Explore the vast range of titles available.

Cystic endometrial hyperplasia (CEH)—pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH—pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH—pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH—pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH—pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder. Summary Sentence Canine CEH—pyometra syndrome is characterized by an inflammatory, proliferative and vascular disorder, with higher uterine blood flow and vascularization.

Pyometra is the most common reproductive disease in female dogs, characterized by the accumulation of purulent content in the uterus. Its etiology is multifactorial, primarily involving hormonal and bacterial factors, with Escherichia coli being the most frequently isolated pathogen. International guidelines recommend bacterial culture and antimicrobial susceptibility testing of uterine content before or, if not feasible, after ovariohysterectomy. However, due to the time required to perform these tests, empirical antibiotic therapy is commonly prescribed, potentially contributing to antimicrobial resistance and treatment failure. Given that E. coli causing pyometra often originates from the intestinal microbiota, we hypothesized that isolates from rectal swabs could serve as predictors of the antimicrobial resistance profile of the E. coli causing pyometra. To evaluate this possibility, this study assessed the antimicrobial susceptibility of E. coli isolates from the uterine content and rectal swabs of bitches with pyometra and evaluated whether there is an association between the resistance profiles at these two sites. Samples from 72 dogs diagnosed with pyometra were collected for bacterial culture and antimicrobial susceptibility testing. E. coli was identified in 40 uterine content samples (55.6%) and 59 rectal swabs (81.9%) using species-specific PCR. E. coli isolates from rectal swabs exhibited higher resistance rates to commonly used antibiotics for pyometra treatment, including amoxicillin/clavulanic acid, ampicillin, enrofloxacin, and doxycycline (P < 0.05). The presence of susceptible isolates in rectal swabs is strongly associated with susceptibility in uterine isolates, yielding a positive predictive value up to 100%. These findings suggested that rectal swab isolates could serve as a reliable predictor of uterine E. coli susceptibility, providing a rapid and non-invasive tool to guide antimicrobial selection for pyometra treatment. RESUMO: A piometra é a doença reprodutiva mais comum em cadelas e caracteriza-se pelo acúmulo de conteúdo purulento no útero. Sua etiologia é multifatorial, envolvendo principalmente fatores hormonais e bacterianos, sendo Escherichia coli o patógeno mais frequentemente isolado. Diretrizes internacionais recomendam a realização de cultura bacteriana e teste de suscetibilidade a antimicrobianos do conteúdo uterino antes ou, se não for viável, após a ovariohisterectomia. No entanto, devido ao tempo necessário para a execução desses testes, a terapia antimicrobiana empírica é comumente prescrita, o que pode contribuir para a resistência aos antimicrobianos e falhas no tratamento. Considerando que E. coli causadora da piometra frequentemente se origina da microbiota intestinal, levantamos a hipótese de que isolados obtidos de swabs retais poderiam servir como preditores do perfil de resistência antimicrobiana de E. coli causadora da piometra. Para avaliar essa possibilidade, este estudo teve como objetivo analisar a suscetibilidade antimicrobiana de isolados de E. coli provenientes do conteúdo uterino e de swabs retais de cadelas com piometra, além de avaliar se existe associação entre os perfis de resistência nesses dois sítios. Amostras de 72 cadelas diagnosticadas com piometra foram coletadas para cultura bacteriana e teste de suscetibilidade a antimicrobianos. E. coli foi identificada em 40 amostras de conteúdo uterino (55,6%) e em 59 swabs retais (81,9%) por PCR. Os isolados de E. coli dos swabs retais apresentaram maiores taxas de resistência a antibióticos comumente utilizados no tratamento da piometra, incluindo amoxicilina/ácido clavulânico, ampicilina, enrofloxacina e doxiciclina (P < 0,05). Por outro lado, a presença de isolados suscetíveis a esses antimicrobianos nos swabs retais está fortemente associada à suscetibilidade também dos isolados uterinos, com valor preditivo positivo chegando a 100%. Esses achados sugerem que os isolados de swabs retais podem servir como preditores confiáveis da suscetibilidade da E. coli uterina, oferecendo uma ferramenta rápida e não invasiva para orientar a escolha antimicrobiana no tratamento da piometra.

