Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs

OBJECTIVE: To identify the normal gastric acid secretion profile in dogs and determine the degree of gastric acid suppression associated with 4 gastric acid suppressants. ANIMALS: 12 healthy Beagles. PROCEDURE: Intragastric pH was measured continuously for 24-hour periods with a digital recording system placed via a gastrostomy tube. Baseline measurements were obtained when food was withheld and when dogs were fed a standard diet. Dogs were then treated with ranitidine (2 mg/kg, IV, q 12 h), famotidine (0.5 mg/kg, IV, q 12 h), pantoprazole (1 mg/kg, IV, q 24 h), omeprazole (1 mg/kg, PO, q 24 h), or saline solution for 7 days; intragastric pH was recorded on days 0, 2, and 6. Subsequently, the effects of administering famotidine (0.5 mg/kg, IV, q 8 h; 6 dogs) and omeprazole as a suspension (1 mg/kg, PO, q 12 h; 6 dogs) were evaluated. Median 24-hour intragastric pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were determined. RESULTS: Median pH, percentage of time pH was > or = 3, and percentage of time pH was > or = 4 were all significantly higher when food was withheld than when dogs were fed. Famotidine, pantoprazole, and omeprazole significantly suppressed gastric acid secretion, compared with saline solution, as determined on the basis of median 24-hour pH and percentages of time pH was > or = 3 or > or = 4. However, ranitidine did not. Omeprazole suspension suppressed gastric acid secretion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs, famotidine, pantoprazole, and omeprazole significantly suppress gastric acid secretion. Twice daily administration of a suspension of omeprazole, was the only regimen tested that approached the potential therapeutic efficacy for acid-related disease when assessed by criteria used for human patients.     

Effect of exercise on age-related changes in collagen fibril diameter distributions in the common digital extensor tendons of young horses

OBJECTIVE: To determine whether specific treadmill exercise regimens would accelerate age-related changes in collagen fibril diameter distributions in the common digital extensor tendon (CDET) of the forelimbs of young Thoroughbreds. ANIMALS: 24 female Thoroughbreds. PROCEDURE: Horses were trained for 18 weeks (6 horses; short term) or 18 months (5 horses; long term) on a high-speed treadmill; 2 age-matched control groups (6 horses/group) performed walking exercise only. Horses were (mean +/- SD) 24 +/- 1 months and 39 +/- 1 months old at termination of the short-term and long-term regimens, respectively. Midmetacarpal CDET specimens were obtained and processed for transmission electron microscopy. Diameter and area of at least 1,000 collagen fibrils/specimen were measured by use of computerized image analysis. Mass-average diameter (MAD) of collagen fibrils and collagen fibril index were calculated for each horse. RESULTS: Collagen fibril MAD for the older horses was significantly less than that for the younger horses. Exercise did not significantly affect fibril diameter or distributions in either age group, and collagen fibril index did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Age-related reduction in collagen fibril MAD agreed with findings for other tendons and species. Training did not accelerate age-related change in the CDET in contrast to a reported decrease in collagen fibril MAD in the superficial digital flexor tendon of horses trained long term. Our results support the concept that the functionally distinct nature of the CDET and superficial digital flexor tendon in horses results in fundamentally different responses to high-speed exercise regimens.     

Bronchoalveolar immune defense in cattle exposed to primary and secondary challenge with bovine viral diarrhea virus

To evaluate immune defense mechanisms against bovine viral diarrhea virus (BVDV), four calves received primary and secondary intrabronchial infections with the cytopathic, type I Singer strain of BVDV. The cellular and humoral responses to these site-specific infections with BVDV were monitored by sequential bronchoalveolar lavages (BAL) conducted prior to infection (day 0, non-infected controls) and on days 4, 7, 10, 17 (day 31, secondary infection), 35, 38, 41, 48 and 62 post-infection. Peak quantities of BVDV were recovered from BAL on day 4. BVDV clearance from the lung was complete between days 17 and 31. Immune clearance of BVDV from the lower airways upon secondary infection was swift, within 4 days, and sustained throughout a 1-month period. Total numbers of BAL CD4(+) and CD8(+) T-lymphocytes increased >200-fold by day 10, and increased to levels >70-fold higher than background by 4 days after a secondary BVDV infection. gammadelta(+) T-lymphocytes increased 100-fold by day 7 and remained at levels at least 10-fold higher than pre-infection throughout the study. B-lymphocytes increased to levels 30-fold greater than pre-infection levels by day 10, and further increased to levels 100-fold higher following secondary BVDV infection. Activation (defined by the phenotype CD25(+)/CD62L(-)) and memory (defined by the phenotype CD45RO(+)/CD45R(-)) profiles of lymphocytes in the lower airways were characterized. Activated subpopulations of CD4(+) and CD8(+) cells increased nearly 300- and 150-fold, respectively, by day 10, and to levels 100- and 50-fold 4 days after the secondary infection. Memory subpopulations of CD4(+) and CD8(+) cells increased to levels 170- and 120-fold, respectively, by day 10, and to levels approximately 400- and 300-fold, respectively, 7 days after the secondary infection. The primary antibody response consisted of increased titers of anti-BVDV-specific IgA in bronchoalveolar lavage fluid (BALF). A strong secondary antibody response with high levels of anti-BVDV-specific IgA and IgG in BALF before day 4 post-secondary BVDV infection, likely contributed, along with cellular defenses, to the rapid clearance of virus from the lung upon secondary exposure. These results demonstrate that primary infection of the bovine lung with BVDV initiates cell-mediated immune responses capable of clearing the virus within 2-3 weeks. Furthermore, populations of immune-activated and memory T-lymphocytes, combined with BVDV-specific antibody production, contribute to rapid BVDV clearance upon secondary exposure to the virus.     

