Hypertrophic osteopathy and dysgerminoma in a mare

A case of hypertrophic osteopathy is described in a mare with a vague history of abdominal discomfort over the preceding 12 months. Bony swellings were obvious in the pastern area of both forelegs. There was a dysgerminoma of the left ovary that had metastasised to several abdominal lymph nodes and had infiltrated the posterior vena cava. There was no gross thoracic involvement although there was histologic evidence of tumour metastasis in pulmonary arterioles.     

Radiation-activated prodrugs as hypoxia-selective cytotoxins: model studies with nitroarylmethyl quaternary salts

Bioreductive drugs are designed to be activated by enzymatic reduction in hypoxic regions of tumours, but activation of these drugs is not always fully suppressed by oxygen in normal tissues. A further limitation is that bioreductive drug activation depends on suitable reductases being expressed in the hypoxic zone. This essay proposes an alternative approach in which prodrugs are reduced, and thereby activated, in hypoxic regions by ionizing radiation rather than by enzymes. This strategy is theoretically attractive, but design requirements for such radiation-activated cytotoxins are challenging. In particular, the reducing capacity of radiation at clinically relevant doses is small, which necessitates the development of prodrugs capable of releasing very potent cytotoxins efficiently in hypoxic tissue. It is shown that nitroarylmethyl quaternary (NMQ) salts possess many of the features required of a radiation-activated prodrug. In some heterocyclic NMQ compounds the cytotoxicity of the latent cytotoxic amine effector is suppressed by > 100-fold in the prodrug form, and the effector is released rapidly by fragmentation following reduction by a single electron. Appreciable cytotoxic activation of NMQ prodrugs can be achieved by irradiation at clinically relevant doses in anoxic plasma. Some of the further drug design challenges required to develop a clinical agent based on this approach are outlined.     

Nutritional Requirements and Diet Choices of the Pygmy Rabbit (Brachylagus idahoensis): A Sagebrush Specialist

Sagebrush (Artemisia tridentata) comprises up to 99% of the winter and 50% of the summer diets of pygmy rabbits (Brachylagus idahoensis). Few animals specialize on such plants as sagebrush, which contain high levels of plant chemicals that can be toxic. We investigated the nutritional requirements of pygmy rabbits and their ability and propensity to consume sagebrush alone and as part of a mixed diet. We compared diet choices of pygmy rabbits with that of a generalist forager, the eastern cottontail (Sylvilagus floridanus). Pygmy rabbits had a moderately low nitrogen requirement (306.5 mg N/kg^0.75/d), but a relatively high energy requirement, needing 750.8 kJ digestible energy/kg^0.75/d to maintain their body mass while residing in small cages. They digested fiber in pelleted diets similarly to other small hindgut fermenters, but both cottontails and pygmy rabbits digested the fiber in sagebrush better than expected based on its indigestible acid detergent lignin content. Pygmy rabbits consumed more sagebrush than cottontails, regardless of the amount and nutritional quality of supplemental pellets provided. When consuming sagebrush alone, they ate barely enough to meet their energy requirements, whereas cottontails ate only enough sagebrush to meet 67% of theirs. Both rabbit species ate more sagebrush as the quality and quantity of supplemental pellets declined, and more greenhouse-grown sagebrush than sagebrush grown outside. Urine was more acidic when consuming sagebrush than when consuming pellets, indicating detoxification by the liver. Pygmy rabbits do not require sagebrush to survive, but seem to tolerate terpenes and other plant chemicals in sagebrush better than cottontails do.     

Effects of local anesthesia and flunixin meglumine on the acute cortisol response,behavior, and performance of young dairy calves undergoing surgical castration

This study assessed the effects of flunixin meglumine (FM) and a local anesthetic block (LA) on postcastration performance, plasma cortisol concentration, and behavior in dairy calves. Thirty 2- to 3-mo-old Holstein-Friesian bull calves were allocated to 5 treatments: castration with LA (2% lidocaine injected into the testes and subcutaneously), castration with FM (1.1 mg/kg, i.v.), castration with LA+FM, castration without drugs (CC), and sham castration (SC). Castration was performed using a Newberry knife and Henderson castrating tool. Feed intake and body weight gain were recorded for 10 d postcastration. Plasma cortisol concentration and behavior frequency and duration were monitored for 8 h postcastration. Variables with repeated measures were analyzed using PROC MIXED (SAS Institute Inc., Cary, NC); one-way ANOVA was used for nonrepeated measures. No differences in feed intake or body weight gain were detected among groups. Calves in the CC, LA, and FM groups had transient (<60, <60, and <45 min, respectively) increases in plasma cortisol concentration after castration, with a second increase at 120 min in the LA group, whereas cortisol concentration remained at baseline in the LA+FM and SC groups. Mean cortisol concentrations were lower for calves in the LA+FM and SC groups than in the CC group. The area under the plasma cortisol concentration curve during the first 3 h postcastration was greater in CC- and LA-treated calves than in SC controls. Castration without drugs was associated with higher frequencies of crouching and statue standing and less oral activity compared with SC controls. Administering LA alone before castration was associated with higher frequencies of head turning, statue standing, and postural changes, and less feeding behavior compared with SC controls. More leg lifting to groom was seen in LA+FM-treated calves than in SC controls. Calves administered FM alone before castration exhibited less crouching than CC calves, fewer postural shifts, and more feeding behavior than LA-treated calves. In summary, FM alone tended to shorten the duration of cortisol response and reduce crouching after surgical castration. Combining LA+FM eliminated the cortisol response to castration but was associated with more leg lifting behavior. Treatment with LA alone did not mitigate the cortisol response and was associated with several behavioral differences compared with SC, FM-treated, or FM+LA-treated calves. Results suggest that LA alone did not effectively control discomfort in young dairy calves castrated using the Henderson castration tool.