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1.
Glycoconj J ; 33(1): 29-39, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26494371

RESUMEN

Human blood plasma chitotriosidase (CHIT1) is a glycoprotein with chitinolytic activity with not fully elucidated biological function. Its increased level is observed in type 2 diabetes mellitus (T2DM) and is associated with development of diabetic complications. The CHIT1 glycosylation profile and degree is still poorly studied and never investigated in T2DM. Therefore the aim of the present study was to examine the association between glycosylation profile and degree and diabetes with accompanying nephropathy. In blood plasma of 28 patients with T2DM and 11 healthy subjects the CHIT1 concentration and specific activity were examined. The profile and degree of CHIT1 glycosylation were determined by lectin-ELISA using lectins specific to O-glycans (Jacalin, MPL, VVL) and sialo-specific SNA and MAA. We revealed that both concentration and specific activity of CHIT1 significantly increased in T2DM, especially in nephropathy with elevated albuminuria. The relative reactivities with lectins, except Jacalin, decreased progressively with T2DM occurrence and albuminuria progression. The most significant differences were observed between control vs. albuminuric group (Micro and Macro). It is also possible that the observed differences in immunoblotting pattern in molecular masses of CHIT1 bands between T2DM patients and healthy subjects may be caused by the differences in degree of CHIT1 glycosylation. The analysis of CHIT1 glycosylation status and the determination of CHIT1 concentration together with its enzymatic activity in blood plasma might constitute additional valuable diagnosis tools for the evaluation the T2DM patients with accompanying nephropathy. Extension of the lectin panel specific to O-glycans occurs useful for the further research using microarray formats, which are expected to accelerate "lectin-based glycan profiling" of glycoproteins.


Asunto(s)
Albuminuria/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Hexosaminidasas/sangre , Procesamiento Proteico-Postraduccional , Albuminuria/enzimología , Biomarcadores/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/enzimología , Nefropatías Diabéticas/enzimología , Glicosilación , Hexosaminidasas/metabolismo , Humanos , Lectinas/metabolismo , Unión Proteica
2.
Biomarkers ; 20(1): 52-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25519006

RESUMEN

OBJECTIVES: To investigate chitotriosidase (CHIT1) activity and chitinase-3-like protein 1 (YKL-40) concentration in plasma of type 2 diabetic patients and evaluate their relationship with kidney dysfunction. MATERIALS AND METHODS: 94 diabetic subjects and 33 controls were enrolled in the study. Plasma CHIT1 activity and YKL-40 concentration were measured along with routine laboratory parameters. RESULTS: Levels of CHIT1 and YKL-40 in plasma of type 2 diabetic patients increased progressively with the degree of albuminuria. CHIT1 discriminated normoalbuminuric subjects from those with abnormal albuminuria better than YKL-40. CONCLUSIONS: CHIT1represent a supportive biomarker connected with development of diabetic vascular complications, especially kidney dysfunction.


Asunto(s)
Adipoquinas/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Hexosaminidasas/sangre , Lectinas/sangre , Anciano , Albuminuria/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Proteína 1 Similar a Quitinasa-3 , Diabetes Mellitus Tipo 2/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad
3.
Clin Invest Med ; 33(2): E109, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20370990

