Skin Microcirculation Research Articles

Evaluation of Skin Microcirculation by Laser Doppler Flowmeter in Healthy Beagle Dogs

Evaluation of Skin Microcirculation by Laser Doppler Flowmeter in Healthy Beagle Dogs

New method of sudomotor function measurement to detect microvascular disease and sweat gland nerve or unmyelinated C fiber dysfunction in adults with retinopathy

BackgroundDiabetes-associated microvascular complications such as retinopathy and neuropathy often lead to end-organ and tissue damage. Impaired skin microcirculation often precedes the detection of other advanced diabetic complications. The ANS-1 system contains a redesigned sympathetic skin response (ANS-1 SSR) device that measures sudomotor function, a photoplethysmography sensor, and a blood pressure device to comprehensively assess cardiac autonomic neuropathy and endothelial dysfunction. The purpose of this study was to determine the relationships between the ANS-1 SSR amplitude measured at the: (a) negative electrode (Nitric Oxide [NO] Sweat Peak) with microvascular diseases and associated vascular blood markers and (b) positive electrode (iSweat Peak) with C fiber function.MethodsAll participants (healthy controls n = 50 and retinopathy patients n = 50) completed the ANS-1 system evaluation and a basic sociodemographic and medical history questionnaire, including a quality of life measure (SF-36). A small sample of blood was drawn to determine levels of homocysteine, blood urea nitrogen (BUN), C-reactive protein (CRP), and fibrinogen. Symptoms of peripheral foot neuropathy were assessed with a scale from 1 (none) to 10 (the worst). We used Spearman rank correlations, independent samples t-tests, and receiver operating characteristic curves to determine the specificity and sensitivity of the NO Sweat Peak as a potential screening marker of retinopathy.ResultsThe ANS-1 System Cardiometabolic Risk Score and all indicators of quality of life on the SF-36, other than Emotional Role Functioning, were significantly worse in the retinopathy patients. The sudomotor response marker NO Sweat Peak had a sensitivity of 88% and a specificity of 68% (Area Under the Curve = 0.81, p < 0.0001) to detect retinopathy. The NO Sweat Peak response marker inversely correlated with BUN (ρ = −0.41, p < 0.0001), homocysteine (ρ = −0.44, p < 0.0001), fibrinogen (ρ = −0.41, p < 0.0001), the Cardiac Autonomic Neuropathy score (ρ = −0.68, p < 0.0001), and the heart rate variability Total Power (ρ = −0.57, p < 0.0001), and it positively correlated with the Photoplethysmography Index (PTGi; ρ = 0.53 p < 0.0001). The ANS-1 system sudomotor response marker iSweat Peak inversely correlated with the severity of symptoms on the peripheral neuropathy scale (ρ = −0.56, p < 0.0001).ConclusionThe results of the study show that this new method of measuring sympathetic skin response should be useful for detecting the earliest manifestations of microvascular disease and symptoms of C fiber dysfunction.

EASApprox® skin-stretching system: A secure and effective method to achieve wound closure.

Large skin defects are commonly observed in the clinic and have attracted much attention recently. Therefore, finding an effective solution for large skin defects is a global problem. The objective of the present study was to assess the effectiveness of the EASApprox® skin-stretching system for closing large skin defects. Skin defects (5×5 cm) were created on the forearms of 9 Bama miniature pigs, which were randomly divided into the following three groups: Direct suture, the new EASApprox® skin-stretching device and Kirschner wires. Microcirculation was assessed before surgery and after wound closure. Following the different treatments, the defects were sutured, and wound healing was assessed based on a clinical score. Furthermore, microscopic and ultramicroscopic structures were evaluated, including collagen, elastic fibers and the microvessel density. Significant differences in the clinical score and microvessel density were observed among the groups. Additionally, the mean length obtained for elastic fibers was larger than that obtained for the other two groups. Finally, the new EASApprox® skin-stretching device resulted in successful wound management and with only minor side effects on skin histology and microcirculation. Therefore, this method has the potential to be used for healing large skin defects.

