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1.
Clin Exp Rheumatol ; 37 Suppl 119(4): 97-101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573479

RESUMO

OBJECTIVES: The fingers, toes, and tips of the nose and ears have specialised structural and functional features for thermoregulation, and are the most common areas of Raynaud's phenomenon in systemic sclerosis. Digital thermal monitoring (DTM) of vascular reactivity assesses Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery and fingertip vascular function. Flow mediated dilation (FMD) is an indirect measure of endothelial function, perfusion, and vasodilator ability. In this study, we investigated the cross-sectional correlation of FMD and DTM variables to inform an optimised noninvasive study of SSc endothelial function. A student's T-test was used to compare means of DTM across binary variables. METHODS: Consented SSc registry patients were included in this analysis. The subjects were prepared for FMD and DTM per standardised guidelines. The SSc clinical features were recorded. Spearman's Rank Correlation was used to assess the strength of a relationship FMD and DTM variables. RESULTS: Thirty-four SSc subjects had FMD and DTM performed on the same day. Relative (0.42, p=<0.02), absolute FMD (0.41, p<0.02), and shear rate (0.32, p<0.07) were weakly, but significantly correlated with the DTM. Reactive hyperemia (-0.44, p=0.000) was weakly inversely, but significantly related with DTM. Baseline diameter and flow were not significantly related to the DTM. CONCLUSIONS: This non-invasive study of SSc endothelial function suggests that macrocirculation (including relative and absolute FMD, shear rate, and peak hyperemia) and microcirculatory thermoregulation (characterised by DTM) are significantly correlated, thus warrants further prospective study.


Assuntos
Microcirculação/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Escleroderma Sistêmico , Pele/irrigação sanguínea , Artéria Braquial , Estudos Transversais , Dilatação , Endotélio Vascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escleroderma Sistêmico/fisiopatologia , Vasodilatação
3.
J Craniofac Surg ; 30(5): 1525-1528, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299759

RESUMO

BACKGROUND: The authors have recently 1st described the use of the facial artery perforator flap (FAP) for intraoral reconstruction. In this study, they discuss technical notes and surgical tips associated with the procedure and the application of this flap in 4 patients with intraoral defects resulting from cancer or osteoradionecrosis. METHODS: A retrospective study of 4 consecutive patients was performed on all patients who underwent reconstruction of an intraoral defect with a FAP flap, over a 12-month period from March 2017 to March 2018.The flap was designed according to the size of the defect centered on the perforator and was tunneled intraorally by means of a 90° rotation or advanced medially. The most constantly encountered perforator 1.5 cm lateral to the oral commissure was used in 3 cases; a cranial perforator was selected in 1 patient. RESULTS: Four FAP flaps were used in 4 patients with intraoral defects. Follow-up was 6 to 12 months. Median defect size was 9.15 cm (range, 3.4-21.5 cm). All reconstructions were successful, without major flap loss or infections. One patient with severe osteoradionecrosis and fungal infection developed minor flap loss and dehiscence, which was treated conservatively. There were no signs of local recurrence and functional outcomes were satisfactory. CONCLUSIONS: The FAP flap is an effective and versatile solution for reconstruction of intraoral defects until 5 cm × 4 cm (20 cm) without significant donor-site morbidity. It may be considered a new reconstructive option for intraoral defects, which warrants further study in a larger series or patients.


Assuntos
Face/irrigação sanguínea , Retalho Perfurante/irrigação sanguínea , Artérias , Humanos , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Reconstrutivos , Recidiva , Estudos Retrospectivos , Pele/irrigação sanguínea
4.
J Stroke Cerebrovasc Dis ; 28(8): 2098-2108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160219

