Metabolic syndrome during gestation and lactation: An important renal problem in dams. selenium renal clearance.

BACKGROUND: Metabolic syndrome (MS) in lactating dams leads to several cardiometabolic changes related to selenium (Se) status and selenoproteins expression which produce hypertension. However, little is known about the state of these dams' kidney functions and their Se deposits. METHODS: Two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65 % and Se: 0.1 ppm). At the end of lactation (21d postpartum) kidney weight and protein content, Se deposits, and the activity of the antioxidant selenoprotein glutathione peroxidase (GPx) were measured in dams. Kidney functional parameters: albuminuria, creatinine clearance, serum aldosterone and uric acid levels and water and electrolyte (Na+ and K+) balance were also evaluated. Systolic blood pressure (SBP) was measured. RESULTS: In MS dams at the end of lactation Se deposits and GPx activity are higher in the kidney; however, lipid renal peroxidation appears, relative Se clearance increases, and the dams have lost Se by urine. MS dams have polyuria and polydipsia, high uric acid serum levels, albuminuria and high creatinine clearance, implying glomerular renal malfunction with protein loss. They also present hypernatremia, hypokalemia and hyperaldosteronemia, leading to high SBP; however, a natriuretic process is taking place. CONCLUSION: Since these alterations appear, at least in part, to be related to oxidative stress in renal cells, Se supplementation could be beneficial to avoiding greater lipid renal oxidation during lactation.

Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Cost-effectiveness analysis of treatment sequences containing tofacitinib for the treatment of rheumatoid arthritis in Spain.

OBJECTIVE: To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). METHODS: A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. RESULTS: In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. CONCLUSIONS: Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.

The Benefits of Administering Folic Acid in Order to Combat the Oxidative Damage Caused by Binge Drinking in Adolescent Rats.

AIMS: An important mechanism in alcohol-induced injury is biomolecular oxidative damage. Folic acid is supplied to chronic alcoholic patients in order to prevent this situation, as this is the main vitamin deficiency that they suffer from. Acute alcohol exposure, such as binge drinking, is one of the most widespread ethanol consumption models practiced by adolescents. However, there is no evidence of folic acid body profiles after this pattern of consumption. METHODS: Four groups of adolescent rats were used: control, alcohol (exposed to intraperitoneal binge drinking), control folic acid-supplemented group and alcohol folic acid-supplemented group. Folic acid levels, protein, lipid and DNA oxidative damage in serum, and liver glutathione (GSH) and reduced/oxidized glutathione ratio (GSH/GSSG) were measured. RESULTS: Binge-drinking rats had higher lipids and DNA oxidation levels. They also had lower hepatic GSH levels and GSH/GSSG ratio. Folic acid supplementation to binge-drinking rats does not change the serum protein oxidation but decreases lipid and DNA oxidation. Finally, GSH increased to control levels with folic acid supplementation. CONCLUSION: Folic acid supplementation is an economic and efficient therapy against the oxidative damage in lipids and mainly in DNA stability caused by binge drinking during adolescence. It has also been demonstrated that folic acid increases GSH levels, improving the antioxidant status and revealing a hepatoprotective effect during binge drinking.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study. / Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF.

BACKGROUND AND OBJECTIVES: Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. PATIENTS AND METHOD: The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. RESULTS: The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. CONCLUSION: Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants.

Use of healthcare resources and costs of acute cardioembolic stroke management in the Region of Madrid: The CODICE Study.

INTRODUCTION: Stroke is the main cause of admission to Neurology departments and cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS: A multicentre prospective observational study was performed in 5 Neurology departments in public hospitals in the Region of Madrid (Spain). The objective was to estimate the use of healthcare resources and costs of acute CS management. Patients with acute CS at<48h from onset were recruited. Patients' socio-demographic, clinical, and healthcare resource use data were collected during hospitalisation and at discharge up to 30 days after admission, including data for rehabilitation treatment after discharge. RESULTS: During an 8-month recruitment period, 128 patients were recruited: mean age, 75.3±11.25; 46.9% women; mortality rate, 4.7%. All patients met the CS diagnostic criteria established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty per cent of the patients had a history of atrial fibrillation and 18.8% presented other major cardioembolic sources. Non-valvular atrial fibrillation was the most frequent cause of CS (33.6%). Data for healthcare resource use, given a mean total hospital stay of 10.3±9.3 days, are as follows: rehabilitation therapy during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8 days), complications (32%), specific interventions (19.5%), and laboratory and diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed diagnostic procedures. Average total cost per patient during acute-phase management and rehabilitation was €13,139. Hospital stay (45.0%) and rehabilitation at discharge (29.2%) accounted for the largest part of resources used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes large amounts of resources (€13,139), mainly due to hospital stays and rehabilitation.

