Erythrocyte Sedimentation Rates and Leukogram Changes in Canine Model of Osteoarthritis.

Inflammatory markers such as erythrocyte sedimentation rates (ESR) have been evaluated in humans withosteoarthritis (OA). However, there has been no record of evaluation of ESR during OA in dogs. Changes in erythrocytesedimentation rates (ESR) and leukogram functions were evaluated following experimental knee osteoarthritis (OA).Tendogs of both sexes with (mean weight = 12.4 ± 1.8kg) were used. Experimental OA was induced in the right knee, using thegroove model and confirmed radiographically using evidence of joint space narrowing and presence of osteophytes. Gaitwas assessed subjectively and scores (GAS) were assigned. Blood was obtained fortnightly for the determination of ESR,total white blood cell (tWBC), neutrophil and lymphocyte counts, while knee radiographs were obtained fortnightly fortwelve weeks. Radiographic scores (RAS), GAS, ESR and leukocyte parameters between the different time points werecompared with ANOVA. Correlation between parameters was evaluated using Pearson's correlation. A "P" value less than0.05 was considered significant. Both ESR and neutrophil/lymphocyte (N/L) ratio increased from week 0 to week 12 of OA.However, tWBC, neutrophil and lymphocyte counts did not differ significantly. Both GAS and RAS increased up to week 4and 6 of OA respectively. Erythrocyte sedimentation rates was significantly (p= 0.033) and positively correlated (r=0.793)with N/L ratio, but negatively and slightly correlated (r= -0.843) with GAS. There was no significant correlation betweenESR and RAS. It was concluded that both ESR and N/L ratio might be useful in monitoring progression of OA in dogs.

Evaluation of immune response in challenged chickens vaccinated with Newcastle disease vaccine using gums from Cedrela odorata and Khaya senegalensis as delivery agents.

Immune response of challenged chickens following previous vaccinations with Newcastle disease vaccine using gums from Cedrela odorata and Khaya senegalensis as delivery agent were evaluated. Two hundred and fifty-two one-day old chickens were divided into vaccine-gum oral (GVOR), vaccine-gum ocular (GVOC), vaccine oral (VOR), vaccine ocular (VOC), gum oral (GOR), gum ocular (GOC), No-gum-no-vaccine/challenged (NGNV/C), and No-gum-no-vaccine/unchallenged (NGNV/U) groups. They were vaccinated at days 21 & 42 and challenged at day 84. Trachea and intestinal washings were collected at intervals as well as weekly serum samples. These were analyzed using enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition (HI) test for mucosal and systemic IgG response (MA and SA). Statistical analysis was done using Omnibus one-way ANOVA. MA and SA were not different (P > 0.05) post first and second vaccination although gum-vaccine groups were marginally higher post second vaccination. Post Infection (PI), there was an early and sustained spike in both MA and SA for the GV groups especially GVOR (P < 0.05). MA and SA for the Gum alone (especially GOR) groups also spiked PI (P < 0.05). Therefore, phytogenic polymers used could be said to possess immunopotentiating property with a possible induction of immunologic memory mechanism.

Preclinical toxicity of a new oral anticancer drug, CI-994 (acetyldinaline), in rats and dogs.

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.

Subacute toxicity of a purine nucleoside phosphorylase inhibitor in rats.

Rats received daily oral doses of 15, 50, 150, or 200 mg/kg CI-1000 for 4 weeks. Doses were selected based on findings from a 2-week range-finding study where doses of 250 and 500 mg/kg resulted in mortality. In the 4-week study, females given 200 mg/kg were sacrificed during Week 2 due to poor condition. Serum creatinine and urea nitrogen increased 2- to 2.5-fold in females given 200 mg/kg. Dose-related increases in urine volume, urinary protein excretion, and osmolar excretion occurred in both sexes beginning at 50 mg/kg. Kidney weights increased 9-40% in both sexes at > or = 50 mg/kg; histopathologic changes were confined to the 150 and 200 mg/kg groups. At Week 4, T-suppressor/cytotoxic lymphocytes were reduced 43% and T-helper/inducer lymphocytes were reduced 22% in males given 200 mg/kg. In females, T-suppressor/cytotoxic lymphocytes were significantly decreased (approximately 40%) at 50 and 150 mg/kg, with no significant effects on T-helper/inducer lymphocyte populations. At Week 8, following 4 weeks without treatment, T-lymphocyte subpopulations were similar in control and drug-treated groups. B-lymphocyte counts and percentages were increased at Weeks 4 and 8 in males receiving 150 or 200 mg/kg. Thymic weights decreased at Week 4 at doses of 150 and 200 mg/kg. Plasma CI-1000 levels were higher in females than in males at all doses except 15 mg/kg; Cmax and AUC values were largely dose proportional in both sexes. In summary, CI-1000 was well-tolerated at doses of 15, 50, and 150 mg/kg with no adverse effects occurring at 15 mg/kg. Drug-induced changes in the kidney were mild and reversible. Immunomodulatory effects were noted at doses of 50 mg/kg or higher.

