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The purpose of the article is to study the dynamics of hormonal activity in ski-racers in the preparatory and competitive period and to establish significant changes that demonstrate the effectiveness of competitive activity. Changes in testosterone, urine estrogens, T4 tyrosine and cortisol were compared in racers under training conditions of alternating middle altitude hypoxia and normoxia (group 1) and only normoxia (group 2). Materials and methods. 17 male ski-racers aged 18-23 years were involved in the study. The first group (1) consisted of cross-country skiers with a training process in the conditions of alternating middle altitude hypoxia (May-August- October) and normoxia (n = 7); the second group - ski-racers with the training process only in conditions of normoxia (n = 10). The study was conducted in the preparatory and competitive period (July and December). The cortisol content was determined using fluorometry with the help of Fluorat-02 ABLFT biofluid analyzer (Lumex, St. Petersburg, Russia) at a fluorescence excitation wavelength of 405 nm and an emission of 546 nm. At the same time, the object of laboratory research was heparinized blood taken from a cubital vein in the morning, on an empty stomach. The levels of total testosterone, urine estrogens, and T4 tyrosine were obtained with the help of a noninvasive AMP blood analyzer (Ukraine). Discriminant analysis was applied for statistical data processing as well as rank correlation analysis and nonparametric analysis of variance (William R. Kleck (1986). Results. It was found that in the 1st group of athletes there was an increase in total testosterone by 11.05% (p> 0.05), a decrease in urine estrogen and cortisol by 17.55% (p <0.05) and 29.91% (p <0.05), respectively. In the 2nd group, by the competitive period, we detected a decrease in testosterone by 6.41% (p> 0.05), urine estrogen by 3.49% (p> 0.05), tyrosine T4 by 0.18% (p> 0, 05) against the background of an increase in the concentration of cortisol by 25.85% (p <0.05). Conclusion. The study showed that people with a combined training process have a more successful competitive activity. The nature of the responses in the process of adaptation is determined by a decrease in catabolic and an increase in anabolic processes. [ABSTRACT FROM AUTHOR]

Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy. [ABSTRACT FROM AUTHOR]

Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that hyperandrogenemia in androgen excess polycystic ovary syndrome (AE-PCOS) is a primary driver in blood pressure (BP) dysregulation via altered sympathetic nervous system activity (SNSA), reduced integrated baroreflex gain and increased renin-angiotensin system (RAS) activation. We measured resting SNSA (microneurography), integrated baroreflex gain, and RAS with lower body negative pressure in obese insulin-resistant (IR) women with AEPCOS [n = 8, 23 ± 4 yr; body mass index (BMI) = 36.3 ± 6.4 kg/m2] and obese IR controls (n = 7, control, 29 ± 7 yr; BMI = 34.9 ± 6.8 kg/m²), at baseline (BSL), after 4 days of gonadotropin-releasing hormone antagonist (ANT, 250 µg/day) and 4 days of ANT þ testosterone (ANT þ T, 5 mg/day) administration. Resting BP was similar between groups for systolic blood pressure (SBP; 137 ± 14 vs. 135 ± 14 mmHg, AE-PCOS, control) and diastolic BP (89 ± 21 vs. 76 ± 10 mmHg, AE-PCOS, control). BSL integrated baroreflex gain was similar between groups [1.4 ± 0.9 vs. 1.0 ± 1.3 forearm vascular resistance (FVR) U/mmHg], but AE-PCOS had lower SNSA (10.3 ± 2.0 vs. 14.4 ± 4.4 burst/100 heartbeats, P = 0.04). In AE-PCOS, T suppression increased integrated baroreflex gain, which was restored to BSL with ANT þ T (4.3 ± 6.5 vs. 1.5 ± 0.8 FVR U/mmHg, ANT, and ANT þ T, P = 0.04), with no effect in control. ANT increased SNSA in AE-PCOS (11.2±2.4, P = 0.04). Serum aldosterone was greater in AE-PCOS versus control (136.5 ± 60.2 vs. 75.7 ± 41.4 pg/mL, AE-PCOS, control, P = 0.04) at BSL but was unaffected by intervention. Serum angiotensin-converting enzyme was greater in AE-PCOS versus control (101.9 ± 93.4 vs. 38.2± 14.7 pg/mL, P = 0.04) and reduced by ANT in AE-PCOS (77.7 ± 76.5 vs. 43.4 ± 27.3 lg/L, ANT, and ANT þ T, P = 0.04) with no impact on control. Obese, IR women with AE-PCOS showed decreased integrated baroreflex gain and increased RAS activation compared with control. NEW & NOTEWORTHY Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS. [ABSTRACT FROM AUTHOR]

