Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Canine atopic dermatitis: systemic immunomodulatory protocol based on clinical phenotype / Dermatite atópica canina: protocolos imunomodulatórios sistêmicos baseados no fenótipo clínico

Canine atopic dermatitis (cAD) is a multifactorial allergic disease associated with immune dysfunction and abnormal skin barrier. Several immunological mediators play a role in its pathogenesis. Such molecules are produced by the activation of T helper lymphocytes (Th) through polarization to Th1 and/or Th2, which contributes to different lesion patterns. Acute lesions are mediated by an activation of the Th2 cytokine axis, which clinically induces erythema and pruritus. Conversely, in chronic injuries a mixed immune response of Th1/Th2 cytokines occurs, leading to hyperpigmented and lichenified skin. The clinical understanding of these patterns and the mode of action of immunomodulators are crucial for the best clinical management of the atopic patient. In this context, this review discussed the role of the immune response and the immunomodulatory drugs in dogs with atopic dermatitis and suggested a therapeutic protocol based on clinical phenotype. Based on the evidences showed in this review, it is considered appropriate to use immunomodulatory drugs that target cytokine spectrum related with the clinical phenotype of cAD.

A dermatite atópica canina (DAC) é uma doença alérgica multifatorial associada à disfunção imune e barreira cutânea anormal. Vários mediadores imunológicos desempenham um papel na sua patogênese. Tais moléculas são produzidas pela ativação de linfócitos T auxiliares (Th) por meio da polarização para Th1 e/ou Th2, o que contribui para diferentes padrões de lesão. Lesões agudas são mediadas pela ativação do eixo de citocinas Th2, que clinicamente induz eritema e prurido. Por outro lado, nas lesões crônicas ocorre uma resposta imune mista de citocinas Th1/Th2, levando à pele hiperpigmentada e liquenificada. O entendimento clínico desses padrões e o modo de ação dos imunomoduladores são cruciais para o melhor manejo clínico do paciente atópico. Esta revisão visa discutir o papel da resposta imune e das drogas imunomoduladoras em cães com dermatite atópica e sugerir um protocolo terapêutico baseado no fenótipo clínico. Baseado nas evidências apresentadas nessa revisão, é considerado apropriado utilizar drogas imunomoduladoras que abrangem o espectro de citocinas relacionadas ao fenótipo clínico da DAC.

Tarantula cubensis extract (Theranekron®) inhibits inflammation in carrageenan-induced acute paw edema in rats / [Extrato de tarântula cubensis (Theranekron®) inibe a inflamação no edema induzido por algas vermelhas na pata de ratos]

The aim of this study was to investigate the anti-inflammatory effect of alcoholic extract of Tarantula cubensis alcoholic extract (TCAE) in experimentally induced inflammation in rats. Fifty-four adult Sprague-Dawley male rats were randomly divided into nine groups. Paw edema was induced by 0.2mL subplantar (s.p.) injection of 1% carrageenan (CAR) into the right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) (10mg/kg, p.o.) or TCAE at different doses (1, 10 or 100µg/kg) injected s.c. for systemic or s.p. for local anti-inflammatory effect. Saline was used as control. Changes in paw thickness, volume, and weight were calculated as percentages. Formalin-fixed paws were used for histopathological examination. We detected that TCAE applied s.c. at 10µg/kg and 100µg/kg doses resulted in thinner paw thickness, lower paw volume, and lower paw weights four hours after the induction of inflammation when compared with the INDO group (p<0.05). The paw edema inhibitory effect of TCAE applied at a dose of 10µg/kg, s.c. was 68% when compared with the INDO which had an inhibitory effect of 56%. These results were verified with similar histopathological findings. The anti-inflammatory feature of 10µg/kg of TCAE given systematically was similar to the effects of INDO. Our results suggest that TCAE has anti-inflammatory effects by reducing edema and decreasing inflammatory reaction. These results may be attributed to the inhibition of the production of proinflammatory mediators. Thus, TCAE may be considered as a potential anti-inflammatory agent for treating acute inflammatory conditions.