Glycogen depletion patterns in horses performing maximal exercise

Muscle biopsy samples were collected from the left middle gluteal muscle of horses participating in competitive barrier trials. Twelve horses were biopsied the day before and within 30 minutes of completion of an 800 m barrier trial. A further six horses were sampled the day before, and within 30 minutes of, completion of a 1200 m barrier trial. Serial muscle sections were examined histochemically for myosin adenosine triphosphatase activity after acid preincubation, to demonstrate type I, IIA and IIB fibres. The glycogen content in the individual fibres was assessed using the periodic acid Schiff (PAS) reaction. Total glycogen in muscle was measured fluorimetrically after hydrolysis to glucose. Significant decreases in total muscle glycogen levels of 167.1 +/- 22.2 and 158.1 +/- 23.2 mmoles glucose units kg-1 (dry weight) (mean +/- standard error) occurred from pre- to post trial samples for horses in both 800 and 1200 m trials respectively. There were no significant differences between the decreases in total muscle glycogen from horses in either 800 m or 1200 m trials. In both 800 m and 1200 m trials there was a significant decrease in the percentage of type IIA and IIB fibres classified as having high PAS staining intensity, and a significant increase in the percentage of fibres classified as having medium staining intensity when samples taken after the trial were compared to those taken before the trial.     

In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis

The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), serotonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses, using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotensin II, norepinephrine, and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of 2,3,2-tetramine as a hepatic copper chelating agent for treatment of copper hepatotoxicosis in Bedlington terriers

Five Bedlington Terriers with inherited copper (Cu) hepatotoxicosis and with hepatic Cu concentrations ranging from 3,000 to 11,000 micrograms/g of dry weight (normal, less than 350 micrograms/g of dry weight) were treated daily for up to 200 days with 2,3,2-tetramine tetrahydrochloride. During treatment, no change was made in the dietary Cu intake, which ranged from 12 to 16 micrograms/g of dry diet. Concentrations of hepatic and serum Cu, iron, and zinc were determined before and at the conclusion of the treatment period. In one dog, 24-hour urinary Cu concentration was measured before and during treatment. A liver biopsy specimen obtained after treatment had significantly (P less than 0.05) reduced hepatic Cu concentration (3,282 micrograms/g of dry weight; a 54.9% reduction), compared with the pretreatment value (7,281 micrograms/g of dry weight). After treatment, there was an overall general lessening of the extent of hepatic morphologic damage. Cytochemical examination for Cu in rhodanine-stained biopsy specimens revealed decreased numbers of Cu-laden hepatic lysosomes. The mean daily urinary Cu concentration increased as much as 25-fold during 2,3,2-tetramine treatment. Hepatic iron and zinc concentrations and serum Cu concentrations remained within normal ranges after treatment. Clinical or laboratory evidence of 2,3,2-tetramine toxicosis was not detected during treatment. These findings indicated that in affected Bedlington Terriers, 2,3,2-tetramine was a safe and rapid chelating agent of hepatic Cu.     

Factors contributing to the public health and economic importance of waterborne zoonotic parasites

This is the first of a series of review articles in a Special Issue publication on waterborne zoonotic parasites. A brief historical overview of the occurrence and importance of waterborne parasites, dating from early civilization is presented. The article considers the diversity of parasites including protozoa, nematodes, cestodes and trematodes and the related zoonotic organism microsporidia. Many of the life cycle stages and their characteristics, which make parasites environmentally resistant and suitable for waterborne transmission are discussed. Surfaces of transmission stages consist of multiple layers of proteins, lipids, chitin or other substances capable of withstanding a variety of physical and chemical treatments. Delivery of waterborne parasites is facilitated by various mass distribution systems to consumers, and by transport and intermediate hosts such as fish and filter-feeding invertebrates which are consumed by humans. The article discusses the trends in global warming and climate change and potential for concurrent rise in waterborne disease outbreaks due to parasites. Impacts of technological modernization and globalization on the transmission of zoonotic waterborne zoonotic parasites are considered, including the effects of large-scale agricultural practices, rapid transportation of goods, and widespread movement of individuals and animals. Finally, transmission features and parasite attributes which contribute to concerns about accidental or orchestrated waterborne disease outbreaks are discussed.