Objectives Sickness behavior, a suite of behavioral changes subsequent to infection that includes depression, decreased social behaviors, and sleep disturbances, has been well described in model organisms. The phenomenon is relatively unexplored in humans due to methodological difficulties, and hormonal correlates of sickness behavior have not been studied. We therefore attempted to use a vaccine to elicit sickness behaviors outside of a clinical setting and uncover any correlations among testosterone, cortisol, and sickness behavior. Methods Eleven participants (five male, six female, mean age 22.8 years) naïve to the rabies vaccine were recruited from the School of Veterinary Medicine at Purdue University. Participants provided daily saliva and urine samples and completed questionnaires to assess mood and social behaviors for a period of 6 weeks. Saliva samples were assayed for cortisol and testosterone. Urine samples were assayed for interleukin-6 and creatinine. Results Analysis revealed an expected decrease in testosterone and an increase in cortisol. While mood did not differ, other behaviors, such as physical activity and hours slept, showed expected changes following vaccination. However, none of these results achieved statistical significance. Conclusion Our results, while generally confirming previous research on sickness behavior and hormone changes during infection, are suggestive, but not statistically significant and so neither confirm nor contradict our hypotheses. We attribute this lack of significance to both the small sample size, as well as possible confounding factors, including the psychosocial stress of entering an intensive study program. Am. J. Hum. Biol. 27:133-135, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

It is critical to identify biomarkers for neurological diseases (NLDs) to accelerate drug discovery for effective treatment of patients of diseases that currently lack such treatments. In this work, we retrieved genotyping and clinical data from 1,223 UK Biobank participants to identify genetic and clinical biomarkers for NLDs, including Alzheimer's disease (AD), Parkinson's disease (PD), motor neuron disease (MND), and myasthenia gravis (MG). Using a machine learning modeling approach with Monte Carlo randomization, we identified a panel of informative diagnostic biomarkers for predicting AD, PD, MND, and MG, including classical liver disease markers such as alanine aminotransferase, alkaline phosphatase, and bilirubin. A multinomial model trained on accessible clinical markers could correctly predict an NLD diagnosis with an accuracy of 88.3%. We also explored genetic biomarkers. In a genome-wide association study of AD, PD, MND, and MG patients, we identified single nucleotide polymorphisms (SNPs) implicated in several craniofacial disorders such as apnoea and branchiootic syndrome. We found evidence for shared genetic risk loci among NLDs, including SNPs in cancer-related genes and SNPs known to be associated with non-brain cancers such as Wilms tumor, leukemia, and colon cancer. This indicates overlapping genetic characterizations among NLDs which challenges current clinical definitions of the neurological disorders. Taken together, this work demonstrates the value of data-driven approaches to identify novel biomarkers in the absence of any known or promising biomarkers. [ABSTRACT FROM AUTHOR]

In women, hormonal fluctuations related to the menstrual cycle may impose a great source of variability for some biomarkers of testosterone (T) administration, which can ultimately disrupt the sensitivity of their longitudinal monitoring. In this study, the sensitivity of the current urinary and haematological markers of the Athlete Biological Passport (ABP), as well as serum steroid biomarkers, was investigated for the monitoring of a 28‐day T gel treatment combined with endogenous fluctuation of the menstrual cycle in 14 healthy female subjects. Additionally, the analysis of urinary target compounds was performed on a subset of samples for endogenous/exogenous origin via isotope ratio mass spectrometry (IRMS). In serum, concentrations of T and dihydrotestosterone (DHT) increased significantly during the treatment, whereas in urine matrix the most affected biomarkers were found to be the ratios of testosterone/epitestosterone (T/E) and 5α‐androstane‐3α,17β‐diol/epitestosterone (5αAdiol/E). The detection capability of both urinary biomarkers was heavily influenced by [E], which fluctuated depending on the menstrual cycle, and resulted in low sensitivity of the urinary steroidal ABP module. On the contrary, an alternative approach by the longitudinal monitoring of serum T and DHT concentrations with the newly proposed T/androstenedione ratio showed higher sensitivity. The confirmatory IRMS results demonstrated that less than one third of the tested urine samples fulfilled the criteria for positivity. Results from this study demonstrated that the 'blood steroid profile' represents a powerful complementary approach to the 'urinary module' and underlines the importance of gathering bundle of evidence to support the scenario of an endogenous prohibited substance administration. [ABSTRACT FROM AUTHOR]

The ready detectability of synthetic androgens by mass spectrometry (MS)‐based antidoping tests has reoriented androgen doping to using testosterone (T), which must be distinguished from its endogenous counterpart making detection of exogenous T harder. We investigated urine and serum steroid and hematological profiling individually and combined to determine the optimal detection model for T administration in women. Twelve healthy females provided six paired blood and urine samples over 2 weeks prior to treatment consisting of 12.5‐mg T in a topical transdermal gel applied daily for 7 days. Paired blood and urine samples were then obtained at the end of treatment and Days 1, 2, 4, 7, and 14 days later. Compliance with treatment and sampling was high, and no adverse effects were reported. T treatment significantly increased serum and urine T, serum dihydrotestosterone (DHT), urine 5α‐androstane‐3α,17β‐diol (5α‐diol) epitestosterone (E), and urine T/E ratio with a brief window of detection (2–4 days) as well as total and immature (medium and high fluorescence) reticulocytes that remained elevated over the full 14 posttreatment days. Carbon isotope ratio MS and the OFF score and Abnormal Blood Profile score (ABPS) were not discriminatory. The optimal multivariate model to identify T exposure combined serum T, urine T/E ratio with three hematological variables (% high fluorescence reticulocytes, mean corpuscular hemoglobin, and volume) with the five variables providing 93% correct classification (4% false positive, 10% false negatives). Hence, combining select serum and urine steroid MS variables with reticulocyte measures can achieve a high but imperfect detection of T administration to healthy females. [ABSTRACT FROM AUTHOR]

