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Higher levels of daily physical activity are associated with better skin microvascular function in type 2 diabetes-The Maastricht Study.
Sörensen, BM, van der Heide, FCT, Houben, AJHM, Koster, A, T J M Berendschot, T, S A G Schouten, J, Kroon, AA, van der Kallen, CJH, Henry, RMA, van Dongen, MCJM, et al
Microcirculation (New York, N.Y. : 1994). 2020;(4):e12611
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Abstract
OBJECTIVE Physical activity may provide a means for the prevention of cardiovascular disease via improving microvascular function. Therefore, this study investigated whether physical activity is associated with skin and retinal microvascular function. METHODS In The Maastricht Study, a population-based cohort study enriched with type 2 diabetes (n = 1298, 47.3% women, aged 60.2 ± 8.1 years, 29.5% type 2 diabetes), we studied whether accelerometer-assessed physical activity and sedentary time associate with skin and retinal microvascular function. Associations were studied by linear regression and adjusted for major cardiovascular risk factors. In addition, we investigated whether associations were stronger in type 2 diabetes. RESULTS In individuals with type 2 diabetes, total physical activity and higher-intensity physical activity were independently associated with greater heat-induced skin hyperemia (regression coefficients per hour), respectively, 10 (95% CI: 1; 18) and 36 perfusion units (14; 58). In individuals without type 2 diabetes, total physical activity and higher-intensity physical activity were not associated with heat-induced skin hyperemia. No associations with retinal arteriolar %-dilation were identified. CONCLUSION Higher levels of total and higher-intensity physical activity were associated with greater skin microvascular vasodilation in individuals with, but not in those without, type 2 diabetes.
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Improvement of skin condition in striae distensae: development, characterization and clinical efficacy of a cosmetic product containing Punica granatum seed oil and Croton lechleri resin extract.
Bogdan, C, Iurian, S, Tomuta, I, Moldovan, M
Drug design, development and therapy. 2017;:521-531
Abstract
Striae distensae are a frequent skin condition associated with pregnancy, weight change or lack of skin elasticity. The aim of this research was to obtain a topical product containing herbal active ingredients with documented antioxidant and anti-inflammatory activity (Punica granatum seed oil and Croton lechleri resin extract) and demonstrate its positive effect on prevention and treatment of striae distensae. First, the cream base formulation was optimized through experimental design. Secondly, the cream containing the two active ingredients was investigated in an interventional nonrandomized clinical trial. The clinical outcome was assessed through biophysical parameters and ultrasonographic evaluation. The state of the skin was evaluated by biophysical measurements and ultrasonography at the beginning of the study and after 3 and 6 weeks. The experimental design was successfully used to set the best ranges for the technological and formulation factors to obtain a cosmetic formulation with optimal characteristics. The study of clinical efficacy on the optimal formulation revealed an increase in the dermis thickness, hydration and elasticity values in both groups after 6 weeks of cream application. The new oil-in-water cream containing P. granatum seed oil and C. lechleri resin extract can be helpful in the prevention or improving of skin changes associated with striae.
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Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation.
Salimi, S, Lewis, JP, Yerges-Armstrong, LM, Mitchell, BD, Saeed, F, O'Connell, JR, Perry, JA, Ryan, KA, Shuldiner, AR, Parsa, A
Journal of the American Heart Association. 2016;(11)
Abstract
BACKGROUND Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function. METHODS AND RESULTS Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (P<0.001). Clopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures. CONCLUSIONS The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396.
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Skin collagen advanced glycation endproducts (AGEs) and the long-term progression of sub-clinical cardiovascular disease in type 1 diabetes.
