Biological and Inflammatory Effects of Antigen 5 from Polybia paulista (Hymenoptera, Vespidae) Venom in Mouse Intraperitoneal Macrophages.

The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen 5 from P. paulista venom, expressed recombinantly (rPoly p 5), on BALB/c mice peritoneal macrophages, activated or not with LPS, was assessed. Here, we analyzed cell viability changes, expression of the phosphorylated form of p65 NF-κB subunit, nitric oxide (NO), proinflammatory cytokines production, and co-stimulatory molecules (CD80, CD86). The results suggest that rPoly p 5 does not affect NO production nor the expression of co-stimulatory molecules in mouse peritoneal macrophages. On the other hand, rPoly p 5 induced an increase in IL-1ß production in non-activated macrophages and a reduction in the production of TNF-α and MCP-1 cytokines in activated macrophages. rPoly p 5 decreased the in vitro production of the phosphorylated p65 NF-κB subunit in non-activated macrophages. These findings suggest an essential role of this allergen in the polarization of functional M2 macrophage phenotypes, when analyzed in previously activated macrophages. Further investigations, mainly in in vivo studies, should be conducted to elucidate Polybia paulista Ag5 biological role in the macrophage functional profile modulation.

Rhipicephalus sanguineus salivary gland extract as a source of immunomodulatory molecules.

Rhipicephalus sanguineus sensu lato (s.l.), popularly known as 'brown dog tick', is the primary vector of pathogens affecting dogs worldwide. To enter the host's organism, these pathogens utilise the anticoagulant, antiplatelet, anti-inflammatory and immunomodulatory actions of compounds present in the tick's saliva; such compounds are released by the ectoparasite in order to attach and feed on dogs. Nitric oxide (NO) is one of the regulatory factors in inflammation, apoptosis and immunomodulation. Here, we evaluated the in vitro activity of salivary gland extract of female dog ticks on the macrophage-derived J774 cell line, with and without lipopolysaccharide (LPS) stimulation. Cultures were evaluated for possible morphological alterations caused by exposure to the extract. There was no apparent in vitro cytotoxicity of the extract. Also, the NO secretory response in the non-LPS-stimulated cells was not inhibited. On the other hand, the extract presented modulatory action in the cultures of LPS-stimulated cells at a concentration of 0.1 µg/mL, possibly through macrophage activation, and induced a significant decrease in NO secretion. These results confirm the modulatory potential of bioactive molecules in the salivary glands of R. sanguineus ticks.

Qualidade de vida entre consumidores de substâncias psicoativas: avaliação do instrumento Medical Outcomes Study Short Form 36 / Life quality among consumers of psychoactive substances: evaluation of the Medical Outcomes Study Short Form 36 / Calidad de vida entre los consumidores de sustancias psicoactivas: evaluación de Medical Outcomes Study Short Form 36

OBJETIVO: o presente trabalho teve por objetivo descrever a utilização e os resultados obtidos com o instrumento Medical Outcomes Study Short Form -36 item (SF-36) para avaliação de qualidade de vida de pessoas em situação de uso, abuso ou dependência de substâncias psicoativas (SPA). MÉTODO: realizou-se um levantamento bibliográfico em artigos e revistas científicas, dissertações e monografias. RESULTADOS: os estudos mostram que o uso de substâncias psicoativas traz prejuízos para saúde e qualidade de vida das pessoas. CONCLUSÃO: observa-se que o instrumento SF-36 se mostra válido e confiável para a avaliação da qualidade de vida entre consumidores de SPA e possui em seus domínios algumas dimensões que são bastante sensíveis a avaliação de aspectos da qualidade de vida desta população.

OBJECTIVE: to describe the use and results obtained with the instrument Medical Outcomes Study Short Form -36 item (SF-36) to evaluate the quality of life of people in situations of use, abuse or dependence of psychoactive substances (SPA). METHOD: a bibliographic survey was carried out in articles and scientific journals, dissertations and monographs. RESULTS: studies show that the use of psychoactive substances affects health and quality of life. CONCLUSION: it can be observed that the SF-36 instrument is valid and reliable for the assessment of the quality of life among SPA users and has in its domains some dimensions that are very sensitive to the evaluation of quality of life aspects of this population.

OBJETIVO: Describir el uso y los resultados obtenidos con el instrumento Medical Outcomes Study Short Form -36 item (SF-36) para evaluar la calidad de vida de las personas en situaciones de uso, abuso o dependencia de sustancias psicoactivas. MÉTODO: Se realizó una encuesta bibliográfica en artículos y revistas científicas, disertaciones y monografías. RESULTADOS: Los estudios muestran que el uso de sustancias psicoactivas afecta la salud y la calidad de vida. CONCLUSIÓN: Se puede observar que el instrumento SF-36 es válido y fiable para la evaluación de la calidad de vida de los usuarios de SPA y tiene en sus dominios algunas dimensiones muy sensibles a la evaluación de los aspectos de calidad de vida de esta población.

