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Medicinas Complementárias
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1.
Autoimmun Rev ; 22(8): 103362, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37230310

RESUMEN

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.


Asunto(s)
Síndrome de Behçet , Productos Biológicos , Vasculitis , Humanos , Síndrome de Behçet/tratamiento farmacológico , Vasculitis/tratamiento farmacológico , Rituximab/uso terapéutico , Terapia Biológica , Productos Biológicos/uso terapéutico
3.
Med Clin (Barc) ; 159(10): 489-496, 2022 11 25.
Artículo en Inglés, Español | MEDLINE | ID: mdl-36049972

RESUMEN

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis.


Asunto(s)
Enfermedades Autoinflamatorias Hereditarias , Vasculitis Sistémica , Vasculitis , Adulto , Masculino , Humanos , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Inflamación/complicaciones , Vasculitis/diagnóstico , Vasculitis/genética , Vasculitis/terapia , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/genética , Vasculitis Sistémica/terapia
4.
Toxicol Pathol ; 50(4): 408-414, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35608030

RESUMEN

Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing. This review article describes the potential rare clinical events in drug-induced kidney injury that might be noted with these new therapies and their potential impact on patients. Potential pathogenic mechanisms related to immunogenicity, immune complex formation, and stimulation of downstream proinflammatory pathways with some of these alternative medicine classes have resulted in the potential for glomerulonephritis, acute interstitial nephritis, renal vasculitis, and other immune-mediated renal disorders in humans. This contrasts with nonclinical toxicity studies, where biologic therapies more often result in vasculitis and glomerulonephritis associated with antidrug antibodies and immunomodulatory pharmacology, and which are not always predictive of clinical effects. While nonclinical antidrug antibody-related renal disease is generally not clinically relevant, other immune-mediated nephrotoxicities associated with immunomodulatory drugs may be predictive of clinical adverse events. Fortunately, these conditions are still rare and account for a small percentage of serious adverse events in kidneys of patients.


Asunto(s)
Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Glomerulonefritis , Nefritis Intersticial , Vasculitis , Antineoplásicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Glomerulonefritis/inducido químicamente , Humanos , Riñón , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/complicaciones , Vasculitis/inducido químicamente
5.
Front Endocrinol (Lausanne) ; 13: 806361, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35250864

RESUMEN

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.


Asunto(s)
Fracturas Óseas , Osteoporosis , Vasculitis Sistémica , Vasculitis , Densidad Ósea , Fracturas Óseas/inducido químicamente , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Inflamación/inducido químicamente , Osteoporosis/inducido químicamente , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Vasculitis Sistémica/inducido químicamente , Vasculitis Sistémica/tratamiento farmacológico , Vasculitis/inducido químicamente , Vasculitis/tratamiento farmacológico
6.
Ocul Immunol Inflamm ; 30(4): 1001-1004, 2022 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33545017

RESUMEN

PURPOSE: To describe a case of outer retinitis with frosted branch angiitis associated with mumps infection treated with hyperbaric oxygen (HBO) therapy. METHODS: Observational case report. CASE REPORT: A four-year-old boy with bilateral blindness was diagnosed with necrotizing outer retinitis with frosted branch angiitis associated with serologically confirmed mumps virus infection. He was treated with HBO therapy. Visual acuity subsequently improved to 20/40 in the right eye and to 20/320 in the left eye. Sequential follow-up optical coherence tomography examinations showed progressive recovery of the outer retinal layers in the right eye. CONCLUSION: HBO therapy appears to be a feasible and safe treatment that might improve the anatomical and functional outcome in patients with mumps retinitis.