Monnier, VM, Sun, W, Gao, X, Sell, DR, Cleary, PA, Lachin, JM, Genuth, S, ,
Cardiovascular diabetology. 2015;:118
Abstract
BACKGROUND We recently reported strong associations between eight skin collagen AGEs and two solubility markers from skin biopsies obtained at DCCT study closeout and the long-term progression of microvascular disease in EDIC, despite adjustment for mean glycemia. Herein we investigated the hypothesis that some of these AGEs (fluorescence to be reported elsewhere) correlate with long-term subclinical cardiovascular disease (CVD) measurements, i.e. coronary artery calcium score (CAC) at EDIC year 7-9 (n = 187), change of carotid intima-media thickness (IMT) from EDIC year 1 to year 6 and 12 (n = 127), and cardiac MRI outcomes at EDIC year 15-16 (n = 142). METHODS Skin collagen AGE measurements obtained from stored specimens were related to clinical data from the DCCT/EDIC using Spearman correlations and multivariable logistic regression analyses. RESULTS Spearman correlations showed furosine (early glycation) was associated with future mean CAC (p < 0.05) and CAC >0 (p = 0.039), [corrected] but not with CAC score <100 vs. >100. Glucosepane and pentosidine crosslinks, methylglyoxal hydroimidazolones (MG-H1) and pepsin solubility (inversely) correlated with IMT change from year 1 to 6(all P < 0.05). Left ventricular (LV) mass (cMRI) correlated with MG-H1, and inversely with pepsin solubility (both p < 0.05), while the ratio LV mass/end diastolic volume correlated with furosine and MG-H1 (both p < 0.05), and highly with CML (p < 0.01). In multivariate analysis only furosine (p = 0.01) was associated with CAC. In contrast IMT was inversely associated with lower collagen pepsin solubility and positively with glucosepane, CONCLUSIONS In type 1 diabetes, multiple AGEs are associated with IMT progression in spite of adjustment for A1c implying a likely participatory role of glycation and AGE mediated crosslinking on matrix accumulation in coronary arteries. This may also apply to functional cardiac MRI outcomes, especially left ventricular mass. In contrast, early glycation measured by furosine, but not AGEs, was associated with CAC score, implying hyperglycemia as a risk factor in calcium deposition perhaps via processes independent of glycation. TRIAL REGISTRATION Registered at Clinical trial reg. nos. NCT00360815 and NCT00360893, http://www.clinicaltrials.gov.
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Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations.
Iredahl, F, Löfberg, A, Sjöberg, F, Farnebo, S, Tesselaar, E
PloS one. 2015;(8):e0133760
Abstract
INTRODUCTION Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. METHOD Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. RESULTS Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p<0.001) and RBC concentration (TiVi: baseline 119±18; 10-min 150±41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0±4.4 PU; 10-min 38.9±5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6±11.8 AU; 10-min 54.4±13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8±3.6 PU; max 112±55 PU; p<0.001, LSCI baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. CONCLUSION LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses.
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Skin and plasma carotenoid response to a provided intervention diet high in vegetables and fruit: uptake and depletion kinetics.
Jahns, L, Johnson, LK, Mayne, ST, Cartmel, B, Picklo, MJ, Ermakov, IV, Gellermann, W, Whigham, LD
The American journal of clinical nutrition. 2014;(3):930-7
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Abstract
BACKGROUND Objective biomarkers are needed to assess adherence to vegetable and fruit intervention trials. Blood carotenoids are considered the best biomarker of vegetable and fruit intake, but collecting blood is invasive and the analyses are relatively expensive for population studies. Resonance Raman spectroscopy (RRS) is an innovative method for assessing carotenoids in skin noninvasively. OBJECTIVE Our objective was to compare blood carotenoid concentrations with skin carotenoid assessments by RRS during a controlled feeding intervention. DESIGN Twenty-nine participants consumed low-carotenoid diets (6 wk, phases 1 and 3), a provided diet containing 6-cup equivalents (1046 g/d) of vegetables and fruit (8 wk, phase 2), and usual diet (final 8 wk, phase 4). RESULTS At baseline, skin and plasma total carotenoid values were correlated (r = 0.61, P < 0.001). Skin and plasma carotenoid values decreased (P < 0.001) 36% and 30%, respectively, from baseline to the end of phase 1 and then increased (P < 0.001) by >200% at the end of phase 2. Plasma carotenoids returned to baseline concentrations by the middle of phase 3 and skin carotenoid concentrations by the middle of phase 4. Skin carotenoid status predicted plasma values by using a mixed linear model including all time points (r = 0.72, P < 0.001), which indicates that changes in skin carotenoid status closely follow changes in plasma across a broad range of intakes. At the individual level, skin carotenoids predicted plasma values (r = 0.70, P < 0.001) over all time points. CONCLUSION Skin carotenoid status assessed by resonance Raman spectroscopy is a noninvasive, objective biomarker of changes in vegetable and fruit intake.
