Inulin Induces IL-10 Secretion and Increased FOXP3 Gene Expression in Human Peripheral Blood Mononuclear Cells

ABSTRACT Inulin is an effective prebiotic and its potential in modulating systemic immunity have been proposed. A subpopulation of T cells, named T regulatory cells (Tregs), expressing the Forkhead boxP3 transcription factor are key mediators of peripheral tolerance and suppress undesirable immune responses. These Tregs can be induced by cytokine transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). This work aimed to evaluate inulin effects on human peripheral blood mononuclear cells (PBMC) in vitro. PBMC were incubated with inulin, and the expression of TGF-(1, FOXP3 and IL-10 was analyzed. Increased supernatant IL-10 levels were observed in PBMC of inulin-treated group (p=0.03). Moreover, FOXP3 gene expression was 7.6 fold higher in inulin-treated PBMC, whereas a trend in TGF-β1 expression was detected (p=0.055). These data suggest that inulin induces an immunosuppressive environment in cultured PBMC by promoting FOXP3 gene expression and IL-10 secretion. These studies offer prospects for further fundamental research in this field.

Leishmanicidal activity of brazilian propolis hydroalcoholic extract in Leishmania amazonensis / Atividade leishmanicida de extrato hidroalcoólico de própolisbrasileira em Leishmania amazonensis

As leishmanioses são consideradas doenças negligenciadas devido às altas incidências, ampla distribuição geográfica e dificuldade no tratamento sendo incluídas na relação de doenças prioritárias pela Organização Mundial da Saúde. Os tratamentos disponíveis para estas doenças apresentam elevada toxicidade,justificando a busca por fármacos alternativos. Estudos prévios com própolis, resina produzida por abelhas,demonstraram sua atividade antiparasitária e imunomoduladora em diversos modelos experimentais. O objetivo deste trabalho foi avaliar o efeito in vitro do extrato hidroalcoólico de própolis brasileira, coletadona cidade de Botucatu no estado de São Paulo, sobre formas promastigotas de Leishmania amazonensis, bem como analisar seu efeito in vivo sobre a carga parasitária em baço de camundongos susceptíveis à infecção. Assim, formas promastigotas tratadas com extrato hidroalcoólico de própolis brasileira nas concentrações 5, 10, 25, 50 ou 100 µg/mL apresentaram efeito inibitório sobre a proliferação desses parasitos nos tempos de 24, 96 e 168 h. No entanto, as concentrações de 50 e 100 µg/mL mostraram-se mais eficazes quando comparadas ao controle e às demais concentrações em todos os tempos avaliados.Em relação à carga parasitária, após 30 dias de infecção com L. amazonensis, camundongos BALB/c foram tratados diariamente com a própolis (5mg/kg), via oral ou intraperitoneal, durante 60 dias. Posteriormente,o baço destes animais foi coletado para análise da carga parasitária. O tratamento por via oral reduziu 40%da carga parasitária. Desta forma, a amostra de própolis brasileira testada apresentou ação leishmanicida sobre L. amazonensis em cultura e em camundongos infectados com este protozoário.

Leishmaniosis are considered neglected diseases due to its high incidence, widespread and difficultyin treatment being included in the list of priority diseases by the World Health Organization. Available treatments for these diseases have high toxicity, which explains the search for more effective drugs. Previous studies with propolis - a resinous substance produced by bees - demonstrated immunomodulatory and anti-parasitic activity in several experimental models. The objective of this study was to evaluatethe effect in vitro of Brazilian propolis hydroalcoholic extract, collected in the city of Botucatu in SãoPaulo State, on promastigotes forms of Leishmania amazonensis as well as its effect on the parasiteload in the spleen of infected mice. Thus, promastigote forms treated with 5, 10, 25, 50 or 100 μg/mLof Brazilian propolis hydroalcoholic extract at 24, 96 and 168 hours showed inhibitory effect on the spread of these pararasite at all indicated times. However, the concentrations of 50 and 100 μg/mL were more effective, reducing the parasite spread when compared to the control and other concentrations at all times. Regarding parasitic load, after 30 days of infection with L. amazonensis, BALB/c mice were treated on a daily basis with propolis (5mg/kg) orally or intraperitoneally for 60 days. Further, the spleen was collected for parasite load analysis. Oral treatment reduced 40% of the parasitic load. Thus, the tested Brazilian propolis sample showed antileishmanial activity on L. amazonensis in culture andin parasite- infected mice.

