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1.
Surg Clin North Am ; 100(4): 807-822, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32681878

RESUMO

Peripheral arterial disease (PAD) affects many individuals worldwide and is associated with increased morbidity and mortality. Controversy exists on whether or not to screen asymptomatic patients. Further complicating this is that many patients with a chronic lower extremity wound are often asymptomatic. PAD and traditional noninvasive vascular studies may be inaccurate in providing a correct diagnosis. A review of current and novel vascular assessment modalities along with their benefits and limitations are presented here. A combination of these vascular assessments may help improve accuracy in diagnosis, providing timely care to those patients in need.


Assuntos
Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/fisiopatologia , Índice Tornozelo-Braço , Monitorização Transcutânea dos Gases Sanguíneos/métodos , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Humanos , Pele/irrigação sanguínea , Dermatopatias Vasculares/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Sístole/fisiologia , Cicatrização/fisiologia
3.
Br J Dermatol ; 183(4): 729-737, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32562567

RESUMO

BACKGROUND: Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established. OBJECTIVES: To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue. METHODS: We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one. RESULTS: Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy. CONCLUSIONS: Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage. What is already known about this topic? Despite the high number of cases of chilblains seen during the COVID-19 pandemic, a definite causative role for SARS-CoV-2 has not yet been proven. Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors. What does this study add? The demonstration of SARS-CoV-2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID-19. Virus-induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID-19 chilblains. Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a pathogenetic role in the severe forms of COVID-19. Linked Comment: Wetter. Br J Dermatol 2020; 183:611.


Assuntos
Pérnio/virologia , Infecções por Coronavirus/complicações , Endotélio Vascular/patologia , Pneumonia Viral/complicações , Dermatopatias/virologia , Vasculite/virologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Biópsia , Pérnio/patologia , Criança , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Endoteliais/patologia , Células Endoteliais/ultraestrutura , Células Endoteliais/virologia , Endotélio Vascular/virologia , Humanos , Imuno-Histoquímica , Microscopia Eletrônica , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Pele/irrigação sanguínea , Pele/patologia , Pele/virologia , Dermatopatias/patologia , Vasculite/patologia
4.
Am J Physiol Heart Circ Physiol ; 319(2): H271-H281, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559139

RESUMO

The purpose of this study was to investigate the effect of race and subclinical elevations in blood pressure (i.e., prehypertension) on cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation. We recruited participants who self-identified as either non-Hispanic black (n = 16) or non-Hispanic white (n = 16). Within each group, participants were subdivided as either normotensive (n = 8 per group) or prehypertensive (n = 8 per group). Each participant was instrumented with four intradermal microdialysis fibers: 1) control (lactated Ringer's), 2) 5% lidocaine (sensory nerve inhibition), 3) 20 mM Nω-nitro-l-arginine methyl ester (l-NAME) (NO synthase inhibition), and 4) lidocaine + l-NAME. Skin blood flow was assessed via laser-Doppler flowmetry, and each site underwent local heating from 33°C to 39°C. At the plateau, 20 mM l-NAME were infused at control and lidocaine sites to quantify NO-dependent vasodilation. Maximal vasodilation was induced via 54 mM sodium nitroprusside and local heating to 43°C. Data are means ± SD. Sensory nerve-mediated cutaneous vasodilation was reduced in prehypertensive non-Hispanic white (34 ± 7%) and both non-Hispanic black groups (normotensive, 20 ± 9%, prehypertensive, 24 ± 15%) relative to normotensive non-Hispanic whites (54 ± 12%). NO-dependent vasodilation was also reduced in prehypertensive non-Hispanic white (41 ± 7%) and both non-Hispanic black groups (normotensive, 44 ± 7%, prehypertensive, 19 ± 7%) relative to normotensive non-Hispanic whites (60 ± 11%). The decrease in NO-dependent vasodilation in prehypertensive non-Hispanic blacks was further reduced relative to all other groups. These data suggest subclinical increases in blood pressure adversely affect sensory-mediated and NO-dependent vasodilation in both non-Hispanic blacks and whites.NEW & NOTEWORTHY Overt hypertension is known to reduce cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation, but the effect of subclinical increases in blood pressure (i.e., prehypertension) is unknown. The combined effect of race and prehypertension is also unknown. In this study, we found that prehypertension reduces cutaneous sensory nerve-mediated and NO-dependent vasodilation in both non-Hispanic white and black populations, with the greatest reductions observed in prehypertensive non-Hispanic blacks.