RESUMO

Sneddon syndrome (SS) is an episodic or chronic, slowly progressive disorder and characterized by generalized livedo racemosa (patchy, violaceous, skin discoloration) and recurrent cerebrovascular events. The histopathology of skin and brain is remarkable for a noninflammatory thrombotic vasculopathy involving medium- and small-sized dermal and cerebral arteries, respectively. Approximately 80% of the SS patients are women with a median age of diagnosis at 40 years. However, the onset of the disease during childhood have been reported. Etiopathogenesis of SS is unknown with 2 primary mechanisms proposed - autoimmune/inflammatory versus thrombophilia. SS is primarily classified as antiphospholipid positive or negative type. Neurological manifestations usually occur in 3 phases: (1) prodromal symptoms such as headaches, dizziness, and vertigo, (2) recurrent strokes, and (3) early onset dementia. Livedo racemosa precedes the onset of recurrent strokes by more than 10 years, but in many instances, the significance of the skin lesion is recognized only after the appearance of the stroke. The involvement of the heart valves, systolic labile hypertension, and retinal changes are also commonly associated with this syndrome. Treatment of SS is primarily based on anecdotal reports. Antiplatelet and antithrombotic agents are used for secondary stroke prophylaxis, and a recent study showed a relatively lower stroke recurrence rate with the universal use of antiplatelet/antithrombotic agents. Routine use of anti-inflammatory or immunosuppressive therapies is controversial. Neuropsychiatric prognosis of SS is relatively poor with predominant deficits in the concentration, attention, visual perception, and visuospatial skills.


Assuntos
Artérias Cerebrais/patologia , Livedo Reticular/etiologia , Pele/irrigação sanguínea , Síndrome de Sneddon/complicações , Acidente Vascular Cerebral/etiologia , Anti-Inflamatórios/uso terapêutico , Artérias Cerebrais/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Livedo Reticular/patologia , Livedo Reticular/fisiopatologia , Livedo Reticular/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Recidiva , Fatores de Risco , Síndrome de Sneddon/tratamento farmacológico , Síndrome de Sneddon/patologia , Síndrome de Sneddon/fisiopatologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 126-129, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250602

RESUMO

OBJECTIVE: To investigate the effects of intermittent negative pressure therapy on the skin microcirculation perfusion of quadriceps in male rowers, and to provide basis for the practical application of this method. METHODS: Fourteen male rowers were selected from the national rowing team and randomly divided into experimental and control groups. The daily training plans of two groups were the same. The recovery intervention for experimental group was implemented by 20 minutes in the cube of Vacusport Regeneration System (German), 5 times per week for 4 weeks, no recovery intervention for control group. Microcirculation markers were collected by PeriFlux5000 system before and after the 4-week intervention. The markers included microcirculatory blood perfusion(MBP), average velocity of blood cells(AVBC), concentration of moving blood cells (CMBC), and values of the markers included basic values and post-heating values (44℃), difference before and after heating of the values was considered as the reserve capacity of those markers. RESULTS: The test results before the 4 weeks intervention showed there was no statistical difference between the two groups(P>0.05). After the 4 weeks intervention: ①MBP: The post-heating value and the difference of the experimental group were significantly higher than those of the control group (P<0.05). But there was no statistical inner-group difference. ②AVBC: The post-heating values and the difference in the experimental group were significantly lower than those in the control group (P<0.05). Intra-group comparison found that the post-heating values after post-intervention were significantly reduced, compared with those of pre-intervention (P< 0.01); the difference after post-intervention was reduced significantly, compared with those in the pre-intervention (P<0.05). ③CMBC: The post-heating values and the difference in the experimental group were significantly higher than those in the control group (P<0.01). There were no statistical significant inner-group difference. CONCLUSION: Lower limb intermittent negative pressure therapy can improve the skin microcirculation of the quadriceps of the male rowers, which has a positive effect on the rapid recovery of physical fitness.


Assuntos
Microcirculação , Pressão , Músculo Quadríceps/irrigação sanguínea , Pele/irrigação sanguínea , Esportes Aquáticos , Humanos , Extremidade Inferior , Masculino
6.
J Dermatol ; 46(7): 584-589, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087594

RESUMO

CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.


Assuntos
Quimiocinas CXC/sangue , Neovascularização Fisiológica/imunologia , Escleroderma Sistêmico/imunologia , Úlcera Cutânea/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Quimiocinas CXC/imunologia , Feminino , Dedos , Voluntários Saudáveis , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia , Úlcera Cutânea/sangue , Úlcera Cutânea/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
7.
Comput Methods Biomech Biomed Engin ; 22(12): 1009-1019, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31084210

RESUMO

Monitoring of skin blood flow oscillations related with mechanical activity of vessels is a very useful modality during diagnosis of peripheral hemodynamic disorders. In this study, we developed a new model and technique for real-time conversion of skin temperature into skin blood flow oscillations, and vice versa. The technique is based on the analogy between the thermal properties of the human skin and electrical properties of the special low-pass filter. Analytical and approximated impulse response functions for the low- and high-pass filters are presented. The general algorithm for the reversible conversion of temperature into blood flow is described. The proposed technique was verified using simulated or experimental data of cold stress, deep inspiratory gasp, and post-occlusive reactive hyperaemia tests. The implementation of the described technique will enable to turn a temperature sensor into a blood flow sensor.


