Epidermal growth factor receptor as a therapeutic target in veterinary oncology

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that stimulates cell proliferation and survival and becomes dysregulated in a range of solid tumours in man. It is recognized as a key oncogenic driver and has become a favoured therapeutic target and a prognostic and predictive marker of cancer in man. In animals, EGFR dysregulation is emerging as a potential factor in the development of a number of naturally occurring tumours including mammary, lung, glial and epithelial cancers. Comparative analyses suggest that these diseases share many features with equivalent diseases in man and EGFR may have value as a prognostic or a biological marker of animal disease. There is still little direct evidence that EGFR is a critical oncogenic driver in naturally occurring animal disease and there are no veterinary trials of EGFR-targeted therapy. These will be critical steps in establishing a role for EGFR in veterinary oncology.     

Comparison of methods for determining the prececal nutrient digestibility and amino acid absorption of swine with ileorectal anastomoses and ileocecal bridge cannulas]

The apparent precaecal nutrient digestibility and amino acid (a.a.) absorption of 10 diets were estimated in pigs with end-to-side ileorectal anastomoses (IRA) as well as with ileocaecal re-entrant cannulae (IZB). The digestibilities of organic matter and crude carbohydrates were significantly higher in IRA pigs than in IZB pigs in two resp. three diets only. There were no practical important differences for the digestibilities of crude protein and crude fat in all diets. Out of the 180 a.a. absorption comparisons only 20 (i.e. 11%) showed differences larger than 5%-units. The absorption rates of several a.a. were lower in IRA than in IZB pigs and of some other a.a. on the contrary. The methionine absorption of five legume diets and one barley + lysine diet were up to 15% resp. 4%-units lower in IRA pigs. Possibly this was due to the activity of microbes in the rectum in connection with a small intake level of protein bound methionine. In order to minimize such a falsification it is proposed to use the end-to-end anastomosis. The deviations in the apparent a.a. absorption between IRA and IZB pigs can be explained partly by differences in the quantity of precaecally excreted endogenous a.a. per 100 g DM intake.     

Bovine viral diarrhea virus isolated from fetal calf serum enhances pathogenicity of attenuated transmissible gastroenteritis virus in neonatal pigs.

A bovine viral diarrhea virus (BVDV-C) was isolated from swine tissue culture cells used to attenuate the transmissible gastroenteritis virus (TGEV) after 68 passes. Piglets given a pure culture of BVDV-C developed clinical signs similar to those of a mild TGEV infection and recovered by 10 days postexposure. Villous blunting and fusion was observed in the small intestine, and a lymphocyte depletion was observed in Peyer's patches in the ileum. Piglets given a combination of BVDV-C and attenuated TGEV developed clinical signs similar to those of a virulent TGEV infection and were euthanized. The combined infection induced a generalized lymphocyte depletion throughout the lymphatic system and villous atrophy in the intestinal tract. Piglets exposed to a another type I strain of BVDV (NY-1) either alone or in combination with the attenuated TGEV had mild clinical signs similar to those of a TGEV infection. Moderate villous atrophy in the ileum and a lymphocyte depletion in the mesenteric lymph node were observed in these piglets postmortem. The data indicate a potential problem for diagnostic laboratories in relation to a diagnosis of virulent TGEV infections and in the field for young piglets exposed to a BVDV-contaminated TGEV vaccine.     

Food safety in a nuclear crisis: The role of the veterinarian

Veterinarians are integrally involved in the maintenance of a safe and sufficient food supply; this involvement may be put to the test when a crisis — particularly a nuclear crisis — occurs. Few people can be said to be experts in how to ensure a safe food supply in a nuclear crisis. However, a working knowledge of radionuclides and how they behave in the food system, and the ability to identify high-risk foods and high-risk consumers in a crisis situation should be a part of the education of all veterinarians. In this paper I review those features of postdisaster radionuclide contamination of the food chain most relevant to veterinary activities in ensuring a safe food supply.     

