Controversias en el uso de la vitamina D como preventivo de la esclerosis múltiple. Revisión de la literatura / Controversies in the use of vitamin D as a preventive of multiple sclerosis. Literature review

La esclerosis múltiple (EM) es una enfermedad desmielinizante que afecta el sistema nervioso central. A pesar de los avances en materia de diagnóstico y tratamiento, se desconocen aún muchos aspectos de su etiopatogenia y fisiopatología. La EM es una de las principales causas de discapacidad neurológica y, por los elevados costos de los tratamientos inmunomoduladores e inmunosupresores, tiene un gran impacto económico en la salud pública. Por ello, se intentaron diversos tratamientos preventivos, como la utilización de la vitamina D. Debido a la acción de la vitamina D sobre el sistema inmune, ha sido prescripta en sujetos de riesgo. Sin embargo, hasta el momento actual, los estudios sobre sus efectos no resultaron concluyentes y persisten las dudas acerca de sus posibles beneficios en materia de prevención. El objetivo de la presente revisión bibliográfica es realizar una puesta al día y destacar los aspectos controversiales en relación al uso de la vitamina D como tratamiento preventivo de la esclerosis múltiple. (AU)

Multiple sclerosis (MS) is a demyelinating disease that affects the central nervous system. Despite advances in diagnosis and treatment, many aspects of its etiopathogenesis and pathophysiology remain unknown. MS is one of the main causes of neurological disability and, due to the high costs of modern immunomodulatory and immunosuppressive treatments, it has a great economic impact on public health. Therefore, numerous efforts have been made in the search for preventive treatments. For this reason, various preventive treatments were tried, such as the use of vitamin D. Due to its action on the immune system, it has been used in subjects at ME risk. However, these studies have been inconclusive to date, and its possible benefits in terms of prevention are still being questioned. The objective of this bibliographic review is to update and highlight the controversial aspects in relation to the use of vitamin D as a preventive treatment of multiple sclerosis. (AU)

Down-regulation of complement genes in lipopolysaccharidechallenged zebrafish (Danio rerio) larvae exposed to Indonesian propolis / Regulação negativa dos genes do complemento em larvas de peixe-zebra (Danio rerio) desafiadas com lipopolissacarídeo expostas à própolis indonésia

Although propolis has been reported for having anti-inflammatory activities, its effects on complement system has not been much studied. This research was conducted to find out the effects of Indonesian propolis on the expression levels of C3, C1r/s, Bf, MBL, and C6 in zebrafish larvae which were induced by lipopolysaccharide (LPS). Counting of macrophages migrating to yolk sac and liver histology were carried out. Larvae were divided into four groups: CON (cultured in E3 medium only), LPS (cultured in a medium containing 0.5 μg/L LPS), LPSIBU (cultured in a medium containing LPS, and then treated with 100 μg/L ibuprofen for 24 hours), and LPSPRO (cultured in a medium containing LPS, and then immersed in 14,000 μg/L propolis for 24 hours) groups. The results showed that complement gene expression in larvae from the LPSIBU and LPSPRO groups were generally lower than in larvae from the LPS group. The number of macrophage migrations to the yolk in the LPSPRO group was also lower than in the LPS group. Histological structure of liver in all groups were considered normal. This study shows that Indonesian propolis has the potential to be used as an alternative to the substitution of NSAIDs.

Embora a própolis tenha sido relatada por ter atividade anti-inflamatória, seus efeitos no sistema complemento, uma parte do sistema imunológico inato, não foram muito estudados. Esta pesquisa foi conduzida para descobrir os efeitos da própolis da Indonésia nos níveis de expressão de C3, C1r/s, Bf, MBL e C6 em larvas de peixe-zebra induzidas por lipopolissacarídeo (LPS). Foram realizadas contagens de macrófagos que migram para o saco vitelino e histologia do fígado. As larvas foram divididas em quatro grupos: CON (cultivadas apenas em meio E3), LPS (cultivadas em meio contendo 0,5 μg/L de LPS), LPSIBU (cultivadas em meio contendo LPS e, em seguida, tratadas com 100 μg/L de ibuprofeno por 24 horas) e LPSPRO (cultivado em meio contendo LPS, e então imerso em própolis 14,000 μg/L por 24 horas). Os resultados mostraram que a expressão do gene do complemento em larvas dos grupos LPSIBU e LPSPRO foi geralmente menor que em larvas do grupo LPS. O número de migrações de macrófagos para a gema no grupo LPSPRO também foi menor que no grupo LPS. A estrutura histológica do fígado em todos os grupos foi considerada normal. Este estudo mostra que a própolis indonésia tem potencial para ser utilizada como alternativa na substituição dos AINEs (anti-inflamatórios não esteroides).