Despite extensive characterisation of uropathogenic Escherichia coli (UPEC) causing urinary tract infections (UTIs), the genetic background of non-urinary extraintestinal pathogenic E. coli (ExPEC) in companion animals remains inadequately understood. In this study, we characterised virulence traits of 104 E. coli isolated from canine pyometra (n = 61) and prostatic abscesses (PAs) (n = 38), and bloodstream infections (BSIs) in dogs (n = 2), and cats (n = 3). A stronger association with UPEC of pyometra strains in comparison to PA strains was revealed. Notably, 44 isolates exhibited resistance to third-generation cephalosporins and/or fluoroquinolones, 15 were extended-spectrum ß-lactamase-producers. Twelve multidrug-resistant (MDR) strains, isolated from pyometra (n = 4), PAs (n = 5), and BSIs (n = 3), along with 7 previously characterised UPEC strains from dogs and cats, were sequenced. Genomic characteristics revealed that MDR E. coli associated with UTIs, pyometra, and BSIs belonged to international high-risk E. coli clones, including sequence type (ST) 38, ST131, ST617, ST648, and ST1193. However, PA strains belonged to distinct lineages, including ST12, ST44, ST457, ST744, and ST13037. The coreSNPs, cgMLST, and pan-genome illustrated intra-clonal variations within the same ST from different sources. The high-risk ST131 and ST1193 (phylogroup B2) contained high numbers of ExPEC virulence genes on pathogenicity islands, predominating in pyometra and UTI. Hybrid MDR/virulence IncF multi-replicon plasmids, containing aerobactin genes, were commonly found in non-B2 phylogroups from all sources. These findings offer genomic insights into non-urinary ExPEC, highlighting its potential for invasive infections in pets beyond UTIs, particularly with regards to high-risk global clones.

Background Pyometra, a life-threatening bacterial infection of the uterus, is classified as open or closed depending on the functional patency of the cervix i.e. presence or absence of vaginal discharge. In closed cervix pyometra, pus and bacterial products accumulate in the uterus, which is thought to induce a more severe illness. The aim of this study was to investigate whether disease severity or outcome differed in dogs with open or closed cervix pyometra. Results Prospectively collected data from 111 female dogs diagnosed with pyometra at the University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, intermittently during 2005–2012 was analyzed. Seventy-two dogs (65%) had open cervix, whereas 39 dogs (35%) had closed cervix. Differences between the two groups were explored by Wilcoxon Two Sample Test for continuous variables and Chi-square or Fisher’s exact test for categorical variables. P  < 0.05 was considered significant. In dogs with open cervix the median age was 9.0 years and the median weight 26.0 kg. In dogs with closed cervix the median age was 9.6 years and the median weight 25.0 kg, with no significant differences between the groups ( p  = 0.69 and 0.24, respectively). Five dogs (4.5%) died, all with open cervix, and 16 dogs (14%) had complications. The general physical condition was moderately or severely depressed in 30% (21/71) of dogs with open cervix (severely depressed in 4 dogs, moderately depressed in 17 dogs) and in 56% (22/39) of dogs with closed cervix (severely depressed in 3 dogs, moderately depressed in 19 dogs). The general physical condition was mildly depressed in 41 dogs with open cervix and 16 dogs with closed cervix, whereas it was normal in nine dogs with open cervix and one dog with closed cervix. None of the included dogs had very severely depressed general physical condition or were non-responsive. Leukocytosis, neutrophilia, monocytosis and moderately to severely depressed general condition was more commonly found in dogs with closed cervix ( p  = 0.003, p  = 0.008, p  = 0.003 and p  = 0.006, respectively). Sepsis was more commonly present in closed cervix pyometra (77%, 30/39 dogs) compared to open cervix pyometra (51%, 36/71 dogs) ( p  = 0.007). Presence of prolonged postoperative hospitalization did not differ significantly between the two groups. Conclusions In dogs with closed cervix, sepsis was more common, the general physical condition more often moderately to severely depressed and leukocytosis, neutrophilia and monocytosis more frequently found. The results showed that closed cervix was associated with a more severe illness than open cervix at admission but not with poorer outcome as measured by postoperative hospitalization. These findings may be clinically valuable for optimizing monitoring and treatments in dogs with the disease.

BACKGROUND: One of the most common diseases in intact bitches is pyometra– a potentially life-threatening disease associated with a variety of clinical and laboratory findings. The aims of the present study were to describe complications of the disease and to investigate clinically useful indicators associated with peritonitis and/or prolonged postoperative hospitalization. RESULTS: A retrospective study was performed using records from 356 bitches diagnosed with pyometra during the years 2006–2007 at the University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, Sweden. Of the 356 bitches, 315 were surgically treated by ovariohysterectomy, 9 were medically treated and 32 were euthanized without treatment. In the surgically treated bitches, univariable associations between clinical and laboratory data, risk for prolonged hospitalization (≥ 3 days) and/or signs of peritonitis, were analyzed by Chi-square and Fisher’s exact test. Logistic regression models were used to assess multivariable associations. The most common complication observed in surgically treated bitches was peritonitis (40 bitches), followed by urinary tract infection (19 bitches), wound infection (8 bitches), uveitis (6 bitches), and cardiac arrhythmia (5 bitches). Leucopenia and fever/hypothermia were associated with increased risk for peritonitis (18-fold and three-fold, respectively). Moderate to severe depression of the general condition, pale mucous membranes and leucopenia were associated with increased risk (seven-fold, three-fold, and over three-point-five-fold, respectively) for prolonged postoperative hospitalization. CONCLUSIONS: Several clinically useful indicators were identified. Leucopenia was the most important marker, associated with 18-fold increased risk for peritonitis and an over three-point-five increased risk for prolonged hospitalization. Fever/hypothermia, depression and pale mucous membranes were associated with increased risk for peritonitis and/or prolonged hospitalization. The results of the present study may be valuable for identifying peritonitis and predicting increased morbidity in surgically treated bitches with pyometra.