Asunto(s)
Oxigenoterapia Hiperbárica , Paperas , Vasculitis Retiniana , Retinitis , Vasculitis , Preescolar , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Masculino , Paperas/complicaciones , Vasculitis Retiniana/diagnóstico , Retinitis/diagnóstico , Retinitis/etiología , Retinitis/terapia , Tomografía de Coherencia Óptica , Vasculitis/diagnóstico
7.
Artículo en Español | LILACS, CUMED | ID: biblio-1408409

RESUMEN

Introducción: El síndrome de Behcet, o enfermedad de Behcet, es un proceso autoinflamatorio crónico, poco frecuente, de etiología desconocida. Es una vasculitis que afecta arterias y venas de todos los calibres, con alteración de la función endotelial, que se expresa clínicamente con lesiones orgánicas variadas. En su fisiopatogenia intervienen factores genéticos, microbianos e inmunológicos. Los síntomas más comunes son las úlceras orales y genitales, inflamaciones oculares (uveítis, retinitis e iritis), lesiones de piel y artritis. Objetivo: Evaluar diversos marcadores de la respuesta inmune en paciente con síndrome de Behcet. Presentación del caso: Paciente masculino. 39 años de edad, con diagnóstico clínico de enfermedad de Behcet con reactantes de fase aguda y marcadores serológicos de autoinmunidad negativa. Las subpoblaciones linfocitarias están dentro de los valores referenciales, sin evidencias de activación linfocitaria. La presencia de una doble población de linfocitos B y los antecedentes familiares, sugieren la existencia de una población de linfocitos B de autoreconocimiento y la posible presencia de factores genéticos, respectivamente. El paciente respondió favorablemente a la terapia con esteroides. Conclusiones: El estudio apoya el criterio de que, en condiciones basales, no se detectan marcadores humorales de autoinmunidad, alteraciones de los valores de las subpoblaciones linfocitarias, ni evidencias de activación linfocitaria, pero no se puede excluir la presencia de una población de linfocitos B de autoreconocimiento(AU)


Introduction: Behcet's syndrome, also known as Behcet's disease is a chronic autoinflammatory process of low frequency and unknown etiology. It's an all sizes arteries and veins affecting vasculitis that causes an alteration of endothelial function and is expressed clinically by organ damage at various levels. Its pathogenesis involves genetic, microbial and immunological factors. The most common symptoms are oral and genital ulcers, eye inflammation (uveitis, iritis and retinitis), skin lesions and arthritis. Objective: to evaluate several inmunological markers in a patient with Behcet syndrome. Case presentation: 39 years old masculine patientwith clinical diagnosis of Behcet disease with negative acute phase reactants and serological authoinmunity markers and lymphocyte populations within referential range, without evidences of lymphocyte activation. The presence of a double B lymphocyte population and familial background, suggest the presence of a self recognitionB lymphocyte population and the probable presence of genetic factors, respectively. There was a good response to steroids treatment. Conclusions: The study supports the idea that at baseline, not humoral autoimmunity markers, changes in the values of lymphocyte subpopulations, and evidence of lymphocyte activation is detected, but can not exclude the presence of a population of B lymphocytes self-recognition(AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Artritis , Uveítis , Vasculitis , Autoinmunidad , Síndrome de Behçet , Genética Microbiana , Factores Inmunológicos , Diagnóstico Clínico
8.
Circ Res ; 128(9): 1344-1370, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33914601

RESUMEN

Calcific aortic valve disease is dramatically increasing in global burden, yet no therapy exists outside of prosthetic replacement. The increasing proportion of younger and more active patients mandates alternative therapies. Studies suggest a window of opportunity for biologically based diagnostics and therapeutics to alleviate or delay calcific aortic valve disease progression. Advancement, however, has been hampered by limited understanding of the complex mechanisms driving calcific aortic valve disease initiation and progression towards clinically relevant interventions.


