scholarly journals Topically applied methyl nicotinate evokes a temporary inflammation on human skin

2021 ◽  
Vol 18 (1) ◽  
pp. 38-47
Author(s):  
Luis Monteiro Rodrigues ◽  
Sérgio Faloni de Andrade ◽  
Clemente Rocha
Keyword(s):  
Clinical Score ◽  
Transepidermal Water Loss ◽  
Maximal Response ◽  
Methyl Nicotinate ◽  
Skin Reactions ◽  
Doppler Flowmetry ◽  
Institutional Ethics ◽  
Human Models ◽  
Forearm Skin ◽  
Skin Responses

Some challengers such as methylnicotinate (MN) have been used in human models to study the anti-inflammatory effect of topical formulations. However, MN skin responses are still poorly understood and widely varied. In the present study we aim to contribute to better characterise those responses. Eight healthy participants were selected. All procedures were approved by the institutional Ethics Committee. Two aqueous MN dilutions (0.5% and 1.0%) were left in contact for 1 minute in the anterior forearm skin. Following exposure, skin reactions were clinically and biometrically assessed at 30, 60 and 120 minutes and compared with baseline. Measurements involved the ICDRG clinical score scale and select analytical technologies - laser Doppler flowmetry, Polarised Spectroscopy, Transepidermal Water Loss Meter, and High Resolution Sonography. Results have shown that MN application evoked a maximal response at 30 minutes with an increase in the ICDRG score between 1-2. Significant changes in TEWL and microcirculation were observed, as was an increased dermal hypoecogenicity (edema), detected by HRS. These effects are compatible with a localised short-duration inflammation and reinforce the interest of MN to be used as a safe and controllable challenger in human models.

Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin

2003 ◽  
Vol 284 (5) ◽  
pp. H1662-H1667 ◽  
Author(s):  
Lacy A. Holowatz ◽  
Belinda L. Houghton ◽  
Brett J. Wong ◽  
Brad W. Wilkins ◽  
Aaron W. Harding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Core Temperature ◽  
The Elderly ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Forearm Skin ◽  
Vascular Responsiveness ◽  
Older Subjects ◽  
Young Subjects ◽  
Reflex Cutaneous Vasodilation

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 ± 2 yr) and seven older (71 ± 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N G-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0°C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 ± 6% maximal CVC (CVCmax) to 53 ± 3% CVCmax in the young subjects and from 64 ± 5% CVCmax to 29 ± 2% CVCmax in the older subjects with a 1.0°C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for ∼23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia ( P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.

scholarly journals Optical coherence tomography in the assessment of acute changes in cutaneous vascular diameter induced by heat stress

2016 ◽  
Vol 121 (4) ◽  
pp. 965-972 ◽  
Author(s):  
Howard H. Carter ◽  
Peijun Gong ◽  
Rodney W. Kirk ◽  
Shaghayegh Es'haghian ◽  
Ceri L. Atkinson ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Skin Temperature ◽  
Ventral Side ◽  
Heating Time ◽  
Optical Coherence ◽  
Doppler Flowmetry ◽  
Skin Physiology ◽  
Forearm Skin ◽  
Acute Changes

There are limited imaging technologies available that can accurately assess or provide surrogate markers of the in vivo cutaneous microvessel network in humans. In this study, we establish the use of optical coherence tomography (OCT) as a novel imaging technique to assess acute changes in cutaneous microvessel area density and diameter in humans. OCT speckle decorrelation images of the skin on the ventral side of the forearm up to a depth of 500 μm were obtained prior to and following 20-25 min of lower limb heating in eight healthy men [30.3 ± 7.6 (SD) yr]. Skin red blood cell flux was also collected using laser Doppler flowmetry probes immediately adjacent to the OCT skin sites, along with skin temperature. OCT speckle decorrelation images were obtained at both baseline and heating time points. Forearm skin flux increased significantly (0.20 ± 0.15 to 1.75 ± 0.38 cutaneous vascular conductance, P < 0.01), along with forearm skin temperature (32.0 ± 1.2 to 34.3 ± 1.0°C, P < 0.01). Quantitative differences in the automated calculation of vascular area densities (26 ± 9 to 49 ± 19%, P < 0.01) and individual microvessel diameters (68 ± 17 to 105 ± 25 μm, P < 0.01) were evident following the heating session. This is the first in vivo within-subject assessment of acute changes in the cutaneous microvasculature in response to heating in humans and highlights the use of OCT as an exciting new imaging approach for skin physiology and clinical research.

scholarly journals Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans

2009 ◽  
Vol 107 (5) ◽  
pp. 1438-1444 ◽  
Author(s):  
Dean L. Kellogg ◽  
Joan L. Zhao ◽  
Yubo Wu
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
No Synthase ◽  
Whole Body ◽  
Doppler Flowmetry ◽  
Vasodilator Response ◽  
Cutaneous Vasodilation ◽  
Forearm Skin ◽  
Whole Body Heat Stress ◽  
Body Heat

Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased local skin temperature (Tloc) and whole body heat stress in humans. In forearm skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat stress. To explore the relative roles and interactions of these isoforms, we examined the effects of a relatively specific eNOS inhibitor, Nω-amino-l-arginine (LNAA), and a specific nNOS inhibitor, Nω-propyl-l-arginine (NPLA), both separately and in combination, on skin blood flow (SkBF) responses to increased Tloc and heat stress in two protocols. In each protocol, SkBF was monitored by laser-Doppler flowmetry (LDF) and mean arterial pressure (MAP) by Finapres. Cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Intradermal microdialysis was used to treat one site with 5 mM LNAA, another with 5 mM NPLA, a third with combined 5 mM LNAA and 5 mM NPLA (Mix), and a fourth site with Ringer only. In protocol 1, Tloc was controlled with combined LDF/local heating units. Tloc was increased from 34°C to 41.5°C to cause local vasodilation. In protocol 2, after a period of normothermia, whole body heat stress was induced (water-perfused suits). At the end of each protocol, all sites were perfused with 58 mM nitroprusside to effect maximal vasodilation for data normalization. In protocol 1, at Tloc = 34°C, CVC did not differ between sites ( P > 0.05). LNAA and Mix attenuated CVC increases at Tloc = 41.5°C to similar extents ( P < 0.05, LNAA or Mix vs. untreated or NPLA). In protocol 2, in normothermia, CVC did not differ between sites ( P > 0.05). During heat stress, NPLA and Mix attenuated CVC increases to similar extents, but no significant attenuation occurred with LNAA ( P < 0.05, NPLA or Mix vs. untreated or LNAA). In forearm skin, eNOS mediates the vasodilator response to increased Tloc and nNOS mediates the vasodilator response to heat stress. The two isoforms do not appear to interact during either response.

scholarly journals P1161CUTANEOUS MICROCIRCULATORY DYSFUNCTION IN PERITONEAL DIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jennifer Williams ◽  
Mark Gilchrist ◽  
Donald Fraser ◽  
David Strain ◽  
Angela Shore
Keyword(s):  
Peritoneal Dialysis ◽  
Statistical Significance ◽  
Microvascular Function ◽  
Healthy Controls ◽  
Dialysis Patients ◽  
Skin Microcirculation ◽  
Doppler Flowmetry ◽  
Microvascular Reactivity ◽  
Co Morbidity ◽  
Forearm Skin

Abstract Background and Aims Microvascular impairment is an early step in cardiovascular disease (CVD), the major cause of morbidity and mortality in patients with CKD. Changes in skin microvascular reactivity have been shown to reflect more widespread changes in the systemic and coronary microcirculation. Microvascular function is attenuated by advancing age and conditions that commonly coexist with CKD such as diabetes and hypertension. We investigated whether skin microvascular reactivity is impaired in peritoneal dialysis (PD) patients compared with healthy controls and whether this impairment is independent of comorbidity. Method Forearm skin vasculature was examined in 27 healthy controls, 27 patients on PD and 27 controls matched to the PD patients for age, gender, diabetes and previous CV events. Microvascular function was assessed using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia (a test of generalised microvascular function) and iontophoretic application of acetylcholine (ACh) and sodium nitroprusside (SNP) to investigate endothelium dependant and non-endothelium dependant vasodilation respectively. Results Peak post-occlusive flow was lower in the PD patients than in both the healthy controls and the co-morbidity matched group; 90.45 AU (60.9-128.35) in healthy controls, 73AU (58.8-134.4) in matched controls and 56.95AU (45.1-89.8) in PD patients (p=0.0239 healthy controls versus patients, p=0.0373 matched controls versus patients). SNP-mediated vasodilatation was statistically lower in the PD group compared with healthy controls (p= 0.016), ACh response was lower but did not reach statistical significance (p= 0.076). ACh and SNP-mediated vasodilatation trended towards being lower in PD patients than matched controls but did not reach statistical significance. Conclusion The PD patients were characterised by a generalised dysfunction of the skin microcirculation compared with healthy controls and controls matched for factors known to affect the microcirculation. This appears to be the result of impaired endothelium dependant and independent vasodilatory mechanisms.

scholarly journals Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

2010 ◽  
Vol 298 (5) ◽  
pp. R1417-R1420 ◽  
Author(s):  
Jonathan E. Wingo ◽  
R. Matthew Brothers ◽  
Juan Del Coso ◽  
Craig G. Crandall
Keyword(s):  
Skeletal Muscle ◽  
Human Skin ◽  
Cholinergic Neurons ◽  
Laser Doppler ◽  
Whole Body ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Intradermal Administration ◽  
Forearm Skin ◽  
Cutaneous Vasoconstriction

Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic “active” vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1×10−4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively ( P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites ( P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

Use of Nanotechnology-Designed Footsock in the Management of Preulcerative Conditions in the Diabetic Foot: Results of a Single, Blind Randomized Study