Case control study to identify risk factors for simple colonic obstruction and distension colic in horses

A case control study was performed to identify risk factors for colic caused by simple colonic obstruction and distension (SCOD) in the horse. Case horses were recruited from 2 veterinary school clinics. Control horses were population based and matched by time of year. A number of risk factors were considered in the following areas: general carer and premises information; exercise information; husbandry information (housing- and pasture-related); feeding information; breeding information; behavioural information; travel information; preventive medicine information and previous medical information. All variables with a P value of <0.2 in the univariable analysis were considered for possible inclusion in a multivariable model. A final model, produced by a forward stepwise method, identified crib-biting or windsucking, an increasing number of hours spent in a stable, a recent change in a regular exercise programme, the absence of administration of an ivermectin or moxidectin anthelmintic in the previous 12 months and a history of travel in the previous 24 h as associated with a significantly increased risk of SCOD. An alternative final model, produced by a backwards elimination method, identified the same variables as the forward model with, in addition, a history of residing on the current establishment for less than 6 months, a history of a previous colic episode and the fewer times per year the teeth were checked/treated as associated with a significantly increased risk of SCOD. Three of the risk factors in this model were associated with a large increase in risk: stabling for 24 h/day, crib-biting/windsucking and travel in the previous 24 h.     

Scanning electron microscopy of the superficial pineal gland of the 15-day-old rat (Rattus norvegicus)

The presence of a cortex and medulla in the superficial pineal gland has been a controversial point in the morphology of this structure in mammals. The published reports indicate contradictory data especially in rodents. In this study the pineal gland of 15-day-old male rats (Rattus norvegicus) were studied, using scanning electron microscopy, in an attempt to determine whether or not a cortex and medulla are apparent in the pineal gland of young rats. The superficial pineal gland of the 15-day-old rat exhibited both a cortex and a medulla; these areas exhibited different structural organizations. The cortex had a thickness of 40-80 microm and the cells did not show a particular arrangement. The center of the gland was composed of a medulla, which had a width of 1000-1200 microm, and consisted of cells arranged in cords; its morphology was distinctly different from that of the cortex.     

The clinical pathology and pathophysiology of heartwater: a review

This paper reviews the available literature on the clinical pathology and pathophysiology of heartwater and makes comparisons with unpublished results obtained from a recent study in experimentally-induced heartwater in calves. The pathophysiological changes seem to center on an increased capillary permeability the result of which is reflected most noticeably in cardiac and lung function. There is a marked drop in cardiac output in severe cases and some workers have recorded a severe drop in diastolic blood pressure in the advanced stage of the disease. Changes in lung function are variable, depending on the stage of the disease, and may change from a respiratory alkalosis in the early febrile stage to a respiratory acidosis in more advanced cases. The basic cause for the increased capillary permeability is not known. The main clinical pathological changes measured include a progressive anaemia, fluctuations in total and differential white cell count, of which an eosinopenia and a lymphocytosis are the most marked, increases in total bilirubin which coincide with darkening of plasma colour, and a drop in total serum proteins mostly shown in the albumin levels.     

Influence of the transport on the outcome of the bacteriological analysis of dog urine comparison of three transport tubes.

A sterile plastic tube, a boric acid-glycerol-sodium formate tube and a dip-slide tube were compared for transport of dog urine for bacteriological examination under practice conditions, at ambient temperature. In a first part, 50 dog urine samples were cultured on agar plates and on a dip-slide kit within 2 h after collection and after storage at 20 degrees C in a sterile tube and in a boric acid tube for 24 h and 48 h. Culture of the samples stored in the boric acid tube and culture on the dip-slide yielded results which correlated very well with those of the culture of fresh urine. However, culture of the samples stored in the sterile tube yielded up to 65% false positive results. In a second part, a comparison was drawn with culture results of 100 dog urine specimens collected by different practitioners and simultaneously mailed to our laboratory in a sterile tube, in a boric acid tube and in a dip-slide kit. Samples sent in the boric acid and in the dip-slide tube showed comparable culture results. Culture of the samples sent in the plastic tube yielded 53% false positive results in comparison with those of the samples preserved in boric acid.     

