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BACKGROUND: As life expectancy is increasing and healthy ageing becomes more and more important, skin ageing is a growing topic of interest from both a medical and a commercial point of view. The urgency to unravel the causes of skin ageing is rising. However, there is a lack of objective, simple, noninvasive methods to assess biological skin age - a term introduced to describe how old someone looks, covering both the appearance and function of the skin. A rapid, noninvasive assessment of biological skin age would greatly facilitate the execution of the studies required to find the causes of skin ageing. OBJECTIVES: To find an objective, easy-to-apply method to assess biological skin age. METHODS: Skin age score (SAS) was compared with skin autofluorescence, a measure of advanced glycation end products in the skin, and several subject characteristics in 32 healthy, white women with little sun-exposed skin and no history of smoking. RESULTS: A moderate, positive correlation (R(2) = 0·32, P = 0·001) between SAS and skin autofluorescence-based biological skin age was found. However, the variation in biological skin age according to SAS could be explained better by body mass index, chronological age and hormonal status (R(2) = 0·86, P < 0·001). CONCLUSIONS: In the current setting skin autofluorescence did not contribute better to the prediction of biological skin age than chronological age. Biological skin age was best predicted by body mass index, chronological age and hormonal status, and this approach provides a considerable simplification of the application of biological skin age.
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Envejecimiento/fisiología , Índice de Masa Corporal , Hormonas/metabolismo , Envejecimiento de la Piel/fisiología , Adulto , Anciano , Estudios Transversales , Femenino , Antebrazo , Voluntarios Sanos , Humanos , Persona de Mediana Edad , Imagen Óptica , Posmenopausia/fisiología , Premenopausia/fisiología , Análisis de Regresión , Fumar/fisiopatología , Encuestas y CuestionariosRESUMEN
Correction to: European Journal of Clinical Nutrition (2015) 69, 309313; doi: 10.1038/ejcn.2014.261; published online 14 January 2015 Since the publication of this article, the authors have noticed that several of the author names were published incorrectly. The correct author names are listed above. The .html and online PDF versions have also been amended. The authors apologise for any inconvenience caused.
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BACKGROUND/OBJECTIVES: The level of skin autofluorescence (AF) at a given moment is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF is a measure of the accumulation of advanced glycation end products (AGEs). The aim of the study was to estimate the influence of nutrition on the 1-year increase of skin AF (ΔAF) in HD patients. SUBJECTS/METHODS: A total of 156 HD patients were enrolled in this study. Skin AF, body mass index (BMI), superoxide dismutase, myeloperoxidase, C-reactive protein, inter-cellular adhesion molecule-1, von Willebrand factor and heart-type fatty acid-binding protein were measured four times at intervals of approximately half a year. Data from the monthly routine blood analysis were also used. Daily calorie, protein and AGE intakes were assessed from food recordings over a period of 1 week. RESULTS: A J-shaped relation was found between baseline BMI and ΔAF (P=0.01). The lowest point of the J-shaped curve is found for BMI=24.3 kg/m(2). In the univariate analysis of the contributors to the 1-year ΔAF, we found that beside BMI=24.3 kg/m(2), AGE and calorie intakes, as well as myeloperoxidase and HD vintage, had a P <0.10. The sole independent predictor of the 1-year ΔAF was BMI=24.3 kg/m(2) (P=0.01). CONCLUSIONS: It appears that calorie, protein and AGE intakes hardly influence the 1-year ΔAF in HD patients. BMI of HD patients of around 24 kg/m(2) resulted in a lower 1-year ΔAF.
