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.

Síndrome autoimune induzida por adjuvantes desencadeada por implantes mamários de silicone: revisão sistemática / Adjuvant-induced autoimmune syndrome triggered by silicone breast implants: systematic review

A síndrome autoimune induzida por adjuvantes (ASIA) e seus critérios diagnósticos foram descritos por Shoenfeld em 2011, relacionando sintomas de autoimunidade a adjuvantes, como o silicone, presente em próteses mamárias. Essa revisão sistemática objetivou reunir dados da literatura sobre a sintomatologia, a incidência e os tratamentos propostos para ASIA causada por implantes mamários de silicone (IMS). Foram realizadas pesquisas nas bases de dados PubMed, LILACS, Embase e Cochrane, utilizando os descritores "Autoimmune Syndrome Induced by Adjuvants", "Breast implant" e "Silicone Implant Incompatibility Syndrome". A estratégia de busca gerou 95 artigos, dos quais 20 foram incluídos na revisão. São as três as principais teorias sugeridas pelos autores para explicar o desenvolvimento da síndrome: predisposição genética, silicone bleeding e a formação de uma cápsula periprótese. As manifestações clínicas mais frequentemente descritas incluem fadiga crônica, artralgia, mialgia, distúrbios cognitivos e do sono. Não há consenso sobre os achados laboratoriais e os fatores de risco associados, além disso, estudos recentes propõem a ampliação dos critérios diagnósticos inicialmente descritos. O tratamento adequado permanece controverso, envolvendo desde o uso de medicações até o explante da prótese. Apesar dos artigos revisados sugerirem a existência da ASIA relacionada aos IMS, sua fisiopatologia precisa é desconhecida, os sintomas relatados são inespecíficos e o tempo entre a exposição e o surgimento das manifestações é incerto. Por meio dessa revisão sistemática, conclui-se que, até o presente momento, não existem evidências científicas suficientes para estabelecer a causalidade do desenvolvimento da síndrome autoimune induzida por adjuvantes decorrente de implantes mamários de silicone.

Adjuvant-induced autoimmune syndrome (ASIA) and its diagnostic criteria were described by Shoenfeld in 2011, relating symptoms of autoimmunity to adjuvants, such as silicone, present in breast implants. This systematic review aimed to gather data from the literature on symptomatology, incidence and proposed treatments for ASIA caused by silicone breast implants (SBI). Searches were carried out in PubMed, LILACS, Embase and Cochrane databases, using the descriptors "Autoimmune Syndrome Induced by Adjuvants," "Breast implant," and "Silicone Implant Incompatibility Syndrome." The search strategy generated 95 articles, of which 20 were included in the review. The authors suggest three main theories to explain the development of the syndrome: genetic predisposition, silicone bleeding and the formation of a periprosthetic capsule. The most frequently described clinical manifestations include chronic fatigue, arthralgia, myalgia, and cognitive and sleep disorders. There is no consensus on laboratory findings and associated risk factors; recent studies propose expanding the diagnostic criteria initially described. Adequate treatment remains controversial, ranging from medications to prosthesis explantation. Although the reviewed articles suggest the existence of ASIA related to SBI, its precise pathophysiology is unknown, the symptoms reported are nonspecific, and the time between exposure and the onset of manifestations is uncertain. This systematic review concludes that, to date, there is not enough scientific evidence to establish the causality of the development of adjuvant-induced autoimmune syndrome resulting from silicone breast implants.

Hallazgos quirúrgicos en pacientes con alogenosis iatrogénica / Surgical findings in patients with iatrogenic allogenosis

INTRODUCCION: los biopolímeros son macromoléculas cuyo uso como sustancias de relleno con fines estéticos ha ido en aumento en los últimos años. Esto ha generado un incremento de complicaciones por alogenosis iatrogénica de difícil tratamiento. OBJETIVO: describir los hallazgos intraoperatorios en las pacientes con alogenosis iatrogénica intervenidas quirúrgicamente en el Departamento de Cirugía Plástica del Hospital Hermanos Ameijeiras. METODO: se realizó un estudio descriptivo, prospectivo, longitudinal y monocéntrico con 15 pacientes femeninas que recibieron tratamiento quirúrgico para extracción de sustancias modelantes desde enero 2017 a diciembre 2019. RESULTADOS: el rango de edad predominante fue entre los 19 y 29 años con un 66.6% y entre los 30 y 40 años de edad con un 33.3%. El procedimiento quirúrgico fue realizado bajo anestesia general en el 33.3% de las pacientes; de ellos el 20% fue en la región mamaria, 40% glúteos y 40% genitales y pubis. Se empleó anestesia local en el 66.6%, distribuidas en 20% en la región frontal y glabelar, 30% en los párpados y 50% en los labios. El 100% mostró hallazgos intraoperatorios similares. CONCLUSIONES: independientemente del producto inyectado, la región anatómica y la expresión clínica de la enfermedad, los hallazgos transoperatorios son los mismos. Tanto en las zonas más inyectadas que fueron la región glútea, genital y púbica como en la de menor frecuencia que correspondió a las zonas frontales y glabelar, la extracción del producto resultó en múltiples nódulos en forma de perlas de pequeño tamaño y cavernas.