RESUMEN

PURPOSE: Advanced oxidation protein products (AOPP) and ischemia-modified albumin (IMA) are forms of oxidatidatively modified albumin and have recently been investigated as indicators of oxidative stress. They are increased in different disorders, including diabetes mellitus, as a result of hyperglycaemia, oxidative stress and hypoxia. The usefulness of the plasma levels of these two parameters in estimating kidney dysfunction in type 2 diabetic patients (T2DM) was compared in this study. METHODS: Plasma levels of AOPP and IMA were determined spectrophotometrically in 218 individuals, 153 patients with T2DM and 65 healthy people.. The urinary albumin/creatinine ratio (UACR) was used as the reference to define the stage of kidney dysfunction by the assessment of the degree of albuminuria. RESULTS: Receiver Operating Characteristic (ROC) curve analysis, likelihood ratio (LR), and Youden's index (J) revealed that AOPP and IMA had acceptable sensitivities and specificities in individuals with different degrees of albuminuria; however, AOPP had higher values of the area under the curve (AUC: 0.934) than IMA, as well as 100% sensitivity and 77.01% specificity for distinguishing patients with micro- and macroalbuminuria. CONCLUSIONS: Both AOPP and IMA may be helpful clinical markers for estimating kidney dysfunction, but AOPP is better able to identify diabetic patients with nephropathy. We suggest that AOPP is almost ideal for discriminating between T2DM patients with micro- and macroalbuminuria.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Anciano , Albuminuria/diagnóstico , Albuminuria/orina , Biomarcadores/sangre , Creatinina/orina , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Curva ROC , Sensibilidad y Especificidad
4.
Pol Merkur Lekarski ; 27(162): 458-62, 2009 Dec.
Artículo en Polaco | MEDLINE | ID: mdl-20120706

RESUMEN

UNLABELLED: Proinflammatory cytokines play the crucial role in the arising and progression of atherosclerotic changes. Between them are: tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). The significant role in the atherosclerotic changes play adhesive molecules produced by endothelium as the answer to the cytokines stimulation. THE AIM OF THE STUDY was the evaluation of the serum concentration of TNF-alpha, IL-6 and selectin E in the patients with chronic lower limb ischaemia with and without diabetes type 2. All patients had antropometric measurements (BMI) as well as the standard biochemic evaluations and the angiologic diagnosis were performed. MATERIAL AND METHODS: The 17 patients with chronic peripheral arterial disease (the mean age 55.9+/-7.8 years) and 23 with chronic arterial ischaemia and diabetes (the mean age 61.8+/-7.6 years) were included into the final evaluation. The control group consist of 14 healthy volunteers; mean age 43.9+/-11.5 years. RESULTS: The concentration of TNF-alpha in both groups was statistically significant higher in comparison to control group. High concentration of IL-6 was in patients with arteriosclerosis, and selectin E in the group with diabetes and chronic arterial ischaemia in course of macroangiopathy. CONCLUSIONS: At the satisfactory metabolic glicemic compensation and without obesity the statistically significant differences at level of analyzed cytokines in the both groups were not shown. The high level of selectin E in the diabetes group shows for the more activation of endothelium cells.


Asunto(s)
Arteriosclerosis Obliterante/sangre , Citocinas/sangre , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Isquemia/sangre , Pierna/irrigación sanguínea , Enfermedades Vasculares Periféricas/sangre , Progresión de la Enfermedad , Selectina E/sangre , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangre
5.
Dis Markers ; 24(6): 311-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18688079

RESUMEN

AIM: The main goal of the present study was the evaluation of ischemia-modified albumin (IMA) in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia and obesity. METHODS: In 76 diabetic patients and 25 control subjects, a plasma level of IMA by manually performed, spectrophotometric Co(II)-albumin binding assay was determined. Other parameters such as glucose, fructosamine, HbA_{1c}, total cholesterol and its fractions (HDL, LDL), triglicerydes were estimated by routine methods. RESULTS: Diabetic patients had significantly higher level of IMA in comparison with control subjects. There were not significant differences between groups with various states of vascular complications although the lowest concentration of IMA was observed in patients with microangiopathy. Patients with poor glycemic control had higher IMA level in comparison with these with good glycemic control. Significant correlation was observed between IMA and HbA_{1c}. Among the risk factors, only blood pressure and LDL showed a weak relationship with IMA level. CONCLUSIONS: Our results revealed, for the first time, higher level of IMA in diabetic patients which confirms that it may be of non-cardiac origin. We can suggest that the albumin molecule in plasma of diabetic patients is modified in the chronic hypoxia conditions provoked mainly by hyperglycemia and oxidative stress in diabetes.