[Cost analysis of the use of botulinum toxin type A in Spain]. / Análisis de costes del uso de toxina botulínica A en España.

OBJECTIVE: To estimate treatment costs of blepharospasm, cervical dystonia(CD), upper limb spasticity (ULS) and spasticity in children with cerebral palsy (SCCP) with botulinum neurotoxin type A (BoNT-A) in Spain. METHOD: Annual BoNT-A treatment costs were calculated (2013 ex-factory price () applying RDL 8/2010 and RDL 9/2011 deductions), based on initial dose (id), average dose (ad) and maximum dose (md) according to Summary of Product Characteristics of Botox® (100U/50U), Dysport®(500U) and Xeomin® (100U) and considering the use of complete vials.In addition, annual treatment costs were calculated considering the useof vials in more than one patient and also patient population annual treatment costs based on diseases' prevalence. RESULTS: Annual BoNT-A treatment costs per patient were estimated at between 265 and 2,120 with savings from 10% to 55% accordingto the selected BoNT-A. CD and ULS treatment provided the greatest cost per patient. Botox® provided greater savings in ULS (id/ad), CD(id), and in blepharospasm and SCCP (id/ad/md). Dysport® treatment was less costly in CD (md) and ULS (md), while Xeomin® was in CD(ad). Based on the estimated treated population in Spain, the annual treatment costs ranged from 368,392 to 13,958,836 depending on indication, dose and BoNT-A considered. CONCLUSIONS: The appropriate BoNT-A choice would lead to considerable savings for the National Health System. Botox® would generate lower costs per patient than other BoNT-A products in 9 out of 12 scenarios considered.

Objetivo: Estimar el coste de tratamiento de blefarospasmo, distoníacervical (DC), espasticidad del brazo del adulto (EBA) yespasticidad del niño con parálisis cerebral infantil (EPCI) con laspresentaciones de neurotoxina botulínica tipo A (NTB-A) enEspaña.Método: Se calculó el coste anual de tratamiento con NTB-A(, 2013; PVL oficial publicado aplicando deducciones del RDL8/2010 y RDL 9/2011), en función de la dosis inicial (di), dosismedia (dm) y dosis máxima (dmax) en base a los viales porsesión según fichas técnicas de Botox® (100U y 50U), Dysport®(500U) y Xeomin® (100U), considerando los músculos comunesen cada indicación. Adicionalmente, se calculó el coste considerandola población total de pacientes según prevalencia y lareutilización de viales en más de un paciente.Resultados: El coste anual/paciente con NTB-A supondría entre265y 2.120con un ahorro entre el 10% y 55% según laNTB-A seleccionada. DC y EBA presentarían el mayor coste/paciente. Botox® generaría un menor coste en EBA (di/dm) y DC(di) y en blefarospasmo y EPCI (di/dm/dmax). Dysport® tiene elmenor coste en DC (dmax) y EBA (dmax) y Xeomin® en DC(dm). El coste anual por población según prevalencia suponeentre 368.392y 13.958.836según indicación, dosis y NTBAseleccionada.Conclusiones: Una selección adecuada de las presentaciones deNTB-A para cada indicación permitiría generar importantesahorros para el Sistema Nacional de Salud. Botox® conseguiríamenores costes anuales/paciente frente al resto de NTB-A en 9de los 12 escenarios considerados.

Retroperitoneal schwannoma. A complex surgical treatment of a tumor with uncertain behavior.

BACKGROUND: Retroperitoneal schwannoma is a rare nerve sheath tumor; the surgical removal of this tumor is sometimes compromised by its location. The aim of this study is to analyze our experience with the diagnosis and treatment of this type of tumor. METHOD: We present our experience between 1999 and 2011 in the diagnosis and treatment of retroperitoneal schwannoma. During that time, we diagnosed and treated five female patients (four adults and one infant) with the condition. The tumors appeared sporadically and were not associated with neurofibromatosis or other syndromes. Diagnosis was performed by computed tomography (CT) imaging in four cases and by magnetic resonance imaging (MRI) in one case. RESULTS: All patients underwent surgical treatment and complete resection of the lesion. An open resection was performed in four cases, and in the most recent case, the excision was conducted laparoscopically. In all of the cases, the histological diagnosis was retroperitoneal schwannoma, and in one case, there was a melanocytic variant that was not associated with Carney syndrome. At the time of this report, there has been no evidence of recurrence. CONCLUSION: Retroperitoneal schwannoma is a tumor that is difficult to diagnose with imaging techniques, and because of its localization, the tumor is difficult to remove surgically.

