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PubMed1994

Placental arsenic and cadmium in relation to lipid peroxides and glutathione levels in maternal-infant pairs from a copper smelter area.

Arsenic exposure may enhance oxidative damage causing adverse health effects in pregnant women. The purposes of this paper are: (i) to evaluate placental arsenic concentration as a biomarker of arsenic exposure for pregnant women; and (ii) to examine the relationship between metal exposure from a copper smelter area in Bulgaria and oxidative damage during pregnancy (as measured by glutathione and lipid peroxides) in 49 maternal-infant pairs. Placental levels of arsenic were highest in areas with the highest environmental contamination, and environmental variables (residency, smoking and occupational exposure) explained a large portion of the observed variability in placental arsenic levels (linear regression R2 = 0.71). The combined exposures of smoking and living in the smelter area were associated with lower glutathione antioxidant protection. The per cent maternal and cord blood glutathione in reduced form was significantly lower for smokers compared to non-smokers in the smelter area (47 versus 66 per cent in maternal blood, P < 0.01, and 60 versus 75 per cent in cord blood, P < 0.05). Higher concentrations of lipid peroxides in maternal blood, cord blood and placenta, though not statistically significant, suggested that pregnant women with both exposures may be at higher risk of oxidative damage.

Adult↗

PubMed2006

Farmworker exposure to pesticides: methodologic issues for the collection of comparable data.

The exposure of migrant and seasonal farmworkers and their families to agricultural and residential pesticides is a continuing public health concern. Pesticide exposure research has been spurred on by the development of sensitive and reliable laboratory techniques that allow the detection of minute amounts of pesticides or pesticide metabolites. The power of research on farmworker pesticide exposure has been limited because of variability in the collection of exposure data, the predictors of exposure considered, the laboratory procedures used in analyzing the exposure, and the measurement of exposure. The Farmworker Pesticide Exposure Comparable Data Conference assembled 25 scientists from diverse disciplinary and organizational backgrounds to develop methodologic consensus in four areas of farmworker pesticide exposure research: environmental exposure assessment, biomarkers, personal and occupational predictors of exposure, and health outcomes of exposure. In this introduction to this mini-monograph, first, we present the rationale for the conference and its organization. Second, we discuss some of the important challenges in conducting farmworker pesticide research, including the definition and size of the farmworker population, problems in communication and access, and the organization of agricultural work. Third, we summarize major findings from each of the conference's four foci-environmental exposure assessment, biomonitoring, predictors of exposure, and health outcomes of exposure-as well as important laboratory and statistical analysis issues that cross-cut the four foci.

Agriculture↗

PubMed2005

Toenail arsenic concentrations, GSTT1 gene polymorphisms, and arsenic exposure from drinking water.

Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (As(in)) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 mug As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dose-dependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (beta = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (beta = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between As(in) exposure and toenail As(in) content.

Adolescent↗

PubMed2007

Salivary cortisol in preterm infants: Validation of a simple method for collecting saliva for cortisol determination.

BACKGROUND AND AIMS: The increased use of salivary cortisol as a biomarker of stress and/or diurnal rhythms has facilitated research of Hypothalamic-pituitary-adrenocortical (HPA)function. Saliva collection remains problematic with preterm infants. The twofold purpose of this study is to 1) establish validity of the filter paper method for saliva collection and 2) apply the filter paper method for saliva collection to preterm infants. DESIGN AND MEASURES: Whole saliva was collected from six normal adult subjects to create a pool. Validation measures included comparison of levels obtained from whole saliva and filter paper, an evaluation of storage effects, assessing spiking recovery, and measurement of linearity of dilution. In the application study, saliva was collected every three hours, before feedings for three consecutive days from 26 hospitalized preterm infants. Diurnal variation in cortisol was examined using hierarchical linear modeling and individual calculation of diurnal pattern using an accepted technique. RESULTS: Validation studies revealed acceptable recovery of whole saliva from filters, no effect of room temperature storage of filters for up to six months, and acceptable linearity of dilution up to 4. Saliva from preterm infants was easily collected. Only 2% of the samples were lost due to inadequate wetting of the filters. An inverse association was found between postconceptional age and one-minute APGAR scores and infant cortisol levels. Variable daily cortisol patterns and no discernable rhythm were found for this sample; however, four infants appeared to show atypical diurnal pattern. CONCLUSIONS: The filter paper method is a valid method of saliva collection that is feasible to use with preterm infants.

