Deeper exploration of inflammatory cell populations in milk to monitor udder health in dairy cows

The present study explored the predictive values of milk leukocyte differentials (MLD) as a basis for improving the diagnosis of intramammary infections (IMIs) and subclinical mastitis. Quarter milk samples were collected for bacteriological analysis, quarter somatic cell count (qSCC), and MLD. The MLD were assessed using the cytospin technique, direct microscopic smears, and flow cytometry. The predictive values of each single leukocyte population and useful potential indices that could better reflect immune complexity were also calculated. Changes in the percentage of any leukocyte alone failed to substantially improve the predictive value of qSCC in diagnosing IMIs. Although certain parameters increased the area under the receiver operating characteristic curve (ROC curve) as a result of increased specificity values, a slight reduction in sensitivity was observed. The so-called CD8 complex was a unique parameter which improved both the sensitivity (78.79 %) and the specificity (80.77 %) in IMI diagnosis, resulting in the highest area under the ROC curve (0.87). To diagnose subclinical mastitis, the percentage of macrophages and the sum of the percentage PMNLs and T CD8+ cells divided by the percentage of macrophages showed the highest predictive values (sensitivity = 79.63, specificity = 73.68, and area under the ROC curve = 0.83) in the differentiation of the inflammatory condition status of cows. In conclusion, this study provides further insights into using T CD8+ lymphocytes in diagnosing bovine IMIs, combined with PMNLs and macrophages. The antidromic trend of macrophages vs. PMNLs and T CD8+ lymphocytes due to the increasing qSCCs was crucial to differentiating quarters under both inflammatory and non-inflammatory conditions.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.516 g/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,516 g/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5-16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5-16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5–16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5–16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios [...].

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5–16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.(AU)

O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5–16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios [...].(AU)

Natural association between bovine leukemia virus and reproductive infectious diseases

Background: Enzootic bovine leukosis (EBL) is a widespread infectious disease caused by the bovine leukemia virus (BLV), which results in immune system dysfunction. The resulting immunosuppression may lead to an increased prevalence of other diseases. Dairy cows infected have altered immune function associated with decreased milk production and shortened lifespan and decreased immune response to immunization. BLV infection, however, is often asymptomatic, so any connection between subclinical infection and common reproductive diseases remains unknown. This study aimed to describe the relationship between naturally occurring subclinical BLV and infectious reproductive diseases seroconversion in the field. Materials, Methods & Results: The diseases investigated included Bovine viral diarrhoea (BVD), Bovine alfaherpesvirus 1 (BoHV-1), Bovine gammaherpesvirus 4 (BoHV-4), Chlamydiosis, Leptospirosis, Brucellosis and Neosporosis in dairy cattle. Six hundred fifty-five sera samples from the northern and south-central regions of Uruguay, from asymptomatic female Holstein and Holstein crosses without a history of vaccination against reproductive diseases were processed using reference diagnostic methods (Seronautalization, ELISA, MAT, Rose Bengal Plate test). The seroprevalence of BLV was 20.0%. Seroprevalence of reproductive diseases BVD, BoHV-1 and BoHV-4 were 99.3%, 41.2% and 27.3% of the populations, respectively, and the total seroprevalence of Leptospirosis, bovine Neospora caninum and Chlamydiosis were 19.8%, 29.8% and 33.0% respectively. The results revealed positive associations between naturally contracted BLV and the presence of antibodies against BoHV-1 (P = 0.002), as well as between naturally contracted BLV and presence of antibodies against Leptospira spp. (P = 0.028). Discussion: BLV infection can impact innate and adaptive immune system cells and alter the proper functioning of uninfected cells. BLV infection may also induce changes in the complex balance of cytokine expression, cell proliferation, and programmed cell death in T- and B-lymphocytes, which is critical for immune competence and effective response to infectious challenges. The progression of BLV infection has a substantial effect on host defense mechanisms. Indeed, lowmagnitude serologic responses to a commercial foot-and-mouth disease vaccine and a J5 Escherichia coli vaccine have been observed. These results are supported by recent trial studies showing a reduced immune response to vaccination against BoHV-1 and Leptospira spp. in asymptomatic animals infected with BLV. These are 2 of the most prevalent infectious reproductive diseases in cattle worldwide, and our results provide evidence that a link between BLV and susceptibility to these diseases may exist. Although there is evidence of the co-occurrence of these diseases, it remains unknown whether there is a direct or indirect effect of BLV on infertility, embryonic loss, or abortion. Another possibility is that natural infection with these reproductive pathogens (BoHV-1, Leptospira, or others) promotes BLV expression, negatively affecting the farms where these pathogens are endemic. Considering the high seroprevalence of BLV in dairy herds in North and South America where the infection is endemic, it was explored BLV's role as an immunosuppressant by quantifying its co-occurrence with diseases that affect reproductive performance in breeding herds. Future work should clarify the role of BLV and the co-occurring pathogens in causing infertility or abortions.

