Quantitation of bioactive components in infant formulas: Milk oligosaccharides, sialic acids and corticosteroids.

Human milk is considered the optimal food for infants with abundant nutrients and bioactive components, which play key roles in infant health and development. Infant formulas represent appropriate substitutes for human milk. There are many brands of infant formula with different ingredient sources and functions on the market. The present study aims to quantify important bioactive components, i.e., milk oligosaccharides (MOS), sialic acids (Sia) and corticosteroids, in different infant formulas and compare these to human milk. In total, 12 different infant formulas available on the Dutch market were analyzed in this study. The concentrations of MOS and Sia were characterized by UHPLC-FLD and LC-MS, while corticosteroids were determined using established UHPLC-MS/MS methods. Among infant formulas, 15 structures of oligosaccharides were identified, of which 2'-Fucosyllactose (2'FL), 3'-Galactosyllactose (3'GL) and 6'-Galactosyllactose (6́'GL) were found in all infant formulas. The oligosaccharide concentrations differed between milk source and brands and were 3-5 times lower than in human milk. All infant formulas contained Sia, N-acetylneuraminic acid (Neu5Ac) was dominant in bovine milk-based formulas, while N-glycolylneuraminic acid (Neu5Gc) was major in goat milk-based formula. All infant formulas contained corticosteroids, yet, at lower concentrations than human milk. Insight in concentrations of bioactive components in infant formula compared to human milk may give direction to dietary advices and/or novel formula design.

Maternal corticosteroids and depression during gestation and decreased fetal heart rate variability.

OBJECTIVE: Maternal depression during gestation is an adverse factor in fetal brain development that manifests in later childhood behavioral problems. Fetal heart rate variability (FHRV) mediated by parasympathetic input is a marker of gestational nervous system development. Biological mediators of adverse effects of maternal depression may involve the mother's corticosteroids; however, links between depression, corticosteroids, and early nervous system development remain inconclusive. METHODS: Heart rate was recorded in 23 fetuses by transabdominal Doppler at 28-33 weeks gestation. The SD of interbeat intervals over 20 min assessed FHRV. Maternal depression ratings and hair concentrations of cortisol and cortisone were assayed. An auditory sensory gating paradigm assessed newborn development of cerebral inhibition. Parents rated their infant's temperament characteristics on the Infant Behavior Questionnaire-Revised Short Form (IBQ-R). RESULTS: Maternal depression was associated with lower FHRV, especially for male fetuses, ß = -0.633, P = 0.045. Maternal depression was associated with lower cortisol to total corticosteroids ratios, ß = -0.519, P = 0.033. Lower cortisol ratios were associated with decreased FHRV, ß = 0.485, P = 0.019. Decreased FHRV was associated with increased newborn sensory gating deficits, ß = -0.992, P = 0.035, indicating poorer development of cerebral inhibition. Higher FHRV was related to increased infant IBQ-R self-regulatory behaviors, r = 0.454, P = 0.029. CONCLUSION: Maternal depression is associated via corticosteroids with decreased development of nervous system control of fetal heart rate. Decreased FHRV indicates developmental alterations in gestation that correlate with altered brain function and subsequent regulatory challenges in early infancy.

Detection of 28 Corticosteroids in Pharmaceutical and Proprietary Chinese Medicinal Products Using Liquid Chromatography-Tandem Mass Spectrometry.

With their potent anti-inflammatory effects, corticosteroids are popular adulterants in illicit health products for allergies, dermatitis and pain control. Their illegal supply over the counter is also a common practice for similar conditions. Prolonged, unsupervised usage of corticosteroids often leads to severe adverse effects including Cushing syndrome, adrenal insufficiency and immunosuppression. Confirming clinical suspicion of unsupervised corticosteroid usage is challenging. Apart from evaluating the adrenal function, identifying the concerned drug is the most direct proof of its consumption. While detecting corticosteroids or their metabolites in biological specimens is convincing evidence of their usage, such approach is analytically difficult. More importantly, this approach would not be useful if the patient has stopped taking the drug for some time-a situation that is often encountered clinically. We advocate a more direct approach by measuring corticosteroids in suspicious medicinal products. In the current study, a liquid chromatography-tandem mass spectrometry method for simultaneous detection of 28 corticosteroids in pharmaceutical and proprietary Chinese medicine products was developed and validated for the purpose. The method was applied to 388 cases of suspected unsupervised corticosteroids usage. Among 1,000 products tested, corticosteroids were found in 276 of them and confirmed the clinical suspicion.