Voltammetric sensors are simple, powerful, and cheap equipment with easy principles, which have been widely used in electrochemical studies to investigate the properties of the electroactive species. Surfactants are frequently used in the construction of voltammetric sensors to enhance the sensitivity and selectivity of the sensor, which significantly impacted the electrode function in terms of dissolving organic compounds, creating a specific orientation of molecules on the surface of the electrodes, and enhancing electron transfer reactions. This review focuses on the recent contributions of surfactants in the development of efficient voltammetric sensors. In addition, other ingredients commonly employed alongside surfactants, such as nanomaterials, conducting polymers, and composite materials, have been discussed. The comprehension of these aspects can guide the expansion and the use of surfactants in the electrochemical sensing scope. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate blood lipid parameters and level of atherogenic indices in acquired premature ejaculation (PE) patients. Between 2020 January and June 2020, 96 patients diagnosed with PE in our clinic and 84 control patients who applied to the urology outpatient clinic for other urological reasons were included in the study. Detailed medical and sexual histories of the patients were taken, and physical examination findings were recorded. In addition, 5‐question premature ejaculation diagnostic tool (PEDT) was applied to patients and estimated intravaginal ejaculation latency times (IELT) were recorded. The mean values of lipid parameters; Risk Index of Castelli‐1 (CRI‐1 (Total cholesterol/ HDL)), CRI‐2 (LDL/ HDL), Atherogenic Index of Plasma (AIP (log10 (triglyceride/ HDL)) and Atherogenic Coefficient (AC (HDL/ non‐HDL)) were calculated. The average PEDT score was 7.68 + 5.05 (2–22), and the IELT arithmetic mean was 150.39 + 121.53 (5–900) seconds. In the APE group, triglyceride and AIP values were found to be higher than the control group (triglyceride: 188.75 + 76.39 versus 157.20 + 87.45; p =.049; AIP: 0.46 + 0.33 versus 0.35 + 0.35; p =.040). A fair positive correlation was found between PEDT scores and AIP values (r =.355, p <.001). AIP was found to be related to APE, and it was also found to be related to symptom severity. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate common in older men. Diallyl sulfide (DAS), a major component of garlic, has been reported to possess antioxidant, anti-inflammatory, and antiproliferative effects. However, the underlying protective immunomodulatory mechanism of DAS on BPH remains vague. Herein, experimental BPH was induced in rats by daily subcutaneous injection of testosterone propionate (TP) (3 mg/kg, s.c.) for 4 weeks. In parallel, finasteride (Fin) (5 mg/kg, p.o) or DAS (50 mg/kg, p.o.) was administered orally during BPH induction. TP-induced histological alterations and the immune-inflammatory cascade. On the other hand, DAS or Fin administration alleviated all abnormalities induced testosterone. Fin and DAS administration markedly reduced prostate weight by 53% with Fin, and by 60% with DAS. Moreover, serum testosterone and DHT were reduced by 55% and 52%, respectively, with Fin and by 68% and 75%, respectively, with DAS, in concordance with decreased protein expression of androgen receptor (AR), and prostate-specific antigen (PSA). Furthermore, both regime lessen immune-inflammatory milieu, as evidenced by decrease CD4+ T-cells protein expression and associated inflammatory cytokines. Concomitantly, Fin and DAS exhibited marked mitigation in insulin-like growth factor-1 (IGF-1), transforming growth factor-beta1 (TGF-β1), and phosphorylated extracellular signal-regulated kinase (ERK1/2) signaling. Besides alleviating oxidative stress by 53% and 68% in prostatic MDA and by 27% and 7% in prostatic iNOS with Fin and DAS, respectively. In conclusion, this work highlighted a potential therapeutic approach of DAS as a dietary preventive agent against BPH via its anti-inflammatory and immunomodulatory effect along with suppression of the ERK pathway. [ABSTRACT FROM AUTHOR]

Androgenic steroids are widely spread amongst athletes and their use in different forms is a major problem in the contemporary world of sports. The Program of the World Anti-Doping Agency (WADA) for biological passports for athletes introduces a standardized module (so-called “steroid profile”) for each athlete, which allows the identification of exogenously taken anabolic androgenic steroids (EAAS) on the Prohibited List. It has been proved that the steroid profile depends on sex, age, physical activity, diet and ethnicity. Aim: Determination of the referent values of steroids in the urine of a representative excerpt of a Bulgarian population of clinically healthy men and women 16-30 years old, sporting in their free time, with a view to establishing national norms of “steroid profile” indices. Materials and Methods: The study was carried out in the period 2016-2017 and involved 1189 persons (840 males - 70,6%; 349 females - 29,4%), 16-30 years old, clinically healthy and recreationally sporting. Geographically, the groups of participants are uniformly distributed within the country. In the urine samples, the following indices have been recorded: testosterone (T), epitestosterone (EpiT) and their ratio (T/EpiT), androsterone (A), etiocholanolone (Etio), 5α-androstane-3α,17β-diol (5α-diol), 5β-androstane-3α,17β-diol (5β-diol). Gas-chromatography with mass-spectrometry was used to qualitatively assess the steroids. Results: The referent values of Т, EpiT, Т/ЕpiT, А, Etio, 5α-diol, 5β-diol have been determined. The range of 2,5-97,5 percentile with 95% confidence interval (CI) of the examined steroid profile components of the both sexes was separately presented. Conclusion: The created national database of the steroid-profile indices would be used to compare the individual results of the “biological passport” of the young generation of Bulgarian athletes, as well as for their prolonged follow-up in-and out-of-competition, in order to eliminate wrong interpretations of deviations that may occur [ABSTRACT FROM AUTHOR]

