Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses

OBJECTIVE: To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. ANIMALS: 6 adult horses. PROCEDURES: A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. RESULTS: Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 micromol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 micromol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean +/- SEM elimination half-life of 86.0 +/- 4.7 minutes, mean body clearance of 6.54 +/- 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 +/- 0.056 L/kg. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.     

Salmon poisoning disease in two Malayan sun bears

CASE DESCRIPTION: 2 captive sun bears (Helarctos malayanus) were evaluated because of acute onset of vomiting, mucoid diarrhea, lethargy, and anorexia 1 week after eating live trout from a northern California reservoir. CLINICAL FINDINGS: In 1 of the bears, a CBC and serum biochemical analyses revealed mild anemia, mild eosinophilia, moderate lymphopenia, moderate hypoalbuminemia, and high serum G-glutamyltransferase activity. Ultrasonographic examination of the same bear revealed ascites and mesenteric lymphadenopathy. Histologic examination of gastrointestinal tract biopsy specimens revealed moderate to severe lymphoplasmacytic and eosinophilic gastritis, enteritis, and colitis. Ova of Nanophyetus salmincola, the trematode vector of Neorickettsia helminthoeca (a rickettsial organism that causes salmon poisoning disease), were detected in fecal samples from both bears. TREATMENT AND OUTCOME: The bears were treated with oxytetracycline, doxycycline, praziquantel, and famotidine. Within 1 week after initiation of treatment, the appetite and fecal consistency of each bear were considered normal. Fecal ova shedding began 4 days after onset of clinical signs and ceased 9 days later. CLINICAL RELEVANCE: Salmon poisoning disease can be rapidly fatal in untreated animals, but if diagnosed early and treated appropriately, full recovery can be achieved. Domestic dogs and captive exotic bears are highly susceptible to clinical disease after ingestion of trematode-infected fish. Salmon poisoning disease may develop outside the geographic range in which the causative organism is endemic as a result of the transplantation of infected fish for sport fishing; veterinarians practicing in areas where infected fish may be transplanted should be aware of appropriate diagnostic and treatment protocols.     

Lack of detection of circulating skin-specific IgE autoantibodies in dogs with moderate or severe atopic dermatitis

Human patients with atopic dermatitis (AD) commonly exhibit IgE reactivity to cutaneous self-antigens. The presence of serum IgE autoantibodies appears to correlate with disease severity, and it is suspected to reflect or contribute to tissue damage. The objective of this study was to determine whether IgE autoantibodies specific for cutaneous antigens could be detected in the serum of dogs with AD. Serum was collected from 19 dogs with untreated moderate to severe AD and four specific-pathogen free (SPF) dogs. Indirect immunofluorescence was performed using normal canine skin collected at four different locations (concave ear, nose, medial thigh and lateral thorax), while Western immunoblotting was done using normal canine ear pinna epidermal and dermal extracts and reducing conditions. In both methods, IgE was detected using a monoclonal antibody specific for heat stable epitopes of canine IgE. At 1:10 dilution, specific IgE autoantibodies against cutaneous autoantigens were not detected, with either method, in AD and SPF canine sera. Either IgE autoreactivity is not associated with moderate to severe AD in dogs, or the methods employed herein were not sensitive enough to permit IgE autoantibody detection.     

Ordering of ruthenium cluster carbonyls in mesoporous silica

The anionic ruthenium cluster carbonylates [Ru6C(CO)16]2- or [H2Ru10(CO)25]2- interspersed with bis(triphenylphosphino)iminium counterions (PPN+) are incorporated from solution into the pores of MCM-41 mesoporous silica (3 nanometers in diameter), where they form tightly packed arrays. These arrays were shown by high-resolution transmission electron microscopy, Fourier transform optical diffraction, and computer simulations to be well ordered both along and perpendicular to the axis of the cylindrical pores. In their denuded state produced by gentle thermolysis, the cluster carbonylates yield nanoparticles of ruthenium that are less well ordered than their assimilated precursors but show good activity as hydrogenation catalysts for hexene and cyclooctene. In both their as-prepared and denuded states, these encapsulated clusters are likely to exhibit interesting electronic and other properties.     

Radiata pine plantations in Chile

The landscape of the southcentral part of Chile is dominated by fast-growing plantations of radiata pine (Pinus radiata D. Don), and in lesser extent bluegum eucalyptus (Eucalyptus globulus Labill.), Italian poplar, and willows. Radiata pine was first introduced in 1885 as an ornamental species. During 1940–1960 it was used to control erosion in the Coastal Range. Finally, since the 1960s it has been used for commercial plantations. The present extent of the plantation resource is 1,694,104 ha, of which 80.9 percent is radiata pine. During 1991, 1992, and 1993, this species was planted at rates of 75,416 ha, 81,868 ha, and 71,411 ha, respectively. Even though the soils are eroded to different degrees, exhibit a variety of nutritional disorders, and contain some physical restrictions, the productivity of radiata pine ranges from 18 m³/ha/yr to 35 m³/ha/yr. Additional stress comes from some potentially serious pests; for example, the European pine shoot moth, Rhyacionia buoliana, has presented a real threat to radiata pine. The main products obtained from radiata pine are exported to Japan, Korea, Middle and Far East countries, and Europe. Sawlogs, sawntimber, pulpwood, clearwood, and wood chips are some of the products comprising sales in 1994 of U.S.$1,564 billion. The purpose of this paper is to show how radiata pine silviculture has changed since the last part of the 1980s in Chile. Also we want to show how forestry activities have produced a profound and positive change in the social and economic environment that surrounds the areas where the industry’s main production areas exist. This revised version was published online in June 2006 with corrections to the Cover Date.     

Performance of Colorado potato beetle larvae,Leptinotarsa decemlineata (Say), reared on synthetic diets supplemented withSolanum glycoalkaloids

Glycoalkaloids are a class of secondary compounds (nitrogenous, steroidal glycosides), ubiquitously distributed throughout the Solanaceae. Numerous studies (in planta) have shown that certain glycoalkaloids, e.g., α-tomatine, solanocardenine, and leptine, have a negative impact on performance of the Colorado potato beetle,Leptinotarsa decemlineata (Say). However, the presence of other secondary compounds, as well as the nutritional status of the plants used, are additional variables in such experiments. By rearing Colorado potato beetle, from egg to prepupal stage, on a synthetic diet supplemented with the glycoalkaloids α-tomatine, α-chaconine, α-solanine, leptine I and the steroidal aglycone solanidine, we have been able to further establish the effects (ex planta) of these compounds on the Colorado potato beetle. Leptine I displayed a dose-dependent negative activity against the Colorado potato beetle (as measured by larval weight gain and tune to molt), when assayed at 0.31, 0.62 and 1.23 mM concentrations; however, by the fourth stadium no effect was found. When Colorado potato beetle were fed a higher concentration of leptine I (2.4 mM), there was a sustained effect in all stadia. At 2.4 mM, leptine I displayed a greater negative impact on Colorado potato beetle growth and development than did α-tomatine. α-Chaconine at 2.4 mM did not impair Colorado potato beetle performance relative to Colorado potato beetle reared on control diets. α-Chaconine plus α-solanine, at concentrations commonly found inSolanum tuberosum L. foliage (0.6 and 0.3 mM respectively), did not impair Colorado potato beetle performance. The steroidal aglycone solanidine (2.4 mM) had a significant negative impact on Colorado potato beetle performance. Results are discussed in the context of host-plant resistance and insect-plant interactions.