Histopathological, immunohistochemical and biochemical alterations in liver tissue after fungicide-mancozeb exposures in Wistar albino rats

Purpose: To evaluate the histopathological, immunohistochemical, and biochemical effects of liver changes after mancozeb administration. Methods: Rats were divided into groups­the control group (n=7) and the mancozeb group (n=7)­, given 500 mg/kg mancozeb dissolved in corn oil daily for four weeks by an orogastric tube. Caspase-3 and tumor necrosis factor-alpha (TNF-α) primary antibodies were used for immunohistochemical analysis. Results: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the mancozeb group increased significantly than ones of the control group. Venous dilatation, inflammation, hepatocyte degeneration, TNF-α, and caspase-3 expression scores increased significantly in the mancozeb group. In the mancozeb group, intensive caspase-3 expression was observed in hepatocyte cells around the central vein in the center of the liver lobule, and there was an increase in TNF-α expression in the inflammatory cells around the enlarged central vein and Kupffer cells and apoptotic hepatocyte cells. Conclusions: Subacute mancozeb exposure in rats leads to elevated toxicity with impaired liver function, increased inflammation in tissue and increased apoptosis due to cellular damage in the liver, and decreased liver regeneration ability due to congestion and degeneration of blood vessels.

Mecanismos inflamatórios da obesidade: o que sabemos em gatos? / Inflammatory mechanisms in obesity: what is known in cats?

O objetivo deste trabalho foifornecer uma visão geral dos mecanismos inflamatórios envolvidos no processo da obesidade, com enfoque nas respostas imunes pró-inflamatórias e no papel das adipocinas nas reações inflamatórias, em humanos e animais, bem como a correlação com a espécie felina. A obesidade é considerada uma doença endócrina cada vez mais prevalente na espécie felina, causada por uma desordem nutricional de balanço energético negativo. É definida como um acúmulo excessivo de tecido adiposo que afeta negativamente a saúde do animal e está associada à diminuição da expectativa de vida, sendo que as causas que a desencadeiam são multifatoriais, sendo atreladas a diversos fatores genéticos e ambientais. O tecido adiposo é um órgão endócrino que participa ativamente do metabolismo energético e concentra fatores hormonais que são secretados pelos adipócitos, os quais modulam o metabolismo e exercem capacidade de envolver diretamente as respostas imunes inatas e adaptativas por meio da atividade dos principais tipos celulares, incluindo adipócitos e macrófagos responsáveis pela ativação e liberação de citocinas que afetam a função fisiológica normal, influenciando no desenvolvimento da inflamação crônica. A produção alterada de adipocinas na obesidade tem sido envolvida na fisiopatologia de diversos grupos de doenças e tem sido relatada sua possível contribuição para o desenvolvimento de resistência insulínica e diabetes mellitus. Apesar do incompleto compreendimento dos fatores desencadeantes da inflamação no tecido adiposo de gatos, sugere-se que estejam envolvidos aspectos associados à disfunção mitocondrial, hipóxia ou, ainda, que estejam associados fatores intrínsecos do adipócito.

