ESBL in positive hemoculture of a Southern-Brazil Teaching Hospital's Intensive Care Units / ESBL em hemoculturas positivas das Unidades de Terapia Intensiva de um Hospital Universitário do sul do Brasil

Bloodstream infections are among the most serious and frequent infections, and the people most exposed are patients in the Intensive Care Unit (ICU). ESBL (extended-spectrum beta-lactate) are resistant bacteria to penicillins, cephalosporins and monobactams. It´s necessary to know how often and which microorganisms are involved, checking their susceptibility. This study was carried out at the University Hospital. Data collection was performed in the Adult and Newborn ICUs, with assessment of microorganisms and their resistance profile. During six-month period, 156 samples were studied, and 42 were positive with microorganism isolation. Isolated species include Staphylococcus aureus, Staphylococcus epidermidis and Klebsiella pneumoniae. Many resistant to carbapenem.

ESBL in Positive Hemoculture of a Southern-Brazil Teaching Hospital's Intensive Care Units As infecções da corrente sanguínea estão entre as infecções mais graves e frequentes, e os indivíduos mais expostos são os pacientes da Unidade de Terapia Intensiva (UTI). As ESBL (Beta-Lactamase de Espectro Estendido) são bactérias resistentes a penicilinas, cefalosporinas e monobactâmicos. Se faz necessário saber com que frequência e quais microrganismos estão envolvidos, verificando sua suscetibilidade. Este estudo foi realizado no Hospital Universitário. A coleta de dados foi realizada nas UTIs Adulto e Neonatal, com avaliação dos microrganismos e seu perfil de resistência. Durante o período de seis meses, foram estudadas 156 amostras, sendo 42 positivas com isolamento dos microrganismos. As espécies isoladas incluem Staphylococcus aureus, Staphylococcus epidermidis e Klebsiella pneumoniae. Muitos resistentes aos carbapenêmicos.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Salmonelose em bezerros pelo sorovar Dublin no estado do Paraná, Brasil - aspectos clínico-patológicos / Salmonellosis in calves by serovar Dublin in Paraná State, Brazil - clinicopathological aspects

Background: Calf diarrhea remains one of the main diseases affecting the cattle industry. Persistence of this significant problem is associated with the complexity of factors that may be involved (infectious, environmental). An accurate diagnosis is essential for confirming the cause and helping clinicians and cattle producers to apply appropriate strategies in a timely manner. This report describes the histological changes according to the degree of salmonellosis severity, which is a contagious infectious disease caused by Salmonella enterica subsp. enterica, a Gram-negative bacterium, in two beef calves in northern Paraná State, southern Brazil. Cases: Two 90-day-old crossbred Angus and Nellore calves from a beef farm in northern Paraná State were referred to a Veterinary Hospital. Animal 1- developed acute clinical signs (enteritis, ataxia, and muscle rigidity) and died the day after the signs began. Gross findings included heavy and non-collapsed lungs, pulmonary oedema, hepatomegaly, enteritis, and severe diffuse typhlitis. Microscopic analysis revealed severe diffuse necrotic enteritis, typhlitis, severe diffuse interstitial pneumonia, moderate centrilobular hepatic necrosis, mild multifocal nephritis, and severe spleen and lymph node necrosis. Paratyphoid nodules were evidenced on the liver, spleen, and mesenteric lymph nodes. Animal 2- presented apathy, green fibrinous diarrhea, and died three days after the onset of clinical signs. The macroscopic examination showed moderate diffuse enteritis and hepatosplenomegaly. At the microscopic examination, many paratyphoid nodules were observed on the liver, spleen, kidneys, and Peyer's patches, which were associated with intralesional and intravascular bacilli. Additional findings included severe diffuse fibrinous necrotic enteritis with intralesional bacilli, diffuse interstitial pneumonia, multifocal splenic necrosis, lymphoid depletion, and moderate multifocal to coalescent lymphocytic nephritis. Histological Gram staining was performed on selected samples, revealing intralesional Gram-negative bacilli in the liver and intestine. Thus, liver and intestine fragments were used for the microbiological examination. Microbiological culture, isolation and biochemical tests identified the genus Salmonella spp. Then, the colonies were subjected to serological tests for serovar identification, according to ISO/TR 6579-3, which determined the serovar Dublin. After identifying the disease etiological agent, the outbreak was controlled by appropriate antibiotic therapy combined with the correction of sanitary measures. Discussion: Enteritis is a frequent disease in calves, posing a diagnostic challenge in identifying the etiological agent. In the present case, the histological, microbiological, and serological results confirmed a disseminated Salmonella spp. infection. The microscopic findings, such as interstitial pneumonia, fibrinous necrotic enteritis markedly in ileum and paratyphoid nodules in various organs, are the most common aspects of the disease. However, fibrinous cholecystitis, which is considered pathognomonic for salmonellosis, was not observed in this study. Therefore, the absence of such a lesion should not exclude the disease in sick animals. A microscopic injury score was used to determine lesion severity by assigning values from 1 to 4, wherein: 1 = no apparent lesions, 2 = mild lesions, 3 = moderate lesions, and 4 = severe lesions. Both calves were scored as 4. Multiple predisposing factors for the condition were identified in this farm such as different age animals in the same paddock and no specific paddock for sick animals, given that the infectious agent remains in feces, saliva, and nasal discharge. The serovar Dublin induces several clinical signs such as septicemic, respiratory, and enteric manifestations, making a clinical diagnosis a challenge