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Índice de Masa Corporal , Productos Finales de Glicación Avanzada/sangre , Fallo Renal Crónico/sangre , Diálisis Renal , Adulto , Anciano , Ingestión de Energía , Femenino , Fluorescencia , Productos Finales de Glicación Avanzada/administración & dosificación , Productos Finales de Glicación Avanzada/efectos adversos , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Peroxidasa/sangre , PielRESUMEN
Objective. To investigate whether advanced glycation endproducts (AGEs) in the skin are increased in patients with systemic sclerosis (SSc) and are related to the presence of disease-related and traditional cardiovascular risk factors. Methods. Skin autofluorescence, as a measure for the accumulation of AGEs, was assessed by measuring UV-A light excitation-emission matrices (AF-EEMS) in 41 SSc patients and 41 age- and sex-matched controls. Traditional cardiovascular risk factors and disease-related risk factors were recorded. Results. Skin AF-EEMS did not differ between SSc patients and controls (1.68 ± 0.58 a.u. versus 1.63 ± 0.41 a.u., P = 0.684). Skin AF-EEMS in SSc patients was associated with levels of CRP (r = 0.44, P = 0.004), Medsger's severity scale (r = 0.45, P = 0.006), and use of agents intervening in the renin-angiotensin system (r = 0.33, P = 0.027). When analysing SSc patients and controls together, in multivariate analysis, only age and use of agents intervening in the renin-angiotensin system were independently associated with AF-EEMS. Conclusion. These data demonstrate that skin AGEs are not increased in SSc patients.
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AIM: Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the normal reference value of advanced glycation end products accumulated in tissue measured by the advanced glycation end product reader--skin autofluorescence--and discusses some factors influencing it. METHODS: The values of autofluorescence in healthy individuals in China were determined by the advanced glycation end product reader; age, gender, skin reflectance, smoking habits and alcohol consumption of the subjects were also recorded. RESULTS: The mean reference values of autofluorescence in healthy Chinese subjects are (95% confidence interval) 20-29 years: 1.54-1.62 arbitrary units; 30-39 years: 1.66-1.75; 40-49 years: 1.78-1.89; 50-59 years: 1.87-2.03; 60-69 years: 1.86-2.09; 70-79 years: 1.97-2.31. The value of autofluorescence is strongly related to age, but no significant difference between males and females were found (all P > 0.05). Autofluorescence was higher in smokers than in non-smokers (P < 0.05). In persons with low skin reflectance (< 10%), skin autofluorescence was dependent on skin colour, but was still related to age. CONCLUSIONS: The mean reference values of autofluorescence we established could be used for a Chinese population in a clinical setting and are agreement with those in a Caucasian population. Future developments are needed to make the advanced glycation end product reader reliable for lower skin reflections as well, independently of the skin colour.
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Pueblo Asiatico , Diabetes Mellitus/metabolismo , Hemoglobina Glucada/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , China/epidemiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Femenino , Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Piel/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Accumulation of advanced glycation end products (AGEs) is accelerated during glycemic and oxidative stress and is an important predictor of complications in diabetes mellitus (DM). STUDY DESIGN: Here we both review and present original data on the relationship between skin autofluorescence (SAF), a noninvasive measure of AGEs, and short- and intermediate-term glycemic variations. RESULTS: Acute changes in glucose levels during an oral glucose tolerance test in 56 persons with varying degrees of glucose tolerance did not influence SAF. AGE-rich meals result in a transient postprandial rise in SAF of 10% 2-4 h later. This could not be attributed to meal-induced glycemic changes and is probably caused by the AGE content of the meal. In type 1 DM major intermediate-term improvements of glycemic control as depicted by multiple hemoglobin A1c (HbA1c) measurements were associated with lower skin AGE levels. In a well-controlled, stable type 2 DM cohort, only a weak correlation was found between SAF and HbA1c. In both studies skin AGE/SAF levels predicted complications of diabetes with an accuracy superior to that of HbA1c. SAF has also been proposed as a new tool in diagnosing impaired glucose tolerance (IGT) and DM. It proved to be more sensitive than either fasting glucose or HbA1c. CONCLUSIONS: SAF is not influenced by short-term glycemic variations. AGE-rich meals may, however, cause a transient rise postprandially. There is a weak correlation between SAF or skin AGEs and current or time-integrated HbA1c levels. SAF has strong added value in risk prediction of complications of diabetes and is a promising tool for early detection of diabetes and IGT.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Femenino , Fluorescencia , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Skin autofluorescence (AF) as measured with the AGE Reader (DiagnOptics Technologies, Groningen, The Netherlands) is a noninvasive prognostic marker in diabetes mellitus and other diseases with increased cardiovascular risk. This study provides reference values of healthy Caucasian control subjects as a function of age, tobacco smoking, and gender. METHODS: The results of skin AF measured in 428 healthy Caucasian control subjects by the AGE Reader (n = 211) and its nonautomated but otherwise similar predecessor, the Autofluorescence Reader (n = 217), were analyzed. Linear regression analysis was performed to obtain reference values for skin AF as a function of age. Further analysis was performed on the effect of tobacco smoking (n = 96) and gender. RESULTS: Skin AF was described by a linear increase with age of approximately 0.023 arbitrary units (AU) per year for subject age up to 70 years. Tobacco smoking was associated with an absolute increase of skin AF by 0.16 AU (P < 0.01), without a significant further increase with age (P = 0.17). Gender had no influence on skin AF in nonsmokers. Among current smokers, female subjects had a 0.2 AU higher skin AF than male subjects (P = 0.02), with no further age-related increase. CONCLUSIONS: The present results provide reference values of skin AF for healthy Caucasian control subjects over a broad age range. A major contribution of age and some interaction of smoking and gender were observed, resulting in reference values of skin AF suitable for clinical settings and future studies.
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Piel/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Análisis de Regresión , Factores Sexuales , Pigmentación de la Piel , FumarRESUMEN
BACKGROUND/AIMS Skin autofluorescence (AF) is a non-invasive marker for advanced glycation endproducts (AGE) in tissues, making use of their characteristic AF pattern. The aim of this study was to investigate whether skin AF is increased in patients with neovascular age-related macular degeneration (AMD) compared with healthy controls. METHODS Skin AF was assessed in 73 consecutive patients with active and documented neovascular AMD without evidence for diabetic or hypertensive retinopathy and in 31 healthy age-matched controls. Exclusion criteria were: known renal disease, current inflammatory or malignant disease, or skin type V or VI. Skin AF was measured on the forearm and was calculated as a ratio of mean intensities detected from the skin between 420-600 and 300-420 nm. Student t test and chi(2) test were used to compare differences between groups. RESULTS Skin AF was increased in neovascular AMD compared with controls (2.57+/-0.68 vs 2.23+/-0.63 arbitrary units x 10(-2); p=0.018). In patients without vascular risk factors or cardiovascular disease, skin AF was not significantly higher than that of the controls. Skin AF correlated with age in both patients and controls. CONCLUSION Skin AF is increased in patients with neovascular AMD, suggesting that AMD is accompanied by enhanced systemic AGE accumulation, which may indicate a role in the pathophysiology of AMD.
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Degeneración Macular/metabolismo , Piel/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Estudios de Casos y Controles , Neovascularización Coroidal/metabolismo , Estudios Transversales , Femenino , Fluorescencia , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND.: ST-elevation myocardial infarction (STEMI) is associated with increased inflammation and oxidative stress, enhancing the formation of advanced glycation endproducts (AGEs). These encompass a characteristic fluorescence pattern, which can be non-invasively measured as skin autofluorescence (AF). In this study we investigate whether skin AF is elevated in STEMI, its association with inflammatory and glycaemic stress and its predictive value for future events. METHODS.: Skin AF was measured in 88 STEMI patients (mean age 64+/-13 years) within 72 hours and around six months after discharge, in 81 stable coronary artery disease (sCAD) patients (64+/-10 years), and in 32 healthy controls (63+/-11 years). The cumulative one-year incidence of all-cause mortality and hospitalisation for myocardial infarction or heart failure was documented. RESULTS.: Skin AF was significantly higher in STEMI compared with sCAD and controls, irrespective of confounders, and was associated with HbA1c and C-reactive protein. Skin AF decreased significantly in STEMI patients, when measured >200 days after discharge. In STEMI patients, skin AF above the median was predictive of future events (hazard ratio 11.6, 95% CI 1.5 to 90.8, p=0.019). CONCLUSION.: Skin AF is elevated in STEMI, is associated with inflammation and glycaemic stress, and predicts future major adverse cardiac events. (Neth Heart J 2009;17:162-8.Neth Heart J 2009;17:162-8.).