Biomarkers↗

PubMed2026

Discovery and validation of a multi-protein panel for predicting non-fatal major adverse cardiovascular events in diabetic kidney disease.

OBJECTIVE: To identify plasma protein biomarkers associated with incident non-fatal major adverse cardiovascular events (MACE) in diabetic kidney disease (DKD) patients. RESEARCH DESIGN AND METHODS: We analyzed 317 DKD patients from the UK Biobank. Plasma proteomics and clinical data (demographics, metabolism, renal function) were integrated. In an exploratory discovery phase, three sequential Cox regression models (crude, socio-demographic-adjusted, socio-demographic-metabolic adjusted) screened non-fatal MACE-associated proteins. To prevent information leakage, the cohort was then randomly split into training (70%) and testing (30%) sets; machine-learning feature selection, hyperparameter optimization, and final model development were performed exclusively within the training set. The associated proteins were input into the four-step machine-learning pipeline (LASSO-Cox, random survival forest, Boruta, XGBoost-Cox). Predictive performance was validated using Kaplan-Meier survival analyses, longitudinal trajectory modeling, and ROC benchmarking. An interactive web application was deployed for clinical implementation. RESULTS: Of 1,463 plasma proteins, 561 were associated with non-fatal MACE across Cox models, with 14 overlapping proteins. Nine core proteins (ANG, IL1R1, CXCL14, ESAM, PTGDS, HAVCR1, FGFR2, IGSF8, CCL3) were validated: ANG showed the strongest non-fatal MACE association (HR = 3.88, 95%CI 2.33-6.48, p<0.001), and all high-expression groups had elevated non-fatal MACE risk. GO/KEGG enrichment highlighted inflammatory-immune pathways like positive regulation of MAPK cascade, Cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway as key mechanisms. The model integrating proteins, demographic factors, and clinical variables achieved the highest predictive performance across non-fatal MACE (AUC = 0.768), myocardial infarction (MI) (0.808), and stroke (0.816) outcomes, with superior stability in cross-validation. CoxBoost + Elastic Net framework was selected as the optimal framework via benchmarking of 101 algorithms. The model demonstrated favorable calibration in high-risk patients and yielded positive net clinical benefit across decision thresholds of 5% to 45%. The web tool (https://jiangli2941.github.io/MACE-prediction-v2/) enables input of 28 variables, outputs non-fatal MACE risk status, risk probability, and highlights abnormal indicators. CONCLUSION: Plasma proteomics combined with machine learning identifies robust non-fatal MACE predictors in DKD.

Humans↗

PubMed2004

Seasonal variations in antioxidant defences in blue mussels Mytilus edulis collected from a polluted area: major contributions in gills of an inducible isoform of Cu/Zn-superoxide dismutase and of glutathione S-transferase.