Assuntos
Sistemas de Computação , Temperatura Cutânea/fisiologia , Pele/irrigação sanguínea , Temperatura Ambiente , Adulto , Algoritmos , Difusão , Feminino , Hemodinâmica , Humanos , Hiperemia/fisiopatologia , Masculino , Fluxo Sanguíneo Regional , Fatores de Tempo , Adulto Jovem
8.
Molecules ; 24(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999565

RESUMO

Raman spectra of human skin obtained by laser excitation have been used to non-invasively detect blood glucose. In previous reports, however, Raman spectra thus obtained were mainly derived from the epidermis and interstitial fluid as a result of the shallow penetration depth of lasers in skin. The physiological process by which glucose in microvessels penetrates into the interstitial fluid introduces a time delay, which inevitably introduces errors in transcutaneous measurements of blood glucose. We focused the laser directly on the microvessels in the superficial layer of the human nailfold, and acquired Raman spectra with multiple characteristic peaks of blood, which indicated that the spectra obtained predominantly originated from blood. Incorporating a multivariate approach combining principal component analysis (PCA) and back propagation artificial neural network (BP-ANN), we performed noninvasive blood glucose measurements on 12 randomly selected volunteers, respectively. The mean prediction performance of the 12 volunteers was obtained as an RMSEP of 0.45 mmol/L and R2 of 0.95. It was no time lag between the predicted blood glucose and the actual blood glucose in the oral glucose tolerance test (OGTT). We also applied the procedure to data from all 12 volunteers regarded as one set, and the total predicted performance was obtained with an RMSEP of 0.27 mmol/L and an R2 of 0.98, which is better than that of the individual model for each volunteer. This suggested that anatomical differences between volunteer fingernails do not reduce the prediction accuracy and 100% of the predicted glucose concentrations fall within Region A and B of the Clarke error grid, allowing acceptable predictions in a clinically relevant range. The Raman spectroscopy detection of blood glucose from microvessels is of great significance of non-invasive blood glucose detection of Raman spectroscopy. This innovative method may also facilitate non-invasive detection of other blood components.


Assuntos
Glicemia/análise , Lasers , Microvasos/metabolismo , Pele , Análise Espectral Raman/métodos , Adulto , Glicemia/metabolismo , Feminino , Humanos , Masculino , Redes Neurais (Computação) , Análise de Componente Principal , Pele/irrigação sanguínea , Pele/metabolismo
9.
Microvasc Res ; 124: 91-96, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959000

RESUMO

BACKGROUND: The burden of type 1 diabetes (T1D) is growing worldwide, stressing the requirement to limit the threat of its long-term complications. In this regard, the development of methods for the early diagnosis and non-invasive monitoring of vascular abnormalities is widely recognized as one of the greatest priorities of the clinical research in this field. OBJECTIVE: To assess the deterioration of physiological properties extracted from laser Doppler flowmetry (LDF) signals of microvascular perfusion and, secondly, to investigate their association with the quality of long-term metabolic control. METHODS: Microvascular perfusion was recorded at the hallux of 63 control subjects and 47 T1D patients, whose glycaemic control was characterized in terms of the annual average levels of glycosylated haemoglobin (HbA1c). Pulse Decomposition Analysis was applied to the LDF data, in order to derive non-invasive markers of vascular stiffness based on a multi-Gaussian representation of the peripheral pulse waveforms; furthermore, wavelet transform analysis was used to evaluate the microvascular myogenic vasomotion and, finally, a physiological model of the reactive hyperaemia to a local thermal stimulus at 43 was used to test the integrity of the neurovascular pathways. RESULTS: Compared to the control group, T1D patients showed a lower microvascular perfusion at baseline, and a larger vasodilatory reserve upon local heating, but no significant difference in myogenic activity. Moreover, the results of the PDA carried out on the LDF pulse waves, indicate the presence of a significant strong relation between large artery stiffness and the overall loss of glycaemic control over the past year.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Fluxometria por Laser-Doppler , Microcirculação , Pele/irrigação sanguínea , Adulto , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Valor Preditivo dos Testes , Análise de Onda de Pulso , Fluxo Sanguíneo Regional , Fatores de Tempo , Rigidez Vascular , Vasodilatação , Análise de Ondaletas
11.
Eur J Appl Physiol ; 119(5): 1195-1201, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30820660

