F. R. Bertin

Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction

REASONS FOR PERFORMING STUDY Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. OBJECTIVES To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand-held delivery devices. METHODS Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP(max) was measured 5 min after administration of 180 µg of albuterol from a pressurised metered dose inhaler, using an aerosol delivery device chosen randomly. This process was repeated every 5 min until maximal bronchodilation was achieved. After a 24 h washout period, lung mechanics data were again collected using the other aerosol delivery device. RESULTS Aerosolised albuterol induced a significant and rapid bronchodilation in the horses using both aerosol delivery devices. No statistically significant difference in pulmonary function was observed in response to albuterol therapy between the 2 devices. The dose required to achieve 50% of maximal bronchodilation was not statistically different between the 2 devices (173.35 ± 78.35 µg with Device 1 and 228.49 ± 144.99 µg with Device 2, P = 0.26). The decrease in lung resistance tended to be more pronounced after albuterol administration with Device 1 (P = 0.066). CONCLUSIONS Aerosolised albuterol is an effective bronchodilator in horses with recurrent airway obstruction. There is no statistically significant difference between the 2 commercially available aerosol delivery devices in terms of efficacy. POTENTIAL RELEVANCE Aerosolised albuterol is effectively delivered using currently available devices leading to maximal bronchodilation in horses with RAO at an average dose of 540 µg.

Clinical and clinicopathological factors associated with survival in 44 horses with equine neorickettsiosis (Potomac horse Fever).

BACKGROUND The epidemiology of equine neorickettsiosis (EN) has been extensively studied but limited clinical and clinicopathological data are available concerning naturally infected horses. HYPOTHESIS Factors predictive of survival will be identified in horses diagnosed with EN. ANIMALS Convenience sample of 44 horses with EN admitted to 2 referral institutions. METHODS A retrospective study was performed. A diagnosis of EN was based on the presence of positive blood or fecal PCR. RESULTS The most common clinical signs included diarrhea (66%), fever (50%), anorexia (45%), depression (39%), colic (39%), and lameness (18%). The median duration of hospitalization was 6 days and 73% of horses survived to discharge. Laminitis was present in 36% of horses, 88% of which were affected in all 4 feet. Serum creatinine and urea nitrogen concentrations, as well as RBC count, blood hemoglobin concentration, hematocrit, band neutrophils, serum AST activity, serum CK activity, and anion gap, were significantly (P < .05) higher in nonsurvivors. Serum chloride and sodium, concentrations as well as duration of hospitalization were significantly lower in nonsurvivors. The results of forward stepwise logistic regression indicated that blood hemoglobin concentration on admission and antimicrobial treatment with oxytetracycline were independent factors associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE Severity of colitis as reflected by electrolyte loss, hemoconcentration, and prerenal azotemia were predictors of survival in horses diagnosed with EN. Treatment with oxytetracycline was associated with increased survival.

What’s New in Old Horses? Postmortem Diagnoses in Mature and Aged Equids

Postmortem findings in 241 equids admitted to a teaching hospital that were at least 15 years old at autopsy were reviewed (1) to determine disease prevalence, (2) to compare the cause of death (or euthanasia) in equids 15 to 19 years of age (n = 116) with that in equids ≥20 years of age (n = 125), and (3) to catalog coexisting lesions in equids with pituitary pars intermedia dysfunction (PPID). Breed and sex were evenly distributed between the age groups. Death or euthanasia was attributed to disease of the digestive system (41.5%), pituitary gland (12.9%), locomotor system (10.0%), nervous system (7.9%), cardiovascular system (4.6%), urinary system (4.6%), reproductive system (4.2%), respiratory system (4.2%), integumentary system (4.2%), lymphoid system (2.5%), liver (2.5%), or systemic neoplasia (1.2%). Nervous system disease was more common in the 15- to 19-year group; urinary tract disease was more common in the ≥20-year group. Neoplastic disease, regardless of systemic location, was the basis for death or euthanasia in 18.7% of all equids. Squamous cell carcinoma, lymphoma, and melanoma were the most common malignant neoplasms. PPID was the most common specific diagnosis, based on the postmortem presence of hyperplasia or adenoma, and was the reason for euthanasia in 47.7% of 65 equids with PPID. The most common nonpituitary causes for death or euthanasia in equids with PPID were colic, lameness, cancer, and spinal cord disease. Coexisting conditions in equids with PPID that were not considered the basis for euthanasia included neoplasms, infections, lameness, and recurrent airway obstruction.

The diagnosis of equine insulin dysregulation

Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we discuss the different tests currently available to diagnose insulin dysregulation in horses: the ones investigating tissue insulin resistance and those investigating the enteroinsular axis, detailing their goals, practicalities and limitations. This review supports the contention that the diagnosis of equine insulin dysregulation should now be based on the investigation of both tissue insulin resistance and the equine enteroinsular axis. Regardless of the tests used many factors of variation, such as breed, diet, fasting state or season, have been identified and could potentially confound the results of a specific test. Therefore, careful interpretation of the results of a given test in each individual situation is required to optimise the detection of horses at risk of laminitis.

Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis

Venous thromboembolism is a common complication of cancer. Based on recent evidence that (1) growth arrest-specific 6 (Gas6) regulates the expression of tissue factor during venous thrombosis, and (2) cancer promotes a procoagulant milieu, we hypothesize that Gas6 may be involved in cancer-induced coagulopathy. Venous thrombi were induced in both wild-type (WT) and Gas6-deficient ((-/-)) mice with cancer. WT mice with cancer developed larger thrombi than their healthy counterparts; these larger thrombi induced by cancer were not seen in Gas6(-/-) mice. Whole genome microarray analysis of differential gene expression in WT and Gas6(-/-) endothelial cells exposed to M27 murine lung carcinoma cells reveal that Gas6 increases prostaglandin E synthase (Ptges) expression in endothelial cells. This was confirmed using real-time polymerase chain reaction and immunofluorescence staining. Culture of WT endothelial cells with M27 increases the secretion of prostaglandin E2 (PGE2), the enzymatic product of Ptges, in WT but not in Gas6(-/-) endothelial cells. In WT endothelial cells, Ptges expression was regulated through extracellular signal-regulated kinase 1/2 phosphorylation (ERK1/2). In vitro, PGE2 activates platelets after binding to its receptor, EP3. In vivo, EP3 receptor antagonism reversed the effect of cancer-induced thrombosis in WT mice. These results show that Gas6, through upregulation of PGE2, contributes to cancer-induced venous thrombosis.

Gas6 Promotes Inflammatory (CCR2 hi CX3CR1 lo ) Monocyte Recruitment in Venous Thrombosis

Objective— Coagulation and inflammation are inter-related. Gas6 (growth arrest–specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Approach and Results— Deep venous thrombosis was induced in wild-type and Gas6-deficient (−/−) mice using 5% FeCl3 and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti–C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti–chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6−/− mice contain less inflammatory (CCR2hiCX3CR1lo) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2hiCX3CR1lo monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). Conclusions— This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2hiCX3CR1lo monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis.

Gas6 (Growth Arrest–Specific 6) Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis

Objective— Coagulation and inflammation are inter-related. Gas6 (growth arrest–specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Approach and Results— Deep venous thrombosis was induced in wild-type and Gas6-deficient (−/−) mice using 5% FeCl3 and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti–C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti–chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6−/− mice contain less inflammatory (CCR2hiCX3CR1lo) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2hiCX3CR1lo monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). Conclusions— This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2hiCX3CR1lo monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis.

Growth arrest‐specific 6 regulates thrombin‐induced expression of vascular cell adhesion molecule‐1 through forkhead box O1 in endothelial cells

Growth arrest‐specific 6 (Gas6)‐deficient mice are protected against venous thromboembolism (VTE), suggesting a role for Gas6 in this disorder. We previously demonstrated that Gas6 induces forkhead box O1 (FoxO‐1) phosphorylation through the phosphoinositide 3‐kinase–Akt pathway. FoxO‐1 regulates the expression of vascular cell adhesion molecule‐1 (VCAM‐1), a molecule that has been implicated in VTE.

Arsenic Toxicosis in Cattle: Meta-Analysis of 156 Cases

BACKGROUND Arsenic toxicosis is uncommon in cattle and successful treatment is rarely reported. OBJECTIVES This analysis reviews all cases of acute arsenic toxicosis in cattle reported in the literature and describes cases from Purdue University that had a favorable outcome. Clinical presentation of the disease, treatments, and variables associated with survival are described. ANIMALS One hundred and fifty-six cattle with arsenic toxicosis from 16 outbreaks. METHODS Meta-analysis. RESULTS The most common clinical signs were sudden death (68%), diarrhea (33%), ataxia (29%), dehydration (22%), and respiratory distress (4%). The most common clinicopathologic abnormalities included azotemia (100%), hematuria (100%), increased liver enzyme activity (86%), and increased hematocrit (60%). One percent of cattle survived and the survival time for nonsurvivors ranged from 20 hours to 21 days. None of the clinical signs or clinicopathologic findings was associated with survival. Treatment was attempted in 24% of cases and was not associated with survival (P = .055), but administration of an antidote and administration of fluids were associated with better outcome (P = .036 and P = .009, respectively). In the animals presented to Purdue University, treatment with IV fluids and sodium thiosulfate resulted in decreased blood arsenic concentrations in all animals (P = .009) and a survival rate of 50%. CONCLUSIONS AND CLINICAL IMPORTANCE Although acute arsenic toxicosis has a poor prognosis, survival is possible if aggressive fluid therapy and antidotes are administered.

The Effect of Fasting Duration on Baseline Blood Glucose Concentration, Blood Insulin Concentration, Glucose/Insulin Ratio, Oral Sugar Test, and Insulin Response Test Results in Horses

Objectives Published descriptions of the oral sugar test (OST) and insulin response test (IRT) have been inconsistent when specifying the protocol for fasting horses before testing. The purpose of our study was to examine the effect of fasting duration on blood glucose concentration, blood insulin concentration, glucose/insulin ratio, OST, and IRT results in horses. Animals Ten healthy adult horses. Procedures Both OST and IRT were performed on horses without fasting and after fasting for 3, 6, and 12 hours. Thus, 8 tests were performed per horse in a randomized order. Blood collected at the initial time point of the OST was analysed for both blood glucose and serum insulin concentrations so that baseline concentrations and the glucose/insulin ratio could be determined. Unless fasted, horses had free‐choice access to grass hay. Results There was no effect of fasting and fasting duration on blood glucose concentration, serum insulin concentration, glucose/insulin ratio, or the OST. Response to insulin in the IRT was decreased in fasted horses. The effect increased with fasting duration, with the least response to insulin administration after a 12‐hour fast. Conclusions and Clinical Relevance These data indicate that insulin sensitivity is not a fixed trait in horses. Fasting a horse is not recommended for a glucose/insulin ratio or IRT, and fasting a horse for 3 hours is recommended for the OST.