Antiparasitic activity of several compounds was evaluated over a long period (about 25 years) in the same flock of sheep. Haemonchus contortus was of special interest, including its relation to drug resistance, especially to thiabendazole and other benzimidazoles, in addition to phenothiazine. Eleven compounds were evaluated in 15 controlled tests, done between 1966 and 1989 in naturally infected lambs (n = 145) born and raised on the same pasture. Sheep were first placed on the pasture in 1962, and a few more were added thereafter. Internal parasites in these sheep were classified in 3 general categories: indeterminate exposure to parasiticides; H contortus, resistant to thiabendazole; and H contortus, resistant to phenothiazine. The parasitic infections probably became more homogeneous after several years because of few introductions of outside sheep after initial establishment of the flock. Activity against naturally acquired internal helminths was evaluated for cambendazole (CBZ: dosage, 20 mg/kg of body weight), fenbendazole (FBZ: 5 or 7.5 mg/kg), mebendazole (MBZ: 10 mg/kg); oxfendazole (OFZ: 3.5 or 10 mg/kg), oxibendazole (OBZ: 10 mg/kg); parbendazole (PBZ: 15 mg/kg), phenothiazine (PTZ: 550 mg/kg); pyrantel pamoate (PRT: 25 mg base/kg), tetramizole (TET: 15 mg/kg); thiabendazole (TBZ: 30 or 44 mg/kg), and trichlorfon (TCF: 100 mg/kg). Thiabendazole was used more often (9 tests) than the other compounds. Thiabendazole was more active against mature H contortus in later years than when first used in 1966, although it was never 100% effective. Efficacy against immature H contortus for TBZ did not exceed 86%. Activity against immature and mature stages of this parasite was good overall for the other benzimidazoles. Results indicated no definite side resistance of non-TBZ benzimidazoles for this species. Removal of both stages of H contortus was generally low for PTZ. For the other nonbenzimidazoles (PRT, TET, and TCF), efficacy against immature and mature H contortus was 93 to 100%, except for 1 test with PRT (79% on mature worms) and 1 with TCF (77% on immature worms). With regard to other abomasal parasites, activity for the compounds tested against 2 species of Ostertagia was greater than or equal to 97%, with 1 exception; numbers of these parasites in nontreated lambs were less than numbers of H contortus. All compounds, except PTZ and TCF, were effective against a third species, Trichostrongylus axei. Activity against several species of intestinal parasites, most present in low numbers, was determined for 5 compounds (TCF, TBZ, CBZ, PTZ, and PRT) in 5 rests. Thiabendazole, CBZ, and PRT were highly effective against trichostrongylus, with a few exceptions. Trichlorfon and PTZ had overall less activity against trichostrongylus than did the other products. Against trichurids, PRT and TCF were highly efficacious.

Stimulation of alpha 2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of alpha 2 adrenergic receptors. The objective of this study was to determine whether blockade of alpha 2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial blood flow. Intravenous infusion of endotoxin (cumulative dose of 0.03 mg/kg) significantly decreased cecal and right ventral colon contractile activity and lateral cecal arterial blood flow. Slow IV infusion of yohimbine (cumulative dose of 75 micrograms/kg) significantly attenuated those effects of endotoxin. On the basis of our findings, we concluded that endotoxemia causes cecal and proximal colonic ileus and cecal hypoperfusion via a mechanism that involves alpha 2 adrenergic receptors.

Intragastric pH monitoring was investigated in ponies. In cadaver stomachs, close contact with the mucosa led to high pH readings if nonweighted electrodes were used. However, pH recorded by weighted electrodes was markedly less affected by mucosal contact (P < 0.001). The latter were used for subsequent trials. In vivo, high correlations were found between pH recorded by weighted electrodes with or without a wire guard to prevent mucosal contact (correlation, r = 0.866; P < 0.001). Readings from each correlated well with those from simultaneous gastric aspirates (r = 0.774 and r = 0.807, respectively; P < 0.001 for both correlations). Plain electrodes recorded more highly variable (temporally heterogeneous) pH than did guarded electrodes. In vitro, trials using equine gastric fluid indicated that this resulted from greater responsiveness of the plain electrode. In vivo, episodes of nearly neutral pH were a common feature, and high pH correlated with intensely yellow-green, neutral fluid in the stomach (rank correlation, p = 0.626; P < 0.01). Concentration of bile acids did not correlate with pH or color score (p = -0.158 and p = 0.076, respectively). Causes of the episodes could include salivary influx, duodenogastric reflux, and variable gastric acid secretion. Pentagastrin infusion (0.6 micrograms/kg of body weight/ h) reduced intragastric pH (P = 0.018), but episodes of neutrality still occurred. Experiments in fed ponies indicated possible existence of a stable pH gradient, from neutral dorsally to heterogeneous and more acidic ventrally. Care was required in the rational choice of summary variables for expression of monitored pH data. Of the frequency distributions of 3 summary variables assessed in this study (mean, median, and percentage of data > pH 4), only that of the mean approached normality. Thus, use of the mean may allow analysis by parametric statistical methods. Intragastric pH monitoring was found to be a useful technique. Episodes of increased pH were often identified. These may represent episodic duodenogastric reflux.

The role of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor a during endotoxin-induced mastitis in cows was characterized. Six cows had 10 microgram of Escherichia coli lipopolysaccharide infused into 1 mammary gland. Three other cows served as nontreated controls. Within 1.5 to 2.5 hours after infusion, endotoxin caused obvious edema of the mammary gland and increased serum albumin concentration in milk of infused glands 6 times. Milk somatic cell count began to increase 3 to 5 hours after infusion in all treated glands. At 7 hours after infusion, somatic cell counts were increased > 10 times, compared with counts in milk from control cows. Pyrexia of > 1 C developed in only 1 cow, but all treated cows had serum cortisol concentrations > 50 ng/ml in response to endotoxin treatment. High concentrations of IL-1 (10 to 600 U/ml) and IL-6 (2 to 22 U/ml) were detected in milk of infused glands beginning 2.5 to 4 hours after infusion. Endotoxin did not induce detectable amounts of tumor necrosis factor activity in milk or serum. Swelling and mammary gland permeability changes preceded any detectable increase in IL-1 and IL-6 activity, indicating that these clinical signs of inflammation were not mediated by these cytokines. Systemic responses and the leukocytic influx into endotoxin-infused glands developed after or concurrently with initial increases in IL-1 and IL-6 activities in milk. These results suggested that IL-1 and IL-6 may have a role in mammary gland defenses and in the pathophysiologic changes during endotoxin-induced mastitis.

A specific polymerase chain reaction (PCR) assay was devised, allowing detection of 1 bovine leukemia virus (BLV)-infected cell in 10(4) bovine lymphocytes. The efficacy of field application of the developed method was verified by evaluating the rate of viral transmission to calves from infected cows, whether they have persistent lymphocytosis. With this objective, 43 calves were simultaneously tested at birth and at 6 months of age for viral antibodies in serum and for proviral DNA in lymphocytes. At birth, 36 calves were BLV-negative and 3 were BLV-positive by results of serologic and DNA-based assays. Conversely, results for 4 calves had lack of correlation between the diagnostic methods. In particular, 2 calves were DNA-positive and antibody-negative for BLV and 2 other calves had the opposite test results. At 6 months of age, when the immunologic pattern more closely reflects the status of calves' immune response, independent of maternal antibodies, all calves DNA-negative for BLV at birth (n = 38), were consistently PCR- and antibody-negative for BLV. On the contrary, the cattle DNA-positive for BLV at birth (n = 5), whether seropositive or not, were PCR- and antibody-positive for BLV, at the time of the second screening. Thus, these results indicate reliability of the PCR to diagnose perinatal BLV infection. Furthermore, the observation that all calves found to be infected at birth were born to BLV-positive cows with persistent lymphocytosis, indicates that the persistent lymphocytosis status of the cow may represent a factor associated with BLV infection in utero.

Undifferentiated distal respiratory tract disease (nasal discharge, cough, pneumonia) in foals (1 to 8 months old) is a burdensome economic problem on breeding farms yet, the infective agents associated with these episodes have not been well described. Possible causes of these episodes of illness were investigated by culturing specimens of proximal and distal airways of clinically diseased foals (n = 101), prior to any treatment, for aerobic and anaerobic bacteria and viruses (rhinoviruses, equine arteritis virus, equine herpesvirus subtype 1 [EHV-1], influenza virus, and adenovirus). Pairs of sera (n = 47) were examined for antibodies to influenza A virus, equine subtypes 1 and 2, EHV-1, and adenovirus antigens, and sera obtained from foals during acute infection were examined for antibodies (by agar gel immunodiffusion [AGID]) to equi factor antigens of Rhodococcus equi. Viruses were not isolated from the proximal (swab) or distal (bronchial lavage) airway specimens in foals, and only 2 of 47 randomly selected foals seroconverted to EHV-1. Serotiters to the other viruses were low and frequently decreasing between samples, which was compatible with maternally derived antibody. Streptococcus zooepidemicus was the predominant isolate from bronchial lavage specimens (88/101 cases), accompanied by alpha-hemolytic streptococci (8 cases), Bordetella bronchiseptica (13 cases), Staphylococcus epidermidis (9 cases), and other organisms in lesser frequency. Only Str zooepidemicus was recovered significantly (P < 0.05) more often in cases than in controls. The AGID test was found useful to detect 1/26 with presumed exposure to R equi, but positive tests results did not correspond well with bacterial culture results; positive AGID results were recorded in 34% of culture-negative foals. However, foals from which R equi was isolated were distinctive from the other foals on the basis of fever (> 39 C), lack of nasal discharge, blood neutrophilia and decreased percentage of neutrophils in bronchial lavage fluid samples. Isolation of Str zooepidemicus was significantly (P < 0.01) associated with increasing neutrophil percentage in bronchial lavage fluid. In conclusion, the pathogenic roles of Str zooepidemicus and R equi were established in this group of foals with distal respiratory tract infections by use of clinical, endoscopic, hematologic, and cytologic methods. There was no evidence of a viral cause for these infections, indicating that manifestations of distal respiratory tract infection are attributable to bacterial infection causing inflammation of the airways. Further studies are warranted to pursue more-sensitive methods for detection of viral antigen or antibody in undifferentiated distal respiratory tract disease episodes in foals.

Haptoglobin (HP), an acute-phase protein, is detected in serum of cows with hepatic lipidosis (fatty liver). To assess the relevance of Hp in fatty liver, induction of Hp was examined, using conditions similar to those involving development of fatty liver in cows. Induction of Hp was achieved by a combination of dexamethasone administration (0.1 mg/kg of body weight) and 2 days' starvation. Haptoglobin appearance in serum was not associated with the increase of alpha 1-acid glycoprotein (a marker for inflammation). This treatment increased serum nonesterified fatty acids concentration and decreased serum triglycerides concentration. Protein kinase C activity was decreased in the cytosolic fractions of liver and mononuclear cells. Reduction of protein kinase C-catalyzed endogenous protein phosphorylation also was observed, particularly in the cytosolic fractions of the tissue and cells. Detection of Hp in serum of cows with fatty liver appears to be explained by the fact that Hp is induced by dexamethasone administration and starvation, which are similar to the condition responsible for fatty liver development. The change of protein kinase C-catalyzed phosphorylation was suggested to be involved in the induction of Hp in cows.

The role of platelet-activating factor in mediating the cardiovascular and peripheral cellular responses to large-colon ischemia and reperfusion, was explored in anesthetized ponies. A specific platelet. activating factor (PAF) antagonist (WEB 2086) was administered to a group of 6 ponies, and another 6 ponies (controls) were given an equivalent volume of saline solution, prior to 1 hour of large-colon torsion. After correction of the torsion, ponies were monitored during the reperfusion period. Significant (P < 0.05) hypotension and metabolic acidosis developed in afl ponies after correction of colonic torsion, cardiac index increased initially, but then decreased significantly (P < 0.05) over the study period. Mean times between correction of torsion and onset of cardiac failure and death were not different between groups. Significant (P < 0.05) thrombocytopenia developed during the reperfusion period in control ponies, but not in WEB-treated ponies. Blood leukocyte concentration in control ponies was more variable and significantly (P < 0.05) decreased immediately upon reperfusion, compared with that in WEB-treated ponies. We conclude that although the cardiovascular responses to colonic ischemia and reperfusion are not prevented by use of a specific PAF-antagonist, specific peripheral cellular responses are mediated by PAF.

Transcutaneous oxygen (PO2.TC) monitoring is commonly used in human medicine for evaluating skin viability. The application of transcutaneous monitoring for evaluating skin viability in dogs was investigated. The changes in PO2-TC values were measured from 16 avascular skin flaps created along the lateral hemithoraces of 4 dogs. Transcutaneous oxygen values were serially recorded from the vascular base and avascular apex of each flap for 12 hours after surgery. A single transcutaneous measurement was obtained from each flap base and apex 24 hours after surgery. Serial arterial blood gas analyses were obtained to compare central oxygen values with PO2-TC values. Full-thickness skin biopsy specimens were harvested from the base and apex of each flap 24 hours after surgery. The flaps were observed for 4 days and then excised for histologic examination. A subjective grading scale was used to assess histologic changes. Throughout the 12-hour period and at 24 hours, a statistically significant difference was found between the PO2-TC values for apices and bases of the flaps. The mean PO2-TC for all bases was 90.9 mm of Hg +/- 3.3 SEM, and the mean PO2-TC for all apices was 21.2 mm of Hg +/- 1.8 SEM. The mean regional perfusion index (apex PO2.TC/base PO2-TC) was 0.23 +/- 0.02. The subjective numbers assigned to the biopsy specimens were statistically evaluated by using a paired Student's t test and a Wilcoxon signed-rank test. A significant difference was found between the numbers for the collective bases and apices with both tests. A statistically significant difference was found between the numbers for the apex biopsy specimens taken 24 hours after creation of the skin flap and those taken when the flap was excised, whereas no difference was found between the numbers for the base biopsy specimens. On the basis of our findings, PO2-TC monitoring is a useful technique for assessing skin viability in dogs.

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after IV administration of a single dose (5 mg/kg of body weight, IV). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 micrograms/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.