Sepsis due to Yersinia enterocolitica in an aborted equine fetus: case report / Sepse por Yersinia enterocolitica em um feto equino abortado: relato de caso

Yersinia enterocolitica is a bacterium with zoonotic potential and there are no previous records of this bacteria being isolated from aborted foals. This report aims to describe a case of sepsis due to Y. enterocolitica in a seven month old aborted equine. The fequinoetus was submitted to necropsy and samples of all the organs were collected for the histological exam. Samples of liver, lung, placenta, and stomach contents were collected for bacterial culture. Macroscopically, the liver was enlarged with yellowish heterogeneous color, heart with pale myocardial areas; lungs not collapsed, heavy and shiny, thickened umbilical cord covered with fibrin and pus. Histopathologically, there was moderate multifocal necrosuppurative myocarditis and thrombosis, moderate diffuse suppurative bronchopneumonia, mild multifocal fibrinonecrotic hepatitis, and moderate diffuse necrosuppurative omphalitis with intralesional bacterial myriads and thrombosis. Mild multifocal suppurative placentitis, nephritis, myositis, cystitis, and dermatitis were also observed, in addition to mild diffuse lymphoid rarefaction. The microbiological evaluation identified Y. enterocolitica in the liver, lung, and stomach fluid. This is the first report of sepsis due to Y. enterocolitica causing an abortion in a horse. This bacterium has zoonotic importance; therefore, it should be investigated in abortion in this species, serving as a differential diagnosis in reproductive disorders.(AU)

Yersinia enterocolitica é uma bactéria com potencial zoonótico, e não há informações desse agente como causa de abortamento em equinos. O objetivo deste relato é descrever um caso de sepse por Y. enterocolitica em um feto equino abortado aos sete meses. O feto foi submetido à necropsia, e amostras de todos os órgãos foram processadas para histopatologia. Para microbiologia, foram coletadas amostras de fígado, pulmão, placenta e conteúdo estomacal. Macroscopicamente, observou-se fígado aumentado com coloração amarelada heterogênea; coração com áreas pálidas no miocárdio; pulmões não colabados, pesados e brilhantes; e cordão umbilical espessado e recoberto por fibrina e pus. Na análise histopatológica, havia miocardite necrossupurativa multifocal moderada e trombose, broncopneumonia supurativa difusa moderada, hepatite fibrinonecrótica multifocal discreta e onfalite necrossupurativa difusa moderada com miríades bacterianas intralesionais e trombose. Observou-se também placentite, nefrite, miosite, cistite e dermatite supurativa multifocal discreta, além de rarefação linfoide difusa discreta. A avaliação microbiológica identificou Y. enterocolitica no fígado, no pulmão e no líquido estomacal. Este é o primeiro relato de sepse por Y. enterocolitica causando abortamento na espécie equina. Essa bactéria tem importância zoonótica, portanto deve ser investigada em casos de abortamento nessa espécie, servindo como diagnóstico diferencial em tal distúrbio reprodutivo.(AU)

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Effect of IL-33 on pyroptosis of macrophages in mice with sepsis via NF-κB/p38 MAPK signaling pathway

ABSTRACT Purpose To demonstrate the effect of IL-33 on the macrophage pyroptosis in mice with sepsis through the NF-kB/p38 MAPK signal pathway. Methods In total, 24 C57BL/6 mice were divided into the sham operation group (sham) and the cecal ligation and puncture group (CLP). After CLP, 24 IL-33-/- mice were divided into the IL-33-/- group and the IL-33-/- intervention group. The latter group was intraperitoneally injected with IL-33. Mouse mortality was observed after CLP. Macrophage apoptosis in peritoneal lavage fluid was detected by flow cytometry. Serum inflammatory factor level was detected by ELISA. Apoptotic protein expression and NF-κB/p38 MAKP signaling pathway protein expression were detected by qRT-PCR and Western blot. Results Knocking out IL-33 significantly reduced the mortality of CLP mice, as well as the mRNA expression of IL-33 and the levels of serum inflammatory factors, including IL-33, IL-1β, and IL-18. It also reduced the rate of macrophage apoptosis and the expression of the apoptotic protein caspase-1 p10; increased the expression of IκBα; and reduced the protein expression of NF-κB and p38 MAPK. These effects were reversed after exogenous injection of IL-33. Conclusions IL-33 can increase the level of macrophage pyroptosis in mice with sepsis (by activating the NF-kB/p38MAPK signal pathway) and the mortality of these mice.