Immunomodulatory and morphophysiological effects of Rhipicephalus sanguineus s. l. (Acari: Ixodidae) salivary gland extracts.

Rhipicephalus sanguineus s. l. is popularly known as the "brown dog tick" since dogs are its preferential hosts, but the species has been reported to parasitize other mammals, including humans, with significant medical-veterinary importance since it transmits several important pathogenic agents during the feeding period. The tick saliva is a complex mixture that has several functions, including the capability to modulate the hemostatic, inflammatory and immunologic systems of the host, allowing pathogens to settle. Despite knowledge about the immunosuppressive action of tick saliva, little is known about the mechanisms involved in this process and the morphophysiological effects caused by exposure to the salivary gland extract, taking into consideration the different periods of the glandular cycle. Thus, the objective of this study was to analyze the in vitro effects of salivary gland extracts obtained from R. sanguineus s. l. females fed on host rabbits for two (SGE2 - Salivary Gland Extracts of 2 days) and four days (SGE4 - Salivary Gland Extracts of 4 days) on J774 cells (monocyte macrophage cell line) and verify the occurrence of morphological and immunomodulatory alterations in these cells when exposed to different concentrations of these extracts. The results showed that: (i) SGE2 and SGE4 at the concentration of 4 µg/mL presented cytotoxicity to the J774 cells exposed for 24 and 48 hours; (ii) SGE2 at the concentrations of 2 µg/mL(48-hour exposure) and 1 µg/mL (24-hour exposure) and SGE4 at the concentrations of 2 and 1 µg/mL (48-hour exposure) showed proinflammatory activity, confirmed by the increased secretion of NO and proinflammatory cytokine (IL-2), and the presence of morphological characteristics detected by microscopy; and (iii) SGE2 and SGE4 at the concentrations of 0.5 and 0.1 µg/mL had immunomodulatory activity, demonstrated by decreases in the secretion of NO and proinflammatory cytokines (IL2, IL-6 and TNF-α) and increase in the synthesis of IL-10, confirmed by the morphophysiological analysis. These unprecedented data are extremely relevant for future research to identify the processes involved in the ectoparasite-host relationship, as well to develop more efficient tick control strategies.

Current Advances in Immunological Studies on the Vespidae Venom Antigen 5: Therapeutic and Prophylaxis to Hypersensitivity Responses.

Although systemic reactions caused by allergenic proteins present in venoms affect a small part of the world population, Hymenoptera stings are among the main causes of immediate hypersensitivity responses, with risk of anaphylactic shock. In the attempt to obtain therapeutic treatments and prophylaxis to hypersensitivity responses, interest in the molecular characterization of these allergens has grown in the scientific community due to the promising results obtained in immunological and clinical studies. The present review provides an update on the knowledge regarding the immune response and the therapeutic potential of Antigen 5 derived from Hymenoptera venom. The results confirm that the identification and topology of epitopes, associated with molecular regions that interact with antibodies, are crucial to the improvement of hypersensitivity diagnostic methods.

Classificação da intolerância à lactose: uma visão geral sobre causas e tratamentos / Classification of lactose intolerance: An overview of causes and treatments

A deficiência total ou parcial da enzima denominada lactase, responsável por hidrolisar em glicose e galactose a lactose presente no leite, é popularmente conhecida como intolerância à lactose. No presente trabalho foram revisadas as causas e tratamentos para intolerância à lactose. Foi realizada uma revisão retrospectiva e integrativa da literatura nas bases SciELO, MedLine e PubMed. A intolerância possui três classificações: primária, secundária e congênita. A intolerância ontogenética à lactose ou hipolactasia primária adulta é a forma mais comum. Já a deficiência secundária consiste em um quadro fisiopatológico que tem como consequência a má absorção de lactose. Por fim, a intolerância congênita à lactose é uma deficiência de herança genética, que acomete recém-nascidos nos primeiros dias de vida. Na hipolactasia, o agravamento surge na vida adulta, justamente com perda da função gradativa da enzima que degrada a lactose. Isso ocorre pelo fato de essa enzima, presente e ativa durante a amamentação em mamífero, perder sua função no início do desmame. Em pacientes não intolerantes, essa mesma enzima passa por um processo de mutação, permanecendo ativa ao longo da vida adulta. O tratamento mais comum para pacientes com intolerância à lactose envolve a retirada total ou parcial do leite e seus derivados, já que a supressão total causa alguns danos à nutrição e à manutenção do organismo.