Asunto(s)
Estenosis de la Válvula Aórtica/etiología , Válvula Aórtica/citología , Válvula Aórtica/patología , Calcinosis/etiología , Progresión de la Enfermedad , Células Endoteliales/fisiología , Válvula Aórtica/inmunología , Válvula Aórtica/fisiología , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/inmunología , Estenosis de la Válvula Aórtica/terapia , Calcinosis/diagnóstico , Calcinosis/inmunología , Calcinosis/terapia , Moléculas de Adhesión Celular/metabolismo , Homeostasis , Humanos , Sistema Inmunológico/fisiología , Mediadores de Inflamación/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo III/metabolismo , Pronóstico , Especies Reactivas de Oxígeno , Factores de Riesgo , Vasculitis/etiología
9.
Arq. Asma, Alerg. Imunol ; 5(1): 79-84, jan.mar.2021. ilus
Artículo en Portugués | LILACS | ID: biblio-1398416

RESUMEN

Introdução: O novo coronavírus causou uma pandemia e desafio na saúde pública em todo o mundo. Até hoje muitos mecanismos do vírus no hospedeiro foram desvendados, cujo conhecimento é essencial para entender a evolução clínica e desenvolver uma estratégia de terapia adequada para a infecção com COVID-19. Contudo, pouco se sabe da infecção por COVID-19 em pacientes com erros inatos da imunidade (EII), principalmente em pacientes com síndromes autoinflamatórias. Objetivo: Descrever a evolução de pacientes com erros inatos da imunidade acometidos por SARS-CoV-2 em um centro de referência em doenças raras e da imunidade no Brasil. Material e métodos: Foram analisados retrospectivamente dados clínicos, radiológicos, patológicos e laboratoriais de pacientes com erros inatos da imunidade infectados por SARS-CoV-2 de março a dezembro de 2020. Resultados: Ao total, dados de 13 pacientes com diversos EII foram coletados para descrever tanto a evolução da doença quanto para buscar mais conhecimento sobre o tratamento desses pacientes. Em nenhum paciente a síndrome da angústia respiratória aguda foi observada, e também não foi observado nenhum óbito. A grande maioria dos pacientes teve evolução com síndrome gripal. Observou-se, em um paciente com CAPS-NLRP3, rash cutâneo vasculítico responsivo ao uso de anti-IL1. Conclusão: Neste pequeno grupo de pacientes com erros inatos da imunidade e com infecção por SARS-CoV-2, o risco de fatalidade foi menor do que observado na literatura. Especialmente, o fato de que a maioria apresenta maior predisposição a inflamação do que infecção deve ser levada em conta na análise dos dados finais. Reportamos pela primeira vez a presença de urticária vasculítica em paciente com CAPS, que habitualmente apresentam-se com urticária neutrofílica. Tal achado ressalta a capacidade de injúria vascular do vírus, mesmo em indivíduos predispostos geneticamente.


Introduction: The pandemic caused by the new coronavirus has become a global public health challenge. To date, many pathophysiological mechanisms of the virus have been explained, which is essential to understand clinical evolution and to develop appropriate therapeutic strategies for patients with COVID-19. However, less is known about COVID-19 in patients with inborn errors of immunity (IEI), especially in those with autoinflammatory disorders. Objective: To report the natural evolution of a group of patients with IEI infected with SARS-CoV-2 treated at a center of excellence in rare diseases and immunity in Brazil. Material and methods: Clinical, radiological, pathological, and laboratory data of patients treated from March to December 2020 were retrospectively retrieved and analyzed. Results: Data of 13 patients with IEI were collected to describe the natural course of the infection with SARS-CoV-2 and to enhance understanding of treatment for these patients. Neither acute respiratory distress syndrome nor death were observed. The vast majority of patients had flu-like symptoms. Urticarial vasculitis was observed in one patient with CAPS-NLRP3 responsive to the use of anti-IL1. Conclusion: In this small group of patients with IEI and SARSCoV- 2 infection, fatality risk was lower than that observed in the literature. Importantly, the fact that our group is composed mainly of patients with predisposition to inflammation instead of infection should be taken into account for final data analysis. Furthermore, we observed for the first time the presence of urticarial vasculitis in a patient with CAPS, which is usually characterized by neutrophilic urticaria. Such finding reinforces the virus ability to cause vascular injury, even in individuals with a genetic predisposition.