Asunto(s)
Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Isquemia/sangre , Albúmina Sérica/metabolismo , Glucemia , Estudios de Casos y Controles , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/complicaciones , Retinopatía Diabética/sangre , Retinopatía Diabética/complicaciones , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hiperglucemia/complicaciones , Metabolismo de los Lípidos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Estrés Oxidativo , Enfermedades Vasculares/sangre , Enfermedades Vasculares/complicaciones
6.
Pol Merkur Lekarski ; 25(146): 120-3, 2008 Aug.
Artículo en Polaco | MEDLINE | ID: mdl-18942329

RESUMEN

UNLABELLED: The aim of our study was to estimate the influence of oxidative stress on the function of vascular endothelium in diabetes mellitus type 2, through the measurement plasma levels of chosen parameters reflecting these disturbances--concentration of advanced oxidation protein products (AOPP) and activity of gamma glutamyltransferase (GGT) and N-acetyl-beta-glucosaminidase (NAG). MATERIALS AND METHODS: 73 patients with type 2 diabetes mellitus and 23 healthy people, which made up the control group were examined. In plasma of these subjects concentration of AOPP by spectrophotometric method with the use of potassium iodide; activity of GGT by spectrophotometric method and NAG activity by spectrofluorymetric method were determined. RESULTS: The plasma levels of all examined parameters were significantly higher in diabetic patients than in healthy people. We observed increase of these parameters in groups of patients clustered on the basis of disease duration, glicemic state of diabetes and vascular area occupied by diabetic complication. The most significant changes in AOPP concentration were observed. There was statistically significant correlation between AOPP and GGT, however there was no any direct connection of these two parameters with NAG activity. CONCLUSIONS: We showed significantly increase in the AOPP concentration and activities of GGT and NAG in plasma of patients with type 2 diabetes, which was induced by hyperglycemia and oxidative stress connected with this disease. The growth of examined parameters had no direct connection with each other, however was connected with chronic nature of this disease, glycemic decomposition and vascular area occupied by diabetic complication.


Asunto(s)
Acetilglucosaminidasa/sangre , Diabetes Mellitus Tipo 2/sangre , Endotelio Vascular/metabolismo , Estrés Oxidativo , gamma-Glutamiltransferasa/sangre , Adulto , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Endotelio Vascular/fisiopatología , Humanos , Persona de Mediana Edad , Valores de Referencia
7.
Wiad Lek ; 61(10-12): 263-8, 2008.
Artículo en Polaco | MEDLINE | ID: mdl-19323066

RESUMEN

Ischemia modified albumin (IMA) is a new biological marker for early identification of chest pain and ruling out myocardial infarction among patients with acute syndromes submitting to emergency department. Recently IMA has been investigated in the light of other cardiac markers (cTnT, CK-MBmas, NT-proBNP) in various states of ischemia (acute coronary syndromes, after percutaneous coronary intervention, in coronary vasospasm). Ischemia modified albumin levels were elevated in these states what suggests myocardial ischemia. However decrease in IMA concentration after exercise-induced skeletal muscle ischemia still remains unclear. Increased IMA concentration in patients with acute ischemic stroke and exposed to trauma limits its ability for detection myocardial ischemia. Specificity of IMA measurement is limited also in patients with peripheral vascular disease, systemic sclerosis, diabetes, end stage renal disease, pulmonary embolism and other pathological states with accompanying oxidative stress.


