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COVID-19 , Factores Activadores de Macrófagos/inmunología , Proteína de Unión a Vitamina D/inmunología , Vitamina D , COVID-19/inmunología , COVID-19/mortalidad , Humanos , Factores Inmunológicos/sangre , Factores Inmunológicos/metabolismo , Mortalidad , Polimorfismo de Nucleótido Simple , Pronóstico , Factores Protectores , SARS-CoV-2 , Vitamina D/sangre , Vitamina D/metabolismo , Proteína de Unión a Vitamina D/genética , Proteína de Unión a Vitamina D/metabolismoRESUMEN
BACKGROUND: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically healthy adult Beagles were evaluated. METHODS: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 µg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD.
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Cistatina C/sangre , Perros , Inmunoglobulina G/orina , Lipocalina 2/orina , Proteínas de Unión al Retinol/orina , Animales , Biomarcadores/sangre , Biomarcadores/orina , Proteína C-Reactiva/orina , Perros/sangre , Perros/orina , Enfermedades Renales/sangre , Enfermedades Renales/diagnóstico , Enfermedades Renales/orina , Enfermedades Renales/veterinariaRESUMEN
Inflammation is a key player in the development of an increasing amount of diseases. The soluble urokinase plasminogen activator receptor (suPAR) is a highly flexible molecule with intrinsic chemotactic properties. This glycoprotein has been evaluated as a biomarker of inflammation, immune activation, organ damage and clinical outcome in several pathologies, including cardiovascular disease, hepatitis, renal disorders and rheumatic pathologies. The use of this early warning inflammatory biomarker could potentially improve the prediction of the severity of these diseases and mortality. In the present paper, we describe the general characteristics of suPAR and its intriguing role as a biomarker in different inflammatory diseases.
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Biomarcadores , Inflamación , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Animales , Quimiotaxis de Leucocito , Humanos , Ratones , Modelos InmunológicosAsunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Persona de Mediana Edad , Posmenopausia/sangre , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Serum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. OBJECTIVES: To evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). ANIMALS: Ninety cats were included: 49 CKD and 41 healthy cats. METHODS: Serum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT < 1.7 mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling. RESULTS: Cats with CKD had significantly higher mean ± SD sCysC (1.4 ± 0.5 mg/L) (P < .001) and uCysC/urinary creatinine (uCr) (291 ± 411 mg/mol) (P < .001) compared to healthy cats (sCysC 1.0 ± 0.3 and uCysC/uCr 0.32 ± 0.97). UCysC was detected in 35/49 CKD cats. R(2) values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr = µ + GFR + ε). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr. CONCLUSION: Serum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats.
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Biomarcadores/sangre , Enfermedades de los Gatos/diagnóstico , Cistatina C/sangre , Insuficiencia Renal Crónica/veterinaria , Animales , Biomarcadores/orina , Estudios de Casos y Controles , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/orina , Gatos , Cistatina C/orina , Femenino , Masculino , Nefelometría y Turbidimetría/veterinaria , Valor Predictivo de las Pruebas , Valores de ReferenciaRESUMEN
Interleukin-17A is an important cytokine in the pathogenesis of psoriatic arthritis. Secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1kappa monoclonal antibody with a selective binding and neutralization of interleukin-17A. By providing an alternative mechanism of action to current treatments, secukinumab has shown efficacy in the key clinical domains of psoriatic arthritis. In the present paper, we discuss the role of interleukin-17A as a clinically relevant target in the treatment of psoriatic arthritis, based on preclinical findings, dose-ranging and regimen-finding, randomized, placebo-controlled clinical trials.
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Anticuerpos Monoclonales/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Interleucina-17/antagonistas & inhibidores , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos como Asunto , Interacciones Farmacológicas , HumanosRESUMEN
Serum cystatin C (sCysC) is a possible marker for early detection of chronic kidney disease (CKD) in cats. In contrast with serum creatinine (sCr), feline sCysC is not affected by age, breed or sex. However, further biological and clinical validation is required. The objectives of this study were: (1) to investigate if food intake and circadian rhythm affect feline sCysC; (2) to determine the stability of sCysC under different storage conditions, and (3) to investigate if plasma concentrations of CysC (pCysC) differed from sCysC. A crossover study with 10 healthy laboratory cats fed the same commercial dry food was performed to study the influence of feeding and diurnal variation. Storage effects and comparison of pCysC with sCysC were determined using healthy cats (n = 3 and n = 10, respectively) and cats with CKD (n= 4 and n = 17, respectively). A significant daily sCysC variation was seen. Pre- and postprandial sCysC and sCr concentrations did not change significantly. Serum CysC significantly increased during storage at room temperature. After freezing, sCysC significantly decreased after 5 and 12 months at both -20 °C and -72 °C. Plasma CysC was significantly lower than sCysC. These findings suggest that it is not mandatory to fast cats before evaluation of sCysC and sCr. Samples were stable during routinely used storage conditions. Based on these findings, freezing for more than 5 months is not recommended, although additional studies are required to evaluate the clinical relevance of decreased sCysC after prolonged storage. Plasma and serum CysC cannot be compared directly.