Bulk to Nanometer-Scale Infrared Spectroscopy of Pharmaceutical Dry Powder Aerosols.

Solid state chemical analysis of pharmaceutical inhalation aerosols at the individual particle level has been an analytical challenge. These particles can range from a few nanometers to micrometers and are a complex mixture of drugs and excipients. Conventional analytical techniques cannot resolve the distribution of excipients and drugs at the submicrometer scale. Understanding the nanochemical composition of individual particles can be critical for pharmaceutical scientists to evaluate drug and excipient stability as well as the drug-drug or drug-excipient interactions that affect the aerosol performance of powders. Herein, we show the novel application of a combination of optical photothermal infrared (O-PTIR) spectroscopy and atomic force microscopy infrared (AFM-IR) spectroscopy to probe nanochemical domains of powders containing the inhaled corticosteroid fluticasone propionate and long-acting ß2-agonist salmeterol xinafoate, which are widely used to treat asthma and chronic obstructive pulmonary disease. Three types of powder formulation were analyzed, including the commercial product Seretide, which is a physical mixture of the drugs with crystalline lactose, and two spray-dried powders containing the drugs along with either amorphous or crystalline lactose. We obtained spatially resolved O-PTIR and AFM-IR spectra confirming the presence of peaks related to fluticasone propionate at 1743, 1661, and 1700 cm-1, salmeterol xinafoate at 1580 cm-1, and lactose at 1030 and 1160 cm-1. The location of the drugs and lactose among the particles varied significantly, depending on the formulation type. For the first time, it was possible to map the drug distribution in individual aerosol particles. This is significant as such information has been lacking, and it will open an exciting research direction on how drug distribution affects the aerosol performance of powders and the consistency of dose uniformity. Further, these advanced spectroscopic techniques can be applied to study a wide range of pharmaceutical formulations.

A Critical Review of Analytical Methods in Pharmaceutical Matrices for Determination of Corticosteroids.

Corticosteroids are a class of hormones released by the adrenal cortex, which includes glucocorticoids and mineralocorticoids. Glucocorticoids have an important role in the metabolism of carbohydrates, proteins and calcium and effective anti-inflammatory and immunosuppressive activity. Due to their intense immunomodulatory and anti-inflammatory activity, glucocorticoids are used in the treatment of various inflammatory, malignant, allergic conditions such as rhinitis, asthma, dermatological, rheumatic, ophthalmic and neurological diseases, as well as after organ transplants. They are the most widely prescribed drugs in the world. The objective of this review is to provide an overview of the analytical methods in pharmaceutical matrices for determination of corticosteroids. In this study, the predominance of liquid chromatography methods for the analysis of corticosteroids from pharmaceutical products is evident for both liquid and semisolid dosage forms as well as for solids. The same can be said for topical, oral and parenteral formulations. Methods such as spectrophotometry are also used, but given the advantages of chromatographic methods such as better selectivity and sensitivity, they have become the choice for analysis of these drugs, however, most methods still do not meet the credentials of "green chemistry."

Steroid Profiling and Immunohistochemistry for Subtyping and Outcome Prediction in Primary Aldosteronism-a Review.

PURPOSE OF REVIEW: Steroid profiling and immunohistochemistry are both promising new tools used to improve diagnostic accuracy in the work-up of primary aldosteronism (PA) and to predict treatment outcomes. Herein, we review the recent literature and present an outlook to the future of diagnostics and therapeutic decision-making in patients with PA. RECENT FINDING: PA is the most common endocrine cause of arterial hypertension and unilateral forms of the disease are potentially curable by surgical resection of the overactive adrenal. Recent studies have shown that adrenal steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be helpful for subtyping unilateral and bilateral forms of PA, classifying patients with a unilateral aldosterone-producing adenoma (APA) according to the presence of driver mutations of aldosterone production in APAs, and potentially predicting the outcomes of surgical treatment for unilateral PA. Following adrenalectomy, immunohistochemistry of aldosterone synthase (CYP11B2) in resected adrenals is a new tool to analyze "functional" histopathology and may be an indicator of biochemical outcomes after surgery. Biochemical and clinical outcomes of therapy in PA vary widely among patients. Peripheral venous steroid profiling at baseline could improve diagnostic accuracy and help in surgical decision-making in cases of a suspected APA; results of "functional" histopathology could help determine which patients are likely to need close post-surgical follow-up for persistent aldosteronism.

Occurrence, distribution, and potential risks of environmental corticosteroids in surface waters from the Pearl River Delta, South China.