Oxidative effects of chronic ethanol consumption on the functions of heart and kidney: folic acid supplementation.

AIMS: The principal aim of this study was to investigate the oxidative effects of chronic ethanol consumption on the functions of the heart and the kidney and the possible modification of this effect by folic acid supplementation. Moreover, in order to find whether this oxidative profile affects cardiovascular function, parameters such as heart rate and glomerular filtration rate were also assessed. METHODS: Four experimental groups of rats were used: control, ethanol-exposed, control supplemented with folic acid and ethanol-exposed plus folic acid. Ethanol-exposed rats were subjected to a chronic ethanol treatment (2 months), in which the level of alcohol reaches 30% v/v. Diet and ethanol solution were provided ad libitum, and folic acid supplementation was 8 vs. 2 ppm. Energy intake, creatinine clearance and heart rate were determined. Antioxidant enzyme activity and lipid and protein peroxidation of the kidney and the heart were measured by the spectrophotometric method. RESULTS: Ethanol increases heart size and catalase (CAT) activity and decreases lipid peroxidation in heart without changing heart rate. However, in the kidney, ethanol decreases CAT activity, increases lipid peroxidation and decreases glomerular filtration rate. Folic acid supplementation avoids these situations; it does not, however, improve glomerular function. CONCLUSION: Chronic ethanol consumption has many effects on the antioxidant enzymatic activity of the heart and the kidney, leading to increased renal lipid peroxidation prevented by folic acid supplementation.

The effects of ethanol upon hydric balance and arterial pressure in rats: folic acid as a possible hypotensor.

AIMS: Chronic alcohol intake is related to hypertension. There are, however, few studies concerning the effect of ethanol upon hydric balance in relation to arterial pressure. Folic acid intake has beneficial effects upon the cardiovascular system decreasing hyperhomocysteinemia, however, more studies imply that it is related with other mechanisms. Therefore, we have studied the effects of chronic alcohol intake (30% v/v) upon hydric-saline balance and hypertension and have found that dietary supplementation with folic acid (8 mg/kg) improves the above parameters. MAIN METHODS: Our study used four experimental groups of rats: control, alcohol, alcohol with folic acid and control with folic acid. In all cases we measured the clearance of Na(+), K(+) and aldosterone; osmolarity in urine, liquid and solid ingestion; homocysteine levels in serum; cardiac frequency and arterial blood pressure. KEY FINDINGS: The alcohol intake increases serum aldosterone and homocysteine, which is reflected in an increase in arterial blood pressure. In addition, we have found that alcohol intake reduces both liquid and solid ingestion (causing a malnourishment status), the clearance of creatinine, aldosterone, Na(+) and K(+), and the ratio ClNa(+)/ClCr; it also increases urine osmolarity. Folic acid supplementation increases the clearance of Na(+) and the ratio ClNa(+)/ClCr. SIGNIFICANCE: Folic acid intake improves the hypertension provoked by alcohol by increasing the aldosterone clearance, drastically reducing the serum levels of this hormone and thus its hypertensor effect.

Retroperitoneal seminoma as a first manifestation of a partially regressed (burnt-out) testicular germ cell tumor.

Regressed (burnt-out) testicular germ cell tumors (TGCT) are rare clinical situations that are clinically difficult to recognize. This 43-year-old patient was admitted because of a suspicion of prostatic carcinoma, which eventually was followed by transrectal ultrasonography and a CT scan, both of which revealed a large retroperitoneal mass. Surgery showed extensive ureteral and vas deferens infiltration. Pathology was consistent with a classical seminoma. Eventually, testes were normal on palpation but ultrasonography only revealed areas of fibrosis and microcalcifications in the left testis, which was followed by a left orchidectomy. Microscopically, there were extensive areas of fibrosis and only a 2 mm area of seminoma was demonstrated. The few areas of uninvolved testicular tissue lacked lesions of intratubular germ cell neoplasia (IGCNU). Retroperitoneal germ cell tumors are rare in the male and consequently, an origin from an occult testicular tumor should always be discarded by image analysis and eventually a biopsy. Immunologic response may be responsible for tumor involution.

Effect of dietary selenite on development and intestinal absorption in offspring rats.