Testosterone doping remains a prevalent and potent form of drug cheating among elite athletes. In men, the urine testosterone (T) to epitestosterone (E) ratio (T/E ratio) can identify administration of exogenous T by its suppression of endogenous T production through strong negative feedback on endogenous T and E production as well as spill over into urine of extra testosterone. However, this mechanism may be partially inoperative in females whose much lower circulating T derives from three sources, none subject to powerful negative T feedback. Hence, additional methods to detect T doping in females are required. In this study we report two cases of elite female athletes who were sanctioned for T doping proven by measurement of serum T using liquid chromatography−mass spectrometry (LC–MS), when serial urine T and T/E ratio in one were not indicative of T doping, and in the other were nullified by incidental genetic inactivation of T glucuronidation through the uridine diphosphoglucuronosyl transferase 2B17 (UGT2B17) deletion genotype–phenotype. These findings indicate the potential for serum T measurement by LC–MS to detect T doping in female athletes, especially if implemented in the Bayesian format of an athlete biological passport. [ABSTRACT FROM AUTHOR]

The use of testosterone and its pro‐drugs, such as dehydroepiandrosterone (DHEA), is currently regulated in horseracing by the application of international testosterone thresholds. However, additional steroidomic approaches, such as steroid ratios, to distinguish overall adrenal stimulation from drug administrations and an equine biological passport for longitudinal steroid profiling of individual animals could be advantageous in equine doping testing. Thus, DHEA concentrations and related ratios (testosterone [T] to DHEA and DHEA to epitestosterone [E]) were assessed in the reference population by quantitative analysis of 200 post‐race gelding urine samples using liquid chromatography–tandem mass spectrometry. DHEA concentrations ranged between 0.9 and 136.6 ng/mL (mean 12.8 ng/mL), T:DHEA ratios between 0.06 and 1.85 (mean 0.43), and DHEA:E ratios between 0.21 and 13.56 (mean 2.20). Based on the reference population statistical upper limits of 5.4 for T:DHEA ratio and 48.1 for DHEA:E ratio are proposed with a risk of 1 in 10 000 for a normal outlier exceeding the value. Analysis of post‐administration urine samples collected following administrations of DHEA, Equi‐Bolic® (a mix of DHEA and pregnenolone) and testosterone propionate to geldings showed that the upper limit for T:DHEA ratio was exceeded following testosterone propionate administration and DHEA:E ratio following DHEA administrations and thus these ratios could be used as additional biomarkers when determining the cause of an atypical testosterone concentration. Additionally, DHEA concentrations and ratios can be used as a starting point to establish reference ranges for an equine biological passport. Steroidomic approaches, such as steroid ratios and an equine biological passport for longitudinal steroid profiling, could be advantageous in equine doping testing. In the current study, references ranges for DHEA concentrations, testosterone to DHEA ratios and DHEA to epitestosterone ratios were established and these were compared with samples taken following administrations of testosterone and related steroids. The results showed that these steroid ratios could be used as additional biomarkers when determining the cause of atypically high testosterone concentrations in geldings. [ABSTRACT FROM AUTHOR]

Background and objectives There have been large increases in testosterone prescribing since 2000. The aim of this study was to identify factors associated with testosterone replacement therapy (TRT) initiation Methods Data were from the 45 and Up Study, an ongoing cohort study involving 266,942 participants from New South Wales aged ≥45 years. Baseline data (2006-09) were linked to administrative data on government-subsidised prescriptions and medical services. Results The study included 105,429 men. In two years following baseline, 2.9 per 1000 men (95% confidence interval: 2.6, 3.2) had initiated TRT. Men with self-rated poor health, those treated for osteoporosis; anxiety, depression or high blood cholesterol, and those who lived in major cities or were aged 55-74 years had greater odds of TRT initiation. In the six months before TRT initiation, 41% of men had a hormone test record. Discussion The high rate of TRT initiation and low rate of recommended investigations suggest TRT may have been prescribed outside recommended indications. [ABSTRACT FROM AUTHOR]

