Cultural adaptation to Brazilian Portuguese of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale of pain assessment / Adaptação cultural para o português do Brasil da escala de avaliação de dor Face, Legs, Activity, Cry, Consolability revised(FLACCr) / Adaptación cultural para el portugués de Brasil de la escala de evaluación del dolor Face, Legs, Activity, Cry, Consolability revised(FLACCr)

AbstractObjective: to perform the translation into Brazilian Portuguese and cultural adaptation of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale, with children under 18 years old, affected by cerebral palsy, presenting or not cognitive impairment and unable to report their pain.Method: methodological development study of translation into Portuguese and cultural adaptation of the FLACCr. After approval by the ethics committee, the process aimed at translation and back-translation, evaluation of translation and back-translation using the Delphi technique and assessment of cultural equivalence. The process included the five categories of the scale and the four application instructions, considering levels of agreement equal to or greater than 80%.Results: it was necessary three rounds of the Delphi technique to achieve consensus among experts. The agreement achieved for the five categories was: Face 95.5%, Legs 90%, Activity 94.4%, Cry 94.4% and Consolability 99.4%. The four instructions achieved the following consensus levels: 1st 99.1%, 2nd 99.2%, 3rd 99.1% and 4th 98.3%.Conclusion: the method enabled the translation and cultural adaptation of the FLACCr. This is a study able to expand the knowledge of Brazilian professionals on pain assessment in children with CP.

ResumoObjetivo:realizar a tradução para a língua portuguesa do Brasil e adaptação cultural da escala Face, Legs, Activity, Cry, Consolability revised(FLACCr), com crianças de até 18 anos de idade, acometidas por paralisia cerebral, apresentando ou não comprometimento cognitivo e impossibilitadas de relatar sua dor.Método:estudo de desenvolvimento metodológico de tradução para o português e adaptação cultural da FLACCr. Após aprovação do comitê de ética, o processo contemplou tradução e retrotradução, avaliação da tradução e da retrotradução utilizando a técnica de Delphi e avaliação da equivalência cultural. O processo incluiu as cinco categorias da escala e as quatro orientações de aplicação, considerando nível de concordância igual ou maior a 80%.Resultados:foram necessários três ciclos da técnica de Delphi para consenso entre os juízes. A concordância obtida para as cinco categorias foi: Face 95,5%, Pernas 90%, Atividade 94,4%, Choro 94,4% e Consolabilidade 99,4%. As quatro orientações alcançaram os seguintes níveis de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% e 4ª 98,3%.Conclusão:o método possibilitou o desenvolvimento da tradução e adaptação cultural da FLACCr. Sendo um estudo capaz de ampliar o conhecimento de profissionais brasileiros sobre a avaliação da dor em crianças com PC.

ResumenObjetivo:realizar la traducción para el portugués de Brasil y la adaptación cultural de la escala, Face, Legs, Activity, Cry, Consolability revised(FLACCr), con niños menores de 18 años de edad, afectados por la parálisis cerebral, presentando o no deterioro cognitivo y que no pueden comunicar su dolor.Método:estudio de desarrollo metodológico de traducción al portugués y adaptación cultural de la FLACCr. Después de la aprobación por el comité de ética, el proceso incluyó la traducción y retrotraducción, evaluación de la traducción y retrotraducción utilizando la técnica Delphi y evaluación de la equivalencia cultural. El proceso incluyó las cinco categorías de la escala y las cuatro orientaciones de aplicación, teniendo en cuenta nivel de concordancia igual o superior al 80%.Resultados:fueron necesarios tres ciclos de la técnica Delphi para el consenso entre los jueces. La concordancia obtenida para las cinco categorías fue: Cara 95,5%, Piernas 90%, Actividad 94,4%, Llanto 94,4% y Capacidad de Consuelo 99,4%. Las cuatro orientaciones alcanzaron los siguientes niveles de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% y 4ª 98,3%.Conclusión:el método permitió el desarrollo de la traducción y adaptación cultural de la FLACCr. Este estudio fue capaz de aumentar el conocimiento de los profesionales brasileños en la evaluación del dolor en niños con PC.

Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.

Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 × 10-3Μ completely inhibited platelet aggregation (p<0.05), decreased TXB2 levels (p<0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p<0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 ± 34, 450 ± 34 and 62 ± 2.4% (p<0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.

Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5) expressing three proteins (E7, E6, and E5) of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id) route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose) induced a strong activation of E7-specific interferon-γ (INF-γ)-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70 percent of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50 percent of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

Pasteurella pneumotropica causa la regresion de tumores humanos trasplantados en ratones inmunodeficientes / Pasteurella pneumotropica produces regression of human tumors transplanted in immunodeficiency mice

La técnica de trasplante de tumores humanos en ratones inmunodeficientes es muy utilizada como modelo en investigaciones sobre el cáncer. De acuerdo con las recomendaciones internacionales, los animales de experimentación deben estar libres de los micoorganismos que interfieren en los resultados finales de las investigaciones, dentro de los cuales se encuentra Pasteurella pneumotropica. En el presente trabajo se evaluó la interferencia que produce esta bacteria en el crecimiento de la línea celular A549 de adenocarcinoma humano trasplantada en ratones de la cepa nude N:NIH (S)-nu. Se utilizaron 40 ratones divididos en 4 grupos de 10 animales cada uno. Grupo 1: inoculados con la línea celular; grupo 2, con la bacteria; grupo 3, con la línea celular y la bacteria y grupo 4, el control sin inoculaciones. Se observaron diferencias significativas en el crecimiento tumoral entre los animales de los grupos 1 y 3. Si bien este microorganismo es un patógeno oportunista no letal, los ratones trasplantados con la línea celular A549 e infectados con P. pneumotropica no son aptos para utilizarse como modelo animal en estudios sobre el cáncer debido a que esta bacteria interfiere en el desarrollo de la línea tumoral, con la consecuente interpretación errónea de los resultados. Pero el hecho que la bacteria haya causado la regresión de un tumor en pleno crecimiento es inesperado y el mecanismo de acción será objeto de futuros experimentos.

The technique of human tumor cell line transplantation in immunodeficient miceis used worldwide as a model for cancer research. In accordance with international recommendations, animals used in biomedical research should be free of microorganisms which can interfere in experimental results; including Pasteurella pneumotropica. The object of this study was to evaluate the interference produced by P. pneumotropica in the human adenocarcinoma cell line A549 transplanted in N:NIH(S)-nu mice. A total of 40 mice divided into 4 groups of 10 animals each was used to perform this study. Group 1: inoculated with the cell line; group 2, with the bacteria; group 3, with the cell line and the bacteria; group 4, as control with no inoculations. Significant differences were observed in tumor growth in groups 1 and 3, infected and not infected with P. pneumotropica. Although this microorganism is non lethal and only opportunistic, the infected animals are to be considered not suitable to be transplanted with the tumor cell line A549 for experimental studies since these bacteria interfere with tumor growth. However, the fact that a growing tumor regresses in the presence of the bacteria is an interesting bservation which deserves further exploration in order to elucidate the mechanism involved.

Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum

The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.

Effect of "rasayanas" a herbal drug preparation on cell-mediated immune responses in tumour bearing mice.

Administration of herbal preparation, Rasayanas has been found to enhance the natural killer cell activity in normal as well asin tumour bearing animals. Brahma Rasayana (BR) was found to have the maximum activity. BRand Aswagandha Rasayana (AR) were found to activate antibody-dependent cellular cytotoxicity significantly. AR was also found to activate macrophages. All the Rasayanas were found to stimulate antibody dependent complement mediated tumour cell lysis. The results of these studies indicate usefullness of Rasayanas for immunostimulation in normal and in disease state.