Evidence-based anti-viral and immunomodulatory potential of Black cumin (Nigella sativa L) in COVID-19 / Potencial antivírico e inmunomodulador en COVID-19 del comino negro (Nigella sativa L) basado en la evidencia

Currently, the whole world is facing a life-threatening novel coronavirus 2019 (COVID-19) pandemic. Natural products are well-known for their potential role against viral disease, and some anti-viral agents have been developed to combat these diseases. Herein, the authors investigated the possible effects of this Holy plant Nigella sativa L. (NS), against coronavirus, using evidence-based and mechanistic approaches to conclude the immune-boosting and alleviation of respiratory systemeffects of NS. The pharmacological studies established a prominent role in treating various respiratory, immune systems, cardiovascular, skin, and gastrointestinal disorders. Literature supported the significant anti-viral role and showed an inhibitory role for NS against MHV-A59 CoV (mouse-hepatitis virus­A59) infected Hela, i.e., HeLaCEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cell. NS is a safe herbal product or dietary supplement and could be an effective and affordable community adjuvant treatment for coronavirus in the current scenario.

Actualmente, el mundo entero se enfrenta a una pandemia del nuevo coronavirus 2019 (COVID-19) que amenaza la vida. Los productos naturales son bien conocidos por su papel potencial contra las enfermedades virales, y se han desarrollado algunos agentes antivirales para combatir estas enfermedades. En este documento, los autores investigaron los posibles efectos de esta planta sagrada Nigella sativa L. (NS), contra el coronavirus, utilizando enfoques mecanicistas y basados en la evidencia para concluir el refuerzo inmunológico y el alivio de los efectos del SN en el sistema respiratorio. Los estudios farmacológicos establecieron un papel destacado en el tratamiento de diversos trastornos respiratorios, del sistema inmunológico, cardiovasculares, cutáneos y gastrointestinales. La literatura apoyó el importante papel antivírico y mostró un papel inhibidor de NS contra células Hela infectadas con MHV-A59 CoV (virus de la hepatitis de ratón-A59), es decir, HeLaCEACAM1a (molécula de adhesión celular 1a relacionada con el antígeno carcinoembrionario epitelial de HeLa). NS es un producto a base de hierbas o un suplemento dietético seguro y podría ser un tratamiento adyuvante comunitario eficaz y asequible para el coronavirus en el escenario actual.

Effects of dexamethasone on the morphometry and biometry of immune organs of broiler chicken / Efectos de la dexametasona en la morfometría y biometría de los Órganos Inmunes del pollo de engorde

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.

El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.

Opioids in the immune system: from experimental studies to clinical practice

SUMMARY INTRODUCTION: Opioids interact with both innate and adaptive immune systems and have direct effects on opioid receptors located on immune cells. Research on this topic has provided evidence of the opioid influence on the immune response associated with surgical stress. The immunological effects of opioids are currently being investigated, particularly whether they influence the outcome of surgery or the underlying disease regarding important aspects like infection or cancer progression. This review addresses background research related to the influence of the opioid receptor on the immune system, the immunosuppressive effect associated with major opioids during the perioperative period, and their clinical relevance. The objective of the study was to review the effects of opioids on the immune system. Methods: A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "surgical procedures," "analgesics," "opioids" and "perioperative care." Results: The immunosuppressive effect of opioids was identified over 30 years ago. They include signaling and acting directly through immune cells, including B and T lymphocytes, NK cells, monocytes, and macrophages, as well as activating the downstream pathways of the hypothalamic-pituitary-adrenal (HPA) axis leading to the production of immunosuppressive glucocorticoids in the peripheral and sympathetic nervous system.