Quinolone arthropathy--acute toxicity to immature articular cartilage.

A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP). Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown. This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis. Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction. Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage.

Causes of lamb morbidity and mortality in the Ethiopian highlands.

A study was conducted to investigate causes of lamb morbidity and mortality on farms and on-station at Debre Berhan during 1989 and 1990. It showed pneumonia (bacterial and/or verminous), starvation-mismothering exposure (SME) complex, gastrointestinal parasites, enteritis, abomasal impaction and physical injuries to be important health constraints on productivity. Neonatal mortalities were 51.5% and 46.3% on farms and on-station respectively and occurred owing to management problems such as SME, abomasal impaction and physical injuries. On the farms the lamb birth weight was 2.56 +/- 0.25 kg and was significantly (p < 0.05) affected by the dam's age, lambing weight, litter size, sex of lamb and year of lambing, but not by the season of lambing. Birth weight significantly (p < 0.05) influenced lamb mortality. Lambs with a low birth weight tended to die from SME. Morbidities and mortalities due to infectious causes increased in older lambs, suggesting that infections were acquired with age when resistance was lowered owing to inadequate nutrition and poor management. Heavy loss of lambs could be overcome by such health management interventions as foster mothering, warming lambs during the cold season and vaccination with polyvalent vaccines against pasteurellosis, clostridial infection and Dictyocaulus filaria.

Repeatability of measurements of packed cell volume and egg count as indicators of endoparasite load and their relationship with sheep productivity.

Monthly measurements of packed cell volume (PCV) and nematode and trematode eggs per gram (EPG) were made in Ethiopian highland sheep at Debre Berhan, Dejen, Deneba, Tulu Meko and Wereilu from June 1988 to December 1989. High frequencies of low PCV, high nematode EPG and high trematode EPG were found at Tulu Meko. Among the productivity traits examined, body condition scores and live-weights were significantly (P less than 0.05) associated with differences in PCV and nematode and trematode EPG levels at most sites. The lambing interval was, however, not significantly (P greater than 0.05) affected by these variables. Monthly repeatabilities of PCV, body weight and body condition scores were 0.44 +/- 0.01, 0.71 +/- 0.01 and 0.35 +/- 0.01, respectively, while those of nematode (0.09 +/- 0.01) and trematode EPGs (0.20 +/- 0.02) were much lower. The high repeatability for PCV indicates that it was less affected by the variable factors influencing egg output, and hence it could be utilized in conjunction with nematode and trematode EPG levels for endoparasite monitoring. Repeatability of the lambing interval across parities was 0.43 +/- 0.14.

Effect of nutrition and endoparasitic treatment on growth, onset of puberty and reproductive activity in Menz ewe lambs.

Ewe lambs of the Ethiopian Menz breed were assigned at weaning (90+/-3 days) to four levels of nutrition (poor, low, medium and high) to achieve different premating growth rates with or without treatment for endoparasites. A concentrate mixture providing 2.5 Mcal/kg dry matter (DM) metabolizable energy and 15.2 g/kg DM digestible protein was used. Improved nutrition increased lamb postweaning average daily weight gain up to puberty by 6 to 26 g/day and the conception rate to first estrus by 9 to 16% while it reduced the mortality rate by 24 to 31% and age at first lambing by 2 to 5 months. Lambs reached puberty (age at first estrus) at 16.9+/-0.1 kg (+/-SEM) or 60% of mature body weight and 350+/-12 days of age. The onset of puberty was advanced by weaning weight (P<0.05), itself being well correlated with birth weight (r = 0.51, P<0.001), and by level of nutrition (high=299+/-19, medium=301+/-18, low=383+/-23 and poor=454+/-31 days, P<0.001) through enhanced growth rate (r = -0.82, P<0.001). No independent effect of drenching for endoparasites on pubertal development was observed (P>0.05), but its interaction with season-of-birth improved the growth of lambs born during the period of short rains (P<0.05). Overall mean litter size at first lambing was 1.07; the twinning rate was 6.5% and the birth weight was 1.9+/-0.1 kg. Up to 13.4% of newborn lambs, averaging 1.3+/-0.6 kg, died on the day of parturition. The results indicate that improved growth rate and body weight, resulting from better postweaning nutrition, affects the attainment of puberty in Menz ewe lambs. Mitigation of nutrition stress and endoparasitic infection depending on season-of-birth would thus increase the annual reproductive rate of breeding ewes and flock productivity.

Comparison of different Fasciola hepatica antigens and their use to detect infection in sheep by an enzyme immunoassay.

Soluble antigens of adult Fasciola hepatica were extracted from homogenized parasites and purified with gel chromatography on Sephadex G-200. Six peaks were obtained, and the second highest in molecular weight showed highest correspondence in a microplate enzyme immuno assay with parasite metabolite antigens. Optimal coating antigen concentration was 5 micrograms/ml and sample dilution 1:20. Total running time of assay was 3 hours. Positive and negative sheep sera was obtained from a group of experimentally infected tracer lambs.

