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Coen D.a. Stehouwer - One of the best experts on this subject based on the ideXlab platform.
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Semi-automatic assessment of Skin Capillary density: Proof of principle and validation
Microvascular research, 2013Co-Authors: Ed H.b.m. Gronenschild, Coen D.a. Stehouwer, Dennis M.j. Muris, Miranda T. Schram, Ü. Karaca, Alfons J.h.m. HoubenAbstract:Abstract Background Skin Capillary density and recruitment have been proven to be relevant measures of microvascular function. Unfortunately, the assessment of Skin Capillary density from movie files is very time-consuming, since this is done manually. This impedes the use of this technique in large-scale studies. We aimed to develop a (semi-) automated assessment of Skin Capillary density. Methods CapiAna (Capillary Analysis) is a newly developed semi-automatic image analysis application. The technique involves four steps: 1) movement correction, 2) selection of the frame range and positioning of the region of interest (ROI), 3) automatic detection of capillaries, and 4) manual correction of detected capillaries. To gain insight into the performance of the technique, Skin Capillary density was measured in twenty participants (ten women; mean age 56.2 [42–72] years). To investigate the agreement between CapiAna and the classic manual counting procedure, we used weighted Deming regression and Bland–Altman analyses. In addition, intra- and inter-observer coefficients of variation (CVs), and differences in analysis time were assessed. Results We found a good agreement between CapiAna and the classic manual method, with a Pearson's correlation coefficient ( r ) of 0.95 (P 2 . The intra- and inter-observer CVs of CapiAna were 2.5% and 5.6% respectively, while for the classic manual counting procedure these were 3.2% and 7.2%, respectively. Finally, the analysis time for CapiAna ranged between 25 and 35 min versus 80 and 95 min for the manual counting procedure. Conclusion We have developed a semi-automatic image analysis application (CapiAna) for the assessment of Skin Capillary density, which agrees well with the classic manual counting procedure, is time-saving, and has a better reproducibility as compared to the classic manual counting procedure. As a result, the use of Skin capillaroscopy is feasible in large-scale studies, which importantly extends the possibilities to perform microcirculation research in humans.
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obesity is associated with impaired endothelial function in the postprandial state
Microvascular Research, 2011Co-Authors: A.m. Jonk, Erik H. Serné, Alfons J.h.m. Houben, Nicolaas C. Schaper, P. W. De Leeuw, Yvo M. Smulders, Coen D.a. StehouwerAbstract:Adequate microvascular perfusion is essential for the regulation of tissue metabolism. Therefore, defects in microvascular function may play a role in obesity-associated insulin resistance. Steady-state hyperinsulinemia during a euglycemic hyperinsulinemic clamp stimulates endothelium-dependent vasodilation and Capillary recruitment, which contribute to increased glucose uptake. These phenomena have been shown to be blunted in obesity. If insulin's effects on microcirculatory function indeed play a physiological role in regulating insulin-mediated glucose uptake, such effects should be demonstrable not only during steady-state hyperinsulinemia, but also after meal ingestion. We investigated whether similar responses occur after ingestion of a glucose load or a mixed meal. We examined the effects of a glucose drink, a mixed meal drink, or a control drink (water) on Skin Capillary density (i.e. baseline Capillary density, hyperemic Capillary recruitment, and density during venous congestion, using capillaroscopy) and Skin endothelium-(in)dependent vasodilation (using laser-Doppler flowmetry with iontophoresis of acetylcholine and sodium nitroprusside) in 20 lean and 19 obese individuals. In lean individuals, neither the glucose nor the mixed meal drink induced a significant effect on Capillary density or endothelium-(in)dependent vasodilation. Possibly this is related to the modest plasma insulin levels as compared to the insulin clamp. In obese individuals, the mixed meal drink, compared to the control drink, decreased baseline Skin perfusion (P<0.05) and acetylcholine-mediated vasodilation (P<0.05), while no effect of the drinks on Capillary density was found. Compared to lean individuals, obese individuals had impaired acetylcholine-mediated vasodilation after meal ingestion (P=0.02). The latter findings are consistent with impaired postprandial microvascular function in obesity.