Association of Microvascular Dysfunction With Late-Life Depression

ImportanceThe etiologic factors of late-life depression are still poorly understood. Recent evidence suggests that microvascular dysfunction is associated with depression, which may have implications for prevention and treatment. However, this association has not been systematically reviewed.ObjectiveTo examine the associations of peripheral and cerebral microvascular dysfunction with late-life depression.Data SourcesA systematic literature search was conducted in MEDLINE and EMBASE for and longitudinal studies published since inception to October 16, 2016, that assessed the associations between microvascular dysfunction and depression.Study SelectionThree independent researchers performed the study selection based on consensus. Inclusion criteria were a study population 40 years of age or older, a validated method of detecting depression, and validated measures of microvascular function.Data Extraction and SynthesisThis systematic review and meta-analysis has been registered at PROSPERO (CRD42016049158) and is reported in accordance with the PRISMA and MOOSE guidelines. Data extraction was performed by an independent researcher.Main Outcomes and MeasuresThe following 5 estimates of microvascular dysfunction were considered in participants with or without depression: plasma markers of endothelial function, albuminuria, measurements of skin and muscle microcirculation, retinal arteriolar and venular diameter, and markers for cerebral small vessel disease. Data are reported as pooled odds ratios (ORs) by use of the generic inverse variance method with the use of random-effects models.ResultsA total of 712 studies were identified; 48 were included in the meta-analysis, of which 8 described longitudinal data. Data from 43 600 participants, 9203 individuals with depression, and 72 441 person-years (mean follow-up, 3.7 years) were available. Higher levels of plasma endothelial biomarkers (soluble intercellular adhesion molecule–1: OR, 1.58; 95% CI, 1.28-1.96), white matter hyperintensities (OR, 1.29; 95% CI, 1.19-1.39), cerebral microbleeds (OR, 1.18; 95% CI, 1.03-1.34), and cerebral (micro)infarctions (OR, 1.30; 95% CI, 1.21-1.39) were associated with depression. Among the studies available, no significant associations of albuminuria and retinal vessel diameters with depression were reported. Longitudinal data showed a significant association of white matter hyperintensities with incident depression (OR, 1.19; 95% CI, 1.09-1.30).Conclusions and RelevanceThis meta-analysis shows that both the peripheral and cerebral forms of microvascular dysfunction are associated with higher odds of (incident) late-life depression. This finding may have clinical implications because microvascular dysfunction might provide a potential target for the prevention and treatment of depression.

EP-1154: Changes in skin microcirculation during radiation therapy for breast cancer

EP-1154: Changes in skin microcirculation during radiation therapy for breast cancer

The measurement of cutaneous blood flow in healthy volunteers subjected to physical exercise with ultrasound Doppler imaging and laser Doppler flowmetry.

We aimed to evaluate hemodynamic parameters in the cutaneous microcirculation during recovery to graded dynamic exercise performed on a cycloergometer by using two distinctive methods: high-frequency ultrasound Doppler flowmetry (UDF) and laser Doppler fluxmetry (LDF). Regarding UDF, the medium linear blood flow velocity (Vam) was estimated, expressed in absolute units (cm/s) whereas blood flow assessed by LDF was registered in arbitrary perfusion units (PU). We compared the corresponding perfusion values obtained by UDF and LDF, respectively, every 20 s during recovery period to physical exercise. Three types of microvascular blood flow dynamics were recorded: blood flow with an occasional paroxysm, a pulsatile blood flow pattern, and a shunting-type blood flow pattern. In the first type, the reaction time of registration and the direction of changes of UDF and LDF values coincided in 77.7%, exhibiting high correlation (r = 0.77; p≤0.001). In the second type, the direction of changes of UDF and LDF showed 85.0% similarity and a moderate correlation (r = 0.66; p = 0.0015), whereas in the third type, there was also a moderate correlation (r = 0.53, p = 0.0024). Our pilot experiments have shown that UDF could be regarded as a comparable substitutional method to LDF for studying skin microcirculation.