The occurrence, spatiotemporal distribution, and potential risks of 21 glucocorticoids (GCs) and 3 mineralocorticoids (MCs) in four rivers were studied by investigating the surface waters from the Pearl River Delta (PRD), South China. These environmental corticosteroids (ECs) were commonly present in the river surface waters with average concentrations varying from <0.17 ng/L for fluticasone propionate to 5.6 ng/L for clobetasone butyrate; and cortisone had the highest concentration, 32.9 ng/L. The total ECs ranged in concentration from undetectable to 83.3 ng/L, with a mean and median of 8.1 ng/L and 4.8 ng/L, respectively. Spatially the total EC concentration levels in the Pearl River system occurred in the following order: Zhujiang River (ZR) > Dongjiang River (DR) > Shiziyang waterway (SW) > Beijiang River (BR). These levels generally demonstrated a trend of increasing from upstream to midstream or downstream then attenuating toward the estuary. Considerable seasonal variations in the ECs differed among rivers. Higher ECs concentrations in winter were mostly found in the ZR, whereas lower levels were found in the DR. Moreover, the temporal variations of the ECs were marginal in the BR and SW. These spatiotemporal distributions of the ECs might have been simultaneously influenced by pollution sources derived from anthropogenic activities and river hydrologic conditions. Correlation analyses indicated that dissolved organic carbon (DOC) could play a key role in the occurrence and distribution of ECs in an aquatic environment. Risk assessment demonstrated that the occurrence of ECs might have posed medium to high risk to aquatic organisms in the Pearl River.

The Use of Feathers from Racing Pigeons for Doping Control Purposes.

The development of accurate and reliable analytical methodologies to detect the abuse of doping agents in sport animals is crucial to ensure their welfare, as well as to support continuing social acceptance of these sports. The detection of doping agents in racing pigeons is difficult, especially owing to the disadvantages and limitations of obtaining samples from conventional matrices. The present study aimed to develop and validate an analytical methodology combining a two-step extraction procedure (liquid-liquid extraction and solid-phase extraction) in feathers from racing pigeons with analysis by liquid chromatography tandem mass spectrometry (LC-MS-MS) that enabled the simultaneous detection of a beta-agonist drug (clenbuterol) and three corticosteroids (prednisolone, betamethasone and budesonide). The method was validated concerning linearity (with coefficients of determination always higher than 0.99), accuracy (87.3-112.4%), precision (repeatability and intermediate precision coefficient of variation (CV%) always below 15%), recovery (71.6-98.2%), limits of detection (0.24-0.52 ng/g) and quantification (0.79 and 0. 1.74 ng/g) and specificity. The applicability of the method was performed using feathers from pigeons administered orally with a daily dose of 0.075 mg of betamethasone. The drug was administered during 60 days and successive analyses of feathers were performed, at the end of the administration protocol and also after ceasing the oral administration of the drug, for a three weeks period.

Multiclass screening method to detect more than fifty banned substances in bovine bile and urine.

A multiclass screening method to detect fifty-three forbidden substances by liquid-chromatography coupled to hybrid high-resolution mass spectrometry (LC-Q-Orbitrap) was developed and validated in bovine bile and urine. Eight classes of compounds were included in the method's scope (ß-agonists, corticosteroids, nitroimidazoles, progestins, resorcylic acid lactones (RALs), sedatives, steroids and stilbenes) plus chloramphenicol and dapsone. After hydrolysis, the sample was divided in two aliquots, which followed two parallel purification steps. The reunified extracts were injected and two chromatographic runs performed in positive and negative ionization mode, respectively. The validation data (60 different samples per matrix) proved that the method was fit for purpose with detection capabilities lower than 1 µg L-1 in both matrices. The combined application of accurate mass acquisition and two-stage mass spectrometry (parallel reaction monitoring) was crucial to achieve suitable selectivity, which is the most critical parameter mainly for urines. Finally, the long-standing problem of the high rate of false positive results for RALs, due to the natural ingestion of mycotoxin, zearalenone, was taken on including all their labelled standards. That allowed a very satisfactory management of this screening test.

Quantification of doping compounds in faecal samples from racing pigeons, by liquid chromatography-tandem mass spectrometry.

