Bromelain as a natural anti-inflammatory drug: a systematic review.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

Resolutividad del tratamiento con Jusvinza en pacientes confirmados de COVID-19. Santiago de Cuba, 2021

Fundamento la infección por SARS-CoV-2 es la enfermedad emergente más importante del presente siglo. En dicho contexto, el Grupo de las Industrias Biotecnológica y Farmacéutica Cubanas (BioCubaFarma) creó alternativas terapéuticas para combatir la COVID-19, entre ellas el uso de Jusvinza, la cual forma parte del protocolo utilizado en el país. Objetivo determinar la resolutividad terapéutica de Jusvinza en pacientes confirmados de COVID-19. Métodos se realizó un estudio descriptivo, durante el periodo de enero a septiembre de 2021, en el Hospital Militar Dr. Joaquín Castillo Duany, de Santiago de Cuba. El universo estuvo constituido por 166 confirmados de COVID-19, a quienes se administró Jusvinza. Se analizaron algunas variables clínicas (estado clínico, enfermedades no transmisibles asociadas, progresión clínica), epidemiológicas (edad, sexo) y farmacológicas (resolutividad, duración en días). Se utilizó una planilla de vaciamiento de datos, los cuales fueron tomados de las historias clínicas. Resultados la morbimortalidad por COVID-19 fue superior en el sexo masculino, asociado a comorbilidades y edad mayor de 60 años; el sexo femenino resultó el de mayor resolutividad al tratamiento con Jusvinza (71,7 %), la cual incrementó su porcentaje en ausencia de enfermedades crónicas no transmisibles asociadas (81,4 %). Los pacientes de alto riesgo fueron los de más baja mortalidad (15,8 %). Conclusiones la resolutividad en pacientes confirmados de COVID-19 tratados con Jusvinza fue más elevada en casos de alto riesgo que en graves y críticos.

Foundation SARS-CoV-2 infection is the most important emerging disease of this century. In this context, the Cuban Biotechnology and Pharmaceutical Industries Group (BioCubaFarma) created therapeutic alternatives to combat COVID-19, including the use of Jusvinza, which is part of the protocol used in the country. Objective to determine the Jusvinza therapeutic resolution in confirmed COVID-19 patients. Methods a descriptive study carried out from January to September 2021, at the Dr. Joaquín Castillo Duany Military Hospital, in Santiago de Cuba. The universe consisted of 166 confirmed COVID-19 cases, to whom Jusvinza was administered. Some clinical variables (clinical status, associated non-communicable diseases, clinical progression), epidemiological (age, sex) and pharmacological (resolving, duration in days) were analyzed. A data extraction form was used, which was taken from the medical records. Results morbidity and mortality from COVID-19 was higher in males, related to comorbidities and age over 60 years; The female sex was the one with the greatest response to treatment with Jusvinza (71.7%), which increased its percentage in the absence of associated chronic non-communicable diseases (81.4%). High-risk patients had the lowest mortality (15.8%). Conclusions resolution in confirmed COVID-19 patients treated with Jusvinza was higher in high-risk cases than in severe and critical cases.

ASIA and BIA-ALCL as adverse reactions to silicone breast implants / ASIA e BIA-ALCL como reações adversas aos implantes mamários de silicone

Adjuvant-induced autoimmune/inflammatory syndrome leads to capsular contracture and fibrosis from the oxidation that takes place in silicone. Anaplastic large cell lymphoma occurs through the development of a seroma, with the formation of a periprosthetic effusion, or through the infiltration of the condition itself. To analyze these conditions, a review of the literature was carried out on the symptoms and pathophysiology of the autoimmune/inflammatory syndrome induced by adjuvants and anaplastic large cell lymphoma, searched using the terms "ASIA breast silicone," "Lymphoma," "Adjuvants" "Immunologic" " Breast Implants" on the PubMed platform. Analyzing the data obtained, it was noted that the symptoms of the autoimmune/inflammatory syndrome induced by adjuvants are nonspecific, such as fatigue, myalgia, arthralgia, morning stiffness, and night sweats, and therefore need attention. Anaplastic large cell lymphoma presents with breast pain, periprosthetic effusion, and palpable mass, among other characteristics. Because of these aspects, it is concluded that a good investigation should be carried out when nonspecific symptoms appear, regardless of the time the surgery was performed since these complications can occur years later.