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tnf α levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf α and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, Mirjam M Van Weissenbruch, John S Yudkin, Henriette Delemarrevan A De Waal, Coen D.a. StehouwerAbstract:: The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
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tnf alpha levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf alpha and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, John S Yudkin, Henriette Delemarrevan A De Waal, Mirjam M Van Weissenbruch, Coen D.a. StehouwerAbstract:The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
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impaired microvascular function in obesity implications for obesity associated microangiopathy hypertension and insulin resistance
Circulation, 2004Co-Authors: Renate T De Jongh, Richard G Ijzerman, Greetje De Vries, Erik H. Serné, Coen D.a. StehouwerAbstract:Background— Obesity is associated with an increased risk of developing microangiopathy, hypertension, and insulin resistance. We hypothesized that obesity is a primary cause of microvascular dysfunction, which may contribute to the development of these obesity-related disorders. Methods and Results— We examined microvascular function in 16 lean (body mass index 30 kg/m2) healthy women (mean age, 38.9±6.7 years) in the basal state and during physiological systemic hyperinsulinemia. We determined Skin Capillary recruitment after arterial occlusion with capillaroscopy and Skin endothelium–(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside. Obese women, compared with lean women, had higher systolic blood pressure (P<0.05), impaired insulin sensitivity (P<0.01), impaired Capillary recruitment in the basal state (P<0.05) and during hyperinsulinemia (P<0.05), and impaired acetylcholine-mediated vasodilation in the basal state (P<0.05) a...
Erik H. Serné - One of the best experts on this subject based on the ideXlab platform.
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proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds which is part of generalized microangiopathy
Diabetes Care, 2014Co-Authors: Jorn Woerdeman, Eelco Van Duinkerken, Frank J. Snoek, Frederik Barkhof, Mike P. Wattjes, Annette C Moll, Martin Klein, M P De Boer, R G Ijzerman, Erik H. SernéAbstract:OBJECTIVE We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS Thirty-three patients with proliferative diabetic retinopathy (PDR+), 34 patients without proliferative diabetic retinopathy, and 33 controls underwent magnetic resonance imaging to assess cerebral microangiopathy (cerebral microbleeds) and ischemic damage (white matter hyperintensities and lacunes). Peripheral microvascular function, i.e., Skin Capillary density and Capillary recruitment, was assessed by Capillary microscopy. RESULTS Cerebral microbleeds, but not ischemic damage, were more prevalent in PDR+ patients versus the other groups (P < 0.05). A trend was found across groups for the lowest baseline Capillary density in PDR+ patients (P for trend = 0.05). In individuals with microbleeds, Capillary recruitment was impaired compared with those without microbleeds (P = 0.04). CONCLUSIONS In PDR+ patients, cerebral microbleed prevalence was higher and seems part of generalized microangiopathy that may affect the Skin and the brain.
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PS9 - 5. Proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds and decreased Skin Capillary density
Nederlands Tijdschrift voor Diabetologie, 2013Co-Authors: Jorn Woerdeman, Richard G Ijzerman, Erik H. Serné, Eelco Van Duinkerken, Frank J. Snoek, Frederik Barkhof, Mike P. Wattjes, Michaela DiamantAbstract:Small vessel disease (SVD) accounts for most of the strokes in type 1 diabetes mellitus (T1DM). Retinal microvascular changes appear to reflect cerebral SVD, but whether diabetic proliferative retinopathy (PDR) is associated with cerebral SVD is unknown. Moreover, it is unclear whether SVD is limited to the brain or part of a generalized microvascular disorder.
