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OBJECTIVES: Experimental and small human studies have indicated that high total adiponectin levels have beneficial cardiometabolic effects. In contrast, however, high total adiponectin levels are also associated with higher all-cause and cardiovascular mortality in thoroughly adjusted epidemiological studies. To gain further insight into these seemingly contradictory results, we report results on total adiponectin from the indigenous Melanesian population of Kitava, Trobriand Islands, Papua New Guinea, where an apparent absence of cardiometabolic disease has been previously reported. METHODS: Fasting levels of serum total adiponectin were measured cross-sectionally in ≥40-year-old Kitavans (n = 102) and Swedish controls matched for age and sex (n = 108). Multivariable linear regression was used for the analysis of associations with total adiponectin when controlled for group, sex, smoking, hypertension and/or type 2 diabetes, age, and body mass index. RESULTS: Total adiponectin was lower for Kitavans compared to Swedish controls (Median [Mdn] 4.6 µg/mL, range 1.0-206 µg/mL and Mdn 9.7 µg/mL, range 3.1-104 µg/mL, respectively, r = .64, p < .001). Lower total adiponectin was associated with Kitavan group, male sex (only in Swedish controls), smoking (only in Kitavans and Swedish controls combined), younger age (not in Swedish controls), higher BMI, lower total, low-density lipoprotein, high-density lipoprotein (HDL) (only in Kitavans and Swedish controls combined), and non-HDL cholesterol, and higher anti-PC IgG (only in Kitavans and Swedish controls combined). CONCLUSION: Total adiponectin in Kitavans was significantly lower than in Swedish controls.
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Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.
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Resistência à Insulina , Obesidade , Adulto , Humanos , Obesidade/metabolismo , Músculo Esquelético/metabolismo , Exercício Físico/fisiologia , Gordura Subcutânea/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Expressão Gênica , Tecido Adiposo/metabolismoRESUMO
Our study aimed to investigate the effects of exercise on HDL composition and functional properties in overweight/obese subjects. Eighteen overweight/obese subjects (nine F and nine M, BMI = 30.3 ± 3 kg/m2) attended supervised training for 7 weeks. The protocol included combined resistance and conditioning training four to five times each week. The activity of the antioxidant enzyme paraoxonase-1 (PON1) associated with HDL was evaluated in all subjects before and after the training intervention. Moreover, myeloperoxidase (MPO) levels and oxidative stress markers (ox-LDLs and total antioxidant capacity) were studied in the serums of the subjects. At the end of the intervention, the activity of PON1 was increased (p < 0.0001), and MPO levels and the MPO/PON1 ratio were decreased (p < 0.0001). In addition, a significant improvement in muscle strength and maximal oxygen uptake (VO2max) (p < 0.0001) and a significant reduction in total and visceral adipose tissue mass (p < 0.001) and waist circumference (p < 0.008), without any significant decrease in body weight, were observed. A significant correlation was established between serum MPO/PON ratios, HDL redox activity and ox-LDLs. In conclusion, our results demonstrate that exercise training, without modifications of dietary habits, improved HDL functionality in overweight/obese adults, without any significant reduction in BMI or modifications of glucose and lipid biochemical parameters.