O objetivo deste estudo foi investigar o efeito anti-inflamatório do extrato alcoólico de Tarantula cubensis (TCAE) na inflamação induzida experimentalmente em ratos. Cinqüenta e quatro ratos Sprague-Dawley adultos machos foram divididos aleatoriamente em nove grupos. O edema da pata foi induzido pela injeção de 0,2mL de subplantar (s.p.) de 1% de carragena (CAR) na pata traseira direita. Ratos foram tratados com o medicamento antiinflamatório não esteróide (NSAID) indometacina (INDO) (10mg/kg, p.o.) ou TCAE em doses diferentes (1, 10 ou 100µg/kg) injetado s.c. para efeito sistêmico ou s.p. para efeito antiinflamatório local. A soro fisiológico foi usado como controle. As mudanças na espessura da pata, volume e peso foram calculadas como porcentagens. As patas fixadas com fórmalina foram usadas para exame histopatológico. Detectamos que o TCAE aplicado s.c. em doses de 10µg/kg e 100µg/kg resultou em menor espessura da pata, menor volume da pata e menor peso da pata quatro horas após a indução da inflamação quando comparado com o grupo INDO (p<0,05). O efeito inibidor do edema da pata de TCAE aplicado na dose de 10µg/kg, s.c. foi de 68% quando comparado com o INDO que teve um efeito inibidor de 56%. Estes resultados foram verificados com resultados histopatológicos semelhantes. A característica anti-inflamatória de 10µg/kg de TCAE dada sistematicamente foi semelhante aos efeitos do INDO. Nossos resultados sugerem que o TCAE tem efeitos anti-inflamatórios reduzindo o edema e diminuindo a reação inflamatória. Estes resultados podem ser atribuídos à inibição da produção de mediadores pró-inflamatórios. Assim, o TCAE pode ser considerado como um agente antiinflamatório potencial para o tratamento de condições inflamatórias agudas.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats

Purpose: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. Methods: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. Results: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. Conclusions: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Abstract Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.

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)

Once upon a time, inflammation

Inflammation has accompanied humans since their first ancestors appeared on Earth. Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: "Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore", defining the four cardinal signs of inflammation as redness and swelling with heat and pain. While inflammation has long been considered as a morbid phenomenon, John Hunter (18th century) and Elie Metchnikoff (19th century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult. Many other famous scientists and some forgotten ones have identified the different cellular and molecular players, and deciphered the different mechanisms of inflammation. This review pays tribute to some of the giants who made major contributions, from Hippocrates to the late 19th and first half of the 20th century. We particularly address the discoveries related to phagocytes, diapedesis, chemotactism, and fever. We also mention the findings of the various inflammatory mediators and the different approaches designed to treat inflammatory disorders.(AU)

Once upon a time, inflammation

Inflammation has accompanied humans since their first ancestors appeared on Earth. Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: "Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore", defining the four cardinal signs of inflammation as redness and swelling with heat and pain. While inflammation has long been considered as a morbid phenomenon, John Hunter (18th century) and Elie Metchnikoff (19th century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult. Many other famous scientists and some forgotten ones have identified the different cellular and molecular players, and deciphered the different mechanisms of inflammation. This review pays tribute to some of the giants who made major contributions, from Hippocrates to the late 19th and first half of the 20th century. We particularly address the discoveries related to phagocytes, diapedesis, chemotactism, and fever. We also mention the findings of the various inflammatory mediators and the different approaches designed to treat inflammatory disorders.(AU)

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.(AU)

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.(AU)

Probiotic Lactobacilli Improved Growth Performance and Attenuated Salmonella Typhimurium Infection Via Jak/Stat Signaling in Broilers

This study aimed to investigate the effect of Lactobacillus plantarum DPP8 and Lactobacillus acidophilus C7282 in feed supplementation on growth performance, Salmonella invasion, inflammation, and mediating signaling in broilers infected with Salmonella Typhimurium (S. Typhimurium). A total of 240 broilers at day old were randomly allocated into four groups, orally infected with S. Typhimurium and supplemented with individual or combined Lactobacilli DPP8 and C7282 at doses of 0 (control), 1010 (individual), or 2.0 × 1010 (combination) cfu/kg of diet for 21 d. The results showed that supplementing Lactobacilli improved (p 0.05) feed intake and body weight gain and decreased (p 0.05) S. Typhimurium load in the caecum, harder gland, spleen and bursa of Fabricius. Also, the supplements decreased (p 0.05) interleukin (1/2/4), tumor necrosis factor and interferon in the serum, enhanced (p 0.05) interleukin 10, and downregulated gene expressions of inflammatory mediators including Janus kinase (Jak2/3), signal transducer and activator of transcription protein (STAT3/4/5/6) in the intestinal mucosa. In contrast, diets containing DPP8 exhibited greater effects on the inhibition of the pathogen and inflammatory response than C7282. The obtained data suggest that Lactobacilli C7282 and DPP8 can be used as feed additives to inhibit colonization and translocation of S. Typhimurium and inflammatory responses via downregulating Jak/STAT signaling in broilers.(AU)

Probiotic Lactobacilli Improved Growth Performance and Attenuated Salmonella Typhimurium Infection Via Jak/Stat Signaling in Broilers