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AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) risk engine has become a standard for cardiovascular risk assessment in type 2 diabetes mellitus. Skin autofluorescence was recently introduced as an alternative tool for cardiovascular risk assessment in diabetes. We investigated the prognostic value of skin autofluorescence for cardiovascular events in combination with the UKPDS risk engine in a cohort of patients with type 2 diabetes managed in primary care. METHODS: Clinical, UKPDS risk engine and skin autofluorescence data were obtained at baseline in 2001-2002 in the type 2 diabetes group (n = 973). Follow-up data concerning fatal and non-fatal cardiovascular events (primary endpoint) were obtained till 2005. Patients were classified as 'low risk' when their 10 year UKPDS risk score for fatal cardiovascular events was <10%, and 'high risk' if >10%. Skin autofluorescence was measured non-invasively with an autofluorescence reader. Skin autofluorescence was classified by the median (i.e. low risk < median, high risk > median). RESULTS: The incidence of cardiovascular events was 119 (44 fatal, 75 non-fatal). In multivariate analysis, skin autofluorescence, age, sex and diabetes duration were predictors for the primary endpoint. Addition of skin autofluorescence information to that from the UKPDS risk engine resulted in re-classification of 55 of 203 patients from the low-risk to the high-risk group. The 10 year cardiovascular event rate was higher in patients with a UKPDS score >10% when skin autofluorescence was above the median (55.8% vs 38.9%). CONCLUSIONS/INTERPRETATION: Skin autofluorescence provides additional information to the UKPDS risk engine which can result in risk re-classification of a substantial number of patients. It furthermore identifies patients who have a particularly high risk for developing cardiovascular events.
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Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/patología , Angiopatías Diabéticas/epidemiología , Piel/efectos de la radiación , Anciano , Análisis de Varianza , Brazo/efectos de la radiación , Presión Sanguínea , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Fluorescencia , Hemoglobina Glucada/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Luz , Masculino , Persona de Mediana Edad , Análisis Multivariante , Médicos de Familia , Pronóstico , Medición de Riesgo , Reino UnidoRESUMEN
Skin autofluorescence (AF) is becoming an accepted clinical method for assessing the risk of chronic complications in diabetes mellitus (DM). In this study, the role of the excitation wavelength in the recognition of increased risk of diabetes-related chronic complications was investigated. An Excitation Emission Matrix Scanner (EEMS) was used to perform noninvasive measurements in four age-matched groups of patients with type 1 and type 2 DM, with and without chronic complications, as well as in a control group (N=97 in total). AF was calculated for excitation wavelengths in the range 355 - 405 nm. Mean spectra were assessed per group. AF values in both type 1 and type 2 DM patients with complications were increased compared to the control subjects (p < 0:01); this ratio remained practically constant, independent of the excitation wavelength. No emission peaks were distinctive for specific patient groups. We conclude that in these groups, no characteristic fluorophores dictate the use of a specific wavelength or set of wavelengths. The results show the validity of applying a broad excitation wavelength range for risk assessment of chronic complications in diabetes.
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Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/fisiopatología , Fluorescencia , Mediciones Luminiscentes , Fenómenos Fisiológicos de la Piel/efectos de la radiación , Rayos Ultravioleta , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
OBJECTIVES: To examine whether skin advanced glycation endproducts (AGEs) accumulation, plasma levels of AGEs-N(epsilon)-carboxymethyllysine (CML) and N(epsilon)-carboxyethyllysine (CEL)-and serum levels of soluble receptor for AGEs (sRAGE) are elevated in SLE patients compared with controls, and whether these parameters are related to disease activity and endothelial cell (EC) activation. METHODS: Ten SLE patients (9 women, age 34 +/- 13 yrs, mean +/- s.d.) and 10 age- and sex-matched controls were included. Patients were analysed during inactive as well as active disease. Skin AGE accumulation was estimated using ultraviolet-A (UV-A) light for measurement of autofluorescence obtained by Excitation-Emission matrix Scanner (AF-EEMS). Levels of CML and CEL were determined by tandem mass spectrometry. Levels of sRAGE and of soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined by ELISAs. RESULTS: Skin AF-EEMS was increased in SLE patients compared with controls (P < 0.05). Levels of CML and CEL were comparable between patients and controls and were not influenced by disease activity. sRAGE and sVCAM-1 levels were higher in quiescent SLE patients compared with controls (P < 0.05) and increased further during active disease (P < 0.05). In patients with quiescent disease and controls, sRAGE levels correlated to sVCAM-1 levels (r = 0.579, P = 0.007). CONCLUSIONS: Skin AGEs and levels of sRAGE and sVCAM-1 were elevated in SLE patients, whereas levels of CML and CEL were comparable with controls. As sRAGE even further increased during endothelial activation, it might be hypothesized that sRAGE acts as a decoy receptor. Why this proposed mechanism is insufficient to prevent increased AGE accumulation in the skin of SLE patients has to be established.