INTRODUCTION: biopolymers are macromolecules whose use as fillers for aesthetic purposes has been increasing in recent years. This has generated an increase in complications due to iatrogenic alogenosis that is difficult to treat. OBJECTIVE: to describe the intraoperative findings in patients with iatrogenic alogenosis who underwent surgery at the Department of Plastic Surgery of the Hermanos Ameijeiras Hospital. METHODS: a descriptive, prospective, longitudinal, single-center study was conducted with 15 female patients who received surgical treatment for removal of modeling substances from January 2017 to December 2019. RESULTS: the predominant age range was between 19 and 29 years old with 66.6% and between 30 and 40 years old with 33.3%. The surgical procedure was performed under general anesthesia in 33.3% of the patients; of them 20% were in the breast region, 40% buttocks and 40% genitalia and pubis. Local anesthesia was used in 66.6%, distributed in 20% in the frontal and glabellar region, 30% in the eyelids and 50% in the lips. 100% showed similar intraoperative findings. CONCLUSIONS: regardless of the product injected, the anatomic region and the clinical expression of the disease, the transoperative findings are the same. Both in the most injected areas which were the gluteal, genital and pubic region and in the less frequently injected areas which corresponded to the frontal and glabellar areas, the extraction of the product resulted in multiple nodules in the form of small pearls and caverns.

OM-85 BV for primary prevention of recurrent airway infections: a pilot randomized, double-blind, placebo-controlled study / OM-85 BV para prevenção primária de infecções recorrentes das vias aéreas: estudo piloto, randomizado, duplo-cego, placebo-controlado

ABSTRACT Objective To compare the frequency of respiratory tract infections in children treated with OM-85 BV and placebo during the 3-month therapy period, and observation for a further 3 months after treatment. Methods A randomized, double-blind, placebo-controlled trial was conducted with 54 children (6 months to 5 years old) with no past history of recurrent respiratory infections attending daycare center. Family members were instructed to administer one capsule per day for 10 consecutive days, for 3 months of OM-85 BV or placebo. Telephone interviews were conducted every 30 days. Results There was no significant difference in the number of respiratory infections between the groups. The mean number of respiratory tract infection in the OM-85 BV Group in the first 3 months was 0.92±0.87, and in the Placebo Group was 0.74±1.02, and at 6 months it was 1.62±1.47 and 1.03±1.34, respectively. Conclusion OM-85 BV was not effective in the primary prevention of respiratory tract infections. Although most authors recommend the use of this immunostimulant in children with a history of recurrent respiratory infections, more studies are needed to define its usefulness in the primary prevention of respiratory infections in healthy children exposed to few risk factors.

RESUMO Objetivo Comparar a frequência de infecções do trato respiratório em crianças tratadas com OM-85 BV e placebo durante o período de terapia de 3 meses, e observação por mais 3 meses após o tratamento. Métodos Foi realizado estudo randomizado, duplo-cego, controlado por placebo com 54 crianças (6 meses a 5 anos) sem história prévia de infecções respiratórias recorrentes, que frequentavam creches. Os membros da família foram instruídos a administrar uma cápsula por dia durante 10 dias consecutivos, durante 3 meses, de OM-85 BV ou placebo. Entrevistas telefônicas foram realizadas a cada 30 dias. Resultados Não houve diferença significativa no número de infecções respiratórias entre os grupos. O número médio de infecções do trato respiratório no Grupo OM-85 BV nos primeiros 3 meses foi de 0,92±0,87 e, no Grupo Placebo, de 0,74±1,02, e aos 6 meses foi de 1,62±1,47 e 1,03±1,34, respectivamente. Conclusão O OM-85 BV não foi eficaz na prevenção primária de infecções do trato respiratório. Embora a maioria dos autores recomende o uso deste imunoestimulante em crianças com história de infecções respiratórias recorrentes, mais estudos são necessários para definir sua utilidade na prevenção primária de infecções respiratórias em crianças saudáveis expostas a poucos fatores de risco.

Research progress in the establishment of allergic rhinitis mouse model / 中华耳鼻咽喉头颈外科杂志

The number of patients with allergic rhinitis (AR) have been increasing in the world. Establishment of AR model in mice is an important method for the study of this disease. However, there is still no consensus standard for the modeling methods, selection of allergens and adjuvants, and evaluation parameter of AR modeling. Here, we introduce the advancement of AR mouse model in recent years from the above, and provide evidence of references for the standardized process of AR mouse model establishment.

Adverse events of vaccines and the consequences of non-vaccination: a critical review / Eventos adversos de vacinas e as consequências da não vacinação: uma análise crítica

ABSTRACT OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society.

