RESUMEN
A significant number of patients with essential thrombocythemia (ET) complain of symptoms including distal parts of the extremities (e.g., paresthesias or Raynaud's phenomenon). The aim of the present study was to examine peripheral circulation in the upper extremities of individuals with ET. The study included 45 ET patients and 30 control subjects. All participants were subjected to thermography, photoplethysmography, impedance plethysmography, and applanation tonometry pulse wave analysis. The patients with ET differed significantly from the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs. 32.45°C), skin temperature gradient (mean 1.82 vs. 0.11°C), photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in the radial artery (more frequent occurrence of type B waveform). Pulse wave parameters correlated with the skin temperature gradient. The study findings imply the altered regulation of peripheral circulation in ET, including a decreased flow and an increased resistance.
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Hemodinámica , Microcirculación , Enfermedades Vasculares Periféricas/etiología , Trombocitemia Esencial/complicaciones , Extremidad Superior/irrigación sanguínea , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Manometría , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/fisiopatología , Fotopletismografía , Pletismografía de Impedancia , Análisis de la Onda del Pulso , Flujo Sanguíneo Regional , Temperatura Cutánea , Termografía , Trombocitemia Esencial/diagnóstico , Resistencia Vascular , Rigidez VascularRESUMEN
Patients with increased thromboembolic risk tend to form denser fibrin clots which are relatively resistant to lysis. We sought to investigate whether essential thrombocythemia (ET) is associated with altered fibrin clot properties in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry and clot lysis time (CLT) were measured in 43 consecutive patients with ET (platelet count from 245 to 991 × 10(3)/µL) and 50 control subjects matched for age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained significant after adjustment for fibrinogen and platelet count. ET was associated with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P-selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001), with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable fibrinolysis inhibitor, plasminogen and α2-antiplasmin activity were found in the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive protein. CLT positively correlated only with PAI-1. Patients with ET display prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which represents a new prothrombotic mechanism in this disease.
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Plaquetas/metabolismo , Fibrina/metabolismo , Fibrinógeno/metabolismo , Trombocitemia Esencial/sangre , Trombosis/sangre , Adulto , Anciano , Biomarcadores/sangre , Plaquetas/patología , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Tiempo de Lisis del Coágulo de Fibrina , Humanos , Janus Quinasa 2/sangre , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría , Selectina-P/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Activación Plaquetaria , Recuento de Plaquetas , Factor Plaquetario 4/sangre , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/patología , Trombosis/complicaciones , Trombosis/patología , Activador de Tejido Plasminógeno/sangreRESUMEN
We evaluate the efficacy of antimicrobial Photodynamic Therapy (APDT) for inactivating a variety of antibiotic-resistant clinical strains from diabetic foot ulcers. Here we are focused on APDT based on organic light-emitting diodes (OLED). The wound swabs from ten patients diagnosed with diabetic foot ulcers were collected and 32 clinical strains comprising 22 bacterial species were obtained. The isolated strains were identified with the use of mass spectrometry coupled with a protein profile database and tested for antibiotic susceptibility. 74% of isolated bacterial strains exhibited adaptive antibiotic resistance to at least one antibiotic. All strains were subjected to the APDT procedure using an OLED as a light source and 16 µM methylene blue as a photosensitizer. APDT using the OLED led to a large reduction in all cases. For pathogenic bacteria, the reduction ranged from 1.1-log to > 8 log (Klebsiella aerogenes, Enterobacter cloaca, Staphylococcus hominis) even for high antibiotic resistance (MRSA 5-log reduction). Opportunistic bacteria showed a range from 0.4-log reduction for Citrobacter koseri to > 8 log reduction for Kocuria rhizophila. These results show that OLED-driven APDT is effective against pathogens and opportunistic bacteria regardless of drug resistance.
