Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization

Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects

Background: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. Methods: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. Results: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 μmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). Conclusions: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus

Osjetljiva spektrofotometrijska metoda za određivanje sulfonamida u farmaceutskim pripravcima

A new, simple and sensitive spectrophotometric method for the determination of some sulfonamide drugs has been developed. The method is based on the diazotisation of sulfacetamide, sulfadiazine, sulfaguanidine, sulfamerazine, sulfamethazine, sulfamethoxazole and coupling with 8-hydroxyquinoline in alkaline media to yield red coloured products, with absorption maximum at 500 nm. The Beer’s law is obeyed from 0.17.0 µg mL1. The limits of quantification and limits of detection were 0.110.18 and 0.030.5 µg mL1, respectively. Intraday precision (RSD 0.10.5%) and accuracy (recovery 97.3100.8) of the developed method were evaluated. No interference was observed from common adjuvants. The method has been successfully applied to the assay of sulpha drug in the pharmaceutical formulations.U radu je opisana nova, jednostavna i osjetljiva spektrofotometrijska metoda za određivanje sulfonamida. Metoda se temelji na prevođenju sulfacetamida, sulfadiazina, sulfagvanidina, sulfamerazina, sulfometazina i sulfametoksazola u diazoderivate koji kondenzacijom s 8-hidroksikinolinom u alkalnom mediju daju crveno obojene produkte s maksimumom apsorpcije pri 500 nm. Beerov zakon vrijedi u koncentracijskom rasponu 0,17,0 µg mL1. Granice kvantifikacije i granice detekcije su 0,11-0,18, odnosno 0,03-0,05 µg mL-1. Za predloženu metodu procijenjene su intermedirska preciznost (RSD 0.1-0,5%) i točnost (analitički povrat 97,3-100,8). Uobičanjene pomoćne tvari u tabletama ne interferiraju tijekom određivanja. Metoda je uspješno primijenjena za analizu sulfonamida u farmaceutskim pripravcima

Національно-демократичні об'єднання та політичні партії в Україні кінця XIX - початку XX століття

Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson's disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give and overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an important technology intensive domain, an "intuitive visualisation" interface for improving management of these data in relation to surgery is suggested

Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods. © The Author(s) 2010.Link_to_subscribed_fulltex

The role of muscle strength on tendon adaptability in old age.

PURPOSE: The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences. METHODS: The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 ± 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging. RESULTS: No between-leg differences in triceps surae muscle strength were identified between dominant (2798 ± 566 N) and non-dominant limb (2667 ± 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P < 0.05) of maximal AT force with AT stiffness (r = 0.500) and Young's modulus (r = 0.414), but only a tendency with the mean AT CSA. However, region-specific analysis revealed a significant relationship between maximal AT force and the proximal part of the AT, indicating that this region is more likely to display morphological adaptations following an increase in muscle strength in older adults. CONCLUSIONS: These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size

Effect of cysteine dosage on erythrocyte glutathione synthesis rate in a patient with cystathionine beta synthase deficiency

Cystathionine β-synthase (CBS)-deficient patients develop premature arteriosclerosis and thrombosis leading to a high risk of a vascular event before the age of 30 years. In CBS deficiency the transsulfuration pathway is impaired, leading to markedly elevated levels of homocysteine and methionine, and severely decreased levels of cystathionine and cysteine. Through autooxidation these elevated levels of homocysteine might induce excessive production of reactive oxygen species (ROS). ROS are involved in endothelial damage and are neutralized by antioxidants. In humans the main antioxidant is glutathione (GSH). Its production mainly depends on the amount of available cysteine. Since cysteine levels in CBS deficiency are decreased, GSH production is presumed to be low. Accordingly, all CBS-deficient patients receive cysteine supplements, which supposedly stimulate GSH synthesis. However, data on the effect of cysteine dosage on GSH synthesis in CBS-deficient patients are lacking. Therefore, in a CBS-deficient pyridoxine non-responsive female patient, concentration and fractional synthesis rate (FSR) of erythrocyte GSH were measured by infusion of l-[3,3-(2)H2]cysteine tracer during prolonged cysteine supplementation with 88 and 40 mg/kg per day. Erythrocyte GSH concentration and its FSR at cysteine supplementation with 88 versus 40 mg/kg per day were 1.25 versus 1.30 mmol/L and 230 versus 254% per day, respectively. These data suggest that in a CBS-deficient patient exogenous supply of 40 mg cysteine/kg per day is sufficient to maintain GSH synthesis in erythrocytes. Further studies in larger patient groups should be initiated to measure the effects on GSH metabolism to further elucidate the correct dose of cysteine supplements in CBS-deficient patient

Report from the HarmoSter study: Impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration. Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials. Using CAL1, intra-laboratory CVs ranged between 2.8-7.4%, 4.4-18.0% and 5.2-22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p&lt;0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from -6.6 to 6.9%, -17.2 to 7.8% and -12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation. Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements