Antinociceptive activity of and clinical experience with buprenorphine in swine.

We performed antinociceptive testing on swine receiving buprenorphine. Intravenous access was achieved, and animals were allowed to recover for 24 h. Baseline skin-twitch latency to a focused light source was determined for each animal. Animals received intravenous (i.v.) buprenorphine at 0.08 (n =1), 0.16 (n = 1), 0.005 (n = 5), 0.01 (n = 5), or 0.02 mg/kg (n = 6). Skin-twitch latency was determined 15, 30, 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 min after buprenorphine administration. Analgesic activity as measured by a significant increase in latency time over baseline values occurred at all time points except 480 min in animals that received 0.02 mg/kg buprenorphine i.v. Analgesic activity to 420 min was demonstrated in animals that received 0.01 mg/kg buprenorphine i.v. Analgesic activity was not demonstrated at any time point in animals that received 0.005 mg/kg buprenorphine i.v. A retrospective analysis of postoperative care records was performed to determine whether 0.01 mg/kg buprenorphine i.v. or intramuscularly (i.m.) postoperatively to swine provided clinically relevant analgesia. Records of swine receiving buprenorphine from 1997 to 2000 were reviewed for indications of treatment failure, such as pain or a change in analgesic regimen from that used routinely. Treatment failure occurred in 18 of 416 (4.3%) cases treated with buprenorphine. This failure occurred in 17% of cases with problems categorized as inflammatory in nature and in 15.5% of those with systemic problems or organ failure. We concluded that antinociceptive testing predicted that buprenorphine administered at 0.01 mg/kg i.v. in swine likely would provide analgesic efficacy for 6 h and when administered at 0.02 mg/kg i.v. likely would provide 10 h analgesia. Clinical signs of pain in animals recovering from surgery were not observed in the majority of cases when buprenorphine was administered twice or thrice daily at 0.01 mg/kg i.m. or i.v. However, buprenorphine was less effective at treating signs of pain associated with inflammation, organ failure, or systemic disease than at ameliorating pain associated with surgical incisions and orthopedic, dental, and ophthalmic procedures.

Effects of dexamethasone on development of immunoglobulin G subclass responses following vaccination of horses.

OBJECTIVE: To determine the effects of dexamethasone on development of IgG subclass responses following vaccination of healthy horses. ANIMALS: 11 mature Thoroughbreds. PROCEDURE: Horses received 2 IM injections at 2-week intervals of a vaccine containing inactivated infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza-3 viral antigens and were then randomly assigned to 2 groups. Six horses received dexamethasone (0.2 mg/kg of body weight, IM) twice weekly for 8 weeks starting the day of the first vaccination. Five control horses received an equivalent volume of saline (0.9% NaCl) solution. Antigen-specific serum IgG subclass titers were determined weekly after vaccination by use of an ELISA. RESULTS: Vaccination resulted in similar antigen-specific serum IgG(T) titers in dexamethasone-treated and control horses. In contrast, although control horses developed IgGa and IgGb responses after vaccination, corticosteroid administration completely inhibited these responses in treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Cortico steroids can have profound effects on primary immune responses in horses and can significantly affect IgG responses to inactivated vaccines. Corticosteroid treatment regimens commonly used to treat diseases in horses may result induction of a nonprotective IgG subclass response, leaving treated horses susceptible to disease. Additionally, mechanisms regulating IgGa and IgGb responses appear to differ from those regulating IgG(T) responses. Further defining these mechanisms is a critical step in designing effective vaccines, and corticosteroid-induced immunomodulation may be a valuable tool for studying immune responses in horses.

Opiates and infection.

This review on the effects of opiate use on infectious diseases discusses the complete spectrum of infections in the opiate user, including those of the lung, the GI tract, the skin, the skeletal system, and the CNS. There is both increased prevalence and increased severity of bacterial and viral infections in injection drug users with the outcome of increased morbidity and mortality. The experimental administration of opiates has lead to a greater understanding of the effects on susceptibility to and progression of infectious diseases. Animal models of opiate dependence and infection are reviewed with specific attention to cases in which the opiate-mediated effects are harmful and in which cases they are beneficial.

Infection of swine with Mycobacterium bovis as a model of human tuberculosis.

Swine were infected with Mycobacterium bovis to develop a model for pulmonary and disseminated tuberculosis in humans. Pigs were inoculated with various doses of M. bovis by intravenous (i.v.), intratracheal (int), or tonsillar routes. Animals were euthanized between 17 and 60 days after inoculation, and tissues were collected for culture and histopathologic examination. Lesions of disseminated tuberculosis were found in pigs given 10(4) or 10(8) cfu of M. bovis i.v. or int; localized pulmonary disease was found in pigs given 10(2) or 10(3) cfu of M. bovis int. Lesions ranged from well-organized tubercles with coagulative necrosis, epithelioid macrophages, and fibrosis to large expansive tubercles with liquefactive necrosis and extracellular growth of M. bovis. Tuberculous meningitis was observed in animals given M. bovis i.v. Swine infected with M. bovis are a useful animal model for elucidating the mechanisms of pathogenesis and host defense to tuberculosis in humans.