RESUMO INTRODUÇÃO: Os opioides interagem com ambos os sistemas imunes, inato e adaptativo, através de efeitos diretos sobre os receptores dos opioides localizados nas células imunes. As pesquisas neste assunto têm fornecido evidência da influência dos opioides sobre a resposta imune associada ao estresse cirúrgico. Os efeitos imunológicos dos opioides estão sendo pesquisados na atualidade, principalmente se eles determinam o resultado da cirurgia ou doença consequente devido a fatos importantes como infecção ou progressão do câncer. Essa revisão tem como alvo ver antecedentes em pesquisa relativa à influência dos receptores dos opioides no sistema imunológico, o efeito imunossupressor associado com opioides maiores durante o período peri-operatório e sua importância clínica. O objectivo da pesquisa foi revisar os efeitos dos opioides no sistema imunológico. MÉTODOS: Uma estrategia de procura foi dirigida na mídia PubMed, e no cadastro de Embase e The Cochrane, usando os termos "imunosuppressão", "sistema imunológico", "procedimentos cirúrgicos", "analgésicos", "opioides" e "cuidado peri-operatório". RESULTADOS: O efeito imunosuppressor dos opioides foi identificado há mais de 30 anos. Os efeitos imunosupressores incluem sinalização e ação diretamente através das células imunes, mesmo com os linfócitos B e T, células NK, monócitos e macrófagos, também como ativando as vias de corrente do eixo hipotálamo- hipófise- adrenal (HPA) levando à produção de glucocorticoides imunossupresores no sistema nervoso periférico e simpático.

Effects of astragaloside IV on inflammation and immunity in rats with experimental periodontitis

Abstract: This study aimed to investigate the effects of astragaloside IV (AsIV) on inflammation and immunity in rats with experimental periodontitis. Periodontitis was established in 48 Wistar rats, which were then randomly divided into model and 10, 20 and 40 mg/kg AsIV groups, with 12 rats in each group. The latter 3 groups were treated with AsIV at doses of 10, 20 and 40 mg/kg, respectively. The control group (12 rats, without periodontitis) and model group were given the same amount of 5% sodium carboxymethyl cellulose. The treatment was performed once per day for 8 weeks. Before and after treatment, the tooth mobility scores of the rats were determined. After treatment, the salivary occult blood index (SOBI), plaque index (PLI), peripheral blood T lymphocyte subsets, and serum inflammatory factor and immunoglobulin levels were determined. The results showed that, after treatment, compared with that in model group, in 40 mg/kg AsIV group, the general state of rats was improved, while the tooth mobility score, SOBI and PLI were significantly decreased (p < 0.05); the peripheral blood CD4+ T cell percentage and CD4+/CD8+ ratio were significantly increased (p < 0.05), while the CD8+ T cell percentage was significantly decreased (p < 0.05); the serum tumor necrosis factor-α, interleukin-1β and interleukin-2 levels were significantly decreased (p < 0.05); the serum immunoglobulin A and immunoglobulin G levels were significantly decreased (p < 0.05). In conclusion, AsIV can alleviate inflammation and enhance immunity in rats with experimental periodontitis.

Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults

OBJECTIVES This study aims to compare the differential gene expression resulting from tocotrienol-rich fraction and α-tocopherol supplementation in healthy older adults. METHODS A total of 71 eligible subjects aged 50 to 55 years from Gombak and Kuala Lumpur, Malaysia, were divided into three groups and supplemented with placebo (n=23), α-tocopherol (n=24) or tocotrienol-rich fraction (n=24). Blood samples were collected at baseline and at 3 and 6 months of supplementation for microarray analysis. RESULTS The number of genes altered by α-tocopherol was higher after 6 months (1,410) than after 3 months (273) of supplementation. α-Tocopherol altered the expression of more genes in males (952) than in females (731). Similarly, tocotrienol-rich fraction modulated the expression of more genes after 6 months (1,084) than after 3 months (596) and affected more genes in males (899) than in females (781). α-Tocopherol supplementation modulated pathways involving the response to stress and stimuli, the immune response, the response to hypoxia and bacteria, the metabolism of toxins and xenobiotics, mitosis, and synaptic transmission as well as activated the mitogen-activated protein kinase and complement pathways after 6 months. However, tocotrienol-rich fraction supplementation affected pathways such as the signal transduction, apoptosis, nuclear factor kappa B kinase, cascade extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2, immune response, response to drug, cell adhesion, multicellular organismal development and G protein signaling pathways. CONCLUSION Supplementation with either α-tocopherol or tocotrienol-rich fraction affected the immune and drug response and the cell adhesion and signal transduction pathways but modulated other pathways differently after 6 months of supplementation, with sex-specific responses.

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

ABSTRACT Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. Objective: To identify predictive genetic markers of immune response to ART. Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. Results: Male patients were overrepresented in non-responder group (p = 0.01). Non-responders also started with lower absolute CD4+ T cell counts (p < 0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p = 0.04), rs1128503 (ABCB1) A allele (p = 0.03) and rs707265 (CYP2B6) A allele (p = 0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p = 0.004) and rs4646437 (CYP3A4) A allele (p = 0.04). Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response.