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Autologous hematopoietic stem cell transplantation (AHSCT) has been approved for multiple sclerosis (MS) in many European countries. A large proportion of patients are women of child-bearing age. For them, AHSCT may have negative consequences for reproductive health, since the ovaries are particularly susceptible to alkylating agents. Anti-Müllerian hormone (AMH) reflects the ovarian reserve and has been suggested as a potential biomarker of fertility in women. The aim of this study was to investigate AMH levels in relation to age and reproductive potential in MS patients treated with AHSCT. The study cohort comprised 38 female patients, aged 20-44 years, who underwent AHSCT for MS using a cyclophosphamide (200 mg/kg)/rabbit-anti-thymocyte globulin (6 mg/kg) conditioning regimen between 2013-2020. Clinal follow-up visits were made 3 months after AHSCT and then yearly. AMH was analysed in blood samples. The median age at transplantation was 28 years (interquartile range, IQR 25-33). The median AMH concentration was 23 pmol/l at baseline (IQR 6.0-30), 0.5 pmol/l at 3 months (IQR 0-1.5) and 1.1 pmol/l at 2 years (IQR 0-2.9). A multiple linear regression model was used to determine if age and/or AHSCT influenced AMH values; both significantly did (age, -0.21 per year, p = 0.018; AHSCT -19, p <0.0001). Seven women became pregnant, six spontaneously and one both spontaneously and with IVF. One patient underwent an abortion, all other pregnancies led to live births. Six of the women became pregnant despite low or very low post-AHSCT serum concentrations of AMH, suggesting that low serum AMH concentrations do not necessarily reflect impaired fertility in patients treated with high-dose cyclophosphamide.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Gravidez , Animais , Coelhos , Feminino , Masculino , Esclerose Múltipla/terapia , Esclerose Múltipla/etiologia , Hormônio Antimülleriano , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida , Ovário , Transplante AutólogoRESUMO
Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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Cistatina C , Nefropatias , Humanos , Proteoma , Creatinina , Proteômica , Taxa de Filtração Glomerular/fisiologia , Nefropatias/diagnóstico , BiomarcadoresRESUMO
OBJECTIVES: Most data on glomerular filtration rate (GFR) originate from subjects <65 years old, complicating decision-making in elderly living kidney donors. In this retrospective multi-center study, we calculated percentiles of measured GFR (mGFR) in donors <65 years old and extrapolated these to donors ≥65 years old. METHODS: mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors <65 years (n=1,983), using quantiles modeled as cubic splines (two linear parts joining at 40 years). Percentiles were extrapolated and validated in an internal cohort of donors ≥65 years (n=147, France) and external cohort of donors and healthy subjects ≥65 years (n=329, Germany, Sweden, Norway, France, The Netherlands) by calculating percentages within the extrapolated 5th-95th percentile (P5-P95). RESULTS: Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5-P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5-P95. CONCLUSIONS: We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.
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Transplante de Rim , Idoso , Creatinina , Taxa de Filtração Glomerular , Humanos , Rim , Doadores Vivos , Estudos RetrospectivosRESUMO
BACKGROUND: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. METHODS: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). RESULTS: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1-48 mg/L and Mdn 1.1 mg/L range 0.1-33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. CONCLUSIONS: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.
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Proteína C-Reativa/análise , Horticultura , Mediadores da Inflamação/sangue , Inflamação/sangue , Ocupações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Regulação para Baixo , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Papua Nova GuinéRESUMO
BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. METHODS: A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. RESULTS: The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. CONCLUSIONS: A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.
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Betacoronavirus , Infecções por Coronavirus , Monitoramento de Medicamentos/normas , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pandemias , Pneumonia Viral , Adulto , Idoso , COVID-19 , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Pessoa de Meia-Idade , Plasma , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Soro , Adulto JovemRESUMO
INTRODUCTION: Standardized commercial kits enable targeted metabolomics analysis and may thus provide an attractive complement to the more explorative approaches. The kits are typically developed for triple quadrupole mass spectrometers using serum and plasma. OBJECTIVES: Here we measure the concentrations of preselected metabolites in cerebrospinal fluid (CSF) using a kit developed for high-resolution mass spectrometry (HRMS). Secondarily, the study aimed to investigate metabolite alterations in patients with secondary progressive multiple sclerosis (SPMS) compared to controls. METHODS: We performed targeted metabolomics in human CSF on twelve SPMS patients and twelve age and sex-matched healthy controls using the Absolute IDQ-p400 kit (Biocrates Life Sciences AG) developed for HRMS. The extracts were analysed using two methods; liquid chromatography-mass spectrometry (LC-HRMS) and flow injection analysis-MS (FIA-HRMS). RESULTS: Out of 408 targeted metabolites, 196 (48%) were detected above limit of detection and 35 were absolutely quantified. Metabolites analyzed using LC-HRMS had a median coefficient of variation (CV) of 3% and 2.5% between reinjections the same day and after prolonged storage, respectively. The corresponding results for the FIA-HRMS were a median CV of 27% and 21%, respectively. We found significantly (p < 0.05) elevated levels of glycine, asymmetric dimethylarginine (ADMA), glycerophospholipid PC-O (34:0) and sum of hexoses in SPMS patients compared to controls. CONCLUSION: The Absolute IDQ-p400 kit could successfully be used for quantifying targeted metabolites in the CSF. Metabolites quantified using LC-HRMS showed superior reproducibility compared to FIA-HRMS.