A síndrome autoimune/inflamatória induzida por adjuvantes leva à contratura capsular e fibrose pela oxidação que acontece no silicone. O linfoma anaplásico de grandes células ocorre através do desenvolvimento de um seroma, com a formação de derrame periprotético ou por uma infiltração da própria afecção. Para análise destes acometimentos, foi realizada uma revisão da literatura acerca da sintomatologia e fisiopatologia da síndrome autoimune/inflamatória induzida por adjuvantes e linfoma anaplásico de grandes células, pesquisada através dos termos "ASIA breast silicone" "Lymphoma" "Adjuvants" "Immunologic" "Breast Implants" na plataforma PubMed. Analisando os dados obtidos, notou-se que os sintomas da síndrome autoimune/inflamatória induzida por adjuvantes são inespecíficos, como fadiga, mialgia, artralgia, rigidez matinal e suores noturnos, e, portanto, necessitam de atenção. Já o linfoma anaplásico de grandes células se apresenta com dor mamária, derrame periprotético, massa palpável, dentre outras características. Em vista destes aspectos, conclui-se que uma boa investigação deve ser realizada ao surgirem sintomas inespecíficos, independentemente do tempo que a cirurgia foi realizada, uma vez que estas complicações podem ocorrer anos após a cirurgia.

Responses Triggered by the Immune System in Hypertensive Conditions and Repercussions on Target Organ Damage: A Review.

BACKGROUND: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature. OBJECTIVE: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage. METHODS: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement. RESULTS: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal. CONCLUSION: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage.

Comparación entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH / Comparison between immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV / Comparação entre imunomoduladores e crioterapia para o tratamento de lesões genitais em mulheres com HPV

El virus del papiloma humano es una infección prevalente, que puede infectar cualquier mucosa del cuerpo y causar verrugas genitales externas o condilomas genitales y cáncer de cuello uterino. El tratamiento es difícil con una alta recurrencia y persistencia de las mismas, lo que afecta mayormente a mujeres jóvenes. El objetivo del presente estudio fue realizar una comparación entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH. Se realizó una revisión bibliográfica de la literatura científica, entre inmunomoduladores y crioterapia para el tratamiento de lesiones genitales en mujeres con VPH de los últimos 20 años, donde se identificaron publicaciones de revisiones sistemáticas y metaanálisis. Se concluyó que la elección de los inmunomoduladores al igual que la crioterapia es mejor utilizarlos cuando existe lesiones clínicas inducidas por el VPH en la región genital y perianal en mujeres, dependiendo de la cantidad, el tamaño, la gravedad, la ubicación de las verrugas y las preferencias del paciente.

Human papillomavirus is a prevalent infection, which can infect any mucosa of the body and cause external genital warts or genital warts and cervical cancer. Treatment is difficult with a high recurrence and persistence of the same, which mainly affects young women. The objective of the present study was to compare immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV. A narrative bibliographic review of the scientific literature was carried out, between immunomodulators and cryotherapy for the treatment of genital lesions in women with HPV of the last 20 years, where publications of systematic reviews and meta-analyses were identified. It was concluded that the choice of immunomodulators, like cryotherapy, is better used when there are clinical lesions induced by HPV in the genital and perianal region in women, depending on the number, size, severity, location of the warts and patient preferences.

O papilomavírus humano é uma infecção prevalente, que pode infectar qualquer mucosa do corpo e causar verrugas genitais externas ou verrugas genitais e câncer cervical. O tratamento é difícil com alta recorrência e persistência da mesma, que acomete principalmente mulheres jovens. O objetivo do presente estudo foi comparar imunomoduladores e crioterapia para o tratamento de lesões genitais em mulheres com HPV. Foi realizada uma revisão bibliográfica narrativa da literatura científica, entre imunomoduladores e crioterapia para tratamento de lesões genitais em mulheres com HPV dos últimos 20 anos, onde foram identificadas publicações de revisões sistemáticas e metanálises. Concluiu-se que a escolha de imunomoduladores, como a crioterapia, é melhor utilizada quando há lesões clínicas induzidas pelo HPV na região genital e perianal em mulheres, dependendo do número, tamanho, gravidade, localização das verrugas e preferências da paciente.