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obesity is associated with impaired endothelial function in the postprandial state
Microvascular Research, 2011Co-Authors: A.m. Jonk, Erik H. Serné, Alfons J.h.m. Houben, Nicolaas C. Schaper, P. W. De Leeuw, Yvo M. Smulders, Coen D.a. StehouwerAbstract:Adequate microvascular perfusion is essential for the regulation of tissue metabolism. Therefore, defects in microvascular function may play a role in obesity-associated insulin resistance. Steady-state hyperinsulinemia during a euglycemic hyperinsulinemic clamp stimulates endothelium-dependent vasodilation and Capillary recruitment, which contribute to increased glucose uptake. These phenomena have been shown to be blunted in obesity. If insulin's effects on microcirculatory function indeed play a physiological role in regulating insulin-mediated glucose uptake, such effects should be demonstrable not only during steady-state hyperinsulinemia, but also after meal ingestion. We investigated whether similar responses occur after ingestion of a glucose load or a mixed meal. We examined the effects of a glucose drink, a mixed meal drink, or a control drink (water) on Skin Capillary density (i.e. baseline Capillary density, hyperemic Capillary recruitment, and density during venous congestion, using capillaroscopy) and Skin endothelium-(in)dependent vasodilation (using laser-Doppler flowmetry with iontophoresis of acetylcholine and sodium nitroprusside) in 20 lean and 19 obese individuals. In lean individuals, neither the glucose nor the mixed meal drink induced a significant effect on Capillary density or endothelium-(in)dependent vasodilation. Possibly this is related to the modest plasma insulin levels as compared to the insulin clamp. In obese individuals, the mixed meal drink, compared to the control drink, decreased baseline Skin perfusion (P<0.05) and acetylcholine-mediated vasodilation (P<0.05), while no effect of the drinks on Capillary density was found. Compared to lean individuals, obese individuals had impaired acetylcholine-mediated vasodilation after meal ingestion (P=0.02). The latter findings are consistent with impaired postprandial microvascular function in obesity.
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tnf α levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf α and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, Mirjam M Van Weissenbruch, John S Yudkin, Henriette Delemarrevan A De Waal, Coen D.a. StehouwerAbstract:: The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
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tnf alpha levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf alpha and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, John S Yudkin, Henriette Delemarrevan A De Waal, Mirjam M Van Weissenbruch, Coen D.a. StehouwerAbstract:The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
Eduardo Tibiriçá - One of the best experts on this subject based on the ideXlab platform.
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evaluation of microvascular endothelial function and Capillary density in patients with infective endocarditis using laser speckle contrast imaging and video capillaroscopy
Microvascular Research, 2018Co-Authors: Amanda Barcelos, Eduardo Tibiriçá, Cristiane LamasAbstract:Abstract Objective To evaluate the systemic microcirculation of patients with infective endocarditis (IE). Methods This is a comparative study of patients with definite IE by the modified Duke criteria admitted to our center for treatment. A reference group of sex- and age-matched healthy volunteers was included. Microvascular flow was evaluated in the forearm using a laser speckle contrast imaging system, for noninvasive measurement of cutaneous microvascular perfusion, in combination with Skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to test microvascular reactivity. Microvascular density was evaluated using Skin video-capillaroscopy. Results We studied 22 patients with IE; 15 were male and seven female. The mean age and standard deviation (SD) were 45.5 ± 17.3 years. Basal Skin microvascular conductance was significantly increased in patients with IE, compared with healthy individuals (0.36 ± 0.13 versus 0.21 ± 0.08 APU/mmHg; P Conclusions The main findings in the microcirculation of patients with IE were greater basal vasodilation and a reduction of the endothelium-dependent and -independent microvascular reactivity, as well as greater functional Skin Capillary density compared to healthy individuals.