Marcación del anticuerpo monoclonal B2C114 con 111In usando un quelante funcional / 111In labelling of B2C114 monoclonal antibody with a bifunctional chelating agent

El anticuerpo monoclonal (AcMo) B2C114, dirigido contra el antígeno carcinoembrionario (CEA) fue conjugado con el anhídrido bicíclico del DTPA (CA-DTPA) usando diferentes relaciones molares CA-DTPA: AcMo desde 1:1 hasta 30:1. Se determinó para cada caso la eficiencia de acoplamiento y el número de moléculas de DTPA por molécula de AcMo. Se realizó la marcación con 111In para todas las relaciones molares CA-DTPA: AcMo y se determinó la pureza radioquímica por cromatografía instantánea en placa delgada (ITLC Gelman SG) y cromatografía en gel (Sephadex G-25). La biodistribución del AcMo marcado en ratones normales Balb/c y en portadores de tumor reactivo (M3), a diferentes horas post-inyección, mostró una acumulación creciente en el tumor al cabo de 72 h, con captación en hígado y riñón. Se observó también que al aumentar la relación molar CA-DTPA se incrementó el porcentaje de radiactividad asociada al riñón, lo cual indicaría una mayor inestabilidad del radiofármaco

Alteraçäo da resposta inflamatória e imunológica em animais portadores de tumor experimental / Alteration on inflammatory and immunological response in animal carriers of experimental tumor

Os autores estudaram em camundongos portadores de tumor de Walker as alteraçöes de resposta a agente inflamatório e as modificaçöes de reaçöes imunológicas, assim como o período no qual se tornam evidentes. Usaram como agente inflamatório a carragenina e como parâmetro imunológico o teste de hipersensibilidade ao BCG. As conclusöes foram que os animais portadores de tumor apresentam diminuiçäo na capacidade de resposta inflamatória inespecífica à carragenina e ao CBG, assim como no teste de hipersensibilidade tardia ao BCG

Influence of nutrition on anti-tumor activity

Nutritionally supporting the malnourished tumor bearing host may not benefit the disease outcome, but, rather, may preferentially "feed the cancer". We hypothesized that repletion is beneficial only when it augments an anti-tumor immune response. To support this hypothesis, 240 A/J mice were assigned to isocaloric dietary groups (24%, 5%, or 2.5% protein). On day 14 the mice received either immunogenic C1300- neuroblastoma (NB) or non-immunizing TBJ-NB. On day 21 half of the restricted animals were repleted with 24% protein chow. At day 35, chromium-release cell-mediated cytotoxicity was measured. In the group of mice that received 2.5% protein chow, nutritional repletion specifically augmented anti-tumor activity for C1300-NB which elicits a host immune response (33.78 L.U. (repleted) vs 3.47 L.U. (depleted) p less than 0.01), in contrast, nutritional repletion was detrimental for non-immunizing TBJ-NB, where further depression of cytotoxicity was seen (1.37 L.U. (repleted) vs 2.06 L.U. (depleted) 0 less than 0.01). This suggests that the influence of nutritional repletion in tumor nearing animals is dependent on the integrity of host's anti-tumor immunity.

Allosensitization induced suppression of various murine tumors: role of non-H-2 antigens in antitumor immunity.

Presence of alloantigens on various murine tumors was tested by tumor rejection in allosensitized Swiss mice. The results indicated the presence of alloantigen on immunogenic tumors like chemically induced fibrosarcoma (FS), ascitic sarcoma 180 (S 180) and immunogenic variant of lymphosarcoma (LS-A) in Swiss mice, while these antigens could not be detected by this procedure on spontaneous lymphosarcoma (LS). Allosensitization with skin graft was found to offer quantitatively higher antitumor resistance than the allosensitization achieved by allogeneic lymphocytes. Antitumor effect was not seen when tumor cells were inoculated earlier than day 3 of grafting. Further, host immunosuppression with whole body irradiation up to day of 3 of skin grafting abrogated the antitumor effect. H-2 compatible and non-H-2 incompatible skin graft sensitization of host could offer resistance against both S 180 and LS-A. Further, tumor immune mice rejected H-2 compatible, non-H-2 incompatible skin graft significantly earlier.