RESUMO

PURPOSE: The facial skin blood flow (SkBF) shows regional differences in the responses to a given stimulation. The facial SkBFs, especially in the eyelid and nose exhibit unique response to physiological and psychological stimuli, but the mechanisms inducing those regional differences remain unclear. To investigate whether the regional differences in the local control of vasomotion in facial vessels correspond to the regional differences in facial SkBF response, we monitored the relative change of facial SkBF to regional thermal stimulation. We hypothesized that heat stimulation dilates the cutaneous vessels in the eyelid, while cold stimulation constricts those in the nose, which was based on previous findings METHODS: A thermal stimulator was used to apply temperature increase (from 20 to 40 °C at 2 °C/min) and decrease (from 40 to 20 °C at 2°C/min) in a randomized order to the right eyelid, nose, right cheek, and forehead of 14 healthy young males. The facial SkBF was measured for 10 s using laser-speckle flowgraphy when temperatures of 20 °C, 30 °C, and 40 °C had been applied for 30 s in both trials. RESULTS: The SkBF in the eyelid did not change significantly during any thermal stimulation, and the nasal SkBF did not decrease significantly during cold stimulation. The SkBFs in the cheek and forehead increased significantly with the applied temperature. CONCLUSIONS: These findings indicate that a large regional variation exists in facial skin blood flow response to local heating or cooling and that the regional variation did not correspond to the unique SkBF responses in the previous studies.


Assuntos
Temperatura Baixa , Pálpebras/irrigação sanguínea , Temperatura Alta , Nariz/irrigação sanguínea , Fluxo Sanguíneo Regional , Pele/irrigação sanguínea , Adolescente , Adulto , Humanos , Masculino , Distribuição Aleatória , Temperatura Cutânea , Vasoconstrição , Vasodilatação
12.
J Ethnopharmacol ; 236: 263-276, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30862523

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sea bass (Lateolabrax maculatus) has been used for dietary therapy practice for wound healing of puerperal or surgery patients in China. Traditional Chinese medicinal books also documented that sea bass can be used to manage inflammation-associated conditions such as wound, miscarriage and cough. Some studies also proved that dietary supplement with fish benefited for treating many inflammatory - associated conditions, such as cardiovascular disease, ulcerative colitis and hyperlipidemia. However, the studies on the pharmacological mechanisms of wound healing efficacy of sea bass remain lack of investigation. AIM OF THE STUDY: The aim of this study is to investigate the molecular mechanisms of sea bass on wound healing efficacy. Establishing a further justification for clinical application of aqueous extract of sea bass (ASB) in treating wound healing. MATERIALS AND METHODS: Transition from inflammation to proliferation phase treated as the critical step in wound repair which were investigated via in vitro and in vivo study. A series of inflammatory mediators associated with wound healing and proliferation effects of fibroblasts upon treatments were studied via Western blotting, enzyme-linked immunosorbent assay (ELISA), real time reverse transcription-polymerase chain reaction (RT-PCR) and scratch assay. The cutaneous wound model was applied on skin wound healing study to observe the healing process in C57BL/6 mice upon ASB treatments. Hematological parameters and tumor necrosis factor-α (TNF-α) secretions in serum were determined. Histopathological examinations were conducted by hematoxylin and eosin (H&E) staining and Masson staining. Immunofluorescence were performed to identify infiltrating neutrophils (MPO) and α-smooth muscle actin (α-SMA). RESULTS: Results showed that ASB significantly reduced the production of inflammatory mediators cyclooxygenase-2 (COX-2), nitrite oxide (NO) production and TNF-α. The phosphorylation and nuclear protein levels of transcription factor nuclear factor-κB (NF-ĸB) in toll-like receptor 4 (TLR4) signaling were decreased by ASB treatment as well. Wound closure rate and cyclin D1 expression level of fibroblasts were significantly increased by ASB treatments. Moreover, cutaneous wound model in C57BL/6 mice presented many similarities in appearance to the process of wound healing. CONCLUSIONS: The in vitro study demonstrated an inhibitory effect of ASB on the inflammatory mediators regulated by TLR4 signaling pathways, providing evidence that ASB treatment potentially accelerate the wound healing through migration and proliferation enhancement. Additionally, the in vivo study suggested that ASB treatment has a potential in accelerating the proliferation phase of wound healing via well-organized abundant collagen deposition, angiogenesis and re-epithelialization in wounds. The present findings can be treated as a pharmacological basis for the folk use of sea bass and further studies in biological and medical fields.