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Skin Capillary density and microvascular reactivity in obese subjects with and without metabolic syndrome
Microvascular Research, 2011Co-Authors: E A Francischetti, Eduardo Tibiriçá, Elba Rodrigues, Elizabete Goes Da Silva, Bruno M J Celoria, Virginia Genelhu De AbreuAbstract:Obesity is associated with increased cardiovascular morbidity and mortality. We hypothesized that microvascular function may be impaired in obese subjects with metabolic syndrome (OB-MetSnd) compared to obese subjects without MetSnd (OB) and healthy subjects (HS). In this cross-sectional study, we evaluated Skin Capillary density (SCD) in OB-MetSnd (n=20, 12 women, BMI=36.5±1.1kg/m(2)), OB (n=25, 16 women, BMI=34.5±0.7kg/m(2)), and HS (n=30, 22 women, BMI=22.8±0.3kg/m(2)) groups. SCD was evaluated by intravital video-microscopy at rest and after post-occlusive reactive hyperemia (PORH) and venous congestion (VC). OB-MetSnd subjects exhibited significant differences in the values of MetSnd components and in leptin and HOMA-IR levels compared to OB and HS individuals. There were no differences in SCD among groups in resting conditions. The OB-MetSnd group failed to show a significant increase in the number of recruited capillaries during PORH and VC compared to the SCD evaluated at rest. A negative correlation of SCD with waist circumference, BMI, blood pressure, and HOMA-IR was observed after PORH and VC. When obese subjects were analyzed according to their HOMA-IR quartiles, a significant decrease in SCD was observed during POHR (P=0.02). Our findings showed that obese subjects have structural and functional alterations in Skin microcirculation that are proportional to the increase in the degree of global and central obesity. In addition, in OB-MetSnd subjects, the cutaneous capillaries at rest are already maximally recruited, indicating an absence of functional Capillary reserve. This may be related to the insulin resistance observed in OB-MetSnd individuals.
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endothelial function in patients with type 1 diabetes evaluated by Skin Capillary recruitment
Microvascular Research, 2007Co-Authors: Eduardo Tibiriçá, Elba Rodrigues, Roberta Arnoldi Cobas, Marilia B GomesAbstract:The aim of the present study was to evaluate Skin Capillary density and recruitment of the upper and lower extremities of patients with type 1 diabetes under chronic treatment without clinical manifestations of diabetes-related complications. This cross-sectional observational study included 59 (27.1+/-10.6 years) consecutive outpatients with type 1 diabetes [duration 10 (1; 45) years] and 41 age- and sex-matched healthy controls. We used intravital video-microscopy to measure basal and maximal (during venous congestion) Skin Capillary densities as well as Capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers and toes. Mean Capillary density (MCD) of the fingers at baseline was not different between controls and patients (123.02+/-22.6 and 132.3+/-28.9 capillaries/mm(2), respectively; P=0.08). In contrast, baseline MCD of the toes was lower in controls, when compared to patients (84.6+/-19.8 and 96.2+/-23.4 capillaries/mm(2), respectively; P=0.01). Capillary recruitment during PORH (% increase of the number of capillaries/mm(2)) was significantly higher in controls compared to patients both in fingers [7 (-8; 33) and -1.0 (-35, 13), respectively; P=0.000] and toes [6 (-20; 46) and 0 (-24; 20), respectively; P=0.000]. During venous occlusion, Capillary density increase (% increase of the number of capillaries/mm(2)) was also higher in controls compared to patients both in fingers [3 (-14; 23) and 0.0 (-30; 29.2), respectively; P=0.02] and toes [9.3 (-18; 51) and -7 (-34; 22), respectively; P=0.000]. Our results showed that patients with type 1 diabetes, although not presenting Skin Capillary rarefaction, display Skin microvascular functional alterations in both extremities characterized by an absence of Capillary reserve.
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impairment of Skin Capillary recruitment precedes chronic complications in patients with type 1 diabetes
The review of diabetic studies : RDS, 2007Co-Authors: Eduardo Tibiriçá, Elba Rodrigues, Roberta Arnoldi Cobas, Marilia B GomesAbstract:Microvascular function in patients with type 1 diabetes without chronic complications was assessed using Skin Capillary recruitment during post-occlusive reactive hyperemia (PORH). Structural (maximal) Capillary density was evaluated during venous occlusion. The study included 48 consecutive outpatients aged 26.3 ± 10.8 years with type 1 diabetes (duration of 9.5 years) without chronic complications and 34 control subjects. Intravital Capillary video-microscopy was used in the dynamic study of Skin capillaries in the dorsum of the fingers and toes. Capillary recruitment during PORH (% increase in mean Capillary density, MCD) was significantly higher in the controls than the patients in both the fingers (p < 0.001) and toes (p < 0.001). During venous occlusion, MCD increase was also higher in the controls than the patients in both the fingers (p < 0.05) and toes (p < 0.0001). In patients, no difference was found between MCD at baseline and after venous occlusion in the fingers but a decrease was observed in the toes (p < 0.001). It is concluded that Skin Capillary function is significantly impaired in both fingers and toes of patients with type 1 diabetes without chronic complications. Moreover, Capillary density during venous occlusion did not increase in either extremity in the patients, suggesting that their capillaries at rest are already maximally recruited.
