Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock.

BACKGROUND: No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model. METHODS: Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers. RESULTS: Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS. CONCLUSION: The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Prognostic role of ΔNp63 expression in canine transitional cell carcinoma of the urinary bladder.

BACKGROUND: Decreased p63 protein expression in canine transitional cell carcinoma (TCC) of the urinary bladder is associated with vascular invasion of the tumor, metastasis, and shortened survival. ΔNp63, an isoform of p63, is downregulated in high-grade invasive urothelial carcinoma in humans. However, the clinical significance of ΔNp63 expression in canine urinary bladder tumors is unknown. Therefore, it is essential to investigate ΔNp63 expression patterns in TCC, the most common urinary bladder tumor in dogs. AIM: This study aimed to evaluate the expression and role of ΔNp63 in canine TCC of the urinary bladder. METHODS: ΔNp63 expression was compared between the normal canine urinary bladder, polypoid cystitis, and TCC. The correlation of ΔNp63 expression with histopathological and clinical findings were further evaluated, and its usefulness as a prognostic factor was examined. RESULTS: We observed that ΔNp63 was highly expressed in dogs' normal urinary bladder and polypoid cystitis, and its expression levels were low in TCC. Furthermore, low levels of ΔNp63 expression were associated with vascular invasion, metastasis, and shortened survival in dogs with TCC. CONCLUSION: These results indicate that ΔNp63 expression could serve as a valuable biomarker for invasion, metastasis, and prognosis of canine TCC of the urinary bladder.

Histological and immunohistochemical evaluation of stroma variations and their correlation with the Ki-67 index and expressions of glucose transporter 1 and monocarboxylate transporter 1 in canine thyroid C-cell carcinomas.

Canine thyroid C-cell carcinomas (CTCCs) are malignant tumors derived from calcitonin-producing C-cells of the thyroid gland. This study aimed to investigate the histological diversity of CTCCs from the viewpoint of stroma variations and to investigate their components by histological and immunohistochemical analyses including semiquantitative analysis of the density of microvessels (MVs) and α-SMA-positive cell count. Moreover, we examined whether the variations correlated with the Ki-67 index and expressions of glucose transporter 1 (GLUT-1) and monocarboxylate transporter 1 (MCT-1). Three stroma types (reticular, R, nest, N, and trabecular, T) were observed in CTCCs, and 21 cases were divided into 3 variations based on their combinations: mixed R and N (R/N) (n=7), simple N (n=7) and mixed T and N (T/N) (n=7). Immunohistochemically, stroma types depended on morphological features of α-SMA/fibronectin/laminin/collagen type IV-positive stroma cells. The density of MVs in R/N tended to be highest, and the density of those in N was significantly higher than the density of those in T/N (P=0.028). The α-SMA-positive cell count for N tended to be the lowest among the 3 variations. The Ki-67 index for R/N was significantly higher than those of the other variations (vs. N, P=0.007; vs. T/N, P=0.03), and that for T/N tended to be higher than that for N. Although there were no significant differences, GLUT-1 and MCT-1 expressions tended to be low in N. We concluded that stroma variations reflect tumor cell proliferation and expressions of GLUT-1 and MCT-1 in CTCCs.

Gastrointestinal basidiobolomycosis in a dog.

An 8-year-old, spayed, female Shiba dog was presented to a referring veterinarian with a complaint of chronic diarrhea and anorexia. Ultrasound and radiographs revealed an irregular mass in the pelvic cavity. The mass and the affected section of colon were surgically removed. Histopathological examination revealed multifocal coalescing granulomas and effaced intestinal structures. Central necrotic debris surrounded by multinucleated giant cells, lymphocytes, plasma cells and neutrophils was observed. Numerous, irregularly branched hyphae with pale basophilic, thin walls and occasional bulbous enlargements at the tips were present. Polymerase chain reaction identified Basidiobolus ranarum, successfully confirming a definitive diagnosis of basidiobolomycosis. To the best of our knowledge, this is the first report of intestinal basidiobolomycosis in a dog.

Epidermal growth factor receptor expression in canine transitional cell carcinoma.

