent to the implantation of the graft artery on the external iliac artery. For clinical and technical reasons, arteriography was only performed on day 67, when serum creatinine was 3.3 mg/dl. It showed a large pseudoaneurysm with an arteriovenous fistula to the right common iliac vein. Compression of the right external iliac artery was clear. In an attempt to close the arteriovenous fistula, the communication with the pseudoaneurysm was embolised with gelfoam and metallic coils with partial success. One week later, by right femoral approach a covered wallstent was placed immediately below the origin of the graft artery.Subsequent Doppler US and arteriography con-firmed closure of the communication with thepseudoaneurysm and of the arteriovenous fistula. The calibre of the right external iliac artery was then normal. By month 18, serum creatinine is stable at 2.1 mg/dl. We can only speculate on the origin of thepseudoaneurysm and of the AV fistula, whichwere not evident until one month post-transplantation. Backtable surgery was performed on thepolar not the main graft artery. Invasive angiography was irreplaceable in this unusual clinical situation.

Hypophosphatemia in critically ill children

The purpose of this paper is to review clinical studies on hypophosphatemia in pediatric intensive care unit patients with a view to verifying prevalence and risk factors associated with this disorder. We searched the computerized bibliographic databases Medline, Embase, Cochrane Library, and LILACS to identify eligible studies. Search terms included critically ill, pediatric intensive care, trauma, sepsis, infectious diseases, malnutrition, inflammatory response, surgery, starvation, respiratory failure, diuretic, steroid, antiacid therapy, mechanical ventilation. The search period covered those clinical trials published from January 1990 to January 2004. Studies concerning endocrinological disorders, genetic syndromes, rickets, renal diseases, anorexia nervosa, alcohol abuse, and prematurity were not included in this review. Out of 27 studies retrieved, only 8 involved pediatric patients, and most of these were case reports. One clinical trial and one retrospective study were identified. The prevalence of hypophosphatemia exceeded 50%. The commonly associated factors in most patients with hypophosphatemia were refeeding syndrome, malnutrition, sepsis, trauma, and diuretic and steroid therapy. Given the high prevalence, clinical manifestations, and multiple risk factors, the early identification of this disorder in critically ill children is crucial for adequate replacement therapy and also to avoid complications.