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Increased Skin Capillary density in treated essential hypertensive patients.
American journal of hypertension, 2006Co-Authors: Haythem Debbabi, Laurent Uzan, Jean-jacques Mourad, Michel E. Safar, Bernard I. Levy, Eduardo TibiriçáAbstract:Background Microvascular rarefaction is a hallmark of essential hypertension. We measured the Skin Capillary density in nondiabetic hypertensive subjects with effective antihypertensive treatment and evaluated possible correlations with arterial blood pressure (BP). Methods This cross-sectional observational study included 76 (55 ± 1 years) consecutive outpatients with essential hypertension under chronic antihypertensive drug treatment (BP Results Baseline and maximal Capillary densities (number/mm2) were significantly lower (59.6 ± 2.0 and 62.0 ± 1.9) in untreated than in treated hypertensive patients (74.0 ± 1.4 and 79.4 ± 1.5; P Conclusions In nondiabetic hypertensive patients, Capillary density is reduced in association with a cluster of cardiovascular risk factors involving tobacco consumption and obesity. The finding of an increased Capillary density in effectively treated antihypertensives suggests that a cause-to-effect relationship between BP and Capillary density should be evaluated in a long-term prospective follow-up.
Richard G Ijzerman - One of the best experts on this subject based on the ideXlab platform.
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PS9 - 5. Proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds and decreased Skin Capillary density
Nederlands Tijdschrift voor Diabetologie, 2013Co-Authors: Jorn Woerdeman, Richard G Ijzerman, Erik H. Serné, Eelco Van Duinkerken, Frank J. Snoek, Frederik Barkhof, Mike P. Wattjes, Michaela DiamantAbstract:Small vessel disease (SVD) accounts for most of the strokes in type 1 diabetes mellitus (T1DM). Retinal microvascular changes appear to reflect cerebral SVD, but whether diabetic proliferative retinopathy (PDR) is associated with cerebral SVD is unknown. Moreover, it is unclear whether SVD is limited to the brain or part of a generalized microvascular disorder.
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tnf α levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf α and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, Mirjam M Van Weissenbruch, John S Yudkin, Henriette Delemarrevan A De Waal, Coen D.a. StehouwerAbstract:: The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
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tnf alpha levels are associated with Skin Capillary recruitment in humans a potential explanation for the relationship between tnf alpha and insulin resistance
Clinical Science, 2006Co-Authors: Richard G Ijzerman, Erik H. Serné, Jasper J Voordouw, John S Yudkin, Henriette Delemarrevan A De Waal, Mirjam M Van Weissenbruch, Coen D.a. StehouwerAbstract:The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in Capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, Skin Capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both Capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, Capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for Capillary recruitment. In the children, neither Capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with Capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.
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impaired microvascular function in obesity implications for obesity associated microangiopathy hypertension and insulin resistance
Circulation, 2004Co-Authors: Renate T De Jongh, Richard G Ijzerman, Greetje De Vries, Erik H. Serné, Coen D.a. StehouwerAbstract:Background— Obesity is associated with an increased risk of developing microangiopathy, hypertension, and insulin resistance. We hypothesized that obesity is a primary cause of microvascular dysfunction, which may contribute to the development of these obesity-related disorders. Methods and Results— We examined microvascular function in 16 lean (body mass index 30 kg/m2) healthy women (mean age, 38.9±6.7 years) in the basal state and during physiological systemic hyperinsulinemia. We determined Skin Capillary recruitment after arterial occlusion with capillaroscopy and Skin endothelium–(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside. Obese women, compared with lean women, had higher systolic blood pressure (P<0.05), impaired insulin sensitivity (P<0.01), impaired Capillary recruitment in the basal state (P<0.05) and during hyperinsulinemia (P<0.05), and impaired acetylcholine-mediated vasodilation in the basal state (P<0.05) a...