Prevalence of Torque teno virus in healthy donors of Paraná State, southern Brazil

OBJECTIVE: To determine the prevalence of the Torque teno virus in healthy donors in the northern and northwestern regions of the state of Paraná, southern Brazil.METHODS: The Torque teno virus was detected by a nested polymerase chain reaction using a set of oligoprimers for the N22 region.RESULTS: The prevalence of the virus was 69% in 551 healthy blood donors in southern Brazil. There was no statistically significant difference between the presence of the virus and the variables gender, ethnicity and marital status. There was significant difference in the prevalence of the virus regarding the age of the donors (p-value = 0.024) with a higher incidence (74.7%) in 18- to 24-year-old donors.CONCLUSION: A high prevalence of Torque teno virus was observed in the population studied. Further studies are needed to elucidate the routes of contamination and the clinical implications of the virus in the healthy population.

Involvement of transforming growth factor beta-1 (TGFβ1) cytokine and FOXP3 transcription factor genetic polymorphisms in hematological malignancies

Hematological malignancies (HM) are a group of neoplastic diseases that arise from hematologic cell lineages. Transforming growth factor beta 1 (TGFβ1) is shown to negatively regulate normal and malignant hematopoiesis and, in immunological context, to promote T cell exhaustion and generation of regulatory T cells, which are shown to be deleterious in cancer, by the induction of transcription factor FOXP3 expression. The present study aimed to evaluate TGFB1 exon-1 rs1800470 and FOXP3 intron-1 rs2232365 polymorphisms in relation to HM susceptibility. DNA was extracted from blood samples of 43 HM patients and 142 neoplasia-free individuals and polymorphisms were analyzed by allelic-specific PCR. Association analysis was assessed by the Odds Ratio (OR) with significance level of 5%. Regarding FOXP3 polymorphism, no significant differences were observed in genotype or allele distribution among the patients and controls. However, there was a positive association between TGFB1 TT genotype and HM susceptibility (OR = 4.07; CI95% = 1.94 - 8.52). In the combined analysis, a positive association was also observed for TGFB1 TT and FOXP3 GG genotypes (OR = 4.00; CI95% = 1.54 - 10.41) in relation to HM susceptibility. Our results indicated promising new markers to be further investigated in hematological malignancies.

Meduloblastoma: aspectos histológicos, moleculares e imunopatológicos / Medulloblastoma: histological, molecular and immunopathological aspects

O meduloblastoma é um tumor cerebelar caracterizado como tumor neuroectodérmico primitivo prevalente em crianças, sendo as do sexo masculinos as mais afetadas. Com relação à classificação histológica,existem cinco variações: clássico, desmoplásico, anaplásico, células gigantes e de extensa nodularidade. Muitos estudos relatam que a patogênese do meduloblastoma está relacionada com mutações em fatores de crescimento do SNC, sendo que as principais vias envolvidas são: Sonic Hedgehog, NOTCH, WNT eOTX. Ainda, com respeito à imunologia, pacientes com meduloblastoma apresentaram alta taxa de IFN-γno soro e células TH17 no sangue periférico, e foi observado que o TGF-β tem sido associado à estimulação mitogênica, o que pode estar relacionado à patogênese da doença. A predominância de uma resposta TH1 relacionada à sobrevivência também foi relatada. O desenvolvimento terapêutico para o meduloblastoma,apesar de limitado, é significativo, uma vez que este vem apresentando melhora na sobrevida de seus pacientes. Entretanto, um maior conhecimento dos mecanismos envolvidos na imunopatogênese é necessário para o desenvolvimento de novos fármacos e formas de tratamento.