The use of performance enhancing drugs is not only common in humans, but also in animal sports, including racing of horses, greyhounds and pigeons. The development of accurate analytical procedures to detect doping agents in sports is crucial in order to protect the fair-play of the game, avoid financial fraud in the attribution of eventual awards and, even more important, to protect the animals from harmful drugs and/or dangerous dosage regimens. The present study aimed to develop and validate, a method that enabled the screening and confirmation of the presence of a beta-agonist (clenbuterol) and three corticosteroids (betamethasone, prednisolone and budesonide) in faeces from pigeons. The extraction procedure entailed the combination of liquid-liquid extraction with solid-phase extraction and the analysis was performed by liquid- chromatography coupled to tandem mass spectrometry, with a single 15 minute chromatographic run-time. The method was validated concerning selectivity, linearity (with coefficients of determination always >0.99), accuracy (87.5-114.9%), inter-day and intra-day precisions, limits of detection (0.14-1.81 ng/g) and limits of quantification (0.49-6.08 ng/g), stability and extraction recovery (71.0%-99.3%). The method was successfully applied for the analysis of samples from two pigeons that had been orally administered betamethasone, demonstrating its suitability for doping control purposes.

Corticosteroids in liver and urine in Sicilian cattle by a LC-MS/MS method.

The presence of corticosteroid residues was assessed in urine and liver samples from livestock of Sicily. A total of 630 bovine samples were collected from farms and slaughterhouses. The samples were analysed using solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). All the corticosteroids found were under the maximum residue limit imposed by Commission Regulation (EC) 37/2010. About 4% of liver samples showed dexamethasone levels above the limit of detection (LOD), with a mean of 1.5 ± 0.2 µg kg-1. Betamethasone was found only in seven liver samples, with a mean of 1.6 ± 0.1 µg kg-1. Furthermore, prednisolone and prednisone were found only in urine and liver samples from slaughterhouse, probably related to the high rate of stress for bovines. These results suggest good control practices adopted by Sicilian farms, able to ensure the quality of food products.

Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy.

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30-21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

OBJECTIVE: To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. METHODS: Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. RESULTS: Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. CONCLUSION: All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements.

Perinatal exposure to venlafaxine leads to lower anxiety and depression-like behavior in the adult rat offspring.

Depression during pregnancy and in the post-partum period is a growing health issue. Venlafaxine, a representative of serotonin and noradrenaline reuptake inhibitors, is used to treat a wide spectrum of mood disorders. However, the limited number of prenatal and perinatal studies raises the question about the long-term consequences of venlafaxine therapy. The aim of this study was to investigate the effect of venlafaxine exposure during pregnancy and lactation on anxiety-like and depression-like behaviors, as well as adrenocortical hormone concentrations in the adult rat offspring. For this purpose, rat dams were treated orally with venlafaxine from day 15 of gestation to postnatal day 20 at doses of 7.5, 37.5, and 75 mg/kg. Administration of venlafaxine during gestation and lactation affected anxiety-like and depression-like behaviors in adult rat offspring of both sexes. The animals exposed through their mothers to venlafaxine, particularly at the lowest and middle doses, were less anxious and less depressive in several relevant behavioral tests, which can be considered a deviation from the normal state. At clinically relevant doses, venlafaxine did not alter circulating level of corticosterone and aldosterone in the adult offspring. In general, the consequences of venlafaxine were dose dependent and more apparent in females. Together, these results suggest that prenatal and early postnatal exposure to venlafaxine may interfere with functional development of the brain, though not necessarily in a negative way.

The concentration of fear: mice's behavioural and physiological stress responses to different degrees of predation risk.

Predation is an unavoidable and dangerous fact in the lifetime of prey animals and some sign of the proximity of a predator may be enough to trigger a response in the prey. We investigated whether different degrees of predation risk by red foxes (Vulpes vulpes) evoke behavioural and physiological stress responses in wood mice (Apodemus sylvaticus). We examined the variation in mice responses due to individual factors (sex and reproductive status) and related them to the concentration of the volatile compounds from fox faeces over time. In our experiment, we introduced predation cues into four plots, each subjected to a different concentration treatment (0, 10, 50 and 100% concentration of fresh faeces of red fox), based on the following outline: initial odourless phase 0, phase1 in which predation treatment was renewed daily, and phase 2 in which we renewed the treatment only on the first day. Wood mice were live trapped during all three phases and the physiological response was measured non-invasively by analysing faecal corticosterone metabolites (FCM) in freshly collected faeces. Data were analysed by Generalized Linear Mixed Models. Overall, males were trapped less often than females, and reproductively active individuals from both sexes avoided traps more than non-reproductively active individuals, especially in medium- and high- concentration plots. Variations in FCM concentrations were explained by plot, the interaction between plot and treatment phase, and the interaction between the treatment phase and the reproductive status. During phase 1, we detected a significant rise in FCM levels that increased with predator faecal odour concentration. Additionally, reproductively active individuals showed a strong physiological response during both phases 1 and 2 in all plots, except the control plot. Our results indicated that wood mice are able to discriminate different degrees of predation risk, which allows them to trigger gradual changes in their behavioural and physiological stress responses.