Beneficial role of oleuropein in sepsis-induced myocardial injury: possible involvement of GSK-3beta/NF-kB pathway

Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3beta/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3beta, p-GSK-3beta (Ser9) and nuclear factor-B (NF-B) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3beta/GSK-3beta and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3beta/GSK-3beta and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3beta signaling.(AU)

Clinical and microbiological characteristics of dogs in sepsis in an academic veterinary hospital in the north of Paraná / Características clínicas e microbiológicas de cães em sepse de um hospital veterinário escola do norte do Paraná

Sepsis is a life-threatening organ dysfunction caused by a patient's unregulated response to an infectious process. In veterinary medicine, the exact incidence of sepsis is unknown. Early recognition of sepsis in critically ill patients is essential for rapid and effective therapeutic intervention. The present study aimed to apply the criteria of an adapted sepsis assessment protocol based on the Second International Consensus Definition for Sepsis and Septic Shock or Sepsis-2 of human medicine, in canine patients with suspected systemic inflammatory response syndrome (SIRS) and/or organ dysfunction, and to identify infectious agents as well as their antimicrobial resistance profile in the focus of infection, in the bloodstream and colonizing the rectal mucosa. Patients were evaluated for survival and severity of sepsis. Of the 37/42 dogs that met the sepsis criteria, six presented septic shock, 26 (70.2%) had at least two signs of SIRS, and sepsis with organ dysfunction was diagnosed in 27 (73%) dogs. The primary dysfunctions observed were decreased level of consciousness in 21/37 (56.8%), hyperlactatemia in 19/37 (51.4%), and hypoalbuminemia in 18/37 (48.6%). Two or more SIRS signs associated with hypotension and hypoalbuminemia were related to more than half of the deaths. The most frequent infectious focus was skin and soft tissue in 20/37 (54%), followed by organs and cavities in 8/37 (21.6%). The survival rate was 56.7%. Blood culture confirmed bacteremia in nine patients (24.3%), with a predominance of Gram-positive microorganisms (Staphylococcus intermedius, Streptococcus spp.) in 66.6% of dogs and one yeast (Candida glabrata). The most frequent bacteria in the focus of infection were gram-negative bacteria (46.2%), mainly Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, in 19.5%, 14.6%, and 12.1%, respectively. We observed colonization by gram-negative bacteria such as E. coli-ESBL (31.5%), K. pneumoniae-ESBL (15.7%), and P. aeruginosa (15.7%), and the presence of ESBL bacteria was more associated with death when compared with other microorganisms. Vancomycin-resistant Enterococcus (VRE) were isolated from rectal mucosa in four dogs. Gram-negative microorganisms were the most frequent in both infections and colonization, and most of them were resistant to fluoroquinolones, sulfonamides, tetracyclines, and cephalosporins. Based on this information, it can be concluded that mortality due to sepsis in dogs was high. Due to the presence of multi-resistant bacteria, the use of antimicrobials should be judicious, suggesting the implementation of the same precautions used in human hospitals to prevent the spread of multi-resistant microorganisms.(AU)

A sepse é uma disfunção orgânica ameaçadora à vida, causada por uma resposta desregulada do hospedeiro à infecção e na medicina veterinária sua incidência exata é desconhecida. O reconhecimento precoce da sepse nos pacientes críticos é essencial para que a intervenção terapêutica seja rápida e eficaz. Assim, os objetivos do presente estudo foram aplicar os critérios de um protocolo de avaliação da sepse adaptado com base no Segundo Consenso Internacional para Sepse e Choque Séptico, ou Sepse-2, da medicina humana, em pacientes caninos com suspeita de infecção e/ou Síndrome da Resposta Inflamatória Sistêmica e/ou disfunção orgânica e identificar os agentes infecciosos bem como seu perfil de resistência a antimicrobianos no foco de infecção, na corrente sanguínea e colonizando a mucosa retal. Os pacientes foram avaliados quanto à sobrevivência e severidade da sepse. Dos 37/42 cães que se enquadraram nos critérios de sepse, seis estavam em choque séptico, 26 (70,2%) apresentaram pelo menos dois sinais de SIRS, e a sepse com disfunção orgânica foi diagnosticada em 27 (73%) cães. As principais disfunções verificadas foram diminuição do nível de consciência em 21/37 (56,8%), hiperlactatemia em 19/37 (51,4%) e hipoalbuminemia em 18/37 (48,6%). A presença de dois ou mais sinais de SIRS associados com hipotensão e hipoalbuminemia estiveram relacionadas com mais da metade dos óbitos. O foco infeccioso mais frequente foi pele e partes moles em 20/37 (54%) seguido por órgãos e cavidades em 8/37 (21,6%). A taxa de sobrevivência foi de 56,7%. Na hemocultura confirmou-se bacteremia em nove pacientes (24,3%), com predominância de microrganismos gram-positivos (Staphylococcus intermedius, Streptococcus spp.) em 66,6% dos cães e uma levedura (Candida glabrata). As bactérias mais frequentes no foco de infecção foram as gram-negativas (46,2%) principalmente Escherichia coli, Klebsiella pneumoniae e Pseudomonas aeruginosa, em 19,5%, 14,6% e 12,1% respectivamente. Foi constatada colonização por bactérias gram-negativas como E. coli-ESBL (31,5%), K. pneumoniae-ESBL (15,7%) e P. aeruginosa (15,7%), sendo que a colonização de cães por bactérias ESBL foi associada ao óbito quando comparada com outros microrganismos. Foram também isolados da mucosa retal Enterococcus resistentes à vancomicina (VRE) em quatro cães. Os microrganismos gram-negativos foram os mais frequentes, tanto nas infecções quanto nas colonizações e a maioria apresentava resistência à fluorquinolonas, sulfonamidas, tetraciclinas e cefalosporinas. Com base nestas informações, conclui-se que a mortalidade em decorrência da sepse em cães foi alta, e devido à presença de bactérias multirresistentes, o uso de antimicrobianos deve ser criterioso, sugerindo-se ainda a implantação das mesmas precauções utilizadas em hospitais humanos para evitar disseminação de microrganismos multirresistentes.(AU)