Background: Implementing a laboratory-developed test sometimes requires incorporating an unconventional device into the laboratory information system (LIS) and customizing an interface to reduce transcription error and improve turnaround time. Such a custom interface is a necessity for complicated high-volume tests such as 25-OH Vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS/MS) when there is no vendor-or LIS-supplied interface available. Here, we describe our work and experience interfacing a API 5000 LC-MS/MS instrument with our newly implemented LIS, Epic Beaker, using a combination of in-house scripting software and a middleware vendor, Data Innovations. Materials and Methods: For input interfacing, custom scripting software was developed to transcribe batched order lists generated by Epic into files usable by the instrument software, Analyst®. For output interfacing, results from the LC-MS/MS system were fed to a unidirectional instrument driver made by Data Innovations and selected data were transferred to the LIS. Results: Creation and validation of a new driver by Data Innovations took approximately 6 months. The interface was adopted for 25-OH Vitamin D and testosterone testing during periods of increasing test volume (4.5-fold over 8 years and 1.25-fold over 5 years). The amount of time spent reporting 25-OH Vitamin D results decreased 82% per order resulting in a savings of 1370 technician work hours and the amount of time spent reporting testosterone results decreased 75% per order resulting in a savings of 400 technician work hours. Conclusions: A mixed model using custom scripting and curated commercial middleware serve as a durable interface solution for laboratory instrumentation such as an LC-MS/MS and are flexible to future changes in instrument software, networking protocols, and the scope of LISs and work area managers. [ABSTRACT FROM AUTHOR]

We hypothesized that low molecular weight urinary proteins play a role in male-male chemical communication in the water vole, Arvicola ampibius L. We studied the effect of placing soiled litter from strange males into the cage of another sexually mature male on the intensity of its digging and scattering, urination on the litter, and alteration in the levels of low molecular weight proteins (15-25 kDa) excreted in the urine before and after 4 days of exposure as determined by chip electrophoresis. The intensity of digging and scattering was positively correlated with levels of testosterone in serum of males exposed to strange male odors ( r = 0.56; P < 0.01), as well as with the concentration of low molecular weight proteins in the donor's urine ( r = 0.52, P < 0.05). At the end of the experiment, the level of low molecular weight protein in excreted urine was elevated in the males exposed to the strange male's litter. These results highlight the importance of quantitative inter-individual variation of low molecular weight urinary proteins in the modulation of the physiology and behavior of conspecifics. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of sex and puberty stage on circadian changes in sodium excretion, sodium-regulating hormones, and hemodynamics. Thirty-nine healthy volunteers (9 prepuberty boys, 10 prepuberty girls, 10 puberty boys, and 10 puberty girls) were included. They all underwent a 24-h circadian in-patient study under standardized conditions regarding activity, diet, and fluid intake. Blood samples were drawn every 4 h, and the urine was collected in fractions. Blood pressure and heart rate were noninvasively monitored. Atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin were measured in blood. Children in puberty had lower plasma levels of renin (P < 0.05) and angiotensin II (P < 0.05) and a 26% reduction in filtered sodium without changes in sodium excretion compared with prepuberty children. A circadian rhythm in sodium excretion, the renin-angiotensin system, ANP, and blood pressure was found with a midnight ANP peak (P < 0.001), a nighttime decrease in hemodynamic parameters (P < 0.001), an increase in plasma renin (P < 0.001) and angiotensin II (P < 0.001), and a decrease in sodium excretion (P < 0.001) mainly on the basis of increased sodium reabsorption (P < 0.001). The timing of the changes did not depend on sex or puberty group. There is a circadian rhythm of sodium excretion and sodium regulation in 7- to 15-yr-old children. This rhythm is similar in boys and girls. As an important new finding, puberty changes the plasma levels of renin and angiotensin II without changing the amount of sodium excreted or the day to night sodium excretion ratio. [ABSTRACT FROM AUTHOR]

Biologically active compounds are found in biological samples at relatively low concentration levels. The sample preparation of target compounds from biological, pharmaceutical, environmental, and food matrices is one of the most time-consuming steps in the analytical procedure. The microextraction techniques are dominant. Metabolomic studies also require application of proper analytical technique for the determination of endogenic metabolites present in biological matrix on trace concentration levels. Due to the reproducibility of data, precision, relatively low cost of the appropriate analysis, simplicity of the determination, and the possibility of direct combination of those techniques with other methods (combination types on-line and off-line), they have become the most widespread in routine determinations. Additionally, sample pretreatment procedures have to be more selective, cheap, quick, and environmentally friendly. This review summarizes the current achievements and applications of microextraction techniques. The main aim is to deal with the utilization of different types of sorbents for microextraction and emphasize the use of new synthesized sorbents as well as to bring together studies concerning the systematic approach to method development. This review is dedicated to the description of microextraction techniques and their application in biomedical analysis. [ABSTRACT FROM AUTHOR]

A boy aged 4 with penoscrotal hypospadias and his brother aged 12 with micropenis had typical changes of homozygous 5 alpha-reductase deficiency. After three injections of chorionic gonadotrophin there was a trivial rise in plasma dihydrotestosterone with a normal increase in plasma testosterone. Urine steroid chromatography showed abnormally high 5 beta: 5 alpha ratios and 5 alpha-reductase activity was appreciably reduced in genital skin fibroblasts. The results indicate that 5 alpha-reductase deficiency is not invariably associated with genital ambiguity. [ABSTRACT FROM AUTHOR]