Medulloblastoma is a cerebellar tumor classified as primitive neuroectodermal tumor and is prevalent in children, especially male. With regard to histological classification, there are five variations: classical, desmoplastic, anaplastic, large-cell variant and with extensive nodularity. Several studies have reported that medulloblastoma pathogenesis is related to mutations in CNS growth factors, and the main pathways involved are Sonic Hedgehog, NOTCH, WNT, and OTX. Also regarding the immunology, patients with medulloblastoma have a high serum concentration of INF-γ and TH17 cells in peripheral blood, and it was observed that TGF-β has been associated with mitogenic stimulation, and possibly associated to the pathogenesis of this disease. The prevalence of a TH1 response related to the survival was also described. The development of therapies for medulloblastoma treatment, though limited, is significant, as they resultin an improvement in the patient’s survival. However, a better understanding of the mechanism involvedin its immunopathogenesis is still necessary for the development of new drugs and ways of treatment.

Torque teno virus among dialysis and renal-transplant patients

Patients who undergo dialysis treatment or a renal transplant have a high risk of blood-borne viral infections, including the Torque teno virus (TTV). This study identified the presence of TTV and its genome groups in blood samples from 118 patients in dialysis and 50 renal-transplant recipients. The research was conducted in a hospital in the city of Maringá, state of Paraná. The viral DNA, obtained from whole blood, was identified by using two nested Polymerase Chain Reactions (PCR). The frequencies of TTV were 17% and 36% in dialysis patients using the methodology proposed by Nishizawa et al. (1997) and Devalle and Niel (2004), respectively, and 10% and 54% among renal-transplant patients. There was no statistically significant association between the frequency of the pathogen and the variables: gender, time in dialysis, time since transplant, blood transfusions, and the concomitant presence of hepatitis B, for either the dialysis patients or the renal-transplant recipients. Among dialysis patients and renal-transplant recipients, genogroup 5 was predominant (48% and 66% respectively), followed by genogroup 4 (37% and 48%) and genogroup 1 (23% and 25%). Genogroup 2 was present in both groups of patients. Some patients had several genogroups, but 46% of the dialysis patients and 51% of the renal-transplant recipients had only a single genogroup. This study showed a high prevalence of TTV in dialysis patients and renal-transplant recipients.

Gestação: um desafio imunológico / Pregnancy: an immune challenge

Diversos estudos demonstram a importância de aspectos imunológicos na gestação. Durante a gestação ocorre a implantação do embrião no útero materno, onde irá se desenvolver até o final da gravidez. Dentre os aspectos imunes, pode-se citar a importância da modulação dos linfócitos T, das células natural killers (NK) e das diversas citocinas existentes no organismo materno. A tolerância materna ao feto parece ser mediada por hormônios maternos específicos e pela expressão do antígeno leucocitário humano G (HLA-G) característico na gravidez. Outros estudos sugerem que a rejeição fetal e complicações durante a gravidez podem ocorrer devido à presença de antígenos de histocompatibilidade menor (mHAg), adquiridos pela mãe a partir do compartilhamento sanguíneo com o feto, e devido à presença de anticorpos maternos contra o espermatozoide e contra o feto. O objetivo desta revisão é descrever os aspectos imunológicos que permitem a tolerância materna ao feto na gestação, assim como possíveis causas para a rejeição do embrião e complicações durante a gravidez.(

Several studies demonstrate the importance of immunological aspects of pregnancy. During pregnancy,the embryo is implanted in the womb, where it will develop until the end of pregnancy. Amongst the immune aspects, the importance of the modulation of T lymphocytes, natural killers (NK) cells and many cytokines in maternal organism can be mentioned. The maternal tolerance to the fetus appearsto be mediated by specific maternal hormones and by the expression of human leukocyte antigen G (HLA-G) - characteristic in pregnancy. Other studies suggest that fetal rejection and complications during pregnancy may occur because of the presence of minor histocompatibility antigens (mHAg), acquired by blood sharing of the mother with the fetus, and because of the presence of maternal antibodies against the sperm and against the fetus. The purpose of this review is to describe the immunological aspects that allow maternal tolerance to the fetus during pregnancy, as well as possible causes forrejection of the embryo and complications during pregnancy.

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC.