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Productos Finales de Glicación Avanzada/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Piel/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Fluorescencia , Productos Finales de Glicación Avanzada/sangre , Humanos , Lupus Eritematoso Sistémico/sangre , Lisina/análogos & derivados , Lisina/sangre , Masculino , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/sangre , Índice de Severidad de la Enfermedad , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
OBJECTIVE: To investigate whether advanced glycation endproducts (AGEs) are increased in patients with systemic lupus erythematosus (SLE), and are related to atherosclerosis, which is accelerated in SLE, and its traditional and non-traditional disease-related risk factors. METHODS: Fifty-five SLE patients with inactive disease and 55 age- and sex-matched controls were included. The amount of skin autofluorescence (AF), as a measure for the accumulation of AGEs, was assessed by measuring UV-A light excitation-emission matrices (AF-EEMS). Traditional risk factors and disease-related factors were recorded. Plasma levels of C-reactive protein (CRP), as a marker for systemic inflammation, were assessed. Intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. RESULTS: Skin AF-EEMS was increased in SLE patients as compared with controls (1.50 +/- 0.5 a.u. vs 1.28 +/- 0.4 a.u., P = 0.006). Regarding all included risk factors, univariate analyses in patients revealed that AF-EEMS was associated with age (r = 0.48, P < 0.001), IMT (r = 0.35, P = 0.01), creatinine (r = 0.29, P = 0.03), SLICC damage index (r = 0.29, P = 0.03) and disease duration (r = 0.32, P = 0.02). In multivariate analysis, age and disease duration were independent predictors of accumulation of AGEs in SLE (P < 0.001, P = 0.03, respectively). CONCLUSION: AGEs are increased in SLE compared with controls. Our findings indicate that AGE accumulation is associated with disease duration and might contribute to the development of accelerated atherosclerosis in SLE and, therefore, could be used for assessment of risk for long-term vascular complications.
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Productos Finales de Glicación Avanzada/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Piel/metabolismo , Adulto , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Biomarcadores/metabolismo , Arteria Carótida Común/patología , Femenino , Fluorescencia , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
INTRODUCTION: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from lifetime low plasma glucose levels and decreased oxidative stress. METHODS: In 8 GSD Ia patients (age 20-34 years) and 30 matched controls we measured carotid intima-media thickness (IMT), skin autofluorescence (AF; a non-invasive index for AGEs), and specific AGEs (pentosidine, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL)) and collagen linked fluorescence (CLF, measured at excitation/emission wavelength combinations of 328/378 and 370/440 nm) in skin samples. RESULTS: Carotid IMT was significantly lower in GSD Ia patients. Skin AF did not differ between patients and controls. The skin samples showed higher CEL levels in the patient group (p = 0.008), but similar levels of pentosidine, CML, and CLF. In the total group, skin AF correlated with CML (r = 0.39, p = 0.031), CLF 328/378 nm (r = 0.53; p = 0.002) and CLF 370/440 nm (r = 0.60; p = 0.001). In the control group, AF also correlated with the maximum carotid IMT (r = 0.6; p = 0.004). CONCLUSION: Although our data confirm that GSD Ia patients present with a reduced burden of atherosclerosis, this phenomenon cannot be explained by differences in AGE accumulation as measured in the skin.