Asunto(s)
Humanos , Predisposición Genética a la Enfermedad , SARS-CoV-2 , COVID-19 , Inmunidad , Pacientes , Síndrome de Dificultad Respiratoria del Recién Nacido , Terapéutica , Urticaria , Vasculitis , Evolución Clínica , Estudios Retrospectivos , Estrategias de Salud , Coronavirus , Enfermedades Raras , Infecciones
10.
Rev. argent. reumatolg. (En línea) ; 32(1): 21-25, mar. 2021. ilus, tab
Artículo en Español | LILACS, BINACIS | ID: biblio-1279755

RESUMEN

Introducción: Diversas entidades clínicas, como enfermedades autoinmunes, infecciones, neoplasias y fármacos pueden manifestarse con lesiones vasculíticas en la piel. Debido a la heterogeneidad de las causas, suelen representar un desafío diagnóstico. El objetivo de este estudio es describir la etiología de las vasculitis cutáneas (VC) y evaluar las características clínicas, histológicas y de laboratorio halladas en estos pacientes. Material y métodos: Se realizó un estudio retrospectivo con revisión de historias clínicas de pacientes mayores de 16 años con VC por diagnóstico clínico y/o histológico evaluados en el período 2010-2018. Resultados: Se incluyeron 74 pacientes. El 69% son mujeres con una edad media al diagnóstico de 41 años (DE 16.5, rango 16-75). Las causas más frecuentes asociadas a las VC fueron las enfermedades autoinmunes (EAI) en un 50% de los pacientes evaluados. En el 29.7% de los casos no pudo identificarse una causa subyacente. En el 2.7% de los casos se asoció a neoplasias, otro 2.7% a fármacos y un 12% a otras etiologías. El 76% de los pacientes presentaron formas clínicas no severas, predominando la púrpura palpable en el 65% de los casos. Entre los pacientes biopsiados, el 76% fueron vasculitis leucocitoclásticas (VLC). Como manifestaciones extracutáneas asociadas, predominó el compromiso articular (43,2%). En las vasculitis asociadas a EAI, el 33 % presentó compromiso renal, en tanto que éste no se observó en ninguno de los pacientes con vasculitis idiopáticas. El 78% de los pacientes recibieron glucocorticoides sistémicos. Conclusión: En nuestro centro, la etiología más común de VC fue la asociada a EAI. La mayoría de los pacientes eran mujeres. Clínicamente predominaron las manifestaciones cutáneas no severas y la VLC fue el hallazgo más frecuente en las biopsias.


Background: Various clinical entities, such as autoimmune diseases, infections, neoplasms and drugs can manifest with vasculitic lesions on the skin. Due to the heterogeneity of causes, they often represent a diagnostic challenge. The aim of this study is to describe the etiology of cutaneous vasculitis (CV) and to assess the clinical, histological and laboratory characteristics found in these patients. Material and methods: A retrospective study was carried out with a review of the medical records of patients over 16 years old with CV by clinical and/or histological diagnosis evaluated in the period 2010-2018. Results: 74 patients were included. 69% are women with a mean age at diagnosis of 41 years (SD 16.5, range 16-75). The most frequent causes associated with CVs were autoimmune diseases (AID) in 50% of the patients evaluated. In 29.7% of the cases, an underlying cause could not be identified. In 2.7% of the cases it was associated with neoplasms, another 2.7% with drugs, and 12% with other etiologies. 76% of the patients presented non-severe clinical forms, with palpable purpura predominant in 65% of the cases. Among the biopsied patients, 76% were leukocytoclastic vasculitis (LCV). As associated extracutaneous manifestations, joint involvement predominated (43.2%). In vasculitis associated with AID, 33% presented renal involvement, while this was not observed in any of the patients with idiopathic vasculitis. 78% of the patients received systemic glucocorticoids. Conclusion: In our center, the most common etiology of CV was associated with AID. Most of the patients were women. Clinically, non-severe skin manifestations predominated and VLC was the most frequent finding in biopsies.