Eculizumab, a successful treatment for atypical postpartum hemolytic-uremic syndrome: a case report / Eculizumab, un tratamiento exitoso en el síndrome hemolítico-urémico atípico puerperal: un caso clínico

Atypical hemolytic-uremic syndrome (aHUS) is a rare entity characterized by the association of acute kidney failure, thrombocytopenia and microangiopathic hemolytic anemia due to the dysregulation of the alternative pathway of the complement system. It is included within the thrombotic microangiopathies. The following aHUS was developed in the immediate puerperium in the context of severe preeclampsia. The patient was a primiparous woman of 30+1 weeks who required hospitalization for anticonvulsant and hypotensive treatment, and who underwent an emergency cesarean section due to a pathological cardiotocographic pattern. 36 hours after delivery, the patient presented with sudden dyspnea and cognitive deterioration, progressing in a few hours to renal and multiorgan failure. Blood test showed severe anemia, thrombopenia and hypertransaminemia. In view of the fast evolution and severity, it was decided to treat with Eculizumab, although the scientific evidence was very poor. Aside from the supportive treatment performed in the Intensive Care Unit, the patient was successfully treated with Eculizumab, with favorable evolution over the following months and restoration of kidney function, although need for chronic hypotensive treatment remained.

El síndrome hemolítico-urémico atípico (SHUa) es una entidad rara caracterizada por la asociación de insuficiencia renal aguda, trombocitopenia y anemia hemolítica microangiopática debido a la desregulación de la vía alternativa del sistema del complemento. Se incluye dentro de las microangiopatías trombóticas. Se presenta un SHUa que se desarrolló en el puerperio inmediato en el contexto de una preeclampsia grave. La paciente era una primípara de 30+1 semanas que requirió hospitalización para tratamiento anticonvulsivo e hipotensor, y a la que se le practicó una cesárea de urgencia por un patrón cardiotocográfico patológico. A las 36 horas del parto, la paciente presentó una disnea súbita y un deterioro cognitivo progresivo, que evolucionó en pocas horas a un fallo renal agudo y multiorgánico. La analítica mostró anemia severa, trombopenia e hipertransaminemia. Ante la rápida evolución y gravedad, se decidió tratar con Eculizumab, aunque la evidencia científica era escasa. Aparte del tratamiento de soporte realizado en la Unidad de Cuidados Intensivos, la paciente fue tratada con éxito con Eculizumab, con evolución favorable en los meses siguientes y restablecimiento de la función renal, aunque se mantuvo la necesidad de tratamiento hipotensor crónico.

Mieloma múltiple en Chile. Uso de drogas noveles en dos centros nacionales / The impact of novel drugs on the survival of patients with multiple myeloma in two chilean centers

BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. Aim: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. Results: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

Biomodulina T® como alternativa de tratamiento en el shock séptico en pediatría / Biomodulina T® as an alternative to the treatment of septic shock in pediatrics

Introducción: La sepsis y el shock séptico se encuentran entre las principales causas de morbilidad y mortalidad en la población pediátrica a nivel mundial. Encontrar soluciones alternativas para combatirlas, mediante el desarrollo de agentes inmunomoduladores, ha atraído el interés de investigadores en los últimos 20 años; Cuba cuenta con Biomodulina T®, un potente inmunomodulador. Objetivo: Demostrar que existe evidencia científica que avale la realización de ensayos clínicos controlados para la incorporación de la Biomodulina T® en las pautas de tratamientos de la sepsis en las terapias intensivas pediátricas. Material y Métodos: Se realizó una búsqueda en las bases de datos Medline, PubMed, SciELO, Lilacs, Cochrane Library y Web of Science, entre marzo de 2019 y marzo de 2020; se seleccionaron los 47 artículos de mayor relevancia para esta investigación. Desarrollo: La inmunopatogenia del shock se centra en un fenotipo complejo y alteraciones funcionales, tanto del sistema inmune innato como del sistema adaptativo, con disminución del número de células efectoras, aumento de subpoblaciones de linfocitos inmunosupresores y agotamiento de células T. Biomodulina T® estimula la producción de linfocitos T y robustece la diferenciación de las células linfoblastoides del timo. La práctica médica sugiere que su administración podría ser una estrategia prometedora para la restauración inmune en pacientes pediátricos con shock séptico. Conclusiones: Existe evidencia científica que respalda el uso de Biomodulina T® en pacientes con shock séptico, lo cual sustenta la fiabilidad de realizar ensayos clínicos controlados en población pediátrica para su posterior incorporación en las pautas de tratamientos en las terapias intensivas(AU)