Asunto(s)
Enfermedad Coronaria/sangre , Enfermedad Coronaria/diagnóstico , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Albúmina Sérica/análisis , Biomarcadores/sangre , Dolor en el Pecho/etiología , Enfermedad Coronaria/complicaciones , Humanos , Isquemia/sangre , Isquemia/diagnóstico , Músculo Esquelético/irrigación sanguínea , Infarto del Miocardio/complicaciones , Sensibilidad y Especificidad
8.
Diabetes Res Clin Pract ; 77(2): 188-92, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17335928

RESUMEN

BACKGROUND: The aim of this study was to evaluate the selected components of the oxidative/antioxidative system in T2DM; estimation of relationships between them; search for the more expressive one and examine their alterations in angiopathy and obesity. METHODS: In 94 diabetic patients and 36 healthy people, plasma levels of TRAP, as a marker of antioxidative defence, as well as concentrations of CO, SH, and NH(2) groups and AOPP, as markers of oxidative protein damage (OPD) were determined. RESULTS: Patients had significantly lower levels of TRAP and SH groups, as well as higher NH(2), CO and AOPP in comparison to control. Significant correlation was observed between TRAP and SH groups and AOPP as well as between AOPP and SH and CO groups. Concentration of AOPP was significantly higher in the macroangiopathy and obese subgroups. CONCLUSIONS: Our results support the idea that diabetes mellitus is a complex metabolic disorder with oxidant/antioxidant defence disturbances. Among the studied parameters AOPP showed the most expressive raise in plasma of diabetic patients and significant differences between their subgroups with vascular complications and overweight. We can conclude that AOPP seems to be considered as a useful marker to estimate the degree of OPD in diabetic patients.


Asunto(s)
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/sangre , Anciano , Presión Sanguínea , Índice de Masa Corporal , Colesterol/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Triglicéridos/sangre
9.
Wiad Lek ; 60(7-8): 329-34, 2007.
Artículo en Polaco | MEDLINE | ID: mdl-18175551

RESUMEN

UNLABELLED: Hyperglycemia in patients with type 2 diabetes induces many pathological states, especially in disturbances cells' metabolism, like disorders of oxidative-antioxidative balance. The advantage of reactive oxygen species (ROS) over antioxidants is a cause of oxidative stress and creates an oxidative molecular damage of proteins, lipids, carbohydrates and nucleotides. It causes tissue degeneration, particularly in vascular system. The aim of our study was to evaluate the oxidative-antioxidative balance in patients with type 2 diabetes on the basis of selected parameters of the oxidative stress protein damage: thiol- (SH), carbonyl- (CO) and amino- (NH2) groups as well as advanced oxidation protein product (AOPP), as AOPP/albumin index as well as concentration of low molecular antioxidants (vitamin C, E, urinary acid, bilirubin). The total radical trapping antioxidant parameter (TRAP) was calculated also according to the mathematics formula. We have examined relationship between this parameters and duration of diabetes and vascular complications as well as risk factors like: hypertension, lipid disorders and obesity. MATERIAL AND METHODS: Fifty-three patients with type 2 diabetes and 21 healthy persons were examined. The concentrations of SH and CO groups, AOPP as well as vitamin C were assessed colorimetrically, NH2 groups fluorimetrically and vitamin E by high-performance liquid chromatography (HPLC) method. The urinary acid and bilirubin were evaluated using routine clinical assays. RESULTS: In patients with type 2 diabetes in comparison to healthy persons were affirmed: the significantly higher concentration of CO groups and AOPP as well as significantly lower concentration of SH groups; the lower concentration of vitamin C and TRAP value (statistically significant) and vitamin E (NS); the higher level of urinary acid (statistically significant) and bilirubin (NS). CONCLUSIONS: The measurement of AOPP seems to be the best marker of oxidative stress in patients with type 2 diabetes, because significant increase of AOPP concentration was observed in patients with long-lasting diabetes (more then 10 years) with macroangiopathy, as well as in obese patients and ones with lipid disorders.