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Noninvasive skin fluorescence spectroscopy is comparable to hemoglobin A1c and fasting plasma glucose for detection of abnormal glucose tolerance.
Olson, BP, Matter, NI, Ediger, MN, Hull, EL, Maynard, JD
Journal of diabetes science and technology. 2013;(4):990-1000
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Abstract
AIM: We compare performance of noninvasive skin fluorescence spectroscopy (SFS), fasting plasma glucose (FPG), and hemoglobin A1c (A1C) for detection of abnormal glucose tolerance (AGT). METHODS The NSEEDS trial evaluated SFS, FPG, and A1C in an at-risk population of 479 previously undiagnosed subjects from nine US centers, each of whom received a 75 g, 2 h oral glucose tolerance test (OGTT). Skin fluorescence spectra were collected and analyzed with SCOUT DS® devices. Disease truth was AGT, defined as OGTT ≥140 mg/dl. Abnormal glucose tolerance sensitivity, false positive rate (FPR), and receiver operating characteristic (ROC) curves were computed for each measurement technique. Skin fluorescence spectroscopy reproducibility was also assessed. RESULTS The AGT sensitivity of SFS was 68.2%, higher than that of FPG (thresholds of 100 and 110 mg/dl) and A1C (thresholds of 5.7% and 6.0%). The FPR of SFS was 37.7%, comparable to A1C at the 5.7% threshold (30.7%). Partial ROC areas of SFS, FPG, and A1C were similar for FPRs of 20-50% (average sensitivities of 64.0%, 59.0%, and 68.6%, respectively). The interday coefficient of variation for SFS was 7.6%. CONCLUSIONS Skin fluorescence spectroscopy has similar screening performance to FPG and A1C and is a viable approach for detection of AGT.
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In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin.
Balu, M, Mazhar, A, Hayakawa, CK, Mittal, R, Krasieva, TB, König, K, Venugopalan, V, Tromberg, BJ
Biophysical journal. 2013;(1):258-67
Abstract
We employ a clinical multiphoton microscope to monitor in vivo and noninvasively the changes in reduced nicotinamide adenine dinucleotide (NADH) fluorescence of human epidermal cells during arterial occlusion. We correlate these results with measurements of tissue oxy- and deoxyhemoglobin concentration during oxygen deprivation using spatial frequency domain imaging. During arterial occlusion, a decrease in oxyhemoglobin corresponds to an increase in NADH fluorescence in the basal epidermal cells, implying a reduction in basal cell oxidative phosphorylation. The ischemia-induced oxygen deprivation is associated with a strong increase in NADH fluorescence of keratinocytes in layers close to the stratum basale, whereas keratinocytes from epidermal layers closer to the skin surface are not affected. Spatial frequency domain imaging optical property measurements, combined with a multilayer Monte Carlo-based radiative transport model of multiphoton microscopy signal collection in skin, establish that localized tissue optical property changes during occlusion do not impact the observed NADH signal increase. This outcome supports the hypothesis that the vascular contribution to the basal layer oxygen supply is significant and these cells engage in oxidative metabolism. Keratinocytes in the more superficial stratum granulosum are either supplied by atmospheric oxygen or are functionally anaerobic. Based on combined hemodynamic and two-photon excited fluorescence data, the oxygen consumption rate in the stratum basale is estimated to be ∼0.035 μmoles/10(6) cells/h.