Evaluación infectológica inicial y seguimiento prospectivo de una cohorte de pacientes sometidos a inmunosupresión inducida / Initial assessment and prospective follow-up of a cohort of patients with immunosuppressive therapy by an infectious diseases physician

El uso de inmunosupresores generó una población creciente de pacientes con defectos en el sistema inmune. Creamos un consultorio especializado en la atención infectológica de dichos pacientes. Objetivos: Describir los antecedentes clínicos y la prevalencia de infecciones latentes, evaluar el estado de vacunación, determinar la necesidad de profilaxis antimicrobiana. Describir la frecuencia de aparición infecciones oportunistas (IO). Materiales y métodos: estudio descriptivo, prospectivo de pacientes atendidos en un consultorio que estuvieran bajo tratamiento inmunosupresor (noviembre 2015-enero 2017). Se recolectaron datos demográficos, clínicos y factores de riesgo para IO. Se realizó pesquisa de tuberculosis (TB), serologías para HIV, hepatitis A, B y C, sífilis, toxoplasmosis, Chagas, búsqueda de Strongyloides spp. Se indicaron vacunas de acuerdo con las recomendaciones actuales. Se realizó seguimiento para detección de IO. Resultados: n=197, media de edad 50,7 años (DE 14), mujeres 79,7%. Enfermedades de base: artritis reumatoidea 52%, lupus 12%. Drogas inmunosupresoras: metotrexato 45%, corticoides 16%, biológicos anti-TNF 15%, micofenolato 10%, ciclofosfamida 4%. Se diagnosticaron 49 (25%) infecciones: 15 Chagas, 15 anti-HBc positivo aislado, 7 sífilis, 4 HIV, 4 TB latentes, 2 HBV, 1 HCV, 1 estrongiloidiosis. Se indicó profilaxis antimicrobiana en 27 (14%) pacientes. En todos se intervino indicando o completando los esquemas de vacunación. Se detectaron 7 IO. Conclusiones: En el 39% de los pacientes, la evaluación sistematizada arrojó hallazgos que motivaron intervenciones, ya sea terapéuticas o de monitoreo. En el 100% fue necesaria la prescripción de vacunas. Esto pone en evidencia la importancia de evaluar sistemáticamente en consultorios especializados a estos pacientes

Introduction: The extensive use of immunosuppressive drugs resulted in a growing population of patients with defects in the immune system. We opened an infectious diseases practice focused on the attention of these patients. Our objectives were to describe the clinical history and prevalence of latent infections, evaluate the vaccination status, determine the need for antimicrobial prophylaxis and describe the frequency of opportunistic infections (OI). Methods: We performed a descriptive and prospective study of patients seen at a medical practice who were under immunosuppressive therapy (November 2015-January 2017). Demographic and clinical history, as well as risk factors for OI were collected. Tuberculosis (TB) screening, serologies for HIV, hepatitis A, B and C, syphilis, toxoplasmosis, Chagas and Strongyloides spp. screening were performed. Vaccines were indicated according to current recommendations. Follow-up was performed for IO detection. Results: n=197. Mean age: 50.7 years (SD 14). Female 79.7%. Underlying diseases: rheumatoid arthritis 52%, 12% lupus. Immunosuppressive drugs: methotrexate 45%, corticoids 16%, biological anti-TNF agents 15%, mycophenolate 10%, cyclophosphamide 4%. Forty-nine (25%) infections were diagnosed: 15 Chagas, 15 anti-HBc positive isolated, 7 syphilis, 4 HIV, 4 latent TB, 2 HBV, 1 HCV, 1 strongyloidiosis. Antimicrobial prophylaxis was indicated in 27 (14%) patients. In all cases, vaccination schemes were indicated or completed. Seven IO were detected. Conclusions: In 39% of the patients, the systematized evaluation revealed findings that motivated interventions, either therapeutic or monitoring. In 100% the prescription of vaccines was necessary. These findings highlight the importance of a systematically evaluation of these patients in specialized care centers.