This study aimed to provide an overview of the inflammatory mechanisms involved in the obesity process focusing on pro-inflammatory immune responses and the role of adipokines in inflammatory reactionsm in animals and humans, as well as the correlation with the feline specie. Obesity is considered an increasingly prevalent endocrine disease in feline species, caused by a nutritional disorder with negative energy balance. It is defined as an excessive accumulation of adipose tissue that negatively affects the animal's health and is associated with a decrease in life expectancy and as triggering causes are multifactorial, being linked to several genetic and environmental factors. Adipose tissue is an endocrine organ that actively participates in energy metabolism and concentrates hormonal factors that are secreted by adipocytes, which modulate metabolism and exert the ability to directly involve innate and adaptive immune responses through the activity of the main cell types, including adipocytes and macrophages responsible for the activation and release of cytokines that affect normal physiological function, influencing the development of chronic inflammation. The altered production of adipokines in obesity has been implicated in the pathophysiology of several groups of diseases and their possible contribution to the development of insulin resistance and diabetes mellitus. Despite the incomplete understanding of the triggering factors of inflammation in the adipose tissue of cats, it is suggested that aspects associated with mitochondrial dysfunction, hypoxia, or even intrinsic factors of the adipocyte are involved.

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

Abstract The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.

Lymphoplasmacytic hemorrhagic cystitis in dog: case report / Cistite hemorrágica linfoplasmocitária em cão: relato de caso

Hematuria is a relatively common manifestation in dogs and cats when secondary with urinary tract disorders, such as bacterial cystitis and urolithiasis, your treatment is limited to treatment of the primary cause. However, when the hematuria is persistent or capable of causing significant haematological disorders, other causes less common should to be investigated. A 12-year-old, male pit bull dog, was admitted presenting intense hematuria for the last 10 days. Laboratory tests showed intense normocytic and normochromic anemia, hypoalbuminemia and albuminuria associated with intense hematuria. The ultrasound images reveled presence of structures compatible with blood clots and increased wall thickness and irregularity of urinary bladder. The bladder wash cytology suggested chronic cystitis. Due to results of de laboratory tests and bladder US images, started treatment which antibiotic therapy associated with blood transfusions were maintained until histopathology results. During the biopsy surgery it was observed The bladder wall was thicker and richly vascularized, with normal elasticity and absence of masses or polyps on the inner and outer wall. Histopathological examination revealed thickening of the muscular layer, hemorrhage and diffuse hyperemia between muscle fibers and lamina propria, intact and ruptured capillaries filled with red blood cells, and a discrete multifoc

A hematúria é uma manifestação relativamente comum em cães e gatos quando secundária a distúrbios do trato urinário, tais como cistite bacteriana e urolitíase, sendo seu tratamento limitado à eliminação da causa primária. Entretanto, quando a hematúria é persistente ou capaz de causar distúrbios hematológicos significativos, outras causas menos comuns devem ser investigadas. Um cão, pit bull, macho de 12 anos de idade deu entrada no Hospital Veterinário da xxx com queixa principal de acentuado sangramento urinário há 10 dias. Os exames laboratoriais mostraram anemia normocítica e normo-crômica e hipoalbuminemia, associadas à proteinúria e hematúria intensa. As imagens ultrassonográficas revelaram à presença de estruturas compatíveis com coágulos sanguíneos e aumento da espessura e irregularidade da parede da bexiga, e a citologia do lavado vesical sugeriu cistite crônica. Com os resultados dos exames laboratoriais e de imagem, iniciaram-se os tratamentos com antibioticoterapia associados às transfusões sanguíneas, e o animal foi encaminhado para a biopsia de bexiga. Durante o procedimento cirúrgico, observou-se que a parede vesical apresentava-se espessa e ricamente vascularizada, com elasticidade normal e ausência de massas ou pólipos nas faces interna e externa. O exame histopatológico revelou tratar-se de cistite hemor-rágica linfoplasmocitária, uma doença rara e muito agressiva, a qual apresenta descrições semelhantes em seres humanos, mas ainda não descrita em cães.

