The effects of dexamethasone immunosuppression on turkey osteomyelitis complex in an experimental Escherichia coli respiratory infection

The results of a field trial conducted in Latin America with two indirect enzyme-linked immunosorbent assays (ELISAs) and two competitive ELISAs (CELISAs) for the detection of bovine antibody to Brucella abortus are reported. One of the CELISA formats performed most accurately. The percentage of positive reactions in the CELISA relative to the selected positive rose bengal agglutination test (RBT) and complement fixation test (CFT) results was 97.47%, the percentage of negatives relative to the selected negative RBT and CFT results for unexposed cattle was 98.32%, and the percentage of negatives in cattle vaccinated with B. abortus 19 was 96.51%. The same assay format under Canadian conditions had an actual sensitivity of 100%, a specificity of 99.90% in nonvaccinates, and a specificity of 97.7% in a strain 19-vaccinated population. Overall, the CELISA performed as expected and the results were not dissimilar from the results obtained in the Canadian study. This provided further evidence that this CELISA can in many instances differentiate infected cattle from those that are vaccinated or infected with a cross-reacting organism while still giving very few false-positive or false-negative results.     

Mood stabilizers: shared mechanisms of action at postsynaptic signal-transduction and kindling processes

Several distinct classes of agents have demonstrated efficacy as mood stabilizers in patients with bipolar disorder. It may be reasonable to assume that these agents share one or more common mechanisms of action. This paper will explore the hypothesis that all effective mood stabilizers exert their actions through inhibition of postsynaptic signal-transduction and kindling processes. A literature search was performed for all currently used mood stabilizers to identify reports of mood-stabilizer action in postreceptor cell-signaling and kindling processes. Most effective mood stabilizers appear to inhibit intracellular calcium mobilization through several distinct mechanisms. In addition, several mood stabilizers appear to diminish generation of second-messenger molecules from the membrane phospholipids phosphatidylinositol and phosphatidylcholine, inhibit the activity of protein kinases, and directly inhibit activity of G-proteins. Finally, all established mood stabilizers also exhibit antikindling effects. All of these mechanisms of action could dampen excessive intracellular and intercellular signaling, which may be a core feature of the pathophysiology of bipolar disorder. The observation that all effective mood stabilizers inhibit both kindling and signal-transduction pathways suggests that these processes are intimately linked. We hypothesize that an effective mood stabilizer must possess some specific minimum inhibitory effects at postsynaptic signal-transduction and kindling processes. If this hypothesis is correct, then a rational search for safer and more effective mood-stabilizing agents can begin.     

Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk

The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.     

Efficacy of injectable abamectin against gastrointestinal tract nematodes and lungworms of cattle

Lymphocyte-tropic (L-tropic) SIVmac predictably causes immunosuppression and AIDS in rhesus macaques. SIV encephalitis, on the other hand, is caused mainly by macrophage-tropic (M-tropic) SIVmac. We have previously described the derivation of M-tropic, neuroadapted SIVmac from molecularly cloned, L-tropic SIVmac239. In this report we show that inoculation of four macaques with neuroadapted virus resulted in L-tropic SIVmac-related diseases in all four but neurological disease in only two of the four animals. Because cocultivation of infected macrophages with CD4+ lymphocytes results in production of tumor necrosis factor alpha and interleukin-6, we asked whether infiltration of supernatant fluids containing these cytokines into the brains of macaques infected with neuroadapted virus would enhance the development of neurological disease. These procedures failed to promote productive virus replication in the brain. Thus, although different degrees of immunosuppression and AIDS could be induced predictably with L-tropic virus, induction of neurological disease was not predictable even when animals were inoculated with neuroadapted M-tropic virus and inflammatory cytokines were infiltrated into the brains of these animals.     

Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia

We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.     