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Aterosclerosis/diagnóstico , Aterosclerosis/metabolismo , Arterias Carótidas/patología , Productos Finales de Glicación Avanzada/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Adolescente , Adulto , Arginina/análogos & derivados , Arginina/química , Colágeno/química , Femenino , Humanos , Lisina/análogos & derivados , Lisina/química , Masculino , Estrés Oxidativo , Riesgo , Piel/patología , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB) surgery. Blood samples were taken before, during, and after operation from 40 coronary artery bypass grafting patients who were operated with CPB and concomitant hemodilution (CPB, n=20) and who without (nonCPB, n=20). Erythrocyte aggregation was determined with a LORCA aggregometer, during which all samples were standardized to a hematocrit level of 40%. Results showed that in the CPB patients the aggregation index (AI) dropped to 44% of its preoperative baseline level 5 minutes after the start of hemodilution (from 47.7+/-10.1 to 26.6+/-11.4, p<0.01). Meanwhile, plasma concentration of fibrinogen (Fb) dropped to 55%, haptoglobin to 85%, ceruloplasmin to 55%, and albumin to 67%. In the nonCPB patients, however, there was only a slight drop in AI and the concentrations of plasma proteins during the similar period of time. On postoperative day 1, AI was rebounded to 37.1+/-12.4 in CPB patients compared with 44.3+/-11.7 in nonCPB patients. At baseline, AI was correlated only with Fb. During CPB and hemodilution, AI was correlated not only with Fb but also with haptoglobin and ceruloplasmin. Postoperatively, significant correlationship was found between AI and Fb, CRP, haptoglobin, ceruloplasmin, as well as albumin. These results indicate that hemodilution of plasma proteins significantly reduces the aggregability of erythrocytes in patients undergoing CPB. Besides Fb, other plasma proteins also contribute to AI during the early postoperative period when patients are recovering from CPB surgery.
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Proteínas Sanguíneas/análisis , Puente Cardiopulmonar/efectos adversos , Agregación Eritrocitaria , Hemodilución/efectos adversos , Proteínas de Fase Aguda/análisis , Anciano , Pruebas Hematológicas , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
AIMS/HYPOTHESIS: The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence Reader (AFR), could be used to assess skin AGE accumulation. We evaluated the relationship between skin autofluorescence and the severity of diabetic neuropathy. MATERIALS AND METHODS: Skin autofluorescence in arbitrary units (AU) was assessed in 24 diabetic patients with a history of neuropathic foot ulceration (NP(+)), 23 diabetic patients without clinical neuropathy (NP(-)) and 21 control subjects, using the AFR. Arterial occlusive disease was excluded in all. The severity of foot ulceration was assessed by the Wagner score. Peripheral nerve function was assessed by neurography, measuring motor and sensory nerve conduction velocity and amplitude of the median, peroneal and sural nerves. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were measured by Finapres to assess autonomic nervous function. RESULTS: Autofluorescence was increased in NP(-) compared with control subjects. In NP(+) patients, autofluorescence was further increased and correlated with the Wagner score. Autofluorescence correlated negatively with nerve conduction velocity and amplitude, HRV and BRS in both NP(+) and NP(-) groups. Autofluorescence correlated with age, diabetes duration, mean HbA(1)c of the previous year, serum creatinine level, presence of microalbuminuria and severity of diabetic retinopathy. CONCLUSIONS/INTERPRETATION: Skin autofluorescence correlates with the severity of peripheral and autonomic nerve abnormalities in diabetes, even before being clinically manifest. The AFR may be a convenient and rapid clinical tool for assessing risk of progression of long-term diabetic complications.