Determination of two progestin metabolites (17α-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, corticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

A highly sensitive and robust method was developed for routine analysis of two progestin metabolites, 17α-hydroxypregnanolone (17OH-Δ5P) and pregnanediol (PD), and 31 other natural and synthetic steroids and related metabolites (estrogens, androgens, corticosteroids, progestins) in river water, as well as influents and effluents of municipal wastewater treatment plants (WWTP) using HPLC-MS/MS combined with solid-phase extraction. For the various matrixes considered, the optimized method showed satisfactory performance with recoveries of 70-120% for most of target steroids. The method detection limits (MDLs) ranged from 0.01 to 3ng/L for river water, 0.02 to 10ng/L for WWTP effluents, and 0.1 to 40ng/L for influents with good linearity and reproducibility. The developed method was successfully applied for the analysis of steroids in rivers and WWTP influent and effluents. WWTP influents concentrations of 17OH-Δ5P and PD were 51-256ng/L and up to 400ng/L, respectively, along with androstenedione (concentration range: 38-220ng/L), testosterone (11-26ng/L), estrone (2.3-37ng/L), 17ß-estradiol (N.D.-8.7ng/L), 17α-hydroxyprogesterone (N.D.-66ng/L), medroxyprogesterone acetate (N.D.-5.3ng/L), and progesterone (2.0-22ng/L), while only androstenedione (ADD), estrone (E1), and estriol (E3) were detected in effluent with concentrations ranging up to 1.7ng/L, 0.90ng/L and 0.8ng/L, respectively. In river water samples, only ADD and E1 were detected with concentrations up to 1.0ng/L and 0.91ng/L. Our procedure represents the first method for analyzing 17OH-Δ5P and PD in environmental samples along with a large series of steroids.

Supplementing electronic health records through sample collection and patient diaries: A study set within a primary care research database.

PURPOSE: To describe a novel observational study that supplemented primary care electronic health record (EHR) data with sample collection and patient diaries. METHODS: The study was set in primary care in England. A list of 3974 potentially eligible patients was compiled using data from the Clinical Practice Research Datalink. Interested general practices opted into the study then confirmed patient suitability and sent out postal invitations. Participants completed a drug-use diary and provided saliva samples to the research team to combine with EHR data. RESULTS: Of 252 practices contacted to participate, 66 (26%) mailed invitations to patients. Of the 3974 potentially eligible patients, 859 (22%) were at participating practices, and 526 (13%) were sent invitations. Of those invited, 117 (22%) consented to participate of whom 86 (74%) completed the study. CONCLUSIONS: We have confirmed the feasibility of supplementing EHR with data collected directly from patients. Although the present study successfully collected essential data from patients, it also underlined the requirement for improved engagement with both patients and general practitioners to support similar studies.

Idiopathic Ulcerative Laryngitis: An uncommon disease / Laringitis Ulcerativa Idiopática: una entidad poco común

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Application of microwave-assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry for the analysis of sex hormones and corticosteroids in sewage sludge samples.

Hormonal compounds are a concern to the international community because they can affect the aquatic biota and are therefore considered to be endocrine-disrupting compounds. These compounds have lipophilic properties, so they tend to accumulate in solid matrices, such as sewage sludge. This work presents the optimization of a microwave-assisted extraction process combined with ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of 15 hormonal compounds in sludge samples. The proposed method has relative standard deviations below 23 %, good recoveries (over 71 %) for all compounds, detection limits that ranged from 1.1 to 7.9 ng g(-1) and quantification limits which ranged from 3.7 to 26.3 ng g(-1). The method was used to analyse sludge samples from four different wastewater treatment plants of Gran Canaria (Spain) with different wastewater treatments. 17ß-estradiol, 17α-ethynylestradiol, norgestrel and cortisone were detected in sludge samples at concentrations that ranged from 17.3 to 1.44 × 10(3) ng g(-1). The developed method permits the use of small quantities of sample and organic solvents, presents short extractions times and is the first one based on microwave-assisted extraction for the analysis of both sex hormones and corticosteroids.

Meningitis aséptica como complicación del tratamiento con inmunoglobulinas en la miastenia grave / Aseptic meningitis as a complication of immunoglobulin treatment in myasthenia gravis

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