Inmunoterapia del Cáncer: transmisión experimental de una neoplasia de un hombre a un animal de distinta especie y ensayo de inmunoterapia pasiva de los tumores malignos / Cancer inmunotherapy

Para que la transmisión espontánea o experimental de las enfermedades infecciosas se realice, es necesaria la confluencia de dos factores fundamentales: Un germen virulento y un sistema inmuno deficiente. Se inoculó sangre de canceroso debidamente comprobado, a un animal de distinta especie, obteniéndose a los pocos días la reproducción del tumor original. Sin embargo, en el curso de estos trabajos se observó que la casi totalidad de los animales inoculados permanecían indemnes. La explicación de este hecho estaría a que el sistema inmune de éstos no sólo había aniquilado a cada uno de los componentes de la sangre inoculada, sino que como contrapartida, habría elaborado para este fin, anticuerpos. Esta circunstancias, permitió considerar teóricamente la posibilidad de intentar la inmunoterapia pasiva. Para comprobarlo se suministró al paciente canceroso sangre del animal inmunizado con la propia sangre del paciente en cuestión. Los resultados consignan tiempos de sobrevida hasta por diecisiete años en pacientes que habían sido desahuciados. Naturalmente para que este ensayo acerca de la inmunoterapia pasiva específica del cáncer tenga vigencia debe ser rigurosamente comprobado. Si se confirma, constituiría una nueva alternativa para el tratamiento del cáncer

Inmunidad concomitante antitumoral: un posible mecanismo de control de las metástasis / Antitumor concomitant immunity: a possible metastasis control mechanism

Se entiende por inunidad concomitante (IC) la falta de desarrollo de un segundo implante tumoral distante del primario, atribuyéndole una explicación inmunológica. El objeto de estos trabajos fue estudiar la IC asociada a tumores espontáneos. En ratones BALB/c, se comprobó que el transplante de varios tumores singenecicos, de indetectable inmunogenicidad, inhibían el desarrollo de un segundo implante del mismo tumor, y a veces de otro tumor, evidenciándose cierta inespecificidad. Esta IC se observada también en ratones atímicos, jóvenes y adultos, y en los tratados con sílica, descartándose la participación de linfocitos T, células NK y macrófagos. La falta de desarrollo del implante secundario no se debía a rechazo tumoral, contrariamente a lo que pudimos observar con un tumor inmunogénico en un sistema alogeneico, sino a citostasis. Este estado de tumor dormido se debería a la falta de aflujo de células del huésped, ya que cualquier estimulo inflamatorio local abrogaba la IC llevando a un rápido crecimiento tumoral. Estaría en juego un fenómeno de anti-inflamación ya que se comprobó que un foco inflamatorio inhibía el desarrollo de un implante tumoral en el flanco contralateral, que el mismo efecto se conseguía con la administración de piroxicam, y que el propio tumor disminuía la reacción inflamatoria creada por la implantación de un cuerpo extraño. Considerando a las metástasis como implantes secundarios naturales, se compararon dos tumores de mama de origen común, pero diferente...

Angiogenic activity of solid and ascites-transformed syngeneic murine tumors

The angiogenic activity of normal and neoplastic animal tissue was studied in the chorioallantoic membrane preparation [CAM]. Reticulated chick erythrocytes within the tumor implant were used as a criterion for angiogenesis. Normal adult rodent tissue from the thyroid, liver, spleen, adrenal, heart muscle, skeletal muscle, small bowel, salivary gland and pituitary did not induce angiogenesis. Fourteen syngeneic mouse tumors of various tissue origin all induced angiogenesis, but to a varying extent. Solid sarcomas and carcinomas and one melanoma had a high incidence of angiogenesis in the CAM test. Ascites tumors in solid form from subcutaneous transplants, with one exception, had lower activities. There was an inverse correlation between angiogenesis and the transplantation dose of the tumors. This indicates a relationship between malignancy-related cell characteristics and tumor vascular-ization. There was no statistical correlation, however, between angiogenesis and growth speed, or propensity to form spontaneous metastases