TT virus in peripheral blood cells from patients with human papillomavirus (HPV): investigating association with cervical carcinoma

Torque Teno Virus (TTV) presence was investigated in peripheral blood of 117 brazilian women by nested polymerase chain reaction. TTV DNA was observed in 18.6% of healthy donors and in 24.32% Human Papillomavirus (HPV) patients. TTV presence was also investigated in the HPV positive group for comparison between the cervical cancer and noncancerous patients. TTV DNA prevalence was significantly higher among the HPV positive patients with cervical cancer (57.14%) than in HPV noncancerous patients (16.67%). Thus, the presence of TTV infection could be a risk factor for cancer development in the patients presenting HPV-TTV coinfection. Further studies are required to clarify the TTV influence in HPV pathogenesis.

Hipoplasia septo-óptica-hipofisária em paciente com septo pelúcido normal porém com risco de morte neonatal e a participação potencial do fator de transcrição hipofisário HESX1 / The potential involvement of the pituitary transcription factor HESX1 in the septo-optic-pituitary hypoplasia with normal septum pellucidum but life-threatening neonatal phenotype

A displasia septo-óptica (DSO) é uma síndrome do desenvolvimento considerada heterogênea, pois envolve anomalias da linhamédia do cérebro associadas a disfunções oftalmológicas, neurológicas e do eixo hipotálamo-hipófise. O fenótipo é altamentevariável dificultando a classificação da doença. Relatamos um caso de hipopituitarismo neonatal grave que levou à descobertade malformações cerebrais e hipoplasia do nervo óptico, sendo caracterizada assim a síndrome DSO-like. Mesmo em presençade um septo pelúcido normal e com poucas alterações na ressonância magnética, este paciente apresentou um fenótipo endócrinode alto risco de morte no período neonatal. Mutações genéticas têm sido raramente descritas no HESX1 e estão associadas avárias deficiências hormonais hipofisárias combinadas com a DSO. O gene HESX1 codifica um fator de transcrição pertencenteà classe de genes chamados homeobox. A partir deste gene candidato, foi isolada a região codificadora no DNA para análise porsequenciamento. Este relato de caso com seguimento clínico de 7 anos e estudo genético preliminar apresenta uma discussãoda investigação diagnóstica a partir do quadro inicial, destacando as alterações de neuroimagem encontradas nesta síndrome.

Vírus linfotrópico de células T humano tipo 1 (HTLV-1): implicações em doenças autoimunes / Human T-Cell Lymphotropic Virus Type I (HTLV-1): implications for autoimmune diseases

A autoimunidade é caracterizada pela destruição tecidual, que acarreta danos funcionais, causados por células autorreativas que escapam dos mecanismos de autotolerância. Doenças autoimunes podem ser iniciadas por infecções virais e o estudo da associação entre essas viroses e a autoimunidade tem possibilitado melhor conhecimento dos mecanismos moleculares envolvidos nas doenças autoimunes. O vírus linfotrópico de células T humano tipo 1 (HTLV-1) é um delta vírus que infecta preferencialmente linfócitos. Partículas semelhantes aos retrovírus foram identificadas em pacientes com doenças autoimunes. Portanto, esta revisão teve por objetivo abordar os principais aspectos envolvendo HTLV-1 com o lúpus eritematoso sistêmico e artrite reumatóide. Estudos demonstram que retrovírus podem integrar seu material genético no DNA do hospedeiro, alterando o perfil de expressão de genes relacionados a apoptose ou a moléculas do sistema imunológico. Sabe-se que o HTLV-1 pode causar diferentes manifestações clínicas em seus portadores e os mecanismos pelos quais se desencadeiam as doenças autoimunes associadas ao HTLV-1 não estão bem esclarecidos. Além da perpetuação e produção acentuada de citocinas pró-inflamatórias, estudos têm demonstrado que tanto as células Th17 quanto as células T regulatórias (Tregs) estão envolvidas na patogênese de doenças autoimunes. Portanto o reconhecimento de partículas virais do HTLV-1 poderia ser utilizado como marcador de risco no desenvolvimento de doenças autoimunes.