Assuntos
Bass , Proliferação de Células/fisiologia , Inflamação/dietoterapia , Alimentos Marinhos , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/sangue , Masculino , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/fisiologia , Células RAW 264.7 , Transdução de Sinais/fisiologia , Pele/irrigação sanguínea , Pele/lesões , Pele/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/sangue , Cicatrização/fisiologia
13.
Nanoscale ; 11(13): 6315-6333, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30882821

RESUMO

Due to the complexity of the skin tissue structure, the regeneration of the entire skin, including skin appendages such as hair follicles, is a big challenge. In addition, skin trauma is often accompanied by bacterial infections that delay the wound healing. Therefore, developing wound dressings, which promote hair follicle regeneration and inhibit bacterial infection in the wound healing process, is of great clinical significance. In this study, Zn doped hollow mesoporous silica nanospheres (HMZS) were synthesized by a sol-gel method and a novel wound healing dressing was prepared by incorporation of drug ciprofloxacin hydrochloride (CiH)-loaded Zn containing mesoporous silica nanospheres (CiH-HMZS) into polycaprolactone (PCL) electrospun fibers. The CiH-HMZS/P nano-composite electrospun fibers exhibit the ability to promote angiogenesis and skin regeneration by releasing Si ions, and the activity to enhance hair follicle regeneration and inhibit bacterial growth by releasing zinc ions and achieve the synergistic antibacterial effect with both Zn ions and CiH in low concentrations. Thus, the CiH-HMZS/P nano-composite membrane is a promising multi-functional wound healing material for inhibiting bacterial growth in infected wounds and enhancing skin wound healing including hair follicle regeneration.


Assuntos
Antibacterianos/química , Folículo Piloso/fisiologia , Nanocompostos/química , Poliésteres/química , Dióxido de Silício/química , Cicatrização/efeitos dos fármacos , Zinco/química , Animais , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ciprofloxacino/química , Ciprofloxacino/farmacologia , Portadores de Fármacos/química , Escherichia coli/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanocompostos/uso terapêutico , Nanocompostos/toxicidade , Neovascularização Fisiológica/efeitos dos fármacos , Porosidade , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos
14.
Microvasc Res ; 124: 54-60, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30877017

RESUMO

BACKGROUND: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be used as a local provocation in the assessment of microcirculation and skin viability. The aims were to measure the effects of increasing doses of MN, to find the concentration that yields the most reproducible effect from day to day and between sites, and to study the variation between skin sites. METHODS: Microvascular responses to topically applied MN at different concentrations were measured in 12 subjects on separate days and on contralateral sides, using laser speckle contrast imaging (LSCI). MN effects were measured in four different body sites. RESULTS: At 20 mmol/L, the response to MN was most reproducible day-to-day and site-to-site, and resulted in a plateau response between 5 and 20 min after application. The skin region of the lower back had a lower perfusion value compared to the epigastric region (p = 0.007). When responses were compared to nearby, unprovoked areas, a significantly larger increase in perfusion was seen in the forearm, compared to all other anatomical sites (p < 0.03). CONCLUSION: A concentration of 20 mmol/L MN generated the most reproducible microvascular response in the skin. The response varies between different body sites.