Asunto(s)
Vasculitis , Manifestaciones Cutáneas , Diagnóstico Clínico
11.
Phytother Res ; 35(2): 1033-1047, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33006176

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Dieta Alta en Grasa/métodos , Células Endoteliales/metabolismo , Glucósidos/uso terapéutico , Interleucina-17/metabolismo , Monoterpenos/uso terapéutico , Vasculitis/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Glucósidos/farmacología , Humanos , Masculino , Monoterpenos/farmacología , Ratas , Transducción de Señal
12.
Biosci Rep ; 40(10)2020 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-33030503

RESUMEN

Bone morphogenetic protein-2 (BMP-2) is commonly applied in spinal surgery to augment spinal fusion. Nevertheless, its pro-inflammatory potential could induce dangerous side effects such as vascular hyper-permeability, posing the need for manners against this condition. The present study aims to investigate the protective effect of Zanthoxylum nitidum (ZN) on BMP-2-related hyperpermeability and inflammation on the human umbilical vein endothelial cells (HUVECs). The results revealed that, in a concentration-dependent manner, BMP-2 enhanced the production of pro-inflammatory cytokines, including interleukin (IL)-1α, IL-1ß, and tumor necrosis factor-α, which were, however, suppressed by ZN. ZN inhibited BMP-2-induced inflammatory response by suppressing the phosphorylation of NF-κBp65 and IκB, and the abnormal nuclear translocation of p65. Moreover, the inhibited expression intercellular tight junction protein VE-cadherin and Occludin caused by BMP-2 was blocked by ZN. The hyper-permeability of HUVECs induced by BMP-2, as expressed as the higher fluorescent intensity of dextran, was also reversed by ZN. Overall, these findings demonstrated that ZN antagonized BMP-2-induced inflammation and hyperpermeability. It could be a therapeutic candidate for the treatment of BMP-2-induced side effects during spinal fusion.


Asunto(s)
Antiinflamatorios/farmacología , Proteína Morfogenética Ósea 2/toxicidad , Permeabilidad Capilar/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Extractos Vegetales/farmacología , Vasculitis/prevención & control , Zanthoxylum , Antiinflamatorios/aislamiento & purificación , Células Cultivadas , Citocinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Mediadores de Inflamación/metabolismo , FN-kappa B/metabolismo , Fosforilación , Extractos Vegetales/aislamiento & purificación , Vasculitis/metabolismo , Vasculitis/patología , Zanthoxylum/química
13.
Pharmacotherapy ; 40(11): 1099-1107, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33090530

RESUMEN

BACKGROUND: Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban. OBJECTIVE: We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to describe clinical characteristics associated with CSVV among DOAC-exposed patients. Furthermore, we characterized this signal in the Sentinel System to relate the clinical data from the individual FAERS cases to population-based electronic healthcare data. METHODS: We queried FAERS for all cases of CSVV associated with DOACs from U.S. approval date of each DOAC through March 16, 2018. Within the Sentinel System, we identified incident CSVV cases using ICD-9 and ICD-10 diagnosis codes among adults aged ≥ 30 years who received a DOAC in the prior 90 days between January 1, 2010, and June 30, 2018. We excluded patients with evidence of select autoimmune diagnoses in the 183 days prior to their CSVV diagnoses and reported patient characteristics in the 183-day period prior to CSVV diagnoses. RESULTS: In FAERS, we identified 50 cases of CSVV reported with rivaroxaban (n=26), apixaban (n=14), dabigatran (n=9), and edoxaban (n=1). Approximately 50% of the cases reported time to onset within 10 days after DOAC exposure. When specified, the predominant type of CSVV reported was leukocytoclastic vasculitis (n=31), followed by Henoch-Schonlein purpura (n=4). Hospitalization occurred in most of the cases (n=37). Switching of the offending agent after the development of CSVV was reported (n=26). Three rivaroxaban (n=3) cases and one dabigatran case (n=1) reported positive rechallenge. In the Sentinel system, we identified 3659 CSVV cases with prior DOAC exposure, with 85% of events occurring within 10 days. CONCLUSIONS: The assessment of FAERS cases, combined with the temporal clustering of the Sentinel System cases suggest a possible causal relationship of DOACs and CSVV. Future efforts should characterize the risk of CSVV among the various DOAC users.