AIM: The present study aims to compare selenium (Se) status in offspring rats born to selenium-deficient and selenium supplemented dams and to analyse Se's influence on intestinal parameters and the intestinal absorption of selenomethionine (Se-Met). MAIN METHODS: Male and female Wistar rats (150-200 g) were randomised in: control (C) (0.1 ppm Se), Se-deficient (SD) (0.01 ppm Se) and Se-supplemented (SS) (0.5 ppm Se) groups; and were mated to obtain their offspring. Se levels in serum, urine and faeces in offspring and in mothers' milk were measured by graphite-furnace atomic absorption spectrometry. Duodenal transport studies in offspring were performed using an in vivo perfusion of different Se-Met concentrations (2, 5, 10, 25, 75 and 150 µM). KEY FINDING: A Se-deficient diet provoked a decrease in the offspring's body weight and intestinal parameters, while the supplemented diet increased these values. Serum Se levels were similar between Se-deficient and control offspring because the urinary excretion of Se was smaller to compensate for Se homeostasis. Intestinal Se-Met absorption obeys the Michaelis-Menten equation with lower apparent constant (K(m)) and maximal velocity (V(max)) in the SD group. However, the C and SS groups presented similar K(m) and different V(max). The V(max) showed greater values in the following order of rank: SS>C>SD groups. SIGNIFICANCE: Selenium intake deficiencies in offspring lead to the development of compensatory mechanisms in order to normalise serum selenium levels. These mechanisms, however, do not permit normal body development; nor do they regulate intestinal parameters and Se-Met transport.

Selenium or selenium plus folic acid intake improves the detrimental effects of ethanol on pups' selenium balance.

The levels of folic acid and selenium, two nutrients with antioxidant properties, decrease in dams exposed to ethanol during gestation and lactation. This decrease affects their antioxidant balance, and consequently the health of their offspring. In this study we have proved that a supplemented diet with Se (0.5 ppm) or with Se (0.5 ppm) plus folic acid (8 ppm) to ethanol-exposed (20%v/v) dams prevents the ethanol-provoked effects in their offspring's Se deposits. Se levels in milk, serum, urine, faeces and several tissues were measured by graphite-furnace atomic absorption spectrometry. Results show that ethanol decreases Se deposits in pups' heart, liver, kidney and testes. However Se levels in pancreas and in serum were increased by ethanol; it also compromised the weight and the length of the offspring at the end of lactation. Our supplemented diets to ethanol dams increased all of these impaired levels, and restored Se pancreas concentration to a control status. However Se-only therapy mainly displaces Se to serum, kidney and spleen, and co-treatment with Se plus folic acid, mainly displaces Se to liver and brain. This data demonstrate that the qualitative and quantitative Se organ deposits depend on ethanol consumption, Se status, and the presence of other antioxidants.

Ultra low dose continuous combined hormone replacement therapy with 0.5mg 17beta-oestradiol and 2.5mg dydrogesterone: protection of the endometrium and amenorrhoea rate.

OBJECTIVES AND STUDY DESIGN: The aim of this open, multicentre study was to demonstrate the endometrial safety and assess the bleeding pattern of ultra low dose continuous combined hormone replacement therapy with 0.5 mg 17beta-oestradiol and 2.5 mg dydrogesterone in 446 healthy, non-hysterectomised, postmenopausal women with symptoms of oestrogen deficiency. MAIN OUTCOME MEASURE: Aspiration endometrial biopsies were performed at baseline and after 1 year of treatment to assess the incidence of endometrial hyperplasia or a more serious endometrial outcome. RESULTS: The only adverse endometrial outcome at the end of the study was one case of simple hyperplasia. This gives an overall incidence of 0.27% (95% CI: 0.01-1.48%) in the per protocol sample (n=395). The overall rate of amenorrhoea in the full sample (n=446) was 68% and 14% had only one or two bleeding/spotting episodes. The rate of amenorrhoea in months 10-12 (n=413) was 88%. The number of bleeding/spotting days per cycle fell during the study. The mean number of bleeding/spotting days was 5.8 and the mean number of days without bleeding was 358.2. Spotting alone was the most prevalent bleeding intensity, whilst heavy bleeding was rare. CONCLUSIONS: In conclusion, 2.5 mg dydrogesterone continuously combined with 0.5 mg 17beta-oestradiol effectively protects the endometrium in postmenopausal women in accordance with the guidelines of the Committee for Medicinal Products for Human Use (CHMP). It has a favourable amenorrhoea rate and is well tolerated by the majority of women.

Dietary selenium plus folic acid as an antioxidant therapy for ethanol-exposed pups.