Introduction: Sepsis and septic shock are among the main causes of morbidity and mortality in the pediatric population worldwide. Finding alternative solutions to combat them through the development of immunomodulatory agents has attracted the interest of researchers in the last 20 years; Cuba has Biomodulina T®, a powerful immunomodulator. Objective: To demonstrate that there is scientific evidence that supports the conduction of controlled clinical trials for the incorporation of Biomodulina T® into the treatment guidelines for sepsis in pediatric intensive care therapies. Material and Methods: A search was carried out in the Medline, PubMed, SciELO, Lilacs, the Cochrane Library and the Web of Science databases between March 2019 and March 2020; the 47 most relevant articlesfor this research were selected. Development: The immunopathogenesis of shock focuses on a complex phenotype and functional alterations of both the innate and adaptive immune systems with a decrease in the number of effector cells, an increase in subpopulations of immunosuppressive lymphocytes, and depletion of T cells. Biomodulina T® stimulates the production of T lymphocytes and strengthens the differentiation of lymphoblastoid cells of the thymus; medical practice suggests that its administration could be a promising strategy for immune restoration in pediatric patients with septic shock. Conclusions: There is scientific evidence that supports the use of Biomodulina T® in patients with septic shock, which supports the reliability of conducting controlled clinical trials in the pediatric population for its subsequent incorporation into treatment guidelines in intensive care therapies(AU)

Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy / Imunossupressores e imunomoduladores em Neurologia - Parte I: um guia para o manejo de pacientes em imunoterapia

ABSTRACT For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.

RESUMO Pacientes com doenças autoimunes exigem uma constante preocupação com os riscos e benefícios do tratamento imunossupressor ou imunomodulador. O conhecimento das rotinas no uso de cada uma dessas drogas é fundamental para o bom desfecho clínico, evitando a piora da doença ou efeitos colaterais. As drogas imunossupressoras e imunomoduladoras agem em diferentes pontos da resposta imunológica a fim de controlar a doença para qual são indicadas. O conhecimento do mecanismo de ação, principais posologias, efeitos adversos e os riscos de infecções e neoplasias relacionadas ao uso dessas medicações são fundamentais para um tratamento seguro. Cada uma delas apresenta um perfil específico de complicações e o manejo deve ser individualizado em diferentes cenários ao longo do seguimento do paciente. O uso de medicações para profilaxia primária de infecções e a vacinação são pontos essenciais no planejamento do tratamento, prevenindo potenciais complicações infecciosas ao longo do acompanhamento. O uso de imunossupressores e imunomoduladores é uma frequente realidade no dia-a-dia do neurologista, e o conhecimento das características de cada droga é crucial para o sucesso do tratamento. A realização de uma rotina antes, durante e depois do uso dessas medicações evita complicações relacionadas com o tratamento e alcança um melhor controle da doença.

Three decades of clinical trials on immunotherapy for human leishmaniases: a systematic review and meta-analysis.

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.

The fibrogenic process and the unleashing of acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.