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Antiinfecciosos , Diabetes Mellitus , Pie Diabético , Fotoquimioterapia , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pie Diabético/tratamiento farmacológico , EnterobacterRESUMEN
Advanced glycation end-products (AGEs) contribute to vascular complications and organ damage in diabetes. The unique AGE epitope (AGE10) has recently been identified in human serum using synthetic melibiose-derived AGE (MAGE). We aimed at developing ELISA for AGE10 quantification, determining whether AGE10 is present in diabetic patients (n = 82), and evaluating its association with diabetic complications. In a competitive ELISA developed, the reaction of synthetic MAGE with anti-MAGE was inhibited by physiological AGE10 present in serum. In this assay, new murine IgE anti-MAGE monoclonal antibodies, which do not recognize conventional AGEs, a synthetic MAGE used to coat the plate, and LMW-MAGE (low molecular mass MAGE) necessary to plot a standard curve were used. AGE10 was significantly higher in patients with microangiopathy, in whom it depended on treatment, being lower in patients treated with aspirin. AGE10 levels were positively correlated with estimated glomerular filtration rate (eGFR) and negatively with creatinine. As a marker of stage ≥3 chronic kidney disease or microangiopathy, AGE10 displayed moderate overall accuracy (respectively, 69% and 71%) and good sensitivity (82.6% and 83.3%) but poor specificity (58.1% and 57.8%). In conclusion, newly developed immunoassay allows for AGE10 quantification. AGE10 elevation is associated with microangiopathy while its decrease accompanies stage ≥3 chronic kidney disease.
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BACKGROUND: Advanced glycation end-products (AGEs) are formed during cascade reactions between reducing sugars or reactive aldehydes and proteins, lipids or DNA molecules. They constitute a group of various stable compounds. Advanced glycation end-products are considered potential biomarkers of metabolic disorders. However, so far only a few methods to determine the level of individual AGEs have been developed. OBJECTIVES: The aim of the study was to compare the efficiency of the slot-dot blot method and direct enzyme-linked immunosorbent assay (ELISA) in detecting non-standard epitopes of methylglyoxal (MGO)-modified proteins (AGE4) found in diabetes serum in trace amounts, and to assess AGE4 in diabetes and associated metabolic abnormalities. MATERIAL AND METHODS: The presence of AGE4 was detected using 2 methods: direct ELISA and the slot-dot blot method - a newly developed immunoassay based on monoclonal, commercially available antibody detection of non-standard AGE epitopes. AGE4 quantification, expressed as median AGE4 in arbitrary units (AU) and AGE4 positivity (the percent of samples with detectable AGE4) was related to diabetes-associated metabolic abnormalities, complications and treatment. RESULTS: Slot-dot blot was significantly more efficient than ELISA in detecting non-standard AGE4 epitopes. AGE4 positivity was less frequent in patients with microangiopathy and in those with polyneuropathy. In patients with abnormal glucose metabolism, metformin treatment was associated with higher AGE4. AGE4 positivity was significantly lower in gliptin-treated patients. Multivariate analysis showed that polyneuropathy and obesity were independently associated with AGE4 positivity, with odds ratios (ORs) of 0.21 and 3.02, respectively. Moreover, logistic regression showed that AGE4 positivity and HbA1c are independent predictors of polyneuropathy. Considering both indicators allows correct classification of 70.4% of cases with a general accuracy of 76%. CONCLUSIONS: The slot dot-blot method detects compounds found in serum in trace amounts. Accumulation of AGE4 was associated with glucose metabolism abnormalities. A tendency toward AGE4 positivity was less frequent in patients with microangiopathy and in non-treated and gliptin-treated diabetes patients.
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Epítopos , Productos Finales de Glicación Avanzada , Obesidad , Polineuropatías , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Productos Finales de Glicación Avanzada/sangre , Productos Finales de Glicación Avanzada/genética , Humanos , Inmunoensayo , Obesidad/genética , Polineuropatías/genéticaRESUMEN
BACKGROUND: Advanced glycation end products (AGEs) are formed during protein modification by a reduction of sugars or reactive aldehydes. Depending on the pathology, various AGEs may be formed. They are stable compounds and are considered as potential diseases markers. OBJECTIVES: The objective of this study was to assess glucose-mediated albumin modification that yields non-standard epitopes of AGEs (AGE-1) in diabetes and in associated metabolic abnormalities. MATERIAL AND METHODS: The AGE-1, expressed as median AGE-1 level and AGE-1 positivity, was determined in 246 individuals (198 with prediabetes/diabetes) using a new slot-dot-blot method (allowing for detection of barely traceable analytes) and related to the presence of diabetes-associated metabolic abnormalities and complications, and treatment. RESULTS: The AGE-1 level was higher in patients with prediabetes/diabetes than in controls. Its elevation was associated with metabolic syndrome (MetS), obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) but not with diabetic control or microand macroangiopathy, except for atherosclerotic plaques formation in carotid arteries. The AGE-1-positive patients had higher triglycerides and lower high-density lipoprotein (HDL)-cholesterol. In patients untreated with aspirin, AGE-1 positivity was associated with higher C-reactive protein (CRP) level. Treatment with aspirin, sulfonylureas and gliptins was associated with higher AGE-1 level and with dyslipidemia medications with higher AGE-1 positivity. In patients with abnormal glucose metabolism, acarbose treatment was associated with lower AGE-1 positivity. Multivariate analysis showed MetS, carotid artery plaques, NAFLD, and treatment with aspirin and acarbose to be independently associated with AGE-1 positivity. CONCLUSIONS: Unlike standard AGEs, AGE-1 is more tightly associated with abnormalities in lipid than glucose metabolism, and lower in patients treated with acarbose but not with other antidiabetics.