RESUMO OBJETIVO: Analisar os riscos relacionados às vacinas e os impactos da não vacinação para a população mundial. MÉTODOS: Revisão narrativa que considerou informações contidas nas bases de dados bibliográficos NCBI-PubMed, Medline, Lilacs e Scientific Electronic Library Online (SciELO), no período compreendido entre novembro de 2015 e novembro de 2016. Para a análise de surtos ocasionados pela não vacinação foram considerados os trabalhos publicados entre 2010 e 2016. RESULTADOS: Foram descritos os principais componentes das vacinas oferecidas pelo sistema público de saúde brasileiro e eventos adversos associados a esses elementos. Com exceção de reações inflamatórias locais e efeitos raros como exacerbação de doenças autoimunes e alergias, não foi demonstrada relação causal entre a administração de vacinas e autismo, mal de Alzheimer ou narcolepsia. Por outro lado, a falta de informações e a divulgação de informações não científicas têm contribuído para a reemergência de doenças infecciosas em diversos países no mundo e põe em risco planos globais para a erradicação de doenças infecciosas. CONCLUSÕES: A população deve estar bem informada quanto aos benefícios da vacinação e os profissionais da saúde devem assumir o papel de divulgar informações verídicas e com respaldo científico sobre o tema, como compromisso ético e profissional junto à sociedade.

Observation of the effect of immunopotentiator combined with antiviral therapy in the treatment of children with recurrent respiratory tract infections / 中国基层医药

Objective To explore the clinical curative effect of immunopotentiator combined with antiviral therapy in the treatment of children with recurrent respiratory tract infections.Methods 56 children with recurrent respiratory tract infections were selected as study subjects,and they were divided into two groups according to different therapeutic methods,28 cases in each group.The control group was given conventional antiviral treatment,the observation group was treated with immunopotentiator combined with antiviral therapy.The serum levels of IgA,IgG,IgM and peripheral blood T cell subsets CD3+,CD4+,CD8+ levels were detected in the two groups before treatment and after treatment.The fading away of the main symptoms and signs,and the clinical efficacy were observed.Results The fever subsided time [(1.98 ± 0.64) d],cough fade time [(1.65 ± 0.47) d] and lung's fading time [(2.38 ± 0.57) d] of the observation group were significantly shorter than those of the control group(all P ＜ 0.05).The total effective rate of the observation group was 92.86％,which was obviously higher than 67.86％ of control group(x2 =5.54,P ＜ 0.05).The serum immunoglobulin IgG [(9.09 ± 3.01) g/L],IgA [(1.75 ± 0.57) g/L],IgM [(1.39 ± 0.42) g/L] of the observation group after treatment had statistically significant differences compared with the control group (t =0.038,0.041,0.027,all P ＜0.05).The T lymphocyte subsets CD~ [(59.4 ± 8.9) ％],CD4+ [(40.5 ±4.4)％],CD8+ [(29.8 ± 4.7) ％] of the observation group after treatment had statistically significant differences compared with the control group (t =0.044,0.039,0.037,all P ＜ 0.05).Conclusion The application of immunopotentiator combined with antiviral therapy in the treatment of children with recurrent respiratory tract infections had exactly clinical curative effect,and it is worthy of popularization and application.

Implantes mamarios, eventos adversos y complicaciones poco frecuentes: hallazgos por mamografía, ecografía y resonancia magnética / Breast Implants, Adverse Events and Rare Complications: Findings by Mammography, US and MR Imaging

Introducción: En la actualidad, la mamoplastia de aumento con implantes es un procedimiento cada vez más común, con fines exclusivamente cosméticos o reconstructivos después de una mastectomía. Existen complicaciones locales ampliamente conocidas, como la ruptura y contracturas capsulares, pero también se le han atribuido otras complicaciones menos frecuentes, como el linfoma anaplásico y el síndrome autoinmune/inflamatorio inducido por adyuvantes (ASIA). Objetivo: Revisar las características por imagen de las complicaciones frecuentes e infrecuentes asociadas al aumento mamario con prótesis. Metodología: Recolección retrospectiva de casos con complicaciones relacionadas con implantes mamarios; revisión y edición de las diferentes modalidades de imágenes en pacientes de la clínica Fundación Valle del Lili de Cali durante los dos últimos años. Resultados: Es frecuente encontrar cambios postquirúrgicos por mamoplastia de aumento con implantes. Aunque la mamografía tiene un papel limitado en la valoración de las complicaciones del implante, continúa siendo la herramienta de tamizaje de cáncer en la mama aumentada. La ecografía es un instrumento muy útil y costo-efectivo en la evaluación de los implantes. La RM con secuencias de silicona es la modalidad con más alta sensibilidad y especificidad si se quiere valorar la integridad del implante y el tejido mamario en su conjunto.

