Role of Luteinizing Hormone in Primiparous Sow Responses to Split Weaning

In 45 primiparous sows, we examined endocrine, ovarian and reproductive responses to split-weaning or five injections per day of 800 ng GnRH from 18 to 21 days of lactation. There was no effect of treatment on absolute or changes in sow weight or backfat depth during lactation. Average piglet growth rates were similar among treatments except that piglets suckling split-weaned sows grew faster (p < 0.05) during days 18–21. On day 18, mean plasma LH concentrations and LH pulse frequency remained relatively stable in conventionally weaned sows but increased (p < 0.01) in response to split-weaning and GnRH. Prior to weaning on day 21, mean plasma LH concentrations remained elevated in GnRH-treated sows but had returned to control levels in split weaned sows. There was no treatment effect on preweaning LH pulse frequency noted on day 21. Weaning was associated with an increase in plasma LH concentrations in all the treatment groups. Mean plasma IGF-I remained relatively constant in conventionally weaned and GnRH sows, decreased in response to split weaning on day 18 (p < 0.02), but were elevated (p < 0.03) in split wean sows on day 21. On the day after weaning, split wean sows had more (p < 0.04) ovarian follicles ≥3 mm than conventionally weaned sows, with GnRH sows being intermediate. The wean-to-oestrus interval was reduced in split-wean sows compared with those conventionally weaned (p < 0.01), with GnRH sows being intermediate. There was no effect of treatment on ovulation rates, numbers of embryos, or embryonic survival rates. These data indicate that split-weaning of litters results in a more rapid return to oestrus after weaning and that this effect is associated with a transient acute increase in circulating gonadotrophins and earlier resumption of ovarian follicular development.     

A Case of Schistosoma Reflexum in a Cat with Chromosomal Aberrations

A 2‐year‐old, female Persian cat was presented with a history of distocia. In her first pregnancy, she had whelped four kittens and had eaten all of them right after parturition. She had mated again with the same tomcat. Well‐developed foetuses with weak foetal heart beats were observed in the ultrasonographic examination. En block ovariohysterectomy was performed. Three live and mature foetuses were obtained from the uterus; two of them were female foetuses and had no anatomical problem but the third one exhibiting multiple malformations was a male and diagnosed as ‘schistosoma reflexum’ (SR). The vertebral column deviated markedly to the right (scoliosis) at thoracolumbar region, and the middle lumbar and the sacral vertebrae were directed dorsocranially (lordosis). The entire small intestine, a part of large intestine, stomach, spleen and the right kidney were displayed out of the body, and it seemed that the listed internal organs were protruded from an abdominal cleft associated with the allantoic membrane. Liver, lungs and heart were hypoplastic. The large intestine was seen to have blind end (atresia recti), but anus was normal. Cerebrum and cerebellum were noticed as normal in sizes. Chromosome preparations from lymphocyte cultures of the foetus showed chromosomal aberrations including chromatid and chromosome breaks, exchange figures, non‐homologous pairing, whereas no abnormalities were detected in the chromosome preparations from mother’s cultures. This is probably the first case of SR in a cat, which was examined in detail from clinical, pathological, radiological and chromosomal angles.     

Comparison of ultrasonographic findings with clinical activity index (CIBDAI) and diagnosis in dogs with chronic enteropathies.

Intestinal wall thickness is neither a specific nor sensitive ultrasound parameter for detecting intestinal inflammation. We hypothesize that mucosal echogenicity, lymphadenomegaly, and secondary findings of the gastrointestinal tract would be more sensitive and specific markers for detecting and differentiating causes of chronic inflammatory bowel disease in dogs. Fifty-six client-owned dogs with chronic diarrhea and 10 control dogs were examined with two-dimensional, gray-scale ultrasound (time 0, 4, and 10 weeks post therapy) and small intestinal mucosal biopsies were performed at the 0- and 4-week time points. The clinical activity was assessed at each time point using the canine inflammatory bowel disease activity index (CIBDAI). Fifty-one dogs had inflammatory infiltration of the duodenal mucosa and were divided into three groups, food-responsive disease, idiopathic inflammatory bowel disease, and protein-losing enteropathy, based on their response to the different treatments and histology. Two different patterns of increased echogenicity of the mucosa were detected: hyperechoic speckles and hyperechoic striations. A normal, hypoechoic bowel mucosa in dogs with chronic diarrhea had a sensitivity of 80% and a specificity of 81% for the diagnosis of food-responsive disease. Hyperechoic striations had a sensitivity of 75% and a specificity of 96% for dogs with protein-losing enteropathy. Hyperechoic speckles were non-specific for diagnosing inflammatory bowel disease. There was a significant relationship between ultrasound score and CIBDAI at t0, but not following therapy. Mucosal echogenicity may be a better parameter for detecting inflammatory bowel disease than bowel wall thickness in dogs with chronic diarrhea.     