Clinical and microbiological characteristics of dogs in sepsis in an academic veterinary hospital in the north of Paraná / Características clínicas e microbiológicas de cães em sepse de um hospital veterinário escola do norte do Paraná

Sepsis is a life-threatening organ dysfunction caused by a patient's unregulated response to an infectious process. In veterinary medicine, the exact incidence of sepsis is unknown. Early recognition of sepsis in critically ill patients is essential for rapid and effective therapeutic intervention. The present study aimed to apply the criteria of an adapted sepsis assessment protocol based on the Second International Consensus Definition for Sepsis and Septic Shock or Sepsis-2 of human medicine, in canine patients with suspected systemic inflammatory response syndrome (SIRS) and/or organ dysfunction, and to identify infectious agents as well as their antimicrobial resistance profile in the focus of infection, in the bloodstream and colonizing the rectal mucosa. Patients were evaluated for survival and severity of sepsis. Of the 37/42 dogs that met the sepsis criteria, six presented septic shock, 26 (70.2%) had at least two signs of SIRS, and sepsis with organ dysfunction was diagnosed in 27 (73%) dogs. The primary dysfunctions observed were decreased level of consciousness in 21/37 (56.8%), hyperlactatemia in 19/37 (51.4%), and hypoalbuminemia in 18/37 (48.6%). Two or more SIRS signs associated with hypotension and hypoalbuminemia were related to more than half of the deaths. The most frequent infectious focus was skin and soft tissue in 20/37 (54%), followed by organs and cavities in 8/37 (21.6%). The survival rate was 56.7%. Blood culture confirmed bacteremia in nine patients (24.3%), with a predominance of Gram-positive microorganisms (Staphylococcus intermedius, Streptococcus spp.) in 66.6% of dogs and one yeast (Candida glabrata). The most frequent bacteria in the focus of infection were gram-negative bacteria (46.2%), mainly Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, in 19.5%, 14.6%, and 12.1%, respectively. We observed colonization by gram-negative bacteria such as E. coli-ESBL (31.5%), K. pneumoniae-ESBL (15.7%), and P. aeruginosa (15.7%), and the presence of ESBL bacteria was more associated with death when compared with other microorganisms. Vancomycin-resistant Enterococcus (VRE) were isolated from rectal mucosa in four dogs. Gram-negative microorganisms were the most frequent in both infections and colonization, and most of them were resistant to fluoroquinolones, sulfonamides, tetracyclines, and cephalosporins. Based on this information, it can be concluded that mortality due to sepsis in dogs was high. Due to the presence of multi-resistant bacteria, the use of antimicrobials should be judicious, suggesting the implementation of the same precautions used in human hospitals to prevent the spread of multi-resistant microorganisms.(AU)

A sepse é uma disfunção orgânica ameaçadora à vida, causada por uma resposta desregulada do hospedeiro à infecção e na medicina veterinária sua incidência exata é desconhecida. O reconhecimento precoce da sepse nos pacientes críticos é essencial para que a intervenção terapêutica seja rápida e eficaz. Assim, os objetivos do presente estudo foram aplicar os critérios de um protocolo de avaliação da sepse adaptado com base no Segundo Consenso Internacional para Sepse e Choque Séptico, ou Sepse-2, da medicina humana, em pacientes caninos com suspeita de infecção e/ou Síndrome da Resposta Inflamatória Sistêmica e/ou disfunção orgânica e identificar os agentes infecciosos bem como seu perfil de resistência a antimicrobianos no foco de infecção, na corrente sanguínea e colonizando a mucosa retal. Os pacientes foram avaliados quanto à sobrevivência e severidade da sepse. Dos 37/42 cães que se enquadraram nos critérios de sepse, seis estavam em choque séptico, 26 (70,2%) apresentaram pelo menos dois sinais de SIRS, e a sepse com disfunção orgânica foi diagnosticada em 27 (73%) cães. As principais disfunções verificadas foram diminuição do nível de consciência em 21/37 (56,8%), hiperlactatemia em 19/37 (51,4%) e hipoalbuminemia em 18/37 (48,6%). A presença de dois ou mais sinais de SIRS associados com hipotensão e hipoalbuminemia estiveram relacionadas com mais da metade dos óbitos. O foco infeccioso mais frequente foi pele e partes moles em 20/37 (54%) seguido por órgãos e cavidades em 8/37 (21,6%). A taxa de sobrevivência foi de 56,7%. Na hemocultura confirmou-se bacteremia em nove pacientes (24,3%), com predominância de microrganismos gram-positivos (Staphylococcus intermedius, Streptococcus spp.) em 66,6% dos cães e uma levedura (Candida glabrata). As bactérias mais frequentes no foco de infecção foram as gram-negativas (46,2%) principalmente Escherichia coli, Klebsiella pneumoniae e Pseudomonas aeruginosa, em 19,5%, 14,6% e 12,1% respectivamente. Foi constatada colonização por bactérias gram-negativas como E. coli-ESBL (31,5%), K. pneumoniae-ESBL (15,7%) e P. aeruginosa (15,7%), sendo que a colonização de cães por bactérias ESBL foi associada ao óbito quando comparada com outros microrganismos. Foram também isolados da mucosa retal Enterococcus resistentes à vancomicina (VRE) em quatro cães. Os microrganismos gram-negativos foram os mais frequentes, tanto nas infecções quanto nas colonizações e a maioria apresentava resistência à fluorquinolonas, sulfonamidas, tetraciclinas e cefalosporinas. Com base nestas informações, conclui-se que a mortalidade em decorrência da sepse em cães foi alta, e devido à presença de bactérias multirresistentes, o uso de antimicrobianos deve ser criterioso, sugerindo-se ainda a implantação das mesmas precauções utilizadas em hospitais humanos para evitar disseminação de microrganismos multirresistentes.(AU)

Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH / Avaliação da função adrenal em cães portadores de doenças críticas com baixa dose de ACTH sintético

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0µg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.(AU)

A função do eixo hipotálamo-hipófise-adrenal pode estar comprometida em pacientes com doenças críticas, em especial casos de sepse, sendo nomeada de Insuficiência Corticosteroide Relacionada à Doença Crítica (ICRDC). O presente trabalho analisou a função do eixo hipotálamo-hipófise-adrenal em cães normais (n=10) e cães portadores de doenças críticas (n=16), por meio de determinações de ACTH (hormônio adrenocorticotrófico) endógeno, de cortisol basal e de cortisol após estímulo com baixa dose de ACTH sintético (1,0µg/kg/IV). Constatou-se que o teste de estimulação com ACTH na dose testada se mostrou eficaz para avaliação da função adrenal em cães sadios e doentes. Os cães doentes diferiram dos sadios ao apresentar valores maiores de cortisol basal. Oito cães doentes apresentaram diminuição do ACTH endógeno, do cortisol basal ou do Δ-cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para os valores de ACTH endógeno, cortisol após estimulação ou Δ-cortisol. Concluiu-se que o teste de estimulação com baixa dose de ACTH mostrou-se eficaz para avaliação da função adrenal, assim como, uma parcela considerável da população de cães críticos aqui estudados, em especial com sepse, apresentaram evidências de resposta corticosteroide inadequada frente ao estresse.(AU)

Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH / Avaliação da função adrenal em cães portadores de doenças críticas com baixa dose de ACTH sintético

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0µg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.(AU)

A função do eixo hipotálamo-hipófise-adrenal pode estar comprometida em pacientes com doenças críticas, em especial casos de sepse, sendo nomeada de Insuficiência Corticosteroide Relacionada à Doença Crítica (ICRDC). O presente trabalho analisou a função do eixo hipotálamo-hipófise-adrenal em cães normais (n=10) e cães portadores de doenças críticas (n=16), por meio de determinações de ACTH (hormônio adrenocorticotrófico) endógeno, de cortisol basal e de cortisol após estímulo com baixa dose de ACTH sintético (1,0µg/kg/IV). Constatou-se que o teste de estimulação com ACTH na dose testada se mostrou eficaz para avaliação da função adrenal em cães sadios e doentes. Os cães doentes diferiram dos sadios ao apresentar valores maiores de cortisol basal. Oito cães doentes apresentaram diminuição do ACTH endógeno, do cortisol basal ou do Δ-cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para os valores de ACTH endógeno, cortisol após estimulação ou Δ-cortisol. Concluiu-se que o teste de estimulação com baixa dose de ACTH mostrou-se eficaz para avaliação da função adrenal, assim como, uma parcela considerável da população de cães críticos aqui estudados, em especial com sepse, apresentaram evidências de resposta corticosteroide inadequada frente ao estresse.(AU)

Disfunção miocárdica secundária a sepse em cão: relato de caso / Myocardial dysfunction secondary to sepsis in dog: case report

A redução do empenho do miocárdio é um achado frequente em casos de sepse ou choque séptico, sendo a piometra uma das principais causas de sepse em cães. No presente trabalho relata-se um caso de sepse secundária à piometra levando à disfunção miocárdica em um canino, fêmea, da raça White West Highland Terrier, de dez anos de idade com histórico de prostração e hiporexia. Ao exame físico foi observada presença de secreção vulvar purulenta, abdômen abaulado e tenso à palpação. Foram realizados exames complementares, incluindo hemograma com resultado compatível com quadro infeccioso, bioquímica revelando hipocalemia e hipocalcemia, e exames de imagem. Observou-se por meio do exame ultrassonográfico presença de grande quantidade de líquido com celularidade em cornos e corpo uterino, compatível com piometra. Alterações compatíveis com sepse foram observadas durante o atendimento e estabilização do animal. No exame ecocardiográfico foi observado aumento dos diâmetros sistólico e diastólico do ventrículo esquerdo com diminuição da fração de encurtamento e ejeção, compatível com disfunção sistólica do ventrículo esquerdo. A referida paciente recebeu alta médica após correção cirúrgica e estabilização dos parâmetros clínicos, incluindo a disfunção sistólica, sendo relatado óbito sete dias após. Sugere-se que a causa mortis tenha sido a disfunção sistólica causada pela sepse. Conclui-se que a disfunção miocárdica é um fator determinante de prognóstico em casos de sepse, o que ressalta a importância de seu diagnóstico e tratamento precoce.

