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- Author or Editor: Jared A. Jaffey x
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Abstract
OBJECTIVE
To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy.
ANIMALS
21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11).
PROCEDURES
In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy.
RESULTS
As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03).
CLINICAL RELEVANCE
These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.
Abstract
OBJECTIVE To determine the in vitro effects of calcitriol on indicators of immune system function in blood samples collected from healthy dogs.
SAMPLE Blood samples from 8 healthy adult dogs.
PROCEDURES Blood samples were incubated with calcitriol (10−7M) or control substance for 24 hours. Afterward, lipopolysaccharide (LPS)-, lipoteichoic acid (LTA)-, and N-acetylmuramyl-l-alanyl-d-isoglutamine hydrate (MDP)-stimulated leukocyte production of tumor necrosis factor (TNF) and interleukin-10 (IL10) were measured with a canine-specific multiplex assay. Phagocytosis of opsonized Escherichia coli and leukocyte expression of constitutive toll-like receptor 4 (TLR4) were evaluated via flow cytometry. Blood samples from 3 dogs were used to create a concentration-response curve to evaluate whether the observed cytokine modulation was concentration dependent.
RESULTS Incubation of canine blood samples with calcitriol resulted in significant decreases in LPS-, LTA-, and MDP-stimulated leukocyte production of TNF but not IL10. Blunting of TNF production was concentration dependent. Leukocyte calcitriol exposure had no significant effect on phagocytosis and TLR4 expression.
CONCLUSIONS AND CLINICAL RELEVANCE These data indicated that calcitriol induced an anti-inflammatory shift in canine leukocytes exposed to LPS, LTA, and MDP in vitro, without altering phagocytosis or TLR4 expression. Thus, calcitriol could represent a novel candidate immunomodulatory treatment for dogs.
Abstract
OBJECTIVE To determine the in vitro effect of calcitriol on indicators of immune system function in endotoxin-primed blood samples from healthy dogs.
SAMPLE Blood samples from 6 healthy adult dogs.
PROCEDURES Leukocytes were primed by incubation of blood samples with lipopolysaccharide (LPS; endotoxin) or PBS solution (unprimed control group) for 1 hour. Following priming, blood samples were incubated with calcitriol (2 × 10−7M) or ethanol (control substance) for 24 hours. After sample incubation, LPS-stimulated leukocyte production of tumor necrosis factor (TNF) and interleukin-10 (IL10) was measured with a canine-specific multiplex assay, and apoptosis and toll-like receptor 4 (TLR4) expression were evaluated via flow cytometry.
RESULTS LPS stimulation of unprimed leukocytes but not endotoxin-primed leukocytes resulted in a significant increase in TNF and IL10 production, confirming the presence of endotoxin tolerance in dogs in vitro. Endotoxin priming significantly increased neutrophil viability with no effect on lymphocyte viability or TLR4 expression by neutrophils and monocytes. Calcitriol exposure significantly decreased LPS-stimulated production of TNF by unprimed and endotoxin-primed leukocytes. Conversely, calcitriol exposure had no effect on IL10 production by unprimed leukocytes but did significantly increase IL10 production by endotoxin-primed leukocytes. Calcitriol had no significant effect on the degree of neutrophil or lymphocyte apoptosis, nor was neutrophil and monocyte TLR4 expression affected in unprimed or endotoxin-primed leukocytes.
CONCLUSIONS AND CLINICAL RELEVANCE These data indicated that calcitriol induced an anti-inflammatory shift in unprimed and endotoxin-primed canine leukocytes in vitro, without compromising neutrophil and monocyte TLR4 expression or altering the viability of neutrophils and lymphocytes in canine blood samples.
Abstract
OBJECTIVE
To identify prognostic indicators and inflammatory markers associated with nonsurvival in dogs with gallbladder mucoceles (GBMs) following cholecystectomy and to evaluate C-reactive protein (CRP) and haptoglobin concentrations in dogs with GBMs compared to healthy controls.
ANIMALS
25 dogs that underwent cholecystectomy for removal of GBM and 20 healthy control dogs.
METHODS
A prospective, multicenter cohort study. Survival outcomes to hospital discharge and 2 weeks postdischarge were recorded from medical records. Laboratory variables, inflammatory markers (CRP and haptoglobin), and 25-hydroxyvitamin(OH) D (25[OH]D) concentrations were measured preoperatively. Associations between signalment, clinicopathologic variables, acute patient physiologic and laboratory evaluation (APPLEFAST) scores, inflammatory markers, 25(OH)D concentration, and survival were analyzed using logistic regression.
RESULTS
76% (19/25) and 68% (17/25) of dogs survived to hospital discharge and 2 weeks postdischarge, respectively. For each additional year of age, the odds of nonsurvival in hospital and 2 weeks postdischarge increased by 2.2 (P = .01; 95% CI, 1.2 to 5.0) and 1.7 (P = .04; 95% CI, 1.0 to 3.2), respectively. Intraoperative systolic blood pressure ≤ 65 mm Hg increased the probability of nonsurvival in hospital (P < .04). Gallbladder perforation, APPLEFAST scores, and preoperative serum concentrations of CRP, haptoglobin, and 25(OH)D were not associated with survival. Serum CRP and haptoglobin concentrations were greater in dogs with GBM compared to controls (P < .001).
CLINICAL RELEVANCE
Increasing age and intraoperative systolic blood pressure ≤ 65 mm Hg were associated with nonsurvival in dogs with GBM undergoing cholecystectomy. Serum CRP, haptoglobin, and 25(OH)D were not associated with nonsurvival postcholecystectomy in this sample population.