This study aimed to investigate the effect of Lactobacillus plantarum DPP8 and Lactobacillus acidophilus C7282 in feed supplementation on growth performance, Salmonella invasion, inflammation, and mediating signaling in broilers infected with Salmonella Typhimurium (S. Typhimurium). A total of 240 broilers at day old were randomly allocated into four groups, orally infected with S. Typhimurium and supplemented with individual or combined Lactobacilli DPP8 and C7282 at doses of 0 (control), 1010 (individual), or 2.0 × 1010 (combination) cfu/kg of diet for 21 d. The results showed that supplementing Lactobacilli improved (p 0.05) feed intake and body weight gain and decreased (p 0.05) S. Typhimurium load in the caecum, harder gland, spleen and bursa of Fabricius. Also, the supplements decreased (p 0.05) interleukin (1/2/4), tumor necrosis factor and interferon in the serum, enhanced (p 0.05) interleukin 10, and downregulated gene expressions of inflammatory mediators including Janus kinase (Jak2/3), signal transducer and activator of transcription protein (STAT3/4/5/6) in the intestinal mucosa. In contrast, diets containing DPP8 exhibited greater effects on the inhibition of the pathogen and inflammatory response than C7282. The obtained data suggest that Lactobacilli C7282 and DPP8 can be used as feed additives to inhibit colonization and translocation of S. Typhimurium and inflammatory responses via downregulating Jak/STAT signaling in broilers.

Leukocytes and albumin in canine leishmaniasis

Canine Leishmaniasis (CanL) is a multisystemic and chronic inflammatory disease characterized by nonspecific clinical manifestations. In CanL, inflammatory cells and chemical mediators released in response to the parasite play a role in disease development and progression. Alterations on hematological parameters have been documented in CanL. These changes can also be assessed in relation to systemic inflammation caused by this disease. The circulating leukocyte counting, such as neutrophils, as well as the albumin level, are considered direct indicators of an inflammatory host environment. Several studies point to the use of biomarkers on the assistance in diagnosis and prognosis of several canine pathologies. The present study investigated the Neutrophils to Lymphocyte Ratio (NLR), Albumin to Globulin Ratio (AGR), and Neutrophils to Albumin Ratio (NAR) on systemic inflammatory response induced by Canine Leishmaniasis (CanL). For this purpose, adult dogs with confirmed diagnosis to CanL were divided into symptomatic (SD, n = 33) and asymptomatic (AD, n = 20) dogs for L. infantum and control dogs (CD, n = 20). Routine hematological and biochemical parameters were determined in blood samples using a veterinary automatic hematology and biochemical analyzers. Asymptomatic dogs (AD) had a higher number of white blood cells and neutrophils (16.48 ± 4.93; 13.41 ± 3.60, respectively) in relation to symptomatic dogs (SD) (13.54 ± 5.13; 10.42 ± 3.69, respectively) (P = 0.015 and P < 0.0001, respectively). Neutrophils to Lymphocyte Ratio (NLR) was higher in dogs with leishmaniasis (9.45 ± 3.76) than in healthy dogs (3.39 ± 1.19) (P < 0.0001). Serum total proteins (STP) and globulins increased in CanL, while albumin and AGR decreased in CanL, when compared to CD and references values to canine species. Neutrophils to Albumin Ratio (NAR) was higher in AD and SD (5.02 ± 1.14; 4.79 ± 1.07, respectively) when compared to CD (2.36 ± 0.55) (P < 0.0001). As reported in scientific researches, dogs with Leishmaniasis present alterations in circulating cell counts. Based on these data, we decided to expand this information using the NLR as a parameter in an attempt to better clarify the changes in these cells in CanL. We observed that NLR was increased on CanL in relation to healthy dogs, which could be a consequence of relative neutrophilia rather than lymphopenia. Neutrophils to Lymphocyte Ratio (NLR) is a biomarker that conveys information about inflammatory conditions. An elevated NLR can reflect an upregulated innate immune response, since neutrophils are effector cells of innate immunity and are involved in several acute and chronic inflammatory processes. Albumin is an acute phase protein that is considered an immune-inflammatory biomarker, which can be found reduced systemically in progressive inflammatory response. Serum total proteins (STP) and globulins were increased in CanL. These data are already well documented in CanL, which serum globulins are mainly associated with the increase of acute phase proteins, cytokines, and increase of specific antibodies to Leishmania infantum. Our results showed neutrophilia with hypoalbuminemia in CanL. So, in an attempt to assess the relationship of these two available markers, we used NAR calculation in order to evaluate the changes induced by CanL. In this study NAR was higher in CanL when compared to control dogs. Thus, our data indicate that NLR and NAR could be used as biomarkers in veterinary medical clinics in order to assess inflammatory profile in CanL, mainly in asymptomatic dogs. These parameters obtained from routine blood tests might be useful as cost-effective, easily accessible and helpful markers in order to distinguish the inflammatory response intensity in CanL.(AU)

