RESUMEN
Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-ß2-glycoprotein I (aß2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aß2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.
Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Anticuerpos Antifosfolípidos/sangre , Femenino , Embarazo , Anticuerpos Anticardiolipina/sangre , Inhibidor de Coagulación del Lupus/sangre , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Ferroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.
Asunto(s)
Ferroptosis , Muerte Celular , Hierro , Peroxidación de Lípido , Especies Reactivas de OxígenoRESUMEN
The new corona virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) causes a disease called COVID-19 (coronavirus disease 2019), that develops mostly in subjects with already impaired immune system function, primarily in the elderly and in individuals with some chronic disease or condition. The reasons for this should be sought in the processes of aging and chronic latent inflammation, i.e. immunosenescence and inflammaging. Laboratory medicine specialists are currently focused on proving the presence of the virus and defining biomarkers that would enable the prediction of disease progression. For now, it has been shown that useful biomarkers can include general biomarkers of inflammation (parameters of complete blood count, C-reactive protein, interleukin-6, procalcitonin), biomarkers of myocardial damage (high sensitivity troponin I/T, B-type natriuretic peptide, and N-terminal B type natriuretic peptide), and vascular biomarkers (D-dimer, prothrombin time, fibrinogen). Their actual diagnostic specificity, sensitivity and predictive value need to be tested on a larger number of subjects. In addition, it is important to find and evaluate specific biomarkers of immunosenescence.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/sangre , Personal de Salud/normas , Mediadores de Inflamación/sangre , Neumonía Viral/sangre , Manejo de Especímenes/normas , COVID-19 , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/metabolismo , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/metabolismo , SARS-CoV-2 , Manejo de Especímenes/métodosRESUMEN
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1ß secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1ß, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1ß. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1ß was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1ß were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1ß, while UCR might be even more informative and useful in overall COPD assessments.
Asunto(s)
Creatinina/análisis , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Ácido Úrico/análisis , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Creatinina/sangre , Citocinas/metabolismo , Femenino , Fibrinógeno/metabolismo , Humanos , Inflamasomas/metabolismo , Inflamación , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Recuento de Leucocitos/métodos , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Índice de Severidad de la Enfermedad , Ácido Úrico/sangreRESUMEN
The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable measure of physiological, i.e. biological age. Biomarkers should meet several criteria. For example, they have to predict the rate of aging, monitor a basic process that underlies the aging process, be able to be tested repeatedly without harming the person. In addition, biomarkers have to be indicators of biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. It is considered that the telomere length is the weak biomarker (with poor predictive accuracy), and there is currently no reliable biomarker that meets all the necessary criteria.
Asunto(s)
Envejecimiento , Senescencia Celular , Biomarcadores/metabolismo , Daño del ADN , Humanos , Sistema Inmunológico/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Homeostasis del TelómeroRESUMEN
There is an increasing number of experimental, genetic and clinical evidence of atopic dermatitis expression as a pre-condition for later development of other atopic diseases such as asthma, food allergy and allergic rhinitis. Atopic dermatitis is a heterogeneous, recurrent childhood disease, also present in the adult age. It is increasingly attributed to systemic features and is characterized by immunological and skin barrier integrity and function dysregulation. To maintain the protective function of the skin barrier, in particular the maintenance of pH, hydration and antimicrobial functions, the filaggrin, among others, plays a significant role. Filaggrin is a multifunctional, histidine-rich, insoluble protein. The lack of filaggrin is associated with various cutaneous (e.g. ichthyosis vulgaris, allergic contact dermatitis) and non-cutaneous (e.g. diabetes, inflammatory conditions of the gastrointestinal tract) diseases and may be a result of genetic, immunological factors combined with environmental factors. In this review we summarised (emphasized) recent findings in understanding the role of filaggrin in atopic dermatitis and other diseases, participants in the atopic march.