Autoimmunity is characterized by tissue destruction that implicates functional damages caused by self-reactive cells that escape self-tolerance mechanisms. Autoimmune diseases can be initiated by viral infections and the study of the association between these viruses and autoimmunity has advanced the understanding of the molecular mechanisms involved in autoimmune diseases. The Human T-Cell Lymphotropic Virus Type I (HTLV-1) is a deltavirus that infects preferentially lymphocytes. Retrovirus particles like has been identified in patients with autoimmune diseases. Therefore this review had by objective approach the main aspects involving HTLV-1 with systemic lupus erythematosus and rheumatoid arthritis. Studies show that retroviruses can integrate their genetic material in host DNA, changing the expression gene profile related with apoptosis and immunologic system molecules. It’s known that HTLV-1 can cause different clinical manifestations in their careers and the mechanisms that triggers the HTLV-1 associated autoimmune diseases are not well known. Besides the perpetuation and marked production of pro-inflammatory cytokines, studies have demonstrated that both Th17 cells and T regulatory cells (Tregs) are involved in autoimmune diseases pathogenesis. Therefore the HTLV-1 viral particles recognized could be used as a risk marker in the development of autoimmune diseases.

Aspectos imunológicos da infecção pelo vírus do papiloma humano (HPV) / Immunological aspects of human papiloma virus (HPV) infection

O vírus do papiloma humano (HPV-human papiloma virus) pode infectar até 80% das pessoas, principalmente as sexualmente ativas. O risco e a sintomatologia da infecção são distintos entre os gêneros. Sabe-se que existem mais de 150 sorotipos e estes são agrupados por seu tropismo. Embora a maioria das infecções siga um curso benigno, a infecção persistente por certos sorotipos pode levar ao desenvolvimento de câncer. Os sorotipos 16 e 18 estão envolvidos com uma forma grave de lesão, acarretando câncer, principalmente do colo do útero. Os sorotipos 6 e 11 são descritos como causadores de verrugas anogenitais. O vírus, de aproximadamente 8.000 pb, se instala na célula e por meio da expressão das oncoproteínas E6 e E7, levando à inibição de proteínas como a p53 e a pRB, importantes na apoptose e na parada do ciclo celular. As vacinas atuais geram imunidade contra os sorotipos 6, 11, 16 e 18. A vacina pode ser tetravalente (quatro sorotipos: 6, 11, 16 e 18) ou bivalente (16 e 18). Ambas apresentam proteção cruzada contra a infecção por sorotipos não inclusos nas vacinas, porém não possuem caráter terapêutico. O presente trabalho teve como proposta revisar os avanços sobre a infecção pelo HPV, os aspectos imunológicos e as vacinas profiláticas disponíveis.

The human papilloma virus (HPV-human papilloma virus) can infect up to 80% of people, especially sexually active. The risk of infection and symptoms are different between the sexes. It is known that there are over 150 serotypes and these are grouped by their tropism. Although most infections follow a benign course, the persistent infection with certain serotypes may lead to the development of cancer. The serotypes 16 and 18 are involved in a severe form of injury, resulting in cancer, particularly cervical cancer. Serotypes 6 and 11 are described as causes of anogenital warts. The virus, approximately 8.000 bp, it installs itself in the cell and through the expression of oncoproteins E6 and E7 leading to inhibition of proteins such as p53 and pRB, important in apoptosis and cell cycle arrest. Current vaccines generate immunity against serotypes 6, 11, 16 and 18. The vaccine can be tetravalent (four serotypes 6, 11, 16 and 18) or bivalent (16, 18). Both have cross-protection against infection by serotypes not included in the vaccines, but have no therapeutic character. This study was proposed to review progress on the HPV infection, the immunological aspects and prophylactic vaccines available.

Higher than normal plasma Iinterleukin-6 concentrations in brazilian patients with mood disorders

The aim of this work was to study the plasma concentration of IL-6 by ELISA in the patients with mood disorders and normal healthy donors. The plasma concentration of IL-6 was higher in the patients than in the control healthy group. Results suggested that IL-6 could serve as an immunological marker in mood disorder pathogenesis as well.