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Acarbosa/uso terapéutico , Diabetes Mellitus/sangre , Productos Finales de Glicación Avanzada/análisis , Estado Prediabético/sangre , Albúmina Sérica/análisis , Estudios Transversales , Glucosa/metabolismo , HumanosRESUMEN
OBJECTIVE: The status of metabolites of the nitric oxide (NO) pathway in patients with chronic wounds in the course of cardiometabolic diseases is largely unknown. Yet arginine supplementation and citrulline supplementation as novel therapeutic modalities aimed at increasing NO are tested. MATERIAL AND METHODS: Targeted metabolomics approach (LC-MS/MS) was applied to determine the concentrations of L-arginine, L-citrulline, asymmetric and symmetric dimethylarginines (ADMA and SDMA), and arginine/ADMA and arginine/SDMA ratios as surrogate markers of NO and arginine availability in ulnar and femoral veins, representing systemic and local levels of metabolites, in patients with chronic wounds in the course of cardiometabolic diseases (n = 59) as compared to patients without chronic wounds but with similar cardiometabolic burden (n = 55) and healthy individuals (n = 88). RESULTS: Patients with chronic wounds had significantly lower systemic L-citrulline and higher ADMA and SDMA concentrations and lower L-arginine/ADMA and L-arginine/SDMA as compared to healthy controls. The presence of chronic wounds in patients with cardiometabolic diseases was associated with decreased L-arginine but with increased L-citrulline, ADMA, and SDMA concentrations and decreased L-arginine/ADMA and L-arginine/SDMA. Serum obtained from the ulnar and femoral veins of patients with chronic wounds differed by L-arginine concentrations and L-arginine/SDMA ratio, both lower in the femoral vein. Wound etiology affected L-citrulline and SDMA concentrations, lower and higher, respectively, in patients with venous stasis, and the L-arginine/SDMA ratio-lower in venous stasis. The wound type affected L-arginine/ADMA and citrulline-lower in patients with ulcerations or gangrene. IL-6 was an independent predictor of L-arginine/ADMA, VEGF-A of ADMA, G-CSF of L-arginine/SDMA, and GM-CSF of L-citrulline and SDMA. CONCLUSION: Chronic wounds in the course of cardiometabolic diseases are associated with reduced NO and arginine availability due to ADMA and SDMA accumulation rather than arginine deficiency, not supporting its supplementation. Wound character seems to affect NO bioavailability and wound etiology-arginine bioavailability. Arginine concentration and its availability are more markedly reduced at the local level than the systemic level.
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Arginina/metabolismo , Enfermedades Cardiovasculares/patología , Extremidad Inferior/patología , Óxido Nítrico/metabolismo , Heridas y Lesiones/diagnóstico , Anciano , Arginina/análogos & derivados , Arginina/análisis , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/metabolismo , Estudios de Casos y Controles , Quimiocinas/análisis , Citrulina/análisis , Citocinas/análisis , Femenino , Hormona del Crecimiento/análisis , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Heridas y Lesiones/complicaciones , Heridas y Lesiones/metabolismoRESUMEN
BACKGROUND: Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies. OBJECTIVES: The aim of this article is to evaluate the effects of wound etiology on a panel of circulating cytokines in patients with non-healing wounds of the lower extremities. MATERIAL AND METHODS: This prospective case-control study involved 104 individuals: healthy elderly people (n = 46) and patients with diabetes and/or cardiovascular disease (n = 58; among them 38 with chronic wounds of venous, ischemic or neurotrophic etiology). Selected serum cytokines - i.e. IL-1ß, IL-4, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-BB - were measured using the Luminex platform. RESULTS: Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, MCP-1 and G-CSF while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and GM-CSF. Among diseased elderly people, having wounds was associated with increased levels of IL-1ß, IL-4, IL-6, IL-8, FGF-2, MIP-1α, PDGF-BB, and VEGF-A. Interleukin 1ß elevation was a sole independent predictor of chronic wounds with an odds ratio (OR) of 6.3. Cytokines in healthy seniors were loosely interrelated, while the levels of cytokines in diseased patients with wounds displayed a tight pattern of association. When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and VEGF-A was disrupted in neurotrophic wounds. CONCLUSIONS: The results presented herein may improve our understanding of the pathomechanisms which lead to chronic wounds and of the effects they exert on a systemic level, as well as providing potential targets for more effective therapies.
