Fecal alpha1-proteinase inhibitor concentration in dogs with chronic gastrointestinal disease

Background: Fecal α₁‐proteinase inhibitor (α₁‐PI) clearance is a reliable, noninvasive marker for protein‐losing enteropathy in human beings. An assay for use in dogs has been developed and validated. Objective: The aim of this study was to evaluate fecal α₁‐PI concentration in dogs with chronic gastrointestinal disease, compared with healthy dogs, and to assess its correlation with serum albumin concentration. Methods: Fecal samples were collected from 2 groups of dogs. Group 1 consisted of 21 clinically healthy client‐owned dogs without signs of gastrointestinal disease. Group 2 consisted of 16 dogs referred for investigation of suspected gastrointestinal disease. On the basis of gastric and duodenal biopsies, group 2 was further subdivided into dogs with normal histology (n = 9) and those with histologic abnormalities (n = 7: inflammatory bowel disease, n = 3; lymphangiectasia, n = 4). An ELISA was used to measure α₁‐PI concentrations in fecal extracts. Results: Fecal α₁‐PI concentrations, expressed as μg/g of feces, were not significantly different between groups 1 and 2 as a whole. However, fecal α₁‐PI concentrations (median, minimum‐maximum) were significantly higher in dogs with gastrointestinal diseases associated with histologic abnormalities (60.6 μg/g, 7.4–201.7 μg/g) compared with dogs with normal histology (3.8 μg/g, 0.7–74.0 μg/g) and control dogs (9.9 μg/g, 0.0–32.1 μg/g). There was no significant correlation between fecal α₁‐PI and serum albumin concentrations in dogs with gastrointestinal disease. Conclusions: Increased fecal α₁‐PI concentration may signal the need to obtain gastrointestinal biopsies for a final diagnosis. Fecal α₁‐PI concentration may be a useful test for early detection of protein‐losing enteropathy before decreases in serum albumin concentration can be detected.     

Protein-losing enteropathy in dogs is associated with decreased fecal proteolytic activity

Background: Measurement of proteolytic activity in feces is a traditional method for the diagnosis of exocrine pancreatic insufficiency (EPI). A drawback of this method is the occurrence of falsely low results that may lead to a false‐positive diagnosis of EPI. We hypothesized that intestinal loss of serum proteinase inhibitors in protein‐losing enteropathy (PLE) may inhibit fecal proteolytic activity and be a potential source of false low results. Objective: The objective of this study was to determine the effect of PLE on fecal proteolytic activity in dogs. Methods: Fecal proteolytic activity was measured using a radial diffusion casein digestion assay in 12 samples from 4 clinically healthy control dogs and 30 samples from 16 dogs with PLE. Gastrointestinal protein loss was assessed using an ELISA to determine fecal canine α₁‐proteinase inhibitor concentration. The relationship between the concentration of canine α₁‐proteinase inhibitor in the feces and the diameter cleared in the casein digestion assay was determined. The mean clearing diameter was compared between control dogs and dogs with PLE. Results: A significant negative correlation was observed between fecal canine α₁‐proteinase inhibitor concentration and casein clearing diameter (P < .001, Pearson r=—.6317, r 2 =.3999). Mean clearing diameter was significantly lower in dogs with PLE than in control dogs (12.63 vs 16.83 mm, P < .001, two‐tailed Student's t‐test). Conclusion: Increased fecal loss of α₁‐proteinase inhibitor in dogs with PLE is associated with a significant decrease in fecal proteolytic activity and may result in a false positive diagnosis of EPI.     

Comparison of amylase and lipase activities in serum and plasma of dogs

BACKGROUND: Amylase and lipase activities are most often determined in serum, although heparinized plasma is more convenient to obtain and is used for many routine biochemical analyses. OBJECTIVE: The purpose of this study was to compare amylase and lipase activities in serum and plasma of dogs and to determine whether either specimen type is acceptable for analysis. METHODS: Serum and heparinized plasma were obtained from 101 randomly selected dogs and analyzed in parallel for alpha-amylase and lipase. Results were compared using Passing-Bablock regression, Bland-Altman difference plots, and correlation analysis. RESULTS: There was a high correlation between the results obtained from serum and those from plasma. Regressions (with 95% confidence intervals in parentheses) were as follows: lipase(plasma) = 0.984 (0.976/0.995) Chi lipase(serum) - 0.9 (2.9/0.7) (r =.999); a-amylase(plasma) = 1.003 (0.977/1.032) Chi alpha-amylase(serum) - 1.9 ( 20.7/23.3) (r =.991). Mean differences (serum - plasma) were 8 U/L and 4 U/L for lipase and alpha-amylase, respectively. Classification of results as normal or abnormal did not differ according to specimen type. CONCLUSION: In dogs, lipase and alpha-amylase activities can be determined with the same level of accuracy in serum and in heparinized plasma.     