The reduction of myocardial commitment is a frequent finding in cases of sepsis or septic shock, and piometra is one of the main causes of sepsis in dogs. In the present study, the case of sepsis secondary to piometra is reported leading to myocardial dysfunction in a canine, female, of the 10-year-old White West Highland Terrier with a history of prostration and hyporexia. On physical examination, the presence of purulent vulvar secretion, bulging abdomen and taut palpation was observed. Complementary tests were performed, including blood count, biochemistry and imaging tests. It was observed through ultrasound examination the presence of a large amount of fluid with cellularity in horns and uterine body, compatible with piometra. Alterations compatible with sepsis were observed during the care and stabilization of the animal. On echocardiographic examination, an increase in systolic and diastolic diameters of the left ventricle was observed with decreased shortening and ejection fraction, compatible with systolic dysfunction of the left ventricle. The patient received medical discharge after surgical correction and stabilization of clinical parameters, and died seven days later. It is suggested that the cause of death was systolic dysfunction caused by sepsis. It is concluded that myocardial dysfunction is a prognostic determinant factor in cases of sepsis, emphasizing the importance of its diagnosis and early treatment.

Differential diagnoses in 83 dogs with icterus / Diagnósticos diferenciais em 83 cães com icterícia

Icterus (jaundice) is a yellowish pigmentation resulting from the depositing of bilirubin in tissues due to its high plasmatic concentration. The pathogenesis of icterus includes metabolic changes or obstructed bilirubin excretion and it is classified as pre-hepatic, hepatic and post-hepatic. This study aimed to evaluate and classify different causes of icterus in dogs during post mortem examination. These dogs were examined from 2014 to 2017, using macroscopic and histologic exams as well as ancillary tests. Eighty-three dogs were examined macroscopically and microscopically. They were separated into groups of icterus types: 24 (28.9%) dogs had pre-hepatic icterus, 45 (54.2%) had hepatic, 13 (15.7%) pre-hepatic and hepatic and one (1.2%) had post-hepatic icterus. Many factors were identified as a cause of icterus, including infectious agents (51/83), neoplasms (13/83), hepatic degeneration (11/83), chronic hepatic diseases (6/83), and obstructive causes (1/87). Among the infectious causes, leptospirosis, ehrlichiosis and disorders suggestive of septicemia were diagnosed. Neoplasms associated with icterus were cholangiocarcinoma, hemangiosarcoma and lymphoma. Other causes of icterus included degenerative diseases, such as lipidosis and glycogen degeneration. Hepatic fibrosis (cirrhosis) as a chronic disease and cholelithiasis also produced icterus. PCR was performed to confirm leptospirosis and ehrlichiosis. Samples of total DNA were used to amplify a fragment of a gene from Leptospira interrogans and Ehrlichia canis. In some dogs, co-infection of these agents was detected. The classification and identification of icterus etiologies in dogs is very important due to the number of diseases with this alteration, where ante mortem diagnosis is not always easily performed when some of these conditions are present.(AU)

Icterícia é a pigmentação amarelada decorrente da deposição de bilirrubina em tecidos devido à elevada concentração plasmática. A patogênese da icterícia inclui alterações no metabolismo ou na excreção de bilirrubina, sendo classificada em pré-hepática, hepática ou pós-hepática. O objetivo desse estudo foi identificar, avaliar e classificar as causas de icterícia em cães necropsiados de 2014 a 2017, associando as lesões macroscópicas, histológicas e exames complementares. Foram avaliados macro- e microscopicamente 83 cães com diferentes intensidades de icterícia. Os cães foram separados em grupos de acordo com o tipo de icterícia: 24 (28,9%) cães com icterícia pré-hepática, 45 (54,2%) cães com icterícia hepática, 13 (15,7%) com icterícia pré-hepática e hepática e um (1,2%) com icterícia pós-hepática. Foram identificadas várias etiologias associadas à icterícia, dentre elas pode-se destacar, agentes infecciosos (51/83), neoplasmas (13/83), processos degenerativos (11/83), crônicos (6/83) e obstrutivos (1/83). Dentre as causas infecciosas, destacam-se a leptospirose, a erliquiose e as lesões sugestivas de septicemia. Entre os neoplasmas associados com icterícia destacaram-se o colangiocarcinoma, hemangiossarcoma e linfoma. Outras causas de icterícia incluiriam os processos degenerativos como as degenerações gordurosa e glicogênica. Fibrose hepática (cirrose) e colelitíase foram também diagnosticados como causa de icterícia. A PCR foi utilizada para o diagnóstico confirmatório de leptospirose e erliquiose. Amostras de DNA total foram utilizadas para amplificar um fragmento dos genes de Leptospira interrogans e de Ehrlichia canis. Em alguns cães foi detectada co-infecção por estes agentes. A classificação e a identificação das causas de icterícia em cães são relevantes devido ao grande número de doenças que apresentam essa alteração, muitas vezes sem diagnóstico ante mortem.(AU)