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Biomarcadores/análisis , Quimiocinas/sangre , Citocinas/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Cicatrización de Heridas/fisiología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Crónica , Citocinas/metabolismo , Femenino , Humanos , Inflamación/sangre , Péptidos y Proteínas de Señalización Intercelular , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
INTRODUCTION: The peroxisome proliferator-activated receptor gamma (PPARgamma), a transcriptor factor, regulates immunological and metabolic processes, which are important for carbohydrate and lipid metabolism. Various polymorphic forms of PPARgamma may promote diabetes mellitus and diabetic complications. AIM OF THE WORK: The assessment of TNFalpha gene expression in peripheral blood monocytes, serum TNFalpha concentration and anti-GAD and ICA antibodies in relation to the polymorphism Pro12Ala in patients with 2 diabetes. PATIENTS AND METHODS: 58 patients with type 2 diabetes (average age 59.0 +/- 11 years) and 18 healthy people were examined. The Pro12Ala polymorphism of PPARy gene were assessed using mini-sequence technic SnaPshot [ABIPRISM-310]. The TNFalpha gene expression were estimated using real-time PCR [Applied Bio-systems]. The TNFalpha concentration [Quantikin Immunoassay, R&D Systems] and ICA and GAD antibodies [immunofluorescence method, DRG] were evaluated in venous blood. RESULTS: A heterozygotous genotype Pro12Ala was estimated in 32 patients and a homozygotous genotype Pro12Pro in 21. Only 6 patients were positive for GAD antibodies and only 6 patients for ICA antibodies. The TNFalpha concentration in serum and the TNFalpha gene expression in monocytes did not refer to the Pro12ala polymorphism of PPARy and neither to antibodies. CONCLUSION: 1) The TNFalpha concentration in serum and the TNFalpha gene expression in monocytes do not refer to the Pro12ala polymorphism of PPARgamma in patients with type 2 diabetes. 2) The Pro12Ala genotype do not influence autoimmunologic processes of diabetes.
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Sustitución de Aminoácidos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/inmunología , Resistencia a la Insulina/genética , PPAR gamma/genética , PPAR gamma/inmunología , Polimorfismo Genético/genética , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Genotipo , Hemoglobina Glucada , Humanos , Resistencia a la Insulina/inmunología , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético/inmunología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Diabetic retinopathy is a micro-angiopathy affecting predominantly small vessels of the retina. Proliferative diabetic retinopathy is characterised by preretinal neovascularisation and fibrosis leading to vitreous heamorrhage and tractional retinal detachment. Chronic hyperglicemia may cause growth factor alterations that are likely to participate in tissue remodeling typical for this late complication. Numerous angiogenic and mitogenic factors have been demonstrated to be present in the eye, including transforming growth factor-beta (TGF-beta), insulin-like growth factors, fibroblast growth factor, tumor necrosis factor and vascular endothelial growth factor. TGF-beta is involved in the control of endothelial cell proliferation, adhesion and deposition of extracellular matrix, thus TGF-beta may play a role in the control of endothelial cell proliferation seen in the disease. The role of TGF-beta in diabetic retinopathy enables better understanding, and thus in the future better intensive antidiabetic therapy in aspect of ophthalmic complications.
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Retinopatía Diabética/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Enfermedad Crónica , Retinopatía Diabética/etiología , Humanos , Hiperglucemia/complicaciones , Retina/metabolismoRESUMEN
The cardiovascular complications of metabolic syndrome are induced by unfavorable environmental and genetic factors. One of the most important genes under consideration codes peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear transcription factor which has wide influence on metabolism. The activation of PPARg controls glycemia, lipidemia, adipogenesis, and endothelium function and diminishes insulin resistance. This review discusses the role of the most frequent mutations of the ppargamma gene in metabolic syndrome: Pro467Leu and Val290Met, which are connected with severe insulin resistance, Pro115Gln, which is connected with obesity, and Pro12Ala, which can influence the development of diabetes or hypertension.