Lymphoplasmacytic hemorrhagic cystitis in dog: case report / Cistite hemorrágica linfoplasmocitária em cão: relato de caso

Hematuria is a relatively common manifestation in dogs and cats when secondary with urinary tract disorders, such as bacterial cystitis and urolithiasis, your treatment is limited to treatment of the primary cause. However, when the hematuria is persistent or capable of causing significant haematological disorders, other causes less common should to be investigated. A 12-year-old, male pit bull dog, was admitted presenting intense hematuria for the last 10 days. Laboratory tests showed intense normocytic and normochromic anemia, hypoalbuminemia and albuminuria associated with intense hematuria. The ultrasound images reveled presence of structures compatible with blood clots and increased wall thickness and irregularity of urinary bladder. The bladder wash cytology suggested chronic cystitis. Due to results of de laboratory tests and bladder US images, started treatment which antibiotic therapy associated with blood transfusions were maintained until histopathology results. During the biopsy surgery it was observed The bladder wall was thicker and richly vascularized, with normal elasticity and absence of masses or polyps on the inner and outer wall. Histopathological examination revealed thickening of the muscular layer, hemorrhage and diffuse hyperemia between muscle fibers and lamina propria, intact and ruptured capillaries filled with red blood cells, and a discrete multifoc

A hematúria é uma manifestação relativamente comum em cães e gatos quando secundária a distúrbios do trato urinário, tais como cistite bacteriana e urolitíase, sendo seu tratamento limitado à eliminação da causa primária. Entretanto, quando a hematúria é persistente ou capaz de causar distúrbios hematológicos significativos, outras causas menos comuns devem ser investigadas. Um cão, pit bull, macho de 12 anos de idade deu entrada no Hospital Veterinário da xxx com queixa principal de acentuado sangramento urinário há 10 dias. Os exames laboratoriais mostraram anemia normocítica e normo-crômica e hipoalbuminemia, associadas à proteinúria e hematúria intensa. As imagens ultrassonográficas revelaram à presença de estruturas compatíveis com coágulos sanguíneos e aumento da espessura e irregularidade da parede da bexiga, e a citologia do lavado vesical sugeriu cistite crônica. Com os resultados dos exames laboratoriais e de imagem, iniciaram-se os tratamentos com antibioticoterapia associados às transfusões sanguíneas, e o animal foi encaminhado para a biopsia de bexiga. Durante o procedimento cirúrgico, observou-se que a parede vesical apresentava-se espessa e ricamente vascularizada, com elasticidade normal e ausência de massas ou pólipos nas faces interna e externa. O exame histopatológico revelou tratar-se de cistite hemor-rágica linfoplasmocitária, uma doença rara e muito agressiva, a qual apresenta descrições semelhantes em seres humanos, mas ainda não descrita em cães.(AU)

Effects of dietary vitamin E on the wound healing induced in Oreochromis niloticus / Efeitos da suplementação com vitamina E na cicatrização de feridas induzidas em Oreochromis niloticus

In the present study, the effect of vitamin E supplementation 450 mg/kg diet was appraised in the process of induced wound healing in Nile tilapias Oreochromis niloticus. Fish were distributed into 18 tanks (10 fish each). Nine tanks were fed the non-supplemented diet and the other 9 tanks were fed 450 mg vitamin E for 60 days. Subsequently, the fish were anesthetized and the epidermis and dermis were surgically removed. The rate of cicatricial retraction and appearance of the wounds, and the histomorphometry of mucous cells, chromatophores, revascularization, inflammatory cells, presence of fibroblasts, collagen fibers, and scales were checked after 3-, 7-, 14-, 21-, and 28-days post-wounding. The retraction rate of the wound was significantly higher in the supplemented fish. The higher concentrations of inflammatory cells, mucous cells, and chromatophores, as well as the production and organization of collagen fibers, resulted in a higher retraction rate. We concluded that a dietary supplementation diet improves specific aspects of the cutaneous healing process in Nile tilapia fish.(AU)

