Objective—To determine the effect of oral administration of a silibinin-phosphatidylcholine complex (SPC) on oxidative stress in leukocytes and granulocyte function in healthy cats.
Animals—10 purpose-bred adult cats.
Procedures—Cats were administered SPC (10 mg/kg/d) orally for 5 days; blood samples were collected prior to and immediately after the 5-day treatment period. Leukocytes were incubated with monochlorobimane for detection of reduced glutathione (GSH) via flow cytometry. Leukocytes were also incubated with dihydrorhodamine 123 and mixed with Escherichia coli conjugated to a fluorescent marker to measure E coli phagocytosis and the subsequent oxidative burst via flow cytometry. Activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, along with the reduced glutathione-to-oxidized glutathione (GSH:GSSG) ratio and a measure of lipid peroxidation (malondialdehyde concentration [Mmol/L of blood]), were measured spectrophotometrically.
Results—The mean fluorescence intensity (MFI), representing GSH content, increased significantly in feline lymphocytes and granulocytes following 5 days of oral administration of SPC. Mean ± SD lymphocyte MFI significantly increased from 27.8 ± 9.0 to 39.6 ± 6.7, and the granulocyte MFI increased from 508.6 ± 135.6 to 612.1 ± 122.9. Following 5 days of SPC administration, the percentage of phagocytic cells that were responding optimally significantly increased (from 37 ± 11.8% to 45 ± 17.5%). Other measures of oxidative stress did not change significantly.
Conclusions and Clinical Relevance—In cats, oral administration of supplemental SPC appears to increase granulocyte GSH content and phagocytic function, both of which would be potentially beneficial in cats with diseases associated with oxidative stress.
Contrast-enhanced CT of the cranial part of the abdomen was performed with 3-mm slice thickness. Postprocessing computer software designed for evaluation of human patients was used to calculate perfusion data for the pancreas and liver by use of 3-mm and reformatted 6-mm slices. Differences in perfusion variables between the pancreas and liver and differences in liver-specific data of interest were evaluated with the Friedman test.
Multiple pancreatic perfusion variables were determined, including perfusion, peak enhancement index, time to peak enhancement, and blood volume. The same variables as well as arterial, portal, and total perfusion and hepatic perfusion index were determined for the liver. Values for 6-mm slices appeared similar to those for 3-mm slices. The liver had significantly greater median perfusion and peak enhancement index, compared with the pancreas.
CONCLUSIONS AND CLINICAL RELEVANCE
Measurement of pancreatic perfusion with contrast-enhanced CT was feasible in this group of dogs. Hepatic arterial and pancreatic perfusion values were similar to previously published findings for dogs, but hepatic portal and hepatic total perfusion measurements were not. These discrepancies might have been attributable to physiologic differences between dogs and people and related limitations of the CT software intended for evaluation of human patients. Further research is warranted to assess reliability of perfusion variables and applicability of the method for assessment of canine patients with pancreatic abnormalities.
Objective—To evaluate changes in pH of peritoneal fluid associated with CO2 insufflation during laparoscopy in dogs.
Animals—13 client-owned dogs and 10 purpose-bred teaching dogs.
Procedures—Laparotomy was performed on control dogs; peritoneal fluid pH was mea-sured at time of incision of the abdominal cavity (time 0) and 30 minutes later. Laparoscopic insufflation with CO2 was performed and routine laparoscopic procedures conducted on the teaching dogs. Insufflation pressure was limited to 12 mm Hg. Intraperitoneal fluid pH was measured by use of pH indicator paper at 4 time points. Arterial blood gas analysis was performed at the same time points.
Results—Peritoneal fluid pH did not change significantly between 0 and 30 minutes in the control dogs. For dogs with CO2 insufflation, measurements obtained were a mean of 8.5, 24.5, 44.5, and 72.0 minutes after insufflation. The pH of peritoneal fluid decreased signifi-cantly between the first (7.825 ± 0.350) and second (7.672 ± 0.366) time point. Blood pH decreased significantly between the first (7.343 ± 0.078), third (7.235 ± 0.042), and fourth (7.225 ± 0.038) time points. The PaCO2 increased significantly between the first (39.9 ± 9.8 mm Hg) and fourth (54.6 ± 4.4 mm Hg) time points. Base excess decreased significantly between the first and all subsequent time points.
Conclusions and Clinical Relevance—Pneumoperitoneum attributable to CO2 insufflation caused a mild and transient decrease in peritoneal fluid pH in dogs. Changes in peritoneal fluid associated with CO2 insufflation in dogs were similar to those in other animals.
Objective—To determine whether results of histologic examination of hepatic biopsy samples could be used as an indicator of survival time in dogs that underwent surgical correction of a congenital portosystemic shunt (PSS).
Design—Retrospective case series.
Animals—64 dogs that underwent exploratory laparotomy for an extrahepatic (n = 39) or intrahepatic (25) congenital PSS.
Procedures—All H&E-stained histologic slides of hepatic biopsy samples obtained at the time of surgery were reviewed by a single individual, and severity of histologic abnormalities (ie, arteriolar hyperplasia, biliary hyperplasia, fibrosis, cell swelling, lipidosis, lymphoplasmacytic cholangiohepatitis, suppurative cholangiohepatitis, lipid granulomas, and dilated sinusoids) was graded. A Cox proportional hazards regression model was used to determine whether each histologic feature was associated with survival time.