Relation between Habitual Diet and Canine Mammary Tumors in a Case-Control Study

In the present case-control study several dietary and nutritional factors were investigated to determine if a relationship exists between diet and development of mammary tumors in female dogs. Control female dogs (n = 86) were compared with a case group of dogs (n = 102) with dysplasias or tumors of the mammary gland. A questionnaire providing information on the dog's body conformation and dietary and reproductive histories was answered by the owners. Serum selenium and retinol concentrations and the fatty acid profile in subcutaneous adipose tissue were analyzed as indicators of nutritional status. Obesity at 1 year of age and 1 year before the diagnosis of mammary nodules was found to be significantly related to a higher prevalence of mammary tumors and dysplasias. The intake of homemade meals (compared to that of commercial foods) was also significantly related to a higher incidence of tumors and dysplasias. Other significant risk factors were a high intake of red meat, especially beef and pork, and a low intake of chicken. The subcutaneous fatty acid profile and the serum selenium concentration were not significantly different in the cases and the controls, with the exception of C18:1 fatty acid (oleic acid) content, which was significantly higher in the cases than in healthy controls. Serum retinol concentration was significantly lower in the cases than in the controls. In the multivariate analysis, older age, obesity at 1 year of age, and a high red meat intake were independently and significantly associated with the risk of developing mammary tumor and dysplasias.     

Immunohistochemical evaluation of p53 expression with different antibodies in malignant canine tumours with or without p53 gene mutation

Six monoclonal antibodies and a polyclonal antibody (CM1) were used to investigate the overexpression of p53 protein by immunohistochemistry (IHC) in six sarcomas and 21 mammary carcinomas from 27 dogs. IHC was compared with p53 gene mutation analysis performed on the same samples. Only the monoclonal PAb240, PAb421 and the CM1 antibodies were able to detect expression of canine p53 protein. CM1 was found to give the highest concordance (8/11) between positive expression of the p53 protein by IHC and the presence of a gene mutation. In the samples that were negative for p53 expression by IHC, but contained a p53 gene mutation according to DNA analysis, the mutation often affected the epitopes that could have been recognized by these antibodies. Only one out of 16 tumours without a p53 gene mutation had a weakly positive IHC result. These findings indicate that in these two types of canine tumours, IHC – particularly with CM1 – can detect many alterations in p53 expression owing to a gene mutation. False‐positive results were very infrequent.     

Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals

The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half-lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals.     

Upregulation of the PI3K/Akt Pathway in the Tumorigenesis of Canine Thyroid Carcinoma

Background

Information on the genetic events leading to thyroid cancer in dogs is lacking.

Hypothesis/Objectives

Upregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs.

Animals

Fifty‐nine dogs with thyroid carcinoma and 10 healthy controls.

Methods

Quantitative RT‐PCR was performed for VEGFR‐1, VEGFR‐2, EGFR, PIK3CA, PIK3CB, PDPK1, PTEN, AKT1, AKT2, COX‐2, and CALCA. Mutation analysis was performed for known hotspots of RAS (N, K, H), PIK3CA, BRAF, RET, and for the entire coding region of PTEN.

Results

Forty‐three dogs (73%) had follicular cell thyroid carcinoma (FTC) and 16 dogs (27%) had medullary thyroid carcinoma (MTC). The relative mRNA expressions of VEGFR‐1 (P < .001), VEGFR‐2 (P = .002), PDPK1 (P < .001), AKT1 (P = .009), and AKT2 (P < .001) were increased in FTC, and those of EGFR (P < .001), VEGFR‐1 (P = .036), and PIK3CA (P = .019) were increased in MTC when compared to normal thyroid glands. Mutation analysis of K‐RAS identified 2 activating missense mutations, which also have been described in thyroid cancer of humans. A G12R substitution was present in 1 FTC and an E63K substitution was present in 1 MTC. No functional mutations were found in the sequenced regions of H‐RAS, N‐RAS, PIK3CA, BRAF, RET, and PTEN.

Conclusions and Clinical Importance

The increased expression of several genes associated with PI3K/Akt signaling suggests the involvement of this pathway in the pathogenesis of thyroid carcinoma in dogs, warranting further research on pathway activation and gene amplification. The mutations most frequently associated with thyroid cancer in humans are rare in dogs.