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 acute case of Pimelea elongata toxicity in cattle in western New South Wales

In May 2019, 96 cattle died from Pimelea toxicity in a period of 19 days after potential exposure, with the first deaths occurring within 5 days. After examining the circumstances, we suspect that several factors contributed to the deaths. These included that recently purchased stock and transported had access to flooded land containing Pimelea elongata. This weed species contains simplexin and 18 other compounds. Roots, flowers and seeds are significantly more toxic than the stem, branches and leaves. We suspect that thirsty and hungry stock consumed seed and roots from flooded pastures and consumed lethal doses of simplexin. Blood tests were not good indicators of the conditions. Management strategies are suggested.     

地膜残留量对新疆棉田蒸散及棵间蒸发的影响

为探讨残膜对干旱区农田蒸散耗水特征的影响,在新疆阿克苏典型覆膜滴灌棉田开展2 a小区试验研究,设计0、225、450 kg/hm2共3种不同的地膜残留量,采用水量平衡法,微型棵间蒸发仪法,于主要生育时期测定并计算土壤含水量、蒸散量、棵间蒸发量、作物蒸腾量、棵间蒸发占蒸散的比例。结果表明:随着地膜残留量增加棵间蒸发量、棵间蒸发占蒸散的比例呈增大趋势,而蒸散量及作物蒸腾量则逐渐减小。与无残膜处理相比,225和450 kg/hm2处理全生育期田间无效耗水的棵间蒸发量分别增加了9.27和22.20 mm,棵间蒸发占蒸散的比例增幅分别为2.6%和6.1%,作物蒸腾量降低34.89和55.94 mm。在棉花生育期内,棵间蒸发占蒸散的比例(E/ET)与叶面积指数(leaf area index,LAI)呈幂函数关系,各处理间棵间蒸发占蒸散的比例对叶面积指数的响应差异不同,450 kg/hm2处理蒸发占蒸散的比例随着LAI的增加,曲线下降趋势较明显;无残膜处理棵间蒸发占蒸散的比例与LAI的决定系数最高,均在0.9以上。土壤水分利用率也随残膜量的增加依次降低,当残膜量由0增加到450 kg/hm2时,土壤水分利用率从28.25%降至24.91%,可见,残膜增大了农田的无效耗水,不利于土壤水分的有效利用。研究可为制定缓解或克服残膜危害的应变调控技术提供依据。     

BMC ecology image competition 2017: the winning images

For the fifth year, BMC Ecology is proud to present the winning images from our annual image competition. The 2017 edition received entries by talented shutterbug-ecologists from across the world, showcasing research that is increasing our understanding of ecosystems worldwide and the beauty and diversity of life on our planet. In this editorial we showcase the winning images, as chosen by our Editorial Board and guest judge Chris Darimont, as well as our selection of highly commended images. Enjoy!     

Identification and validation of cold responsive microRNAs of <Emphasis Type="Italic">Hevea brasiliensis</Emphasis> using high throughput sequencing

Cold stress is one of the major abiotic factors that influence the productivity and geographical distribution of many agriculturally important crops like Hevea brasiliensis. Cultivation of H. brasiliensis in India is being extended to northeastern regions, where low temperature during winter adversely affects its survival, growth, and productivity. Developing cold-tolerant genotypes is a primary requisite to maximize the productivity under such challenging environmental conditions. However, lack of methods for early evaluation of cold tolerance in the newly developed clones and the extensive time required for assessing their tolerance in the field are major constraints for clonal selection. The present study was initiated with an objective to identify and characterize cold stress responsive miRNAs from H. brasiliensis that show stronger association with cold tolerance. Next generation sequencing using Illumina HiSeq method revealed the expression of 21 and 29 conserved miRNA (from clone RRIM 600) families in cold-stressed and control samples, respectively. Forty-two novel miRNAs were identified from this study. Upon differential expression analysis, eight conserved miRNAs were found commonly expressed in both the samples. When expression analyses were performed subsequently with six selected miRNAs in two Hevea clones (viz. RRII 105 and RRIM 600), miR169 showed a strong association with cold tolerance. miRNAs such as miR482 and miR159 also exhibited association with cold tolerance. This study suggests the possibility of employing these miRNAs as markers for cold tolerance after validation in more number of genotypes with varying levels of cold tolerance.     