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Resistencia a la Insulina/genética , Síndrome Metabólico/genética , Mutación , PPAR gamma/genética , Polimorfismo Genético , Humanos , Obesidad/genéticaRESUMEN
Diabetic retinopathy is one of the main causes of blindness. This review will discuss the role of IGF-I in the pathogenesis of diabetic retinopathy. IGF-I is a growth factor with a very wide spectrum of biological activities. It especially controls cell growth and metabolic processes. Disorders of IGF-I activity, which are observed during diabetes, contribute to pathologic vascularization of the eye, particularly in the retina. Reasons for this is local hypoxia, which results from chronic hyperglycaemia; damage of blood retina barrier and disorder of the axis IGF-I--growth hormone. In the first stage of diabetic retinopathy the deficit of the systemic IGF-I can also be of importance. The role of IGF-I in diabetic retinopathy enables better understanding, and thus in the future better intensive antidiabetic therapy in aspect of ophthalmic complications.
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Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neovascularización Patológica/fisiopatología , Humanos , Hiperglucemia/fisiopatología , Vasos Retinianos/fisiopatología , Factores de RiesgoRESUMEN
BACKGROUND: [corrected] Etiology and pathogenesis of thromboangiitis obliterans, an uncommon disease, but connected with high risk of leg amputation, is still unknown. Genetic predisposition and inconvenient factors of environment, especially nicotine, could initiate an immunological process, which evokes endothelial dysfunction. In histological preparation inflammation and thrombus are observed. Endo-thelin-1 could affect these processes. It is a strong vasa-constrictor and has a wide spectrum of biological activity, often opposed to effect of prostacycline analogs. The aim of study was a role of endothelin-1, antielastin antibodies and selectin P, L, E in the pathogenesis Buerger's disease and influence of alprostadil on these parameters. MATERIAL AND METHODS: We examined 10 patients with Buerger disease in the active phase, which were divided in two subgroups. Four persons with necrosis of toes were in the first subgroup, and six patients with rest pain but without trophic changes in the second subgroup. 13 healthy persons composed the control group. Index of antielastin antibodies, concentration of endotehlin-1, selectin P, L and E were measured in venous and arterial serum. These parameters by patients were determined twice: before and after 10-days treatment with alprostadil 20-40 microg per day. Concentration of endothelin-1, selectins and index antielastin antibodies were measured by enzyme-linked immuno-sorbent assay. RESULTS: We observe increase in endothelin-1 concentration by persons with necrosis of toes compared to patients without these changes (p=0.024) and to control (p=0.022). In the subgroup I index of antielastin antibodies IgA was higher than in control group (p=0.020). After alprostadil treatment endothelin-1 concentration, antielastin antibodies index was not statistically significant compared to results before treatment or control group. We observed correlation between concentration of endo-tehlin-1 before treatment and index of antielastin antibodies IgG (p=0.0475). We observed significant diffrance of concentration of selectin P, L and E compared to control (p=0.038). Especially we noticed higher concentration of selectin P (p=0.001) than in control group. The after treatment reduction of concentration was only for selectin L statistically significant (p=0.038). CONCLUSION: 1. Plasma endothelin-1 level play a role in the exacerbation of clinical symtpoms of thromboangiitis obliterans. 2. Endothelial injury is connected with increase in concentration of selectin P in patient's serum. 3. Alprostadil didn't influence on concentration of endothelin-1 in these patients.
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Endotelina-1/fisiología , Tromboangitis Obliterante/fisiopatología , Adulto , Alprostadil/farmacología , Alprostadil/uso terapéutico , Anticuerpos/inmunología , Elastina/inmunología , Elastina/metabolismo , Endotelina-1/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selectinas/inmunología , Selectinas/metabolismo , Tromboangitis Obliterante/tratamiento farmacológico , Tromboangitis Obliterante/inmunología , Vasodilatadores/farmacología , Vasodilatadores/uso terapéuticoRESUMEN
The high risik of cardiovascular diseases in diabetes is connected with wide and premature atheromatosis. It is caused by systemic metabolic disorders like hyperglycaemia, insulin resistance, dyslipidaemia, endothelium dysfunction. This review will discuss the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in the pathogenesis diabetes and atheromatosous injury of vessels. PPARgamma is a nuclear transcript factor with a very wide spectrum of biological activities. It influences important risik factors of atheromathosis, especially by patients with metabolic syndrome in diabetes type 2. Thiazolidinediones, which is activators PPARgamma, could be a turning-point in the treatment of diabetic angiopathy.
