Intracellular trafficking of the DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) is repaired by sodium 4-phenylbutyrate (4PBA) by an undetermined mechanism. 4PBA downregulates protein and mRNA expression of the heat shock cognate protein HSC70 (the constitutively expressed member of the 70-kDa heat shock protein family) by approximately 40-50% and decreases formation of a HSC70-DeltaF508 CFTR complex that may be important in the intracellular degradation of DeltaF508 CFTR. We examined the potential mechanisms by which 4PBA decreases HSC70 mRNA and protein expression. In IB3-1 cells, 1 mM 4PBA did not alter the activity of the Chinese hamster ovary HSC70 promoter or of a human HSC70 promoter fragment in luciferase reporter assays nor did it alter HSC70 mRNA synthesis in nuclear runoff assays. In contrast, preincubation with 4PBA increased the rate of HSC70 mRNA degradation by approximately 40%. The initial rate of 35S-HSC70 protein synthesis in 4PBA-treated IB3-1 cells was reduced by approximately 40%, consistent with the steady-state mRNA level, whereas its rate of degradation was unaltered by 4PBA. 4PBA also reduced the steady-state accumulation of (35)S-HSC70 by approximately 40%. These data suggest that 4PBA decreases the expression of HSC70 mRNA and protein by inducing cellular adaptations that result in the decreased stability of HSC70 mRNA.

Objective: To document the clinical and clinicopathologic changes in cats presenting with trauma from bite wounds, identify common abnormalities associated with bite wounds, and to determine whether the calculated animal trauma triage (ATT) score is related to any clinicopathologic abnormalities.Design: Retrospective descriptive study. Setting: University veterinary teaching hospital.Animals: Forty-three client-owned cats that presented for bite wounds to a large, urban, veterinary hospital between 1998 and 2009. Interventions: None.Measurements and main results: Pertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. Animal triage trauma score was calculated based on the physical examination at presentation in cats with adequate available information. Patients were classified as having either a low (<5) ATT (n = 20) or a high (≥5) ATT (n = 23) score. Male cats were overrepresented (65.1%), and a majority of cats had outdoor access (53.4%). Low venous blood pH (P = 0.047), high plasma lactate concentration (P = 0.018), and low ionized calcium concentration (P = 0.004) were associated with higher ATT scores. Conclusions:There is a significant association between low venous blood pH, high plasma lactate concentration, and low ionized calcium concentration and higher ATT scores at presentation in cats suffering from bite wounds. Early recognition of these abnormalities may help to identify more severely injured patients. K E Y W O R D Scats, ionized hypocalcemia, lactic acidosis, trauma wileyonlinelibrary.com/journal/vec J Vet Emerg Crit Care. 2019;29:296-300.

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Sepsis is currently defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis may occur secondary to infection anywhere in the body, and its pathogenesis is complex and not yet fully understood. Variations in the host immune response result in diverse clinical manifestations, which complicates clinical recognition and fluid therapy both in humans and veterinary species. Septic shock is a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Although septic shock is a form of distributive shock, septic patients frequently present with hypovolemic and cardiogenic shock as well, further complicating fluid therapy decisions. The goals of this review are to discuss the clinical recognition of sepsis in dogs and cats, the basic mechanisms of its pathogenesis as it affects hemodynamic function, and considerations for fluid therapy. Important pathophysiologic changes, such as cellular interaction, microvascular alterations, damage to the endothelial glycocalyx, hypoalbuminemia, and immune paralysis will be also reviewed. The advantages and disadvantages of treatment with crystalloids, natural and synthetic colloids, and blood products will be discussed. Current recommendations for evaluating fluid responsiveness and the timing of vasopressor therapy will also be considered. Where available, the veterinary literature will be used to guide recommendations.

