Hypocalcemia and Hypovitaminosis<scp>D</scp>in Dogs with Induced Endotoxemia

Holowaychuk, Marie K.; Birkenheuer, Adam J.; Li, J.; Marr, Henry S.; Boll, A.P.M.; Nordone, Shila K.

doi:10.1111/j.1939-1676.2012.00886.x

Cited by 38 publications

(38 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the expression of CYP24A1 and CYP27B1 in inflamed tissue (as with the expression of CYP27B1 in colonic tissue of CD patients 41 ) results in the consumption of 25(OH)D thereby placing downward pressure on vitamin D status. Consistent with this, lipopolysaccharide (LPS) induces the expression of CYP27B1 in human monocytes and dendritic cells 29, 42 , and induced endotoxemia causes vitamin D status to fall in dogs 43 . For some perspective on the likelihood of vitamin D deficiency as a cause of IBD, we turn first to the field of epidemiology.…”

Section: Observational Studiesmentioning

confidence: 71%

Linking Vitamin D Deficiency to Inflammatory Bowel Disease

Palmer¹,

Weaver²

2013

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Inflammatory bowel disease is associated with industrialization, and its incidence has increased markedly over time. The prospect of reversing these trends motivates the search for the agent(s) involved. Modernity entails several physical and behavioral modifications that compromise both the photosynthesis of cholecalciferol in the skin, and of its bioavailability. Although deficiency in this “vitamin” has therefore emerged as a leading candidate, and despite the publication of a randomized control trial that showed a trend towards statistically significant benefit in Crohn’s disease, its causal agency has yet to be demonstrated by an adequately powered study. We discuss the strengths and weaknesses of the case being made by epidemiologists, geneticists, clinicians and basic researchers, and consolidate their findings into a model that provides mechanistic plausibility to the claim. Specifically, converging data sets suggest that local activation of vitamin D coordinates the activity of the innate and adaptive arms of immunity, and of the intestinal epithelium, in a manner that promotes barrier integrity, facilitates the clearance of translocated flora and diverts CD4 T cell development away from inflammatory phenotypes. Since smoking is an important risk-altering exposure, we also discuss its newly established melanizing effect, as well as other emerging evidence linking tobacco use to immune function through vitamin D pathways.

show abstract

Section: Observational Studiesmentioning

confidence: 71%

Linking Vitamin D Deficiency to Inflammatory Bowel Disease

Palmer¹,

Weaver²

2013

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

show abstract

“…There was no significant decrease in mean arterial pressure (MAP) or increase in body temperature after saline injection. No clinical or laboratory abnormalities were detected in any of the dogs …”

Section: Resultsmentioning

confidence: 92%

“…Although endotoxemia in dogs secondary to LPS administration continues to be a common experimental model to simulate sepsis, the sources, concentrations and kinetics of LPS in dogs, and subsequent expression of PCT with naturally occurring sepsis are likely to be highly variable. In 2 previous studies evaluating PCT in dogs with naturally occurring sepsis, PCT was significantly elevated compared to healthy controls, however there was considerable variability in the PCT concentrations within these subjects . Interestingly, serial PCT concentrations were assessed in 1 of these groups, with survivors having significantly improved PCT concentrations by 48 hours compared to nonsurvivors …”

Section: Discussionmentioning

confidence: 98%

“…Hypocalcemia is widely recognized in septic animals though the pathophysiology remains poorly understood . Several mechanisms of hypocalcemia have been suggested, including the influence of calcitonin precursors, such as PCT . Furthermore, studies in human medicine have identified correlations between ionized hypocalcemia and increased PCT in sepsis, particularly in those with positive blood cultures .…”

Section: Discussionmentioning

confidence: 99%

“…All dogs were initially treated with a placebo (saline solution; 0.9% NaCl; 1 mL, IV) and then undiluted lipopolysaccharide ( Escherichia coli serotype 0127:B8, Sigma‐Aldrich, St. Louis, Missouri; LPS; 2 lg/kg, IV) after a 5‐day washout period. The injection and monitoring of this population were previously described . Briefly, each of the 6 dogs received a single IV injection of saline (0.9% NaCl; 1 mL) and then 5 days later, a single IV injection of LPS ( E. coli serotype 0127:B8, Sigma‐Aldrich; 2 μg/kg).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Serum procalcitonin concentrations in dogs with induced endotoxemia

Easley

Holowaychuk²,

Lashnits

et al. 2020

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background Procalcitonin (PCT) is an important biomarker for sepsis in human medicine, but there is little information regarding PCT as a biomarker for sepsis in dogs. There are no controlled studies evaluating serial concentrations of PCT in dogs. Hypothesis/Objective That PCT would be rapidly detectable in serum after injection of LPS and would remain increased for at least 24 hours. Objective was to evaluate serial serum PCT concentrations in dogs after a single IV injection of LPS compared to placebo. Animals Six healthy mixed breed dogs. Methods A nonrandomized, placebo‐controlled, crossover study was performed. Dogs were initially injected with placebo (0.9% NaCl; 1 mL, IV) and then experimental endotoxemia was induced by injecting lipopolysaccharide (LPS; 2 μg/kg, IV, once) after a 5‐day washout period. Serial blood samples were collected for measurement of serum PCT after each injection. Difference in median PCT concentration between serial time points was assessed using a mixed effects model. Results After LPS administration, blood pressure decreased and body temperature increased along with the development of lethargy, vomiting, and diarrhea. Procalcitonin was significantly increased compared to baseline by 2 hours after injection of LPS (median = 67.9 versus 172.8, range = 46.0‐74.1 versus 99.5‐295.9, P = .0002) and remained significantly increased for 12 hours (median = 205.9, range = 119.9‐297.4) with return to baseline by 48 hours. Procalcitonin was significantly higher than placebo 2, 4, 6, 8, 10, 12, and 24 hours after injection. There were no significant differences in PCT between time 0 and any of the subsequent time points in the saline group. Conclusions and Clinical Importance Procalcitonin expression is likely to be a clinically useful biomarker for sepsis in dogs and might have an additional role in prognostication and therapeutic decision‐making.

show abstract