Asunto(s)
Anticoagulantes/efectos adversos , Vasculitis/epidemiología , Administración Oral , Adolescente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , United States Food and Drug Administration , Vasculitis/etiología , Adulto Joven
14.
Medicine (Baltimore) ; 99(22): e20369, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32481419

RESUMEN

BACKGROUND: This study aims to explore the efficacy and safety of prostaglandina E1 (PE1) for the treatment of patients with thrombo-occlusive vasculitis (TOV). METHODS: Electronic databases (Cochrane Library, PUBMED, EMBASE, Web of Science, Scopus, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be sought from onset to the March 1, 2020 without language and publication status restrictions. We will include any potential randomized controlled trials that examined the efficacy of PE1 for the treatment of patients with TOV. We will appraise study quality using Cochrane risk of bias tool, and will assess the evidence quality using Grading of Recommendations Assessment Development and Evaluation. We will use RevMan 5.3 Software for statistical analysis. RESULTS: A high-quality synthesis of present evidence of PE1 for the treatment of patients with TOV will be provided in this study. CONCLUSION: This study will provide evidence to judge whether PE1 is an effective intervention for TOV. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040081.


Asunto(s)
Alprostadil/uso terapéutico , Trombosis/complicaciones , Vasculitis/tratamiento farmacológico , Humanos , Resultado del Tratamiento , Vasculitis/etiología , Metaanálisis como Asunto
15.
Minerva Cardioangiol ; 68(2): 146-152, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32429631

RESUMEN

BACKGROUND: The aim of this pilot study was the supplementary management of minimal, residual symptoms of systemic Lupus (SLE) with vasculitis (LV) in remission phases, using a natural, anti-inflammatory, antioxidant agent (Pycnogenol®) extracted from French maritime pine bark. Pycnogenol® has a significant clinical anti-inflammatory activity; it is a standardized supplement with a high-safety profile. METHODS: Subjects with Lupus vasculitis were included in the study. The standard management (SM) was used in all subjects for 8 weeks; one group added Pycnogenol® (150 mg/day) to SM. RESULTS: The two groups completing 8 weeks were comparable at baseline with 12 subjects managed with SM and 14 subjects supplemented with Pycnogenol®. No side effects due to Pycnogenol® were observed; Pycnogenol® was associated with an optimal tolerability. The proportion of patients with photosensitivity, oral ulcers, renal-associated hematuria (minimal), leukopenia, lymphopenia, thrombocytopenia, positive anti-DNA and positive antiphospolipids tests were significantly lower in the Pycnogenol® group (P<0.05) at 8 weeks in comparison with controls. No difference in activity between SM and supplementation was observed for rash, serositis, anemia, neurological symptoms (all mild at inclusion) and anti-Smith. Considering additional clinical parameters such as the need for corticosteroids, peripheral ischemia, oxidative stress, the effects of Pycnogenol® appeared to be superior to SM alone (P<0.05). The decrease in oxidative stress was significantly higher with Pycnogenol® (P<0.05) compared to SM. This is particularly interesting as it has not been observed before in LV. Considering microvascular parameters, the number of subjects with 'cold' hypoperfused thermographic areas was significantly lower in the supplement group (P<0.05) and distal flux (laser Doppler) was higher with the supplement (P<0.05) at 8 weeks. CONCLUSIONS: This pilot registry indicates that Pycnogenol® can be safely used in subjects with LV with mild symptoms (in remission) possibly avoiding some drug treatments that may cause side effects. A larger study in progress is evaluating the effects of Pycnogenol® on recurrent symptoms in subjects in remission.


Asunto(s)
Antioxidantes/administración & dosificación , Flavonoides/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Vasculitis/tratamiento farmacológico , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Antioxidantes/efectos adversos , Antioxidantes/farmacología , Femenino , Flavonoides/efectos adversos , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Estrés Oxidativo/efectos de los fármacos , Proyectos Piloto , Extractos Vegetales/efectos adversos , Sistema de Registros , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vasculitis/etiología , Vasculitis/fisiopatología
16.
G Ital Nefrol ; 37(1)2020 Feb 12.
Artículo en Italiano | MEDLINE | ID: mdl-32068357

RESUMEN

The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.