Intestinal rupture due to a non-perforating foreign body

Background: Intestinal obstruction by a foreign body is a common occurrence in domestic animals, needing the attention of veterinarians and owners, given that a serious complication of this condition is intestinal rupture, with consequentperitonitis. Perforating objects are the ones most often associated with rupture, but any object that obstructs the intestinaltract, if not removed properly, can lead to intestinal rupture, generating a poor prognosis. This article reports a case ofintestinal rupture caused by a non-perforating foreign body in a dog.Case: A 1-year-old Chow-Chow dog was taken by its owner to the Portal Pet private clinic, with a history of foreignbody ingestion and emesis. The owner reported that he took the animal to veterinary care in another establishment on theday he noticed vomiting, with no other abnormality being detected. An injectable medication was administered, but theowner did not know what it was, and the dog was discharged. After 15 days, the owner sought care at the clinic initiallymentioned, due to the persistence of emesis, in addition to the onset of diarrhea and apparent apathy. On physical examination, the dog was apathetic, with pale mucosa and pain on abdominal palpation. A firm structure was felt, located in theepigastric region, compatible with a foreign body. The dog was referred for hospitalization and an abdominal ultrasoundwas requested, in addition to blood samples for hematological and serum biochemical tests (urea, creatinine, alanineaminotransferase, and alkaline phosphatase). Serology for parvovirus was also performed. The blood count revealedleukopenia (4,800 thousand/mm3) and biochemical analysis showed an increase in alkaline phosphatase (895.5 U/l). Theresults for parvovirus were negative. Ultrasonography confirmed the presence of a foreign body. The animal was referred...

Intestinal rupture due to a non-perforating foreign body

Background: Intestinal obstruction by a foreign body is a common occurrence in domestic animals, needing the attention of veterinarians and owners, given that a serious complication of this condition is intestinal rupture, with consequentperitonitis. Perforating objects are the ones most often associated with rupture, but any object that obstructs the intestinaltract, if not removed properly, can lead to intestinal rupture, generating a poor prognosis. This article reports a case ofintestinal rupture caused by a non-perforating foreign body in a dog.Case: A 1-year-old Chow-Chow dog was taken by its owner to the Portal Pet private clinic, with a history of foreignbody ingestion and emesis. The owner reported that he took the animal to veterinary care in another establishment on theday he noticed vomiting, with no other abnormality being detected. An injectable medication was administered, but theowner did not know what it was, and the dog was discharged. After 15 days, the owner sought care at the clinic initiallymentioned, due to the persistence of emesis, in addition to the onset of diarrhea and apparent apathy. On physical examination, the dog was apathetic, with pale mucosa and pain on abdominal palpation. A firm structure was felt, located in theepigastric region, compatible with a foreign body. The dog was referred for hospitalization and an abdominal ultrasoundwas requested, in addition to blood samples for hematological and serum biochemical tests (urea, creatinine, alanineaminotransferase, and alkaline phosphatase). Serology for parvovirus was also performed. The blood count revealedleukopenia (4,800 thousand/mm3) and biochemical analysis showed an increase in alkaline phosphatase (895.5 U/l). Theresults for parvovirus were negative. Ultrasonography confirmed the presence of a foreign body. The animal was referred...(AU)

Differential diagnoses in 83 dogs with icterus / Diagnósticos diferenciais em 83 cães com icterícia

Icterus (jaundice) is a yellowish pigmentation resulting from the depositing of bilirubin in tissues due to its high plasmatic concentration. The pathogenesis of icterus includes metabolic changes or obstructed bilirubin excretion and it is classified as pre-hepatic, hepatic and post-hepatic. This study aimed to evaluate and classify different causes of icterus in dogs during post mortem examination. These dogs were examined from 2014 to 2017, using macroscopic and histologic exams as well as ancillary tests. Eighty-three dogs were examined macroscopically and microscopically. They were separated into groups of icterus types: 24 (28.9%) dogs had pre-hepatic icterus, 45 (54.2%) had hepatic, 13 (15.7%) pre-hepatic and hepatic and one (1.2%) had post-hepatic icterus. Many factors were identified as a cause of icterus, including infectious agents (51/83), neoplasms (13/83), hepatic degeneration (11/83), chronic hepatic diseases (6/83), and obstructive causes (1/87). Among the infectious causes, leptospirosis, ehrlichiosis and disorders suggestive of septicemia were diagnosed. Neoplasms associated with icterus were cholangiocarcinoma, hemangiosarcoma and lymphoma. Other causes of icterus included degenerative diseases, such as lipidosis and glycogen degeneration. Hepatic fibrosis (cirrhosis) as a chronic disease and cholelithiasis also produced icterus. PCR was performed to confirm leptospirosis and ehrlichiosis. Samples of total DNA were used to amplify a fragment of a gene from Leptospira interrogans and Ehrlichia canis. In some dogs, co-infection of these agents was detected. The classification and identification of icterus etiologies in dogs is very important due to the number of diseases with this alteration, where ante mortem diagnosis is not always easily performed when some of these conditions are present.(AU)