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Alimentación Animal/análisis , Anticoagulantes/farmacología , Recolección de Muestras de Sangre/veterinaria , Cistatina C/sangre , Animales , Biomarcadores , Gatos , Estudios Cruzados , Cistatina C/química , Femenino , MasculinoRESUMEN
The recent Armstrong case, where more than 250 negative doping tests are confronted with the athlete's confession of erythropoietin use, blood doping, steroid, and growth hormone abuse, illustrates the limitations of current laboratory tests in detecting doping in sport. Despite numerous doping controls and simultaneous indications of common doping abuse among professional athletes in the last two decades, the number of positive urine tests for recombinant human erythropoietin (rHuEPO) remains remarkably low. Athletes are using various masking strategies, among them protease inhibitors, intravenous injections of rHuEPO and alternative erythropoiesis stimulating agents. As one of the countermeasures, the Athlete's Biological Passport has been introduced. The sensitivity of the Athlete's Biological Passport is limited if the effect of a low-dose doping remains within the intra-individual reference range. A possible solution could be the use of a novel Epo test (MAIIA Diagnostics). Another performance-enhancing strategy is the return to 'old' doping techniques, such as autologous blood transfusions. Several indirect methods to detect autologous blood transfusions have been proposed with the majority relying on changes in erythropoiesis-sensitive blood markers. Currently, an algorithm based on the haemoglobin (Hb) level concentration and the percentage of reticulocytes (OFF-hr model; Hb(g/l)-60·â%ret) is approved by the World Anti-Doping Agency. Genetic factors have been identified which may interfere with test interpretation. A large inter- and intra-ethnic variation in testosterone glucuronidation and excretion has been described. Consideration of genetic variation should improve performance of the testosterone doping test. Taking into account the pre-analytical care and better tailoring of the threshold values could increase test sensitivity. Anti-doping laboratories should routinely adjust for multiple testing as failure of doping control to detect cheaters could lead to more frequent controls. Finally, despite the huge technological progress, there is a need for increased collaboration between physiologists, analytical chemists, biostatisticians, and ethicists to reduce doping in sport.
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Doping en los Deportes , Detección de Abuso de Sustancias/métodos , Transfusión de Sangre Autóloga , Doping en los Deportes/métodos , Doping en los Deportes/prevención & control , Hematínicos/análisis , Hormona de Crecimiento Humana/análisis , Humanos , Testosterona/análisisRESUMEN
BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the most frequent skin cancer after organ transplantation. Currently, the pre-identification of transplant patients at increased risk for non-melanoma skin cancer remains difficult. OBJECTIVE: To investigate the Hp polymorphism as a marker for the identification of a subset of patients with an increased susceptibility to develop SCC/Bowen's disease. METHODS: Haptoglobin phenotyping was performed with haemoglobin-supplemented starch gel electrophoresis in 300 kidney transplant patients. High-performance gel permeation chromatography was used in case of low serum haptoglobin concentration. RESULTS: Cox regression analysis (adjusted for age, gender and Mediterranean origin) showed a significant association of the Hp 1-1 phenotype with a higher risk of SCC/Bowen's disease (P = 0.035) and multiple primary SCCs (P = 0.002). No significant difference between the Hp phenotypes was found for the development of Bowen's disease and SCCs in the first 10 years following renal transplantation. However, after a follow-up of >10 years, a significant association between the Hp 1-1 phenotype and the occurrence of Bowen's disease and SCC was reported (P = 0.002 and P = 0.001 respectively). CONCLUSIONS: This study shows an increased risk for the development of (multiple) SCCs in kidney transplant patients with the Hp 1-1 phenotype. This finding points to the role of Hp 1-1 phenotype as an important predictor in identifying a subset of patients with an increased need for preventive measures and is in agreement with the decreased anti-inflammatory capacity of this phenotype.