Teaching veterinary clinical pathology to undergraduate students: an integrated European project

BACKGROUND: Veterinary clinical pathology is a relatively new and emerging discipline in Europe that has gained momentum with the recent establishment of a specialty college. In this situation, veterinary faculties may face challenges in understanding and defining what clinical pathology is and how it can best be integrated into existing curricula. In addition, many schools in Europe may not yet have available a critical mass of suitably qualified faculty capable of teaching in all areas of clinical pathology. OBJECTIVE: The main purpose of this report is to describe the goals, procedures adopted, teaching material produced, and proposed future activities of a major European initiative designed to develop a veterinary clinical pathology curriculum. METHODS: Four working subgroups were formed to establish a list of course objectives and topics and prepare a series of lectures. These contents were reviewed and discussed several times at a series of general meetings. RESULTS: An undergraduate course on veterinary clinical pathology was designed with course objectives, a list of topics and a CD-ROM consisting of 24 lectures. CONCLUSIONS: The results of this project could be useful in the establishment or improvement of training programs in veterinary clinical pathology at the undergraduate level in Europe and in other places around the world. The provision of teaching resources for faculty could help to instill in veterinary students a strong understanding of the discipline and promote development of advanced training programs and career opportunities in clinical pathology in Europe.     

Two cases of disseminated toxoplasmosis

Two cases of disseminated fatal toxoplasmosis of a pet mouse and a red panda are described. The pet mouse had a private owner; the red panda lived in a zoological garden in Saxony. At necropsy, both animals suffered from a systemic toxoplasmosis. A severe necrotizing hepatitis was the main histological feature in both animals. Parasitic cysts could be abundantly found in the liver, moderately in the brain and in a low number in other organs. With the PAS-reaction, cysts showed a weak staining in the mouse and a strong staining in the red panda. Diagnosis was confirmed by PCR and immunohistochemistry.     

Pharmacokinetics of tobramycin in ducks and sex-related differences

The aims of the present study were to determine the disposition of tobramycin after single intravenous (IV) and intramuscular (IM) injections in ducks, and to establish any sex-related differences. Tobramycin sulfate was administered as a 2.5% water solution in a cross-over design at a dose of 5 mg/kg to 12 healthy ducks (six males and six females). Concentrations of the drug in serum were determined by a microbiological assay. The serum pharmacokinetic values for tobramycin were best represented using a one- or two-compartment open model, depending on the method of administration. Non-compartment analysis was also performed after IV administration. Tobramycin had a low degree of distribution and a relatively fast elimination. The mean volume of distribution in ducks (males and females) was higher than that reported in pigeons but lower than in chickens, with a slower rate of elimination. The IM injection resulted in a fast and complete absorption. The rate of elimination after IM administration was about twice as slow as in other avian species. Sex-related variations in tobramycin pharmacokinetics were similar to those reported for kanamycin and apramycin in hens and roosters.     

Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus Temminck, 1827)

Despite the increasing importance of cane rat (Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known. A survey of a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the observation of several suspected tumors and the confirmation of three cases of neoplasms. Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such a short period is uncommon. Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication. Although the etiology remains undetermined, these cases are described to provide baseline data on the pathology of this species in captivity.     