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Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/fisiopatología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , PPAR gamma/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Tiazolidinedionas/uso terapéuticoRESUMEN
BACKGROUND: Insufficiency of blood vessels supplying a limb allograft may lead to loss of the extremity. Thus, a regular evaluation of perfusion of transplants seems a reasonable approach. The purpose of the present study was assessment of allograft perfusion by means of non-invasive methods. MATERIAL/METHODS: Six hand allografts transplanted in 5 patients were included in the study group. The transplant procedure occurred on average 45 months before. The study group comprised 2 allografts at forearm level, 2 transplants of the arm, and 1 bilateral transplant of the forearm. Parameters of blood flow using Doppler ultrasonography, impedance plethysmography, Doppler measurement of segmental pressures, optical pulse oscillography (OPO), and thermography were performed in all participants. RESULTS: DUS revealed increased resistive index in ulnar arteries of transplant hands compared to native hands and an altered blood supply was confirmed by IP. Flow-mediated dilatation within the transplanted extremity was abnormal in most patients and was inversely correlated with number of episodes of acute rejection. Analysis of oscillographic spectrum revealed flattening of the dicrotic notch in transplant hands. A tendency for lower temperature of the skin of transplanted hands compared to native extremities was also observed. CONCLUSIONS: In asymptomatic patients after limb transplantation, non-invasive methods disclosed discreet abnormalities of graft perfusion. Thus, regular measurement of perfusion parameters using these methods appears to be a promising approach to detect early and potentially reversible disturbances of blood supply. Further observational studies are required to determine its clinical significance.
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Aloinjertos Compuestos/irrigación sanguínea , Trasplante de Mano , Isquemia/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Adulto , Aloinjertos Compuestos/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Isquemia/etiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pletismografía de Impedancia , Ultrasonografía Doppler en ColorRESUMEN
Thrombotic complications of unknown etiology remain a serious diagnostic and therapeutic problem. Occurrence of the inherited polymorphisms of genes encoding proteins involved in the coagulation cascade is one of the possible causes of these complications. In recent years, protein Z (PZ) and PZ-dependent protease inhibitor (ZPI) have been added to the list of prothrombotic factors. PZ is a glycoprotein serving as a cofactor of ZPI, which is responsible for the inhibition of prothrombinase. Expression of the PZ gene is under the control of many transcriptional factors; several polymorphisms alternate the rate of gene expression. The present article describes the significance of the ZPI-PZ system in venous and arterial thrombosis, adverse pregnancy outcomes and antiphospholipid syndrome complications.
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UNLABELLED: Cytokines secreted by the monocyte-macrophage system play a key role in the progression of atherosclerotic lesions in Type 2 diabetes. The objectives of this study were to assess the influence of cytokine gene expression in monocytes from patients with Type 2 diabetes on direct markers of endothelial injury with regard to clinically manifest atherosclerosis. METHODS: Monocytes from 58 patients with Type 2 diabetes and from 22 age-matched healthy volunteers of a control group were isolated in order to assess expression of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8 and IL-10 cytokines (RTPCR, Applied Biosystems). Thrombomodulin concentration was determined using a Diagnostica Stago Immunoenzymatic assay, and circulating endothelial cell numbers were assayed using immunofluorescence studies with CLB-HEC19 antibodies. RESULTS: In 28 patients, TNFalpha expression in monocytes was observed. In these patients, as compared to those with undetectable levels of this cytokine's expression, higher hemoglobin A(1c) (P=.012) and thrombomodulin (P=.005) concentrations were found. IL-8 expression was determined in 36 patients. Higher expression of TNFalpha (P=.048) and IL-8 (P=.049) was detected in patients with peripheral arterial disease in contrast to those free from this complication. CONCLUSION: TNFalpha and IL-8 play a significant role in the proatherogenic activity of monocytes in Type 2 diabetes. The TNFalpha-connected activity of monocytes may directly determine endothelial dysfunction and injury. The location of atherosclerosis should be taken into account in the assessment of the proinflammatory activity of peripheral blood monocytes.