Assuntos
Eritema/induzido quimicamente , Eritema/fisiopatologia , Microcirculação/efeitos dos fármacos , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/efeitos adversos , Pele/irrigação sanguínea , Administração Cutânea , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de Tempo , Adulto Jovem
15.
Food Chem Toxicol ; 127: 42-52, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30836108

RESUMO

This study focused on defining the in vitro behavior of amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles toward whole blood, blood plasma and blood cells in order to assess nanoparticle blood compatibility. In addition, possible effects on endothelium cell growth/viability were evaluated. The Amph-PVP nanoparticles were formed via self-assembling in aqueous media and composed of a hydrophobic alkyl core and a hydrophilic PVP outer shell. Their blood compatibility was evaluated by investigating their effect on red blood cells (RBCs) or erythrocytes, white blood cells (WBCs) or leukocytes, platelets (PLTs) and on complement system activation. Our results clearly demonstrate that the Amph-PVP nanoparticles are stable in presence of blood serum, have no significant effects on the function of RBCs, WBCs, PLTs and complement system activation. The Amph-PVP nanoparticles did not show considerable hemolytic or inflammatory effect, neither influence on platelet aggregation, coagulation process, or complement activation at the tested concentration range of 0.05-0.5 mg/ml. The Amph-PVP nanoparticles did not exhibit any significant effect on HMEC-1 microvascular skin endothelial cells' growth in in vitro experiments. The excellent blood compatibility of the Amph-PVP nanoparticles and the lack of effect on endothelium cell growth/viability represent a crucial feature dictating their further study as novel drug delivery systems.


Assuntos
Materiais Biocompatíveis , Plaquetas/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Pirrolidinonas/toxicidade , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Nanopartículas/química , Pirrolidinonas/química , Pele/irrigação sanguínea , Pele/citologia
16.
Plast Reconstr Surg ; 143(3): 527e-533e, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30817649

RESUMO

BACKGROUND: Botulinum toxin type A has gained popularity in many clinical fields, for a variety of aesthetic and therapeutic purposes. In addition, there have been reports regarding the positive effect of botulinum toxin type A on flap survival by various mechanisms. This study examines the role of botulinum toxin type A and lidocaine in augmentation of flap survival and decreasing the rate of necrosis in random pattern cutaneous flaps. METHODS: In 45 male Sprague-Dawley rats, random pattern skin flaps with different width-to-length ratios were elevated. Botulinum toxin type A, lidocaine, or saline was administered to the base and whole length of the flap. Flap survival was evaluated on day 10 after surgery. The area of flap survival was determined grossly on the basis of its appearance, color, and texture. RESULTS: The botulinum toxin type A group had a greater survival area (p < 0.05) compared with the lidocaine or saline group in flaps with width-to-length ratios of 1:2 and 1:3; however, compared with a width-to-length ratio of 1:1, the flap survival rate shows no statistically significant variations. CONCLUSION: Injection of botulinum toxin type A in random pattern skin flaps improves tissue perfusion and increases the rate of flap survival more than lidocaine in flaps with width-to-length ratios of 1:2 and 1:3.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Lidocaína/administração & dosagem , Procedimentos Cirúrgicos Reconstrutivos/métodos , Retalhos Cirúrgicos/transplante , Animais , Injeções , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Retalhos Cirúrgicos/efeitos adversos
17.
Plast Reconstr Surg ; 143(4): 769e-779e, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30921127

RESUMO

BACKGROUND: The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. METHODS: Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. RESULTS: Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. CONCLUSION: Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.


Assuntos
Aminoácidos Dicarboxílicos/farmacologia , Inibidores de Prolil-Hidrolase/farmacologia , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Isquemia/patologia , Precondicionamento Isquêmico/métodos , Masculino , Necrose/prevenção & controle , Período Pré-Operatório , Ratos Pelados , Pele/irrigação sanguínea , Transplante de Pele/métodos , Retalhos Cirúrgicos/patologia
18.
Nat Commun ; 10(1): 871, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787295

RESUMO

Chemically modified mRNA is an efficient, biocompatible modality for therapeutic protein expression. We report a first-time-in-human study of this modality, aiming to evaluate safety and potential therapeutic effects. Men with type 2 diabetes mellitus (T2DM) received intradermal injections of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) or buffered saline placebo (ethical obligations precluded use of a non-translatable mRNA control) at randomized sites on the forearm. The only causally treatment-related adverse events were mild injection-site reactions. Skin microdialysis revealed elevated VEGF-A protein levels at mRNA-treated sites versus placebo-treated sites from about 4-24 hours post-administration. Enhancements in basal skin blood flow at 4 hours and 7 days post-administration were detected using laser Doppler fluximetry and imaging. Intradermal VEGF-A mRNA was well tolerated and led to local functional VEGF-A protein expression and transient skin blood flow enhancement in men with T2DM. VEGF-A mRNA may have therapeutic potential for regenerative angiogenesis.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Neovascularização Fisiológica/fisiologia , RNA Mensageiro/efeitos adversos , RNA Mensageiro/uso terapêutico , Pele/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Terapia Genética , Humanos , Injeções Intradérmicas , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , RNA Mensageiro/genética , Fluxo Sanguíneo Regional/genética
19.
Med Sci Sports Exerc ; 51(3): 395-404, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30779715