2008 ◽  
Vol 7 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Banchellini Elisa ◽  
Macchiarini Silvia ◽  
Dini Valentina ◽  
Rizzo Loredana ◽  
Tedeschi Anna ◽  
...  
Keyword(s):  
Treatment Group ◽  
Adverse Events ◽  
Water Loss ◽  
Diabetic Foot ◽  
Randomized Study ◽  
Clinical Score ◽  
Transepidermal Water Loss ◽  
Group A ◽  
Group B ◽  
Single Blind

The Difoprev system constituted by a sock loaded with nanocapsules containing a hydrating agent in the diabetic foot is tested. A total of 30 neuropathic outpatients with foot anhydrosis were randomized into group A, treated with the application of the sock with the nanocapsules, and group B wearing only the socks without the nanocapsules. Patients were blindly evaluated with a clinical score, hygrometry, transepidermal water loss, skin temperature, and skin hardness at baseline and after 6 weeks. No difference between the groups emerged at baseline. Although group B showed no changes at the end of the treatment, group A significantly ( P < .05) improved in all the parameters evaluated. No adverse events were recorded in both groups during the study. The use of hydrating agents carried by nanocapsules-loaded socks is safe and effective for the neuropathic diabetic foot.

Experimental adiaspiromycosis in rabbits. Evaluation of protoplasmic proteins and Sephadex G-100 fractions as specific antigens

1974 ◽  
Vol 20 (7) ◽  
pp. 987-991 ◽  
Author(s):  
Raul J. Cano ◽  
John J. Taylor
Keyword(s):  
Skin Test ◽  
Skin Reactions ◽  
Test Antigen ◽  
Homologous Strain ◽  
Skin Responses ◽  
Specific Antigens ◽  
Specific Fraction

Laboratory rabbits experimentally infected with aerosolized conidia of Chrysosporium parvum or C. parvum var. crescens were skin-tested with partially purified protoplasmic protein (P) antigens extracted from the fungi, and with several components of P antigens separated by Sephadex G-100 fractionation. Ten micrograms of conidial or 5 μg of adiaspore P antigen produced delayed type skin responses only in those animals infected with the homologous strain. Large quantities of antigens elicited skin reactions in both homologously and heterologously infected rabbits. Skin-reactive components of P antigens were either strain-specific or non-specific, and were recovered from aleuriospores, or adiaspores, or from both. One strain-specific fraction (21) recovered from both aleuriospores and adiaspores may merit clinical and (or) epidemiological trial as a skin-test antigen.

Rho kinase-mediated local cold-induced cutaneous vasoconstriction is augmented in aged human skin

2007 ◽  
Vol 293 (1) ◽  
pp. H30-H36 ◽  
Author(s):  
Caitlin S. Thompson-Torgerson ◽  
Lacy A. Holowatz ◽  
Nicholas A. Flavahan ◽  
W. Larry Kenney
Keyword(s):  
Rho Kinase ◽  
Age Difference ◽  
Local Cooling ◽  
Kinase Inhibition ◽  
Doppler Flowmetry ◽  
Forearm Skin ◽  
Older Subjects ◽  
Young Subjects ◽  
Effects Of Aging ◽  
Cutaneous Vasoconstriction

Cutaneous vasoconstriction (VC), a critical thermoregulatory response to cold, is generally impaired with aging. However, the effects of aging on local cooling-induced VC and its underlying mechanisms are poorly understood. We tested whether aged skin exhibits attenuated localized cold-induced VC and whether Rho kinase-mediated cold-induced VC is augmented with age. Skin blood flow was monitored with laser Doppler flowmetry (LDF) on seven young and seven older subjects. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). In protocol 1, two forearm skin sites were cooled to six temperatures (31.5–19°C) for 10 min each or two temperatures (29°C, 24°C) for 30 min each, with no age differences in the magnitude of VC. In protocol 2, three forearm skin sites were instrumented for intradermal microdialysis and cooled to 24°C for 40 min. During minutes 1–5, there was no age difference in CVC responses at control sites (young: −45 ± 6% vs. older: −46 ± 3%, P > 0.9). Adrenoceptor antagonism (yohimbine + propranolol) abolished VC in young (to +15 ± 13%, P < 0.05) but only partially inhibited VC in older subjects (to −23 ± 6%, P < 0.05). Rho kinase inhibition plus adrenoceptor antagonism (yohimbine + propranolol + fasudil) abolished VC in both groups. During minutes 35–40, there was no age difference in control (young: −77 ± 4% vs. older: −70 ± 2%, P > 0.3) or adrenoceptor-antagonized responses (young: −61 ± 3% vs. older: −55 ± 2%, P > 0.3); however, Rho kinase inhibition plus adrenoceptor antagonism blocked more VC in older compared with young subjects (−19 ± 11% vs. −35 ± 3%, P < 0.05). Although its magnitude remains unaffected, cold-induced VC becomes less dependent on adrenergic and more dependent on Rho kinase signaling with advancing age.

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