Icterícia é a pigmentação amarelada decorrente da deposição de bilirrubina em tecidos devido à elevada concentração plasmática. A patogênese da icterícia inclui alterações no metabolismo ou na excreção de bilirrubina, sendo classificada em pré-hepática, hepática ou pós-hepática. O objetivo desse estudo foi identificar, avaliar e classificar as causas de icterícia em cães necropsiados de 2014 a 2017, associando as lesões macroscópicas, histológicas e exames complementares. Foram avaliados macro- e microscopicamente 83 cães com diferentes intensidades de icterícia. Os cães foram separados em grupos de acordo com o tipo de icterícia: 24 (28,9%) cães com icterícia pré-hepática, 45 (54,2%) cães com icterícia hepática, 13 (15,7%) com icterícia pré-hepática e hepática e um (1,2%) com icterícia pós-hepática. Foram identificadas várias etiologias associadas à icterícia, dentre elas pode-se destacar, agentes infecciosos (51/83), neoplasmas (13/83), processos degenerativos (11/83), crônicos (6/83) e obstrutivos (1/83). Dentre as causas infecciosas, destacam-se a leptospirose, a erliquiose e as lesões sugestivas de septicemia. Entre os neoplasmas associados com icterícia destacaram-se o colangiocarcinoma, hemangiossarcoma e linfoma. Outras causas de icterícia incluiriam os processos degenerativos como as degenerações gordurosa e glicogênica. Fibrose hepática (cirrose) e colelitíase foram também diagnosticados como causa de icterícia. A PCR foi utilizada para o diagnóstico confirmatório de leptospirose e erliquiose. Amostras de DNA total foram utilizadas para amplificar um fragmento dos genes de Leptospira interrogans e de Ehrlichia canis. Em alguns cães foi detectada co-infecção por estes agentes. A classificação e a identificação das causas de icterícia em cães são relevantes devido ao grande número de doenças que apresentam essa alteração, muitas vezes sem diagnóstico ante mortem.(AU)

Anti-inflammation and anti-apoptosis effects of growth arrest-specific protein 6 in acute liver injury induced by LPS/D-GalN in mice

Purpose To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. MethodsThirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. Results Compared with the control group, AST, ALT, IL-1β, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. Conclusions Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.(AU)

Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model

Purpose. This experimental sepsis model created with Escherichia coli aimed to investigate the histopathological effects of two different doses of ozone combined with antibiotherapy on lung tissue.. Methods. Rats were divided into 5 groups. Then sepsis was induced intraperitoneally in the first 4 groups. The 1st group was treated with cefepime, the 2nd and 3rd groups were treated with cefepime combined with ozone at a dose of 0.6 mg/kg and 1.1 mg/kg. Lung tissue sections were stained with hematoxylin-eosin and assessed under light microscope and scored between 0-4 in terms of histopathological findings.. Results. In the comparisons between Group 1 and Group 4 in terms of cellular damage (p=0.030), inflammation (p=0.000) and overall score (p=0.007), statistically significant positive effects were observed in favor of Group 1. In the comparisons of Groups 2 and 3 with Group 4, only positive effects were observed in terms of inflammation (p=0.020, p=0.012, respectively).. Conclusion. Although negative histopathological effects of ozone on tissue injury were detected, it was noteworthy that the increase in the ozone dose reduced the number of damaged parameters.(AU)

Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model

Purpose This experimental sepsis model created with Escherichia coli aimed to investigate the histopathological effects of two different doses of ozone combined with antibiotherapy on lung tissue. Methods Rats were divided into 5 groups. Then sepsis was induced intraperitoneally in the first 4 groups. The 1st group was treated with cefepime, the 2nd and 3rd groups were treated with cefepime combined with ozone at a dose of 0.6 mg/kg and 1.1 mg/kg. Lung tissue sections were stained with hematoxylin-eosin and assessed under light microscope and scored between 0-4 in terms of histopathological findings. Results In the comparisons between Group 1 and Group 4 in terms of cellular damage (p=0.030), inflammation (p=0.000) and overall score (p=0.007), statistically significant positive effects were observed in favor of Group 1. In the comparisons of Groups 2 and 3 with Group 4, only positive effects were observed in terms of inflammation (p=0.020, p=0.012, respectively). Conclusion Although negative histopathological effects of ozone on tissue injury were detected, it was noteworthy that the increase in the ozone dose reduced the number of damaged parameters.(AU)

Diagnostic accuracy of 18F-FDG-PET in abdominal sepsis in rats

Purpose The objective of this study was to investigate the accuracy of 18F-FDG-PET in the diagnosis of multibacterial abdominal sepsis by cecum ligation and puncture (CLP) in rats. Methods Adult Wistar rats ( Rattus norvegicus ), weighing 227±35g, were allocated into a sepsis group by CLP (n=10) and sham group (n=10). 18F-FDG-PET using microPET was performed on all rats after 24 hours. Results All animals survived for postoperative 24h. The abdomen/liver ratio of the standardized uptake value (SUV) percentage was significantly higher in the sepsis group than in the sham (p=0.004). The ROC curve showed an accuracy of 18F-FDG-PET to detect abdominal sepsis of 88.9% (p=0.001), sensitivity of 90% and specificity of 88.9%. When a cut-off point of 79% of the ratio between the SUV on the abdominal region and liver was established, the sensitivity was 90%, specificity of 88.9%; positive and negative predictive values of 90.0% and 88.9%, respectively. Conclusions The diagnostic accuracy of 18F-FDG-PET in rats with abdominal sepsis was significantly high. It was also demonstrated the predictive ability of the abdomen/liver SUV ratio to diagnose abdominal sepsis. These findings may have implications for the clinical setting, locating septic foci with PETscan.(AU)