Asunto(s)
Dermatitis Atópica , Proteínas de Filamentos Intermediarios , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/genética , Dermatitis Atópica/metabolismo , Proteínas Filagrina , Humanos , Proteínas de Filamentos Intermediarios/análisis , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismoRESUMEN
NEW FINDINGS: What is the central question of this study? What is the effect of cigarette smoke on cell death, oxidative damage, expression of heat shock proteins (HSPs) and activation of mitogen-activated protein kinases (MAPKs) in A549 alveolar epithelial cells? What is the main finding and its importance? Cigarette smoke induces cytotoxicity and oxidative damage to A549 cells, increases expression of different HSPs and activates MAPK signalling pathways. This could be related to inflammatory response and apoptosis observed in lungs of patients with smoking-related diseases. ABSTRACT: Cigarette smoking is one of the main risk factors for development of chronic obstructive pulmonary disease (COPD). We previously reported that cigarette smoke (CS) induces damage to proteins and their ineffective degradation. Here, we hypothesize that CS could induce oxidative stress and cytotoxicity in lung epithelial cells through alterations of heat shock protein (HSP) expression and mitogen-activated protein kinase (MAPK) signalling pathways. We exposed A549 alveolar epithelial cells to various concentrations of cigarette smoke extract (CSE). Higher concentrations of CSE caused apoptosis of A549 cells after 4 h, while after 24 h cell viability was decreased, and lactate dehydrogenase in cell culture medium was increased as well as the number of necrotic cells. Concentrations of malondialdehyde (MDA) were elevated, while total thiol groups were decreased. Changes in the expression of HSPs (HSP70, HSP32 and HSP27) were time-dependent. After 6 h, CSE caused an increase in the expression of HSP70 and HSP32, while after 8 h all examined HSPs were up-regulated and remained increased up to 48 h. Treatment of A549 cells with CSE stimulated phosphorylation of extracellular signal-regulated kinase and p38 in a dose-dependent manner, while c-Jun N-terminal kinase activation was not detected. By using specific inhibitors, we demonstrated that MAPKs and HSPs interplay in CSE effects. In conclusion, our results show that MAPKs and HSPs are involved in the mechanism underlying CSE-induced cytotoxicity and oxidative damage to A549 alveolar epithelial cells. These processes could be related to inflammatory response and apoptosis observed in lungs of patients with smoking-related diseases, such as COPD.
Asunto(s)
Células Epiteliales Alveolares/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Nicotiana/efectos adversos , Humo/efectos adversos , Fumar/metabolismo , Células A549 , Apoptosis/fisiología , Línea Celular Tumoral , Supervivencia Celular/fisiología , Proteínas de Choque Térmico/metabolismo , Humanos , L-Lactato Deshidrogenasa/metabolismo , Pulmón/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Malondialdehído/metabolismo , Estrés Oxidativo/fisiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Regulación hacia Arriba/fisiologíaRESUMEN
[This corrects the article DOI: 10.11613/BM.2018.020501.].
RESUMEN
The initial laboratory approach in the diagnosis of allergies is to detect the type of allergic reaction, i.e. whether the patient's allergy is mediated by immunoglobulin E (IgE) or not. For this purpose, the concentration of total serum IgE (tIgE) and specific IgE (sIgE) are determined. Progress in laboratory diagnostics is the use of component-resolved diagnosis (CRD) which implies determination of sIgE against purified native and recombinant allergenic molecules. Component-resolved diagnosis is used in laboratory practice as singleplex and multiplex assays. The choice of allergen for singleplex assay is based on anamnesis, clinical findings of a patient and on skin prick test results. Multiplex-microarray assays simultaneously determine multiple sIgE's against numerous allergens. The goal of CRD is to distinguish the true allergens from the cross-reactive allergen molecules. Component-resolved diagnosis allows predicting the risk of severe symptoms, as well as anticipating the development of allergies. Thus, determination of sIgE against allergenic components may significantly improve current diagnostics of allergy. Since this method is applied in laboratory practice just a few years, it is necessary to acquire new knowledge and experience, to establish good co-operation between specialist in medical biochemistry and laboratory medicine and the specialist allergologist, so that the method can be applied in a rational manner. Component-resolved diagnosis will significantly improve the diagnostics of IgE-mediated allergy in the future. The aim of this article is to present potentials of CRD in the laboratory diagnostics of allergy mediated by IgE.