Factors associated with adherence to immunomodulator treatment in people with multiple sclerosis

Abstract To determine the association between factors and adherence to immunomodulator treatment in people with multiple sclerosis treated in reference centers. Cross-sectional study conducted with 188 people who used immunomodulators in three reference centers in Ceará from March to July 2012. Adherence was assessed using the Moriskscale and factors were assessed using a questionnaire addressing socioeconomic and personal characteristics, the disease, the use of immunomodulator and educational activities. The determination of the association was expressed in crude and adjusted odds ratio with a 95% confidence interval. Adherence rate was 46% and after the logistic regression model the adherence to immunomodulator treatment was positively associated with the following factors: age 18-38 years, time of diagnosis and treatment between 6 and 24 months, 0-3.5 score in the Expanded Disability Status Scale, perception of treatment benefits, intrinsic and extrinsic motivation, phone contact with the doctor and not missing the return visit. This study is important because it allowed to determine the association between factors and adherence to immunomodulator treatment in multiple sclerosis, contributing to prevention and control actions.

Curbing Inflammation in hemorrhagic trauma: a review / "Curbing Inflammation" e hemorragia por trauma: uma revisão

Trauma is one of the world's leading causes of death within the first 40 years of life and thus a significant health problem. Trauma accounts for nearly a third of the lost years of productive life before 65 years of age and is associated with infection, hemorrhagic shock, reperfusion syndrome, and inflammation. The control of hemorrhage, coagulopathy, optimal use of blood products, balancing hypo and hyperperfusion, and hemostatic resuscitation improve survival in cases of trauma with massive hemorrhage. This review discusses inflammation in the context of trauma-associated hemorrhagic shock. When one considers the known immunomodulatory effects of traumatic injury, allogeneic blood transfusion, and the overlap between patient populations, it is surprising that so few studies have assessed their combined effects on immune function. We also discuss the relative benefits of curbing inflammation rather than attempting to prevent it.

O Trauma é uma das principais causas de morte até 40 anos de idade em todo o mundo e, portanto, um significativo problema de saúde. Esta doença é ainda responsável por quase um terço dos anos perdidos de vida produtiva até os 65 anos de idade e esta associada com infecção, choque hemorrágico, síndrome de reperfusão e inflamação. O controle da hemorragia, coagulopatia, utilização dos produtos derivados do sangue, equilibrando hipo e hiperperfusão, e reanimação hemostática melhoraram a sobrevida em casos de trauma com hemorragia volumosa. Esta revisão discute a inflamação no contexto de choque hemorrágico associado ao trauma. Quando consideradosos efeitos imunomoduladores conhecidos da lesão traumática e transfusão de sangue alogênico em relação aos doentes, é surpreendente que tão poucos estudos avaliaram os seus efeitos combinados sobre a função imunológica. Discutimos também os benefícios relativos de reduzir a inflamação ao invés de tentar impedi-la.

Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - Part 1

Leprosy is caused by Mycobacterium leprae and has been known since biblical times. It is still endemic in many regions of the world and a public health problem in Brazil. The prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in Brazil. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims to update dermatologist on epidemiological, clinical, and etiopathogenic leprosy aspects.

Omalizumab: opción terapéutica para la urticaria crónica espontánea de difícil control con vasculitis asociada, reporte de tres casos / Omalizumab: therapeutic option in chronic spontaneous urticaria difficult to control with associated vasculitis, report of three cases

Introducción. Aproximadamente el 50 % de los casos de urticaria crónica no mejoran adecuadamente con las dosis convencionales de antihistamínicos, por lo cual se han planteado múltiples opciones terapéuticas, entre las cuales el omalizumab es una herramienta novedosa que ahora cuenta con evidencia de alta calidad que soporta su uso en los casos difíciles, que mejora rápidamente el índice sintomático y el uso de medicamentos, y cuenta con un buen perfil de seguridad. Objetivo. Presentar tres casos de mujeres adultas con urticaria crónica espontánea de más de ocho años de evolución, que no mejoraron con el tratamiento con altas dosis de antihistamínicos, asociados a antileucotrienos e inmunomoduladores y en quienes se combinaban varios mecanismos fisiopatológicos: urticaria crónica espontánea con componente de autoinmunidad, componente de presión y urticaria vasculítica. Materiales y métodos. Se reportan los casos con sus respectivas evaluaciones clínicas y de laboratorio, los medicamentos usados y la respuesta después del inicio de omalizumab y se hace una revisión de la literatura científica sobre uso de este medicamento en la urticaria crónica. Resultados. En los tres casos presentados se obtuvo una mejoría completa de los síntomas tras el inicio del omalizumab. Conclusión. El omalizumab es una opción terapéutica exitosa en casos de urticaria crónica de difícil control con vasculitis asociada, cuando se han agotado las opciones propuestas por las guías internacionales.