Assuntos
Pressão Sanguínea , Vasos Sanguíneos/inervação , Vasos Sanguíneos/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Pré-Hipertensão/fisiopatologia , Células Receptoras Sensoriais , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adolescente , Adulto , Afro-Americanos , Anestésicos Locais/administração & dosagem , Vasos Sanguíneos/efeitos dos fármacos , Estudos de Casos e Controles , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Grupo com Ancestrais do Continente Europeu , Feminino , Georgia/epidemiologia , Humanos , Masculino , Microdiálise , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/etnologia , Pré-Hipertensão/metabolismo , Fatores Raciais , Células Receptoras Sensoriais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Adulto Jovem
5.
Lasers Med Sci ; 35(8): 1681-1687, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32514864

RESUMO

Laser surgery is becoming an increasingly efficacious and customizable treatment modality for the management of pediatric vascular lesions. Proper use requires a thorough understanding of the scientific principles of laser surgery and knowledge of the various lasers available. Moreover, each laser has a multitude of settings that can be employed to properly target the lesion at hand. Each patient will present with unique challenges and variations in the presentation of their vascular lesion. This requires understanding of the most effective laser to use for each lesion and the factors that may alter the desired device settings. Using key search terms, a literature search was conducted on laser surgery for pediatric vascular lesions using PubMed/MEDLINE and Embase for articles published in English or French. Ultimately, 52 articles met our search criteria. The laser indications, limitations, and settings utilized for each type of vascular lesion were compiled for the purposes of this summative review. Laser surgery is an effective and appropriate option for the treatment of certain pediatric vascular lesions. Knowledge of optimal device parameters in every setting is essential to good clinical practice.


Assuntos
Terapia a Laser/instrumentação , Anormalidades da Pele/cirurgia , Pele/irrigação sanguínea , Pele/patologia , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/efeitos da radiação
6.
Diab Vasc Dis Res ; 17(3): 1479164120928303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538145

RESUMO

AIM: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes. METHODS: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging. RESULTS: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores. CONCLUSION: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Microcirculação , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Feminino , Antebraço , Humanos , Iontoforese , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Angioscopia Microscópica , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem
7.
Proc Natl Acad Sci U S A ; 117(25): 14354-14364, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513697

RESUMO

Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Isquemia/imunologia , Neovascularização Fisiológica/imunologia , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Cicatrização/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Humanos , Isquemia/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Cultura Primária de Células , RNA-Seq , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Transdução de Sinais/imunologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/lesões , Pele/patologia , Transcrição Genética/imunologia
8.
Br J Dermatol ; 183(3): 431-442, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32479680

RESUMO

BACKGROUND: The infection caused by the recently identified SARS-CoV-2, called coronavirus disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID-19. OBJECTIVES: To provide a brief overview of cutaneous lesions associated with COVID-19. METHODS: A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID-19-associated skin manifestations. RESULTS: The literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: (i) urticarial rash; (ii) confluent erythematous-maculopapular-morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain-like acral pattern; (v) livedo reticularis-livedo racemosa-like pattern; and (vi) purpuric 'vasculitic' pattern. These six patterns can be merged into two main groups: the first - inflammatory and exanthematous - includes the first three groups listed above, and the second includes the vasculopathic and vasculitic lesions of the last three groups. CONCLUSIONS: The possible presence of cutaneous findings leading to suspect COVID-19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic values of such cutaneous manifestations.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Dermatopatias/diagnóstico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diagnóstico Diferencial , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Dermatopatias/patologia
9.
Am J Physiol Heart Circ Physiol ; 319(1): H123-H132, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469638