Oscillatory pattern of acral skin blood flow within thermoneutral zone in healthy humans

The acral skin contains arteriovenous anastomoses, which probably is the main part of skin microcirculation for blood flow adjustments and thermoregulation in the thermoneutral zone. The objective was to investigate if an increase in sympathetic activation during cooling influences the oscillatory pattern of acral skin blood flow.We had measurements of bilateral acral skin blood flow (n = 12) during lowering of ambient temperature from 32 °C to 18 °C. We quantified the oscillatory pattern as the time averaged wavelet spectral powers, coherence and phase angles in three frequency intervals (0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz). The differences were tested by Wilcoxon signed rank sum method between adjacent intervals.The absolute fluctuations in laser Doppler flux at 0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz were similar at 32 °C and 25 °C, and decreased at 18 °C (p < 0.001). The relative fluctuations (amplitude of the fluctuations relative to median flux value) in laser Doppler flux at 0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz were higher at 25 °C and 18 °C as compared to 32 °C (p < 0.002). The coherence between the oscillations of signals from right and left finger tips was highest (median coherence > 0.89) at 25 °C, and lower at 32 °C and at 18 °C.The median phase angles between the flux signals from right and left finger tips were close to 0 radians.We found that the relative fluctuations in acral skin blood flow increased during vasoconstriction due to cooling. Wavelet analysis of acral skin blood flow oscillations could serve as a future clinical tool.

Temporal and spatiotemporal variability in comprehensive forearm skin microcirculation assessment during occlusion protocols

Forearm skin hyperemia during release after brachial occlusion has been proposed for evaluating peripheral arterial disease and endothelial dysfunction. We used a novel fiberoptic system integrating Laser Doppler Flowmetry and Diffuse Reflectance Spectroscopy for a comprehensive pointwise model based microcirculation characterization. The aim was to evaluate and compare the temporal and the spatiotemporal variabilities in forearm skin microcirculation parameters (speed resolved perfusion; low speed <1mm/s, PerfSR, <1; mid-speed 1–10mm/s, high speed >10mm/s, and total perfusion (PerfSR, tot); the concentration and oxygenation of red blood cells, CRBC and SO2). Ten healthy subjects underwent arterial and venous forearm occlusions (AO, VO), repeated within one week. The repeatability was calculated as the coefficient of variation (CV) and the agreement as the intra-class correlation coefficient (ICC). The temporal CVs for conventional perfusion, Perfconv, PerfSR, tot, CRBC and SO2 were 14%, 12%, 9% and 9%, respectively, while the ICC were >0.75 (excellent). The perfusion measures generally had a higher spatiotemporal than temporal variability, which was not the case for SO2 and CRBC. The corresponding spatiotemporal CVs were 33%, 32%, 18% and 15%, respectively. During VO, CRBC had a CV<35% and ICC>0.40 (fair-good), and after release this was the case for CRBC (AO and VO), SO2 (VO) and PerfSR, <1 (VO).In conclusion, the skin microcirculation parameters showed excellent temporal repeatability, while the spatiotemporal repeatability especially for perfusion was poorer. The parameters with acceptable repeatability and fair-good agreement were: CRBC during and after release of VO, the PerfSR, <1 after release of VO, the SO2 and the CRBC after release of AO. However, the value of these parameters in discriminating endothelial function remains to be studied.

Core and Surface Temperature Modification During Road Transport and Physical Exercise in Horse After Acupuncture Needle Stimulation

In this study, the effect of acupuncture on skin temperature (TSKIN), including six body regions (neck, shoulder, ribs, flank, internal thigh, and back), rectal temperature (TRECTAL), serum levels of total proteins, hematocrit, magnesium, calcium (Ca), phosphorus, and chloride was evaluated in five Thoroughbred horses. Horses competed in two official races. For each race, animals were transported from their stables to the racetrack. Horses transported and competed in the first race represent the control group. Two weeks later, the same horses competed in the second race. Before road transport, they were treated with acupuncture. From animals, the TSKIN, TRECTAL, and blood samples were collected at rest; after unloaded, 30 minutes after unloaded, at rest in the transit box, at the end of the race, and 30 minutes after the race. A significant effect of transport and exercise was found on all studied parameters (P < .01), except for Ca and TSKIN of neck (P > .05), in both groups. Transported and exercised horses subjected to acupuncture treatment showed statistically significant higher values of TRECTAL and TSKIN of flank (P < .01). Thoroughbred horses display a classic hemodynamic response to transport and exercise; acupuncture affects body temperature and skin temperature of flank region in both transported and exercised horses suggesting a controlling effect of acupuncture on thermoregulatory function, probably, by decreasing the activities of sympathetic function and manifested as vasodilatation, arterial blood flow, and skin microcirculation increase.