The tongue of Leopard Gecko (Eublepharis macularius): LM,SEM and confocal laser study

The leopard gecko is a crepuscular and insectivorous reptile. The role of the tongue in this reptile is fundamental for the prey capture and ingestion and is not related with eyes cleaning as usual in other geckos. The elongated tongue can be divided into a foretongue with a slightly bifurcated apex and a hindtongue. Scanning electron microscopy demonstrated that several different papillae are present on the dorsal surface, foliate and dome-shaped in the foretongue, becoming thicker and stouter with reduced interpapillary spaces in the lateral parts. The hindtongue is characterised by wide foliate papillae with indented margins and deep fissures of the mucosa. Light microscopy showed the presence of a stratified slightly keratinized squamous epithelium in the apex of the foretongue, a stratified non-keratinized squamous epithelium in the fore and in the hindtongue. In the foretongue, numerous muciparous caliciform cells were observed. Moreover, the presence of taste buds on the tongue ventral surface was demonstrated for the first time in this species and the confocal laser study revealed a strong immunoreactivity for the S-100 protein in the sensory cells. Therefore, the results obtained could give a contribution to the knowledge of the tongue anatomy and are a basis for eventual further studies regarding the feeding habits in a reptile become a popular pet.     

Methods for Permanent Conservation of Biological Objects and Anatomic Preparations in Synthetic Resins

The first method is applied when adding corrosive preparations to epoxid resin. The corrosive preparation is soaked in a mixture of epoxid resin and hardener in a ratio, experimentally determined. The induration proceed at room temperature for 12 h. The second method has two options and is applied for the conservation of biological objects and anatomical preparations in polymethylmethacrilate by a successive immersing of the object in a system of dehydrating mixtures: 50%, 70%, 90% and 96% water solution of methanol and ethanol and in a mixture of acetone and ethanol (1:1) and in acetone or in methylenechloride. The object, thus prepared, is impregnated in vacuum with forpolymer of methylmethacrylate, benzoil peroxide and stearine acid or in a composition containing: methylmethacrylate, benzoilperoxide, dibutilphtalat and tertiary aromatic amin, in optimum correlations of the components, experimentally determined. The induration proceed by heating in a water bath (37 + 3°C) for 3 h and at 30°C temperature in the course of 6-8 h in the first option or at room temperature for about 3 days in the second option. The advantages of the proposed methods are: the use of cheap and available materials for the production of a simplified technological scheme of strongly transparent packages, preserved over a long period; preserving the sizes, the form and natural colour of the objects and preparations as well as a possibility for selective tinting of the separate tissues and systems in the preserved biological objects and anatomical preparations; a possibility for stereomicroscopic observation of the objects and preparations preserved.     

Inherited lysosomal storage disease in an English springer spaniel.

Alpha-L-fucosidosis was diagnosed in a 17-month-old English Springer Spaniel with a history of slow development and progressive visual impairment. Lymphocytes and mononuclear cells with vacuolated cytoplasm were seen in a blood smear and in CSF, respectively. A severe deficiency of alpha-L-fucosidase activities in plasma and leukocytes was determined. Histologic examination revealed vacuolation of neurons, macrophages, and epithelial cells in most organ tissues. Canine fucosidosis is a progressive and fatal lysosomal storage disease in English Springer Spaniels. Affected dogs develop a neurologic disorder characterized by progressive motor and mental deterioration. Visual impairment is an unusual primary sign in a dog with alpha-L-fucosidosis.     

In Vitro Maturation and Development of Porcine Oocytes Cultured in a Straw or Dish Using a Portable Incubator with a CO2 Chamber

We investigated the effects of a portable incubator with a CO₂ chamber on the viability and development of porcine oocytes/embryos for their transportation and examined the operational suitability of a straw or dish as a container for culturing the oocytes or embryos in the portable incubator. In the first experiment, the cumulus‐oocyte complexes (COCs) were placed either in a dish or straw; and they were then cultured for 44 h in a standard CO₂ incubator, in the CO₂ chamber in an incubator, or in the CO₂ chamber in a portable incubator. The matured oocytes were fertilized with frozen‐thawed spermatozoa and then cultured in a dish in the standard CO₂ incubator for 8 days. There were no differences in the proportions of oocytes reaching metaphase II stage among the groups. However, the proportions of cleavage and development to blastocysts derived from oocytes matured in a straw were lower than those from oocytes matured in a dish, irrespective of the type of incubator used. In the second experiment, the COCs were matured in a dish in the standard CO₂ incubator, and the matured oocytes were fertilized and then placed either in a dish or straw. These were then cultured for 8 days in the standard CO₂ incubator or portable incubator. Some zygotes cultured in the portable incubator developed to the blastocyst stage. The proportions of cleavage and development to blastocysts were significantly lower for putative zygotes cultured in straw than for those cultured in dish, irrespective of the type of incubator used. Our results indicate that a portable incubator with a CO₂ chamber can maintain the viability and development of oocytes/embryos, but the straw is not a suitable system for in vitro culture of the oocytes/embryos during transportation.     