Asunto(s)
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/etiología , Hiperglucemia/complicaciones , Estrés Oxidativo , Angiopatías Diabéticas/metabolismo , Femenino , Humanos , Hiperglucemia/metabolismo , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Factores de Riesgo
10.
Arch Med Sci ; 12(5): 977-984, 2016 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-27695487

RESUMEN

INTRODUCTION: Chitotriosidase (CHIT1) is a chitinolytic enzyme involved mainly in the immune and inflammatory response. It shows increased activity in many pathologies, including in newly diagnosed type 2 diabetes (T2D). This study aimed to investigate this enzyme's activity in plasma of patients with ongoing T2D and indicate factors related to the increased activity of this enzyme. MATERIAL AND METHODS: Ninety-one patients and 46 control subjects without abnormalities in carbohydrate metabolism and inflammatory states were enrolled in the study. Plasma CHIT1 activity was measured by a spectrofluorometric method. Routine laboratory parameters such as blood glucose, total cholesterol and HDL fraction, triglyceride, glycated hemoglobin, white blood cell count and C-reactive protein were measured by standard methods. RESULTS: We found that the chitotriosidase activity was significantly higher (p < 0.001) in type 2 diabetic patients and positively associated with parameters of glycemic control (levels of glucose and glycated hemoglobin) and blood pressure. Plasma glucose level and systolic blood pressure were independent determinants of increased CHIT1 activity in T2D patients, even after adjustment for disease duration, body mass index, parameters of inflammation and lipid metabolism. We also found that increased CHIT1 activity was associated with occurrence of diabetic angiopathies. CONCLUSIONS: This investigation indicates a possible role of chitotriosidase in the course of T2D, especially in relation to development of diabetic angiopathies.

11.
PLoS One ; 10(10): e0141730, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26517273

RESUMEN

PURPOSE: The pathophysiological role of human chitinases and chitinase-like proteins (CLPs) is not fully understood. We aimed to determine the levels of neutrophil-derived chitotriosidase (CHIT1), acidic mammalian chitinase (AMCase) and chitinase 3-like protein 1 (YKL-40) in patients with type 2 diabetes (T2D) and verify their association with metabolic and clinical conditions of these patients. METHODS: Neutrophils were obtained from the whole blood by gradient density centrifugation from 94 T2D patients and 40 control subjects. The activities of CHIT1 and AMCase as well as leukocyte elastase (LE) were measured fluorometrically and concentration of YKL-40 immunoenzymatically. Also, routine laboratory parameters in serum/plasma were determined by standard methods. RESULTS: The levels of all three examined proteins were about 2-times higher in diabetic patients in comparison to control subjects. They were significantly correlated with the activity of LE and increased progressively across tertiles of LE activity. Moreover, the activities of CHIT1 and AMCase were significantly correlated with each other. Metabolic compensation of diabetes did not influence the levels of these proteins. In the subgroup of patients with inflammatory evidence only YKL-40 concentration was significantly higher compared to those without inflammation. The highest levels of all three proteins were observed in patients with macroangiopathies. Insulin therapy was associated with lower levels of examined proteins. CONCLUSIONS: We revealed that neutrophils may be an important source of the increased levels of chitinases and CLPs in T2D, and these proteins may participate in inflammatory mechanisms in the course of the disease and consequent development of diabetic angiopathies.


Asunto(s)
Adipoquinas/metabolismo , Quitinasas/metabolismo , Diabetes Mellitus Tipo 2/inmunología , Hexosaminidasas/metabolismo , Lectinas/metabolismo , Neutrófilos/metabolismo , Estudios de Casos y Controles , Proteína 1 Similar a Quitinasa-3 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/inmunología , Angiopatías Diabéticas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Insulina/administración & dosificación , Insulina/farmacología
12.
Pol Merkur Lekarski ; 14(83): 425-7, 2003 May.
Artículo en Polaco | MEDLINE | ID: mdl-12939818

RESUMEN

The aim of the study was an assessment of alpha 1-antitrypsin (alpha 1-AT) serum concentration in patients with abdominal aortic aneurysm and investigation the relationship between alpha 1-AT and parametric and non-parametric atherosclerosis risk factors. A statistically significant increase of alpha 1-AT concentration was demonstrated in the group of patients as compared to healthy subjects; the alpha 1-AT concentration demonstrated no correlation with aneurysm diameter. A positive correlation was found between alpha 1-AT level and the age of the studied patients; the alpha 1-AT concentration demonstrated no correlation with the remaining risk factors of atherosclerosis. alpha 1-AT may be regarded as a marker of inflammatory lesions in abdominal aortic aneurysms, directly independent of atherosclerosis risk factors.


