piperidines and Swine-Diseases

Cystoisospora suis is a common diarrheal pathogen of piglets and typically controlled by metaphylactic toltrazuril application. Recently, toltrazuril resistance has been reported in the field; however, both evaluation of toltrazuril efficacy against field isolates and the anticoccidial drug development for pigs is hampered by costs and labor of animal experimentation. Therefore an in vitro merozoite development assay was developed to evaluate the efficacy of compounds against C. suis in vitro. Monolayers of IPEC-1 cells were infected with sporozoites derived from oocysts of defined C. suis laboratory strains and the optimal infection dose as well as concentration, time point and duration of treatment were evaluated by quantitative real-time PCR. Cell cultures were treated with bumped kinase inhibitor (BKI) 1369 at different time points to evaluate the possibility to delineate effects on different developmental stages in vitro during invasion and early infection, and to determine different inhibitory concentrations (IC

Topics: Animals; Cell Line; Coccidiosis; Coccidiostats; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Resistance; Inhibitory Concentration 50; Merozoites; Pilot Projects; Piperidines; Pyrimidines; Quinolines; Real-Time Polymerase Chain Reaction; Sarcocystidae; Sulfones; Sulfoxides; Swine; Swine Diseases; Triazines

Bumped kinase inhibitors (BKIs) are a new class of antiprotozoal drugs that target calcium-dependent protein kinase 1 (CDPK1) in various apicomplexan parasites. A multiple dose regimen of BKI 1369 has been shown to be highly effective against Cystoisospora suis (syn. Isospora suis), the causative agent of neonatal porcine coccidiosis. However, multiple dosing may not be widely applicable in the field. The present study aimed to determine the efficacy of reduced treatment frequencies with BKI 1369 against porcine cystoisosporosis in vitro and in vivo. Pre-incubation of sporozoites with BKI 1369 completely failed to inhibit the infection in vitro unless treatment was prolonged post-infection. Notably, a single treatment of infected cell cultures 2 days post-infection (dpi) resulted in a significant reduction of merozoite replication. In an experimental infection model, treatment of suckling piglets experimentally infected with C. suis 2 and 4 dpi with 20 mg BKI 1369/kg body weight completely suppressed oocyst excretion. A single treatment on the day of infection or 2 dpi suppressed oocyst excretion in 50% and 82% of the piglets and reduced the quantitative excretion in those that shed oocysts by 95.2% and 98.4%, respectively. Moreover, a significant increase in body weight gain and reduced number of diarrhea days were observed in BKI 1369 treated piglets compared to the control piglets, irrespective of time points and frequencies of treatment. Given that reduced treatment frequencies with BKI 1369 are comparable in efficacy to repeated applications without any adverse effects, this could be considered as a practical therapeutic alternative against porcine cystoisosporosis.

Topics: Animals; Coccidiosis; Piperidines; Pyrimidines; Quinolines; Sarcocystidae; Swine; Swine Diseases

Topics: Alkaloids; Animals; Congenital Abnormalities; Female; Piperidines; Plant Poisoning; Pregnancy; Swine; Swine Diseases

Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

Topics: Alkaloids; Animals; Animals, Newborn; Chromatography, Gas; Cleft Palate; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Pregnancy Complications; Pyridines; Seeds; Swine; Swine Diseases

Collections of Nicotiana glauca containing from 0.45-1.14 mg anabasine per gram dry weight of plant induced moderate - severe toxic signs in pregnant ewes and teratogenic effects in their offspring when the ewes were given single daily doses of the plant that provided from 1.66 - 3.42 mg anabasine per kg body weight. Toxic signs included excess salivation, irregular gait, wobbling while walking or standing, recumbency and death. Teratogenic effects occurred in offspring from animals fed those doses the 30th - 60th day of gestation. Terata expression included limb defects such as a fixed excessive carpal flexure with or without lateral or medial rotation of fore or rear limbs, lordosis, irregular shaped head or cleft palate.

Topics: Abnormalities, Drug-Induced; Alkaloids; Anabasine; Animals; Cattle; Cattle Diseases; Female; Gas Chromatography-Mass Spectrometry; Limb Deformities, Congenital; Male; Nicotiana; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Sheep; Sheep Diseases; Swine; Swine Diseases

Nicotiana glauca consumption by pregnant cows or sows produced arthrogryposis and other congenital deformities in their offspring. The plant material administered contained 0.11% anabasine, the suspect teratogen. But concentration varied among various plant parts; woody material was very low but leaves and bark were high. The anabasine was identified by mass spectral fragmentation analysis.

Topics: Anabasine; Animals; Arthrogryposis; Cattle; Cattle Diseases; Congenital Abnormalities; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Swine; Swine Diseases; Teratogens

Opium tincture and Spasmentral were applied to piglets early after weaning and reduced their gastro-intestinal motility, which, however, caused only very minor changes in quantitative germ flora composition in those first days. Short-time suppression of gastro-intestinal motility obviously does not result in detrimental consequences to the organism as a whole, since there seem to be several factors which are involved in the control and regulation of the intestinal germ flora. Impairment of gastro-intestinal motility appeared to be of no importance to the pathogenesis of coli-enterotoxaemia, as it was not followed by higher incidence of the disease.

Topics: Animals; Bacteria; Dexetimide; Digestive System; Escherichia coli Infections; Gastrointestinal Motility; Opium; Piperidines; Species Specificity; Swine; Swine Diseases

Topics: Anesthesia; Anesthetics; Animals; Blood Pressure; Body Temperature; Halothane; Hematocrit; Hemoglobinometry; Phencyclidine; Piperidines; Pulse; Respiration; Swine; Swine Diseases; Time Factors

Topics: Amines; Animals; Chromatography, Ion Exchange; Chromatography, Thin Layer; Diarrhea; Intestine, Small; Intestines; Piperidines; Pyrrolidines; Swine; Swine Diseases; Weaning