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ObjectiveTo document the clinical and clinicopathological changes in cats presenting with vehicular trauma (VT) and to determine whether the calculated animal trauma triage (ATT) score was associated with any clinicopathological abnormalities.DesignRetrospective descriptive study conducted between 1998 and 2009.SettingUniversity veterinary teaching hospital.AnimalsSeventy‐five client‐owned cats that presented for VT to an urban veterinary hospital.InterventionsNone.Measurements and main resultsPertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. ATT score was calculated based on physical examination. Patients were classified as having either a low (<5) ATT (n = 30) or a high (≥5) ATT (n = 45) score. Male cats were overrepresented (60.0%), and a majority of cats had outdoor access (65.3%). Low PCV (P = 0.024), low total plasma protein concentration (P = 0.032), low venous blood pH (P = 0.047), high plasma lactate concentration (P = 0.047), low plasma bicarbonate concentration (P = 0.047), low base excess (P = 0.047), and high plasma glucose concentration (P = 0.047) were associated with higher ATT scores. In addition, low noninvasive blood pressure measurements (P = 0.008) were associated with higher ATT scores.ConclusionsThere was a significant association between lower PCV, lower total plasma protein concentration, lower venous blood pH, higher plasma lactate concentration, lower plasma bicarbonate concentration, lower base excess, higher whole blood glucose concentration, and lower noninvasive blood pressure and higher ATT scores at presentation in feline patients suffering from VT. Prospective evaluation of these values may prove useful in furthering understanding of the pathophysiology of trauma in cats.

Thoracic radiographs are used as a screening tool for dogs and cats with a variety of disorders that have no clinical signs associated with thoracic structures. However, this practice has never been supported by an evidence-based study. The objective of this retrospective observational study was to determine if certain canine and feline populations have a higher proportion of radiographic abnormalities, and whether any of these abnormalities are associated with patient hospitalization and outcome. Patients were excluded if current or previous examinations revealed evidence of primary respiratory or cardiac disease, malignant neoplasia, or an abnormal breathing pattern consistent with pulmonary pathology. Any notable thoracic change in the radiology report was considered important and evaluated in this study. One hundred and sixty-six of these included patients were dogs and 65 were cats. Of the 166 dog radiographs evaluated, 120 (72.3%) had normal thoracic radiographs, while 46 (27.7%) had radiographic abnormalities. Of the sixty-five cats included, 36 (55.4%) had normal radiographs, while 29 (44.6%) had abnormal radiographs. Canine patients with abnormal radiographs had a significantly higher lactate level (P-value 0.0348) and feline patients with abnormal radiographs had a significantly lower packed cell volume (P-value 0.012). A large proportion of patients that had screening thoracic radiographs (32.5%) had documented abnormalities, but a relatively low percentage (6.5%) of our total population had their clinical plan changed as a consequence of detection of these abnormalities. Findings indicated that abnormal screening thoracic radiographs are more likely in dogs with an elevated lactate and cats with anemia, or a low normal hematocrit.

The use of bromethalin rodenticides has risen since 2011, and in some states, it is the most common rodenticide ingestion reported to poison control. Although intravenous lipid emulsion (ILE) has been previously reported to lower serum desmethylbromethalin levels in an asymptomatic dog, and repeated mannitol has been investigated in a laboratory setting, there are no published reports of successful treatment of symptomatic bromethalin toxicosis in dogs. A 9 yr old castrated male Norwich terrier was evaluated for obtunded mentation, seizures, cranial nerve deficits, and tetraparesis secondary to bromethalin toxicosis. The patient was treated with ILE, mannitol, and ginkgo biloba and returned to normal neurological function. Bromethalin exposure was confirmed by serum desmethylbromethalin levels. Previous literature indicates that the prognosis for patients who suffer from symptomatic bromethalin toxicosis is poor to grave, and the return to normal neurological function after severe toxicosis has not been reported. ILE, mannitol, and ginkgo biloba are readily available and relatively inexpensive, and in combination may be of benefit in symptomatic bromethalin intoxication.