Asunto(s)
Aneurisma de la Aorta Abdominal/sangre , Enfermedad de la Arteria Coronaria/sangre , Proteínas de Plantas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Inhibidores de Tripsina , alfa-Amilasas/antagonistas & inhibidores
13.
Pol Merkur Lekarski ; 17(102): 600-2, 2004 Dec.
Artículo en Polaco | MEDLINE | ID: mdl-15771132

RESUMEN

Physical effort is possible to perform by increasing blood flow in working muscles. The endothelial cells produce vasoactive factors that regulate vessel wall tension, among others endothelin 1 (ET1) a potent vasoconstrictor and adrenomedullin (AD1)--vasodilatatory peptide. It was investigated in volunteers whether the ET-1 and ADM concentration in plasma changes by exercise. Bicycle exercise test was performed in 28 healthy persons. There were used standard RIA kits to measure ADM and ELISA method to determine ET-1 concentration in plasma. Average ET-1 and ADM levels in plasma were different before and after the exercise, the standard exercise test significantly decrease ET-1 and ADM concentration in plasma. The investigation indicates that with the decrease of the vessel resistance under the physical exercise the concentration of ET-1 obtains lower level. The lack of stimulating ET-1 influence on secretion of ADM can be the effect of the decrease of ADM concentration.


Asunto(s)
Endotelina-1/fisiología , Ejercicio Físico , Péptidos/fisiología , Adrenomedulina , Endotelio/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Fumar/epidemiología
14.
Arch Med Res ; 45(1): 36-43, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24316113

RESUMEN

BACKGROUND AND AIMS: Hyperglycemia and oxidative stress in type 2 diabetes (T2DM) provoke neutrophil overstimulation and the release and/or translocation of proteases from granules to the cell surface. Although the expression of neutrophil membrane-bound elastase (MLE) is well documented, the presence of the membrane-bound form of cathepsin B (MCB) is unknown. The aim of our study was to evaluate the neutrophil MLE and MCB activities in T2DM patients and their associations with the metabolic and clinical parameters of the disease. METHODS: Neutrophils were obtained from 47 T2DM patients and 20 control subjects. The activities of MLE and MCB and the intracellular activities of the examined proteases (ILE and ICB, respectively) were measured using fluorometric substrates. Additionally, the percentage equivalents of the activities, namely, MLEtot/ILEtot and MCBtot/ICBtot, were calculated. The susceptibility to inhibitors of both forms of the studied proteases was also determined. RESULTS: A significant increase in the activities of MLE, MCB, ILE, and ICB was found in neutrophils from T2DM patients compared with the control group. The percentage equivalent (contribution of the total membrane-bound activities to the total intracellular activities) was also higher. A partial resistance of the membrane-bound forms toward their inhibitors was revealed. Higher activities of both the membrane-bound and the intracellular proteases were also observed in patients with poor glycemic and metabolic control. The differences between subgroups with different therapeutic schemes were also revealed. CONCLUSIONS: The pathophysiological implications of the neutrophil membrane-bound forms of leukocyte elastase and cathepsin B are of great importance in the development of T2DM and its complications.