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Carcinoma de Células Escamosas/genética , Haptoglobinas/genética , Trasplante de Riñón , Neoplasias Cutáneas/genética , Adulto , Cromatografía en Gel , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
BACKGROUND: Depressive disorder after myocardial infarction (MI) is associated with increased cardiac morbidity and mortality. Immune activity such as inflammation might be implicated as an underlying mechanism. The purpose of this study is to investigate whether the response to an antidepressant in post-MI depression is associated with changes of inflammatory markers in serum. METHODS: In a double-blind placebo-controlled study with mirtazapine 30 mg/day (50 patients), the antidepressive effect was related to immune activation parameters. The cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), the soluble cytokine receptors sIL-6R, sTNF-R1 and sTNF-R2, and the inflammation-sensitive plasma proteins C-reactive protein and neopterin were assessed. RESULTS: Subgroup analyses revealed a highly significant correlation of pronounced sTNF-R1 increase with a decrease in depressive symptoms in antidepressant responders. CONCLUSION: Significant effects on inflammation accompany the therapeutic efficacy of mirtazapine in contrast to the therapeutic efficacy of placebo and the nontherapeutic efficacy of mirtazapine.
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Antidepresivos Tricíclicos/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/inmunología , Mianserina/análogos & derivados , Infarto del Miocardio/complicaciones , Infarto del Miocardio/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/efectos de los fármacos , Adulto , Anciano , Antidepresivos Tricíclicos/farmacología , Depresión/sangre , Depresión/complicaciones , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Mianserina/farmacología , Mianserina/uso terapéutico , Persona de Mediana Edad , Mirtazapina , Infarto del Miocardio/sangre , Infarto del Miocardio/tratamiento farmacológico , Receptores Tipo I de Factores de Necrosis Tumoral/sangreAsunto(s)
Deficiencia de Ácido Ascórbico/complicaciones , Ácido Ascórbico/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares , Deficiencia de Ácido Ascórbico/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Humanos , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND/AIM: Little is known about biochemical markers related to change in visual acuity after vitrectomy. The potential use of transthyretin (TTR), a carrier of the retinol/retinol-binding protein, as a biochemical marker protein, was investigated. METHODS: TTR was measured using immunonephelometry in a group of patients (n = 77) in longstanding (>1 week) retinal detachment (n = 29), fresh (<1 week) retinal detachment (n = 17), macular holes (n = 20) or diabetic retinopathy (n = 11). Vitreous samples were taken at the start of every vitrectomy procedure. For reference values, cadaver specimens (n = 73) were used. RESULTS: Reference values for vitreous TTR (median 18 mg/l; IQR 4 to 24 mg/l) comprised 2.2% of reference values for vitreous protein levels (median 538 mg/l; IQR 269 to 987 mg/l). Vitreous TTR values of patients were comparable in all disorders. Vitreous TTR values were higher in phakic (median 22.5 mg/l; IQR 10 to 27 mg/l) than in pseudophakic patients (median 12 mg/l; IQR 8 to 19 mg/l; p = 0.06). Postoperative change in visual acuity correlated well with vitreous TTR values found peroperatively (r(s) = 0.408; p = 0.012). Both change in visual acuity and lens status were the only variables which proved to explain the variance of TTR (multiple correlation coefficient: 0.494; phakic status: t = 2.767; p = 0.0084; and change in visual acuity t = 2.924: p = 0.0056). CONCLUSION: Vitreous fluid concentrations of TTR can be regarded as a biochemical marker for retinal function.
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Complicaciones Posoperatorias/diagnóstico , Prealbúmina/metabolismo , Trastornos de la Visión/diagnóstico , Agudeza Visual/fisiología , Vitrectomía , Cuerpo Vítreo/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Cadáver , Estudios de Casos y Controles , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Valores de Referencia , Desprendimiento de Retina/fisiopatología , Desprendimiento de Retina/cirugía , Perforaciones de la Retina/fisiopatología , Perforaciones de la Retina/cirugía , Trastornos de la Visión/etiología , Adulto JovenRESUMEN
Cerebral small vessel disease results in silent ischemic lesions (SIL) among which is leukoaraiosis. In this process, endothelial damage is probably involved. Endothelial progenitor cells (EPC), are involved in endothelial repair. By restoring the damaged endothelium, EPC could mitigate SIL and cerebral small vessel disease. Haptoglobin 1-1, one of three phenotypes of haptoglobin, relates to SIL and may therefore attenuate the endothelial repair by EPC. Our aim was to quantify EPC number and function and to assess haptoglobin phenotype and its effect on EPC function in patients with a high prevalence of SIL: lacunar stroke patients. We assessed EPC In 42 lacunar stroke patients and 18 controls by flow cytometry and culture with fetal calf serum, patient and control serum. We determined haptoglobin phenotype and cultured EPC with the three different haptoglobin phenotypes. We found that EPC cluster counts were lower in patients (96.9 clusters/well +/- 83.4 (mean +/- SD)), especially in those with SIL (85.0 +/- 64.3), than in controls (174.4 +/- 112.2). Cluster formation was inhibited by patient serum, especially by SIL patient serum, but not by control serum. Patients with haptoglobin 1-1 had less clusters in culture, and when haptoglobin 1-1 was added to EPC cultures, cluster numbers were lower than with the other haptoglobin phenotypes. We conclude that lacunar stroke patients, especially those with SIL, have impaired EPC cluster formation, which may point at decreased endothelial repair potential. The haptoglobin 1-1 phenotype is likely a causative factor in this impairment.
