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.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

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)

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.

Torção uterina unicornual em cadela gestante / Unicornual uterine torsion in pregnant bitch

Uterine torsion can be defined as the rotation of the uterine horn or body of the uterus, and it can be present in both clockwise and counterclockwise, its rotation can vary which directly affects the prognosis. It is a rare condition in bitches, and pregnancy is a factor commonly involved in this condition. The ovariosalpingohisterectomy (OSH) technique is the treatment of choice. A bitch of two years old of Pinscher breed was attend with a history of copulafor approximately 30 days ago, manifesting anorexia, apathy and abdominal pain for two days. Animal was hypothermic, dehydrated, hypotensive, hypoglycemic and presented neutrophilia lynfocytosis with a left shift. By performing the ultrasound examination, the presence of dead fetuses was observed. It was decided to initially stabilize the patient, subsequent OSH surgery was performed. Antibiotics and analgesics were administered during the hospitalization period, observing an improvement in the condition on the third day. The patient was discharged from hospital and a good recovery was observed on return. Despite the rare involvement of bitches in cases of uterine torsion, pregnancy can increase the risk of occurrences, the rapid intervention is of paramount importancef or the prognosis, since in this case the treatment proposed by the literature was carried out, obtaining the total recovery of the patient.

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)

Torção uterina unicornual em cadela gestante / Unicornual uterine torsion in pregnant bitch

Uterine torsion can be defined as the rotation of the uterine horn or body of the uterus, and it can be present in both clockwise and counterclockwise, its rotation can vary which directly affects the prognosis. It is a rare condition in bitches, and pregnancy is a factor commonly involved in this condition. The ovariosalpingohisterectomy (OSH) technique is the treatment of choice. A bitch of two years old of Pinscher breed was attend with a history of copulafor approximately 30 days ago, manifesting anorexia, apathy and abdominal pain for two days. Animal was hypothermic, dehydrated, hypotensive, hypoglycemic and presented neutrophilia lynfocytosis with a left shift. By performing the ultrasound examination, the presence of dead fetuses was observed. It was decided to initially stabilize the patient, subsequent OSH surgery was performed. Antibiotics and analgesics were administered during the hospitalization period, observing an improvement in the condition on the third day. The patient was discharged from hospital and a good recovery was observed on return. Despite the rare involvement of bitches in cases of uterine torsion, pregnancy can increase the risk of occurrences, the rapid intervention is of paramount importancef or the prognosis, since in this case the treatment proposed by the literature was carried out, obtaining the total recovery of the patient.(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)

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)

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)

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)

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 (1.0g/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 -cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or -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.

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 (1,0g/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 -cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para os valores de ACTH endógeno, cortisol após estimulação ou -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 ina

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)

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)

MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model

Purpose: To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI.Methods: Serum from sepsis and healthy patients was collected, sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved caspase-3 and Bcl-2, cell viability, relative caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay. Results: MiR-106a was up-regulated in serum of sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells. Conclusion: MiR-106a aggravated LPS-induced inflammation and apoptosis of TCMK-1 cells via regulating THBS2 expression.(AU)

Suppurative splenitis in a filly

Splenic abscess is an uncommon condition in humans and animals. The present report describes a rare case of suppurative splenitis in a 14-month-old filly, presented with signs of mild colic, depression and hyporexia. After clinical and laboratorial evaluation, a suppurative process of undetermined location was suspected. Medical therapy and supportive care were initiated, general condition has degraded in few days, and a paracentesis was performed diagnosing peritonitis. Given the poor prognosis, euthanasia was elected. At necropsy, multiple splenic abscess and diffuse peritonitis were identified. The etiology was not determined.