Craig B. Webb

S-adenosylmethionine (SAMe) in a feline acetaminophen model of oxidative injury

S-adenosylmethionine (SAMe) is reported to have hepatoprotective and antioxidant functions. Acetaminophen (paracetamol) was used to induce oxidative damage in cats, and to then determine the effect of SAMe treatment on erythrocyte morphology, PCV, liver histopathology, thiobarbituate reacting substances (TBARS), reduced glutathione (GSH), and oxidised glutathione (GSSG). Cats receiving acetaminophen had a significant increase in methemoglobin and Heinz body production. A significant effect for the interaction of time and treatment was found for Heinz body production and changes in PCV. No significant changes were found in blood or hepatic TBARS. Blood GSH increased significantly in all cats, while the blood GSH:GSSG ratio tended to increase the most in cats given acetaminophen only. The hepatic GSH:GSSG ratio tended to increase in cats given SAMe and decrease in cats given acetaminophen, but this effect was not significant. SAMe protected erythrocytes from oxidative damage by limiting Heinz body formation and erythrocyte destruction and maybe useful in treating acetaminophen toxicity.

Oxidative Stress and Neutrophil Function in Cats with Chronic Renal Failure

BACKGROUND Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. HYPOTHESIS Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. ANIMALS Twenty cats with previously diagnosed renal failure were compared with 10 age-matched control cats. METHODS A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2-tailed t-test) were reported as mean +/- standard deviation. RESULTS The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 +/- 197, 61.7 +/- 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 +/- 0.21, 0.81 +/- 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 +/- 253, 524 +/- 54; P < .05). CONCLUSIONS The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF.

Oxidative Stress and Liver Disease

Pro-oxidants are numerous and varied. Antioxidants are equally varied in their mechanism of action, and oxidative stress is likely not a simple arithmetic summation of these two opposing forces. More likely, it is a complex set of interrelated formulas with large areas of overlap and small areas of unique effect. In this article, the language of oxidative stress is reviewed, the consequences of oxidative stress are presented, the pathophysiology of oxidative stress in the liver is briefly discussed, and various antioxidant treatment options most relevant to small animal patients with liver disease are reviewed.

Stem cell therapy in cats with chronic enteropathy: a proof-of-concept study

Objectives The current treatment of cats with chronic enteropathy frequently includes use of a prescription diet and daily medication administration, with the potential for side effects or problems with owner compliance, and may still result in treatment failure in some cases. The objective of this study was to determine if stem cell therapy was a safe and viable treatment in cases of feline chronic enteropathy. Methods Allogeneic adipose-derived feline mesenchymal stem cells (fMSC) were used to treat seven cats with diarrhea of no less than 3 months’ duration, while four cats with a similar clinical condition received placebo, in a blinded manner. Three additional cats were treated with an identical fMSC protocol, but owners were not blinded to the treatment. Owners completed a questionnaire characterizing clinical signs both before entering the study and 2 weeks following the second of two fMSC or placebo treatments. Owners were also surveyed for similar input by email 1–2 months later before being unblinded to their cat’s study group. Besides the fMSC or placebo treatment, no other changes were made in diet, supplement or medication administration during the study. Results No adverse reactions or side effects were attributed to the fMSC therapy in any of the cats. Owners of 5/7 fMSC-treated cats reported significant improvement or complete resolution of clinical signs, while the owner of the remaining two cats reported modest but persistent improvement. Owners of placebo-treated cats reported no change or worsening of clinical signs. Of the owners not blinded to the treatment, one reported marked improvement, one reported no change and one was lost to follow-up. Conclusions and relevance Although allogeneic adipose-derived fMSC therapy appears to be a safe and potentially effective treatment for cats suffering from chronic enteropathy, these preliminary results require significant follow-up study.

Open-label trial of a multi-strain synbiotic in cats with chronic diarrhea

This study was designed to test the hypothesis that in cats with chronic diarrhea the daily administration of a proprietary synbiotic (Proviable-DC) would result in an improvement in stool character, as assessed by the owner. Adult cats with chronic diarrhea were recruited for the study and screened for systemic diseases. Fecal flotation, wet mount, immunofluorescence assay (IFA) for Giardia and Cryptosporidium species, and Tritrichomonas species polymerase chain reactions (PCRs) were used to screen for intestinal parasitism. The synbiotic was administered for 21 days; otherwise, no changes were made to ongoing treatment(s) or diet. The severity of the diarrhea was assessed using a standardized fecal scoring system and the owner’s subjective perception before, and after, supplementation. The mean fecal score for the 53 cats completing the study decreased from 6.0 to 4.4, representing a significantly (P <0.001) firmer stool character. Seventy-two percent of owners perceived an improvement in their cat’s diarrhea following a 21-day course of synbiotic supplementation.

Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats:

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (≥16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66–0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.

Feline Laparoscopy for Gastrointestinal Disease

Laparoscopy offers a minimally invasive route by which to evaluate the abdominal cavity, assess abdominal organs and tissues, and obtain a histopathologic diagnosis in a variety of feline gastrointestinal diseases. This article concentrates on the diagnostic utility of the procedure, but there are a number of surgical procedures that can be performed with laparoscopy as well. The most common use of diagnostic laparoscopy in the feline is to obtain a biopsy of the liver, but a variety other extra-intestinal tissues can be sampled relatively easily; biopsy of the pancreas and aspiration of the gallbladder are particularly relevant to feline gastrointestinal disease. Laparoscopy is often performed on an outpatient basis, there are very few absolute contraindications to the procedure, and laparoscopy results in minimal morbidity or mortality. The skill set required for the use of laparoscopy in the vast majority of feline cases can be readily mastered by the practitioner to a level of proficiency that makes this procedure a high-yield, efficient, and cost-effective diagnostic tool.

Rectal Strictures in 19 Dogs: 1997–2005

The etiologies for nonneoplastic rectal strictures in dogs included foreign bodies, postoperative formation, inflammatory disease, and congenital malformation. Sixteen of 19 dogs underwent balloon dilatation therapy, and 14 of these 16 dogs received intralesional triamcinolone injections. Following dilatation, clinical signs persisted in one dog, improved with continued medical therapy in five dogs, and resolved in nine dogs for the duration of their follow-up period (mean 18 months; median 12 months); one dog was lost to follow-up. Balloon dilatation and triamcinolone were parts of a treatment regimen that improved clinical signs in the majority of dogs diagnosed with nonneoplastic rectal strictures.

Diagnostic laparoscopy in the cat: 1. Rationale and equipment.

Practical relevance: The integration of minimally invasive techniques into feline practice seems to be an intuitive step forward, especially for those cases where the owner may be reluctant to subject their cat to major surgery ‘just for a biopsy’. Although ultrasound is frequently employed as a diagnostic tool in similar cases, this modality can only provide information on gross abnormalities in organ size and shape, echogenicity and internal architecture; even with ultrasound-guided fine-needle aspiration a definitive diagnosis is rarely achieved. So the clinician and owner are left with unanswered questions that are central to the diagnosis, the most appropriate treatment to pursue and the prognosis for the cat. Laparoscopy does require anesthesia and is more expensive than ultrasound; however, when performed correctly, it is only marginally more invasive and vastly more informative, with a proven track record of minimal morbidity. Audience: This article is aimed at all feline practitioners, from first opinion through to the referral setting. It is intended to encourage practitioners untrained in minimally invasive procedures to seek formalized training, especially those who want to expand their diagnostic capabilities. For those already performing minimally invasive surgery, it describes how laparoscopic techniques can be applied to many feline gastrointestinal cases. Evidence base: Information provided in this article is based on published literature, comprising original studies, case review series and textbook chapters, and the authors’ own clinical experience.

Oxidative stress and innate immunity in feline patients with diabetes mellitus: The role of nutrition

This study was undertaken to test the hypothesis that oxidative stress is increased and neutrophil function is decreased in cats with diabetes mellitus (DM). Measures of oxidative stress and neutrophil function were evaluated in 20 control and 15 diabetic cats. Cats were then fed a diet designed specifically for feline diabetics (Purina DM Dietetic Management Feline Formula) for 8 weeks, after which all assays were repeated. Cats with DM had significantly less plasma superoxide dismutase (SOD) than control cats, consistent with a greater degree of oxidative stress in the DM group. Following 8 weeks of consuming a diabetes-specific diet glutathione peroxidase, an antioxidant enzyme increased significantly in both groups. Other parameters of oxidative stress, as well as neutrophil function, were similar between groups and did not change following dietary intervention. The DM cats were significantly older and heavier than the control cats, which may have contributed to differences in parameters of oxidative stress and levels of antioxidant enzymes between these groups, but the decreased level of SOD enzyme in the diabetic group would appear to support the continued development of targeted antioxidant supplementation for this cats with this disease.