Introduction: Approximately 50% of chronic urticaria cases do not respond adequately to conventional doses of antihistamines, so a number of other therapeutic options have been suggested. Among these, omalizumab is an innovative tool, which now has high-quality evidence that supports its use in difficult cases, rapidly improving the symptom index and the use of medications with a good safety profile. Objective: To report three cases of adult women with spontaneous chronic urticaria with an evolution of more than eight years, which did not improve with high doses of antihistamines and leukotriene receptor blockers, associated with immunomodulatory therapy in which several etiologic mechanisms were combined: chronic spontaneous urticaria with autoimmune and pressure components, and vasculitis. Materials and methods: We report the cases with their clinical and laboratory evaluations, used medication, the response after the start of omalizumab and we performed a review of the literature on the use of this drug in chronic urticaria. Results: In all the presented cases, we obtained complete improvement of symptoms after starting omalizumab. Conclusion: Omalizumab is a successful treatment option in cases of difficult to control chronic urticaria with associated vasculitis in which the options proposed by international guidelines have been exhausted.

Efeitos de imunomoduladores na doença de Crohn / Effects of immunomodulators in crohn's disease

A doença de Crohn é caracterizada por processo inflamatório crônico, persistente ou recidivante, de intensidade variável e transmural que pode acometer de forma descontínua qualquer parte do trato gastrointestinal. Trata-se de doença de etiologia ainda desconhecida que acomete pessoas de ambos os sexos em qualquer idade. Este trabalho teve como objetivo apresentar revisão da literatura sobre potenciais efeitos benéficos no processo inflamatório e tempo de remissão da doença de Chron relacionados ao uso de nutrientes imunomoduladores como glutamina, arginina, ômega-3, prebióticos e probióticos. A pesquisa bibliográfica foi realizada nas bases de dados Scielo, Biblioteca Virtual em Saúde (BVS) e Google Acadêmico, Os artigos pesquisados compreenderam 23 publicações entre os anos de 2002 e 2012. Os descritores utilizados foram: Doença de Crohn, Fatores Imunológicos e Terapia Nutricional . Os imunonutrientes mais utilizados nos estudos incluídos neste trabalho foram glutamina, arginina, ômega-3, prebióticos e probióticos, e a maioria dos estudos apontou efeitos positivos de imunomoduladores na recuperação de processos inflamatórios e na reabilitação de pacientes com doença de Crohn. Os imunomoduladores mais eficazes no prolongamento da remissão da doença foram arginina e probióticos. No entanto, existem poucas evidências na literatura relacionando a recomendação de imunonutrientes na reabilitação em pacientes com doença de Crohn com resultados consistentes quanto ao tipo e quantidade definidas dos imunomoduladores.

Crohn's disease is characterized by chronic inflammation, persistent or relapsing, transmural and variable intensity that can affect discontinuously any part of the gastrointestinal tract. It is disease of unknown etiology that affects people of both sexes at any age. This work aims to present a review of the literature on potential beneficial effects on the inflammatory process and time of remission of Crohn's related to the use of immunomodulatory nutrients such as glutamine, arginine, omega-3, probiotics and prebiotics. A literature search was conducted in the databases SciELO, Virtual Health Library (VHL) and Google Scholar, The respondents comprised 23 articles published between the years 2002 and 2012. The keywords used were: Crohn's Disease, Immunologic Factors and Nutritional Therapy. The immunonutrients most used in the studies included were glutamine, arginine, omega-3, probiotics and prebiotics, and most studies showed positive effects of immunomodulators in inflammatory processes of recovery and rehabilitation of patients with Crohn's disease. Immunomodulators more effective in prolonging remission were arginine and probiotics. However, there is little evidence in the literature relating the recommendation immunonutrients rehabilitation in patients with Crohn's disease with consistent results regarding the type and quantity of defined immunomodulators.

Epigenetic therapy in allogeneic hematopoietic stem cell transplantation.

DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG) islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graft-versus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.

Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG) islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graftversus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.