Asunto(s)
Alérgenos/sangre , Hipersensibilidad/diagnóstico , Inmunoensayo , Inmunoglobulina E/sangre , Reacciones Cruzadas , Humanos , Hipersensibilidad/sangre , Hipersensibilidad/inmunología , Sensibilidad y Especificidad , Pruebas CutáneasRESUMEN
Extracellular Hsp70 (eHsp70) can act as damage-associated molecular pattern (DAMP) via Toll-like receptors TLR2 and TLR4, and stimulate immune and inflammatory responses leading to sterile inflammation and propagation of already existing inflammation. It was found elevated in the blood of patients with chronic obstructive pulmonary disease (COPD), who might suffer occasional bacterial colonizations and infections. We used a monocytic THP-1 cell line as a cellular model of systemic compartment of COPD to assess inflammatory effects of eHsp70 when present alone or together with bacterial products lypopolysaccharide (LPS) and lypoteichoic acid (LTA). THP-1 cells were differentiated into macrophage-like cells and treated with various concentrations of recombinant human Hsp70 protein (rhHsp70), LPS (TLR4 agonist), LTA (TLR2 agonist), and their combinations for 4, 12, 24, and 48 h. Concentrations of IL-1α, IL-6, IL-8, and TNF-α were determined by ELISA. Cell viability was assessed by MTS assay, and mode of cell death by luminometric measurements of caspases-3/7, -8, and -9 activities. rhHsp70 showed cell protecting effect by suppressing caspases-3/7 activation, while LPS provoked cytotoxicity through caspases-8 and -3/7 pathway. Regarding inflammatory processes, rhHsp70 alone induced secretion of IL-1α and IL-8, but had modulatory effects on release of all four cytokines when applied together with LPS or LTA. Combined effect with LPS was mainly synergistic, and with LTA mainly antagonistic, although it was cytokine- and time-dependent. Our results confirmed pro-inflammatory function of extracellular Hsp70, and suggest its possible implication in COPD exacerbations caused by bacterial infection through desensitization or inappropriate activation of TLR2 and TLR4 receptors.
Asunto(s)
Proteínas HSP70 de Choque Térmico/metabolismo , Inflamación/patología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Interleucina-1alfa/biosíntesis , Interleucina-8/biosíntesis , Lipopolisacáridos , Células THP-1 , Ácidos Teicoicos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
CONTEXT: Increased oxidative burden is found in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To assess the association of ceruloplasmin, albumin, bilirubin, transferrin, thiols and malondialdehyde (MDA) with stable COPD. MATERIALS AND METHODS: Oxidative stress markers measured in 106 COPD patients and 45 healthy subjects were evaluated. RESULTS: Higher ceruloplasmin and MDA, and lower albumin, transferrin and thiols in COPD patients were found. Ceruloplasmin was the strongest single predictor of COPD. The model combining ceruloplasmin, albumin and thiols improved their individual diagnostic performances. CONCLUSIONS: Diagnostic characteristics of ceruloplasmin, albumin, transferrin, thiols and MDA suggest their potential value as additional tools in disease diagnosis.
RESUMEN
INTRODUCTION: Paraoxonase 1 (PON1) is an antioxidative enzyme manly associated with high density lipoproteins (HDL) in the peripheral blood. The aim of this study was to determine the PON1 paraoxonase and arylesterase activities in patients with chronic obstructive pulmonary disease (COPD). We also aimed to determine the concentration of reduced thiol groups as a marker of protein oxidation. MATERIALS AND METHODS: The study included 105 patients with stable COPD and 44 healthy controls. PON1 activities and thiols concentration were assayed in sera by spectrophotometry. RESULTS: PON1 basal (POX) and salt-stimulated paraoxonase activity (POX1) as well as arylesterase activity (ARE) were significantly reduced in COPD patients. In addition, concentration of reduced thiol groups was significantly decreased in COPD group. PON1 activities were similar in patients with different disease severity (GOLD stages). However, a significant reduction in POX, POX1 and ARE was observed already in GOLD II stage when compared to controls. POX and POX1 showed modest while ARE yielded very good power for discrimination between healthy subjects and COPD patients. Univariate and multivariate logistic regression analysis indicated that ARE is a good COPD predictor. CONCLUSION: Reduction of PON1 activity observed in COPD patients could be partly caused by oxidative environment. Lower concentrations of reduced thiol groups in COPD patients suggest that a decrease in PON1 activity could reflect oxidative changes of enzyme free cysteine residues. Furthermore, decreased PON1 arylesterase activity might indicate a down-regulation of PON1 concentration. Our results suggest that ARE could be considered as potential biomarker for COPD diagnosis.