Introduction: At present, breast augmentation with implants is an increasingly common procedure, be it solely for cosmetic reasons or for reconstructive purposes after mastectomy. There are widely known local complications associated with this intervention, such as implant rupture and encapsulation, but there are other less common complications too, such as anaplastic lymphoma and autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Objective: To review the imaging characteristics of frequent and infrequent complications associated with breast augmentation with implants. Methodology: Cases of different complications were retrospectively collected, in order to review mammography, ultrasound, CT and MRI images of patients with such complications at the Fundación Valle del Lili Clinic (Cali, Colombia) over the past two years. Conclusions: It is common to find post-surgical changes due to breast augmentation with implants. The study concludes that although mammography has a limited role in the assessment of implant complications, it remains the main screening tool for cancer in augmented breasts. Ultrasound is a very useful and cost-effective tool in evaluating implants. MRI with silicone sequences has the highest sensitivity and specificity when assessing the integrity of the implant and breast tissue as a whole. Key words (MeSH) Breast implants Implant capsular contracture Seroma Adjuvants, immunologic

Effect of α-glycan isolated from Isatis indigotica on humoral and cellular immunities in mice immunized with H1N1 influenza vaccine / 中国药理学与毒理学杂志

OBJECTlVE To investigate the effect of α-glycan isolated from Isatis indigotica on humoral immunity and cellular immunity functions in mice immunized with H1N1 influenza vaccine. METHODS BALB/c mice were immunized intramuscularly once with H1N1 influenza vaccine ( 3 μg) plusα-glycan ( 100μg) each mouse. The serum total antibody titer and its isotype antibody titer of immu-nized mice were analyzed by ELlSA at 5, 8, 10, 12 and 14 d after injection at vaccine. The proliferation activities of spleen T and B lymphocytes were determined with MTT method. The levels of cytokines interferon-γ( lFN-γ) , tumor necrosis factorα( TNF-α) , interleukin-4( lL-4) and lL-12 were measured by ELlSA kits. The populations of CD4+, CD8+, CD3+ and CD19+ lymphocytes were determined by flow cytometry. Furthermore, the proliferation rate of macrophages was studied with MTT method in vitro. RESULTS The α-glycan from I.indigotica could gradually induce high specific-antibody production 5-14 d after immunization with H1N1 influenza antigen plus theα-glycan in mice compared to immunization with antigen alone ( P<0.01) . After injection of antigen withα-glycan for 5 d, the main lgG isotype was lgM, and the titer levels of total lgG, lgG1 , lgG2a and lgG2b were also significantly raised following 5-14 d after immunization. The α-glycan significantly promoted the spleen T and B lymphocytes proliferation ( growth rate 44.2%and 37.8%) , stimulated the secretion of lFN-γand lL-12 of splenocytes ( P<0.01, P<0.05) , and also promoted lL-4 secretion of thymocytes (P<0.01). The polysaccharide significantly raised the percent age of CD3+T cells ( P<0.01) , CD3+/CD19+ T lymphocytes ( P<0.01) , and CD8+ T cells ( P<0.01) but decreased the percentage of CD4+/CD8+ T lymphocytes compared with antigen alone group ( P<0.01) . Furthermore, the α-glycan exhibited significant effects on the proliferation and TNF-α secre-tion of MH-S macrophages. CONCLUSlON Theα-glycan isolated from I.indigotica can improve humoral and cellular immunity response in mice immunized with H1N1 influenza vaccine.

Immunogenicity of a recombinant chimeric antigen using Aβ1-15 epitope fused to a T helper epitope / 军事医学

Objective To explore the immunogenicity of recombinant chimeric 6Aβ15-T including the Aβ1-15 epitope and a T-helper epitope formulated with different adjuvants and to evaluate its feasibility as a candidate vaccine for Alzheimer disease (AD).Methods The recombinant chimeric antigen 6Aβ15-T formulated with Al adjuvant, Freund′s adjuvant or MF59 adjuvant was administered to two strains of mice .The 6Aβ15-T-immunized group without adjuvants ( Mock) and non-immunized group (Control) were included in this study as control groups .The specific antibody and cellular immune response of the chimeric antigen were evaluated .Results In BALB/c strain mice, three types of adjuvants could substan-tially boost the immunogenicity of chimeric antigen 6Aβ15-T and produce a high level of specific-Aβ(β-amyloid) antibod-ies.In C57BL/6 strain mice, the existence of adjuvants enhanced the immune response of 6Aβ15-T antigen, but the mice in Mock group also produced a strong antibody response .In two strains of mice, prevalence of anti-AβIgG1, which was an indicator of Th2 polarization, was observed in the 6Aβ15-T-immunized mice.Additionally, the Al adjuvant induced a high-er level of IgG1 antibody titers, and the ratio of IgG1/IgG2a was the largest.As expected, the 6Aβ15-T antigen formulated with or without adjuvants induced PADRE-specific, but not Aβ42-specific T cellular immune response .Conclusion The 6Aβ15-T antigens formulated with different types of adjuvants could induce strong Th 2-polarized Aβ42-specific antibody re-sponses without activating self-reactive Aβ42-specific T cells in two strains of mice .The results suggested that the recombi-nant chimeric antigen 6Aβ15-T is a good candidate vaccine for AD .