When testing a urine sample for testosterone abuse, a ratio of testosterone glucuronide (T) to epitestosterone glucuronide (ET) of 4.0 or above is considered suspicious. A degree of variation, however, has been observed in T/ET ratio between individuals from both the same and different ethnic backgrounds. The majority of this variation might be due to UGT2B17 deletion genotype (UGT2B17 deletion-type). The aim of this study was to investigate the use of the same urine sample for the analysis of T/ET ratio and UGT2B17 deletion-type. Japanese men were deletion-typed via a UGT2B17 copy number assay using DNA from blood. Urinary T and ET levels were determined using gas chromatography-mass spectrometry before ( n = 112) and after a testosterone injection ( n = 25). Basal T level and the increase in T/ET ratio after injection were dependent on UGT2B17 deletion-type, being lower in subjects with deletion ( del/del) than nondeletion ( ins/del or ins/ins) genotype. UGT2B17 deletion-typing was first performed using DNA from urine cryopreserved for 1-1.5 years ( n = 66). The concentration of DNA required for discrimination between the deletion and nondeletion genotype by copy number assay was more than 0.1 ng/ml urine. Discrimination was possible in 94.0 % of urine samples (5-7 ml each). These findings show that T/ET ratio and UGT 2B17 deletion-type can be analyzed exclusively via urine samples, removing the need for the collection of other samples, such as blood or buccal cells. The combination of T/ET ratio and UGT 2B17 deletion-type may help inform decisions regarding a genotype-specific T/ET cutoff ratio. [ABSTRACT FROM AUTHOR]

Acne vulgaris in infants and children often triggers extensive laboratory evaluation out of concern about associated endocrinopathy. Clinical parameters to help guide evaluation of these children have not been defined. This was a retrospective chart review of 24 preadolescent patients with acne and a review of related medical literature. Two age-related subsets were identified: 12 patients who developed acne before the age of 15 months, 75% male, with comedonal and inflammatory lesions; and 12 patients who developed acne between the ages of 2 and 7 years, 75% female, with primarily comedonal lesions. Laboratory evaluation in 13 of the patients was unremarkable. Bone age was advanced in 1 of the 11 children imaged. Premature adrenarche was diagnosed in four patients; all four had additional clinical signs of puberty and growth parameters >90th percentile. None required additional treatment. Our cohort of preadolescent children presenting with acne included an equal number of patients in two distinct subsets: infantile and childhood-onset acne. Literature review identified a rare third subset presenting with acne, signs of advanced puberty, and associated endocrinopathy. There was no evidence of endocrinopathy in our patients with infantile acne. Two-thirds of our patients with childhood-onset acne had no additional clinical signs of puberty and no evidence of endocrinopathy. A focused history and physical examination is sufficient to evaluate the majority of infants and children with acne. Hand X-ray for bone age is a useful screening test. Further evaluation and endocrinology referral are warranted in preadolescents with acne and advanced bone age or additional clinical evidence of early puberty. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) are novel solvents that display a number of unique properties, such as negligible vapor pressure, thermal stability (even at high temperatures), favorable viscosity, and miscibility with water and organic solvents. These properties make them attractive alternatives to environmentally unfriendly solvents that produce volatile organic compounds. In this article, a critical review of state-of-the-art developments in the use of ILs for the separation and preconcentration of bioanalytes in biological samples is presented. Special attention is paid to the determination of various organic and inorganic analytes-including contaminants (e.g., pesticides, nicotine, opioids, gold, arsenic, lead, etc.) and functional biomolecules (e.g., testosterone, vitamin B, hemoglobin)-in urine, blood, saliva, hair, and nail samples. A brief introduction to modern microextraction techniques based on ILs, such as dispersive liquid-liquid microextraction (DLLME) and single-drop microextraction (SDME), is provided. A comparison of IL-based methods in terms of their limits of detection and environmental compatibilities is also made. Finally, critical issues and challenges that have arisen from the use of ILs in separation and preconcentration techniques are also discussed. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Human cytosolic sulfotransferases (SULT) 2A1 is the main enzyme involved in the sulfate conjugation of dehydroepiandrosterone, a weak androgen, and the main androgen pre-cursor, whereas estrogens are mainly conjugated by SULT1A1. Here we have identified a copy number variation (CNV) polymorphism in the SULT2A1 gene in a Swedish population including healthy men (N =30). Moreover, the CNV of SULT1A1 and SULT2A1 was further characterized in relation to urinary levels of androgen sulfate metabolites before and after an intramuscular dose of 500 mg testosterone enanthate. Individuals expressing two or more CNVs excrete 80 and 40% higher levels of DHEAS (p =0.02) and androsteroneS (p =0.01), respectively as compared to individuals with one gene copy. The mean area under the urine concentration time-curve from time 0 (prior to the administration of 500mg testosterone) to 15 days post dose values were 80% higher for DHEAS (p =0.046) and testosteroneS (p =0.019) in individuals with two and three SULT2A1 gene copies as compared to individuals with one gene copy. The SULT1A1 CNV on the other hand did not affect the sulfation activity toward the androgens. In conclusion our results indicate that functional CNV polymorphisms in SULT2A1 and SULT1A1 are common in a Swedish population and that SULT2A1 CNV is associated with the urinary concentrations of androgen sulfate metabolites. [ABSTRACT FROM AUTHOR]