Asunto(s)
Arildialquilfosfatasa/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Fumar/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Anciano , Estudios de Casos y Controles , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Paraoxon/metabolismo , Fenilacetatos/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Espectrofotometría , Capacidad VitalRESUMEN
Over the past three decades, the goal of many researchers is analysis of exhaled breath condensate (EBC) as noninvasively obtained sample. A total quality in laboratory diagnostic processes in EBC analysis was investigated: pre-analytical (formation, collection, storage of EBC), analytical (sensitivity of applied methods, standardization) and post-analytical (interpretation of results) phases. EBC analysis is still used as a research tool. Limitations referred to pre-analytical, analytical, and post-analytical phases of EBC analysis are numerous, e.g. low concentrations of EBC constituents, single-analyte methods lack in sensitivity, and multi-analyte has not been fully explored, and reference values are not established. When all, pre-analytical, analytical and post-analytical requirements are met, EBC biomarkers as well as biomarker patterns can be selected and EBC analysis can hopefully be used in clinical practice, in both, the diagnosis and in the longitudinal follow-up of patients, resulting in better outcome of disease.
Asunto(s)
Biomarcadores/análisis , Pruebas Respiratorias , Espiración/fisiología , Humanos , Humedad , Manejo de Especímenes/métodos , Manejo de Especímenes/normas , TemperaturaRESUMEN
Systemic inflammation and oxidative stress are the most important features of chronic obstructive pulmonary disease (COPD). The presence of oxidative stress in the airways of smokers, the largest population of COPD patients, is a consequence of direct inhalation of cigarette smoke and increased inflammation-related production of reactive oxygen species. On the other hand, oxidative stress appears to be the key component of many processes associated with chronic inflammation. We intend to examine whether serum C-reactive protein (CRP) concentration and gamma-glutamyltransferase (GGT) activity might be used as auxiliary markers in monitoring level of oxidative stress and inflammation in clinically stable COPD. We also investigated influence of cigarette smoking on these two systemic parameters. Catalytic activity of GGT and concentration of CRP were determined in sera of COPD patients (N = 109) and in healthy controls (N = 51) by using standard spectrophotometric method and immunoturbidimetric method, respectively. Concentration of CRP and activity of GGT were increased in COPD patients, as compared to healthy controls (p < 0.05). We found a significant positive correlation between those two parameters in COPD patients (r = 0.202, p = 0.0371). Our results showed no difference in GGT activity (p = 0.606) or CRP concentration (p = 0.573) between groups of patients when subdivided according to the severity of the disease. Smoking did not have a significant impact on CRP and GGT values in COPD patients and healthy controls. We showed an increase of serum CRP and GGT values in COPD patients, and we suggest that serum GGT activity might also represent an inflammation/oxidative stress marker. It seems that COPD patients present higher serum CRP and GGT values than healthy subjects independently from their smoking habits.
Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/sangre , Fumar/efectos adversos , gamma-Glutamiltransferasa/sangre , Anciano , Estudios de Casos y Controles , Catálisis , Progresión de la Enfermedad , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría/métodos , Estrés Oxidativo , Curva ROC , Factores de RiesgoRESUMEN
AIM: The main processes modulated by Ca and involved in the cause of schizophrenia are alteration in the dopamine and glutamate neurotransmitter system. Intracellular effects of Mg-ions are opposite to Ca-ions in competition at K-ion channels, in Na/K-ATP-ase activity, cAMP/cGMP concentration and Ca-ion currents in pre- and postsynaptic membranes. We conducted this research due to the incongruent results on Ca and Mg concentration that have been published until now and to determine platelet Mg concentration in suicidal and non-suicidal schizophrenic patients. METHODS: A group of schizophrenic patients consisted of 23 patients with attempted suicide (S-SCH) and 48 patients without suicidal behavior (K-SCH) diagnosed according to ICD-10 diagnosis (F20.0) with or without intentional self-harm (X60-X84). The control group (K) included 99 healthy voluntary blood donors. The Mg and Ca concentration in platelets and serum was determined by atomic absorption spectrophotometry on the AAnalyst 200. RESULTS: Using one-way anova test and manifold application of the Student-Newman-Keuls post-hoc test we established that there were higher concentrations of platelet Mg (µmol/109 platelets) (P=0.009, F=4.89) and lower concentrations of serum Ca (mmol/L) (P<0.001, F=19.18) in the S-SCH group of patients and higher concentrations of platelet Ca/Mg ratio in the K-SCH group of patients (P=0.006, F=5.37). CONCLUSION: A higher Ca/Mg ratio in the platelets of non-suicidal patients confirms indirect higher Ca concentration. Higher Mg concentration in the platelets of suicidal patients, considered a Ca antagonist, may represent a compensatory attempt to restrain Ca activity.