Avaliação do pigmento de Lawsonia inermis (henna) como carreadorde antígenos inoculados por via transcutânea em camundongos / Evaluation of Lawsonia inermis (henna) pigment as a carrier of antigens inoculatedby transcutaneous immunization pigment in mice

Objetivos: Avaliar o papel do pigmento de Lawsonia inermis (henna) como carreador de antígenos em esquema de vacinação transcutânea em camundongos.Métodos: Camundongos foram imunizados por via transcutânea na pele do abdômen e na pele da orelha com antígeno bruto de Paracoccidioides brasiliensis e com albumina sérica bovina nas concentrações de 1, 10 e 50 mg/mL, por três vezes em intervalos de uma semana, na presença ou ausência de pigmentos de L. inermis. Uma semana após a última imunização, foram avaliadas a presença de anticorpos anti-antígenos no soro, das citocinas interleucina-4 e interferon-? e de óxido nítrico em sobrenadante de cultura.Resultados: Não foram detectados anticorpos específicos anti-antígenos de P.brasiliensis ou albumina sérica bovina no soro. No foram encontradas diferenças significativas na produção de óxido nítrico e nos níveis de interleucina-4 e interferon-? em sobrenadantes de cultura celular.Conclusões: As vacinações transcutâneas com antígeno bruto de P. brasiliensis e albumina sérica bovina em suspensão de pigmento de L. inermis não produziram resposta antigênica detectável em camundongos.

Aims: To evaluate the role of pigment Lawsonia inermis (henna) as a carrier of antigens in transcutaneous vaccination in mice.Methods: Mice were immunized transcutaneously into the skin of the abdomen and the ear?s skin with crude antigen of Paracoccidioides brasiliensis and with bovine serum albumin at concentrations of 1, 10 and 50 mg/mL, three times at one week intervals in the presence or absence of pigments L. inermis. One week after last immunization, the animals were evaluated for the presence of serum antibodies, interleucin-4 and interferon-g cytokines, and nitric oxide in culture supernatants.Results: No specific antibodies were detected to P. brasiliensis or bovine serum albumin antigens. There were no significant differences in the production of nitric oxide, interleucin-4 and interferon-g in supernatants of cell culture.Conclusions: Transcutaneous immunization with crude antigen of P. brasiliensis or bovine serum albumin suspended in pigment of L. inermis produced no detectable antigenic response in mice.

Terapia adjuvante pós tratamento cirúrgico no carcinoma renal: revisão sistemática da literatura com meta-análise / Adjuvant therapy after surgical treatment in renal carcinoma: systematic review of the literature with meta-analysis

Pacientes com câncer renal localmente avançado são de alto risco para recidiva após ressecção cirúrgica com intuito curativo. Muitos estudos têm sido realizados na tentativa de se descobrir alguma intervenção adjuvante capaz de reduzir este risco. No entanto, até o momento não foi observado nenhum benefício clínico nas intervenções avaliadas nos estudos. O objetivo desta revisão sistemática foi avaliar o exato papel da terapia adjuvante nos pacientes com câncer renal localmente avançado após cirurgia. Foram selecionados estudos clínicos randomizados que comparavam terapia adjuvante (quimioterapia, vacinas, imunoterapia, bioquimioterapia, hormonioterapia) versus nenhum tratamento ativo após cirurgia em pacientes com câncer renal. Os desfechos clínicos avaliados foram sobrevida global (SG), sobrevida livre de doença (SLD) e toxicidades severas. A análise dos dados extraídos foi realizada no programa estatístico Review Manager 5.0 (RevMan 5; Cochrane Collaboration Software). As diferentes estratégias de tratamento adjuvante foram avaliadas em conjunto e separadamente. Dez estudos (2609 pacientes) foram incluídos. Terapia adjuvante não mostrou benefício em termos de SG (HR 1.07; IC95% 0.89 a 1.28; P = 0.48 I2= 0%) ou SLD (HR 0,96; IC95% 0.83 a 1.10; P =0.52 I2= 36%) quando comparado a nenhum tratamento adjuvante. Nenhuma análise de subgrupo (imunoterapia,vacinas, bioquimioterapia) atingiu resultado relevante. A avaliação de toxicidades mostrou uma frequencia significativamente maior de eventos adversos graves no grupo tratado (OR 73.86; IC 95% 28,32 a 192,62; P < 0,00001 I2 = 37%). O resultado final da análise não forneceu nenhum suporte para a hipótese de que os agentes estudados forneçam qualquer benefício clínico para pacientes com câncer renal no contexto adjuvante, além de aumentarem o risco de efeitos adversos graves.

Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy, hormone therapy) versus no active treatment after surgery among renal cell cancer patients. Clinical outcomes were overall survival (OS), disease-free survival (DFS), and severe toxicities. The extracted data was performed using the statistical software Review Manager 5.0 (RevMan 5; Cochrane Collaboration Software).Different strategies of adjuvant treatment were evaluated together and separately. Ten studies (2,609 patients) were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0%) or DFS (HR 0,96; CI 95% 0.83 to 1.10; P =0.52 I2 = 36%) when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy) had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group(OR 73.86; CI 95% 28,32to 192,62; P < 0,00001 I2 = 37%).The result of the analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients in the adjuvant setting, in addition to increasing the risk of serious adverse events.

Treatment of common warts with the immune stimulant Propionium bacterium parvum / Tratamento das verrugas vulgares com o imunoestimulante Propionium bacterium parvum

BACKGROUND: Warts are epithelial proliferations in the skin and mucous membrane caused by various types of HPV. They can decrease spontaneously or increase in size and number according to the patient's immune status. The Propionium bacterium parvum is a strong immune stimulant and immune modulator and has important effects in the immune system and it is able to produce antibodies in the skin. OBJECTIVE: To show the efficacy of the Propionium bacterium parvum in saline solution in the treatment of skin warts. METHODS: A randomized double-blind study. Twenty patients with multiple warts were divided into two groups: one received 0,1ml intradermal injection of placebo solution in just one of the warts and the other received 0,1 ml of saline solution of Propionium bacterium parvum, one dose a month, for 3 to 5 months. RESULTS: Among the 20 patients who participated in the study, ten received the placebo and ten received the saline solution with Propionium bacterium parvum. In 9 patients treated with the Propionium bacterium parvum solution the warts disappeared without scars and in 1 patient it decreased in size. In 9 patients who received the placebo no change to the warts was observed and in 1 it decreased in size. CONCLUSIONS: The immune modulator and immune stimulant Propionium bacterium parvum produced antibodies in the skin which destroyed the warts without scars, with statistically significant results (P<0,001), and cured 90 % of the patients. We suggest the use of the immune stimulant in the treatment of warts.

FUNDAMENTOS: Verrugas são proliferações epiteliais na pele e mucosas causadas por diversos tipos de HPV. Elas podem involuir espontaneameme ou aumentar em número e tamanho de acordo com estado imunitário do paciente. O Propionium bacterium parvum é urn potente imunoestimulador e imunomodulador e tem efeitos importantes no sistema imune e é capaz de produzir anticorpos na pele. OBJETIVO: Mostrar a eficácia do Propionium bacterium parvum diluído em solução salina no tratamento de verrugas cutâneas. MÊTODOS: Estudo duplo-cego randomizado. Vinte pacientes com verrugas múltiplas foram divididos em dois grupos, um recebeu aplicação intradérmica do placebo em uma (1) única verruga e o outro da solução salina com Propionium bacterium parvum, uma dose por mês por 3 a 5 meses. RESULTADOS: Dos 20 pacientes do estudo, dez receberam placebo e 10 de solução salina com Propionium bacterium parvum. Dos pacientes tratados com Propionium bacterium parvum nove (9) foram curados e um teve diminuição das lesões. Do grupo do placebo nove (9) não apresentaram alterações e 1 (um) apresentou diminuição das lesões. CONCLUSÔES: O imunomodulador e imunoestimulador Propionium bacterium parvum produz anticorpos na pele que destroem as verrugas sem cicatrizes e mostrou uma significância de P<0,001, com cura de 90% dos pacientes submetidos à terapia. Sugerimos a utilização de imunoestimulante para o tratamento de verruga vulgar.

Vacunas y autoinmunidad: una rara asociación bajo debate / Vaccines and autoimmunity: a strange association under debate

La posible asociación entre vacunas y enfermedades autoinmunes es un tema controversial. Existen elementos a favor de esta relación basados en modelos teóricos, ensayos de laboratorio y varios casos clínicos publicados. En cambio, los estudios epidemiológicos no han confirmado esta asociación y, de ellos, puede inferirse que las vacunas no constituyen una causa demostrada de enfermedades autoinmunes. En este trabajo se analizan las evidencias a favor y en contra de esta controversial asociación, además, se aborda un nuevo síndrome asociado con la administración continuada de adyuvantes vacunales. Se concluye que debido al gran impacto en beneficio de la salud logrado con las vacunas, es necesario continuar desarrollando esta tecnología, pero también se debe seguir perfeccionando los diseños de las nuevas formulaciones y profundizando estudios básicos, preclínicos, ensayos clínicos y farmacovigilancia de los nuevos candidatos vacunales para establecer el riesgo real de desarrollo de un evento autoinmune posvacunación.