No presente estudo, o efeito da suplementação com vitamina E de 450 mg / kg de dieta foi avaliado no processo de cicatrização induzida de feridas em tilápias do Nilo, Oreochromis niloticus. Os peixes foram distribuídos em 18 tanques (N=10), sendo 9 tanques com dieta não suplementada e os outros 9 tanques suplementados com 450 mg de vitamina E por 60 dias. Posteriormente, os peixes foram anestesiados e a epiderme e derme foram removidas cirurgicamente. Nos tempos pré-determinado de 3, 7, 14, 21 e 28 dias após a ferida foi analisado a taxa de retração cicatricial, a aparência das feridas e a histomorfometria das células mucosas, dos cromatóforos, das células inflamatórias, a revascularização, a presença de fibroblastos, de fibras de colágeno e escamas. A taxa de retração da ferida foi significativamente maior nos peixes suplementados. As maiores concentrações de células inflamatórias, mucosas e cromatóforos, bem como a produção e organização das fibras de colágeno, resultaram em uma maior taxa de retração. Concluímos que a dieta de suplementação melhora aspectos específicos do processo de cicatrização cutânea em peixes de tilápia do Nilo.(AU)

Effects of dietary vitamin E on the wound healing induced in Oreochromis niloticus / Efeitos da suplementação com vitamina E na cicatrização de feridas induzidas em Oreochromis niloticus

In the present study, the effect of vitamin E supplementation 450 mg/kg diet was appraised in the process of induced wound healing in Nile tilapias Oreochromis niloticus. Fish were distributed into 18 tanks (10 fish each). Nine tanks were fed the non-supplemented diet and the other 9 tanks were fed 450 mg vitamin E for 60 days. Subsequently, the fish were anesthetized and the epidermis and dermis were surgically removed. The rate of cicatricial retraction and appearance of the wounds, and the histomorphometry of mucous cells, chromatophores, revascularization, inflammatory cells, presence of fibroblasts, collagen fibers, and scales were checked after 3-, 7-, 14-, 21-, and 28-days post-wounding. The retraction rate of the wound was significantly higher in the supplemented fish. The higher concentrations of inflammatory cells, mucous cells, and chromatophores, as well as the production and organization of collagen fibers, resulted in a higher retraction rate. We concluded that a dietary supplementation diet improves specific aspects of the cutaneous healing process in Nile tilapia fish.(AU)

No presente estudo, o efeito da suplementação com vitamina E de 450 mg / kg de dieta foi avaliado no processo de cicatrização induzida de feridas em tilápias do Nilo, Oreochromis niloticus. Os peixes foram distribuídos em 18 tanques (N=10), sendo 9 tanques com dieta não suplementada e os outros 9 tanques suplementados com 450 mg de vitamina E por 60 dias. Posteriormente, os peixes foram anestesiados e a epiderme e derme foram removidas cirurgicamente. Nos tempos pré-determinado de 3, 7, 14, 21 e 28 dias após a ferida foi analisado a taxa de retração cicatricial, a aparência das feridas e a histomorfometria das células mucosas, dos cromatóforos, das células inflamatórias, a revascularização, a presença de fibroblastos, de fibras de colágeno e escamas. A taxa de retração da ferida foi significativamente maior nos peixes suplementados. As maiores concentrações de células inflamatórias, mucosas e cromatóforos, bem como a produção e organização das fibras de colágeno, resultaram em uma maior taxa de retração. Concluímos que a dieta de suplementação melhora aspectos específicos do processo de cicatrização cutânea em peixes de tilápia do Nilo.(AU)

Effect of flunixin or ketoprofen in caudectomy by elastration in lambs: pain and neutrophil function / Efeito de flunixin ou cetoprofeno em cordeiras submetidas a caudectomia por elastração: dor e função neutrofílica