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Skin bleeding time for the evaluation of uremic platelet dysfunction and effect of dialysis.
Soyoral, YU, Demir, C, Begenik, H, Esen, R, Kucukoglu, ME, Aldemir, MN, Demirkiran, D, Erkoc, R
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2012;(2):185-8
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Abstract
INTRODUCTION In patients with chronic kidney disease (CKD) predisposition to bleeding is frequently seen due to disturbances in platelet adhesion and aggregation. Various tests have been utilized to evaluate the disturbance of hemostasis in end-stage renal disease patients. In this trial; we evaluated skin bleeding time in patients admitted to our hospital with uremic symptoms and having hemodialysis (HD) for the first time. We also examined the effects of HD and uremia on this test and investigated its effectiveness in predicting the hemorrhagic complications before implementation of invasive procedures in uremic patients. MATERIAL-METHOD Twenty nine patients (13 men,16 women; mean age 59.7 ± 18.1) with CKD who presented with symptoms of uremia and treated with HD for the first time were enrolled in this trial. The skin bleeding time were measured before initiation of first hemodialysis and after the second hemodialysis session. RESULTS The skin bleeding time after the second dialysis was significantly shorter when compared to pre-dialysis values (p < 0.05). Correlation analysis between the skin bleeding time and urea, creatinine, hemoglobin, platelet, and bicarbonate showed no correlation. CONCLUSIONS Skin bleeding time could reveal the uremic platelet dysfunction and beneficial effect of dialysis in the patients who presented with uremic symptoms and treated with HD for the first time. We suggest that skin bleeding time may be an appropriate test for the evaluation of hemostasis disturbance in uremic patients and prediction of the bleeding risk before invasive procedures.
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Divergent roles of plasma osmolality and the baroreflex on sweating and skin blood flow.
Lynn, AG, Gagnon, D, Binder, K, Boushel, RC, Kenny, GP
American journal of physiology. Regulatory, integrative and comparative physiology. 2012;(5):R634-42
Abstract
Plasma hyperosmolality and baroreceptor unloading have been shown to independently influence the heat loss responses of sweating and cutaneous vasodilation. However, their combined effects remain unresolved. On four separate occasions, eight males were passively heated with a liquid-conditioned suit to 1.0°C above baseline core temperature during a resting isosmotic state (infusion of 0.9% NaCl saline) with (LBNP) and without (CON) application of lower-body negative pressure (-40 cmH2O) and during a hyperosmotic state (infusion of 3.0% NaCl saline) with (LBNP + HYP) and without (HYP) application of lower-body negative pressure. Forearm sweat rate (ventilated capsule) and skin blood flow (laser-Doppler), as well as core (esophageal) and mean skin temperatures, were measured continuously. Plasma osmolality increased by ∼10 mosmol/kgH2O during HYP and HYP + LBNP conditions, whereas it remained unchanged during CON and LBNP (P ≤ 0.05). The change in mean body temperature (0.8 × core temperature + 0.2 × mean skin temperature) at the onset threshold for increases in cutaneous vascular conductance (CVC) was significantly greater during LBNP (0.56 ± 0.24°C) and HYP (0.69 ± 0.36°C) conditions compared with CON (0.28 ± 0.23°C, P ≤ 0.05). Additionally, the onset threshold for CVC during LBNP + HYP (0.88 ± 0.33°C) was significantly greater than CON and LBNP conditions (P ≤ 0.05). In contrast, onset thresholds for sweating were not different during LBNP (0.50 ± 0.18°C) compared with CON (0.46 ± 0.26°C, P = 0.950) but were elevated (P ≤ 0.05) similarly during HYP (0.91 ± 0.37°C) and LBNP + HYP (0.94 ± 0.40°C). Our findings show an additive effect of hyperosmolality and baroreceptor unloading on the onset threshold for increases in CVC during whole body heat stress. In contrast, the onset threshold for sweating during heat stress was only elevated by hyperosmolality with no effect of the baroreflex.