Protective effect of ß-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C) / Efeito protetor do ß-glucano e glutamina em lesões intestinais e imunológicas induzidas por ciratabina (Ara-C) em camundongos

Recently, glutamine and ß-glucan have been demonstrated to play an important role in modulation of the immune system and in promoting intestinal health benefits. The aim of this study was to investigate the effect of this intervention on inflammatory responses and intestinal health in mice orally pretreated with soluble Saccharomyces cerevisiae derived 1,3/1,6-ß-glucan (80mg/kg) with or without glutamine (150mg/kg) and then challenged with cytarabine (Ara-C) (15mg/kg). Improvements in villi and crypts were not observed in the ß-glucan group. The intestinal morphometry in the glutamine group showed the best results. ß-glucan in combination with glutamine presented the highest values of IL-1ß and IL-10 and lowest values for leukocytes and INF-γ. Based on these results, combined ß-glucan and glutamine pretreatment reduced intestinal inflammation and improved the immune response after Ara-C challenge.(AU)

Recentemente, glutamina e ß-glucano têm demonstrado desempenhar um papel importante na modulação do sistema imune e na promoção de benefícios para a saúde intestinal. O objetivo deste estudo foi investigar o efeito dessa intervenção sobre as respostas inflamatórias e saúde intestinal de camundongos pré- tratados por via oral com 1,3/1,6-ß-glucano (80mg/kg) derivado de Saccharomyces cerevisiae com ou sem glutamina (150mg/kg) e posteriormente desafiados com citarabina (Ara-C) (15mg/kg). Melhoras em vilosidades e criptas não foram observadas no grupo de tratamento com ß-glucano. A morfometria intestinal no grupo de tratamento com glutamina apresentou os melhores resultados. O grupo em que foi utilizado ß-glucano em combinação com glutamina apresentou os maiores valores de IL-1ß e IL -10 e valores mais baixos para os leucócitos e INF-γ. Com base nestes resultados, o pré-tratamento de ß-glucano combinado com glutamina reduziu a inflamação intestinal e melhorou a resposta imune após o desafio com Ara-C.(AU)

Effects of herbal medicine Sijunzi decoction on rabbits after relieving intestinal obstruction

Intestinal obstruction leads to blockage of the movement of intestinal contents. After relieving the obstruction, patients might still suffer with compromised immune function and nutritional deficiency. This study aimed to evaluate the effects of Sijunzi decoction on restoring the immune function and nutritional status after relieving the obstruction. Experimental rabbits (2.5±0.2 kg) were randomly divided into normal control group, 2-day intestinal obstruction group, 2-day natural recovery group, 4-day natural recovery group, 2-day treated group, and 4-day treated group. Sijunzi decoction was given twice a day to the treated groups. The concentration of markers was analyzed to evaluate the immune function and nutritional status. The concentration of interleukin-2, immunoglobulins and complement components of the treated groups were significantly higher than the natural recovery group (P<0.05). The levels of CD4+ and CD4+/CD8+ increased then decreased in the treated groups. The levels of tumor necrosis factor-α and CD8+ were significantly lower than the natural recovery group. The level of total protein in the treated groups also increased then decreased after relieving the obstruction. The levels of albumin, prealbumin and insulin-like growth factor-1 were significantly higher in the treated groups than in the natural recovery group (P<0.05). Transferrin level in the treated groups was significantly higher than the obstruction group (P<0.05). Sijunzi decoction can lessen the inflammatory response and improve the nutrition absorption after relieving the obstruction.

Effects of levamisole on immune responses and resistance against density stress in rainbow trout fingerling [Oncorhynchus my kiss]

Background: It is necessary to potentiate the immune system of fishes against stresses in farms

Objectives: This study was carried out to address the potential effect of Levamisole on immune system of rainbow trout against density stress

Methods: 1500 fish [average weight of 50 g] were divided into 5 test groups, in which each test group was repeated three times with average density of 33 kg/m[3]. They were fed with commercial diet supplemented with Levamisole at concentrations of 0 [control], 100, 250, 500 and 1000 mg / kg for a period of 45 days. The fishes of all groups were then fed with Levamisole free diet and exposed to 2 and 3-fold density stress for the following 15 days. Blood samples were collected on days 0, 15, 30, 45 and 60 to evaluate the serum compliment and lysozyme activity as well as total immunoglobulins

Results: The results showed that all used concentrations of Levamisole just had significant effect on compliment activity after 45 days feeding period [p<0.05]. Higher levels of lysozyme and complement activity as well as total immunoglobulin were observed in 1000 mg/kg Levamisole treated group when exposed to density stresses 2 and 3-fold at the end of trial [day 60] [p<0.05]. The highest overall survival was found in group which was treated with 1000 mg/kg of Levamisole

Conclusions: Our results revealed that using 0/1% Levamisole as an im-munostimulator in commercial diet could potentiate rainbow trout against outbreak of high density stresses and increase its overall survival

Opioides e o sistema imunológico: relevância clínica / Opioids and the immune system: clinical relevance / Los opioides y el sistema inmunológico: relevancia clínica