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Células Madre Adultas/fisiología , Infarto Encefálico/patología , Trastornos Cerebrovasculares/patología , Endotelio/patología , Haptoglobinas/metabolismo , Fenotipo , Células Madre Adultas/efectos de los fármacos , Anciano , Antígenos CD/metabolismo , Encéfalo/patología , Infarto Encefálico/etiología , Células Cultivadas , Trastornos Cerebrovasculares/complicaciones , Femenino , Citometría de Flujo , Haptoglobinas/farmacología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Characteristics of the intrafollicular environment to which the preovulatory oocyte is exposed may be one of the major factors determining subsequent fertility. The aim of our study was to examine to what extent metabolic changes that occur in early post partum high-yielding dairy cows are reflected in the follicular fluid (FF) of the dominant follicle (>8 mm). Nine blood samples were taken per cow from nine high-yielding dairy cows between 7 days before and 46 days after parturition. From Day 14 post partum on and together with blood sampling, FF samples of the largest follicle were collected from the same cows by means of transvaginal follicle aspiration. Serum and FF samples were analyzed using commercial clinical and photometric chemistry assays for glucose, beta-hydroxybutyrate (beta-OHB), urea, total protein (TP), triglycerides (TG), non-esterified fatty acids (NEFA) and total cholesterol (TC). All cows lost body condition during the experimental period (0.94+/-0.09 points) illustrating a negative energy balance during the experimental period. In FF, glucose concentrations were significantly higher and the TP, TG, NEFA and TC concentrations were significantly lower than in serum (P<0.05). The concentrations of glucose, beta-OHB, urea and TC in serum and in FF changed significantly over time (P<0.05). Throughout the study, changes of all metabolites in serum were reflected by similar changes in FF. Especially for glucose, beta-OHB and urea the correlations were remarkably high. The results from the present study confirm that the typical metabolic adaptations which can be found in serum of high-yielding dairy cows shortly post partum, are reflected in follicular fluid and, therefore, may affect the quality of both the oocyte and the granulosa cells.
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Bovinos/metabolismo , Líquido Folicular/metabolismo , Lactancia , Folículo Ovárico/anatomía & histología , Folículo Ovárico/metabolismo , Periodo Posparto , Ácido 3-Hidroxibutírico/análisis , Ácido 3-Hidroxibutírico/sangre , Animales , Glucemia/análisis , Proteínas Sanguíneas/análisis , Colesterol/análisis , Colesterol/sangre , Ácidos Grasos no Esterificados/análisis , Ácidos Grasos no Esterificados/sangre , Femenino , Líquido Folicular/química , Edad Gestacional , Glucosa/análisis , Embarazo , Proteínas/análisis , Succión/veterinaria , Triglicéridos/análisis , Triglicéridos/sangre , Urea/análisis , Urea/sangreRESUMEN
Metabolic changes in blood serum may be reflected in the biochemical composition of follicular fluid and could indirectly influence oocyte quality. The purpose of this study was to examine the biochemical composition of follicular fluid harvested from different-sized follicles and its relationship with that of blood serum in dairy cattle. Following slaughter, blood samples were collected from dairy cows n=30 and follicular fluid aspirated from three size classes of non-atretic follicles (<4 mm, 6-8 mm and >10 mm diameter). Samples remained independent between cows and between size classes within cows. Serum and follicular fluid samples were assayed using commercial clinical and photometric chemistry assays for ions (sodium, potassium and chloride) and metabolites (glucose, beta-hydroxybutyrate (beta-OHB), lactate, urea, total protein, triglycerides, non-esterified fatty acids (NEFA) and total cholesterol). Results showed that follicular fluid concentrations of glucose, beta-OHB and total cholesterol increased from small to large follicles and decreased for potassium, chloride, lactate, urea and triglycerides. There was a significant concentration gradient for all variables between their levels in serum and follicular fluid (P<0.05). Significant correlations were observed for chloride (r=0.40), glucose (r=0.56), beta-OHB (r=0.85), urea (r=0.95) and total protein (r=0.60) for all three follicle size classes and for triglycerides (r=0.43), NEFA (r=0.50) and total cholesterol (r=0.42) for large follicles (P<0.05). The results from the present study suggest that the oocyte and the granulosa cells of dairy cows grow and mature in a biochemical environment that changes from small to large follicles. Furthermore, the significant correlation between the composition of serum and follicular fluid for the above-mentioned metabolites suggests that metabolic changes in serum levels will be reflected in the follicular fluid and, therefore, may affect the quality of both the oocyte and the granulosa cells.
