Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

“无我”的宁静与“有我”的振动——陶渊明与华兹华斯诗歌中“自然”观比较

陶渊明和华兹华斯同出于对各自现实政治不满的目的 ,返始归根回到了自然。由于诗人分属于东西方完全不同的文化系统 ,且在各自的文学土壤上滋生、发展 ,因此在自然之中呈现出“无我”与“有我”的明显差异。     

R-41, a sunflower restorer inbred line, carrying two genes for resistance against a highly virulent Spanish population of Orobanche cernua

The inheritance of resistance to a highly virulent population of sunflower broomrape (Orobanche cernua) has been studied in R-41, a Spanish sunflower restorer inbred line. Using the cytoplasmic male-sterile inbred line HA-89 (cms; very susceptible to this population of broomrape) as a female parent, progenies of the cross with R-41, i.e. Fl, F2 and BC1 to both parents, as well as the parental lines, were analysed for their reaction to the broomrape population EC-94. The goodness of fit of the observed vs expected segregation ratios indicated that the inheritance of resistance to broomrape in line R-41 is conferred by two independent dominant genes.     

In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondrial defect model

The uptake and distribution of intramuscularly (IM) administered tritium-labeled polysulfated glycosaminoglycan (³H-PSGAG) in serum, synovial fluid, and articular cartilage of eight horses was quantitated, and hyaluronic acid (HA) concentration of the middle carpal joint was evaluated in a pharmacokinetic study. A full-thickness articular cartilage defect, created on the distal articular surface of the left radial carpal bone of each horse served as an osteochondral defect model. ³H-PSGAG (500 mg) was injected IM, between 14 and 35 days after creation of the defects. Scintillation analysis of serum and synovial fluid, collected from both middle carpal joints at specific predetermined times up to 96 hours post-injection, revealed mean ³H-PSGAG concentrations peaked at 2 hours post-injection. ³H-PSGAG was detected in cartilage and subchondral bone 96 hours post-injection in samples from all eight horses. There were no statistically significant differences in ³H-PSGAG concentration of synovial fluid or cartilage between cartilage defect and control (right middle carpal) joints.

HA assay of synovial fluid revealed concentrations significantly increased at 24, 48, and 96 hours post-injection in both joints. The concentration nearly doubled 48 hours post-injection. However, no statistically significant differences were found between synovial concentrations of HA in cartilage defect and control joints.

³H-PSGAG administered IM to horses, was distributed in the blood, synovial fluid, and articular cartilage. HA concentrations in synovial fluid increased after IM administration of polysulfated glycosaminoglycan.     

Residue management for reducing evaporation in relation to soil type and evaporativity1

Abstract. Usual residue-management options are to remove the residue, use it as mulch with or without undercutting or to incorporate it into the soil. While the role of surface mulch in evaporation has been widely studied, the information on the effect on evaporation of mulch with undercutting or residue incorporated into soil, particularly in relation to soil type and evaporativity (E_o) is lacking. We studied the effect of wheat straw used in various ways on the course of evaporation loss from soil columns with three soils at Ludhiana, India and one soil at Bushland, Texas, USA, under two E_o's Energy-limited evaporation rates under mulch (E_om) followed the soil-specific relation E_om/E_o= a e^(bRes+cEo), where Res is residue rate t/ha and a, b and c are constants; E_o, is expressed in mm/d. In an effort to model the total evaporation (CE) during the energy-limited stage ‘U’ was obtained from appropriate CE versus time curves and (CE-U) was regressed over (t - ti)^0.5 to obtain the slope ‘α’ (Ritchie 1972) for the soil-limited evaporation stage. The observed ‘U’ was independent of mulch rate and E_o but was strongly affected by soil type, Values of ‘α’ decreased with increase in mulch rate and decrease in E_o and coarseness of soil. The otherwise short lived benefit of evaporation reduction with mulch per se, which peaked after a few days was maintained when residue was mixed with soil at the stage when evaporation reduction reached a maximum; this benefit continued for several weeks. Cumulative evaporation values computed from ‘U’ and ‘α’ agreed closely with the observed values under straw mulch for loamy sand and clay loam soils and for ‘undercut’ and ‘residue mixed’ treatments on all soils regardless of E_o, and for all situations under small E_o. However, for sandy loam and silt loam soils under E_o of 10 mm/d, the modified square root of the time function of Jalota et al. (1988) gave a better fit.     

Responses of ponies to equid herpesvirus-1 Iscom vaccination and challenge with virus of the homologous strain

An experimental (Iscom) vaccine previously shown to protect hamsters from lethal challenge with equid herpesvirus-1 (Ehv-1), was tested in horses. Vaccination with Ehv-1 Iscoms induced serum antibodies to the major virus glycoproteins gp10, 13, 14, 17, 18 and 21/22a, whereas antibody responses to gp2 were weak or absent. High levels of virus neutralising antibody of long duration were induced, but did not prevent challenge infection with virus of the homologous strain. However, in the vaccinated ponies there was a significant reduction in clinical signs, nasal virus excretion and cell associated viraemia compared with age-matched unvaccinated controls. There was a strong correlation between pre-challenge levels of serum virus neutralising antibody and the duration and total amount of virus excreted from the nasopharynx.     