RESUMO

Cold exposure causes cutaneous vasoconstriction via a reflex increase in sympathetic activity and a local effect to augment adrenergic constriction. Local cooling also initiates cutaneous dilatation, which may function to restrain cold-induced constriction. However, the underlying mechanisms and physiological role of cold-induced dilatation have not been defined. Experiments were performed to assess the role of endothelial-derived mediators in this response. In isolated pressurized cutaneous mouse tail arteries, cooling (28°C) did not affect the magnitude of dilatation to acetylcholine in preconstricted arteries. However, inhibition of nitric oxide (NO) [NG-nitro-l-arginine methyl ester (l-NAME)] and prostacyclin (PGI2) (indomethacin) reduced acetylcholine-induced dilatation at 37°C but not at 28°C, suggesting that cooling increased NO/PGI2-independent dilatation. This NO/PGI2-independent dilatation was reduced by inhibition of endothelial SK (UCL1684) and IK (TRAM34) Ca2+-activated K+-channels (KCa), consistent with endothelium-derived hyperpolarization (EDH). Cooling also increased dilatation to direct activation of KCa channels (SKA31, CyPPA) but did not affect dilatation to exogenous NO (DEA-NONOate). This cooling-induced increase in EDH-type dilatations was associated with divergent effects on potential downstream EDH mechanisms: cooling reduced dilatation to K+, which mimics an intercellular K+ cloud, but increased direct communication between endothelial and smooth muscle cells (myoendothelial coupling), assessed by cellular transfer of biocytin. Indeed, inhibition of gap junctions (carbenoxolone) abolished the EDH-type component of dilatation to acetylcholine during cooling but did affect NO-dominated dilatation at 37°C. Cooling also inhibited U46619 constriction that was prevented by inhibition of IK and SK KCa channels or inhibition of gap junctions. The results suggest that cooling dilates cutaneous arteries by increasing myoendothelial communication and amplifying EDH-type dilatation.NEW & NOTEWORTHY Cold causes cutaneous vasoconstriction to restrict heat loss. Although cold also initiates cutaneous dilatation, the mechanisms and role of this dilatation have not been clearly defined. This study demonstrates that cooling increases myoendothelial coupling between smooth muscle and endothelial cells in cutaneous arteries, which is associated with increased endothelium-derived hyperpolarization (EDH)-type dilatation. Dysfunction in this process may contribute to excessive cold-induced constriction and tissue injury.


Assuntos
Artérias/fisiologia , Temperatura Baixa , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Pele/irrigação sanguínea , Vasodilatação , Acetilcolina/farmacologia , Alcanos/farmacologia , Animais , Artérias/efeitos dos fármacos , Carbenoxolona/farmacologia , Endotélio Vascular/metabolismo , Epoprostenol/farmacologia , Indometacina/farmacologia , Masculino , Potenciais da Membrana , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Pirazóis/farmacologia , Compostos de Quinolínio/farmacologia , Vasoconstrição , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
11.
Life Sci ; 254: 117813, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428597