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Metabolômica , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/metabolismo , Cromatografia Líquida , Estudos de Coortes , Feminino , Análise de Injeção de Fluxo , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Esclerose Múltipla/patologiaRESUMO
BACKGROUND: Oligoclonal bands (OCB) are widely believed to be stable over time and rarely affected by disease-modifying treatment in MS. It is presently unknown how intrathecal immunoglobulin production and other cerebrospinal fluid (CSF) biomarkers are impacted by a highly efficacious procedure such as autologous haematopoietic stem cell transplantation (aHSCT). OBJECTIVE: To describe the evolution of intrathecal immunoglobulin and neurofilament light (NFL) over time in MS patients treated with aHSCT. METHODS: In this retrospective study, available data from previously made CSF investigations in 46 patients treated with aHSCT were analysed. RESULTS: After a median follow-up time of 745 days, immunoglobulin G (IgG) OCB remained detectable in 74% of patients, the proportion of patients with a pathological IgG index went down from 70% to 46%, and the proportion of patients with a pathological NFL went down from 72% to 24%. In patients with follow-up time >1500 days, IgG OCB were detectable in 50% of patients, 14% had a pathological IgG index and none a pathological NFL. CONCLUSIONS: Intrathecal immunoglobulin production and NFL were lower after treatment with aHSCT, decreased over time and were normalised in a significant portion of patients. This challenges the notion that OCB are unaffected by therapeutic intervention in MS.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Imunoglobulina G , Filamentos Intermediários , Esclerose Múltipla/terapia , Bandas Oligoclonais , Estudos Retrospectivos , Transplante AutólogoRESUMO
OBJECTIVES: To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Case series of patients with relapsing-remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as "no evidence of disease activity-4," sustained for a period of at least 5 years without any ongoing disease-modifying treatment. Furthermore, MS was considered as "resolved" if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well. RESULTS: Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved. CONCLUSIONS: Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible.
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Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla Recidivante-Remitente/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum. STUDY DESIGN: Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS. RESULTS: Low limit of quantification (LLOQ) was 25 pg/mL and low limit of detection (LLOD) was 12.5 pg/mL. Precision and accuracy bias were <10%. LNG in serum samples from Mirena® users ranged between 37 to 219 pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26-1272 pg/mL). CONCLUSION: A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG.
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Dispositivos Intrauterinos , Levanogestrel/análise , Extração em Fase Sólida , Cromatografia Líquida , Espectrometria de MassasRESUMO
OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP). METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values. RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata. CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.
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HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Triglicerídeos/sangue , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de Risco , Fatores Sexuais , SuéciaRESUMO
To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.
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Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Cinurenina/metabolismo , Masculino , Metaboloma , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Fenilalanina/metabolismo , Pirimidinas/metabolismo , Serotonina/metabolismo , Triptofano/metabolismoRESUMO
Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS). Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability. Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), tumor necrosis factor alpha (TNF-α), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20ß-dihydrocortisol (20ß-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20ß-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression. Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression.