The UDP Glucuronosyl Transferase (UGT) enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) as well as anabolic androgenic steroids (AAS). Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In vitro studies show inhibitory potential on UGT2B7, 2B15, and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG) as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test. The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 male healthy volunteers, with either two, one or no allele (ins/ins, ins/del, or del/del) of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac) for 6 days. On day three, 500mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash-out period of 4 months the volunteers received 500mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs. [ABSTRACT FROM AUTHOR]

Background: Laboratory tests are extensively used for diagnosis and monitoring in UK primary care. Test usage by GPs, and associated costs, have grown substantially in recent years. Aim: This study aimed to quantify temporal growth and geographic variation in utilisation of laboratory tests. Design and setting: Retrospective cohort study using data from general practices in the UK. Method: Data from the General Practice Research Database, including patient demographics, clinical details, and laboratory test results, were used to estimate rates of change in utilisation between 2005 and 2009, and identify tests with greatest inter-regional variation, by fitting random-effects Poisson regression models. The study also investigated indications for test requests, using diagnoses and symptoms recorded in the 2 weeks before each test. Results: Around 660 000 tests were recorded in 230 000 person-years of follow-up. Test use increased by 24.2%, from 23 872 to 29 644 tests per 10 000 person-years, between 2005 and 2009. Tests with the largest increases were faecal occult blood (121%) and C-reactive protein (86%). There was substantial geographic variation in test utilisation; GPs in some regions requested tests such as plasma viscosity and cardiac enzymes at a rate more than three times the national average. Conclusion: Increases in the use of laboratory tests have substantial resource implications. Rapid increases in particular tests may be supported by evidence-based guidelines, but these are often vague about who should be tested, how often, and for how long. Substantial regional variation in test use may reflect uncertainty about diagnostic accuracy and appropriate indications for the laboratory test. There is a need for further research on the diagnostic accuracy, therapeutic impact, and effect on patient health outcomes of the most rapidly increasing and geographically variable tests. [ABSTRACT FROM AUTHOR]

Research on vocal communication in African elephants has increased in recent years, both in the wild and in captivity, providing an opportunity to present a comprehensive review of research related to their vocal behavior. Current data indicate that the vocal repertoire consists of perhaps nine acoustically distinct call types, 'rumbles' being the most common and acoustically variable. Large vocal production anatomy is responsible for the low-frequency nature of rumbles, with fundamental frequencies in the infrasonic range. Additionally, resonant frequencies of rumbles implicate the trunk in addition to the oral cavity in shaping the acoustic structure of rumbles. Long-distance communication is thought possible because low-frequency sounds propagate more faithfully than high-frequency sounds, and elephants respond to rumbles at distances of up to 2.5 km. Elephant ear anatomy appears designed for detecting low frequencies, and experiments demonstrate that elephants can detect infrasonic tones and discriminate small frequency differences. Two vocal communication functions in the African elephant now have reasonable empirical support. First, closely bonded but spatially separated females engage in rumble exchanges, or 'contact calls,' that function to coordinate movement or reunite animals. Second, both males and females produce 'mate attraction' rumbles that may advertise reproductive states to the opposite sex. Additionally, there is evidence that the structural variation in rumbles reflects the individual identity, reproductive state, and emotional state of callers. Growth in knowledge about the communication system of the African elephant has occurred from a rich combination of research on wild elephants in national parks and captive elephants in zoological parks. Zoo Biol 29:192-209, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the bone health of post renal transplantation children and adolescents. All patients underwent clinical evaluation, dual energy x-ray absorptiometry (DXA) for bone mineral density (BMD), and spinal imaging for vertebral fractures. The study concluded that the immediate post-transplantation and pubertal years pose the greatest risk for skeletal health, especially in girls.

A reversed phase high performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of anabolic steroids: testosterone (TES), epitestosterone (EPI), and nandrolone (NAN). The analytical column, Inertsil C8, 5 µm, 250 × 4 mm, was operated at ambient temperature. Isocratic elution was performed using a mixture of 50% buffer solution CH3COOH 0.11% -CH3COONa 7.5 mmol/L, pH = 4, 45% CH3CN and 5% CH3OH, at a flow rate of 1.1 mL/min. UV detection was performed at 238 nm. The detection limits of the method were 2.4 ng for NAN, 3.6 ng for TES, and 2.6 ng for EPI in blood plasma, and 2.7 ng for NAN, 1.1 ng for TES, and 3.8 ng for EPI in urine, per 20 µL injection volume. Alprazolam was used as internal standard at a concentration of 2 ng/µL. Validation of the method was performed in terms of accuracy and precision: intra-day assay (n = 6) and inter-day assay (n = 3 × 6) and was found to be satisfactory, with high accuracy and precision results. Sample preparation involved solid phase extraction on Nexus cartridges with high recoveries. The developed method was successfully applied to the analysis of urine samples of one female and 9 male volunteers. [ABSTRACT FROM AUTHOR]