Evidence of impaired microvascular dilatation in preterms with acute respiratory distress syndrome

BackgroundEvaluating microcirculatory function in severely ill neonates is a relevant, unmet clinical need. Inappropriate peripheral microvascular vasodilatation is thought to contribute to cardiovascular alterations in preterm infants with acute respiratory distress syndrome (ARDS). We directly evaluated microcirculatory function in preterms with ARDS. MethodsPeripheral microvascular function was assessed in 50 newborns, divided in three groups: preterms with ARDS; at-term newborns with mild-moderate congenital cardiac disease (Cardio group); healthy controls. Skin microvascular perfusion was assessed using an operator-independent, laser-Doppler camera, under basal conditions and during post-ischemic hyperemia, allowing objective quantification of microcirculatory flow reserve (MFR). ResultsAt baseline, perfusion was similar among the three groups. During post-ischemic phase, microcirculatory perfusion significantly increased in controls compared to baseline (baseline perfusion units [PU] 3.65±1.8 to 4.59±2.1 during hyperemia; p for trend=0.041), whereas in ARDS group perfusion tended to decrease. Comparing results across groups, ARDS showed lower values compared to either controls or Cardio groups (p<0.05). Controls, and to a lesser extent Cardio group, showed recruitable MFR (1.78±1.13 and 1.19±0.30 in controls and Cardio group, respectively). MFR was absent in ARDS (0.88±0.48; p<0.05), documenting impaired microcirculatory response. ConclusionWe demonstrate that it is possible to assess, non-invasively and quantitatively, vasodilator response of skin microcirculation to physiological stimuli in neonates. We also documented that microvascular vasodilation is impaired in preterms with ARDS.

Intravital Microscopy and Thrombus Induction in the Earlobe of a Hairless Mouse

Thrombotic complications of vascular diseases are one leading cause of morbidity and mortality in industrial nations. Due to the complex interactions between cellular and non-cellular blood components during thrombus formation, reliable studies of the physiology and pathophysiology of thrombosis can only be performed in vivo. Therefore, this article presents an ear model in hairless mice and focuses on the in vivo analysis of microcirculation, thrombus formation, and thrombus evolution. By using intravital fluorescence microscopy and the intravenous (iv) application of the respective fluorescent dyes, a repetitive analysis of microcirculation in the auricle can easily be performed, without the need for surgical preparation. Furthermore, this model can be adapted for in vivo studies of different issues, including wound healing, reperfusion injury, or angiogenesis. In summary, the ear of hairless mice is an ideal model for the in vivo study of skin microcirculation in physiological or pathophysiological conditions and for the evaluation of its reaction to different systemic or topical treatments.

Intravital Microscopy and Thrombus Induction in the Earlobe of a Hairless Mouse.

Thrombotic complications of vascular diseases are one leading cause of morbidity and mortality in industrial nations. Due to the complex interactions between cellular and non-cellular blood components during thrombus formation, reliable studies of the physiology and pathophysiology of thrombosis can only be performed in vivo. Therefore, this article presents an ear model in hairless mice and focuses on the in vivo analysis of microcirculation, thrombus formation, and thrombus evolution. By using intravital fluorescence microscopy and the intravenous (iv) application of the respective fluorescent dyes, a repetitive analysis of microcirculation in the auricle can easily be performed, without the need for surgical preparation. Furthermore, this model can be adapted for in vivo studies of different issues, including wound healing, reperfusion injury, or angiogenesis. In summary, the ear of hairless mice is an ideal model for the in vivo study of skin microcirculation in physiological or pathophysiological conditions and for the evaluation of its reaction to different systemic or topical treatments.

Effect of Noradrenergic Blockade on Low‐frequency Oscillations of Human Skin Microcirculation.