Asunto(s)
Plaquetas/química , Calcio/sangre , Magnesio/sangre , Esquizofrenia/sangre , Psicología del Esquizofrénico , Intento de Suicidio/psicología , Adulto , Análisis de Varianza , Estudios Transversales , Femenino , Humanos , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Fenotipo , Espectrofotometría Atómica , Ideación SuicidaRESUMEN
The pathophysiology and treatment of depression involves monoamine neurotransmitters and the magnesium (Mg)-modulated monoaminergic pathway. Serum and platelet Mg concentrations and platelet serotonin concentrations were measured in 79 depressed patients who had attempted suicide, and 101 patients without suicidal behaviour, according to the ICD-10 diagnoses F 33.2 and F32.2, with or without intentional self-harm (X60-X84). The control group consisted of 77 voluntary blood donors. The platelet serotonin concentration was determined using the competitive enzyme immunoassay test: Mg concentrations in platelets and serum were determined by atomic absorption spectrophotometry. The ANOVA test showed significantly lower serum Mg in the group of depressive patients who had attempted suicide (N = 257, F = 8.32, p<0.001), compared to depressive patients who had not, and the control group. Serum albumin was lower in the group of depressive patients who had attempted suicide and showed a significant, positive correlation with serum Mg concentrations. Platelet Mg concentrations were found to be higher in depressive patients who had not attempted suicide (N = 257, F = 3.90, p = 0.012) compared to the control group, with no difference compared to depressive patients who had attempted suicide. The Kruskal Wallis test (N = 257, H = 48.54, p<0.0001) showed the lowest concentration of platelet serotonin in the groups of depressed patients with and without suicidal behaviour, compared to the healthy control group. A positive correlation was found between platelet Mg and serotonin concentrations only in the healthy control group. In conclusion, differences were observed in serum and platelet Mg concentrations, which represent progress in the study of Mg status and its relation to serotonin.
Asunto(s)
Plaquetas/metabolismo , Depresión/sangre , Magnesio/sangre , Serotonina/sangre , Intento de Suicidio , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Albúmina Sérica/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: The objective of this study was to measure soluble dipeptidyl peptidase IV (sDPPIV) activity in sera of patients with stable chronic obstructive pulmonary disease (COPD) in comparison to healthy controls. The main goal was to assess changes in the enzyme activity in relation to severity of the disease, age and smoking history and to evaluate diagnostic accuracy for prediction of COPD by level of serum sDPPIV activity. DESIGN AND METHODS: The study included 106 patients with stable COPD (GOLD II-GOLD IV stages) and 38 healthy controls. Serum sDPPIV activity as well as some inflammatory markers (CRP, total and differential leukocyte counts) was measured. Multivariate logistic regression models were applied to analyze association of sDPPIV activity and inflammatory markers in risk estimation for COPD development. RESULTS: sDPPIV activity in COPD patients was significantly reduced when compared to healthy controls. Decrease was observed already in GOLD II stage. Age and smoking history did not influence sDPPIV activity. Very good diagnostic accuracy (AUC=0.833; sensitivity and specificity of 85.7% and 78.9%, respectively) for GOLD II and good diagnostic accuracy (AUC=0.801; sensitivity and specificity of 65.1% and 86.8%, respectively) for total cohort of COPD patients were found. The multivariate logistic regression model showed that the use of sDPPIV in combination with CRP and lymphocyte proportion improved diagnostic strength and gave an AUC of 0.933. CONCLUSIONS: sDPPIV activity is decreased in COPD patients as early as in GOLD II stage. Very good diagnostic accuracy of sDPPIV activity suggests it as a candidate biomarker for early diagnosis of COPD.