RESUMO

AIMS: This study aimed to investigate the effect of lymphocytes in wound healing and the underlying mechanisms, in diabetic and non-diabetic mice, using Balb/c recombination activating gene (Rag)-2 and interleukin 2 receptor gamma (IL-2Rγ) double knockout (KO) (RAG2-/- IL-2Rγ-/-) mice. MAIN METHODS: Wound healing in vivo was performed in control and STZ-induced diabetic mice, in both KO and WT mice. Inflammation and ROS production were evaluated by immunofluorescence microscopy analysis, antioxidant enzymes and angiogenesis were evaluated by quantitative PCR and immunofluorescence microscopy analysis, and wound closure kinetics evolution was evaluated by measurement of acetate tracing of the wound area. KEY FINDINGS: Wound closure was significantly delayed in KO mice, where the M1/M2 macrophage ratio and basal ROS levels were significantly increased, while antioxidant defenses and angiogenesis were significantly decreased. Moreover, the expected increase in matrix metallopeptidase (MMP)-9 protein levels in diabetic conditions was not observed in KO mice, suggesting that the mechanisms leading to the increase in MMP-9 observed in diabetic wounds may in part be lymphocyte-dependent. SIGNIFICANCE: Our results indicate that lack of lymphocytes compromises wound healing independent of diabetes. The lack of these cells, even in non-diabetic mice, mimics the phenotype observed in wounds under diabetic conditions. Moreover, the combination of diabetes and the lack of lymphocytes, further impair the wound healing conditions, indicating that when the innate regulatory function is lost in these KO mice, excessive M1 polarization, poor angiogenesis and impaired wound healing are worsen.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Diabetes Mellitus Experimental/fisiopatologia , Subunidade gama Comum de Receptores de Interleucina/fisiologia , Linfócitos/fisiologia , Neovascularização Fisiológica/fisiologia , Cicatrização/fisiologia , Animais , Proteínas de Ligação a DNA/genética , Inflamação/metabolismo , Subunidade gama Comum de Receptores de Interleucina/genética , Ativação de Macrófagos/fisiologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Pele/irrigação sanguínea , Pele/metabolismo
12.
Am J Cardiol ; 125(11): 1725-1731, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278465

RESUMO

Hookah (waterpipe) smoking is a growing tobacco epidemic. Though perceived as a safer tobacco alternative, hookah smoke contains, in addition to tobacco combustion products, large amounts of charcoal combustion products-implicated in cardiovascular disease-from the burning charcoal used to heat the flavored tobacco. To date, little is known on the vascular effects of hookah smoking. The aim of this study was to characterize the peripheral circulatory response to acute hookah smoking in cutaneous and muscular beds. In 21 healthy young adult habitual hookah smokers who did not smoke cigarettes (age 24 ± 1 years, mean ± SE), we measured plasma nicotine, exhaled carbon monoxide, skin blood flow (laser Doppler velocimetry) and calf muscle blood flow (strain-gauge plethysmography) before and for up to 60 minutes after ad lib hookah smoking. In nine subjects, nonsmoking time-control studies were performed. Hookah smoking, which increased plasma nicotine by 5.8 ng/ml (from 0.6 ± 0.1 to 6.4 ± 1.3, p <0.001) and exhaled carbon monoxide by 27 ppm (from 2.7 ± 0.2 to 29.5 ± 2.2, p <0.001), decreased skin blood flow by 23% (20.1 ± 2.8 to 14.8 ± 1.9 units, p <0.001) and increased skeletal muscle blood flow by 34% (2.3 ± 0.1 to 2.9 ± 0.2 units, p = 0.010). These responses required more than one hour to recover after smoking cessation. All cardiovascular parameters were unchanged in the nonsmoking time-control studies. Although perceived to be innocuous, hookah smoking produces acute cutaneous vasoconstriction with skeletal muscle vasodilation, a dissociated pattern of peripheral blood flow responses that is characteristic of nicotine and carbon monoxide. In conclusion, these findings provide objective evidence to challenge the perception that hookah smoking is a safer tobacco alternative.