Recent spreading of a divergent canine parvovirus type 2a (CPV-2a) strain in a CPV-2c homogenous population

Canine parvovirus type 2 (CPV-2), which causes acute hemorrhagic enteritis in dogs, is comprised of three antigenic variants (2a, 2b, and 2c) that are distributed worldwide with different frequencies. Variant prevalence was analyzed in 150 CPV-2-positive samples collected from the Uruguayan dog population in 2007-2010. Samples were analyzed with polymerase chain reaction, restriction fragment length polymorphism, and sequencing of the coding region for the largest and most variable loop of the VP2 capsid protein. CPV-2c was the only strain detected from 2007 to 2009. Uruguayan CPV-2c showed high homogeneity in both nucleotide and amino acid sequences, indicating a low level of genetic variability. In 2010, an unexpected epidemiological change occurred in Uruguay as a consequence of the appearance of a novel CPV-2a strain. This variant rapidly spread through the Uruguayan dog population and was detected in 20 of the 52 cases (38%) analyzed in 2010. CPV-2a sequences were identical in all field viruses analyzed, and in addition to the characteristic 426Asn residue, the sequences showed amino acid substitutions (267Tyr, 324Ile, and 440Ala) not observed in the Uruguayan CPV-2c. These data and the first detection in April 2010 suggest that the CPV-2a variant recently emerged in Uruguay and underwent clonal expansion. This observation is the first case in which a CPV-2a variant increased its frequency in a dog population where CPV-2c was prevalent. Our results emphasize the dynamic changes in CPV variants and highlight the importance of ongoing surveillance programs to provide a better understanding of virus epidemiology.     

林周河谷高寒草甸和灌丛草场可饲用天然牧草时空变化特征

为研究西藏"一江两河"流域高山草甸和灌丛草场的时空变化特征,在牧草发青季(2017年7月份)、丰草季(2017年9月份)和枯草季(2018年3月份),对不同海拔梯度林周河谷南山阴坡和北山阳坡草地进行调查分析。结果表明:(1)林周河谷南山阴坡低海拔处以白草为优势种,海拔升高100 m左右时出现灌丛植被类型;山坡中段为草甸草场,主要以高山嵩草和苔草为主。总盖度最高月份为7—9月,随海拔升高,盖度相应增加,不同季节同一海拔高度总盖度间均差异不显著(P>0.05),而不同海拔高度、同一季节中总盖度差异极显著(P<0.01)。(2)季节显著影响牧草含水率(P<0.01),可饲用牧草含水率7—9月份最高,10月份后随牧草枯萎而下降,进入冬季降至0%;同一季节不同海拔梯度中,低海拔和中段海拔可饲用牧草中含水率较高。(3)不同季节可饲用牧草的产草量间差异极显著(P<0.01),单位面积总可饲用牧草产草量10月末最高,夏秋季最低;随海拔高度升高,可饲用牧草的产草量显著增高(P<0.05)。(4)经三维响应曲线拟合,总盖度y、海拔梯度x_1、月份x_2之间的关系为:y=a_1+a_2×x_2~2+a_3×x_1+a_4×x_2(a_1,a_2,a_3,a_4分别为-657.137 4、-0.882 8、0.167 1、12.507 0);含水率y、海拔梯度x1、月份x2的关系为:y=a_1+a_2×x_2~2+a_3×x_1+a_4×x_2(a_1,a_2,a_3,a_4分别为-146.147 1、-3.883 9、-0.010 0、62.100 6);产草量y、海拔梯度x1、月份x2的关系为:y=a_1+a_2×x_2~2+a_3×x_1+a_4×x_2(a_1,a_2,a_3,a_4分别为-131.065 5、2.977 2、0.069 0、-36.511 1)。结论:通过研究,建立了林周河谷南山阴坡主要高山草甸放牧草场的总盖度、含水率与产草量的立体时空变化特征;北山阳坡主要为高山灌丛,非天然放牧场所,作为饲用牧场,研究意义不大。     