Asunto(s)
Dipeptidil Peptidasa 4/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Curva ROC , Fumar/sangreRESUMEN
OBJECTIVE: To test for possible association of hsp70-2 (+1267A/G), hsp70-hom (+2437T/C), HMOX-1 (number of GT repeats) and TNF-α (+489G/A) polymorphisms with chronic obstructive pulmonary disease (COPD) in Croatian population. METHODS: Genotyping of DNA isolated from whole blood of 130 COPD patients (as defined by spirometry) and 95 healthy controls was performed. Fragment size analysis upon restriction enzyme digestion and/or sequencing was used for genotype/allele definition. Significance of findings was tested using χ(2) test. RESULTS: hsp70-2 (+1267A/G) polymorphism was significantly associated with COPD. Results of genotyping analysis indicated that a genotype carrying G allele was preferentially associated with COPD; odds ratio (OR)=1.50, 95% confidence interval (CI)=1.00-2.24 and P=0.061. OR for the GG genotype was 3.47 with CI=1.26-9.56 and P=0.04. No association for hsp70-hom (+2437T/C), TNF-α (+489G/A) and HMOX-1 (number of GT repeats) polymorphisms were found. In addition, comparison of genotype frequencies among different stages of disease severity (GOLD II-IV) revealed no discrimination for any of the tested polymorphisms. CONCLUSION: This study is supporting the association of hsp70-2 (+1267A/G) polymorphism and COPD. Higher frequency of G allele and GG genotype in Croatian COPD patients was observed. There was no evidence for the association of hsp70-hom (+2437T/C), TNF-α (+489G/A) SNPs and HMOX-1 (number of GT repeats) polymorphism with COPD. Allele and genotype frequencies for all of the tested polymorphisms show no association with disease severity (GOLD II-IV).
Asunto(s)
Proteínas HSP70 de Choque Térmico/genética , Hemo-Oxigenasa 1/genética , Polimorfismo Genético , Enfermedad Pulmonar Obstructiva Crónica/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Alelos , Croacia , Repeticiones de Dinucleótido/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad Pulmonar Obstructiva Crónica/patología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Urate levels may be a marker of oxidative stress. The aim of the present study was to find out are there any differences in urate concentrations in exhaled breath condensate (EBC) between children with obstructive sleep apnea (OSA) and healthy children. MATERIALS AND METHODS: EBC was collected in children with obstructive sleep apnea (OSA) and clinically healthy children. Urate measurements in EBC and serum were performed by enzymatic color test. RESULTS: The higher concentration of urates in EBC of children with OSA than clinically healthy children indicate the oxidative stress in their airways. Since there was no significant difference in serum concentration of urates between children with OSA and healthy children, it could be considered that urates are sintetized in the airways of children with OSA. CONCLUSIONS: The present study indicated that urates in EBC (but not in serum) may be used as a marker of local synthesis of antioxidant compounds, but definitive conclusion must be supported by investigations involving larger number of participants.
Asunto(s)
Pruebas Respiratorias/métodos , Estrés Oxidativo , Apnea Obstructiva del Sueño/fisiopatología , Ácido Úrico/análisis , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Niño , Preescolar , Estudios Transversales , Espiración , Femenino , Humanos , Masculino , Óxido Nítrico/análisis , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
Heterogeneity exists across Europe in the definition of the profession of clinical chemistry and laboratory medicine and also in academic background of specialists in this discipline. This article provides an overview of the standards of education and training of laboratory professionals and quality regulations in Croatia. Clinical chemistry in Croatia is almost exclusively practiced by medical biochemists. Although term Medical biochemist often relates to medical doctors in other European countries, in Croatia medical biochemists are not medical doctors, but university degree professionals who are qualified scientifically. Practicing the medical biochemistry is regulated by The Health Care Law, The Law of the Medical Biochemistry Profession and The Law of the State and Private Health Insurance. According to the law, only medical biochemists are entitled to run and work in the medical biochemistry laboratory. University degree is earned after the 5 years of the studies. Register for medical biochemists is kept by the Croatian Chamber of Medical Biochemists. Licensing is mandatory, valid for 6 years and regulated by the government (Law on the Health Care, 1993). Vocational training for medical biochemists lasts 44 months and is regulated by the national regulatory document issued by the Ministry of Health. Accreditation is not mandatory and is provided by an independent, non-commercial national accreditation body. The profession has interdisciplinary character and a level of required competence and skills comparable to other European countries.