Morphine alteration of histamine release in vivo.

Studies were performed to evaluate the effects of either acute or chronic morphine exposure on histamine release in vivo and supporting studies in vitro. In order to effectively assess histamine release in swine, studies were undertaken to evaluate the effectiveness of compound 48/80 as an intradermal skin test and determine its ability to release histamine in swine cells. Compound 48/80 skin testing was found to be a useful measure of histamine release in swine as evidenced by dose dependent wheal and flare reaction in vivo and histamine release from swine cells in vitro. Acute effects of morphine were determined on swine administered a single injection of morphine alkaloid. Skin tests using intradermal compound 48/80 and histamine, were performed using compound 48/80 both prior to, and 24 h following initiation of morphine treatment. Morphine tolerant swine were subjected to in vivo skin tests and the resulting wheal and flare responses measured. In select swine skin samples from the test sites were measured for mast cell numbers. Swine dermal mast cells were found to release histamine in a dose dependent manner upon compound 48/80 exposure. Both acute and chronic morphine-treated swine had significantly depressed responses to compound 48/80, however this difference was not due alteration in mast cell number or morphology, and skin responsiveness to histamine remained intact.

Effects of morphine dependence on the pathogenesis of swine herpesvirus infection.

To further understand the effects of opiates on the pathogenesis of infectious disease, naturally occurring pathogens were studied in a swine model. Swine were given morphine for 21-42 days to establish a tolerant, dependent state. On day 7 after morphine initiation, pigs were challenged with swine herpesvirus-1 (SHV-1); on day 14, selected animals were superinfected with Pasteurella multocida. Evaluations were made of the clinical disease, protective effect of SHV-1 vaccination, and pathology. Morphine-dependent animals developed significantly greater virus-induced and secondary bacterial pneumonia. Prior vaccination with SHV-1 was not protective against pneumonia in morphine-dependent pigs. Unexpectedly, clinical signs associated with neurologic disease were less pronounced, and mortality from viral encephalitis was decreased in morphine-treated animals. Collectively, the findings demonstrate that morphine dependence is associated with a marked alteration of the pathogenesis of SHV-1 and that the effects of this opiate on pathogenesis are determined by the specific site of infection.

Acute and chronic morphine administration in swine.

Functional responses to acute and chronic morphine administration in domestic swine were examined and correlated with pharmacokinetic profiles. Acute effects of morphine sulfate were monitored in pigs for 24 h and the chronic actions of morphine alkaloid were monitored for 21 days. Serum morphine levels, nociception, locomotor activity, respiratory rate, body temperature, and body weight were monitored during all studies. To assess nociception in a large laboratory animal, a portable thermal stimulating device was constructed. Morphine sulfate administered IV and SC had a half-life of approximately 1 h whereas delayed-release morphine alkaloid delivered SC had a half-life of 28 h. The degree of antinociception paralleled decline in blood morphine levels for both SC- and IV-administered animals. Tolerance occurred to both antinociception as well as weight gain despite morphine levels remaining constant over the 21-day period. Morphine dependence was demonstrated by precipitation of an abstinence syndrome using naloxone. Animals in withdrawal displayed consistent signs, including wet-dog shakes, posture changes, vocalization, and salivation. Collectively, these results indicate that swine may be reliably employed as a model to study the actions of morphine and opiate-like compounds.

Chronic morphine administration impairs cell-mediated immune responses in swine.

Swine were used as an experimental animal model to evaluate immunomodulating effects of the opiate drug, morphine, on antigen-specific humoral and cell-mediated immune responses. Morphine free base in peanut oil was administered at 4-day intervals for up to 42 days to maintain drug levels at or above 100 ng/ml. The effect of morphine administration on humoral immune responses was evaluated by immunization on day 7 of morphine treatment with a battery of antigens, including swine herpes virus (also known as pseudorabies virus, PRV), Brucella abortus and the Escherichia coli pilus antigens K88, K99, 987P and F41. Fourteen days later, swine were reimmunized with B. abortus and E. coli pilus antigens. Antibody titers to these antigens were evaluated on a weekly basis. Cell-mediated immunity was evaluated by measuring skin immune responses to the antigen 2,4-dintroflurobenozene (DNFB). In one experiment, swine were sensitized with DNFB on day 7 of morphine treatment at the same time as immunization with the other antigens. In a second series of experiments, swine were sensitized either 7 days before or 7 days after initiation of morphine treatment. Pigs were challenged with DNFB administered 27 days after the initiation of morphine treatment and skin responses were evaluated 24 h later. The ability of swine to resist PRV infection was evaluated by exposure to virulent virus on day 28 of morphine treatment. Chronic morphine administration did not impair the induction of the humoral immune responses to bacterial or viral antigens. In addition, morphine treatment did not alter the resistance of immunized swine to PRV infection.(ABSTRACT TRUNCATED AT 250 WORDS)