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direct evidence for insulin induced Capillary recruitment in Skin of healthy subjects during physiological hyperinsulinemia
Diabetes, 2002Co-Authors: Erik H. Serné, Richard G Ijzerman, Greetje De Vries, Reinder Evertz, Reinold Gans, Ab J M Donker, Robin Nijveldt, Coen D.a. StehouwerAbstract:It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on Skin microvascular function in eight healthy nondiabetic subjects. In addition, the effects of locally administered insulin on Skin blood flow were assessed in 10 healthy subjects. During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion plethysmography, Skin Capillary density with capillaroscopy, endothelium-(in)dependent vasodilatation of Skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and Skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude nonspecific changes in the hemodynamic variables, a time-volume control study was performed. Insulin iontophoresis was used to study the local effects of insulin on Skin blood flow. Compared to the control study, systemic hyperinsulinemia caused an increase in leg blood flow (−0.54 ± 0.93 vs. 1.97 ± 1.1 ml · min −1 · dl −1 ; P 2 ; P 2 ; P P P P P 1 ) induces recruitment of capillaries, 2 ) augments nitric oxide−mediated vasodilatation, and 3 ) influences vasomotion. In addition, locally administered insulin 4 ) induces a rapid increase in total Skin blood flow, independent of systemic effects.
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Skin Capillary density in infants born to normotensive mothers a comparison between singleton and twin infants
Microcirculation, 2014Co-Authors: Rajendra Raghuraman, Isaac Manyonda, Rohan Dsouza, Preetha Nathan, Duolao Wang, Tarek F AntoniosAbstract:Objective: Twin infants tend to have LBW and microvascular alterations but do not appear to have an increase in cardiovascular mortality later in life as singleton infants. We hypothesized that twin infants born to normotensive mothers would not have Capillary rarefaction at birth. Methods: We studied 26 dizygotic twin infants and compared them with 115 consecutive singleton infants to normotensive mothers. We used orthogonal polarized spectroscopy to measure basal (i.e., functional) and maximal (i.e., structural) Skin Capillary density according to a well-standardized protocol. Results: Twin infants have significantly higher BCD (mean difference 4.3 capillaries/mm2, 95% CI: 0.4, 8.1, p = 0.03) and have marginally significantly higher MCD (mean difference 3.9 capillaries/mm2, 95% CI: -0.6, 8.3, p = 0.086) compared to singleton infants. Birth weight was significantly associated with BCD and MCD (p = 0.003 and 0.006). Conclusions: Twin infants with low and NBWs tend to have higher functional and structural Capillary densities compared to singleton infants. Further longitudinal studies of Skin Capillary density and of retinal vascular parameters commencing from birth to various stages in early childhood are essential to identify the dynamics and the exact timing, if any, of the remodeling of microcirculation in these individuals. © 2013 John Wiley & Sons Ltd.
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142 Onset of preeclampsia is preceded by structural Capillary rarefaction
Heart, 2012Co-Authors: Vivek Nama, Isaac Manyonda, Joseph Onwude, Tarek F AntoniosAbstract:Introduction Microvascular rarefaction, defined as reduced vascular density, is a consistent finding in hypertension. Functional and structural Capillary rarefaction occurs in individuals with sustained and borderline essential hypertension, and in their normotensive offspring. Women who develop preeclampsia are at increased risk of hypertension in later life. We hypothesised that Capillary rarefaction precedes the onset of preeclampsia and could play a role in its pathogenesis. Methods In this longitudinal cohort study we recruited 322 Caucasian women, of which 305 subjects completed the study. We used intravital video-microscopy to measure basal (ie, functional) and maximal (ie, structural) Skin Capillary densities according to a well-validated protocol and measured plasma angiogenic and anti-angiogenic factors. Subjects were studied at five consecutive visits. Results Preeclampsia occurred in 16 women (mean onset at 35.6±4.8 weeks) and 272 women had normal pregnancy. In women with normal pregnancy significant structural reduction in Capillary density occurred at 27–32 weeks, which had resolved by the puerperium (mean change: −2.2 capillaries/field, 95% CI −3.6 to −0.7). In contrast, in women who developed preeclampsia, more significant structural rarefaction was observed earlier at 20–24 weeks (mean change: −6.1 capillaries/field, 95% CI −9.2 to −2.9), which persisted into the puerperium. We also found that the change in soluble Endoglin from 11–16 weeks to 27–32 weeks was significantly correlated with the change in structural Capillary density. Conclusions This is the first study to show that significant structural Capillary rarefaction precedes the onset of preeclampsia. Capillary rarefaction could play a role in the pathogenesis of this disease.
