Cardiopulmonary effects of hypercapnia during controlled intermittent positive pressure ventilation in the horse.

The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/- 2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/- 12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume controlled intermittent positive pressure ventilation (IPPV) and neuromuscular blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP), systemic vascular resistance (SVR), and venous admixture (QS/QT) increased significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular resistance was significantly decreased, while MBP levels were not different from those during moderate hypercapnia. No cardiac arrhythmias were recorded with any of the ranges of PaCO2. Norepinephrine levels increased progressively with each increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2 despite an increase in MBP, while moderate and severe hypercapnia produce an augmentation of the cardiopulmonary performance and DO2.     

A Review of Paclitaxel and Novel Formulations Including Those Suitable for Use in Dogs

Paclitaxel is a commonly used chemotherapeutic agent with a broad spectrum of activity against cancers in humans. In 1992, paclitaxel was approved by the U.S. Food and Drug Administration (FDA) as Taxol^® for use in advanced ovarian cancer. Two years later, it was approved for the treatment of metastatic breast cancer. Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia in 1971. Taxanes are a family of microtubule inhibitors. As a member of this family, paclitaxel suppresses spindle microtubule dynamics. This activity results in the blockage of the metaphase‐anaphase transitions, and ultimately in the inhibition of mitosis, and induction of apoptosis in a wide spectrum of cancer cells. Additional anticancer activities of paclitaxel have been defined that are independent of these effects on the microtubules and may include the suppression of cell proliferation as well as antiangiogenic effects. Based on its targeting of a fundamental feature of the cancer phenotype, the mitotic complex, it is not surprising that paclitaxel has been found to be active in a wide variety of cancers in humans. This review summarizes the evidence in support of paclitaxel's broad anticancer activity and introduces the rationale for, and the progress in development of novel formulations of paclitaxel that may preferentially target cancers and that are not associated with the risks for hypersensitivity in dogs. Of note, a novel nanoparticle formulation of paclitaxel that substantially limits hypersensitivity was recently given conditional approval by the FDA Center for Veterinary Medicine for use in dogs with resectable and nonresectable squamous cell carcinoma and nonresectable stage III, IV and V mammary carcinoma.     

Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells

The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.     

Methicillin resistant Staphylococcus aureus colonization in pigs and pig farmers

Methicillin resistant Staphylococcus aureus (MRSA) colonization has recently been identified in pigs and people that work with pigs, raising concerns about the role of pigs as reservoirs of MRSA for human infection. The objectives of this study were to evaluate the prevalence of MRSA colonization in pigs and pig farmers in Ontario, Canada and to characterize MRSA strains. Nasal and rectal swabs were collected from 285 pigs from three different age groups from 20 pig farms. Nasal swabs were collected from farm personnel and a brief questionnaire was also administered. The prevalence of MRSA colonization in farms was 45% (9/20) whereas the prevalence in pigs was 24.9% (71/285). There was no difference in MRSA colonization between age groups. The prevalence of MRSA colonization in pig farmers was 20% (5/25). There was a correlation between the presence of MRSA in pigs and humans on farms (P value=0.001). The results of spa typing revealed the predominant strain in pigs and humans was eGenomics spa type 539 (Ridom t034, clonal complex 398) which accounted for 59.2% of isolates and has been reported in pigs in Europe. A common human epidemic clone, CMRSA-2 (USA100, clonal complex 5) was also found in both pigs and pig personnel. Indistinguishable strains were found in pigs and pig personnel on all five farms with a colonized human. This study demonstrates that MRSA is common in pigs in Ontario, Canada, and provides further support to concerns about transmission of MRSA between pigs and humans.     

Modelling of sorption experiments and seepage data of an Amazonian Ultisol subsoil under cropping fallow

The results of physico-chemical investigations of an Ultisol subsoil under a 2-year old fallow in eastern Amazonia are presented. Subsoil chemistry was studied using 4 different approaches: i) concentrations of H, Na, K, Ca, Mg, Mn, Al, and Fe in seepage water were measured under field conditions, ii) the equilibrium soil chemistry was studied in sequential batch experiments where the soil was treated with different solutions, iii) results of batch experiments were simulated with a chemical equilibrium model, and iv) the seepage data were calculated using selectivity coefficients obtained by modelling the batch experiments. The model included multiple cation exchange, precipitation/dissolution of Al(OH)₃ and inorganic complexation. Cation selectivity coefficients were pK_x/Ca^sel: X = Na: 0.3, K: 0.8, Mg: ?0.1, and Al: 0.4. The amount of cations sorbed ranged from ?0.2 to 2.0 (K), ?0.7 to 2.3 (Mg), ?1.6 to 1.8 (Ca), ?4.8 to 3.6 (Al) and 0.0 to 8.5 (Na) mmol_c kg^?1. The model predictions were good with values lying within 0.3 pH units (for the pH range 3.7 to 7.2), and 3% of CEC for individual cations. The most important proton buffer reaction seemed to be the dissolution of gibbsite and a large release of Al into the soil solution. When selectivity coefficients obtained by the modelling procedure were used to predict the field data for cation concentrations in the seepage water, they decreased in the following order: Na > K > Ca > Mg > Al. These calculated values were similar to the measured order: Na > Ca > K ≈ Mg > Al. Thus the options for managing these soils should be carefully chosen to avoid soil acidification which may result from inappropriate use of fertilizer during the cropping period.     