Diagnostic and public health investigation of Mycobacterium tuberculosis infection in a dog in Ontario,Canada

A 4-y-old, female mixed-breed dog was presented to the Ontario Veterinary College for further evaluation of multiple pulmonary and hepatic masses, intrathoracic lymphadenitis, and recent development of a pyogranulomatous pleural effusion. Along with other comprehensive tests, a thoracic lymph node biopsy was performed, and Mycobacterium tuberculosis complex infection was confirmed by real-time PCR. The dog’s condition declined post-operatively, and euthanasia was elected. Postmortem examination confirmed severe granulomatous pneumonia, hepatitis, intrathoracic and intraabdominal lymphadenitis, omentitis, and nephritis. Line-probe assays performed on samples collected postmortem confirmed the species as M. tuberculosis. 24-loci MIRU-VNTR genotyping, spoligotyping, and whole-genome sequencing revealed relations to known human isolates, but no epidemiologic link to these cases was investigated. Given the concern for potential human exposure during this animal’s disease course, a public health investigation was initiated; 45 individuals were tested for M. tuberculosis exposure, and no subsequent human infections related to this animal were identified. Our case highlights the need for more readily available, minimally invasive testing for the diagnosis of canine mycobacteriosis, and highlights the ability of canid species to act as potential contributors to the epidemiology of M. tuberculosis infections.     

Response of Pacific White Shrimp,Litopenaeus vannamei,to Three Sources of Solvent Extracted Soybean Meal

Three sources of soybean meal (SBM) were biochemically characterized and evaluated in diets for juvenile Litopenaeus vannamei. Three biological techniques were utilized to evaluate the nutritional quality of the meals including an outdoor growth trial as well as determination of in vivo apparent digestibility and in vitro digestibility including pepsin digestibility (0.0002%), pH Stat degree of hydrolysis, and immobilized digestive enzyme assay (IDEA). The growth trial was conducted over a 10‐wk period using soybean meal as the primary protein source with each meal being included at 54–58% of the diet based on an equal protein inclusion. At the conclusion of the growth trial there were no significant differences between the test diets indicating equivalent biological availability under practical conditions. The in vivo digestibility trial utilized chromic oxide as the inert marker and 70:30 replacement techniques resulted in typical results. Apparent protein digestibility (APD) and apparent energy digestibility (AED) of the diets ranged from 66.8 to 80.2% and 65.4 to 74.7%, respectively. Ingredient digestibility values for protein and energy ranged from 78.8 to 93.5% and 60.5 to 85.0%, respectively. One of the three SBM evaluated had numerically lower protein digestibility and significantly lower energy digestibility than the other two meals .     

The source of autumn and spring downstream migrating juvenile Atlantic salmon in a small lowland river

Over 3 years, 32,444 age‐0 group Atlantic salmon (Salmo salar) parr tagged with passive integrated transponder tags throughout the River Frome catchment were assigned to one of three groups, nonmigrants, autumn migrants and spring smolts, depending on the detection and the timing of detection at downstream tag readers (situated 8.6 km above the tidal limit). We examined the effect of density at the time of tagging (n·m^?2), distance upstream from the tidal limit (km), fish length (mm), Fulton condition index, habitat type (divided into two types, main river and carrier), days after 1 September that each fish was tagged and year (replication) on the proportions of fish in each of the migration groups. Distance upstream from tidal limit was strongly negatively related to the proportion of autumn migrants and positively related to the proportion of spring smolts. Nonmigrants had a lower average body size than migrants, although there were no differences in the sizes of autumn migrants and spring smolts in September prior to migration. Fish density had no effect on migration strategy. A lower proportion of fish migrated as autumn migrants from the smaller carrier habitats than the main river channel. There is some evidence that those parr destined to become autumn migrants underwent a lower mortality rate during September before tagging than those destined to become spring migrants indicating possible physiological or behavioural differences between these two groups of fish at that time. More research into the factors responsible for initiating the autumn migration is required.