The occurrence and significance of autoimmune manifestations after administration of vaccines remain controversial. Evidence for immunization triggered autoimmunity come from several sources including theoretical models, animal studies, single and multiple case reports. In contrast, several epidemiological studies don’t report this association, which is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. We analyzed current scientific data concluded that vaccines bring a positive impact on public health, so it is necessary to continue developing this technology. Evaluation methods should be improved to avoid or anticipate the possible autoimmune side effects that can be presented.

Imunonutrição em pacientes com sepse?: [revisão] / Immunonutrition in patients with sepsis?: [review]

Objetivos: revisar os conhecimentos atuais sobre o uso de imunonutrientes em pacientes críticos, especialmente naqueles com sepse.Fonte de dados: foi realizada uma revisão narrativa da literatura, utilizando as bases de dados Medline/Pubmed. Os artigos pesquisados compreendem publicações entre 2000 e 2011. Foram incluídos também artigos obtidos em referências bibliográficas dos artigos com maior relevância. Foram selecionados trabalhos referentes a indivíduos humanos adultos.Síntese dos dados: os estudos utilizaram diferentes fórmulas contendo imunonutrientes, nem sempre com os mesmos imunomoduladores. A quantidade administrada também variou de acordo com o tipo de fórmula, a tolerância do paciente e a via de administração. Efeitos favoráveis e desfavoráveis resultaram da administração de dietas enriquecidas com nutrientes imunomoduladores em pacientes com sepse.Conclusões: a literatura é bastante controversa em relação à recomendação do uso de imunonutrientes em pacientes críticos, sobretudo naqueles com sepse. Ainda não há resultados consistentes sobre a eficiência e a segurança da imunonutrição nesses pacientes. São necessários estudos com desenho metodológico e população mais homogêneos, utilizando imunonutrientes isolados e com quantidades definidas.

Aims: To review the current knowledge on the use of immunonutrients in critically ill patients, especially those with sepsis.Source of data: A narrative review of the literature was conducted, using the Medline/Pubmed data bases. The selected articles included publications between 2000 and 2011. Articles cited in reference lists of articles with the highest relevance were also included. Works on adult human individuals were selected.Summary of findings: Studies used different formulas containing immunonutrients, not always with the same immunomodulators. The given amount varied according to the type of formula, the patient?s tolerance and the route of administration. Favorable and unfavorable effects appeared as a result of administration of diets enriched with immunomodulator nutrients in patients with sepsis.Conclusions: Literature is controversial regarding the recommendation to use immunonutrients in critically ill patients, especially those with sepsis. There is currently no evidence to define the efficiency and safety of immunonutrition in these patients. For more consistent results, studies should be conducted with more homogeneous methodological design and population, using isolated immunonutrients in defined dosis.

Hemocianinas, una herramienta inmunológica de la biomedicina actual / Hemocyanins as immunostimulants

Hemocyanins, the giant oxygen transporter glycoproteins of diverse mollusks, are xenogenic to the mammalian immune system and they display a remarkable immuno-genicity. Therefore they are ideal non-specific immunostimulants to treat some types of cancer. They are used as an alternative therapy for superficial urinary bladder cancer (SBC), that has been traditionally treated with Bacillus Calmette-Guerin (BCG). In contrast to BCG, hemocyanins do not cause side-effects, making them ideal for long-term repetitive treatments. Hemocyanins have also been exploited as carriers to develop antibodies against hapten molecules and peptides, as carrier-adjuvants for cutting-edge vaccines against cancer, drug addiction, and infectious diseases and in the diagnosis of parasitic diseases, such as Schistosomiasis. The hemocyanin from Megathura crenulata, also known as keyhole limpet hemocyanin (KLH), has been used for over thirty years for the purposes described above. More recently, hemoc yanin from the Chilean mollusk Concholepas concholepas (CCH) has proved to be a reliable alternative to KLH, either as carrier protein, and as a likely alternative for the immunotherapy of SBC. Despite KLH and CCH differ significantly in their origin and structure, we have demonstrated that both hemocyanins stimulate the immune system of mammals in a similar way by inducing a potent Thl-polarized cellular and humoral response.

The analysis of clinical characteristics and treatment of 234 patients with intractable ulcerative colitis / 中华消化杂志