Effects of water availability and fertilization on nitrogen cycling in a stand of Pinus radiata

Nitrogen cycling was studied for four years (1983–1987) in an N-deficient 10-year-old stand of Pinus radiata growing on a yellow podzolic soil which had a low water-holding capacity. Trees were subjected to combinations of irrigation of N-fertilization resulting in a wide range of N uptake and tree growth. Net mineralization, plant uptake and leaching of soil N was monitored using a sequential coring and in-situ incubation technique. Nitrogen concentrations were measuredd monthly in live needles and litterfall. Average rates of weight loss and release of N from decomposing litter were estimated over a 3-year period using a budgeting approach.

Trees responded only to N (not to P, and there was no N×P interaction), but there was a large positive interaction between N supply and water availability. Response to fertilizer averaged + 24% over a 4-year period, but was zero during a growing-season which contained a 4-month drought. Irrigation alone increased growth by 60%, but in combination with high N availability growth increased 2–3 fold. Annual uptake of N ranged from <10 (irrigated plots in years 2 and 3 after enhanced mineralization during the initial year) to 166 kg ha⁻¹ (during a wet growing season following heavy N fertilization). Although soil mineral-N concentrations were elevated for only about 1 year after fertilization, fertilization enhanced rates of N mineralization throughout the soil N mineralization may have resulted from re-mineralization of the large quantity (147 kg soil N mineralization may have resulted from re-mineralization of the large quantity (147 kg ha⁻¹) of fertilizer N immobilized by the soil during the initial 8 months after fertilization, or the N released from decomposition of fine roots having higher N content. Nitrification was negligible in unfertilized soils, but increased markedly 50–100 days after fertilization and resulted in the leaching of about 60 kg N ha⁻¹ during autumn and winter of the first year after fertilization. Fertilized soils have continued to nitrify readily. Irrigation increased rates of weight loss and N release from decomposing litter.

The rate of N uptake by trees markedly affected the concentrations of N in newly emerging and older needles, and the concentration of N in needlefall. The weighted mean concentration of N in annual needlefall ranged from 0.42% in the irrigated-only plot (most N-stressed) to 0.94% in the heavily fertilized plot during the first year after treatment. These weighted concentrations are a useful index of N uptake from the soil and of growth rate where water supply is not limiting. Except for the initial year after heavy N fertilization, annual uptake of N was equivalent to annual soil N mineralization, and N uptake was positively linearly correlated with annual basal-area increment of trees.     

Assessing nitrogen fixation in mixed- and single-species plantations of Eucalyptus globulus and Acacia mearnsii

Mixtures of Eucalyptus globulus Labill. and Acacia mearnsii de Wildeman are twice as productive as E. globulus monocultures growing on the same site in East Gippsland, Victoria, Australia, possibly because of increased nitrogen (N) availability owing to N(2) fixation by A. mearnsii. To investigate whether N(2) fixation by A. mearnsii could account for the mixed-species growth responses, we assessed N(2) fixation by the accretion method and the (15)N natural abundance method. Nitrogen gained by E. globulus and A. mearnsii mixtures and monocultures was calculated by the accretion method with plant and soil samples collected 10 years after plantation establishment. Nitrogen in biomass and soil confirmed that A. mearnsii influenced N dynamics. Assuming that the differences in soil, forest floor litter and biomass N of plots containing A. mearnsii compared with E. globulus monocultures were due to N(2) fixation, the 10-year annual mean rates of N(2) fixation were 38 and 86 kg ha(-1) year(-1) in 1:1 mixtures and A. mearnsii monocultures, respectively. Nitrogen fixation by A. mearnsii could not be quantified on the basis of the natural abundance of (15)N because such factors as mycorrhization type and fractionation of N isotopes during N cycling within the plant confounded the effect of the N source on the N isotopic signature of plants. This study shows that A. mearnsii fixed significant quantities of N(2) when mixed with E. globulus. A decline in delta(15)N values of E. globulus and A. mearnsii with time, from 2 to 10 years, is further evidence that N(2) was fixed and cycled through the stands. The increased aboveground biomass production of E. globulus trees in mixtures when compared with monocultures can be attributed to increases in N availability.