Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

OBJECTIVE: To evaluate whether the leukotriene (LT) D4 receptor antagonist L-708,738 is therapeutically beneficial in treating horses with recurrent airway obstruction (heaves). ANIMALS: 12 adult horses with heaves and healthy lung lobes from 20 slaughtered horses. PROCEDURE: Lung lobes were used for smooth muscle tension and radioligand binding studies. Horses with heaves were given a placebo for 14 days and administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h) or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from days 14 to 28. Pulmonary function was measured weekly for 36 days, and bronchoalveolar cells were collected on days 0,14, and 29 for cytologic examination. RESULTS: Nanomolar concentrations of L-708,738 were effective at antagonizing LTD4-induced bronchoconstriction and LTD4-receptor binding in lung lobes. Mean peak and trough L708,738 plasma concentrations during the treatment period were 1.54 and 0.28 microM, respectively. On days 21 and 29, lung mechanics were significantly improved in the dexamethasone-treated horses but not in the L-708,738-treated horses. Neither dexamethasone nor L-708,738 had a significant effect on cytologic findings. CONCLUSIONS AND CLINICAL RELEVANCE: L-708,738 was bioavailable after oral administration and sustained concentrations in plasma during the dosing period that exceeded in vitro efficacy values. However, airway function did not improve, suggesting that either drug concentrations in the lungs were subtherapeutic or that cysteinyl LT may not be important mediators of airway inflammation in heaves. Results provide the first evidence of cysteinyl LT1 receptors in airways of horses.     

IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves

Heaves is a common condition of horses of cold climate that is characterized by small airway inflammation and obstruction following exposure of susceptible horses to moldy hay and straw. It has been shown that helper T lymphocytes (Th) orchestrate the inflammatory response in asthma and in various animal models of allergic lung diseases by the release of Th2-type cytokines. Results of previous studies indicate that a predominant expression of Th2-type response by airway cells may also be present in heaves. To evaluate the temporal mRNA expression of Th1 (IFN-gamma) and Th2 (IL-4, IL-5) type cytokines in heaves and their relationship to clinical disease, we studied the pulmonary mechanics and cytokine mRNA expression (IL-4, IL-5 and IFN-gamma) in bronchoalveolar lavage lymphocytes of horses with heaves (n=6) and control (n=6) before and after 24h and 9 days of continuous natural inhalation challenge. Starting 24h after challenge horses with heaves, but not control horses, had a significant increase in pulmonary elastance and the number of lymphocytes expressing mRNA for IL-4 and IL-5. These changes were further increased at 9 days, at which time the number of cells positive for IFN-gamma mRNA was decreased. In this study we have shown that BAL lymphocytes of horses with heaves during clinical exacerbation have a predominant Th2-type cytokine response and that this response coincides in time with the presence of airway obstruction.     

Application of Soil Fractionation Methods to the Study of the Distribution of Pollutant Metals

Three agricultural Fluvisols polluted by sewage sludge were dispersed by shaking in water or in organic solvent for particle size and density separations. The perturbations caused by the ultrasonic treatment were discussed. Only the carbonate particles were disrupted to very fine particles. The pollutant metals were not displaced by the treatments, except perhaps Cd that is partly soluble in water and in other solvents. We discussed the relationship between soil constitution and major element chemical analyses. We obtained enough different fractions by using the ultrasonic and other dispersion treatments and by fractionating versus two physical parameters (i.e. particle size and density), for a correlation study between the contents of major and trace elements. We found that Cu was the only element to be more concentrated in the “free” organic matter. Other metals were more concentrated within an organo-mineral compartment, containing evoluted organic matter, fine clay and hydrous oxides. No pollutant metals were associated with carbonates, feldspars, and quartz. Other less general features were discussed.     

Teaching veterinary clinical pathology to undergraduate students: an integrated European project

BACKGROUND: Veterinary clinical pathology is a relatively new and emerging discipline in Europe that has gained momentum with the recent establishment of a specialty college. In this situation, veterinary faculties may face challenges in understanding and defining what clinical pathology is and how it can best be integrated into existing curricula. In addition, many schools in Europe may not yet have available a critical mass of suitably qualified faculty capable of teaching in all areas of clinical pathology. OBJECTIVE: The main purpose of this report is to describe the goals, procedures adopted, teaching material produced, and proposed future activities of a major European initiative designed to develop a veterinary clinical pathology curriculum. METHODS: Four working subgroups were formed to establish a list of course objectives and topics and prepare a series of lectures. These contents were reviewed and discussed several times at a series of general meetings. RESULTS: An undergraduate course on veterinary clinical pathology was designed with course objectives, a list of topics and a CD-ROM consisting of 24 lectures. CONCLUSIONS: The results of this project could be useful in the establishment or improvement of training programs in veterinary clinical pathology at the undergraduate level in Europe and in other places around the world. The provision of teaching resources for faculty could help to instill in veterinary students a strong understanding of the discipline and promote development of advanced training programs and career opportunities in clinical pathology in Europe.     

Variations saisonnieres des composantes de l'alcalinite des eaux dans le haut-estuaire du fleuve Saint-Laurent (Quebec)

Measurements of the total alkalinity and its components have been made on waters collected from the St.` Lawrence River during the year 1980–1981. Analyses of the total inorganic carbon, the borates, the phosphates and the silicates along with the pH and the total alkalinity permitted an evaluation of each component. In all seasons, the carbonate system was the major component (96%) of the total alkalinity. The residual alkalinity accounting for only 2 to 3% and obtained by the difference between the total alkalinity and the sum of the components appears attributable to weak organic acids. The saturation state of calcite coincided with a river saturated by dissolved calcium carbonate during the summer season and only 45% saturated during the winter season.     

