DOSIMETRIC CONSEQUENCES OF USING CONTRAST‐ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY‐MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING

Potential benefits of planning radiation therapy on a contrast‐enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity‐modulated stereotactic body radiotherapy (IM‐SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross‐sectional study. All IM‐SBRT plans were constructed on a pre‐ or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM‐SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre‐ and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM‐SBRT for tumors near “reservoirs” for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM‐SBRT treatment planning.     

Making Sense of the Metaphor: How Acupuncture Works Neurophysiologically

Dropping the veil of mystery surrounding acupuncture's effects exposes the compelling and vibrant inner workings of acupuncture based on anatomy and physiology. Shining the light on the mechanisms of acupuncture with a methodical, scientific, and evidence-based approach to equine acupuncture holds the promise of improving treatment consistency and effectiveness. Disentangling acupuncture actions from arcane notions of body function that originated millennia ago requires in-depth study of the nervous system and modern scientific evidence. Abundant information exists concerning the connections between acupuncture anatomy, nerve stimulation, and neuromodulation of the peripheral, central, and autonomic nervous systems. This body of evidence can assist equine practitioners and researchers in approaching acupuncture from a scientific, rather than a metaphorical, platform.     

A dose‐finding study with a novel water‐soluble formulation of paclitaxel for the treatment of malignant high‐grade solid tumours in dogs

A new formulation of water‐soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre‐medication (traditionally required in non‐water‐soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression‐free and overall survival and to evaluate single‐dose pharmacokinetics in tumour‐bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m^–2 intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression‐free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water‐soluble formulation of paclitaxel suggesting successful administration and being safely used without pre‐medication in dogs.     

Progressive resistance‐loaded voluntary wheel running increases hypertrophy and differentially affects muscle protein synthesis,ribosome biogenesis,and proteolytic markers in rat muscle

We examined if 6 weeks of progressive resistance‐loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6 weeks, 8 male Sprague‐Dawley rats (~9–10 weeks of age, ~300–325 g) rats were assigned to the progressive resistance‐loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel‐loading paradigm was as follows – days 1–7: free‐wheel resistance, days 8–15: wheel resistance set to 20%–25% body mass, days 16–24: 40% body mass, days 25–32: 60% body mass, days 33–42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p < .01), relative (body mass‐corrected) gastrocnemius mass (+16%, p < .001), raw plantaris mass (+13%, p < .05), and relative plantaris mass (+15%, p < .01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p < .01), a 125% increase in pan 4EBP1 levels (p < .001) and a 31% decrease in pan eIF4E levels (p < .05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c‐Myc protein levels (p < .05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F‐box protein 32 and poly‐ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p < .001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.     

中兽医药学与免疫学的关系及其在犬猫疾病中的应用

免疫,即免除疾病,中兽医和西兽医均有相同的基本意义。然而,如何防治疾病的论述,却不相同,各家均有各自不同的优缺点。中兽医学中的"正气"就是机体抵抗疾病的能力,也就是适应新环境和维持内外环境稳定的能力。"邪气"就是"病源",也就是引起各种疾病的原因。许多常用的免疫调节剂常有副作用,而且不能去除疾病之本。许多中草药具有免疫促进、免疫抑制以及免疫调正作用。中草药可以单独使用,或在西药将产生副作用时与西药结合使用,可改善治疗效果。中西结合防治疾病以及生产保健食品和饲料,乃是保证人类和动物健康的最佳途径。     

从转化医学走向转化（中）兽医药

简述了转化医学产生的背景、概念及当前国内发展现状,分析了转化医学在中（兽）医药研发过程中应用的模式和难点,针对中（兽）医药转化研究的特点提出加强中（兽）医药转化研究的几点建议。盼望中国农业科学院兽医药物监督所率先创建中兽医药临床疗效评价中心。     

Glyoxalase 1 expression is downregulated in preimplantation blastocysts of diabetic rabbits

