Age-related normograms of serum antimüllerian hormone levels in a population of infertile women: a multicenter study.

Objective: To produce age-related normograms for serum antimullerian hormone (AMH) level in infertile women without polycystic ovaries (non-PCO).Design: Retrospective cohort analysis.Setting: Fifteen academic reproductive centers.Patient(s): A total of 3,871 infertile women.Intervention(s): Blood sampling for AMH level.Main Outcome Measure(s): Serum AMH levels and correlation between age and different percentiles of AMH.Result(s): Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. We found that the curves of AMH by age for the 3rd to 50th percentiles fit the model and appearance of linear relation, whereas the curves of >75th percentiles fit cubic relation. There were significant differences in AMH and FSH levels and in antral follicle count (AFC) among women aged 24-33 years, 34-38 years, and >= 39 years. Multivariate stepwise linear regression analysis of FSH, age, AFC, and the type of AMH kit as predictors of AMH level shows that all variables are independently associated with AMH level, in the following order: AFC, FSH, type of AMH kit, and age.Conclusion(s): Age-related normograms in non-PCO infertile women for the 3rd to 97th percentiles were produced. These normograms could provide a reference guide for the clinician to consult women with infertility. However, future validation with longitudinal data is still needed. (Fertil Steril (R) 2011; 95: 2359-63. (C) 2011 by American Society for Reproductive Medicine.)

Diagnosis of 5α-reductase type 2 deficiency: Contribution of anti-Müllerian hormone evaluation

Aim: To evaluate anti-Müllerian hormone (AMH) levels in patients with clinical and molecular diagnosis of 5α-reductase 2 deficiency. Patients and methods: Data from 14 patients whose age ranged from 21 days to 29 years were analyzed according to age and pubertal stage. Sexual ambiguity was rated as Prader III in 11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum levels were measured in all but two patients, who had been previously submitted to gonadectomy; T and DHT were also measured in 20 age-matched controls. Results: Gonadotropin levels were normal in all but one patient who retained gonads (six of whom had reached puberty) and T/DHT ratio was elevated in all patients when compared to controls. All prepubertal patients had AMH levels < -1 SD for age, while most pubertal patients had AMH levels compatible with pubertal stage. Conclusions: Prepubertal patients with 5α-reductase 2 deficiency have AMH values in the lower part of the normal range. These data indicate that T does not need to be converted to DHT to inhibit AMH secretion by Sertoli cells. © Freund Publishing House Ltd., London.

Measurement of melatonin in body fluids: Standards, protocols and procedures

Background and Purpose: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body's endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues. Data Identification: A search of the English-language literature (Medline) and a systematic review of published articles were carried out. Study Selection: Articles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review. Data Extraction: The authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures). Results of Data Synthesis: Melatonin measurements are useful for evaluating problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. They have also become an important tool for psychiatric diagnosis, their use being recommended for phase typing in patients suffering from sleep and mood disorders. Additionally, there has been a continuous interest in the use of melatonin as a marker for neoplasms of the pineal region. Melatonin decreases such as found with aging are or post pinealectomy can cause alterations in the sleep/wake cycle. The development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids has increasingly been shown to have direct relevance for clinical decision making. Conclusions: Due to melatonin's low concentration, as well as the coexistence of numerous other compounds in the blood, the routine determination of melatonin has been an analytical challenge. The available evidence indicates however that these challenges can be overcome and consequently that evaluation of melatonin's presence and activity can be an accessible and useful tool for clinical diagnosis. © Springer-Verlag 2010.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

EXPOSICAO DE CIRURGIOES-DENTISTAS AO MERCURIO

The professional exposure of dental surgeons to mercury has attracted a great deal of attention from governmental organs and institutions in different countries. Considering that the normal ratio is 10 μg/1000 ml of urine, it was verified from tests that 72.7% of the professionals working in the dental practice in the city of Araraquara (SP) Brazil, show mercury levels above this limit. These results demonstrated the almost complete unawareness of many dentists to mercury and, consequently, precautionary measures were almost nonexistent.

Effects of the application of α1- and α2-adrenoceptor agonists and antagonists into the ventromedial hypothalamus on the sodium and potassium renal excretion

The effects of sodium and potassium excretion after intrahypothalamic administration of two α-adrenoceptor agonists and the effect of α-adrenoceptor antagonists were studied in groups of rats. Prazosin was equally effective at blocking the natriuretic and kaliuretic responses to the α1-adrenoceptor agonist phenylephrine and the mixed α1/α2-adrenoceptor agonist noradrenaline, while yohimbine which acts preferentially on α2-adrenoceptors was effective in potentiating these responses. These results suggest the presence of two types of α-adrenoceptors for the modulation of ventromedial hypothalamic pathways that interfere with the regulation of the two cations: stimulation of α1-adrenoceptors facilitates, while stimulation of α2-adrenoceptors inhibits the excretion of the ions.

Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine

The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

Renal excretion of zinc in normal individuals during zinc tolerance test and glucose tolerance test

The urinary excretion, renal clearance, and tubular reabsorption of zinc were investigated in 30 adult healthy subjects under basal conditions and during the zinc and glucose tolerance tests. After a 12h overnight fast, each subject was submitted to renal clearance of zinc. The procedures were performed between 8.00 and 12.00 a.m., after emptying the bladder and ingestion of 4 ml deionized water/kg body weight at 8.00 a.m. The first urine sample was collected at 10.00 a.m., and the second at 12.00 a.m. A dose of 110 mg ZnSO47H2O was administered orally to each subject, diluted in 20 ml deionized water, at time 0 min. Blood samples were collected from an antecubital vein at times -30, 0, and 30 min and at 30 min intervals up to 240 min. Glucose was administered intravenously (0.5 ml 50%/kg body weight) during the first 3 min of the test, and blood samples were collected from an unconstricted, contralateral, antecubital vein at times -30, 0, 3, 5, 10, 20, 30, 45, 60, and 90 min. The results showed that urinary zinc excretion, and renal zinc clearance were significantly higher during the zinc and glucose tolerance tests than in the control condition. On the other hand, renal zinc clearance was more elevated during tile glucose tolerance test than during the zinc tolerance test. Variations in zinc tubular reabsorption and glomerular filtration rate were not detected. The results suggest that urinary excretion and renal clearance of zinc in healthy subjects increase during acute zinc ingestion and glucose infusion, Although zinc ingestion raised urinary zinc excretion, glucose infusion was more effective in increasing renal zinc clearance. These normal parameters are important in the investigation of diabetic patients with serum and urine zinc changes.

Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: Pharmacokinetics, cardiopulmonary and endocrine effects

Pharmacokinetics and some pharmacological effects of anaesthesia induced by a combination of detomidine, ketamine and guaiphenesin were investigated in eight ponies. Cardiopulmonary function was studied and plasma met-enkephalin, dynorphin, β-endorphin; arginine vasopressin, adrenocorticotrophin, cortisol, 11-deoxycortisol and catecholamine concentrations were measured. The combination produced slight cardiorespiratory depression, hyperglycaemia and a reduction in haematocrit. There were no changes in plasma opioids, pituitary peptides or catecholamines. Plasma cortisol concentration decreased and plasma 11-deoxycortisol increased indicating a suppression of steroidogenesis. Steady state ketamine and guaiphenesin concentrations were attained during the infusion period, and ketamine concentrations likely to provide adequate analgesia for surgical operations were achieved (more than 2.2 μg ml-1). Steady state detomidine concentration was not attained. The ponies took on average 68 minutes to recover to standing and the recovery was uneventful.

EFEITOS DO SULFATE DE MAGNESIO NA HEMODINAMICA E FUNCAO RENAL DE CAES ANESTESIADOS CORN PENTOBARBITAL SODICO

Background and objectives - The use of magnesium sulphate for the prevention of seizures in pre-eclampsia may induce hypermagnesemia. Clinical and experimental studies are not in agreement about the effects of magnesium on the renal hemodynamics and function. We therefore studied the effects of hypermagnesemia on the renal hemodynamics and function of dogs anesthetized with pentobarbitone. Methods - Sixteen mongrel dogs were anesthetized with pentobarbitone 30 mg.kg-1 and submitted to extracellular ) and mechanical ventilation with room air. The dogs were volume expansion with Ringer's solution (0.4 ml.kg.min allocated into two groups of 8 animals, for the study of renal hemodynamics and function following the administration of 5 mg.kg-1 of pentobarbitone (Group 1 - control or of pentobarbitone associated with magnesium sulphate in the dose (Group 2). The parameters studied were: PAH of 140 mg.kg, administered in 15 minutes, followed by 80 mg.kg-1.h-1 clearance, creatinine clearance, osmolar clearance, free water clearance, renal blood flow, renal vascular resistance, filtration fraction, urinary volume, plasmatic and urinary osmolarity, urinary and fractionary excretion of sodium and potassium, measured at five moments: 15 (M1), 30 (M2), 60 (M3) and 75 (M4) minutes after the first supplementary dose of pentobarbitone and 15 minutes (M5) after the second supplementary dose in Group 1. In Group 2, the moments M3, M4, M5 were 15, 30 and 60 minutes after the priming dose of magnesium sulphate and during the maintenance dose. Results - In Group I no significant changes were observed in renal hemodynamic parameters and creatinine clearance. The extracellular volume expansion increased urinary volume and decreased urinary osmolarity as a consequence of sodium, potassium and free water clearance. The fractionary excretion of sodium was maintained. The plasmatic osmolarity increased. In Group 2, renal hemodynamic parameters and creatinine clearance were also maintained. There was an increase in renal sodium clearance, as detected by the increase in the fractionary excretion of sodium. Conclusions - Magnesium sulphate did not produce significant changes in renal hemodynamics and facilitated the renal excretion of sodium in dogs anesthetized with pentobarbitone.

On a dual role for clonidine stimulation of the ventromedial nucleus of the hypothalamus in sodium and potassium renal excretions of rats

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α 1-adrenergic receptor antagonist) and yohimbine (an α 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α 1-adrenoceptors and that inhibitory effects require α(2A)-adrenoceptors.

Superoxide radical and nephrotoxic effect of cadmium exposure

Pollution and industrial practices result in concentrations of metals and other environmental agents that are related to environmental toxicity. Concentrations of metals are widely related to biochemicals values which are used in disease diagnosis due to environmental toxicity. This work was carried out in order to verify the nephrotoxic effect of cadmium and to clarify the contribution of reactive oxygen species (ROS) in this process. Cadmium chloride was tested for nephrotoxic damage in rats by a single intraperitoneal (i.p.) injection Cd 2+ (2 mg/kg) and oral intake (Cd2 +-100 mg/l-from CdCl 2). The cadmium-induced biochemical alterations included significant increased levels of serum creatinine concentrations, in rats with i.p. injection. Total urinary protein concentrations were only increased in rats with cadmium intake. Lipoperoxide was also increased after 3 and 7 days of the Cd 2+ treatment. No changes were observed in glutathione peroxidase activities. Cadmium-induced damage might be due to superoxide radicals (O 2 -), since Cu-Zn superoxide dismutase activities were decreased by Cd 2+ treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in cadmium nephrotoxicity. We concluded that the superoxide radical may be produced as a mediator of nephrotoxic action of cadmium.