Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

An analysis of the effects of water stress on leaf growth and yield of three barley cultivars

The main objective of the study was to evaluate the sensitivity of Iraqi local barley cultivar (Black) to soil water deficit as compared to other barley cultivars, namely: CM-72 and Arivat. The local cultivar proved to be susceptible during germination and emergence, but it developed resistance during the vegetative growth and yield formation stages. Growth analysis of individual leaves clearly showed that Black barley produced leaves of long growth duration which could affect the growth processes especially cell division. Thus, the reduction in the number of cells composing those leaves was small in the cultivar Black. Leaf growth rates as soil matric potential decreased, were reduced considerably, although, no clear trends were observed between cultivars. On the other hand, the smaller cell volume of local cultivar may have a role in its ability to tolerate water deficit. Some evidence that the local cultivar is post-flowering resistant is discussed.     

Production of Interesting Peptide Fractions by Enzymatic Hydrolysis of Tuna Dark Muscle By-Product Using Alcalase

ABSTRACT

A protein hydrolysate was prepared from proteins of tuna dark muscle by-product. The hydrolysis conditions (time, temperature, pH, and enzyme concentration) using Alcalase was optimized by response surface methodology (RSM). The regression coefficient close to 1.0, observed during experimental and validation runs, indicated the validity of the model. The hydrolysate produced under the optimum conditions determined by RSM has a low rate of peptide fraction of molecular weight of 4–1 kDa. Meanwhile, the results obtained by hydrolysis under optimal conditions determined by a complementary study (temperature 55°C, time 60 min, 1% enzyme concentration, and pH 8.5) show that the hydrolysate produced has a height rate of the peptide fraction of molecular weight of 4–1 kDa. The amino acid composition of the protein hydrolysate prepared proved to have the potential for application as an ingredient in balanced fish diets and as a source of nitrogen in microbial growth media.     

Comparison of different bronchial closure techniques following pneumonectomy in dogs

The comparison of the histologic healing and bronchopleural fistula (BPF) complications encountered with three different BS closure techniques (manual suture, stapler and manual suture plus tissue flab) after pneumonectomy in dogs was investigated for a one-month period. The dogs were separated into two groups: group I (GI) (n = 9) and group II (GII) (n = 9). Right and left pneumonectomies were performed on the animals in GI and GII, respectively. Each group was further divided into three subgroups according to BS closure technique: subgroup I (SGI) (n = 3), manual suture; subgroup II (SGII) (n = 3), stapler; and subgroup III (SGIII) (n = 3), manual suture plus tissue flab. The dogs were sacrificed after one month of observation, and the bronchial stumps were removed for histological examination. The complications observed during a one-month period following pneumonectomy in nine dogs (n = 9) were: BPF (n = 5), peri-operative cardiac arrest (n = 1), post-operative respiratory arrest (n = 1), post-operative cardiac failure (n = 1) and cardio-pulmonary failure (n = 1). Histological healing was classified as complete or incomplete healing. Histological healing and BPF complications in the subgroups were analyzed statistically. There was no significant difference in histological healing between SGI and SGIII (p = 1.00; p > 0.05), nor between SGII and SGIII (p = 1.00; p > 0.05). Similarly, no significant difference was observed between the subgroups in terms of BPF (p = 0.945; p > 0.05). The results of the statistical analysis indicated that manual suture, stapler or manual suture plus tissue flab could be alternative methods for BS closure following pneumonectomy in dogs.     

Changes in fatty acids profile,monosaccharide profile and protein content during batch growth of Isochrysis galbana (T.iso)

To investigate the nutritional value of the marine micro‐alga Isochrysis galbana Tahitian Isochrysis strain (T.iso) as an alternative feed for aquaculture during culture age, its biochemical composition was studied under autotrophic and controlled culture conditions at different growth stages: exponential phase, early and late stationary phases and decay phase. Analysis showed that C14:0, C16:0, C16:1, C18:4 (n‐3) and C22:6 (n‐3) were the most abundant fatty acids in this alga at different growth stages. The highest values of monounsaturated fatty acids were recorded at the late stationary and the decay phases. However, the highest levels of polyunsaturated fatty acids were observed at the early stationary phase. At all growth stages, I. galbana (T.iso) contained arabinose, xylose, mannose, galactose and glucose. Glucose represented the main sugar, and its content per dry alga biomass weight increased with increasing age of the culture and reached about fourfold in the decay phase. The maximum protein content was also observed during this last phase.     

