Three novel mutations in CYP21 gene in Brazilian patients with the classical form of 21-hydroxylase deficiency due to a founder effect

Three different new mutations were found after CYP21 gene sequencing in three unrelated patients with the classical form of the 21-hydroxylase deficiency. These mutations were also screened in their affected relatives. In one patient and her brother, both affected with the simple virilizing form and in their aunt, with the nonclassical form, an AG>GG transition was found in the acceptor site of intron 2. In another patient with the salt wasting form, we found a 1003 1004 insA, in exon 4, that altered the reading frame and created a stop codon in codon 297. In the third patient and his sister, we found a C>T transition in codon 408. This transition led to the substitution of arginine by cysteine (R408C) in a conserved region where arginine is conserved in at least four different species. These siblings with the R408C mutation, both affected with the salt wasting form, have the IVS2-13A/C>G mutation in the other allele, suggesting that the R408C should lead to complete impairment of enzymatic activity. To rule out the possibility of polymorphism, R408C was screened through allele specific PCR, and it was not found in 100 normal alleles. The screening of these three new mutations by allele-specific PCR or enzymatic restriction in 212 CAH patients disclosed their presence in 2.3% (9/387) of the alleles. All three new mutations were found in compound heterozygous state with previously known mutations. Microsatellite studies, using markers flanking CYP21 gene, revealed that each new mutation presents the same haplotype, suggesting a gene founder effect, similar to what was previously observed with the G424S mutation also described in our population. Although microconversion events are the main cause of mutations in the CYP21 gene, random mutations with a common origin can also be the cause of 21-hydroxylase deficiency.     

Body composition and hormonal responses to a carbohydrate-restricted diet

The few studies that have examined body composition after a carbohydrate-restricted diet have reported enhanced fat loss and preservation of lean body mass in obese individuals. The role of hormones in mediating this response is unclear. We examined the effects of a 6-week carbohydrate-restricted diet on total and regional body composition and the relationships with fasting hormone concentrations. Twelve healthy normal-weight men switched from their habitual diet (48% carbohydrate) to a carbohydrate-restricted diet (8% carbohydrate) for 6 weeks and 8 men served as controls, consuming their normal diet. Subjects were encouraged to consume adequate dietary energy to maintain body mass during the intervention. Total and regional body composition and fasting blood samples were assessed at weeks 0, 3, and 6 of the experimental period. Fat mass was significantly (P 相似文献   

Acute Sildenafil Use Reduces 24‐Hour Blood Pressure Levels in Patients With Resistant Hypertension: A Placebo‐Controlled,Crossover Trial

The authors previously demonstrated that acute administration of sildenafil—a phosphodiesterase 5 (PDE5) inhibitor—improves hemodynamic parameters in patients with resistant hypertensive (RH), but its effect on ambulatory blood pressure monitoring (ABPM) is unknown. This interventional, nonrandomized, single‐blinded, placebo‐controlled, crossover trial included 26 patients with RH. A dose of sildenafil (187.5mg) was given, and after a washout period of 14 days the patients received a single oral dose of placebo and the protocol was repeated. The patients underwent 24‐hour ABPM recordings the day before and immediately after the protocols. The reduction of systolic (−8.8±1.4 vs 1.3±1.2 mm Hg, P=.02), diastolic (−5.3±3.3 vs 1.8±1.1 mm Hg, P=.03), and mean (−7.9±3.6 vs 0.8±0.9 mm Hg, P=.01) 24‐hour BP were found after the use of sildenafil compared with placebo. Improvement in daytime BP levels was also observed (systolic −6.0±4.7 vs 4.4±1.5 mm Hg [P=.02] and mean −4.8±3.9 vs 3.5±1.4 mm Hg [P=.02] for sildenafil vs placebo, respectively). Considering its antihypertensive effect, sildenafil may represent a therapeutic option for RH treatment.