Asunto(s)
Síndrome Cardiorrenal/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Rigidez Vascular/fisiología , Aorta , Arginina/análogos & derivados , Arginina/metabolismo , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Síndrome Cardiorrenal/etiología , Síndrome Cardiorrenal/metabolismo , Síndrome Cardiorrenal/mortalidad , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/mortalidad , Enfermedad Crónica , Endotelio Vascular/fisiopatología , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Inflamación/metabolismo , Inflamación/fisiopatología , Infarto del Miocardio/etiología , Estrés Oxidativo , Fósforo/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Toxinas Biológicas/metabolismo , Túnica Íntima/diagnóstico por imagen , Ácido Úrico/metabolismo , Vasculitis/etiología
17.
Mol Nutr Food Res ; 63(20): e1900514, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31368236

RESUMEN

SCOPE: A gut-microbiota-dependent metabolite of L-carnitine, trimethylamine-N-oxide (TMAO), has been recently discovered as an independent and dose-dependent risk factor for cardiovascular disease (CVD). This study aims to investigate the effects of pterostilbene on reducing TMAO formation and on decreasing vascular inflammation in carnitine-feeding mice. METHODS AND RESULTS: C57BL/6 mice are treated with 1.3% carnitine in drinking water with or without pterostilbene supplementation. Using LC-MS/MS, the result shows that mice treated with 1.3% carnitine only significantly increased the plasma TMAO and pterostilbene supplementation group can reverse it. Additionally, pterostilbene decreases hepatic flavin monooxygenase 3 (FMO3) mRNA levels compared to carnitine only group. It appears that pterostilbene can alter host physiology and create an intestinal microenvironment favorable for certain gut microbiota. Gut microbiota analysis reveals that pterostilbene increases the abundance of Bacteroides. Further, pterostilbene decreases mRNA levels of vascular inflammatory markers tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin). CONCLUSION: These data suggest that amelioration of carnitine-induced vascular inflammation after consumption of pterostilbene is partially mediated via modulation of gut microbiota composition and hepatic enzyme FMO3 gene expression.


Asunto(s)
Microbioma Gastrointestinal/fisiología , Metilaminas/metabolismo , Estilbenos/farmacología , Vasculitis/prevención & control , Animales , Carnitina/toxicidad , Femenino , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción , Oxigenasas/genética , Factor de Necrosis Tumoral alfa/genética
18.
Am J Chin Med ; 47(1): 97-117, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30776912

RESUMEN

Elevated palmitic acid (PA) levels are associated with the development of inflammation, insulin resistance (IR) and endothelial dysfunction. Clinopodium chinense (Benth.) O. Kuntze has been shown to lower blood glucose and attenuate high glucose-induced vascular endothelial cells injury. In the present study we investigated the effects of ethyl acetate extract of C. chinense (CCE) on PA-induced inflammation and IR in the vascular endothelium and its molecular mechanism. We found that CCE significantly inhibited PA-induced toll-like receptor 4 (TLR4) expression in human umbilical vein endothelial cells (HUVECs). Consequently, this led to the inhibition of the following downstream adapted proteins myeloid differentiation primary response gene 88, Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon- ß and TNF receptor-associated factor 6. Moreover, CCE inhibited the phosphorylation of Ikappa B kinase ß , nuclear factor kappa-B (NF- κ B), c-Jun N-terminal kinase, extracellular regulated protein kinases, p38-mitogen-activated protein kinase (MAPK) and subsequently suppressed the release of tumor necrosis factor- α , interleukin-1 ß (IL-1 ß ) and IL-6. CCE also inhibited IRS-1 serine phosphorylation and ameliorated insulin-mediated tyrosine phosphorylation of IRS-1. Moreover, CCE restored serine/threonine kinase and endothelial nitric oxide synthase (eNOS) activation and thus increased insulin-mediated nitric oxide (NO) production in PA-treated HUVECs. This led to reverse insulin mediated endothelium-dependent relaxation, eNOS phosphorylation and NO production in PA-treated rat thoracic aortas. These results suggest that CCE can significantly inhibit the inflammatory response and alleviate impaired insulin signaling in the vascular endothelium by suppressing TLR4-mediated NF- κ B and MAPK pathways. Therefore, CCE can be considered as a potential therapeutic candidate for endothelial dysfunction associated with IR and diabetes.