Interações entre candida albicans e hospedeiro / Interactions between candida albicans and host

Candida albicans pode causar graves infecções em pacientes que estão imunocomprometidos por doenças, por cirurgias ou por terapia imunossupressiva. Os altos níveis de morbidade e mortalidade resultantes de infecções em pacientes hospitalizados mostraram que C. albicans tornou-se um patógeno humano de grande relevância clínica. Mesmo o sistema imune sendo o principal fator que define a transição do fungo de comensal para patogênico, fatores de virulência expressos por C. albicans, tais como adesinas, mudança fenotípica, comportamento dimórfico, e secreção de enzimas hidrolíticas, podem contribuir para a persistência da colonização, assim como o desenvolvimento de episódios sintomáticos. A defesa do hospedeiro compreende ingestão e eliminação do fungo por células fagocíticas que possuem vários receptores, como o Toll-4, dectina-1 associado a receptores tipo Toll-2 e receptores de manose. A interleucina-10 (IL-10) produzida por fagócitos determina a susceptibilidade do hospedeiro a infecção fúngica, enquanto a IL-10 produzida por células T reguladoras é responsável pelo comensalismo. Em contraste, a produção de fator de necrose tumoral- α (TNF-α), interleucina –1 β (lL-1 β), (IL-6), (Il-12) e IL-17 conferem imunidade protetora. O interferon-γ (IFN- γ) produzido por células natural “killer” e células Th1 estimula a migração de fagócitos e maior eficácia na destruição do fungo. Nas células epiteliais de mucosas os receptores NOD-like e defensinas-β citoplasmáticos evitam a translocação de C. albicans da microbiota para os tecidos os quais são modulados por citocinas IL-1 β,IL-17 e IL-22.

Candida albicans can cause grave infections in patients who are immunocompromised by diseases, by surgery, or by immunesupresive therapy. The high levels of morbidity and mortality resulting from those infections in hospitalized patients show that C. albicans became a prominent human pathogen. Although the host immune system is the major factor balancing the transition from commensalisms to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans by phagocytic cells, which present receptors Toll-like 4, dectin–1 associated to receptors Toll-like2 and mannose receptors. The cytokine IL-10 (IL-10) produced by phagocytes has a crucial role on susceptibility of host fungal infection, whereas IL-10 produced by regulatory T cells is mainly responsible by commensalisms. In contrast, productions of tumour necrosis factor - α (TNF-α), interleukin–1 β (lL-1 β), (IL-6) and (Il-12) provided protective cell–mediated immunity. The interferon-γ produced by natural killer and TH1 cells stimulates migration of phagocytes and major efficacy on destruction of fungi. In epithelial cells from mucosas the NOD-like receptors and defensins-β cytoplasmatic prevent the translocation of C. albicans from microbiota to tissues, which are modulated by IL-1 β, Il-17 and Il-22 cytokines.

Ação do extrato de própolis na Leishmaniose / Propolis extract action in Leishmaniasis

A leishmaniose causa mortalidade e morbidade em mais de 80 países e caracteriza-se como uma doença parasitária com diversas manifestações, por isso constitui um sério problema de saúde pública. No Novo Mundo ocorre a Leishmaniose Visceral (LV) e Leishmaniose Tegumentar Americana (LTA). A LTA é considerada uma enfermidade polimórfica, espectral da pele e das mucosas, agrupada em diferentes formas clínicas: a leishmaniose cutânea, a cutaneomucosa e a cutânea difusa. A Organização Mundial da Saúde recomenda os antimoniais pentavalentes como drogas de primeira escolha no tratamento da leishmaniose. Entretanto, devido aos efeitos indesejados dessas drogas, tem sido proposto o estudo para o desenvolvimento de novos fármacos para seu tratamento. Assim, tem-se investigado o uso da própolis, visto que está relacionada a muitas atividades biológicas, como antibacteriana, antifúngica, antiulcerativa, antiviral, antiprotozoária, antiinflamatória, hepatoprotetora, antioxidante, antitumoral, entre outras. Estudos recentes mostraram que a própolis verde ativa macrófagos e estimula os linfócitos B a produzirem anticorpos. A própolis tem demonstrado potencial atividade leishmanicida, por diminuir o diâmetro das lesões, causar alterações morfológicas nas formas promastigotas ou ainda por melhorar a resposta imunológica frente às Leishmanias, ativando macrófagos.Portanto, o objetivo deste trabalho foi relatar as principais atividades leishmanicidas da própolis, por meio de pesquisa bibliográfica eletrônica no PubMed e Scielo durante o ano de 2009. .