The total or partial deficiency of lactase, responsible for hydrolyzing lactose into glucose and galactose, is popularly known as lactose intolerance. In this work we reviewed the causes and treatments for lactose intolerance. An integrative and retrospective literature review was carried out at the SciELO, MedLine and PubMed databases. Intolerance has three classifications: primary, secondary and congenital. The ontogenetic lactose intolerance or adult primary hypolactasia is the most common form. The secondary deficiency consists of a pathophysiological which results in the absorption of lactose. Congenital lactose intolerance is a genetic inheritance disability that affects infants in the first days of life. In the hypolactasia, aggravation arises in adulthood, just with gradual loss of function of the enzyme that breaks down lactose. This enzyme, present and active during breastfeeding in mammalian, starts losing its function at the weaning. In non intolerant patients this same enzyme passes through a changing process which remains active throughout adult life. The most common treatment for patients with lactose intolerance involves partial or total removal of the milk and its products since the total withdrawal causes some damage to nutrition and maintenance of body.

The modulation of enzyme indoleamine 2,3-dioxygenase from dendritic cells for the treatment of type 1 diabetes mellitus.

Diabetes mellitus type 1 (DM1) is an autoimmune disease in which ß-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism. Current studies on immunotherapies describe the use of DC and IDO to control the progression of the immune response that triggers DM1. The initial results obtained are promising and indicate the possibility of developing therapies for the treatment or prevention of the DM1. Clinical trials using these cells in DM1 patients represent an interesting alternative treatment. However, clinical trials are still in the initial phase and a robust group of assays is necessary.

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies.

Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D. These monoclonal antibodies, alone or in association with radiotherapy or chemotherapy, are presenting good results and are increasing patient survival, despite the side effects. Due to the limited number of molecules available, several studies are trying to develop new monoclonal antibodies for the treatment of colorectal tumors. Among those being studied, some recent molecules are in phase I and/or II trials and are yielding advantageous results, such as anti-DR5, anti-Fn14, anti-IGF-1R, anti-EGFR, anti-NRP1, and anti-A33 antibodies. This has been successful in reducing side effects and in treating nonresponsive patients.

Principais patógenos envolvidos em casos de sepse em pacientes queimados: uma revisão de literatura / Main pathogens involved in the cases of sepsis in burned patients: a review on the literature / Principales patógenos en los casos de sepsis em pacientes quemados: una revisión de literatura

Objetivo: Buscou-se no presente trabalho identificar os principais patógenos envolvidos em infecções em pacientes queimados, bem como enfatizar a relevância do diagnóstico adequado para o tratamento de sepse. Método: Para a realização do presente trabalho, foi feito levantamento bibliográfico de caráter exploratório e obtidos 33 estudos relevantes. A coleta de informações ocorreu nos meses de março a novembro de 2016. Resultados: Dentre os principais patógenos presentes em queimados, que podem gerar quadro de sepse, estão Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter sp, Candida albicans e Proteus sp. Esses podem, ou não, estar relacionados à própria microbiota do paciente. O processo de infecção, com perda da primeira linha de defesa imunológica, deixa o organismo suscetível à entrada e instalação de microrganismos. O tratamento da sepse depende de fatores relevantes, que incluem a gravidade da lesão e o agente causador da infecção. Conclusão: O risco de ocorrência de sepse, associada às infecções em queimados nas unidades de tratamento intensivo, pode ser reduzido com o diagnóstico adequado e acompanhamento do paciente.

Objective: This article aimed to identify the main pathogens involved in infections in burned patients, as well as to emphasize the relevance of the appropriate diagnosis for the treatment of sepsis. Methods: For the accomplishment of the present work, it was carried out a bibliographic survey of exploratory character and 33 relevant studies were obtained. Data collection was carried out from March to November 2016. Results: Among the main pathogens present in burnt patient related with sepsis are Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter sp, Candida albicans and Proteus sp. These pathogens may or may not be related to the patients microbiota. The infection process, with loss of the first line of immune defense, leaves the organism susceptible to the entry and installation of microorganisms. Treatment of sepsis depends on relevant factors including the severity of the lesion and the agent of the infection. Conclusion: The risk associated with sepsis in burned patients may be reduced with appropriate diagnosis and monitoring.