Results—Median follow-up time was 35.7 months, and median survival time was 50.6 months. Thirty-eight dogs were alive at the time of final follow-up; 15 had died of causes associated with the PSS, including 4 that died immediately after surgery; 3 had died of unrelated causes; and 8 were lost to follow-up. None of the histologic features examined were significantly associated with survival time.
Conclusions and Clinical Relevance—Findings suggested that results of histologic examination of hepatic biopsy samples obtained at the time of surgery cannot be used to predict long-term outcome in dogs undergoing surgical correction of a PSS.
Objective—To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses.
Animals—9 healthy horses.
Procedures—Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week).
Results—Bioavailability of orally administered silibinin phospholipid was 0.6% PO in feed and 2.9% via nasogastric tube. During the multidose phase, silibinin had nonlinear pharmacokinetics. Despite this, silibinin did not accumulate when given twice daily for 7 days at the evaluated doses. Dose-limiting toxicosis was not observed.
Conclusions and Clinical Relevance—Silibinin phospholipid was safe, although poorly bio-available, in horses. Further study is indicated in horses with hepatic disease.
Objective—To evaluate antioxidant capacity and inflammatory cytokine gene expression in horses fed silibinin complexed with phospholipid.
Animals—5 healthy horses.
Procedures—Horses consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Dose-related changes in plasma antioxidant capacity, peripheral blood cell glutathione concentration and antioxidant enzyme activities, and blood cytokine gene expression were evaluated.
Results—Plasma antioxidant capacity increased throughout the study period with increasing dose. Red blood cell nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase I activity decreased significantly with increasing doses of silibinin phospholipid. No significant differences were identified in glutathione peroxidase activity, reduced glutathione or oxidized glutathione concentrations, or expression of tumor necrosis factor α, interleukin-1, or interleukin-2.
Conclusions and Clinical Relevance—Minor alterations in antioxidant capacity of healthy horses that consumed silibinin phospholipid occurred and suggest that further study in horses with liver disease is indicated.
Case Description—A 6-year-old castrated male Llewelyn Setter was evaluated because of an acute onset of myalgia and respiratory distress.
Clinical Findings—Physical examination revealed a stiff stilted gait, swollen muscles that appeared to cause signs of pain, panting, and ptyalism. The dog had a decrease in palpebral reflexes bilaterally and a decrease in myotatic reflexes in all 4 limbs. The panniculus reflex was considered normal, and all other cranial nerve reflexes were intact. Serum biochemical analysis revealed markedly high cardiac troponin-I concentration and creatine kinase and aspartate aminotransferase activities. Urinalysis revealed myoglobinuria. Results for thoracic and abdominal radiography, blood pressure measurement, and an ECG were within anticipated limits. Echocardiographic findings were consistent with secondary systolic myocardial failure. Arterial blood gas analysis confirmed hypoxemia and hypoventilation. The dog had negative results when tested for infectious diseases. Examination of skeletal muscle biopsy specimens identified necrotizing myopathy.
Treatment and Outcome—Treatment included ventilatory support; IV administration of an electrolyte solution supplemented with potassium chloride; administration of dantrolene; vasopressor administration; parenteral administration of nutrients; use of multimodal analgesics; administration of clindamycin, furosemide, mannitol, and enrofloxacin; and dietary supplementation with L-carnitine and coenzyme Q10. Other medical interventions were not required, and the dog made a rapid and complete recovery.
Clinical Relevance—Necrotizing myopathy resulting in rhabdomyolysis and myoglobinuria can lead to life-threatening physical and biochemical abnormalities. Making a correct diagnosis is essential, and patients require intensive supportive care. The prognosis can be excellent for recovery, provided there is no secondary organ dysfunction.
Over the past 15 to 20 years, we have seen what we believe to be an increased incidence of copper-associated hepatopathy in dogs. The onset of this increase appears to have coincided with a change in the type of copper used in premixes added to commercial dog foods. And, more recently, the increased incidence may have been exacerbated by consumer-driven desire for pet foods formulated with a high content of animal-based ingredients (eg, evolutionary diets), including certain organ meats, that might introduce additional copper and by trends favoring foods containing vegetables with a high copper content (eg, sweet potatoes).
OBJECTIVE To determine the effect of hospitalization on gastrointestinal motility and pH in healthy dogs.
DESIGN Experimental study.
ANIMALS 12 healthy adult dogs.
PROCEDURES A wireless motility capsule (WMC) that measured pressure, transit time, and pH within the gastrointestinal tract was administered orally to dogs in 2 phases. In the first phase, dogs received the WMC at the hospital and then returned to their home to follow their daily routine. In the second phase, dogs were hospitalized, housed individually, had abdominal radiography performed daily, and were leash exercised 4 to 6 times/d until the WMC passed in the feces. All dogs received the same diet twice per day in both phases. Data were compared between phases with the Wilcoxon signed rank test.
RESULTS Data were collected from 11 dogs; 1 dog was excluded because the WMC failed to exit the stomach. Median gastric emptying time during hospitalization (71.8 hours; range, 10.7 to 163.0 hours) was significantly longer than at home (17.6 hours; range, 9.7 to 80.8 hours). Values of all other gastric, small bowel, and large bowel parameters (motility index, motility pattern, pH, and transit time) were similar between phases. No change in gastric pH was detected over the hospitalization period. High interdog variability was evident for all measured parameters.
CONCLUSIONS AND CLINICAL RELEVANCE Hospitalization of dogs may result in a prolonged gastric emptying time, which could adversely affect gastric emptying of meals, transit of orally administered drugs, or assessments of underlying motility disorders.