Epidural Morphine in Goats after Hindlimb Orthopedic Surgery

Morphine (0.1 mg/kg) diluted with 0.9% saline to a volume of 0.13 mL/kg was administered into the epidural space at the lumbosacral junction in 10 halothane-anesthetized goats immediately before discontinuation of halothane. The same volume of 0.9% saline was given to control group of eight anesthetized goats. Both groups had undergone an orthopedic procedure that replaced the anterior cruciate ligament with a patellar tendon autograft. The appearance and unprovoked behavior of goats in the morphine group were significantly different (p < .05) from the saline groups. The goats in the morphine group were more sedate and struggled less during recovery. Epidural morphine did not produce respiratory depression or bloat during a 9 hour observation period. Heart rate, respiratory rate, and blood pressure (mean, systolic, and diastolic) of the morphine group did not differ from those of the control group.     

Parenteral Anticholinergics in Dogs With Normal and Elevated Intraocular Pressure

Dogs given parenteral anticholinergic drugs have been thought to be at risk for development or exacerbation of elevated intraocular pressure (IOP). In a randomized, blinded, placebo-controlled study, we evaluated the effect of intramuscular glycopyrrolate (0.01 mg/kg) on pupil diameter and IOP in unanesthetized normal dogs. Treatment with glycopyrrolate did not change pupil diameter or IOP from baseline, nor were there differences between glycopyrrolate and saline-treated (control) dogs. In addition, the authors retrospectively reviewed the medical records of 2,828 dogs undergoing general anesthesia between April 1987 and September 1990 to determine if there was an association between parenteral anticholinergic medication and postanesthetic elevation in IOP. The authors also determined the frequency of bradycardia requiring anticholinergic therapy during anesthesia in dogs with glaucoma. Of the 2,828 cases reviewed, the records of 46 dogs coded for glaucoma were examined in detail. The 46 dogs underwent 62 episodes of anesthesia, with 23 episodes including exposure to an anticholinergic drug. An increase in IOP from preanesthetic to postanesthetic measurement occurred in three dogs. One of these dogs received anticholinergic medication for bradycardia during anesthesia. The postanesthetic elevation in IOP in this dog was probably not drug related. Preanesthetic anticholinergic administration did not affect the incidence of anticholinergic administration for bradycardia during the anesthetic episode. Anticholinergic therapy during anesthesia was more frequent when the preanesthetic medication included an opiate drug. These studies do not indicate an association between parenteral anticholinergic administration and elevations in IOP.     

Anatomía del Desarrollo del Tracto Digestivo y Forma Corporal Externa Durante el Período Embrionario en el Caprino (Copra hircus)

Anatomy of the digestive tract and external body development during the embryonic stages of the caprine (Copra, bircus) The purpose of this work has been to establish the pattern of prenatal growth and normal development of the digestive tract and annex glands during goat embryonic stages. 21 embryos with ages ranging from 14 to 34 days (1.69 to 5.90 cm CR) as determined by registering the mating time, were obtained by cesarea. This material was histologically processed to obtain complete serial sections of the stomatodaeum, foregut, midgut, hindgut and cloaca. In this work, it is chronologically described the morphogenesis and histogenesis of the mouth, hypophysis, pharynx and its derivatives, stomach, intestine, liver, pancreas and cloaca. The results obtained establish chronological comparisons with the development of the lamb and gives information on the unitary origin of the gastric compartments in ruminants.     

In vitro activity of danofloxacin, tylosin and oxytetracycline against mycoplasmas of veterinary importance

The activities of danofloxacin, a novel fluoroquinolone, and two other antimicrobials were determined in vitro against field isolates of seven Mycoplasma species of veterinary importance isolated from cattle, swine and poultry in five European countries. The minimum inhibitory concentrations (MIC) of danofloxacin, tylosin and oxytetracycline were determined against a total of 68 isolates. Danofloxacin showed excellent activity against isolates of all Mycoplasma species (range 0·008 to 0·5 μg ml⁻¹), but in some isolates there was evidence of reduced sensitivity to tylosin (range 0·008 to 2·0 μg ml⁻¹) and oxytetracycline (range 0·008 to over 16·0 μg ml⁻¹). Danofloxacin was more active than other antimicrobials against, M hyopneumoniae, M dispar and M bovigenitalium, and showed activity similar to that of tylosin against M bovis and M gallisepticum. Tylosin was the most active against M synoviae and M hyosynoviae. Generally, oxytetracycline showed the poorest activity, but was superior to tylosin against M bovigenitalium. A second (final) MIC reading was taken for all isolates 14 or 21 days after the initial reading, and MIC values rose during that time. However, the increase seen in danofloxacin values (typically one to two dilutions) was less than that seen for tylosin and oxytetracycline. It is concluded that danofloxacin is highly active in vitro against all of the Mycoplasma species tested, and thus shows great potential for the treatment of respiratory and other infections caused by Mycoplasma species in cattle, pigs and poultry.