Assuntos
Músculo Esquelético/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Pele/irrigação sanguínea , Fumar Cachimbo de Água/fisiopatologia , Adulto , Testes Respiratórios , Monóxido de Carbono/metabolismo , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Fluxometria por Laser-Doppler , Masculino , Nicotina/metabolismo , Pletismografia , Fumar Cachimbo de Água/metabolismo , Adulto Jovem
13.
Lasers Med Sci ; 35(7): 1589-1597, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32277406

RESUMO

Laser therapy has been widely used to treat port-wine stain (PWS) and other cutaneous vascular lesions via selective photothermolysis. High incident laser fluence is always prohibited in clinic to prevent the thermal damage in normal skin tissue, leading to insufficient energy deposition on the target blood vessel and incomplete clearance of PWS lesion. In this study, repeated multipulse laser (RMPL) irradiation was proposed to induce acute thermal damage to target blood vessels with low incident fluence (40 J/cm2 for 1064-nm Nd:YAG laser). The feasibility of the method was investigated using animal models. Repeated multipulse irradiation cycles with 10-min intervals were performed in RMPL. A hamster dorsal skin chamber model with a visualization system was constructed to investigate the instant generation of thermal coagulum and relevant hemostasis by thrombus formation during and after irradiation under 1064 nm Nd:YAG single multipulse laser (SMPL) and RMPL irradiation. The diameter of the target blood vessel and the size of thermal coagula were measured before and after laser irradiation. The reflectance spectra of the dorsal skin were measured by a reflectance spectrometer during RMPL. Stasis thermal coagula that clogged the vessel lumen were generated during SMPL irradiation with low incident fluence. However, there was no acute thermal damage of blood vessels. Reflectance spectra measurement showed that the generation of thermal coagula and subsequent thrombus formation increases blood absorption by more than 10% within the first 10 min after laser irradiation. Acute vessel thermal damage could be induced in the target blood vessel by RMPL with low incident fluence of 40 J/cm2. Compared with our previous SMPL study, nearly 30% reduction in incident laser fluence was achieved by RMPL. Low fluence RMPL may be a promising approach to improve the therapeutic outcome for patients with cutaneous vascular lesions by improving energy deposition on the target blood vessel.


Assuntos
Vasos Sanguíneos/efeitos da radiação , Hemostasia/efeitos da radiação , Lasers de Estado Sólido/uso terapêutico , Pele/irrigação sanguínea , Pele/efeitos da radiação , Temperatura , Animais , Cricetinae , Feminino , Humanos , Camundongos , Mancha Vinho do Porto/cirurgia
14.
Transplantation ; 104(7): e208-e213, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32235257

RESUMO

BACKGROUND: Histologic criteria for diagnosing acute rejection in vascularized composite tissue allograft (VCA) have been established by the Banff 2007 Working Classification of Skin-Containing Composite Tissue Allograft, but the role of early vascular lesions in graft rejection warrants additional analysis. METHODS: We performed a retrospective study of 34 skin biopsies performed over 430 d for rejection surveillance, in Canada's first face allotransplant recipient. Three observers reviewed all biopsies to assess the nature and intensity of the inflammatory skin infiltrate. A complete histological and immunohistochemical review of the vascular components was performed with a focus on lymphocytic vasculitis, intravascular fibrin, vessel caliber, extent of injury, C4d positivity, and inflammatory cell phenotyping. We then correlated these data points to clinical and immunosuppression parameters. RESULTS: Acute vascular damage in biopsies that would be classified as mild acute rejection correlates with troughs in immunosuppression and subsides when immunosuppressive tacrolimus doses are increased. Grade 0 Banff rejection and Grade I without lymphocytic vasculitis were almost indistinguishable, whereas Grade I with lymphocytic vasculitis was an easy and reproducible histologic finding. CONCLUSIONS: Our results highlight the possible relevance of vascular injury in the context of VCA, as its presence might underlie a more aggressive form of immune rejection. If these findings are validated in other VCA patients, vascular injury in mild rejection might warrant a different clinical approach.