Ligno-Cellulose Composting: Case Study on Monitoring Oil Palm Residuals

Oil palm empty fruit bunches (EFB) composting is increasingly being considered by tropical farmers as a worthwhile alternative to direct spreading in the field. EFB are ligno-cellulose residues comprising 46% cellulose and 16.5% lignin with a high C:N ratio ranging from 45 to 70. In hot regions, it is essential to control variations in the water content of the substrate. This case study set out to optimize the EFB composting procedure by monitoring two key factors, namely the nutritional balance of the biomass and its water content. The trial was conducted on a composting platform belonging to the PT SMART Tbk company (Indonesia) in windrows comprising shredded EFB watered weekly with oil mill effluents. The quantity of effluent to be added was calculated so as to systematically top up to 60% humidity. The initial C:N ratio of the EFB was reduced by urea and/or ripe compost applications (seeding). Application times and rates were studied on two windrows, one in an open area, the other in an area sheltered by a roof to prevent over-rapid drying. After ten weeks the compost could be considered ripe for all the treatments; at that stage, composting had reduced the volume and initial weight of the fresh EFB by 85% and 50% respectively. The combined action of a temperature rise and windrow turning led to substantial water losses through evaporation, resulting in a sudden drop in windrow humidity at the start of composting. When rainfall was insufficient, effluent applications became essential. The total amount of effluent to be applied during composting (without rainfall) was around 3 m³ per initial tonne of EFB. This amount approximately corresponded to the standard effluents : EFB ratio in the oil mill. Inoculation of the mass of EFB to be composted with ripe compost had a significant effect on the speed with which the mixture was reduced. A urea application a fortnight after the start of fermentation seemed to be beneficial. The resulting compost had a good agronomic value. However, the mineral balance was considerably affected, as the nutrients provided by the effluents were poorly retained by the substrate, and partially lost in percolation water following the weekly watering operations. For instance, almost 50% of the phosphorus, 70% of the potassium, 45% of the magnesium and between 10% and 20% of the calcium theoretically applied were lost ten weeks into the trial. Better distribution of the effluent applications, combined with a system to recover the leachings, should substantially reduce these losses, while maintaining suitable humidity for microbial degradation.     

Metabolic fate of 2,4-dichlorophenol and related plant residues in rats

This study compared the metabolic fate of [(14)C]-DCP, [(14)C]-residues from radish plants, and purified [(14)C]-DCP-(acetyl)glucose following oral administration in rats. A rapid excretion of radioactivity in urine occurred for [(14)C]-DCP, [(14)C]-DCP-(acetyl)glucose, and soluble residues, 69, 85, and 69% within 48 h, respectively. Radio-HPLC profiles of 0-24 h urine from rats fed [(14)C]-DCP and [(14)C]-DCP-(acetyl)glucose were close and qualitatively similar to those obtained from plant residues. No trace of native plant residues was detected under the study conditions. The structures of the two major peaks were identified by MS as the glucuronide and the sulfate conjugates of DCP. The characterization of a dehydrated glucuronide conjugate by MS and NMR of DCP was unusual. In contrast to soluble residues, bound residues were mainly excreted in feces, 90% within 48 h, whereas total residues were eliminated in both urine and feces. For total residues, the radioactivity in feces was higher than expected from the percentage of soluble and bound residues in radish plants. This result highlighted that less absorption took place when residues were present in the plant matrix as compared to plant-free residues and DCP.     

Two new benzylbenzoate glucosides from Curculigo orchioides

An extract from in vitro cultures of Curculigo orchioides grown as bulbils in shake flasks, afforded two new glucosides of substituted benzylbenzoate - curculigoside C (3) and curculigoside D (4) - together with two known compounds - curculigoside A (1) and curculigoside B (2). Their structures were elucidated on the basis of spectral evidence, in particular by using 2D NMR methods. Their vasoactive properties were assessed in isolated rat aortic rings.     

Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant rats

The distribution of bisphenol F (4,4'-dihydroxydiphenyl-methane, BPF) was studied in female Sprague-Dawley rats. Pregnant and nonpregnant animals were gavaged with a single dose of 7 or 100 mg/kg [3H]BPF and were kept for 96 h in metabolic cages. The excretion of BPF residues occurred mainly in urine (43-54% of the administered dose), which was found to contain at least six different metabolites, and to a lesser extent in feces (15-20% of the administered dose). Sulfatase treatment and subsequent high-performance liquid chromatography analyses suggest that the major urinary metabolite (more than 50% of the radioactivity present in urine) is a sulfate conjugate of BPF. At 96 h, BPF residues were detectable in all tissues examined with the largest amounts in the liver (0.5% of the dose). In pregnant rats dosed at day 17 of gestation, BPF residues were detected in the uterus, placenta, amniotic fluid, and fetuses (0.9-1.3% of the administered dose). Large amounts of radioactivity (8-10% of the dose) were still located in the digestive tract lumen at the end of the study. After administration of a single oral dose of [3H]BPF, 46% of the distributed radioactivity was excreted in bile over a 6 h period. In rats, BPF and/or its metabolites very likely undergo enterohepatic cycling, which could be responsible for the relatively high amounts of residues still excreted 4 days after BPF administration. This bisphenol is efficiently absorbed and distributed to the reproductive tract in female rats, and its residues pass the placental barrier at a late stage of gestation in rats.