Background Pyometra is commonly seen in intact bitches and is usually treated by ovariohysterectomy. Few studies have reported the frequency of postoperative complications, particularly beyond the immediate postoperative period. Swedish national antibiotic prescription guideline provides suggestions about which antibiotics should be used and when in individuals undergoing surgery. Studies on how well clinicians adhere to these guidelines, and on the outcome for these patients, have not been evaluated for cases of canine pyometra. This retrospective study conducted at a private Swedish companion animal hospital assessed complications that developed within 30 days of pyometra surgery, and whether clinicians followed the current national guidelines in regard to antibiotic use. We also assessed whether antibiotic use affected the rate of postoperative complications seen in this cohort of dogs, where antibiotics were predominantly used in cases presenting with a more severely depressed general demeanour. Results The final analysis included 140 cases, 27 of which developed complications. In total, 50 dogs were treated with antibiotics before or during surgery and in 90 cases, antibiotics were either not given at all or treatment was initiated postoperatively (9/90) due to a perceived risk of infection developing. Superficial surgical site infection was the most common complication, followed by an adverse reaction to the suture material. Three dogs died or were euthanised during the immediate postoperative period. Clinicians adhered to national antibiotic prescription guidelines on when antibiotics should be given in 90% of cases. SSI only developed in dogs that were not given pre- or intra-operative antibiotics, while suture reactions did not appear to be affected by antibiotic use. Ampicillin/ amoxicillin was used in 44/50 cases given antibiotics before or during surgery, including most cases showing signs of concurrent peritonitis. Conclusion Serious complications following the surgical treatment of pyometra were uncommon. Excellent adherence to national prescription guidelines was observed (90% of cases). SSI was relatively common and only seen in dogs that were not given antibiotics before or during surgery (10/90). Ampicillin/ amoxicillin was an effective first choice antimicrobial in cases requiring antibiotic treatment. Further studies are needed to identify cases benefiting from antibiotic treatment, as well as the duration of treatment needed to reduce the infection rate while also avoiding unnecessary preventive treatment.

Background Sepsis, defined as a dysregulated inflammatory response to infection inducing organ dysfunction, is a common cause of mortality in both humans and animals. Early detection and treatment is essential for survival, but accurate diagnosis is challenging due to the lack of specific biomarkers for sepsis. This study explored the potential of the keratinocyte-derived chemokine (KC)-like protein in dogs as a biomarker of sepsis in dogs with bacterial uterine infection (pyometra). The aim was to compare KC-like concentrations in dogs with pyometra with or without sepsis and to assess associations between KC-like and clinical variables, including days of hospitalization as an outcome. Results A mouse KC ELISA was validated and used to determine the concentrations of KC-like in serum from 34 dogs with pyometra and 18 healthy controls. Dogs with pyometra were classified as having sepsis based on two different criteria for systemic inflammatory response syndrome (SIRS), resulting in 74% and 30% sepsis-positive, respectively. The concentration of KC-like protein was higher in pyometra dogs with sepsis than in pyometra dogs without sepsis ( p  < 0.05) and in healthy controls ( p  < 0.0001) when using either of the two SIRS criteria. Moreover, KC-like was slightly increased in dogs with pyometra without sepsis compared with healthy controls when using the more stringent SIRS criteria ( p  < 0.05). Analyses of all dogs showed that KC-like concentrations correlated positively with hospitalization days, C-reactive protein (CRP) concentrations, white blood cells, and percentage of band neutrophils; however, KC-like correlated negatively with hemoglobin and did not correlate with circulating creatinine. Conclusions Our results suggest that circulating KC-like protein increases in dogs with sepsis in pyometra and that KC-like is associated with more severe clinical illness. These findings support a potential role of KC-like as a biomarker of sepsis; however, the true identity of KC-like in dogs has yet to be uncovered.