Tylosin-responsive chronic diarrhea in dogs

Fourteen dogs had shown chronic or intermittent diarrhea for more than 1 year. Diarrhea had been successfully treated with tylosin for at least 6 months but recurred when treatment was withdrawn on at least 2 occasions. Tylosin-responsive diarrhea (TRD) affects typically middle-aged, large-breed dogs and clinical signs indicate that TRD affects both the small and large intestine. Treatment with tylosin eliminated diarrhea in all dogs within 3 days and in most dogs within 24 hours. Tylosin administration controlled diarrhea in all dogs, but after it was discontinued, diarrhea reappeared in 12 (85.7%) of 14 dogs within 30 days. Prednisone given for 3 days did not completely resolve diarrhea. Probiotic Lactobacillus rhamnosus GG did not prevent the relapse of diarrhea in any of 9 dogs so treated. The etiology of TRD, a likely form of antibiotic-responsive diarrhea (ARD) is unclear. The following reasons for chronic diarrhea were excluded or found to be unlikely: parasites, exocrine pancreatic insufficiency, inflammatory bowel disease, small intestinal bacterial overgrowth, enteropathogenic bacteria (Salmonella spp., Campylobacter spp., Yersinia spp., or Lawsoni intracellularis), and Clostridium perfringens enterotoxin and Clostridium difficile A toxin. A possible etiologic factor is a specific enteropathogenic organism that is a common resident in the canine gastrointestinal tract and is sensitive to tylosin but difficult to eradicate. Additional studies are required to identify the specific cause of TRD.     

Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs

Objective

We investigated the plasma concentrations and cardiovascular effects of intramuscularly (IM) administered medetomidine, administered alone or with three different doses of MK-467.

Serum α‐1‐acid glycoprotein concentration in clinically healthy puppies and adult dogs and in dogs with various diseases

Background: α‐1‐acid glycoprotein (AGP) is an acute‐phase protein and a serum marker of inflammation and neoplasia in humans. AGP concentrations in diseased dogs and the potential effects of age, breed, and sex have not been elucidated. Objective: The purpose of this study was to examine differences in AGP concentration based on age, sex, and breed in a large population of clinically healthy dogs and to compare AGP concentrations in dogs with various diseases. Methods: Serum was obtained from clinically healthy puppies (n=74) and adults (n=172) of both sexes, and included mongrels (n=205) and Beagles (n=41). Serum also was obtained from 192 dogs with various diseases, including 8 with pyometra that were sampled before, and 1, 2, 3, and 10 days after surgery. AGP concentration was measured by single radial immunodiffusion. Statistical comparisons were made among age, sex, breed, and disease groups. Results: Serum AGP in healthy adult mongrels was 364±106 mg/L (reference interval, 152–576 mg/L). AGP was lowest in newborns (n=11, 122±54 mg/L) and gradually increased to adult levels by 3 months of age. Median AGP concentration was highest in dogs with parvovirus (n=17, 2100 mg/L), distemper (n=7, 1250 mg/L), and pyometra (n=18, 2480 mg/L) and was also significantly higher in dogs with acute filariasis, renal failure, urolithiasis, pancreatitis, hepatitis, trauma, hyperadrenocorticism, and immune‐mediated hemolytic anemia. Dogs with acute filariasis and acute hepatopathy had significantly higher AGP concentrations than dogs with chronic filariasis and chronic hepatopathy. Serum AGP concentration decreased gradually following surgery for pyometra but remained increased after 10 days (896±175 mg/L). Conclusions: Because of significantly lower AGP in puppies, the age of dogs should be considered when using AGP as a marker of disease. Serum AGP may be a useful marker of inflammatory disease in dogs and may help differentiate acute and chronic stages of disease.     

Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis

A randomized, controlled clinical trial investigated the effect of early enteral nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after admission (EEN group). All other treatments were identical. Intestinal permeability was assessed by 6-hour urinary lactulose (L) and rhamnose (R) recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was quantified by fecal alpha1-proteinase inhibitor concentrations (alpha1-PI). Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1 day shorter for the EEN group for each variable. Body weight increased insignificantly from admission in the NPO group (day 3: 2.5 +/- 2.8%; day 6: 4.3 +/- 2.3%; mean +/- SE), whereas the EEN group exhibited significant weight gain (day 3: 8.1 +/- 2.7%; day 6: 9.7 +/- 2.1%). Mean urinary %L was increased, %R reduced, and L/R recovery ratios increased compared to reference values throughout the study for both groups. Percent lactulose recovery decreased in the EEN group (admission: 22.6 +/- 8.0%; day 6: 17.9 +/- 2.3%) and increased in the NPO group (admission: 11.0 +/- 2.6%; day 6: 22.5 +/- 4.6%, P = .035). Fecal alpha1-PI was above reference values in both groups and declined progressively. No significant differences occurred for %R, L/R ratios, or alpha1-PI between groups. Thirteen NPO dogs and all EEN dogs survived (P = .48). The EEN group showed earlier clinical improvement and significant weight gain. The significantly decreased %L in the EEN versus NPO group might reflect improved gut barrier function, which could limit bacterial or endotoxin translocation.     