Leishmaniasis is a public health problem causing morbidity and mortality in over 80 countries and features a parasitic disease with several manifestations. In the New World occur Visceral Leishmaniasis (VL) and American Cutaneous Leishmaniasis (ACL). The ACL is considered a disease polymorphic of skin and mucous membranes, grouped in different clinical forms: cutaneous leishmaniasis in the skin and mucosa and diffuse cutaneous, and the evolution of this disease is closely related to the mechanisms of escape of the protozoan Leishmania from the immune response, allowing the development of the disease and consequently the onset of clinical manifestations known. The World Health Organization recommends the pentavalent antimony as the first choice drugs. However, they usually give unsatisfactory results, requiring the development of new and affordable drugs for its treatment. It has been investigated that use of propolis it is related to exhibit several biological activities such as antibacterial, antifungal,anti-ulcer agents, antiviral, anti-protozoan, anti-inflammatory, hepatoprotective, antioxidant, antitumor, among others. Recent studies have shown that green propolis active macrophages and stimulates lymphocytes B to produce antibodies. It was also reported that propolis shows a potential antileishmanial activity by reducing the diameter of the lesions, avoiding complications of the lesions by bacteria or by improving the immune response against the Leishmania through macrophages activation. The aim of this work was related the main activities leishmanicida using propolis, by searched the electronic literature PubMed and Scielo during the year 2009..

Envolvimento das quimiocinas CCL2 e CCL5 na patogênese do câncer de mama / Involvement of CCL2 and CCLS chemokines in breast cancer pathogenesis

No Brasil, o câncer de mama é o que mais causa mortes entre as mulheres com um risco de 51 casos a cada 100 mil mulheres. A metástase, principal causa de morte pelo câncer de mama, e dirigida a urna variedade de órgaos vitais, como ossos, pulmões, cerebra e fígado. Ocorre quando células tumorais geneticamente instáveis adaptam-se ao microambiente do tecido que esta distante do tumor primário. A natureza heterogênea da metástase no câncer de mama dificulta não apenas a cura, mas também a estimativa dos fatores de risco. A disseminação das células tumorais é realizada através da circulação sanguínea sistêmica atingindo outros órgãos. Tern sido verificado que essas células utilizam-se da expressão dos receptores de quimiocinas, para encontrar órgaos alvo que produzem um particular conjunto de quimiocinas. Mais recentemente, foi estabelecido que as células do câncer aproveitam-se da sinalização através dos receptores para quimiocinas para a iniciação e progressão do tumor primário e da metástase. Embora grande número de moléculas tenha sido implicada na metástase do câncer de mama, o mecanismo exato que determina a direção da migração parece incerto. Tem sido demonstrado que CCL2 e CCL5 estão expressas em grande quantidade pelas células tumorais do câncer de mama e são a causa da malignidade e metástase neste órgão. A expressão dessas duas quimiocinas pelas células do tumor de mama acompanha eventos de transformação maligna, e está associada com o curso avançado e progressão da doença. Desse modo, vários estudos sugerem que a determinação e o prognóstico das quimiocinas CCL2 e CCL5 será de grande para uma melhor identificação do risco de progressão e determinação das implicações terapêuuticas em pacientes com câncer de mama.

In Brazil, breast cancer is the major cause death among women with a risk of 51 cases to 100 thousand women. The metastasis, the main cause of death by breast cancer, is directed to a variety of vital organs such as bones, lungs, brain and liver. Occurs when genetically unstable tumor cells adapt to the microenvironment of the tissue that is distant from the primary tumor. The heterogeneous nature of metastasis in breast cancer is difficult not only for the definition of cure for this disease, but also to estimate their risk factors. The spread of tumor cells is achieved through the systemic bloodstream to reach other organs. It has been verified that these cells are used the expression of chemokine receptors to find on target organs that produce a particular set of chemokines. It was established that the cancer cells use the signaling through the receptors for chemokines in the initiation and progression of primary tumor and metastasis. Although large number of molecules has been implicated in metastasis of breast cancer, the exact mechanism that determines the direction of migration seems uncertain. In a review conducted recently, the authors argue that CCL2 and CCL5 are expressed in large amounts by tumor cells of breast cancer and are the cause of malignancy and metastasis in this organ. The expression of these chemokines by the tumor cells of breast accompanying events of malignant transformation, and is associated with the advanced course and progression of disease. Thus several studies suggest that the determination and validation of the prognostic value of the chemokines CCL2 and CCL5 will be of great value for better identification of risk of progression and determine the therapeutic implications in patients with breast cancer.