Role of horn flies (Haematobia irritans) in Staphylococcus aureus-induced mastitis in dairy heifers

OBJECTIVE: To determine whether Staphylococcus aureus can colonize in horn flies and whether colonization is sufficiently persistent for transmission of the organism to cows by flies. ANIMALS: 2 Jersey heifers exposed to infected horn flies. PROCEDURE: Staphylococcus aureus was allowed to colonize in horn flies, and duration of colonization was determined. Flies with colonized S aureus were allowed to feed on teats of uninfected heifers to determine whether intramammary infection could be transmitted from fly to heifer. Scab material from naturally infected heifers was submitted for bacteriologic culture to determine whether S aureus was present and whether scabs could serve as a possible source of S aureus for flies. RESULTS: Staphylococcus aureus colonized in horn flies and remained for up to 96 hours after exposure. Exposure of teats of uninfected heifers to horn flies colonized with S aureus resulted in intramammary infection in 3 of 4 exposed teats. Culture of scab material from teats of naturally infected heifers revealed high concentration of S aureus (> 107 colony-forming units/mg), and flies without previously colonized S aureus were allowed to feed on scabs; S aureus colonized in them just as readily as it did in flies that had fed on experimentally infected blood. CONCLUSIONS: Horn flies are capable of transmitting S aureus-induced intramammary infection to heifers, and scabs on teats are a potential source of S aureus. Fly control on dairy cows in herds with known S aureus problems is recommended as a method to help prevent these infections.     

Immune and physiological responses of turkeys with green-liver osteomyelitis complex

A study of field turkeys was undertaken in order to determine the involvement of relative immunological differences in the etiology of turkey osteomyelitis complex (TOC). Lame and normal turkeys were sampled from commercial flocks just prior to processing in two separate trials. After testing for functions of both humoral and cellular immunity, the turkeys were necropsied and examined for lesions of TOC. There were significantly higher relative spleen and over weights and significantly lower body weights and relative bursal weights in birds with TOC. The birds with TOC had lower response to phytohemagglutinin-P in both in vivo and in vitro tests as well as lower circulating lymphocyte counts and higher monocyte, heterophil, and total white blood cell counts. There was a significantly higher antibody response to sheep red blood cells in turkeys with TOC, whereas antibody response to Salmonella pullorum antigen was not different. There were no significant differences in the percentages of mononuclear cells or heterophils able to phagocytize bacteria or latex particles, or kill bacteria; however, the heterophils from turkeys with TOC lesions did phagocytize significantly fewer latex particles per cell than did those of the healthy turkeys. Total serum protein, uric acid, and blood urea nitrogen levels were higher in birds with TOC, whereas hemoglobin, iron, alkaline phosphatase, and gamma-glutamyl-transferase levels were lower. Although many of the differences in birds with TOC could be caused by the normal host reaction to infection, further study may reveal innate differences that contribute to susceptibility to TOC.     

Lipid composition of hepatic and adipose tissues from normal cats and from cats with idiopathic hepatic lipidosis

Physical restraints are a frequently used but disputed method to prevent falls. The aim of the present study was to investigate how the use of restraints in institutional elder care relates to previous falls and to the estimated fall risk of the individual patient. A total of 1142 patients, mean age 82 years, were included in the study. A questionnaire, the Multi-Dimensional Dementia Assessment Scale (MDDAS), was used to measure motor function, vision, hearing, ADL performance, behavioral symptoms, psychiatric symptoms, cognitive impairment and use of medication. Questions concerning the use of physical restraints and known previous falls were added to the instrument. Based on data from the questionnaire (MDDAS), a score on the Downton Fall Risk Index was calculated for each patient. All in all, 248 (22%) of the patients had been subject to restraints and for 155 of them (14%) such measures had been taken to prevent falls. Only weak connections were found between the restraining of patients to prevent falls and the prevalence of known previous falls during hospital stay (phi = 0.05), and estimated fall risk (phi = 0.07). The results indicate that the use of physical restraints is poorly connected with the estimated fall risk. Therefore, this study may point to a possible overuse of these measures.