In the present work, we investigated in the blue mussel (Mytilus edulis) the seasonal variations in the activity of several enzymes, which participate in the cellular defence system that is involved in the adaptive response of organisms to pollution. The activity levels of glutathione S-transferase, glutathione peroxidase, glutathione reductase and three isoforms of Cu/Zn-superoxide dismutase in gills and digestive glands of this bivalve species were used as biomarkers. Adult wild mussels were collected in Le Havre harbour (north-west coast of France) from four sites with different environmental conditions. Measurements of enzymatic activities were performed on tissue homogenates except for Cu/Zn-superoxide dismutase for which the activity of each isoform was detected on gel after isoelectric focusing. Seasonal variations in antioxidant enzyme activities were observed, characterized by low activity levels during winter, a period where oxidative stress is known to be high in bivalves. A clear-cut discrepancy between tissues was noted concerning inter-individual variability of data, which was low in gills but high in digestive gland, leading to the conclusion that gills could preferentially be used in biomonitoring studies dealing with oxidative stress in the blue mussel. As compared to animals from the reference site, mussels from the most polluted sites exhibited changes in the Cu/Zn-superoxide dismutase pattern characterized by an increase in the activity of the more acidic isoform without significant variation of the total activity of the enzyme. The most striking data were recorded in mussels collected at the outlet of a thermoelectric power plant. When compared to animals from the reference site, not only their gills showed a highly significant induction of the most acidic isoform of the Cu/Zn-superoxide dismutase (+340%, P < 0.001) but also high levels of glutathione S-transferase activity (+269%, P < 0.001). This study points out the usefulness of Cu/Zn-superoxide dismutase expression pattern as a biomarker of exposure to environmental stress rather than measurement of total activity of the enzyme, in field studies using Mytilus edulis. It also indicates the informative potential for glutathione S-transferase measurements in gills and underlines the advantages of selecting a battery of biomarkers for evaluating the impact of contamination on marine organisms.

Analysis of Variance↗

PubMed2006

Toxicant exposure in cigarette reducers versus light smokers.

BACKGROUND: The extent of exposure to tobacco toxicants in smokers who have reduced their cigarette intake compared with smokers who are light smokers is relatively unknown. The goal of this study is to investigate the occurrence of compensatory smoking in reducers compared with light smokers by measuring toxicant exposure. METHODS: Participants in two smoking reduction intervention studies (N = 64) were selected for comparison with a group of light smokers (N = 62) who smoked the same number of cigarettes as the reducers. A compensatory smoking score was defined (biomarker level for reducer/biomarker level for light smoker) and calculated for urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (total NNAL), metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone, to measure the degree of smoking compensation in reducers when compared with the light smokers. RESULTS: The mean level of creatinine-adjusted total NNAL for reducers was over twice that of light smokers even when they smoked about the same number of cigarettes per day. The difference of the mean total NNAL concentrations between light smokers and reducers was highly significant (P < 0.0001). Wide variability in total NNAL concentrations was also observed in reducers, with the extent of this variability between light smokers and reducers being significantly different (P = 0.0005). The level of individual reduction was shown to be a consistent predictor of compensatory smoking (r = 0.50; adjusted Ps = 0.002), with greater cigarette reduction associated with more compensation. CONCLUSIONS: Compensatory smoking limits the harm reduction value of decreased smoking of cigarettes.

Administration, Cutaneous↗

PubMed2026

Plasma Exosome Metabolomics Reveal Stage-Specific Alterations in Elderly Women With Premetabolic and Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a chronic disorder that poses a major threat to global health. Exosomes have emerged as promising biomarkers for diagnosing and monitoring chronic diseases. However, stage-specific alterations in the exosomal metabolome during MetS development remain poorly understood. This study aimed to characterize the plasma exosomal metabolome and explore candidate exosomal biomarkers in individuals with MetS. METHODS: This study included 20 patients with MetS, 23 individuals with pre-MetS, and 45 healthy controls. Plasma exosomes were isolated and analyzed using untargeted liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were defined by a dual-threshold, that is, p < 0.05 from t-test and variable importance in projection > 1 from partial least squares discriminant analysis, with fold change indicating their expression changes. Further, we employed machine learning algorithms to predict MetS status. RESULTS: We identified 27 differential metabolites between the pre-MetS and control groups, mainly enriched in histidine metabolism and the tricarboxylic acid cycle. Of these, 12 metabolites were upregulated, and 15 were downregulated, with 1-methylhistidine and isocitrate playing central regulatory roles. Comparison between the MetS and control groups revealed 45 differentially expressed metabolites, mainly enriched in thiamine metabolism, including 13 upregulated and 32 downregulated. In the pre-MetS group, cladribine showed the highest area under the curve (AUC) (0.743, p < 0.05), whereas 3-methylxanthine yielded the largest AUC (0.714, p < 0.05) in the MetS group. CONCLUSION: Our study characterized stage-dependent alterations in the plasma exosome-derived metabolome in MetS and suggests that exosomal metabolomics may provide complementary molecular information on early MetS metabolic perturbations.