Objetivo: El objetivo de este artículo fue identificar los principales patógenos asociados en infecciones en pacientes com quemaduras, así como enfatizar la relevancia del diagnóstico adecuado para el tratamiento de la sepsis. Métodos: Para el desarrollo del presente trabajo, se realizó una búsqueda bibliográfica de caracter exploratório, siendo considerados relevantes 33 estudios. La búsqueda de datos se realizó de marzo a noviembre de 2016. Resultados: Entre los principales patógenos presentes en pacientes quemados relacionados con la sepsis se destacaron Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter sp, Candida albicans y Proteus sp. Estos patógenos pueden o no estar relacionados con la microbiota del paciente. El proceso de infección, con la pérdida de la primera línea de defensa inmunológica, deja el organismo susceptible a la entrada e instalación de microorganismos. El tratamiento de la sepsis depende de factores relevantes, incluyendo la gravedad de la lesión y el agente de la infección. Conclusión: El riesgo asociado con la sepsis en pacientes quemados puede reducirse con un diagnóstico y seguimiento adecuados.

Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage.

Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulated ex vivo in order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile.

Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type.

BACKGROUND: Numerous plants from have been investigated due to their anti-inflammatory activity and, among then, extracts or components of ginger (Zingiber officinale Roscoe) and rosemary (Rosmarinus officinalis L.), sources of polyphenolic compounds. 6-gingerol from ginger rhizome and carnosic acid and carnosol from rosemary leaves present anti-tumor, anti-inflammatory and antioxidant activities. However, the evaluation of the mechanisms of action of these and other plant extracts is limited due to their high hydrophobicity. Dimethylsulfoxide (DMSO) is commonly used as a vehicle of liposoluble materials to mammalian cells in vitro, presenting enhanced cell penetration. Liposomes are also able to efficiently deliver agents to mammalian cells, being capable to incorporate in their structure not only hydrophobic molecules, but also hydrophilic and amphiphilic compounds. Another strategy is based on the use of Pluronic F-68, a biocompatible low-foaming, non-ionic surfactant, to disperse hydrophobic components. Here, these three delivery approaches were compared to analyze their influence on the in vitro anti-inflammatory effects of ginger and rosemary extracts, at different concentrations, on primary mammalian cells and on a tumor cell line. METHODS: Ginger and rosemary extracts free of organic solvents were obtained by supercritical fluid extraction and dispersed in DMSO, Pluronic F-68 or liposomes, in variable concentrations. Cell viability, production of inflammatory mediators and nitric oxide (NO) release were measured in vitro on J774 cell line and murine macrophages primary culture stimulated with bacterial lipopolysaccharide and interferon-γ after being exposed or not to these extracts. RESULTS: Ginger and rosemary extracts obtained by supercritical CO2 extraction inhibited the production of pro-inflammatory cytokines and the release of NO by peritoneal macrophages and J774 cells. The delivery vehicles influenced the anti-inflammatory effects. Comparatively, the ginger extract showed the highest anti-inflammatory activity on the tumor cell line. Controversially, rosemary extract dispersed on DMSO induced a more significant IL-1 and TNF-α reduction than ginger extract in primary macrophages. CONCLUSIONS: Amongst the tested delivery vehicles, DMSO was the most suitable, presenting reduced cytotoxicity, followed by Pluronic F-68 and liposomes, provably due to differences in their form of absorption, distribution and cellular metabolism. Co-administration of liposomes and plant extracts may cause death of macrophages cells and induction of NO production. It can be concluded that some of the beneficial effects attributed to extracts of ginger and rosemary may be associated with the inhibition of inflammatory mediators due to their high antioxidant activity. However, these effects were influenced by the type of delivery vehicle.

Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments.

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn's disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

Phenotypical and functional analysis of intraepithelial lymphocytes from small intestine of mice in oral tolerance.

In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8(+) and CD4(+) T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103(+) cells in CD4(+) T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8ß(+) T-cell subset in IELs of TGN. The frequency of Foxp3(+) cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25(+) subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-ß, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

Oral tolerance and OVA-induced tolerogenic dendritic cells reduce the severity of collagen/ovalbumin-induced arthritis in mice.

Dietary proteins play an important role in the regulation of systemic immune response, in a phenomenon known as oral tolerance (OT). To evaluate the effects of OT on a murine model of type II collagen (CII) plus ovalbumin (OVA)-induced arthritis (CIA), mice were fed with OVA either before or after CIA induction. OT significantly reduced the paw edema and synovial inflammation, as well as serum levels of anti-CII, the ex vivo proliferation and inflammatory cytokine production by spleen cells from CIA mice. The frequencies of Foxp3(+) and IL-10(+) cells were higher, whereas IFNγ(+) cells and IL-17(+) cells were lower, among gated CD4(+) spleen T cells from tolerized CIA mice than in those from non-tolerized CIA mice. Adoptive transfer of tolerogenic dendritic cells (DCs) before CIA induction mimics the effects observed in the OT. We demonstrate here that bystander suppression induced by OT can modify the course of CIA and tolerogenic DCs play a role this phenomenon.