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Bovinos/sangre , Líquido Folicular/química , Folículo Ovárico/anatomía & histología , Ácido 3-Hidroxibutírico/análisis , Ácido 3-Hidroxibutírico/sangre , Animales , Glucemia/análisis , Proteínas Sanguíneas/análisis , Bovinos/metabolismo , Cloruros/análisis , Cloruros/sangre , Colesterol/análisis , Colesterol/sangre , Ácidos Grasos no Esterificados/análisis , Ácidos Grasos no Esterificados/sangre , Femenino , Glucosa/análisis , Ácido Láctico/análisis , Ácido Láctico/sangre , Folículo Ovárico/metabolismo , Potasio/análisis , Potasio/sangre , Proteínas/análisis , Sodio/análisis , Sodio/sangre , Triglicéridos/análisis , Triglicéridos/sangre , Urea/análisis , Urea/sangreRESUMEN
BACKGROUND: Hemopexin is a heme-binding plasma glycoprotein which, after haptoglobin, forms the second line of defense against hemoglobin-mediated oxidative damage during intravascular hemolysis. A decrease in plasma hemopexin concentration reflects a recent release of heme compounds in the extracellular compartment. Heme-hemopexin complexes are delivered to hepatocytes by receptor-mediated endocytosis after which hemopexin is recycled to the circulation. METHODS OF ANALYSIS: Immunonephelometric and -turbidimetric hemopexin assays are available as more precise and rapid alternatives to the radial immunodiffusion technique. INTERPRETATIONS: Hemopexin determinations are not subject to interference by in vitro hemolysis. Altered serum or plasma concentrations of hemopexin are found not only in hemolytic anemias but also in other conditions such as chronic neuromuscular diseases and acute intermittent porphyria. In laboratory medicine, while hemopexin determination in tandem with haptoglobin has potential applications in the assessment of intravascular hemolysis and allows for the monitoring of the severity of hemolysis after depletion of haptoglobin, its diagnostic utility is less clear in other pathological conditions. Further studies are necessary to fully establish the clinical significance of hemopexin determination.
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Hemopexina/fisiología , Antioxidantes/metabolismo , Química Clínica/métodos , Heterogeneidad Genética , Hemo/metabolismo , Hemopexina/química , Homeostasis , Humanos , Hierro/metabolismo , Receptores de Péptidos/metabolismo , Valores de ReferenciaRESUMEN
INTRODUCTION: In patients with chronic hepatitis C infection, the haptoglobin (Hp) 1-1 phenotype is overrepresented. Data regarding the occurrence of the Cys282Tyr missense mutation in these patients are less clear. We studied the prevalence of both variables in a cohort of patients with chronic hepatitis C and looked for interaction between the two variables. MATERIALS AND METHODS: The study group consisted of 142 patients chronically infected with the hepatitis C virus. All patients were examined for the occurrence of the Cys282Tyr missense mutation, and in 132 of them the Hp phenotype was determined. The Cys282Tyr missense mutation was detected by restriction fragment length polymorphism (RFLP) using a standard polymerase chain reaction (PCR) technique and RsaI digestion. Hp phenotypes were determined using starch gel electrophoresis of haemoglobin-supplemented serum followed by peroxidase staining. RESULTS: A significant overrepresentation of the Hp 1-1 phenotype was found (36/132, 27%, P < 0.01 v. control population). This overrepresentation was observed only in the patients homozygous for the wild-type allele of the HFE gene. The Cys282Tyr allele was significantly overrepresented in hepatitis C patients (0.12 v. 0.07, P < 0.05) and principally in patients with the Hp 2-1 and 2-2 phenotypes. CONCLUSION: In patients with chronic hepatitis C infection, both the Hp 1-1 and the Cys282Tyr allele occur more frequently than in a control population. Remarkably, these genes seem to determine each other's occurrence, such that the overrepresentation of the Hp 1-1 phenotype is seen only in Cys282Tyr-negative subjects, while the overrepresentation of the Cys282Tyr allele is observed in Hp 1-1-negative subjects. Differences in immunomodulating and in oxidative stress-inducing capacities between the two genes may explain this finding.