Painful procedures can affect the function of innate immune cells, such as neutrophils and macrophages, increasing the risk of infectious diseases. The present work aimed to verify if the analgesics flunixin meglumine or ketoprofen can attenuate the pain/discomfort of newborn lambs submitted by elastration tail docking and thereby avoid the impairment of blood granulocytes function. Twenty-one neonate lambs were divided into three treatments: the control group (n=7), not subjected to caudectomy; the flunixin group (n=7), subjected to caudectomy under local anesthesia and analgesia with two doses of flunixin meglumine; and the ketoprofen group (n=7), subjected to caudectomy under local anesthesia and two doses of ketoprofen. Pain indicators were observed by pain posture score (PS), the number of vocalizations (V), frequency of the movement of the ears (EF), and respiratory rates (RR), observed by a 10 minutes videos for each time points: -15min, 6h, 48h, and 144h. At the same time points, the reactive oxygen species (ROS) production and phagocytosis of blood granulocytes were measured by flow cytometry. At 6h after caudectomy, there was a pain indicator increase (RR, V, and PS), a blood granulocyte percentage increase, and a granulocytes phagocytosis reduction for both groups. At 48h, the ketoprofen group spend more time in pain posture and, at 144h, they exhibited a ROS production granulocyte reduction without signs of pain. We conclude the flunixin meglumine and ketoprofen did not prevent the acute pain/discomfort caused by caudectomy, because the groups showed a pain behavior and impaired of the innate immune response however, the flunixin meglumine was effective in controlling the chronic pain and their effects on blood granulocytes function in compare ketoprofen.(AU)

Procedimentos dolorosos podem afetar a função das células imunes inatas como neutrófilos e macrófagos, aumentando o risco de ocorrer doenças infeciosas. Desta maneira, o presente trabalho pretendeu verificar se os analgésicos flunixin meglumine ou cetoprofeno conseguem atenuar a dor/desconforto de cordeiros neonatos submetidos a caudectomia por elastração, evitando assim o comprometimento da função dos granulócitos sanguíneos. Para tanto 21 cordeiras foram aleatoriamente divididas em três tratamentos: grupo controle (n=7) não submetido a caudectomia, grupo flunixin (n=7) submetido a caudectomia precedida por anestesia local e duas doses de flunixin meglumine, e cetoprofeno (n=7) submetido a caudectomia precedida por anestesia local e duas doses de cetoprofeno. Mensurou-se os indicadores de dor/desconforto após caudectomia por observações de escore de postura de dor (EP), número de vocalizações (V), frequência de movimentar as orelhas (FO) e frequência respiratória (FR), observados em vídeos de 10 minutos nos momentos -15 min e 6, 48 e 144h. Nos mesmos momentos, avaliou-se a as funções de produção de espécies reativas de oxigênio (ERO) e de fagocitose por granulócitos sanguineos em citometria de fluxo. Notou-se aumento dos indicadores de dor (FR, de V e de EP), da porcentagem dos granulócitos sanguíneos e redução da eficiência de fagocitose em ambos os grupos as 6h. As 48h, os animais do grupo cetoprofeno ainda apresentava mais tempo em postura de dor que os demais grupos e as 144h, apresentou redução da produção ERO por granulócitos. Tais achados permitem concluir que tanto o flunexin meglumine como o cetoprofeno não preveniram dor/desconforto agudo promovido pela elastração, pois os dois grupos manifestaram comportamento de dor e redução da resposta imune inata. Ainda, o analgésico flunixin meglumine foi efetivo em controlar a dor mais tardia e seus efeitos na função de granulócitos sanguíneos em comparação ao cetoprofeno.(AU)

Effect of flunixin or ketoprofen in caudectomy by elastration in lambs: pain and neutrophil function / Efeito de flunixin ou cetoprofeno em cordeiras submetidas a caudectomia por elastração: dor e função neutrofílica

Painful procedures can affect the function of innate immune cells, such as neutrophils and macrophages, increasing the risk of infectious diseases. The present work aimed to verify if the analgesics flunixin meglumine or ketoprofen can attenuate the pain/discomfort of newborn lambs submitted by elastration tail docking and thereby avoid the impairment of blood granulocytes function. Twenty-one neonate lambs were divided into three treatments: the control group (n=7), not subjected to caudectomy; the flunixin group (n=7), subjected to caudectomy under local anesthesia and analgesia with two doses of flunixin meglumine; and the ketoprofen group (n=7), subjected to caudectomy under local anesthesia and two doses of ketoprofen. Pain indicators were observed by pain posture score (PS), the number of vocalizations (V), frequency of the movement of the ears (EF), and respiratory rates (RR), observed by a 10 minutes videos for each time points: -15min, 6h, 48h, and 144h. At the same time points, the reactive oxygen species (ROS) production and phagocytosis of blood granulocytes were measured by flow cytometry. At 6h after caudectomy, there was a pain indicator increase (RR, V, and PS), a blood granulocyte percentage increase, and a granulocytes phagocytosis reduction for both groups. At 48h, the ketoprofen group spend more time in pain posture and, at 144h, they exhibited a ROS production granulocyte reduction without signs of pain. We conclude the flunixin meglumine and ketoprofen did not prevent the acute pain/discomfort caused by caudectomy, because the groups showed a pain behavior and impaired of the innate immune response however, the flunixin meglumine was effective in controlling the chronic pain and their effects on blood granulocytes function in compare ketoprofen.(AU)