The pathogenesis of canine pyometra is multifactorial, involving hormonal imbalances, aberrant immune responses, and metabolic dysregulation includes lipid metabolism and oxidative stress. This study focuses on lipid metabolism and oxidative stress, revealing the key regulatory role of AMPK and PLIN2 in canine pyometra. Bitches with open cervix pyometra (n:8) and healthy bitches undergoing elective ovariohysterectomy (n:4) were enrolled to the study. In experiment one, the serum and tissue levels of Malondialdehyde (MDA) and Superoxide Dismutase (SOD) activity were assessed. Additionally, uterine histopathological analysis, AMPK and PLIN2 expressions were determined through immunohistochemistry. Furthermore, inflammation, oxidative stress, and lipid metabolism-related factors were evaluated using Western blot analysis. In experiment two, primary cell cultures were prepared from healthy uterine endometrial cells of the dogs in control group. Cultured canine endometrial epithelial cells were treated with lipopolysaccharide (LPS) along with oleic acid (OA) to induce an inflammatory response. Tissue and serum MDA and SOD levels were greater in dogs with pyometra. Accumulated lipid droplets were observed in the uterine tissue of bitches with pyometra. The phosphorylation of AMPK and the expression of PLIN2 significantly increased in the pyometra group. The expression of related lipid synthesis proteins such as ACC1, FASN, SREBP-1c, and PLIN2 was upregulated, while PPARα and PGC1α were downregulated in bitches with pyometra. In experiment two, activation of AMPK and PLIN2 not only restores the expression of PGC1α, but also effectively alleviates inflammation and oxidative stress. The role of lipid metabolism and oxidative stress in canine pyometra is elucidated, thus contributing to the pathogenesis of pyometra in dogs.

Canine pyometra frequently occurs in middle-aged to older intact bitches, which seriously affects the life of dogs and brings an economic loss to their owners. Hence, finding a key metabolite is very important for the diagnosis and development of a new safe and effective therapy for the disease. In this study, dogs with pyometra were identified by blood examinations, laboratory analyses and diagnostic imaging, and fifteen endometrium tissues of sick dogs with pyometra and fifteen controls were collected and their metabolites were identified utilizing a UHPLC-qTOF-MS-based untargeted metabolomics approach. The results indicated that the elevated inflammatory cells were observed in dogs with pyometra, suggesting that sick dogs suffered systemic inflammation. In the untargeted metabolic profile, 705 ion features in the positive polarity mode and 414 ion features in the negative polarity mode were obtained in endometrium tissues of sick dogs with pyometra, with a total of 275 differential metabolites (173 in positive and 102 in negative polarity modes). Moreover, the multivariate statistical analyses such as PCA and PLS-DA also showed that the metabolites were significantly different between the two groups. Then, these differential metabolites were subjected to pathway analysis using Metaboanalyst 4.0, and Galactose metabolism, cAMP signaling pathway and Glycerophospholipid metabolism were enriched, proving some insights into the metabolic changes during pyometra. Moreover, the receiver operating characteristic curves further confirmed kynurenic acid was expected to be a candidate biomarker of canine pyometra. In conclusion, this study provided a new idea for exploring early diagnosis methods and a safe and effective therapy for canine pyometra.

Background Nesfatin-1 is a neuropeptide that regulates the hypothalamic-pituitary-gonadal axis and may play a role in uterus function. It is co-expressed with other peptides, such as phoenixin, which can influence sex hormone secretion. Our previous research has confirmed that phoenixin-14 is involved in the development of cystic endometrial hyperplasia (CEH) and pyometra in dogs. Therefore, based on the similarities and interactions between these neuropeptides, we hypothesized that nesfatin-1 might also regulate the reproductive system in dogs. This study aimed to determine the expression of nesfatin-1 and its interaction with phoenixin-14 in dogs with CEH or pyometra compared to healthy females, and concerning animals’ body condition score (BCS 4–5/9 vs. BCS > 5/9). Results The analysis of nesfatin-1 in the uterus of bitches consisted of qPCR, western blot and immunofluorescence assays, and ELISAs. The results showed significantly higher nesfatin-1 encoding gene, nucleobindin-2 mRNA ( Nucb2 ) and nesfatin-1 protein expression in overweight females and those suffering from CEH or pyometra compared to healthy animals. The immunoreactivity of nesfatin-1 was elevated in the uteri of bitches with higher BCS > 5/9. Moreover, nesfatin-1 blood concentrations increased in all examined overweight bitches. In the case of phoenixin signals, we found opposite results, regardless of the female body condition score. Conclusion The etiology of CEH and pyometra are not fully known, although we have expanded the level of knowledge with respect to the possible interaction of nesfatin-1 and phoenixin in female dogs’ uteri. They interact oppositely. With increasing female body weight, the expression of nesfatin-1 in the uterus and its peripheral blood concentration increased. However, for female dogs affected by CEH and pyometra, a decreased level of phoenixin-14, irrespective of their body condition score is characteristic. This knowledge could be crucial in the development of biomarkers for these conditions, which may lead to earlier recognition.