exosomal features↗

PubMed2003

Urine cytology in renal glomerular disease and value of G1 cell in the diagnosis of glomerular bleeding.

The objectives of the present study were to evaluate the cytology of urine sediments in patients with glomerular diseases, as well as the value of G1 dysmorphic erythrocytes (G1DE) or G1 cells in the detection of renal glomerular hematuria. Freshly voided urine samples from 174 patients with glomerular diseases were processed according to the method used for semiquantitative cytologic urinalysis. G1DEs (distorted erythrocytes with doughnut-like shape, target configuration with or without membranous protrusions or blebs), non-G1DEs (distorted erythrocytes without the above-mentioned morphologic changes), normal erythrocytes (NEs), and renal tubular cells (RTCs) were evaluated. Erythrocytic casts (ECs) were counted and graded as abundant (>1 per high-power field) or rare (1 per 5 high-power fields). G1DE/total erythrocyte ratios were calculated by counting 200 erythrocytes including G1DEs, non-G1DEs, and NEs. Only abundant NEs were found in 13 cases; abundant G1DEs, non-G1DEs, NEs, and no ECs in 95 cases; abundant NEs, non-G1DEs, and ECs and no G1DEs in 31 cases; and abundant NEs, G1DEs and non-G1DEs, and rare ECs in 35 cases. In 130 cases in which G1DEs were present, the G1DE/total erythrocyte ratios varied from 10% to 100%. This parameter was greater or equal to 80%, 50%, 20%, and 10% in 58 (44.6%), 29 (22.3%), 28 (21.5%), and 15 (11.5%) patients, respectively. In all cases, the number of RTCs was within normal limits or slightly increased, and a variable number of non-G1DEs were present in 161 cases. Thus, abundant ECs and/or G1DEs with a G1DE/total erythrocyte ratio of 10-100% proved to be specific urinary markers for renal glomerular diseases.

Biomarkers↗

PubMed2000

Clinical and serological aspects of patients with anti-Jo-1 antibodies--an evolving spectrum of disease manifestations.

The aim of this study was to compare ELISA, immunodiffusion and immunoblot for the detection of anti-Jo-1 antibodies, and to investigate the association of the results with clinical manifestations. In two medical centres for rheumatology and one for pulmonology, all patients with suspected connective tissue disease were screened over a 5-year period for anti-Jo-1 antibodies by ELISA. Positive sera were controlled in another laboratory by immunodiffusion. If immunodiffusion was negative, sera were controlled again by ELISA. ELISA-positive immunodiffusion-negative sera were tested by immunoblotting. The patients were characterised clinically, and their clinical signs and symptoms were compared with those of 257 patients with anti-Jo-1 antibodies published in 15 case series and 30 case reports. Twenty-five patients had a positive ELISA test. Fifteen sera were positive by ELISA and immunodiffusion (group 1). Three sera showed high titres in both ELISA tests with negative immunodiffusion and immunoblot (group 2). Seven sera showed low titres in both ELISA tests. The results were negative in the other tests (group 3). Patients in groups 1 and 2 could be classified as Jo-1 syndrome patients. Of these 18 patients, 15 had arthritis, 14 had myositis and 14 had interstitial lung disease. Only four patients had myositis at disease onset. We describe four unusual patients with Jo-1 syndrome in detail: 1. Long history of seronegative rheumatoid arthritis; 2. Sjögren's syndrome with Ro- and La-antibodies; 3. Scleroderma and bronchial carcinoma with centromere antibodies; 4. Corticoid-sensitive psychosis. Patients with suspected connective tissue disease may be screened for anti-Jo-1 antibodies by ELISA. It detects some patients that are missed by immunodiffusion. Especially lower ELISA titres should be controlled by another method because of the low specificity of the test. The clinical picture is variable. Most patients have features other than myositis at disease onset.