Advances in topical glaucoma therapy

Significant advances have recently been achieved in the development of topical glaucoma medications. The primary advantage of a topical preparation is the reduced incidence of adverse systemic effects attributable to a given drug compared to its systemically administered counterpart. However, the strong protective barrier of the eye forces topical ophthalmic preparations to be highly concentrated and in some cases, they have the potential to produce unwanted systemic effects, particularly in smaller animals. Oral carbonic anhydrase inhibitors are commonly associated with adverse effects in both humans and animals. Two recently developed topical carbonic anhydrase inhibitors, dorzolamide and brinzolamide, have shown promise in reducing intraocular pressure in animals and systemic side effects are apparently limited with their use. The topical alpha2-agonist apraclonidine, on the other hand, effectively reduces intraocular pressure in cats and dogs, but in its currently available form is likely to induce unwanted systemic effects. Latanoprost is a topical prostaglandin F2alpha analog that has proven effective in reducing intraocular pressure in dogs and horses, but while systemic side effects have not yet been reported, this topical preparation may exacerbate pre-existing or concurrent ocular inflammatory disease.     

Relationship between the melanocortin-1 receptor (MC1R) variant R306ter and physiological responses to mechanical or thermal stimuli in Labrador Retriever dogs

Objective

Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs.

Safety of alternate-day treatment with TS-1TM (tegafur/gimeracil/oteracil) in tumor-bearing dogs: a pilot study

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1^TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.     

Regulation of uterine function by cytokines in cows: Possible actions of tumor necrosis factor-α, interleukin-1α and interferon-τ

When animals do not become pregnant, regression of the corpus luteum (CL) is essential for normal cyclicity because it allows the development of a new ovulatory follicle. Luteal regression is caused by a pulsatile release of prostaglandin (PG) F_2α from the uterus in the late luteal phase in most mammals including cattle. Although it has been proposed in ruminants that pulsatile PGF_2α secretion is generated by a positive feedback loop between luteal and/or hypophyseal oxytocin and uterine PGF_2α, the bovine endometrium may possess other mechanisms for initiation of luteolytic PGF_2α secretion. There is increasing evidence that several cytokines mainly produced by immune cells modulate CL and uterine function in many species. Tumor necrosis factor‐α (TNF‐α) stimulates PGF_2α output from bovine endometrium not only at the follicular phase but also at the late luteal phase. Administration of TNF‐α at a high concentration prolongs luteal lifespan, whereas administration of a low concentration of TNF‐α accelerates luteal regression in cows. The data obtained from the authors’ previous in vitro and in vivo studies strongly suggest that TNF‐α is a crucial factor in regulating luteolysis in cows. The authors’ recent study has shown that interleukin‐1α mediates PG secretion from bovine endometrium as a local regulator. Furthermore, interferon‐τ (IFN‐τ) suppresses the action of TNF‐α on PGF_2α synthesis by the bovine endometrium in vitro, suggesting that IFN‐τ plays a luteoprotective role by inhibiting TNF‐α‐induced PGF_2α production in early pregnancy. The purpose of the present review is to summarize current understanding of the endocrine mechanisms that regulate uterine function by cytokines during the estrous cycle and early pregnancy in cows.     

Relationship between paraoxonase 1 activity and high density lipoprotein concentration during naturally occurring babesiosis in dogs

Paraoxonase 1 (PON1) is a negative acute phase protein bound to high density lipoproteins (HDL) and during the acute phase response (APR) protects HDL from peroxidation. The aim of this study was to assess the relationship between PON1 and HDL in canine babesiosis, a disease characterized by oxidative damages and by an APR. PON1, HDL and C-reactive protein (CRP), were measured in blood collected from 15 controls and 29 dogs with babesiosis sampled at admission, and on days 1 and 7 after treatment. At admission, PON1 and HDL were significantly lower in affected dogs. HDL concentration increased at day 1 while PON1 increased and CRP decreased at day 7. This suggests that the decrease of PON1 at admission is in part due to an increased consumption, the decreased HDL may depend on lipid peroxidation and its rapid increase after treatment may depend on the antioxidant activity of PON1.