The pathogenesis of resistant hypertension (RH) is multifactorial,¹ impacting a worse prognosis when compared with controlled hypertension.² The mechanisms of resistance to antihypertensive therapy are not completely understood and can be modulated by several interrelated factors such as (1) hyperactivation of the sympathetic nervous and renin‐angiotensin‐aldosterone system,³, ⁴ (2) volume expansion,⁵ (3) endothelial dysfunction,⁶, ⁷ (4) inflammatory processes,⁸ and (5) increased peripheral vascular resistance.⁹ Although there is little evidence related to populations with RH, effective blood pressure (BP) control reduces the risk of cardiovascular events in general hypertensive patients and should be targeted.¹⁰ New drug therapies have been proposed, but BP control remains a challenge for patients with RH.¹¹ Phosphodiesterase type 5 (PDE5) inhibitors are safe and effective drugs presenting vasodilatory effects that provide office BP reductions in untreated¹² and resistant hypertensive patients.¹³ Recently, our group has shown an improvement in hemodynamic parameters after acute administration of sildenafil in patients with RH.¹⁴ Although ambulatory BP monitoring (ABPM) is superior to casual BP for predicting organ damage in hypertensive patients,¹⁵, ¹⁶ the influence of sildenafil on ABPM was never assessed in patients with RH.The present study sought to evaluate the effects of sildenafil on ABPM in patients with RH. We hypothesized that acute administration of sildenafil—a PDE5 inhibitor—compared with placebo improves 24‐hour BP levels in patients with resistance to antihypertensive therapy.     

Propylthiouracil and thiamazole do not alter in vitro neutrophil oxidative burst

Propylthiouracil and thiamazole are thionamides used in the treatment of hyperthyroidism. In addition to reducing thyroid hormone synthesis, these drugs have other activities that improve the hypermetabolic state of the patients as well as adverse and toxic effects. The capacity of these 2 drugs to interfere with the production of reactive oxygen species of human neutrophils exposed in vitro to these drugs was evaluated. The production of reactive oxygen species was assessed by chemiluminescence assays and the cells were stimulated with zymosan particles opsonized with a pool of normal human serum. No alteration was found in the chemiluminescence response of treated human neutrophils when compared to controls. The results show that these drugs, at the studied concentrations and with the experimental approach used, have no direct effect on the production of oxidative burst of neutrophils. We conclude that if these drugs have any action on the oxidative metabolism of neutrophils these might include some metabolization steps that do not take place in this in vitro model.     

Disturbed right ventricular ejection pattern as a new Doppler echocardiographic sign of acute pulmonary embolism

Transthoracic echocardiography (TTE) is frequently performed in patients with suspected acute pulmonary embolism (APE) to search for right ventricular (RV) pressure overload. We prospectively assessed the diagnostic value of a new Doppler echocardiographic sign of APE based on the disturbed RV ejection pattern ("60/60 sign") and compared its diagnostic performances with that of the presence of RV pressure overload, as well as with "McConnell sign" based on RV regional wall motion abnormalities. We assessed 100 consecutive patients with clinical suspicion of APE, including those with previous cardiorespiratory diseases. After TTE, all of the patients underwent reference diagnostic tests for APE. The 60/60 sign required RV acceleration time of 相似文献   

Detection of carbapenemases and other mechanisms of enzymatic resistance to β-lactams in Enterobacteriaceae with diminished susceptibility to carbapenems in a tertiary care hospital

Introduction

Our objective was to characterize the enzymatic β-lactam resistance in clinical Enterobacteriaceae isolates with diminished susceptibility to carbapenems from 2013 to 2014 at Hospital Universitario Miguel Servet.

Impacto de la puntuación de calcio en la concordancia entre la tomografía computarizada con multidetectores y la coronariografía invasiva

Introduction and objectives

Multidetector computed tomography (MDCT) has been demonstrated as a feasible alternative to invasive coronary angiography (ICA). However, contradictory results have been reported regarding the effect of coronary artery calcium score (CS) on the diagnostic accuracy of MDCT. Our aim was to assess the agreement of MDCT and ICA and to evaluate the influence of CS on this agreement.

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online

Background and objective

Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.