Under normothermic conditions, the skin of the leg has higher sympathetic activity than the skin of the forearm; by contrast, after locally heating the skin to 42°C, the skin of the forearm has higher sympathetic activity. Work in human skin free flaps suggested that the vasomotion waves around 0.021–0.52 Hz corresponded to sympathetic activity.PURPOSENo study has verified the low‐frequency oscillations corresponding to sympathetic activity (0.021–0.052 Hz) in intact, healthy human skin. We hypothesized that sympathetic blockade would reduce the power in this low‐frequency band under normothermic conditions as well as in response to local skin heating. We examined the effects of acute, localized sympathetic nerve blockade on the low‐frequency oscillations of skin blood flow (SkBF) of the forearm and leg.METHODSNine volunteers (6 male, 3 female) had 2 sites on each limb prepared with microdialysis fibers, one perfused with Lactated Ringer's (study vehicle, CTRL) the other bretylium tosylate (BT). Local skin heaters and laser‐Doppler flux (LDF) probes were used to control local temperature and assess SkBF. Skin vasomotion data were analysed using wavelet analysis of the LDF signal. LDF data were collected for 10 min at 33°C and for 35 min after locally heating to 42°C. Data are presented as wavelet amplitude in arbitrary units (au).RESULTSBaselineIn the leg, neurogenic activity was reduced at BT treated sites (0.401 ± 0.049 au) compared to CTRL sites (0.569 ± 0.077 au; P = 0.04). There was no difference between the forearm CTRL and BT sites (P = 0.09). Nor were there differences between the forearm and leg CTRL (P = 0.69) and BT treated sites (P = 0.89).Onset of heatingNeurogenic activity was significantly higher at CTRL sites of the forearm (0.812 ± 0.091 au) and leg (0.854 ± 0.112 au) than at BT treated forearm (0.471 ± 0.064 au; P = 0.03) or leg (0.503 ± 0.094 au; P = 0.01). There was no difference between forearm and leg CTRL (P = 0.78) or BT treated sites (P = 0.75).Prolonged HeatingNeurogenic activity was higher at leg CTRL sites (1.272 ± 0.195 au) compared to BT treated sites (0.776 ± 0.152 au; P &lt; 0.01). Forearm CTRL and the BT treated sites were not different (P = 0.08). Forearm CTRL and leg CTRL sites did not differ (P = 0.3) and neither did the BT treated sites (P = 0.57)CONCLUSIONThese data indicate that acute pharmacological blockade of the sympathetic nerves reduced the low‐frequency oscillations of SkBF of the forearm and leg reported to be associated with neural activity. During normothermia, neural activity was only reduced in the skin of the leg and not the forearm. Neurogenic activity was reduced at the onset of heating for both the forearm and leg at BT treated sites. Following prolonged local skin heating at 42°C, we found that neural activity of only the leg was reduced by noradrenergic blockade. These data suggest that the neural frequency band is representative of sympathetic activity. Furthermore, these data indicate that the skin of the leg has a higher noradrenergic component than that of the forearm which is congruent with previous in vivo human work.Support or Funding InformationBall State University Department of Kinesiology

The effect of LED on blood microcirculation during chronic wound healing in diabetic and non-diabetic patients-a prospective, double-blind randomized study.

Chronic wounds, especially in diabetic patients, represent a challenging health issue. Since standard treatment protocols often do not provide satisfactory results, additional treatment methods-like phototherapy using low-level light therapy-are being investigated. The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients. Since a sufficient blood supply is mandatory for wound healing, the evaluation of microcirculation in the healthy skin at a wound's edge was the main outcome measure. Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were randomized to the treated and control groups. The treated group received phototherapy with LED 2.4J/cm2 (wavelengths 625, 660, 850nm) three times a week for 8weeks, and the control group received phototherapy with broadband 580-900nm and power density 0.72J/cm2. Microcirculation was measured using laser Doppler. A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients (p = 0.040 and p = 0.033), while there was no difference in the control groups. Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group. According to our results, phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients.

Changes in skin microcirculation during radiation therapy for breast cancer

Background: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.Material and methods: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.Results: In the treated breast, perfusion and RBC concentration were increased after 1–5 fractions (2.66–13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.Conclusion: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

Skin microvascular function in patients with type 1 diabetes: An observational study from the onset of diabetes.

The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p < 0.01). PRH% was lower than in the reference group after 7-9 years ( p < 0.01), and lower than baseline after 24-29 years of diabetes ( p < 0.05). All but one patient developed retinopathy and the first signs were found after 10 years of diabetes. Functional disturbances in total skin microcirculation were observed after seven years in patients with type 1 diabetes and preceded diabetic complications such as retinopathy.

Alterations in skin microvascular function in patients with rheumatoid arthritis and ankylosing spondylitis.