Adult↗

PubMed2006

The metabolic syndrome in relation to complement component 3 and postprandial lipemia in patients from an outpatient lipid clinic and healthy volunteers.

We investigated the relationship between complement component 3 (C3), fasting and postprandial lipemia and the metabolic syndrome (MetabS). Herefore fasting and postprandial samples after an acute oral fat load were obtained in 40 MetabS+ (50+/-8 years) and 70 MetabS- (48+/-7 years) subjects. Fasting C3 was higher in MetabS+ (1.21+/-0.33g/L versus 0.91+/-0.14g/L, P<0.001). Postprandially, MetabS+ had a higher total and incremental triglyceride response (TG-AUC: +77%; P<0.001 and TG-dAUC: +48%; P<0.05, respectively) and a higher total free fatty acid (FFA-AUC: +13%, P<0.05) and C3 response (C3-AUC: +26%, P<0.001) when compared to MetabS-. In both groups, fasting C3 was strongly associated with fasting TG, TG-AUC, TG-dAUC and insulin sensitivity (HOMA) (R=0.68, 0.67, 0.41 and 0.67, respectively, for the whole group; P<0.001 for each). Fasting C3 showed a dose-dependent relation with the number of MetabS components and, following exclusion of these components, it was after TG-AUC, the second best determinant of the MetabS (adjusted R(2)=0.47, P<0.001). In conclusion, C3 and postprandial lipema are closely associated with the metabolic syndrome and with several metabolic variables linked to insulin resistance. C3 may be a useful marker to identify subjects with the metabolic syndrome.

Adult↗

PubMed2005

P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment.

BACKGROUND: Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. RESULTS: As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.

Acoustic Stimulation↗

PubMed2006

Does high-sensitivity C-reactive protein add prognostic value to the TIMI-Risk Score in individuals with non-ST elevation acute coronary syndromes?

BACKGROUND: C-reactive protein (CRP) measured at hospital arrival of patients with non-ST elevation acute coronary syndromes (ACS) may add prognostic information to the TIMI-Risk Score. METHODS: Eighty-six consecutive patients admitted with unstable angina or non-ST-elevation acute myocardial infarction and symptoms onset within the prior 48 h were included. Recurrent cardiovascular events during hospitalization were defined as non-fatal myocardial infarction or death. Serum CRP was measured immediately at hospital arrival and its prognostic value in relation to in-hospital cardiovascular events was tested by the area under the ROC curve and adjusted for TIMI risk predictors by logistic regression analysis. In addition, a CRP modified TIMI-Risk score was created by adding 2 points if CRP greater than the cut-off proposed by the ROC curve analysis. The accuracy of this new score was compared with the usual TIMI-Risk Score. RESULTS: A significant predictive value of CRP in relation to in-hospital cardiovascular events was indicated by an area under the ROC curve of 0.80 (95% CI=0.66 to 0.93, p=0.009). C-reactive protein cut-off point of best prognostic performance was 7.2 mg/l. In the multivariate analysis, increased CRP (>7.2 mg/l) remained a significant predictor of events after adjustment for TIMI risk predictors (OR=14; 95% CI=1.6-121; p=0.018). The area under the ROC curve for the TIMI-Risk Score was 0.87 (95% CI=0.76-0.99, p=0.001). The addition of CRP to the TIMI-Risk Score improved its prognostic value (area under the ROC curve=0.93; 95% CI=0.87-0.99, p<0.001). The additional value of the new score is demonstrated by a higher specificity (86% vs. 63%, p<0.001) and positive predictive value (39% vs. 19%) in relation to the TIMI-Risk Score. CONCLUSIONS: CRP measured at admission of patients with non-ST-elevation acute coronary syndromes adds prognostic information to the TIMI-Risk Score. Additionally, the incorporation of this variable into the TIMI-Risk Score calculation is an effective manner to utilize CRP for risk stratification.