Procedimentos dolorosos podem afetar a função das células imunes inatas como neutrófilos e macrófagos, aumentando o risco de ocorrer doenças infeciosas. Desta maneira, o presente trabalho pretendeu verificar se os analgésicos flunixin meglumine ou cetoprofeno conseguem atenuar a dor/desconforto de cordeiros neonatos submetidos a caudectomia por elastração, evitando assim o comprometimento da função dos granulócitos sanguíneos. Para tanto 21 cordeiras foram aleatoriamente divididas em três tratamentos: grupo controle (n=7) não submetido a caudectomia, grupo flunixin (n=7) submetido a caudectomia precedida por anestesia local e duas doses de flunixin meglumine, e cetoprofeno (n=7) submetido a caudectomia precedida por anestesia local e duas doses de cetoprofeno. Mensurou-se os indicadores de dor/desconforto após caudectomia por observações de escore de postura de dor (EP), número de vocalizações (V), frequência de movimentar as orelhas (FO) e frequência respiratória (FR), observados em vídeos de 10 minutos nos momentos -15 min e 6, 48 e 144h. Nos mesmos momentos, avaliou-se a as funções de produção de espécies reativas de oxigênio (ERO) e de fagocitose por granulócitos sanguineos em citometria de fluxo. Notou-se aumento dos indicadores de dor (FR, de V e de EP), da porcentagem dos granulócitos sanguíneos e redução da eficiência de fagocitose em ambos os grupos as 6h. As 48h, os animais do grupo cetoprofeno ainda apresentava mais tempo em postura de dor que os demais grupos e as 144h, apresentou redução da produção ERO por granulócitos. Tais achados permitem concluir que tanto o flunexin meglumine como o cetoprofeno não preveniram dor/desconforto agudo promovido pela elastração, pois os dois grupos manifestaram comportamento de dor e redução da resposta imune inata. Ainda, o analgésico flunixin meglumine foi efetivo em controlar a dor mais tardia e seus efeitos na função de granulócitos sanguíneos em comparação ao cetoprofeno.(AU)

Effect of flunixin or ketoprofen in caudectomy by elastration in lambs: pain and neutrophil function

ABSTRACT: Painful procedures can affect the function of innate immune cells, such as neutrophils and macrophages, increasing the risk of infectious diseases. The present work aimed to verify if the analgesics flunixin meglumine or ketoprofen can attenuate the pain/discomfort of newborn lambs submitted by elastration tail docking and thereby avoid the impairment of blood granulocytes function. Twenty-one neonate lambs were divided into three treatments: the control group (n=7), not subjected to caudectomy; the flunixin group (n=7), subjected to caudectomy under local anesthesia and analgesia with two doses of flunixin meglumine; and the ketoprofen group (n=7), subjected to caudectomy under local anesthesia and two doses of ketoprofen. Pain indicators were observed by pain posture score (PS), the number of vocalizations (V), frequency of the movement of the ears (EF), and respiratory rates (RR), observed by a 10 minutes videos for each time points: -15min, 6h, 48h, and 144h. At the same time points, the reactive oxygen species (ROS) production and phagocytosis of blood granulocytes were measured by flow cytometry. At 6h after caudectomy, there was a pain indicator increase (RR, V, and PS), a blood granulocyte percentage increase, and a granulocytes phagocytosis reduction for both groups. At 48h, the ketoprofen group spend more time in pain posture and, at 144h, they exhibited a ROS production granulocyte reduction without signs of pain. We conclude the flunixin meglumine and ketoprofen did not prevent the acute pain/discomfort caused by caudectomy, because the groups showed a pain behavior and impaired of the innate immune response however, the flunixin meglumine was effective in controlling the chronic pain and their effects on blood granulocytes function in compare ketoprofen.