To evaluate the relationship between systemic inflammation and skin microcirculation in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We assessed skin microcirculation flux (laser Doppler flowmetry), classical cardiovascular risk factors, inflammatory markers and disease activity (Disease Activity Score 28, Bath Ankylosing Spondylitis Disease Activity Index) in 75 patients with arthritis with amedian disease duration of 4 years, and in 26 healthy subjects. In patients with arthritis inflammatory markers (C-reactive protein, interleukin 6, fibrinogen) were increased, peak flux velocity after the occlusion at the temperature of 36.6°C and maximal heat flux velocity after the heating were significantly lower. These findings were accompanied by the slower increase in the flux rate during local heating. There were positive correlations between inflammatory markers and microcirculation parameters in patients with RA and AS, but only for RA patients between peak flux velocity and disease activity. There were no significant intergroup differences when the classical cardiovascular risk factors were compared except for the lower HDL cholesterol in arthritis patients. Patients with chronic systemic inflammatory arthritis presented altered microvascular function and reduced vasodilator capacity of the forearm skin microcirculation.

Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for cosmetic applications

Blocking the TRPV1 receptor is an interesting approach for the treatment of sensitive skin. Here we investigated the potential of grifolin derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their potential to serve as cosmetic active ingredients. Binding characteristics of grifolin derivatives from Albatrellus ovinus were determined in competitive and functional in vitro assays to achieve IC50 values. The TRPV1 receptor was activated in vivo with capsaicin and noxious heat to investigate skin reddening, microcirculation, skin sensations and heat pain thresholds. Grifolin derivatives extracted from Albatrellus ovinus proved to inhibit the TRPV1 receptor in vitro and in vivo. Besides suppression of the TRPV1 receptor activity upon chemical stimulation with capsaicin, thermal activation was shown to be inhibited as well by application of cosmetic formulations containing 3% Albatrellus ovinus extract. The reduction of stinging and burning sensations as well as reduction of reddening and microcirculation upon irritation with capsaicin or thermal stress proved efficacy in vivo. Grifolin derivatives from Albatrellus ovinus are able to serve as fungal-derived TRPV1 receptor blockers with capability to serve as a cosmetic active ingredient on sensitive skin.

Endothelial dysfunction during long-term follow-up in children with STEC hemolytic-uremic syndrome.

Shiga-toxin-producing Escherichia coli (STEC)-associated hemolytic-uremic syndrome (HUS) is a major cause of acute kidney injury (AKI), especially in children. Its long-term outcome with respect to endothelial damage remains largely elusive. This was a cross-sectional study in 26 children who had suffered from STEC-HUS in the past and achieved a complete recovery of renal function (eGFR >90ml/min/1.73m2). Skin microcirculation after local heating was assessed by laser Doppler fluximetry, carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), 24-h ambulatory blood pressure, and angiopoietin (Ang) 1 and 2 serum levels after a median follow-up period of 6.1years. The results were compared to those of healthy controls. All patients were normotensive, mean eGFR was 102 (range 91-154) ml/min/1.73m2, and 13 of the 26 patients showed albuminuria. Endothelial dysfunction was present in 13 patients, and the mean serum Ang2/Ang1 ratio was increased compared to healthy children (each p < 0.05). In contrast, mean values for PWV and cIMT in the patients did not differ from those of the controls. Endothelial dysfunction was significantly associated with younger age at STEC-HUS manifestation, time after HUS, and presence of albuminuria. The results of this study highlight the need for long-term follow-up of STEC-HUS patients even after complete recovery of eGFR and lack of hypertension with respect to microvascular damage.

Assessing the evidence: Exploring the effects of exercise on diabetic microcirculation

Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro- and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested. Physical exercise improves vascular dysfunction through various mechanisms, and is regarded as an additional effective treatment strategy of DM as it positively impacts glycemic control, improves insulin sensitivity and glucose uptake in the target tissues, thus affecting glucose and lipid metabolism, and increases the endothelium dependent vasodilation. Yet, not all patients respond in the same way so titrating the exercise type individualy would be desirable. Resistance training has, apart from aerobic one, been shown to positively correlate to glycemic control, and improve vascular reactivity. It has been prescribed in various forms or in combination with aerobic training. This review would assess the impact of different modes of exercise, the mechanisms involved, and its potential positive and negative effects on treating patients with Type I and Type II DM, focusing on the recent literature.