RESUMO

INTRODUCTION: Impairments in sudomotor function during passive whole-body heating have been reported in multiple sclerosis (MS), a demyelinating disease of the CNS that disrupts autonomic function. However, the capability of the thermoregulatory system to control body temperature during exercise has never been assessed in MS. Thus, the aim of the present study was to test the hypothesis that thermoregulatory function is impaired in MS patients compared with healthy controls (CON) exercising at similar rates of metabolic heat production. METHODS: Sweating and skin blood flow responses were compared between 12 individuals diagnosed with relapsing-remitting MS (9 females, 3 males) and 12 sex-, age-, mass-, and BSA-matched CON during a single bout of cycling exercise (rate of metabolic heat production: ∼4.5 W·kg) for 60 min in a climate-controlled room (25°C, 30% RH). RESULTS: Individuals with MS exhibited an attenuated increase in cumulative whole-body sweat loss after 30 min (MS, 72 ± 51 g; CON, 104 ± 37 g; P = 0.04) and 60 min (MS, 209 ± 94 g; CON, 285 ± 62 g; P = 0.02), as well as lower sweating thermosensitivity (MS, 0.49 ± 0.26 mg·cm·min·°C; CON, 0.86 ± 0.30 mg·cm·min·°C; P = 0.049). Despite evidence for thermoregulatory dysfunction, there were no differences between MS and CON in esophageal or rectal temperatures at 30- or 60-min time points (P > 0.05). Cutaneous vasculature responses were also not different in MS compared with CON (P > 0.05). CONCLUSION: Taken together, MS blunts sweating responses during exercise while cutaneous vasculature responses are preserved. Altered mechanisms of body temperature regulation in persons with MS may lead to temporary worsening of disease symptoms and limit exercise tolerance under more thermally challenging conditions.


Assuntos
Regulação da Temperatura Corporal , Exercício , Esclerose Múltipla/fisiopatologia , Pele/irrigação sanguínea , Sudorese , Adulto , Metabolismo Energético , Tolerância ao Exercício , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Termogênese , Termometria
20.
Clin Anat ; 32(4): 509-514, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784119

RESUMO

The posterior approach is a commonly employed exposure of the elbow that provides excellent visualization and efficacy for various orthopedic procedures, including total elbow arthroplasty (TEA) and fracture care. The posterior approach to the elbow has been associated with an increased rate of wound complications, including infection, skin necrosis, and wound dehiscence. Despite an association between these complications and decreased elbow perfusion, data regarding the intrinsic anatomic etiology for preferential complications in this area has been scarcely reported in the literature. This study characterizes the subdermal and cutaneous vascular perfusion about the elbow by describing the predominant direction of circulation, subdermal anastomoses, and volume of perfusion through cadaveric modeling using computed tomography angiography (CTA). Fifteen upper extremity cadaver specimens were prepared with injection of radiographic contrast directly into the axillary artery immediately preceding CTA imaging of each specimen. Sectra IDS7 software for Windows was used for analysis of all images to produce superimposed axial and 3-D reconstructions of each CTA series. From these images it was discerned that the predominant direction of flow in the posterior elbow integument is anterior medial to posterior lateral. Both the posterior medial and posterior lateral subdermal vascular networks emanate from proximally derived medial arterial sources with few anastomoses and minimal collateral perfusion from the anterolateral location. Consequently, it is important to preserve medial subdermal vascular structures to prevent ischemic wound complications. This is especially true in previously incised elbow integuments. Clin. Anat. 32:509-514, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Cotovelo/irrigação sanguínea , Pele/irrigação sanguínea , Angiografia por Tomografia Computadorizada , Humanos
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