JUSTIFICATIVA E OBJETIVO: O crescente uso de opioides para o tratamento da dor é uma realidade em vários países. Com o aumento do uso aparecem questionamentos menos usuais, como a influência dos opioides nas respostas imunológicas. O presente estudo tem como objetivo detalhar a resposta imunológica explorando as influências dos efeitos dos opioides sobre a resposta inflamatória em situações experimentais e clínicas, bem como sua importância para a prática diária. CONTEÚDO: Após revisão de artigos publicados em revistas indexadas no Medline, foi descrita a resposta imunológica de forma geral, especialmente em seu aspecto celular. Após essa abordagem, foram identificados os mecanismos de liberação dos opioides endógenos e a modulação da resposta imune aos opioides exógenos na dor aguda e crônica, sempre finalizando com as implicações clínicas e sua aplicabilidade na rotina de atendimento. CONCLUSÕES: Embora vários estudos apontem para um efeito imunodepressor dos opioides, a relevância clínica dessas observações continua incerta e serve apenas como um prerrequisito para que novas investigações nessa área sejam conduzidas. Recomendações definitivas para a aplicação de opioides, nas mais variadas situações da prática clínica em relação às consequências imunológicas desses fármacos, ainda não podem ser dadas até o momento presente.

BACKGROUND AND OBJECTIVES: The increasing use of opioids for pain treatment is a reality in several countries and, therefore, unusual questions arise, such as the influence of opioids on immune responses. The present study aims to detail the immune response by exploring the influences of opiate effects on inflammatory response in experimental and clinical situations, as well as its importance in daily practice. CONTENT: After reviewing the articles published in journals indexed in Medline, we found that immune response has been generally described, especially regarding its cellular aspect. Following this approach, we identified the mechanisms of endogenous opioid release, modulation of immune response to exogenous opioids in acute and chronic pain, always ending with the clinical implications and applicability in routine care. CONCLUSIONS: Although several studies point to an immunosuppressive effect of opioids, the clinical relevance of these observations remains uncertain and only serves as a prerequisite for further investigations in this area. Definitive recommendations for the use of opioids in various situations of clinical practice regarding the immunological consequences of these drugs still cannot be provided until the present moment.

JUSTIFICATIVA Y OBJETIVOS: El creciente uso de opioides para el tratamiento del dolor es una realidad en varios países. Con el incremento de su uso van surgiendo cuestionamientos menos comunes, como la influencia de los opioides en las respuestas inmunológicas. El presente estudio tiene el objetivo de detallar la respuesta inmunológica explorando las influencias de los efectos de los opioides sobre la respuesta inflamatoria en situaciones experimentales y clínicas, como también su importancia para la práctica diaria. CONTENIDO: Después de la revisión de los artículos publicados en revistas indexadas en el Medline, se describió la respuesta inmunológica de forma general, especialmente en su aspecto celular. Después de ese abordaje, se identificaron los mecanismos de liberación de los opioides endógenos y la modulación de la respuesta inmune a los opioides exógenos en el dolor agudo y crónico, siempre finalizando con las implicaciones clínicas y con su aplicabilidad en la rutina de atención. CONCLUSIONES: Aunque varios estudios nos indiquen un efecto inmunodepresor de los opioides, la relevancia clínica de esas observaciones continúa sin conocerse por completo y solo sirve como un prerrequisito para que nuevas investigaciones en esa área puedan llegar a buen puerto. Las recomendaciones definitivas para la aplicación de los opioides en las más variadas situaciones de la práctica clínica con relación a las consecuencias inmunológicas de esos fármacos, todavía no han salido a la luz.

[Effect of different levels of oil-extracted propolis on immune system of broiler chicks against newcastle virus]

Biosecurity in the production of broiler chickens is very important but it is hard or even impossible to maintain; hence, promotion of immune responses could control diseases in chickens. At present study, the effect of six levels of oil-extracted propolis [0, 50, 100, 150, 200 and 250 mg/kg ration] on immune system against Newcastle virus was studied using a completely randomized design with 360 chickens. Blood antibody ratio against the Newcastle virus [HI test], the weight of thymus, bursa fabricius and the percentage of lymphocytes were measured for a period of 42 days and the data were analyzed. The results indicated that the rate of antibody has significantly [p<0.05] increased with an increase in the amount of propolis in diets and with the levels of 250 mg/kg ration the antibody rose to 10.42 titre at the age of 42 compare to control [6.42]. The weight of thymus gland also increased significantly [p<0.05] with the increase in the levels of propolis and at the levels of 250 mg/kg in ration, weight of thymus increased up to 14.54g in compared to control [8.47 g]. Similarly the weight of bursa fabricius significantly increased [p<0.05] from 2.42 g in contral to 4.62 g in 250 mg propolis/kg of ration [p<0.05]. Intake of 200 and 250 mg propolis/kg of ration has significantly increased the lymphocytes to the levels of 50.18 and 51.25 percent compared to the control [48.93%], respectively. Results indicate that the efficiency of immune-system for immunizing of broiler chickens against Newcastle virus has been promoted using 50 up to 250 mg of propolis per kg of ration