Assuntos
Transplante de Face/efeitos adversos , Rejeição de Enxerto/diagnóstico , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Vasculite/complicações , Idoso , Biópsia , Canadá , Aloenxertos Compostos/irrigação sanguínea , Aloenxertos Compostos/patologia , Relação Dose-Resposta a Droga , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/farmacocinética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/irrigação sanguínea , Pele/patologia , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Vasculite/diagnóstico , Vasculite/tratamento farmacológico , Vasculite/imunologia
15.
Microvasc Res ; 130: 104008, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32330479

RESUMO

Endothelial dysfunction (ED) plays a key role in developing of cardiovascular diseases and is an important predictor of future cardiovascular events. Nevertheless, there is no established method assessing endothelial function in general population. The most popular protocol includes the ultrasound-flow-mediated-dilation, but its repeatability is operator-dependent. We intended to compare the two other operator-independent methods assessing endothelial function - the EndoPAT and Laser Doppler flowmetry (LD), and we endeavored to place them on current individual profile of biochemical cardiovascular risk and endothelial function. A total of 61 clinically healthy subjects (aged 29 ± 1y) were investigated. The blood was collected for conventional cardiovascular risk markers, the NO-pathway metabolites (ADMA, L-arginine, SDMA), oxidative-stress-markers (MDA, thiol-index) as well as endothelial and platelet activation markers (sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF). Subsequently, all participants underwent examination by both EndoPAT and LD. There was a poor correlation between EndoPAT and LD results. No significant differences between participants with preserved and impaired endothelial function regarding endothelial activation nor cardiovascular risk markers were observed. Both methods assess endothelial function independently from the profile of endothelial pro/anti-inflammatory status and conventional risk factors, therefore further prospective studies are needed in order to verify their additional value in the cardiovascular risk stratification.


Assuntos
Endotélio Vascular/fisiopatologia , Fluxometria por Laser-Doppler , Manometria , Microcirculação , Pele/irrigação sanguínea , Adulto , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Feminino , Humanos , Hiperemia/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Procedimentos Desnecessários
16.
Microvasc Res ; 130: 104006, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32320708

RESUMO

OBJECTIVE: A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis. METHODS: Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud's phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 'early') and 60 healthy controls. RESULTS: Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p = 0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p = 0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p = 0.0007). Perfusion positively correlated with oxygenation (r = 0.23, p < 0.001), and capillary density negatively with skin thickness (r = -0.26, p < 0.001). CONCLUSION: Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.


Assuntos
Fluxometria por Laser-Doppler , Angioscopia Microscópica , Microvasos/diagnóstico por imagem , Doença de Raynaud/diagnóstico por imagem , Esclerodermia Difusa/diagnóstico por imagem , Esclerodermia Limitada/diagnóstico por imagem , Pele/irrigação sanguínea , Ultrassonografia , Adulto , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Microcirculação , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo , Oxigênio/sangue , Valor Preditivo dos Testes , Doença de Raynaud/sangue , Doença de Raynaud/patologia , Doença de Raynaud/fisiopatologia , Fluxo Sanguíneo Regional , Esclerodermia Difusa/sangue , Esclerodermia Difusa/patologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/sangue , Esclerodermia Limitada/patologia , Esclerodermia Limitada/fisiopatologia , Pele/metabolismo , Pele/patologia , Análise Espectral
17.
Plast Reconstr Surg ; 145(4): 757e-768e, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32221215