Asunto(s)
Aterosclerosis/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Inflamación/fisiopatología , Interleucina-8/metabolismo , Monocitos/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Aterosclerosis/etiología , Biomarcadores/sangre , Índice de Masa Corporal , Citocinas/sangre , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/complicaciones , Células Endoteliales/citología , Femenino , Humanos , Inflamación/complicaciones , Resistencia a la Insulina/fisiología , Interleucina-8/sangre , Interleucina-8/genética , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trombomodulina/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Monocytes and macrophages play a key role in the progression of atheromatous changes. The peroxisome proliferator-activated receptor gamma (PPAR gamma) can limit macroangiopathy through the control of cytokine transcription. The objectives of this study were to examine the influence of PPAR gamma and its agonist (rosiglitazone) on the TNFalpha, IL-6, IL-8 and IL-10 gene expression in monocytes of patients with diabetic macroangiopathy and to analyse obtained results in context of selected atherogenic factors ant direct indicators of endothelial lesion. TNFalpha, IL-6, IL-8, IL-10 and PPAR gamma gene expression was assessed in peripheral blood monocytes in 45 patients with type 2 diabetes before and following 22 weeks of rosiglitazone therapy (real-time PCR [Applied Biosystems]). As indicators of endothelial lesion, concentration of thrombomodulin (immunoassay [Diagnostica Stago]) and amount of circulating blood endothelial cells (immunofluorescence method with MoAb CLB-HEC19) were determined. Following rosiglitazone therapy, a statistically significant downward tendency of TNFalpha (p=0.026) and IL-8 (p=0.008) gene expression was noted. Before and following rosiglitazone treatment, PPAR gamma, IL-6 and IL-10 gene expression was undetectable in studied monocytes in vivo. In conclusion, TNFalpha and IL-8 play an important role in monocyte atherogenic activity. Rosiglitazone reduces monocyte proinflammatory readiness by influencing the expression of selected atherogenic cytokines (PPAR gamma-independent pathway).
Asunto(s)
Aterosclerosis/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Monocitos/efectos de los fármacos , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Adulto , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Regulación hacia Abajo , Células Endoteliales , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas , Rosiglitazona , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
UNLABELLED: The peroxisome proliferator-activated receptor gamma (PPARgamma) influences wide on metabolism and atheromatosus processes in vessels. The common polymorphic form of PPARy, Pro12Ala, could promote diabetes mellitus and diabetic vascular complications. AIM OF WORK: The assessment of indicators of endothelium destruction in patients with diabetes mellitus t.2 in relation to the polymorphism Pro12Ala of PPARgamma. PATIENTS AND METHODS: Circulating blood endothelium cells (immunofluorescens method with MoAb CLB-HEC19), thrombomodulin (Asserchrom Immunoassay) and polymorphism Pro12Ala [minisequence technic SnaPshot (Applera); ABI+PRISM310] were investigated in 58 patients with diabetes mellitus typ 2 and 22 healthy persons. Fibrinogen, uric acid, lipids, HbA1c, glucose, insulin concentration, blood pressure, BMI and WHR were evaluated too. RESULTS: The significant higher systolic (137.92 +/- 15.88 vs 122.0 +/- 15,67 [mmHg]; p < 0.025) and diastolic (85.00 +/- 7.38 vs 75.50 +/- 7.61 [mmHg]; p < 0.011) was determined in the group of healthy people, who have got a homozygous genotyp Pro12Pro in comparison with heterozygous genotyp Pro12Ala. The significant higher value of HbA1c was determined in the patients with diabetes mellitus t.2, who have got genotyp Pro12Ala in comparison with genotyp Pro12Pro (7.01 +/- 1.54 vs 8.39 +/- 1.81 [%]; p < 0.006). There was any significant difference for others parameters. Among people, which have got genotyp Pro12Pro there was significant difference between healthy and patients for circulating blood endothelium cells (2.19 +/- 1.53 vs 0.78 +/- 0.09 [EC/ml]; p < 0.009). On the contrary among people with genotype Pro12Ala there was not significant difference between healthy and patients for circulating blood endothelium cells (2.95 +/- 1.64 vs 1.61 +/- 1.08; p = 0.077 [EC/ml]). CONCLUSIONS: 1) The polymorphism Pro12Ala is not connected with the endothelium destruction. 2) Other researches are necessary to estimate influence of mutated allele on the control of diabetes. 3) The genotyp Pro12Pro promotes higher blood pressure by healthy people.