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Fatores Biológicos/análise , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/química , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Crônica Progressiva/diagnóstico , Proteínas/análise , Adulto , Idoso , Cromatografia Líquida , Diagnóstico Precoce , Feminino , Humanos , Imunoensaio , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Estudos Prospectivos , ProteômicaRESUMO
The present work investigated serum vitamin D (25(OH)D) status in relation to bone and muscle qualities and functions in 19 female soccer players (13-16 years) resident at northern latitude with very low sun exposure (â¼32-36â h/month) during winter season (late January to early March). Serum 25(OH)D, parathyroid hormone and bone turnover markers osteocalcin (OC) and beta carboxy-terminal collagen cross-links (ß-Ctx), as well as body composition and muscle performance were examined. Hormones were tested using routine laboratory methods. Fat mass, lean mass, and bone mineral density in whole body, as well as femur and lumbar spine were evaluated with dual-energy X-ray absorptiometry. Muscle performance was assessed through isokinetic knee extension and flexion, countermovement jump, and sprint running. 25(OH)D was low (50.5 ± 12.8â nmolâ l-1), whereas the values of bone turnover markers were markedly high (OC: 59.4 ± 18.6â µgâ l-1; ß-Ctx: 1075 ± 408â ngâ l-1). All bone and muscle measurements were normal or above normal. 25(OH)D was not significantly correlated with most of the parameters of bone and muscle quality or function, except the knee extension time to peak torque (r = -0.50, p = .03). In conclusion, the level of vitamin D is markedly low in adolescent female soccer players during the winter in Sweden. However, vitamin D levels did not significantly correlate with measures of bone and muscle except a moderate correlation in time to peak torque in the knee extensors. The practical implication of low vitamin D levels in young growing female athletes remains unclear.
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Densidade Óssea/fisiologia , Fenômenos Fisiológicos Musculoesqueléticos , Futebol/fisiologia , Vitamina D/sangue , Adolescente , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Suécia/epidemiologiaRESUMO
Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R2 = .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R2 = .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.
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Eletroforese Capilar/normas , Hemoglobinas Glicadas/análise , Hemoglobinometria/normas , Automação Laboratorial/instrumentação , Eletroforese Capilar/instrumentação , Hemoglobinometria/instrumentação , Humanos , Imunoensaio/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.
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Reação de Fase Aguda/sangue , Reação de Fase Aguda/diagnóstico , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Miostatina/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Reação de Fase Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Endostatin is an endogenous inhibitor of angiogenesis that inhibits neovascularisation. The aim of the study was to evaluate the effect of elective surgery on endostatin levels. METHODS: Blood samples were collected prior to elective surgery and 4 and 30 days postoperatively in 2 patient groups: orthopedic surgery (n =27) and coronary bypass patients (n =21). Serum endostatin levels were measured by ELISA. RESULTS: Serum endostatin was significantly reduced 30 days after surgery in comparison with presurgical values in both the orthopedic (P =0.03) and cardiopulmonary surgery (P =0.04) group. CONCLUSION: Serum endostatin is reduced 30 days after surgery. This reduction would favor angiogenesis and wound-healing.
Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária , Endostatinas/sangue , Procedimentos Ortopédicos , Cicatrização/fisiologia , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Adipose tissue cells produce cathepsins L and S, which have proatherogenic effects. Obesity is strongly linked to atherogenesis, cardiovascular morbidity, and mortality. OBJECTIVE: The aim of the present study was to see if life style interventions/weight reduction could decrease cathepsin L and S levels in blood plasma. METHOD: Study subjects (n=31) were recruited to a life style intervention program aiming at increased physical activity, more healthy eating habits, and weight reduction for most of the participants. Blood samples were collected at inclusion and after 4 and 8 weeks. RESULTS: Cathepsin L was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks (p=0.008). No significant change in fractalkine values was observed at 4 weeks (p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002). CONCLUSION: The intervention program resulted in significant reductions of cathepsin L and S levels in plasma after 4 and 8 weeks of intervention.