Production and metabolism studies on bovine trichostrongylosis

In this thesis the sequential development of naturally occurring bovine trichostrongylosis in the same animals was studied, for the first time, over a two year period. The species of gastro-intestinal trichostrongyle most frequently present were primarily Ostertagia ostertagi and Cooperia oncophora; a few Trichostrongylus axei were also recorded. In a control group of 16 calves, overwintered larvae of O. ostertagi and C. oncophora were acquired in the spring of their first grazing season. The eggs resulting from these infections gave rise to another generation of larvae on the pastures by August, which was sufficient in number to cause the type I disease, characterised by loss of appetite, diarrhoea and weight loss. One animal was destroyed in extremis just prior to the type I disease, clinical signs of parasitic bronchitis occurred namely, increased respiratory rate and coughing necessitating treatment with diethylcarbamazine and then levamisole. At housing in October, five calves were slaughtered and the post-mortem worm burdens consisted almost entirely of early 4th stage larvae of O. ostertagi and C. oncophora, which were arrested in development. Following housing in October, the animals were clinically normal during the so-called pre-type II phase, until late February and early March when some reduction in appetite was noted which was followed by clinical diarrhoea and weight loss in April and May in the so called type II disease. During the second grazing season, the animals acquired a solid immunity to C. oncophora and a good immunity to O. ostertagi and this was reflected in the low numbers of eggs in the faeces, relatively low numbers of larvae an the pasture and low worm burdens at final slaughter two months after housing in October. A second group of 16 calves, which were grazed on immediately adjacent but separate fields, received a sustained release device containing the anthelmintic morantel tartrate, which was introduced by a special dosing gun into the rumen of each calf prior to grazing in the spring of each year. The boli were designed to release the drug over a 90-day period and their introduction prevented the build-up of larval infection on the pasture and the occurrence of the type I and the type II disease. The advantage in live weight gain alone over the two year period amounted to a mean of 33 kg over the controls. Furthermore, the introduction of the boli did not interfere with the acquisition of immunity in the second grazing season. Several biochemical parameters were monitored of which two, serum pepsinogen and gastrin levels, proved particularly interesting. All values of these parameters became markedly elevated when large numbers of parasites were actively developing to the adult stage i.e. during the type I and type II disease, but not during the pre-type II phase when the worm populations consisted mainly of arrested larval stages, or when the animals become immune. The single and combined linear relationship between pepsinogen, gastrin and numbers of developing and adult Ostertagia parasites was very highly significant. Although further information is necessary to define normal bovine plasma gastrin levels and the affecting factors, the results in this study suggest that the evaluation of plasma gastrin could be a useful adjunct to plasma pepsinogen as a combination diagnostic test for ostertagiasis, particularly when pepsinogen values may be only moderately elevated in Immune cattle under larval challenge. (Abstract shortened by ProQuest.)

Scanning electron microscopic study of the lower respiratory tract in cattle

The surface characteristics of the bovine lower respiratory tract were studied with the use of the scanning electron microscope (SEM). The first step in the investigation was to become familiarized with the methods of SEM. Thereafter two different projects were designed and performed. The first project was to assess the pattern of ciliated cells in normal one week old calves and compared this with the pattern in adult cattle. Two groups of animals, one calves and the other adult cattle, were studied and none of them had gross morphological evidence of pulmonary disease. The trachea was examined as well as bronchi, bronchioles and alveoli in both the cranial and caudal lobes of the right lung. In general in both groups, the lumenal surface of the large airways was completely covered by cilia apparently forming an efficient "mucociliary escalator". However, in the adult cows some areas of ciliated cells were found devoid of cilia, and these were considered to be abnormal. The non-ciliated cells in this part of the lower respiratory tract were not easily identified unless they were discharging secretion. In small bronchi, non-ciliated cells v/ere more evident and based on the fact that these cells were present sometimes as frequently as the ciliated cells, they were thought likely to be epithelial secretory cells, either mucous or serous cells. The bronchioles had many non-ciliated cells and almost no significant ciliated cells capable of forming a complete ciliary carpet. Type I and Type II alveolar epithelial cells, as well as alveolar macrophages, were identified in both groups of animals. Pores of Kohn were found in the alveolar walls in all the animals and considered to be normal. No brush cells were found. Distinctive respiratory bronchioles were not seen and there was a relatively sudden transition from terminal bronchioles to alveolar ducts. After the normal pattern of the surface morphology was established for normal bovine lower respiratory tract, a second investigation was designed. This was done to assess the changes that could be observed with SEM on the surface of the respiratory tract of calves infected with Dictyocaulus viviparus and calves vaccinated against lungworm and experimentally infected with D. viviparous Ten Friesian cross calves were divided into three groups which received different treatments. Group 1 comprised two calves vaccinated with Dictol as recommended by the manufacturers. Group 2 comprised four calves experimentally infected with approximately 5,000 infective larvae of D. viviparus and Group 3 comprised four calves vaccinated with Dictol at the same time as Group 1 and challenged orally with the same dose of D. viviparus larvae at the same time as Group 2. One calf from Group 1, Group 2 and Group 3 was killed on 15, 25, 35 and 45 days after challenge. The changes observed in the luminal surface of the trachea, as well as the bronchi, bronchioles and alveoli of both the cranial and the caudal lobes of the right lung were recorded on the pleural surface of the lungs. In Group 2 the infected calves appeared with a variety of pathological changes as the infection progressed. These changes were mainly described as adult parasites and eggs in the bronchi, a severe cellular infiltration of the lung with worm eggs and aspirated larvae occupying the lumena of the alveoli. Intercurrent infection was diagnosed occurring on the surface of the conducting airways, where microorganisms were found colonising the tips of the cilia. In addition, areas devoid of cilia and extruded cells were observed and considered to have resulted from viral infection. The relative proportions of epithelial ciliated cells and non-ciliated cells were also affected at these levels. The surface of the conducting airways of the calves in Group 3 were slightly modified. The lung showed infiltration of cells, lymphocytic nodules implanted in the lung parenchyma in close relation in close relation to bronchioles and small bronchi, was the most relevant finding. The SEM results produced three dimensional pictures which strikingly illustrated the modified epithelium and the reactions present during the course of prepatent and patent lungworm infection in susceptible and immune calves

Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression

AbstractThe high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo conditions. The current work evaluated the relationship among systemic drug exposure, target tissue availabilities and the pattern of drug accumulation within resistant Haemonchus contortus for moxidectin, abamectin and ivermectin. Drug concentrations in plasma, target tissues and parasites were measured by high performance liquid chromatography. Additionally, the efficacy of the three molecules was evaluated in lambs infected with resistant nematodes by classical parasitological methods. Furthermore, the comparative determination of the level of expression of P-glycoprotein (P-gp2) in H. contortus recovered from lambs treated with each drug was performed by real time PCR. A longer persistence of moxidectin (P<0.05) concentrations in plasma was observed. The concentrations of the three compounds in the mucosal tissue and digestive contents were significant higher than those measured in plasma. Drug concentrations were in a range between 452ng/g (0.5day post-treatment) and 32ng/g (2days post-treatment) in the gastrointestinal (GI) contents (abomasal and intestinal). Concentrations of the three compounds in H. contortus were in a similar range to those observed in the abomasal contents (positive correlation P=0.0002). Lower moxidectin concentrations were recovered within adult H. contortus compared to abamectin and ivermectin at day 2 post-treatment. However, the efficacy against H. contortus was 20.1% (ivermectin), 39.7% (abamectin) and 89.6% (moxidectin). Only the ivermectin treatment induced an enhancement on the expression of P-gp2 in the recovered adult H. contortus, reaching higher values at 12 and 24h post-administration compared to control (untreated) worms. This comparative pharmacological evaluation of three of the most used macrocyclic lactones compounds provides new insights into the action of these drugs

Estrategias farmacológicas contra la resistencia a drogas antihelmínticas en ovinos: modulación in vivo de la glicoproteína-P en el huésped y en los parásitos resistentes

En los últimos años, un nuevo paradigma se ha incorporado al estudio farmacocinético de diversos grupos de drogas con la participación de diferentes transportadores celulares de membrana en los procesos de absorción, distribución tisular y excreción de compuestos farmacológicamente activos. De todos los transportadores celulares identificados, la glicoproteína-P (gp-P) ha sido la más estudiada. Si bien la gp-P fue inicialmente descripta por su sobreexpresión en células tumorales resistentes a múltiples drogas anticancerígenas, también se localiza en células normales de tejidos involucrados en los procesos de absorción, distribución, y excreción de fármacos (Ballent et al., 2005). Esta proteína actúa como una bomba de eflujo que es capaz de bombear una amplia gama de compuestos hacia el exterior celular por un proceso dependiente de energía. La localización específica en estos tejidos sugiere que la gp-P cumpliría un importante rol en la regulación del transporte de fármacos, modificando de este modo el comportamiento cinético y la biodisponibilidad de los mismos (Schinkel, 1997).Trabajo galardonado con el Premio Fundación Pérez Companc, versión 2011Academia Nacional de Agronomía y Veterinari

Estrategias farmacológicas contra la resistencia a drogas antihelmínticas en ovinos: modulación in vivo de la glicoproteína-P en el huésped y en los parásitos resistentes

En los últimos años, un nuevo paradigma se ha incorporado al estudio farmacocinético de diversos grupos de drogas con la participación de diferentes transportadores celulares de membrana en los procesos de absorción, distribución tisular y excreción de compuestos farmacológicamente activos. De todos los transportadores celulares identificados, la glicoproteína-P (gp-P) ha sido la más estudiada. Si bien la gp-P fue inicialmente descripta por su sobreexpresión en células tumorales resistentes a múltiples drogas anticancerígenas, también se localiza en células normales de tejidos involucrados en los procesos de absorción, distribución, y excreción de fármacos (Ballent et al., 2005). Esta proteína actúa como una bomba de eflujo que es capaz de bombear una amplia gama de compuestos hacia el exterior celular por un proceso dependiente de energía. La localización específica en estos tejidos sugiere que la gp-P cumpliría un importante rol en la regulación del transporte de fármacos, modificando de este modo el comportamiento cinético y la biodisponibilidad de los mismos (Schinkel, 1997).Trabajo galardonado con el Premio Fundación Pérez Companc, versión 2011Academia Nacional de Agronomía y Veterinari

Scanning electron microscopic study of the lower respiratory tract in cattle

SIGLEAvailable from British Library Document Supply Centre- DSC:D65270/86 / BLDSC - British Library Document Supply CentreGBUnited Kingdo