[Effect of single, double and multi-stain probiotics on performance, morphology of small intestine and immunological and hematological parameters of broiler chickens]

Probiotics are live microorganisms with beneficial health effects on host animals which exert their effects on performance, gastrointestinal tract and immune system. Various probiotic products are available in the market. This study compared the effects of various probiotic products on broiler performance, intestinal morphology and some immunological and hematological parameters. Five probiotic products were fed to v480 1-d old broilers for 49 days. Performance was studied in starting, growing, finishing and whole periods. Samples of small intestine were studied at 21.35 and 49 days of age. Antibody titers against sheep red blood cells and new castle vaccine virus determined as immune response of birds. Probiotic type influenced the performance of birds. Morphological characteristics of intenstine have been affected by probiotic type. Probiotic type has not been affected by immune and blood related factors [p>0.05]. Type and ingredients of probiotcs should be considered when used for a special goal

Estatinas en influenza: momento de un estudio clínico controlado / Statins in influenza: time for a controlled clinical study

Mexico recently experienced the impact of an influenza epidemic. This outbreak, the H1N1 strain, affected a large number of citizens and caused panic, economic instability and increased health care costs to the federal government and public and private institutions. Influenza outbreaks are periodic. They may or may not be seasonal, and severity of the disease is linked to host immunity and to the virus strain. In the event of a pandemic as happened in 1918, it is estimated that approximately 175-350 million people may die, and health systems would face a catastrophic situation due to the insufficiency of antivirals and vaccines, as well as affecting hospital infrastructure.

Imipramine induced elevation of prolactin levels in patients with HIV/AIDS improved their immune status / La elevación de niveles de prolactina mediante inducción con imipramina mejoró el estatus inmune de pacientes con VIH/SIDA

Prolactin is known to have significant immunomodulatory properties. Imipramine, a monoamine oxidase inhibitor, stimulates prolactin production because it decreases dopamine which inhibits secretion of prolactin. The study objective was to determine if use of imipramine can result in immunological benefits for HIV-positive patients by restoration and preservation of immunological function. A cohort of 19 retroviral positive patients was identified for the prospective study which continued for a 28-week period. Three patients dropped out before the study began. Inclusion criteria accepted only patients on the same highly active antiretroviral therapy (HAART) regimen for a nine-month period and who had reached a plateau with respect to the CD4 cell count and also had no prior history of antidepressant use for a 12-month period. This study had a "before and after" design, patients serving as their own control. The study drug imipramine was prescribed for a 12-week period up to visit 4, and then discontinued for 4-weeks (washout period) at which time blood investigations were done at visit 5. Finally, patients were prescribed the study drug for a further 12-week period to the end of the trial (visit 7). At the 95 per cent probability level, significant differences in average prolactin and CD4 levels from visit 4 to the end of the trial period were recorded. Results showed a trend of prolactin levels decreasing after washout (p = 0.015) and increasing by the end of the trial period once imipramine dispensation had recommenced (p = 0.006). With respect to the CD4 cell count, there was a significant increase after wash-out (p = 0.022). These results indicate a trend to immune boosting in HIV-positive patients who had obtained the maximum response from HAART.