Asunto(s)
Endotelio Vascular , Resistencia a la Insulina/genética , Lamiaceae , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Ácido Palmítico/efectos adversos , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Receptor Toll-Like 4/metabolismo , Vasculitis/inducido químicamente , Vasculitis/tratamiento farmacológico , Animales , Glucemia/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Vasculitis/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
J Allergy Clin Immunol ; 143(2): 458-466, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30268388

RESUMEN

Urticarial vasculitis (UV) is a difficult-to-treat condition characterized by long-lasting urticarial rashes and histopathologic findings of leukocytoclastic vasculitis. Treatment is dictated by the severity of skin and systemic involvement and the underlying systemic disease. This is a comprehensive systematic review of the efficacy of current UV treatment options. We searched for relevant studies in 7 databases, including MEDLINE, Scopus, and Web of Science. In total, 261 eligible studies and 789 unique patients with UV were included in the systematic review. Most patients with UV are adult women with chronic (≥6 weeks) and systemic disease. UV is mostly idiopathic but can be associated with drugs, malignancy, autoimmunity, and infections. It usually resolves with their withdrawal or cure. Corticosteroids are effective for the treatment of skin symptoms in more than 80% of patients with UV. However, their long-term administration can lead to potentially serious adverse effects. The addition of immunomodulatory or immunosuppressive agents often allows corticosteroid tapering and improves the efficacy of therapy. Biologicals, including omalizumab, as well as corticosteroids, cyclophosphamide, dapsone, mycophenolate mofetil, plasmapheresis, colchicine, hydroxychloroquine, intravenous immunoglobulin, nonsteroidal anti-inflammatory drugs, and cyclosporine, can be effective for both skin and systemic symptoms in patients with UV. H1-antihistamines, montelukast, danazol, H2-antihistamines, pentoxifylline, doxepin, and tranexamic acid are not effective in most patients with UV. As of yet, no drugs have been approved for UV, and management recommendations are based mostly on case reports and retrospective studies. Prospective studies investigating the effects of treatment on the signs and symptoms of UV are needed.


Asunto(s)
Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Piel/patología , Urticaria/tratamiento farmacológico , Vasculitis/tratamiento farmacológico , Adulto , Animales , Terapia Biológica , Femenino , Humanos , Masculino , Omalizumab/uso terapéutico
20.
Explore (NY) ; 14(5): 357-366, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30100128

RESUMEN

INTRODUCTION: This study was performed to evaluate the clinical effect of a Korean medicine treatment for livedoid vasculopathy (LV). METHODS: Five patients with LV were selected who exhibited blood stasis due to qi stagnation () caused by external cold () or dual deficiency of qi and blood () and who had suffered from chronic episodic LV for at least 2 years. The treatment consisted of Korean herbal medicine, Haechungtang (, HC). Five cases were evaluated based on visual symptoms. The symptoms at first visit were scored on a visual analogue scale (VAS) from 1 to 10. RESULTS: Following treatment, all of the symptoms except pigmentation disappeared completely in all cases. No symptom control with corticosteroids or warfarin was necessary. CONCLUSION: These case reports suggest that HC could be effective for treating LV. Follow-up studies and further clinical studies are needed to evaluate recurrence and to provide more efficient treatment.


Asunto(s)
Medicina Tradicional Coreana , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Enfermedades Vasculares/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Vasculitis/tratamiento farmacológico , Adulto Joven
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