Asunto(s)
Membrana Celular/enzimología , Diabetes Mellitus Tipo 2/enzimología , Elastasa de Leucocito/metabolismo , Neutrófilos/enzimología , Estudios de Casos y Controles , Catepsina G , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Elastasa de Leucocito/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Inhibidores de Proteasas/farmacología
15.
Pol Arch Med Wewn ; 123(7-8): 364-70, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23648800

RESUMEN

INTRODUCTION: In type 2 diabetes, chronic hyperglycemia induces multi-faceted disturbances and contributes to late diabetic complications. Nonenzymatic glycation, leading to formation of advanced glycation end-products (AGEs), is one of the most important consequences of hyperglycemia. Alterations in the function of some proteolytic enzymes are also observed in diabetes. OBJECTIVES: The aim of the study was to assess the changes in and correlations between the plasma levels of AGEs and the activity of a proteolytic enzyme - cysteine cathepsin B - in plasma and neutrophils derived from patients with type 2 diabetes. PATIENTS AND METHODS: In 102 patients with type 2 diabetes and 55 healthy adults, the plasma levels of total AGEs, low-molecular-weight AGEs (LWM-AGEs), and high­molecular-weight AGEs (HWM-AGEs) as well as cathepsin B activity in plasma and neutrophils were measured by fluorescence methods. Diabetic complications in patients were also evaluated. RESULTS: Diabetic patients had significantly higher levels and activities of all the parameters compared with the control group. Moreover, in these patients, HMW-AGEs correlated negatively with plasma cathepsin B and LMW-AGEs with neutrophil cathepsin B. In the quartiles of the increasing levels of HMW-AGEs and LMW-AGEs, a successive decrease of cathepsin B in plasma and neutrophils, respectively, was observed. In patients with different late diabetic complications only the plasma level of LMW-AGEs was significantly different. CONCLUSIONS: Our study showed a significant increase of all forms of AGEs and corresponding changes in the activity of cathepsin B, both in plasma and neutrophils. A significant correlation between AGEs and cathepsin B as well as the ambiguous character of their alterations in patients with late diabetic complications indicate that they exert a complex effect on the course of diabetes.


Asunto(s)
Catepsina B/sangre , Diabetes Mellitus Tipo 2/sangre , Productos Finales de Glicación Avanzada/sangre , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peso Molecular , Espectrometría de Fluorescencia/métodos
16.
Adv Clin Exp Med ; 21(5): 601-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23356196

RESUMEN

BACKGROUND: Very often it is necessary to make a decision or to establish a diagnosis on the basis of great amounts of different kinds of data. In this paper the principal component analysis procedure was applied to anthropometrical data analysis. OBJECTIVES: The aim was to simplify the process of decision making by data dimensionality reduction. A second aim was to check how the reduction affected an analysis of the pubertal growth process. MATERIAL AND METHODS: A group of 400 boys was investigated. Three main components were calculated and interpreted. In order to investigate growth changes, the variability of each component was approximated by fourth order polynomials. RESULTS: It was shown that the loss of information resulting from data dimensionality reduction is about 25%, so the three calculated principal components contained 75% of the entire information. It seems possible to make an appropriate decision on the basis of that amount of information. CONCLUSIONS: The results obtained fully supported using the approach presented for data analysis in the case under consideration.


Asunto(s)
Antropometría , Tamaño Corporal , Modelos Estadísticos , Análisis de Componente Principal , Pubertad , Adolescente , Factores de Edad , Estatura , Niño , Interpretación Estadística de Datos , Humanos , Masculino , Grosor de los Pliegues Cutáneos , Circunferencia de la Cintura
17.
Diabetes Metab Res Rev ; 24(7): 549-53, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18613218