RESUMO: Procedimentos dolorosos podem afetar a função das células imunes inatas como neutrófilos e macrófagos, aumentando o risco de ocorrer doenças infeciosas. Desta maneira, o presente trabalho pretendeu verificar se os analgésicos flunixin meglumine ou cetoprofeno conseguem atenuar a dor/desconforto de cordeiros neonatos submetidos a caudectomia por elastração, evitando assim o comprometimento da função dos granulócitos sanguíneos. Para tanto 21 cordeiras foram aleatoriamente divididas em três tratamentos: grupo controle (n=7) não submetido a caudectomia, grupo flunixin (n=7) submetido a caudectomia precedida por anestesia local e duas doses de flunixin meglumine, e cetoprofeno (n=7) submetido a caudectomia precedida por anestesia local e duas doses de cetoprofeno. Mensurou-se os indicadores de dor/desconforto após caudectomia por observações de escore de postura de dor (EP), número de vocalizações (V), frequência de movimentar as orelhas (FO) e frequência respiratória (FR), observados em vídeos de 10 minutos nos momentos -15 min e 6, 48 e 144h. Nos mesmos momentos, avaliou-se a as funções de produção de espécies reativas de oxigênio (ERO) e de fagocitose por granulócitos sanguineos em citometria de fluxo. Notou-se aumento dos indicadores de dor (FR, de V e de EP), da porcentagem dos granulócitos sanguíneos e redução da eficiência de fagocitose em ambos os grupos as 6h. As 48h, os animais do grupo cetoprofeno ainda apresentava mais tempo em postura de dor que os demais grupos e as 144h, apresentou redução da produção ERO por granulócitos. Tais achados permitem concluir que tanto o flunexin meglumine como o cetoprofeno não preveniram dor/desconforto agudo promovido pela elastração, pois os dois grupos manifestaram comportamento de dor e redução da resposta imune inata. Ainda, o analgésico flunixin meglumine foi efetivo em controlar a dor mais tardia e seus efeitos na função de granulócitos sanguíneos em comparação ao cetoprofeno.

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.(AU)

Acute kidney injury caused by venomous animals: inflammatory mechanisms

Either bites or stings of venomous animals comprise relevant public health problems in tropical countries. Acute kidney injury (AKI) induced by animal toxins is related to worse prognostic and outcomes. Being one the most important pathways to induce AKI following envenoming due to animal toxins, inflammation is an essential biological response that eliminates pathogenic bacteria and repairs tissue after injury. However, direct nephrotoxicity (i.e. apoptotic and necrotic mechanisms of toxins), pigmenturia (i.e. rhabdomyolysis and hemolysis), anaphylactic reactions, and coagulopathies could contribute to the renal injury. All these mechanisms are closely integrated, but inflammation is a distinct process. Hence, it is important to improve our understanding on inflammation mechanisms of these syndromes to provide a promising outlook to reduce morbidity and mortality. This literature review highlights the main scientific evidence of acute kidney injury induced by bites or stings from venomous animals and their inflammatory mechanisms. It included observational, cross-sectional, casecontrol and cohort human studies available up to December 2019. Descriptors were used according to Medical Subject Headings (MeSH), namely: "Acute kidney injury" or "Venom" and "Inflammation" on Medline/Pubmed and Google Scholar; "Kidney disease" or "Acute kidney injury" on Lilacs and SciELO. The present review evidenced that, among the described forms of renal inflammation, it can occur either directly or indirectly on renal cells by means of intravascular, systemic and endothelial hemolysis, activation of inflammatory pathway, as well as direct action of venom cytotoxic components on kidney structures.(AU)

Effects of venoms on neutrophil respiratory burst: a major inflammatory function

Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Effects of venoms on neutrophil respiratory burst: a major inflammatory function

Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)