Evaluation of certification in the Milk and Dairy Beef Quality Assurance Program and associated factors on the risk of having violative antibiotic residues in milk from dairy farms in Michigan

OBJECTIVE: To determine whether certification in a Milk and Dairy Beef Quality Assurance Program (MDBQAP) was associated with a reduced risk of having antibiotic residues in milk and to define specific management factors that may have predisposed dairy farms to having violative antibiotic residues in milk. SAMPLE POPULATION: 124 dairy farms in Michigan that had > 1 violative residue in milk during 1993 and 248 randomly selected control farms in Michigan that did not have violative residues in milk during 1993. PROCEDURE: A pretested structured questionnaire was mailed to case and control farms. A conditional multivariate logistic regression model was developed to determine risk factors associated with having a violative antibiotic residue in milk. RESULTS: Certification in the MDBQAP did not significantly reduce the risk of having a violative antibiotic residue. Annual treatment of > 10% of a herd for metritis was associated with a reduced risk of having a violative residue. Evidence suggested that a routine request for a milk processor to perform residue testing was associated with a decreased risk of having had a violative antibiotic residue, but routine on-farm residue testing was associated with an increased risk of having had a residue. CONCLUSIONS AND CLINICAL RELEVANCE: MDBQAP certification was associated, although not significantly, with a reduced risk of having violative antibiotic residues in milk. Risk factors significantly associated with violative antibiotic residues are addressed by various critical control points in the MDBQAP and may be indicators for strengths and weaknesses of MDBQAP.     

Ocular albinism and hypopigmentation defects in Slc24a5-/- mice

As part of a high-throughput mutagenesis and phenotyping process designed to discover novel drug targets, we generated and characterized mice with a targeted mutation in Slc24a5, a gene encoding a putative cation exchanger. Upon macroscopic examination, Slc24a5-/- mice were viable, fertile, and indistinguishable by coat color from their heterozygous and wild-type litter mates. Ophthalmoscopic examination revealed diffuse retinal hypopigmentation, and a histologic examination of the eye confirmed the presence of moderate-to-marked hypopigmentation of the retinal pigmented epithelium (RPE), ciliary body, and iris pigment epithelium (IPE). Hypopigmentation was most severe in the anterior layer cells of the IPE, where melanosomes were smaller, paler, and more indistinct than those of the anterior stroma and posterior IPE. The pigment granules of the posterior IPE appeared to be nearly as dark as those in stromal melanocytes; however, both cell layers were thinner and paler than corresponding layers in wild-type mice. Ultrastructural analysis of the RPE, IPE, and ciliary body pigmented cells confirmed that mutation of Slc24a5 results in marked hypopigmentation of melanosomes in optic cup-derived pigmented neuroepithelium in the eyes. Milder reductions in melanosome size and pigmentation were noted in neural crest-derived melanocytes. The severe hypopigmentation of neuroepithelium-derived cells in the eyes resulted in a novel form of ocular albinism in Slc24a5-/- mice. Our findings suggest that SLC24A5 may be a candidate gene for some forms of ocular albinism and for the BEY1/EYCL2 locus previously associated with central brown eye color in humans.