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA+ e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA+.(AU)

The goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA+ cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA+ cells.(AU)

Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA+ e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA+.(AU)

The goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA+ cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA+ cells.(AU)

Effect of Bitis gabonica and Dendroaspis angusticeps snake venoms on apoptosis-related genes in human thymic epithelial cells

Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from Bitis gabonica and Dendroaspis angusticeps. Methods: Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 μg/mL (as used in previous TaqMan Array study). Gene expressional changes restricted to apoptosis were assayed by TaqMan Array (Human Apoptosis Plate). Results: The most prominent gene expressional changes were shown by CASP5 (≈ 2.5 million-fold, confirmed by dedicated quantitative polymerase chain reaction) and CARD9 (0.016-fold) for B. gabonica, and BIRC7 (6.46-fold) and CASP1 (0.30-fold) for D. angusticeps. Conclusion: The observed apoptotic environment suggests that pyroptosis may be the dominant pathway through which B. gabonica and D. angusticeps snake venoms trigger thymic epithelial apoptosis following envenomation.(AU)

Effect of Bitis gabonica and Dendroaspis angusticeps snake venoms on apoptosis-related genes in human thymic epithelial cells

Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from Bitis gabonica and Dendroaspis angusticeps. Methods: Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 μg/mL (as used in previous TaqMan Array study). Gene expressional changes restricted to apoptosis were assayed by TaqMan Array (Human Apoptosis Plate). Results: The most prominent gene expressional changes were shown by CASP5 (≈ 2.5 million-fold, confirmed by dedicated quantitative polymerase chain reaction) and CARD9 (0.016-fold) for B. gabonica, and BIRC7 (6.46-fold) and CASP1 (0.30-fold) for D. angusticeps. Conclusion: The observed apoptotic environment suggests that pyroptosis may be the dominant pathway through which B. gabonica and D. angusticeps snake venoms trigger thymic epithelial apoptosis following envenomation.(AU)

Tromboflebite jugular em equinos submetidos à laparotomia para o tratamento de afecção gastrointestinal

ABSTRACT: Coagulation abnormalities are usually associated with equine gastrointestinal disease due to the increased levels of inflammatory mediators, which promotes hemostasis and inhibit fibrinolysis, creating a hypercoagulable state. Horses underwent laparotomy to treat colic usually require a venous catheter for several days to administrate fluids and drugs during the postoperative period, and the jugular vein is the most frequent site for catheterization. Therefore, the persistent vascular trauma caused by an implanted catheter, associated with the prothrombotic environment induced by the gastrointestinal disorder, increases the risk for the development of jugular thrombophlebitis. The purpose of the present investigation was to evaluate physical and ultrassonographic features of the jugular vein cannulated with a polyurethane catheter during the postoperative period of horses underwent colic surgery. The catheter was inserted aseptically on admission and dwell time was seven days. Upon ultrasound examination, one horse developed thrombophlebitis 48 hours after surgery and the other horses showed thickened venous wall at puncture site and small clots associated to the catheter. Ultrasound monitoration showed that long-term catheterization in horses underwent colic surgery following the present protocol minimizes vascular trauma and could prevent jugular thrombophlebitis.

RESUMO: Afecções do trato gastrointestinal de equinos podem causar distúrbios de coagulação devido à concentração elevada de mediadores inflamatórios que estimulam a hemostasia e inibem a fibrinólise, gerando um estado de hipercoagulação. Equinos submetidos à laparotomia no tratamento da síndrome cólica permanecem com cateter venoso durante vários dias para a administração de fluidos e fármacos no período pós-operatório e, a veia jugular é o principal local para a implantação de cateteres. Assim, o trauma vascular persistente causado pelo cateter, associado ao ambiente pró-trombótico induzido pela afecção gastrointestinal, aumenta o risco para o desenvolvimento de tromboflebite jugular. Objetivou-se avaliar as características físicas e ultrassonográficas da veia jugular canulada com cateter de poliuretano durante o período pós-operatório de equinos submetidos à laparotomia. O cateter foi inserido de forma asséptica à admissão e permaneceu por sete dias. A avaliação ultrassonográfica revelou o desenvolvimento de tromboflebite em um equino, 48 após o procedimento cirúrgico. Os demais equinos demonstraram espessamento da parede vascular no local de punção e pequenos trombos junto ao cateter. A monitoração ultrassonográfica demonstrou que a cateterização prolongada em equinos submetidos à laparotomia, seguindo o protocolo proposto, minimiza a lesão vascular e pode prevenir a tromboflebite jugular.

Effects of Brazilian scorpion venoms on the central nervous system

In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus, T. bahiensis, T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus, T. silvestres, T. brazilae, T. confluens, T. costatus, T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis. Little information is available regarding the other Brazilian Tityus species.(AU)