The effects of nitric oxide on the immune response during giardiasis

Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.

Determinação da lactate desidrogenase (LDH) e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica / Determination of lactate dehydrogenase (LDH) and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia

Leucemia mieloide crônica (LMC) é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH), considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentração de LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A concentração de LDH no plasma foi maior nos pacientes com LMC. Todos pacientes com LMC neste estudo estavam em tratamento, mesmo assim quatro pacientes apresentavam o transcrito Bcr-Abl (b3a2) no sangue periférico. Dois dos quatro pacientes com o transcrito b3a2 apresentavam LDH elevado (486 U L-1 e 589 U L-1). Embora o estudo tenha sido realizado com um pequeno número de amostras, é possível sugerir alteração de terapia para os dois pacientes que apresentam o transcrito b3a2 na amostra de sangue periférico com concentração de LDH elevada.

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease

Participação de células T regulatórias (Tregs) na imunopatogênese da infecção pelo vírus da imunodeficiência humana 1 (HIV-1) / Regulatory T cells participation in the infection immunopathogenesis by the Human Immunodeficiency Vírus

A sobrevivência de pacientes infectados pelo vírus da imunodeficiência humana (HIV-1) é relacionada à prevenção e ao tratamento eficaz de infecções oportunistas. É conhecido que os principais parâmetros para avaliar a progressão da doença causada pelo HIV-1 são contagem de células T CD4+ e carga viral do HIV-1. Células T regulatórias têm sido foco de intensas investigações dentro do sistema imunológico como também na patogênese de diversas doenças. Sabe-se que as células T reguladoras (Tregs) CD4+CD25+FoxP3+ atuam na modulação da ativação imune, funcionando como mediadores críticos da homeostasia imune e da auto-tolerância. Além disso, recentes estudos têm demonstrado que as células Tregs não se limitam à prevenção de auto-imunidade, mas são importantes no controle todas as formas de respostas imunes no contexto de inflamação, infecção, alergia, transplantes e imunidade tumoral. Muitos autores têm identificado as Tregs como células efetoras benéficas no contexto da AIDS, porém há discordância. Tregs podem sustentar importante função na imunopatologia da infecção pelo HIV devido a atividade supressora sobre ativação celular e função efetora. Neste contexto, esta revisão aborda os aspectos moleculares e imunológicos das Tregs no sistema HIV.

The survival of patients infected with human immunodeficiency virus (HIV-1) is related to the prevention and effective treatment of opportunistic infections. It is known that the main parameters to evaluate the progression of disease caused by HIV-1 is the counting of CD4 + T cells and viral load of HIV-1. Regulatory T cells has been considered the focus of intense research within the immune system as well as in the pathogenesis of several diseases. Natural regulatory T cells (Tregs) CD4+CD25+ act in the modulation of immune activation, functioning as critical mediators of immune homeostasis and self-tolerance. Furthermore, recent studies has shown that the function of Tregs cells is not limited to the prevention of autoimmunity, but is also important to control all forms of immune responses in the context of inflammation, infection, allergy, transplantation and tumor immunity. Many authors have identified Tregs as beneficial effector cells in the context of AIDS, but other researchers disagree. Tregs can exert an important role in the immunopathology of HIV infection due to the suppressor activity on cellular activation and effector function. Thus, this review discusses the molecular and immunological aspects of Tregs in the HIV system.

Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica / Expression of genes related to the adrenocortical function in the neoplastic cachexia process

A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4) foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina), 3ßHSD I (3β-hidroxiesteroidedesidrogenas e tipo I) e TSPO (proteína translocadora) em animais com caquexia neoplásica(valores de P=0,037; 0,0097 e 0,052, respectivamente), revelando falência do córtex da adrenal.

The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexiaprocess, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In this assignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4) were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of geneexpression related to the steroidogenesis control by semi-quantitative RT-PCR. Dataanalysis showed a significant reduced expression of MC2R (melancortin type 2 receptor), 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I) and TSPO (translocator protein)genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively), revealing adrenal cortex failure.