In a diabetic pregnancy, an altered maternal metabolism led to increased formation of reactive α‐dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO) in the reproductive organs and embryos. The enzyme glyoxalase (GLO) 1 detoxifies reactive α‐dicarbonyls thus protecting cells against malfunction or modifications of proteins by advanced glycated end products (AGEs). The aim of this study was to analyse the influence of a maternal insulin‐dependent diabetes mellitus (IDD) on GLO1 expression and activity in preimplantation embryos in vivo and human trophoblast cells (Ac‐1M88) in vitro. Maternal diabetes was induced in female rabbits by alloxan before conception and maintained during the preimplantation period. GLO1 expression and activity were investigated in 6‐day‐old blastocysts from healthy and diabetic rabbits. Furthermore, blastocysts and human trophoblast cells were exposed in vitro to hyperglycaemia, GO and MGO and analysed for GLO1 expression and activity. During gastrulation, GLO1 was expressed in all compartments of the rabbit blastocyst. Maternal diabetes decreased embryonic GLO1 protein amount by approx. 30 per cent whereas the enzymatic activity remained unchanged, indicating that the specific GLO1 activity increases along with metabolic changes. In in vitro cultured embryos, neither hyperglycaemia nor MGO and GO had an effect on GLO1 protein amount. In human trophoblast cells, a stimulating effect on the GLO1 expression was shown in the highest GO concentration, only. Our data show that maternal diabetes mellitus affects the specific activity of GLO1, indicating that GLO1 was post‐translationally modified due to changes in metabolic processes in the preimplantation embryos.     

EVALUATION OF CANINE PROSTATE INTRAFRACTIONAL MOTION USING SERIAL CONE BEAM COMPUTED TOMOGRAPHY IMAGING

This study used kilovoltage (kV) cone beam computed tomography (CBCT) imaging to characterize canine intrafractional prostate motion during hypofractionated stereotactic radiotherapy treatment. Serial CBCT images taken just prior to initiating treatment, and at several times during the treatment session, were acquired throughout the course of treatment for canine patients. All patients were immobilized in dorsal recumbency while using an air‐inflated rectal balloon. For each treatment session, rigid registration of intrafraction CBCT images with the interfraction CBCT used for setup verification was performed. Contours of the prostate and urethra were drawn on each CBCT image set and the center of mass for each structure was evaluated as a function of time. A total of seven canine patients was included in the study, resulting in 41 CBCT images collected during a total of 12 treatment sessions. Over 70% of our data were collected for CBCTs taken between 20 and 51 min after final patient setup was complete. The mean intrafraction movement in a single direction for the prostate and urethra was ≤0.14 mm and ≤0.22 mm, respectively. The maximum intrafraction movement for the prostate and urethra was ≤ 1.60 mm and ≤ 2.00 mm, respectively. The maximum variability in intrafraction movement for the prostate and urethra, as defined by two standard deviations, was ≤1.40 mm and ≤1.50 mm, respectively. Minimal intrafraction variability using appropriate patient positioning and rectal balloon, combined with kV CBCT image‐guided radiation therapy tools to account for interfraction changes, permit accurate and precise targeting of structures of interest.     

Descriptive analysis of haemangiosarcoma occurrence in dogs enrolled in the Golden Retriever lifetime study

Haemangiosarcoma is a relatively common malignant tumour in dogs, and one of the primary outcomes of interest for the Golden Retriever Lifetime Study. This study collects longitudinal data and samples from a cohort of golden retrievers, with the aim of identification of nutritional, genetic, environmental, lifestyle and reproductive risk factors for cancers and other important diseases in dogs. This analysis describes the accumulating data and samples, which are available for use by researchers to fulfil the study's objectives. As of September 2022, 233/3044 dogs enrolled in the study had been diagnosed with haemangiosarcoma (7.65%), with an incidence rate of 1.10 cases per 100 dog-years. Visceral haemangiosarcoma was the most common, affecting 211/3044 study dogs (6.9%). One hundred and twenty eight visceral haemangiosarcoma diagnoses specified the presence of splenic tumours (60.7%) and 119 specified the presence of cardiac tumours (56.4%). The probability of remaining without a haemangiosarcoma diagnosis declined from 100% from approximately 4 years of age, to a 12 year probability of 91.1% in intact females (95% CI 84.4%–98.3%), 60.7% in neutered females (95% CI 41.6%–88.6%), 72.9% in intact males (95% CI 62.9%–84.6%) and 70.0% in neutered males (95% CI 53.4%–92.0%). The 1 year survival probability for visceral haemangiosarcoma was 1.42% (95% CI 0.37%–5.47%); for cutaneous haemangiosarcoma, it was 84.6% (95% CI 67.1%–99.99%). The accumulated data and samples are a considerable resource for further investigation of canine haemangiosarcoma and have a potential role in translational medicine.