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effect of modest salt reduction on Skin Capillary rarefaction in white black and asian individuals with mild hypertension
Hypertension, 2010Co-Authors: Maciej Marciniak, Tarek F AntoniosAbstract:Microvascular rarefaction occurs in hypertension. We carried out a 12-week randomized double-blind crossover trial to determine the effect of a modest reduction in salt intake on Capillary rarefaction in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. Both basal and maximal (during venous congestion) Skin Capillary density were measured by capillaroscopy at the dorsum and the side of the fingers. In addition, we used orthogonal polarization spectral imaging to measure Skin Capillary density at the dorsum of the fingers and the hand web. With a reduction in salt intake from 9.7 to 6.5 g/day, there was an increase in Capillary density (capillaries per millimeter squared) from 10121 to 10623 (basal) and 10822 to 11522 (maximal) at the dorsum, and 10125 to 10726 (basal) and 11026 to 11626 (maximal) at the side of the fingers (P0.001 for all). Orthogonal polarization spectral imaging also showed a significant increase in Capillary density both at the dorsum of the fingers and the web. Subgroup analysis showed that most of the changes were significant in all of the ethnic groups. Furthermore, there was a significant relationship between the change in 24-hour urinary sodium and the change in Capillary density at the side of the fingers. These results demonstrate that a modest reduction in salt intake, as currently recommended, improves both functional and structural Capillary rarefactions that occur in hypertension, and a larger reduction in salt intake would have a greater effect. The increase in Capillary density may possibly carry additional beneficial effects on target organs. (Hypertension. 2010;56:253-259.)
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rarefaction of Skin capillaries in normotensive offspring of individuals with essential hypertension
Heart, 2003Co-Authors: Tarek F Antonios, Nirmala D Markandu, Donald R. J. Singer, Peter S. Mortimer, F Rattray, Graham A MacgregorAbstract:Background: Rarefaction of Skin capillaries in people with intermittent borderline essential hypertension suggests a primary or an early abnormality that may antedate the onset of sustained hypertension. Objective: To compare Skin Capillary density in subjects with and without a family history of essential hypertension. Subjects: 21 normotensive individuals, one or both of whose parents had essential hypertension (mean age 39.3 years; blood pressure 124/79 mm Hg); 21 normotensive controls with no family history of hypertension (age 46.3 years; blood pressure 124/78 mm Hg). Methods: The Skin of the dorsum of the fingers was examined by intravital Capillary microscopy before and after venous congestion at 60 mm Hg for two minutes. Results: By analysis of variance, both baseline and maximum Skin Capillary density were lower in subjects with a family history of essential hypertension than in those with no family history (baseline: 67 v 79 capillaries per field, p = 0.008; maximum: 74 v 93 capillaries per field, p < 0.0005). Conclusions: Capillary rarefaction in essential hypertension may occur before the increase in blood pressure and could, at least in part, reflect a primary rather than a secondary abnormality.
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Skin Capillary density changes in normal pregnancy and pre-eclampsia.
Journal of hypertension, 2002Co-Authors: Khaled M. Hasan, Isaac Manyonda, Donald R. J. Singer, Tarek F AntoniosAbstract:Background Many abnormalities are known to occur in the microcirculation in essential hypertension, including reduction in Capillary density or rarefaction. Peripheral vasodilatation and angiogenesis are critical components of the physiological adaptation in normal pregnancy.Objective To investigate