Toxoplasmosis in sheep, goats and cattle in central Ethiopia.

In a seroepidemiological survey using an indirect haemagglutination assay, the prevalence rate of toxoplasmosis in central Ethiopia was 22.9% of 899 sheep, 11.6% of 753 goats and 6.6% of 785 cattle. There were high titres of 1:256 or more which suggest current infections. These results indicate that toxoplasmosis may be an important cause of reproductive wastage in small ruminants. The public health significance of this disease is discussed. Improved hygiene and management could reduce the prevalence of the disease.

The effect of handling methods on subsequent plasma progesterone levels in sheep.

The mean progesterone concentration in the plasma of 10 adult Ethiopian Highland sheep obtained immediately after slaughter was 10.56 +/- 3.98 ng/ml. Samples were subsequently incubated at 4 degrees C, room temperature (19-22 degrees C) or 26 degrees C as either plasma or intact but citrated blood. Failure to separate plasma affected the progesterone content at 2-72 h at room temperature or 26 degrees C (p less than 0.01 - p less than 0.0001). Incubation temperature affected the plasma concentration at 18 h (p less than 0.05) and 24 h (p less than 0.001). Although progesterone values were generally higher in separated plasma, disparity with the values from plasma separated from incubated citrated blood was small (r = 0.76-0.98). Progesterone concentration declined haphazardly after collection but sometimes exceeded the initial readings. This kept the average concentration of progesterone in plasma separated immediately after collection fairly constant and within 15% of zero time samples during the first 48 h.

The influence of watering practices on the transmission of Fasciola among sheep in the Ethiopian highlands.

As many ewes and lambs watered at concrete ponds in well-drained sites acquired fluke infection as those watered at natural ponds in areas suitable for the snail intermediate hosts of Fasciola hepatica. Fasciola transmission, as evidenced by the increasing number of seropositive hosts in an enzyme-linked immunosorbent assay (ELISA), occurred during the heavy rainy period of July-September and declined with the onset of the dry season, being succeeded by the emergence of faecal positive hosts. This indicates the superiority of ELISA over coprological techniques in the early diagnosis and seroepidemiology of this parasitic infection. Host productivity, as reflected in weight gains and haematological parameters, was not significantly affected by the fluke infections.

The prevalence of cysticercosis and hydatidosis in Ethiopian sheep.

Five hundred and sixty sheep, slaughtered at an Addis Ababa abattoir, were examined for cysticercosis and hydatidosis. The prevalence of the metacestodes of Taenia hydatigena was 37.1% and that of Echinococcus granulosus 16.4%. In addition, the age and sex prevalences of hydatid cysts, their organ distribution and the ratio of fertile cysts were determined.

Abomasal impaction associated with anorexia and mortality in lambs.

Anorexia in forty-six (6.1%) out of 753 neonatal lambs was investigated. Thirty-five of these lambs (76.1%) died while eleven (23.9%) recovered after treatment. Coagulated rubber-like milk clots were found in fifteen (42.9%), phytobezoars in nine (25.7%) and trichophytobezoars and coarse straws in eleven (31.4%) of the dead lambs.

Subacute toxicity of dietary 3-acetyldeoxynivalenol in mice.

3-Acetyldeoxynivalenol was incorporated into a semisynthetic diet at levels of 2.5, 5, 10 or 20 ppm and fed to mice for up to 48 days. Body weights and feed consumption were determined, and blood samples for hematological evaluation were taken. Selected tissues were examined microscopically and the humoral immune response was assessed using the Jerne plaque assay. 3-Acetyldeoxynivalenol caused a dose-related depressed feed consumption within the first seven days and reduced body weight until day 14 when fed at levels up to 10 ppm. When fed at a level of 20 ppm, an initial depression in body weight gain and a general malaise were followed by a return to normal. At necropsy, no macroscopic or microscopic lesions could be found. The immune response was not significantly affected after seven or 14 days, but at 21 days, a dose-dependent enhanced response was observed. The findings indicate that, after an initial period of reduced feed intake, animals are apparently able to overcome the toxic effects of 3-acetyldeoxynivalenol.

Pathology of acute 3-acetyldeoxynivalenol toxicity in mice.

Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3-acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3-acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes.

Effect of hemagglutinin extracts on acetylcholinesterase activity in some brain areas of weanling rats.

Two trials involving male and female weanling albino rats (Wistar strain) were conducted to investigate the effects of cowpea and limabean hemagglutinin extracts on acetylcholinesterase (AChE) activity in different parts of the brain. The results show that AChE activity varies with brain region. Cowpea hemagglutinin significantly inhibited AChE activity in the pons of male and female rats, while limabean hemagglutinin significantly inhibited AChE activities in the pons of both male and female rats, in the hippocampus of female rats and in the medulla, cerebellum and midbrain of male rats. Inhibition of AChE activities was more pronounced in male or female rats inoculated with a mean lethal dose of either phytohemagglutinin, than in those inoculated with a sublethal dose.