Açäo do BCG na imunoterapia ativa de ratos nude recém-nascidos heterotransplantados com linhagem tumoral humana KB / Action of BGG in the active immunotherapy of nude nude mice heterotransplanted with human tumor lineage (KB)

O efeito antitumoral do BCG já foi atribuído àtivaçäo de células T, macrófagos, células NK, resposta do SRE e respostas inespecíficas. Neste trabalho, foi utilizado um modelo experimental (rato nude atímico), cogenitamente desprovido de células T e em faixa etária que ainda näo tenha tido maturaçäo de células NK. O tumor inoculado e desenvolvido nesses ratos foi o KB (carcinoma epidermóide de boca, humano) em suas passagens 6 a 14; o modificador de resposta biológica (MRB) foi o onco BCG (cepa Moreau-Säo Paulo), produzido pelo Instituto Butantä. Os resultados demonstraram que, quando o BCG era administrado oito dias antes da inoculaçäo do tumor, desenvolvia uma proteçäo, que se traduzia pela diminuiçäo da percentagem de pega tumoral e da incidência de metástases, bem como pelo aumento da sobrevida dos animais portadores de tumor. Ao que tudo indica, tais efeitos säo independentes da presença de células T e NK

Regulación de la respuesta inmune mediada por interacciones celulares: su relación con la inmunidad anti-tumoral / Regulation of the immune responce mediated by cellular interactions: its relation to anti-tumor immunity

Se describen los posibles mecanismos de regulación de la respuesta inmune en el ratón, fundamentalmente los mediados por interacciones celulares. Los macrófagos presentan el antígeno a células T que se caracterizan por poseer el marcador de superficie Lyt 1, y reconocen a antígenos del complejo mayor de histocompatibilidad de clase II en al superficie de la célula presentadora del antígeno. Estos macrófagos liberan un factor solubre, 1a IL-1, que activa a las células Lyt 1 las que como consecuencia de ello liberan otro factor soluble, 1a IL-2, que permite la proliferación y diferenciación celular. Las células T participan en la regulación de la respuesta inmune. Se sugiere que las células T colaboradoras estimulan una cascada de células T supresoras, cada una de ellas activando la próxima hasta llegar a la última que transmite una señal que reduce la actividad de las células colaboradoras. Por otra parte, las células supresoras hiperactivadas pueden reestimular a las células colaboradoras y así, por un mecanismo de feed-back se produciría la reactivación de las células B productoras de anticuerpos, de las células citotóxicas o de los macrófagos. También los macrófagos son esenciales en la regulación de la respuesta inmune ya que factores supresiones de las células que los producen a las células aceptoras. El sistema regulatorio también actuaría contra los antígenos específicos de tumor, los que pueden estar constituídos por antígenos que no se expresen al mismo tiempo, en la misma cantidad o en la misma localización que en las células normales

Induçäo de resistência a tumores / Induction of resistance to tumors

No Laboratório de Microbiologia Geral do Instituto Biomédico da UFF têm sido realizadas observaçöes sobre alteraçöes de reatividade imunológica específica em camundongos inoculados com tumores (Sarcoma de Ehrlich, Sarcoma 180 e Tio II). Para provocar essas alteraçöes as células tumorais foram colocadas na água de beber ou instiladas diretamente na língua ou no nariz. Das diversas experiências realizadas ao longo de vários anos foi observado inicialmente que camundongos que foram inoculados com células tumorais viáveis colocadas sobre a língua ou diretamente nas narinas näo desenvolvem tumores. Em várias experiências, esses camundongos que tiveram contato prévio com células tumorais colocadas diretamente sobre as mucosas da língua ou do nariz, quando inoculados, após um período de incubaçäo, com células viáveis por via intramuscular comportam-se como se tivessem recebido um estímulo secundário e mostram alteraçöes na reatividade imunológica, quando comparados com animais usados como controle