Predicting lumber grade and by-product yields for Scots pine trees

The purpose of this study was to develop models for estimating yields of lumber grades and by-products of individual Scots pine (Pinus sylvestris L.) trees using stem and crown dimensions as explanatory variables. Two separate data sets were used: (1) one simulated by the process-based growth model, PipeQual, which provides information about stem form and branch properties. The model was used to predict the 3D structure of Scots pine stems from thinning regimes of varying intensity and rotation periods and (2) an empirical data set with detailed 3D measurements of stem structure. The stems were sawn using the WoodCim sawing simulator and the yields and grades of the individual sawn pieces, as well as by-products, were recorded. The sawn timber was classified on A, B, C and D-grades for side and centre boards separately (Nordic Timber grading). By-products were pulpwood, sawmill chips, sawdust and bark.     

Optimal management of uneven-aged Norway spruce stands

An optimization model is specified to analyze forest management without any restrictions on the forest management system. The data on forest growth comes from unique field experiments and is used to estimate a nonlinear transition matrix or size-structured model for Norway spruce. The objective function includes detailed harvesting cost specifications and the optimization problem is solved in its most general dynamic form. In optimal uneven-aged management, stand density is shown to be dominated by limitations in natural regeneration. If the goal is volume maximization, even-aged management with artificial regeneration (and thinnings from above) is superior to uneven-aged management. After including regeneration and harvesting costs, the interest rate, and the price differential between saw timber and pulpwood, uneven-aged management becomes superior to even-aged management. However, in the short term the superiority is conditional on the initial stand state.     

Amalthea's density is less than that of water

Radio Doppler data from the Galileo spacecraft's encounter with Amalthea, one of Jupiter's small inner moons, on 5 November 2002 yield a mass of (2.08 +/- 0.15) x 10(18) kilograms. Images of Amalthea from two Voyager spacecraft in 1979 and Galileo imaging between November 1996 and June 1997 yield a volume of (2.43 +/- 0.22) x 10(6) cubic kilometers. The satellite thus has a density of 857 +/- 99 kilograms per cubic meter. We suggest that Amalthea is porous and composed of water ice, as well as rocky material, and thus formed in a cold region of the solar system, possibly not at its present location near Jupiter.     

Mild photochemical synthesis of the antioxidant hydroxytyrosol via conversion of tyrosol

Hydroxytyrosol, a naturally occurred orthodiphenolic antioxidant molecule found in olive oil and olive mill wastewaters, was obtained from the wet hydrogen peroxide photocatalytic oxidation of its monophenolic precursor tyrosol. The liquid-phase oxidation of tyrosol to hydroxytyrosol was performed by use of an iron-containing heterogeneous catalyst (Al-Fe)PILC with the assistance of UV irradiation at 254 nm and at room temperature. The spectroscopic and HPLC data of the synthesized compound proved to coincide fully with those of a pure sample obtained by continuous countercurrent extraction. This reaction was found to be light-induced. The hydroxytyrosol synthesis reaction reached its maximum yield of 64.36% under the optimized operating conditions of 3.6 mM tyrosol, 0.5 g L(-1) catalyst, and 10(-2) M H2O2 with the assistance of UV light. Increasing the initial hydrogen peroxide concentration more than 10(-2) M has a diminishing return on the reaction efficiency. Catalyst can be recuperated by means of filtration and then reused in a next run after regeneration since its activity did not significantly decrease (<10%). The reaction synthesis is operationally simple and could find application for industrial purposes.     

Trait phenotyping and molecular marker characterization of barley (Hordeum vulgare L.) germplasm from Western Himalayas

Genetic Resources and Crop Evolution - Barley (Hordeum vulgare L.) is one of the principal cereal crops grown in Western-Himalayas of India. A set of 105 barley&nbsp;genotypes including 38...