Early studies on nickel essentiality with rats and goats indicated that nickel deprivation impaired reproductive performance. Nickel also has been found to influence cyclic nucleotide gated channels (CNG); these types of channels are important in sperm physiology. Thus, two experiments were conducted to test the hypothesis that nickel deficiency affects sperm physiology in a manner consistent with nickel having an essential function related to CNG channel functions. The experiments were factorially arranged with four treatment groups of eight weanling rats in each. In experiment 1, the treatments were supplemental dietary nickel of 0 and 1 mg/kg and Nω-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) added to the drinking water (50 mg/100 mL) the last 3 wk of an 8-wk experiment. In experiment 2, the treatments were supplemental dietary nickel at 0 and 1 mg/kg and supplemental dietary sodium chloride (NaCl) at 0 and 80 g/kg. The NaCl and L-NAME variables were included to act as stressors affecting CNG channel activity. The basal diet contained per kilogram about 27 μg of nickel and 1 g of sodium. After 8 wk in experiment 1 and 16 wk in experiment 2, urine while fasting and testes and epididymis in both experiments, and seminal vesicles and prostates in experiment 2 were harvested for analysis. Nickel deprivation significantly decreased spermatozoa motility and density in the epididymides, epididymal transit time of spermatozoa, and testes sperm production rate. Nickel deficiency also significantly decreased the weights of the seminal vesicles and prostate glands. Excessive NaCl had no effect on sperm physiology; however, it decreased prostate gland weights. The findings support the hypothesis that nickel has an essential function that possibly could affect reproductive performance in higher animals, perhaps through affecting a CNG channel function. [ABSTRACT FROM AUTHOR]

Androgenic steroids are used in female greyhound dogs to prevent the onset of estrus; moreover, these steroids also have potent anabolic activity. As anabolic steroids increase muscle mass and aggression in animals, the excessive use of these agents in racing greyhounds gives an unfair performance advantage to treated dogs. The biotransformation of most anabolic steroids has not been determined in greyhound dogs. The objective of the present study was to identify the urinary metabolites of testosterone, methyltestosterone, mibolerone, and boldenone in greyhound dogs. These steroids were administered orally (1 mg/kg) to either male or female greyhound dogs and urine samples were collected pre-administration and at 2, 4, 8, 12, 24, 72, and 96 h post-administration. Urine extracts were analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) to identify major metabolites and to determine their urinary excretion profiles. Major urinary metabolites, primarily glucuronide, conjugated and free, were detected for the selected steroids. Sulfate conjugation did not appear to be a major pathway for steroid metabolism and excretion in the greyhound dog. Phase I biotransformation was also evaluated using greyhound dog liver microsomes from untreated dogs. The identification of several in vivo steroid metabolites generated in this study will be useful in detecting these steroids in urine samples submitted for drug screening. [ABSTRACT FROM AUTHOR]

Interspecies comparisons suggest that the weaning pig is a suitable surrogate for man in percutaneous absorption studies. Despite known anatomical and physiological similarities between porcine and human skin, very few investigations of percutaneous absorption phenomena have been conducted in pigs. This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of six C-radioIabeled compounds in weanling Yorkshire sows. Radiolabel recovery from excrement collected over 6 days following iv doses in physiological saline (200 μg, 10 μCi) showed that malathion (M), parathion (P), caffeine (C), and benzoic acid (B) were primarily excreted into urine (>80%), while greater fractions of testosterone (T, 72%) and progesterone (R, 35%) were fecally eliminated. Percutaneous absorption was determined from total urine and fecal excretion of radiolabel after topical application, corrected for incomplete excretion following iv administration. Topical doses in ethanol (200 μg, 10 μCi) were applied at a surface concentration of 40 μg cm and penetrated in the following rank order (percentage dose): B (25.7%) > R (16.2%) > C (11.8%) > T (8.8%) > P (6.7%) > M (5.2%). Fecal clearances of radiolabel, expressed as a percentage of total excretion, were greater after topical administration for four of the six compounds (B, C, P, and T, < 0.05). Calculations based on urinary excretion alone underestimated percutaneous absorption determined from total excretion by 5–30%, although the difference between the two estimates was statistically significant only for C ( < 0.05). These results suggest that percutaneous absorption estimates based on urinary radiolabel excretion alone should be interpreted with caution whenever compounds with unknown penetration characteristics arc used. Factors known to affect human skin absorption, such as applied dose, anatomical region, sex, age, various vehicles and solvents, and differences in cutaneous metabolism, should be more closely examined in all animal species used to model percutaneous absorption phenomena in man. [ABSTRACT FROM PUBLISHER]

More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making. [ABSTRACT FROM AUTHOR]

The article informs about the estimation of testosterone in biological fluids. It further describes a method for the estimation of testosterone in urine. This is a double isotope dilution derivative procedure similar to the method for the estimation of testosterone in peripheral plasma. Testosterone was found in three fraction from urine. In the free fraction extracted at neutral PH 1 fraction in which testosterone is released after incubation with mineral acid at PH 1 at 40 degree Celsius, and following incubation with glucoronidase.