RESUMO

BACKGROUND: Transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. The consequent side effects and looming specter of chronic rejection portend eventual allograft loss. Development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation. METHODS: With a modified delayed tolerance induction protocol, 10 cynomolgus macaques received hand (n = 2) or face vascularized composite allografts across both full and haploidentical major histocompatibility complex barriers before donor bone marrow transplantation at a later date. Protocol and for-cause allograft skin biopsies were performed for immunohistochemical analysis and analysis of donor-recipient leukocyte contribution; mixed chimerism in peripheral blood and in vitro immune responses were assessed serially. RESULTS: Before bone marrow transplantation, maintenance immunosuppression for 4 months led to lethal complications, including posttransplant lymphoproliferative disorder (in two of four recipients), which necessitated early study termination. Shortening the maintenance period to 2 months was clinically relevant and allowed all subsequent subjects (n = 6) to complete the delayed tolerance induction protocol. Acute rejection developed within the first 2 to 4 weeks after transplantation, with corresponding near-complete turnover of allograft leukocytes from donor to recipient origin, but donor-specific antibodies remained negative. After bone marrow transplantation, mixed chimerism failed to develop, although carboxyfluorescein succinimidyl ester mixed lymphocyte reaction demonstrated generalized unresponsiveness. However, the accrual of subsequent rejection episodes eventually culminated in graft vasculopathy and irreversible allograft loss. CONCLUSIONS: Despite the various advantages of the delayed tolerance induction protocol, it failed to reliably induce mixed chimerism and thus immunologic tolerance to vascularized composite allografts, given currently available immunosuppression treatment options. Ongoing work shows promise in overcoming these limitations.


Assuntos
Aloenxertos Compostos/imunologia , Rejeição de Enxerto/prevenção & controle , Tolerância Imunológica , Condicionamento Pré-Transplante/métodos , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Animais , Biópsia , Transplante de Medula Óssea/métodos , Aloenxertos Compostos/patologia , Aloenxertos Compostos/transplante , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Leucócitos/imunologia , Teste de Cultura Mista de Linfócitos , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Macaca fascicularis , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Falha de Tratamento , Alotransplante de Tecidos Compostos Vascularizados/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-32142355

RESUMO

The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linköping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P < 0.001) and the highest baseline low-speed perfusion (P < 0.001). Women had higher peak oxygen saturation (P < 0.001), lower RBC tissue fraction, in general (P < 0.001), lower baseline perfusion in all speed regions (P = 0.01), and lower peak high-speed perfusion at hyperemia (P < 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity.NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of microvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis, prognosis, and treatment in disease-specific populations.


Assuntos
Fluxometria por Laser-Doppler/normas , Microcirculação , Pele/irrigação sanguínea , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Valores de Referência , Fluxo Sanguíneo Regional , Fatores Sexuais
19.
Lasers Med Sci ; 35(7): 1649-1652, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32193822

RESUMO

Pulse laser treatment is useful for aesthetic improvement in children with capillary vascular malformation and residual superficial haemangiomas. However, pulse laser treatment is painful, and repeated procedures are usually required to achieve a satisfactory clinical result. Evidence shows that analgesia in children undergoing pulse laser treatment may vary from general anaesthesia to no treatment at all. This report describes our institutional experience with deep sedation in children with capillary vascular malformation, undergoing laser pulse treatment.


Assuntos
Sedação Profunda , Lasers , Pele/irrigação sanguínea , Malformações Vasculares/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
20.
Microvasc Res ; 130: 104000, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32194082

RESUMO

INTRODUCTION: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. MATERIALS AND METHODS: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (CRBC,TiVi), oxygenation (ΔCOH,TiVi) and deoxygenation (ΔCDOH,TiVi) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). RESULTS: During arterial occlusion, CRBC,TiVi remained unchanged while ΔCOH,TiVi decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, CRBC,TiVi increased to 39.2 (18.8) AU (p < 0.001), ΔCOH,TiVi increased to 38.5. During venous occlusion, CRBC,TiVi increased to 28.9 (11.2) AU (p < 0.001), ΔCOH,TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. CONCLUSION: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.


Assuntos
Hemoglobinas/metabolismo , Microcirculação , Oxiemoglobinas/metabolismo , Pele/irrigação sanguínea , Adulto , Velocidade do Fluxo Sanguíneo , Contagem de Eritrócitos , Feminino , Antebraço , Voluntários Saudáveis , Humanos , Hiperemia/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Fluxo Sanguíneo Regional , Análise Espectral , Fatores de Tempo , Adulto Jovem
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