Aged↗

PubMed2006

Pain assessment: current status and challenges.

Neonatal pain assessment has received much attention over the past decade. Behavioural indicators of pain include facial action, body movement and tone, cry, state/sleep, and consolability. Physiological indicators of pain include increased heart rate, respiratory rate, and blood pressure, as well as decreased heart rate variability and oxygen desaturation. Pain assessment in neonates is difficult in neurologically compromised, chemically paralyzed, and non-responsive infants. Multiple pain assessment tools are summarized. Pain assessment and management protocols are delineated.

Biomarkers↗

PubMed2004

Searching the Internet for information on prostate cancer screening: an assessment of quality.

OBJECTIVES: To identify how on-line information relating to prostate cancer screening (PCS) is best sourced, whether through general, medical, or meta-search engines, and to assess the quality of that information. METHODS: Websites providing information about PCS were searched across 15 search engines representing three distinct types: general, medical, and meta-search engines. The quality of on-line information was assessed using the DISCERN quality assessment tool. Quality performance characteristics were analyzed by performing Mann-Whitney U tests. Search engine efficiency was measured by each search query as a percentage of the relevant websites included for analysis from the total returned and analyzed by performing Kruskal-Wallis analysis of variance. RESULTS: Of 6690 websites reviewed, 84 unique websites were identified as providing information relevant to PCS. General and meta-search engines were significantly more efficient at retrieving relevant information on PCS compared with medical search engines. The quality of information was variable, with most of a poor standard. Websites that provided referral links to other resources and a citation of evidence provided a significantly better quality of information. In contrast, websites offering a direct service were more likely to provide a significantly poorer quality of information. CONCLUSIONS: The current lack of a clear consensus on guidelines and recommendation in published data is also reflected by the variable quality of information found on-line. Specialized medical search engines were no more likely to retrieve relevant, high-quality information than general or meta-search engines.

Adenocarcinoma↗

PubMed2001

Lack of influence of the androgen receptor gene CAG-repeat polymorphism on sex steroid status and bone metabolism in elderly men.

OBJECTIVE: Population means for serum testosterone (T) levels in healthy men decrease with ageing but there is considerable interindividual variability of serum T in elderly men. Ultimate androgen action is mediated through the androgen receptor. Subtle differences in androgen sensitivity might contribute to serum T variability through the T negative feedback regulation. The androgen receptor gene (AR) contains in exon 1 a polymorphic trinucleotide CAG-repeat, whose length modulates androgen receptor action. The aims of the study were to assess the potential contribution of the AR CAG-repeat polymorphism in the interindividual variability of serum T and in the determination of bone metabolism in ambulatory elderly men. DESIGN AND PATIENTS: We used cross-sectional baseline data of a longitudinal study investigating the process of ageing, in particular the changes in hormonal status and bone metabolism, in a cohort of 273 community-dwelling healthy men, between age 71 and 86 years. MEASUREMENTS: AR CAG-repeat length was determined by automated DNA sequencing of exon 1 of the AR gene. Serum T, sex hormone binding globulin, LH and oestradiol were measured by specific immunoassays. Bone mineral density (BMD) was determined by dual energy X-ray absorptiometry. Bone turnover was assessed by measurement of serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-terminal type I procollagen peptide, serum and urinary C-terminal telopeptides of type I collagen and urinary deoxypyridinoline levels, with use of immunoassays. RESULTS: No significant association was found between the AR CAG-repeat length and either total or free T, LH or the androgen sensitivity index (LHxT). BMD measurements at the hip and the forearm were not associated with AR CAG-repeat length and there was no association of this AR polymorphism with any of the biochemical markers of bone turnover. Results were not different after adjustments for age and body mass index. CONCLUSIONS: The findings of the present study do not support the view that in community-dwelling, healthy elderly men the androgen receptor gene CAG-repeat polymorphism has a substantial impact on interindividual variability of serum testosterone levels or on the determination of bone turnover and bone mineral density.