Transitional cell carcinoma (TCC), a urinary bladder tumor with high mortality, is encountered commonly in dogs. Whereas overexpression of epidermal growth factor receptor (EGFR) is associated with development of human urinary bladder cancer, information on EGFR expression in canine TCC is lacking. In this study, EGFR protein and mRNA expression in canine normal bladder (n=5), polypoid cystitis (n=5) and TCC (n=25) were examined by immunohistochemistry and real-time polymerase chain reaction. EGFR protein expression was significantly higher in TCC than that in normal healthy bladder (P<0.001) and polypoid cystitis (P<0.005). High EGFR protein expression was significantly (P<0.01) associated with TCC with a sensitivity of 72% and specificity of 100%. Comparative analysis of protein and mRNA expression levels in TCC showed significant positive correlation (r=0.88, P<0.05) between mRNA and protein expression. These findings suggest that intense expression of EGFR protein could be used as a marker to help canine TCC diagnosis.

(Pro)renin receptor blocker improves survival of rats with sepsis.

BACKGROUND: The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP. RESULTS: Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1ß, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB. CONCLUSIONS: PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.

Jejunal intussusception associated with lymphoma in a horse.

A 2-year-old Thoroughbred horse presented with acute onset of colitis, and the intussuscepted jejunum was surgically resected. A transmural mass protruding into the lumen was found at the leading edge of the intussusceptum. Based on histological and immunohistochemical examinations, the mass was diagnosed as diffuse large B-cell lymphoma with metastasis to the mesenteric lymph nodes. Anatomical localization of the mass in the intussusception and absence of other obvious underlying diseases indicated that the intussusception had occurred in association with the mass. To our knowledge, this case is the first report of equine intussusception associated with focal intestinal lymphoma.

High-dose immunoglobulin preparations improve survival in a CLP-induced rat model of sepsis.

PURPOSE: The efficacy of intravenous immunoglobulin G in the treatment of patients with severe sepsis or septic shock is still being debated. We investigated the impact of high-dose immunoglobulin administration on the survival rate and serum high-mobility group box chromosomal protein 1 (HMGB1) level in a rat model of sepsis created by cecal ligation and puncture (CLP). METHODS: Rats received either CLP-induced sepsis or had additional immunoglobulin treatment in 1,500 or 300 mg/kg. After induction of sepsis and respective treatment conditions, pulmonary and renal tissues were examined histologically for pathological changes at postoperative hour (POH) 4, and serum cytokine and HMGB1 levels were measured at POH 4, 8, 20, and 44. Using other rats, we also observed the survival rate after CLP for 7 days. RESULTS: Treatment with immunoglobulin significantly improved survival rate at postoperative day 7 (73% in the high-dose group vs. 33% in the control group; p = 0.037). The serum lactate dehydrogenase, endotoxin, creatinine, and blood urea nitrogen levels were significantly lower in the high-dose group than in the other groups. The serum HMGB1 level had increased at 4 h postoperatively in the control group (10.2 ± 3.3 ng/mL) and low-dose group (10.3 ± 4.0 ng/mL), but it was significantly reduced in the high-dose group (4.2 ± 0.8 ng/mL) compared with the control group (p = 0.03). CONCLUSIONS: Our results suggest that high-dose immunoglobulin therapy may improve the serum endotoxin and HMGB1 levels and overall survival rate in sepsis by inhibiting the inflammation.

Hepatocellular carcinoma in a Hokkaido brown bear (Ursus arctos yesoensis).

Hepatocellular carcinoma with metastases to lymph nodes and adrenal glands was found in a 26-year-old male Hokkaido brown bear (Ursus arctos yesoensis). Left hepatic lobe was largely replaced by well-differentiated neoplastic cells, whereas poorly differentiated tumor cells had proliferated in part of the left hepatic lobe, in scattered nodules in the remaining liver tissue, and at the metastatic sites. Immunoreactivity for hepatocyte antigen (hepatocyte paraffin 1 antibody) and alpha-fetoprotein was observed in both well- and poorly differentiated neoplastic cells in the liver and metastatic foci. To our knowledge, this case is the first report of hepatocellular carcinoma in brown bears.