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Neuropatías Diabéticas/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Piel/metabolismo , Anciano , Albuminuria , Barorreflejo/fisiología , Estudios Transversales , Pie Diabético/patología , Neuropatías Diabéticas/fisiopatología , Femenino , Fluorescencia , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Examen Neurológico , Nervios Periféricos/fisiopatologíaRESUMEN
Not much is known about red cell aggregation during cardio-pulmonary bypass surgery (CPB). Blood samples from 19 patients undergoing CPB were anticoagulated with EDTA. Hematocrit was adjusted to 40%. A red blood cell aggregometer (LORCA) measured changes in light reflection from each blood sample after cessation of the rotation, and calculated an aggregation index (AI). Reflection measurements were stored. Because LORCA software failed for 87 of 171 samples, we developed new software, and applied it to the stored reflection measurements. This software failed only in 7 out of 171 cases and showed that all LORCA failures occurred for AI < 40%. The new calculations revealed that the aggregation index significantly decreased from 46.6 +/- 10.1 (mean +/- standard deviation) baseline to 22.8 +/- 8.3 at the end of CPB and recovered to 37.1 +/- 13.5 at day 1. It is concluded that the new software can be used to study decreased red cell aggregation during CPB.
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Puente de Arteria Coronaria , Agregación Eritrocitaria/fisiología , Hemorreología/instrumentación , Humanos , Modelos Cardiovasculares , Nefelometría y Turbidimetría/instrumentación , Programas InformáticosRESUMEN
AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. METHODS: Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). RESULTS: Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p=0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA(1)c of the previous year and creatinine levels. CONCLUSIONS/INTERPRETATION: The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.
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Arginina/análogos & derivados , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Productos Finales de Glicación Avanzada/metabolismo , Lisina/análogos & derivados , Piel/patología , Adulto , Arginina/sangre , Biopsia , Femenino , Fluorescencia , Productos Finales de Glicación Avanzada/análisis , Humanos , Lisina/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Análisis de Regresión , Piel/citología , Piel/metabolismoRESUMEN
In this review, we hypothesise that, next to biocompatibility, optimal blood compatibility depends on a combination of biomaterials wettability and the shear stress prevailing in the device. The wettability is discussed in seven different categories of devices, that differ substantially from each other with regard to shear stress and exposure time. These seven categories are stents, prosthetic heart valves, vascular prostheses, cardiopulmonary bypass, hemodialysis, vena cava filters and blood bags. In high shear applications, in combination with blood activation, platelet deposition and thrombosis appear to be major problems and platelet inhibitors are most effective. Exposure of blood to a large biomaterial surface, with or without antithrombotic coating, results in reduction of platelet function. Material-independent activation aggravates this process. In low shear applications, platelets only seem supportive for coagulation and anticoagulants should be used.
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Materiales Biocompatibles/efectos adversos , Activación Plaquetaria , Prótesis e Implantes/efectos adversos , Trombosis/etiología , Trombosis/fisiopatología , Animales , Velocidad del Flujo Sanguíneo , Conservación de la Sangre/efectos adversos , Prótesis Vascular/efectos adversos , Puente Cardiopulmonar/efectos adversos , Corazón Artificial/efectos adversos , Humanos , Riñones Artificiales/efectos adversos , Resistencia al Corte , Stents/efectos adversos , HumectabilidadRESUMEN
To investigate the feasibility of instrument-independent perfusion units for laser Doppler flowmetry, a comparison was performed of two commercial fiberoptic laser Doppler perfusion monitors measuring the same flux situation for two different types of probes. In vivo measurements were performed on the cortex of pig's kidney, with an ultrasonic arterial flow meter as reference. The flow was mainly varied by internal arterial constriction using a balloon catheter. For each probe, instruments are compared in terms of the ratio of laser Doppler flux and arterial flow. For a given probe, the flux-to-flow ratios of the two instruments show a linear mutual relationship for a wide variety of arterial flows and laser Doppler fluxes. In vitro measurements were performed on an aqueous suspension of polystyrene microspheres. For the probe with interfiber distance 500 microm the ratio of the in vivo fluxes appears to agree within 16% to the value found in vitro, while for the 250-microm probe a difference of 28% was found. For a wide range of fluxes, the in vivo flux values of one instrument can be translated into flux values for the other instrument, in spite of the instrumental differences. This enables the user to render experimental results independent of the specific instrument, thus facilitating multi-center studies.