Objective To investigate the clinical characteristics and currently treatment status of intractable ulcerative colitis (IUC). Methods A retrospective analysis was conducted on the data of inflammatory bowel disease patients, who were hospitalized in Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, from January 1999 to December 2009. According to the reaction to glucosteroids (GCS) treatment, they were divided into GCS effective group and intractable group. The general data, lesion, clinical symptoms and laboratory findings of these two groups were compared.Further treatments and the results of intractable group were analyzed. Results Totally 234 UC patients were enrolled, of which 37.6％ (88/234) patients received GCS treatment, intractable group and effective group took up 23.9％ (21/88) and 76.1％ (67/88) respectively. There was no significant difference of lesion between two groups (P＞0.05). Compared with effective group, the proportion of intractable group was higher in moderately severe bellyache[38. 1 ％ (8/21) vs 13. 4％ (9/67), P＝0.012, OR＝3.97, 95％CI:1.29～12.23], anemia[61.9％(13/21) vs 32.8％(22/67), P＝0.018,OR＝3.32, 95％CI:1.20～9.20], thrombocytosis[57.1％(12/21) vs 29.9％(20/67), P＝0.023,OR＝3.13, 95％ CI: 1.14 ～8.61]and hypoalbuminemia[38.1 ％ (8/21) vs 11.9％ (8/67), P＝0.007, OR＝4.54, 95％CI: 1.44～ 14.32]. Some patients of intractable group could be remission through extending period of GCS treatment, adding the immunomodulators or biological agents and intestinal segment excision. Conclusion UC patients with moderately severe bellyache, anemia,thrombocytosis, hypoalbuminemia at the onset of disease, which may indicate relatively poor response to GCS treatment. Immunomodulators, biological agents and surgery are the further treatment for IUC patients.

Construction of DNA vaccine with Neisseria gonorrhoeae porin B fused with B subunit of Escherichia coli heat-labile enterotoxin and study on its immune responses in mouse / 中华传染病杂志

Objective To investigate the specific humoral immune response and cellular immune response induced by DNA vaccine with Neisseria gonorrhoeae porin B (PorB) fused with B subunit of Escherichia coli heat-labile enterotoxin B (LTB) in mice. Methods Target genes of porB, ltB and ltB-porB were amplified by polymerase chain reaction (PCR) and cloned into eukaryotic vector pcDNA3.1(-). The recombinants were identified by PCR, enzyme digestion and DNA sequencing.The vectors were transfected into Hela cells, and expressed proteins were checked by cytoimmunofluorescence. Female BALB/c mice were intranasally immunized with recombination vectors. The humoral immune response and cellular immune response were detected by enzyme linked immunosorbent assay (ELISA) and methyl thiazolyl tetrazolium (MTT) colorimetric assay. The expressions of recombination vectors in intranasal mucosal tissues of the immunized mice were detected by immunohistochemistry. The means between groups were compared by analysis of variance. Results All the three recombinants were expressed in Hela cells and intranasal mucosal tissues. The PorB specific IgG in serum and sIgA in vaginal secretions in DNA vaccine immunized mice were significantly higher than those in controls (P＜0.01 ; P＜0.05). Moreover, the sIgA level in pcDNA3.1 (-)/ltB-porB group was higher than that in peDNA3, 1(-)/porB group (P＝0. 002). The levels of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in the supernatants and stimulation index (SI) of spleen lymphocyte culture in pcDNA3, 1(-)/porB group were (170.04±23.89) pg/mL, (114.68±14.27) pg/mL and 1. 68±0.19, respectively; and those in pcDNA3, 1(-)/ltB-porB group were (161.42±27.50) pg/mL, (124.16±19.04) pg/mL and 1.73±0.28, respectively; which were both higher than those in pcDNA3.1(-)/ phosphate buffered saliae (PBS) group (P＜0. 01; P＜0.05) and pcDNA3.1 (-)/ltB group (all P＜0.05), while there was no significant difference between pcDNA3.1 (-)/ltB-porB group and pcDNA3. 1 (-)/porB group (0. 998, 0. 696, 0. 994; all P＞0.05). Conclusions The constructed DNA vaccines are all successfully expressed in Hela cells and murine intranasal mucosal tissues. The mucosal immunization of the vaccines [pcDNA3. 1 (- )/porB and pcDNA3.1 ( -)/ltBporB] could induce humoral immune response and cellular immune response, especially mucosal immune response. It is confirmed that mucosal adjuvant LTB could promote PorB to induce higher level of mucosal immune response in mice.

Improving vaccines by targeting antigens to dendritic cells

A new approach to enhancing the effectiveness of vaccines is to deliver antigens selectively to dendritic cells (DC) in situ, via monoclonal antibodies specific for particular DC surface molecules. This can markedly enhance CTL responses and, via helper T cells, also enhance antibody responses. DC activation agents or adjuvants must also be administered for effective CTL responses, but in some cases good antibody responses can be obtained without adjuvants. Here we review the role of different DC subsets and different DC target molecules in obtaining enhanced immune responses.

Improving vaccines by targeting antigens to dendritic cells

A new approach to enhancing the effectiveness of vaccines is to deliver antigens selectively to dendritic cells (DC) in situ, via monoclonal antibodies specific for particular DC surface molecules. This can markedly enhance CTL responses and, via helper T cells, also enhance antibody responses. DC activation agents or adjuvants must also be administered for effective CTL responses, but in some cases good antibody responses can be obtained without adjuvants. Here we review the role of different DC subsets and different DC target molecules in obtaining enhanced immune responses.