Aged↗

PubMed2006

Metabolic factors affecting residual beta cell function assessed by C-peptide secretion in patients with newly diagnosed type 1 diabetes.

BACKGROUND: In recent onset of type 1 diabetes, the residual beta cell function, assessed by baseline and/or stimulated C-peptide secretion, can be a useful parameter to establish the extension of beta cell destruction. How metabolic parameters at diagnosis influence residual C-peptide secretion is not well established. PATIENTS AND METHODS: We analyzed 553 consecutive patients with recent onset (<4 weeks) of type 1 diabetes (250 females and 303 males, mean age 15+/-8 years). Baseline and stimulated C-peptide by i.v. glucagon were evaluated using a highly sensitive radio-immunoassay. Metabolic parameters including blood glucose, HbA1c, insulin dose, and BMI were also evaluated. RESULTS: Baseline and stimulated C-peptide were 0.26+/-0.22 and 0.47+/-0.38 nmol/l and correlated positively with age (p<0.001). There was no significant correlation between C-peptide and blood glucose at diagnosis. BMI was positively correlated with both baseline and stimulated C-peptide secretion (p<0.001). By contrast, HbA1c levels inversely correlated with both baseline and stimulated C-peptide secretion (p<0.001). CONCLUSION: In type 1 diabetes at diagnosis, baseline and stimulated C-peptide are higher in pubertal and young adult patients compared with pre-pubertal patients suggesting that such parameter can be used as an end point marker for studies aimed at protecting and/or restoring beta cells in patients with substantial beta cell function. High levels of HbA1c and lower BMI are dependent variables of C-peptide values.

Adolescent↗

PubMed1998

Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation.

OBJECTIVE: To reevaluate platelet serotonin (5-HT) levels in autism, measuring and controlling for effects of race and puberty. The specificity of hyperserotonemia for autism versus cognitive impairment is also assessed. METHOD: Platelet 5-HT levels were measured in 77 individuals, aged 2 through 37 years, with autistic disorder; 65 normal controls; and 22 mentally retarded or otherwise cognitively impaired (MR/CI) prepubertal children. Effects of diagnosis, race, and pubertal status were evaluated by analysis of variance in separate pre- and postpubertal groups. 5-HT levels were expressed as ng/mL blood and ng/microL platelet volume. RESULTS: Among prepubertal children, significant effects of diagnosis (ng/mL; F2,109 = 5.9, p = .004) and race (F2,109 = 14.7, p < .0005) were found. Autistic youngsters had significantly higher 5-HT concentrations than controls, although the elevation (25%) was less than typically reported; MR/CI children had levels very similar to those of controls. White children had significantly lower 5-HT levels than black or Latino youngsters, regardless of diagnosis. Diagnosis and race effects were nonsignificant in the postpubertal group. Postpubertal subjects had lower 5-HT concentrations than prepubertal subjects (ng/mL; F1,114 = 28.5, p < .0005). CONCLUSIONS: The data underscore the importance of matching for race and pubertal status in neuropsychiatric research and suggest that the prevalence of hyperserotonemia in autistic individuals may have been overestimated because of a failure to control for both variables. Hyperserotonemia was not found in MR/CI youngsters without autistic features.

Adolescent↗