BACKGROUND: Nutrients such as folic acid and selenium are decreased in dams exposed to ethanol during gestation and lactation, affecting their metabolism, antioxidant balance, and the future health of their progeny. We will study whether the supplementation of the maternal diet with folate and selenium can prevent ethanol-induced oxidative liver disorders in the offspring. METHODS: Dams were randomised into four groups: control, alcohol, alcohol+folic acid+Se, and control+folic acid+Se. We determined selenium by graphite-furnace atomic absorption and antioxidant enzyme activities, lipid peroxidation, and protein carbonyl by spectrophotometry in the offspring. RESULTS: Alcohol increased serum Se levels and glutathione peroxidase (GPx) activity. However, in the liver of pups from ethanol-exposed dams a decrease in selenium was provoked and GPx activity increased with the double supplementation. Glutathione reductase (GR) and catalase (CAT) activities increased with ethanol, while double supplementation significantly decreased the GR activity. The supplemented diet reduced the protein peroxidation found in ethanol pups. CONCLUSIONS: These results suggest that folic acid+Se could be effective in neutralising the damage of ethanol consumption in pups since it prevents peroxidation protein products.

Uterine adenosarcomas overgrown by sex-cord-like tumour: report of two cases.

Müllerian adenosarcomas are tumours of low malignant potential with proliferation of benign glands and low grade endometrial stromal sarcoma (LGESS). Unusually, the latter may include foci of uterine tumours resembling ovarian sex-cord tumours (UTROSCT). Two cases of uterine adenosarcomas massively overgrown by UTROSCT are reported, for the first time. The patients, aged 71 and 64, one receiving tamoxifen, presented with intracavitary polypoid adenosarcomas; each was overgrown by an immunopathologically characteristic UTROSCT that constituted more than 75% of its volume. Periglandular CD10+LGESS represented less than 25%. Both are alive and well after 5 and 3 years, respectively. Compared to the poor prognosis of adenosarcomas overgrown by high grade sarcomata, the cases reported here had a benign behaviour. Quantitative assessment of volume percentage of the potentially aggressive LGESS, CD10+ areas should be considered as a relevant prognostic histological parameter in these tumours.

Selenium tissue distribution changes after ethanol exposure during gestation and lactation: selenite as a therapy.

Ethanol consumption affects maternal nutrition and antioxidant status together with the future health of their progeny. Selenium (Se) is a trace element with antioxidant activity; we will study the effect of ethanol in dams on Se bioavailability, antioxidant balance and gestational parameters. We also will study if a Se-supplemented diet (0.5 ppm) administered to ethanol-exposed dams avoids the undesirable effects provoked by ethanol. We have used four experimental groups: control (C); chronic ethanol (A); control+Se (CS) and chronic ethanol+Se (AS). Se levels in serum, urine, faeces, and several tissues were measured by graphite-furnace atomic absorption spectrometry. Serum glutathione peroxidase (GPx) activity was determined by spectrometry. Se bioavailability is altered by ethanol, causing a decrease in Se retention, reducing Se levels in cortex, muscle, mammary gland and salivary gland while elevating Se values in heart, liver and spleen. On the other hand, Se supplementation increases some of these parameters. Serum GPx activity was decreased by ethanol, while a Se-supplemented diet restores these values to those found in controls. We have demonstrated that ethanol decreased Se retention in dams, affecting their tissues' Se deposits, decreasing GPx activity in serum, gestational parameters and the weight of their progeny. Selenite supplementation counteracts these decreasing effects, except in cortex.

Expression of platelet-derived growth factor receptor in low-grade endometrial stromal sarcomas in the absence of activating mutations.

AIMS: To investigate platelet-derived growth factor receptor (PDGFR)alpha and PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS). Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors, which act through an inhibitory effect on class 3 receptor tyrosine kinase members such as PDGFRalpha, PDGFRbeta and c-kit. METHODS AND RESULTS: The immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37 archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour cells) and positive (weakly positive 11-50% positive cells; strongly positive > 50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by 19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for PDGFRbeta, but endothelial cells stained positive. A mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen metastatic ESS from three patients detected no mutations leading to amino acid changes in the mature protein. CONCLUSIONS: Patients with PDGFRalpha+ ESS may benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and paracrine stimulation loops, blocking neovascularization and enhancing the effects of chemotherapy.

Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma.

We report a case of a 9-cm mixed epithelial and stromal tumour of the kidney in an obese 70-year-old woman with diabetes. The ovarian-type stroma had a spindle cell component that was positive for progesterone receptors and had the hitherto unreported presence of abundant foci of luteinised stromal cells with characteristic immunohistochemical positivity to alpha-inhibin, calretinin, aromatase and gonadotropin-releasing hormone (GnRH) receptors. We conclude that the stromal component is identical to ovarian cortical stroma. We believe that ovarian-type stroma occurs in extragenital tumours as a result of an epithelial-stromal interaction in an environment of hormonal hyperstimulation.