RESUMEN

BACKGROUND: In diabetes mellitus, hyperglycaemia accelerates non-enzymatic glycation and oxidative stress leading to damage of macromolecules, among others proteins. This manifests in the increased levels of advanced glycation end products (AGE) and advanced oxidation protein products (AOPP). OBJECTIVES: To assess the plasma levels of AGE and AOPP in the patients with type 2 diabetes mellitus (T2DM) and to estimate its relation and connection with the degree of nephropathy. MATERIAL AND METHODS: In 121 diabetic patients and 22 healthy people plasma levels of AGE and AOPP were determined with fluorimetric and spectrophotometric methods, respectively. To estimate nephropathy stage, albumin/creatinine ratio was calculated on the basis of albumin and creatinine concentrations in early morning urine samples. RESULTS: Diabetic patients had significantly higher levels of AGE and AOPP in comparison to healthy people. Both parameters were increasing progressively from normoalbuminuria, through microalbuminuria to macroalbuminuria. Statistically, the most significant differences were observed in AOPP concentration between separated groups. AGE fluorescence was significantly different on the same low, statistical level between patients with normoalbuminuria when compared to those with micro- and macroalbuminuria. Plasma AGE correlated significantly with urinary albumin/creatinine ratio whereas AOPP correlated with plasma creatinine level. CONCLUSIONS: The connection between plasma levels of both glycooxidation protein products-AGE and AOPP with nephropathy severity, measured by the degree of albuminuria, in T2DM patients was observed. We can suggest that the AOPP better reflect the progression of kidney damage than AGE in examined diabetic patients.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Productos Finales de Glicación Avanzada/sangre , Adulto , Anciano , Albuminuria/sangre , Albuminuria/orina , Creatinina/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo/fisiología
18.
Med Sci Monit ; 12(5): CR210-4, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16641878

RESUMEN

BACKGROUND: The proximal kidney tubule contains a large number of lysosomes involved in the breakdown of intracellular as well as reabsorbed proteins. When tubular protein reabsorption is overburdened or when there is tubular cell damage, higher urinary excretion of lysosomal enzymes, e.g. cathepsins and N-acetyl-beta-D-glucosaminidase (NAG), can be found. We compared urinary cathepsin B (CB) activity with NAG in diabetic patients. MATERIAL/METHODS: Using fluorogenic substrates, urinary and plasma CB and NAG activities in 130 type 2 diabetic patients with varying stages of albuminuria and 42 control subjects were determined. Early morning urine samples were used. RESULTS: In the patients, only higher values of plasma NAG were found. In urine, CB and NAG activities increased progressively from normoalbuminuria, through microalbuminuria to macroalbuminuria group. The normoalbuminuria group had both enzyme activities higher than healthy controls. Urine CB activity in the patients also increased gradually to tertiles of urinary NAG. Only urinary CB activity was significantly associated with glycemic state. The correlation was stronger in the patients with poor glycemic control. The plasma/urine ratios for both CB and NAG decreased in the patients compared with controls. CONCLUSIONS: Determination of urinary CB activity might be useful as a non-invasive surrogate marker of incipient nephropathy.


Asunto(s)
Acetilglucosaminidasa/orina , Albuminuria/enzimología , Albuminuria/orina , Catepsina B/orina , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/orina , Acetilglucosaminidasa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/orina , Estudios de Casos y Controles , Catepsina B/sangre , Nefropatías Diabéticas/enzimología , Nefropatías Diabéticas/orina , Humanos , Lactante , Masculino , Persona de Mediana Edad
19.
Pol Arch Med Wewn ; 113(1): 63-7, 2005 Jan.
Artículo en Polaco | MEDLINE | ID: mdl-16130603

RESUMEN

We present case of 55 years old female with systemic lupus erythematosus (SLE) and necrotic ulcerations in lower limbs. Etiology of this lesions was complex. In the presented case, vasculitis (microvasculitis) accompanying systemic inflammatory connective tissue disease coincides with deficiency of protein S and venous insufficiency lower limbs. It could determine necrotic type of ulcerations and location of lesions. In this case vasculitis was crucial importance and ulcerations were healed after immunosuppressive therapy. In similar cases it is often difficult to find factors responsible for development of ulcerations and it need different investigations. But detailed determine of etiopathogenesis gives guarantee therapeutic success.


Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades Cutáneas Vasculares/etiología , Vasculitis/etiología , Ciclofosfamida/administración & dosificación , Diagnóstico Diferencial , Femenino , Humanos , Inmunosupresores/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/tratamiento farmacológico , Factores de Tiempo , Resultado del Tratamiento , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológico
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