Se sabe que la prolactina posee importantes propiedades inmunomudolatorias. La imipramina, un inhibidor de la monoamino oxidasa, estimula la producción de la prolactina porque disminuye la dopamina, que a su vez inhibe la secreción de prolactina. El objetivo de este estudio fue determinar si el uso de la imipramina puede traer beneficios inmunológicos a los pacientes VIH positivos mediante la restauración y preservación de la función inmunológica. Se identificó una cohorte de 19 pacientes retrovirales positivos, a fin de realizar este estudio prospectivo que continuó por un período de 28 semanas Tres pacientes se retiraron antes de que el estudio comenzara. Los criterios de inclusión aceptaban sólo pacientes que tuvieran el mismo régimen de terapia antiretroviral altamente activa (HAART) por un período de nueve meses, que hubieran alcanzado un nivel de estabilización con respecto al conteo de células CD4, y que no hubieran además tenido con anterioridad una historia de uso de anti-depresantes por espacio de 12 meses. Este estudio tuvo un diseño "antes y después", sirviendo los pacientes como su propio control. La imipramina para el estudio fue prescrita por un período de 12 semanas hasta la visita 4, y luego descontinuada por 4 semanas para un reposo farmacológico (período de lavado), realizándose entonces pruebas de sangre en la visita 5. Finalmente se prescribió el medicamento de estudio a los pacientes por un nuevo período de 12 semanas hasta el final del ensayo (visita 7). En el nivel de probabilidad del 95 por ciento, se registraron diferencias significativas en los niveles promedio de prolactina y CD4 desde la visita 4 hasta el final del período de ensayo. Los resultados mostraron una tendencia de los niveles de prolactina a descender tras el lavado (p = 0.015) y a aumentar hacia el final del período de ensayo, una vez que la dispensación de imipramina hubiese recomenzado (p = 0.006). Con respecto al conteo de células de CD4, hubo un aumento significativo luego del lavado (p = 0.022).

Mecanismos moleculares de acción de algunas drogas inmunosupresoras / Molecular mechanisms of action of some immunosuppresive drugs

Los tratamientos utilizados para desordenes inmunológicos son de origen empírico, utilizando drogas inmunosupresoras identificadas a través de la selección de un gran número de compuestos naturales y sintéticos. Las drogas inmunosupresoras son ampliamente utilizadas en tratamientos clínicos de desordenes autoinmunes, en la prevención de rechazo a transplantes así como también en desordenes de carácter no autoinmune tales como las alergias. El diseño de las terapias inmunosupresoras está basado en controlar una respuesta inmune exacerbada. La base fisiopatológica de este concepto es en modular la acción de células mononucleares, siendo el principal punto de control las células T. Estas drogas inhiben la función normal de protección del sistema inmune llevando a la aparición de complicaciones en las terapias de inmunosupresión. Las drogas inmunosupresoras tienen diferentes blancos en el proceso de inmunidad celular. Según su modo de acción pueden clasificarse en cuatro categorías: drogas antinflamatorias de la familia de los corticosteroides, inmunosupresoras específicas inhibidoras de la calcineurina, citotóxicas o antiproliferativas y anticuerpos específicos. En este trabajo describimos el mecanismo de acción molecular de agentes inmunosupresores tales como, esteroides, ciclosporina, tacrolimo, azatioprina, ciclofosfamida, sirolimus, mofetil mecofenolato, leflunomida y anticuerpos específicos, para contribuir a la comprensión de cómo utilizar y mejorar estos agentes.

A number of natural and synthetic substances are used in the treatment of immunological disorders. The immunosuppressive drugs are widely utilized in clinical treatments of autoimmune disorders, in the prevention of transplant rejection as well as in non-autoimmune diseases such as allergy. The design of immunosuppressive therapies is based on the control of the exacerbated immune response. The pathophysiologic mean of this concept is to modulate the action of mononuclear cells, being T cells the main targets. Immunosuppressive agents have different molecular targets, and an important drawback in their use is that they also inhibit the normal immune system response. Depending on their mode of action, immunosuppressive drugs can be classified in four different groups: antinflammatory drugs of the corticosteroid family, inhibitors of the calcineurin pathway, cytototoxic or antiproliferative drugs and specific antibodies. In this article, we focus on the molecular action of immunosuppressive drugs such as steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, sirolimus, mycophenolate mofetil, leflunomide and specific antibodies, providing data to characterize and improve the use of these agents.

Biochemical toxicity of benzene.

Human exposure to benzene in work environment is a global occupational health problem. After inhalation or absorption, benzene targets organs viz. liver, kidney, lung, heart and brain etc. It is metabolized mainly in the liver by cytochrome P450 multifunctional oxygenase system. Benzene causes haematotoxicity through its phenolic metabolites that act in concert to produce DNA strand breaks, chromosomal damage, sister chromatid exchange, inhibition of topoisomerase II and damage to mitotic spindle. The carcinogenic and myelotoxic effects of benzene are associated with free radical formation either as benzene metabolites or lipid peroxidation products. Benzene oxide and phenol have been considered as proheptons. Liver microsomes play an important role in biotransformation of benzene whereas in kidney, it produces degenerative intracellular changes. Cohort studies made in different countries suggest that benzene induces multiple myeloma in petrochemical workers. Though extensive studies have been performed on its toxicity, endocrinal disruption caused by benzene remains poorly known. Transgenic cytochrome P450 IIE1 mice may help in understanding further toxic manifestations of benzene.