The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins, an integral part of the acute phase response, have been a focus of many applications in human diagnostic medicine and recently have been identified in common animal species. Potential applications to diagnosis, prognosis, assessment of animal health, and laboratory animal welfare are readily apparent.

Acute phase response in animals: a review.

Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and alpha(1) acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease.

Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine

Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics.

Translation of new cancer treatments from pet dogs to humans.

Canine tumors: a spontaneous animal model of human carcinogenesis.

Dogs with osteosarcoma provide an important model for the same disease in humans. In this report, the comparative nature of human and canine osteosarcoma including incidence and risk factors, clinical presentation and diagnosis, genetic abnormalities, biologic behaviour and prognostic factors, as well as treatment options are reviewed.

Comparative biology of human and canine osteosarcoma.

To investigate the clinical utility of C-reactive protein (CRP) determination in dogs, its plasma concentration was measured by a laser nephelometric method in 928 dogs with various diseases, and was compared with other inflammatory parameters CRP concentration was elevated in various inflammatory diseases, this was most frequently observed in cases with neoplastic and immune-mediated diseases All cases of pyometra, panniculitis, acute pancreatitis, polyarthritis, and hemangiosarcoma showed significantly elevated CRP concentrations On the other hand, the CRP concentration was elevated only in few cases of neurological diseases such as epilepsy, meningoencephalitis, and hydrocephalus and endocrine diseases such as hypothyroidism, hyperadrenocorticism, and diabetes mellitus Only a weak correlation was observed between the CRP concentration and white blood cell (WBC) counts (r=044) but no correlation with band neutrophil counts There was no correlation between the CRP and albumin concentrations, but a weak negative correlation (r=-040) when excluding chronic intestinal diseases and nephrotic syndrome, which can cause protein loss Thus, CRP can be useful to detect inflammations that cannot be detected by WBC and, or band neutrophil counts, suggesting that the examination of CRP concentration is essential as routine diagnostic test

https://www.jstage.jst.go.jp/article/jvms/70/2/70_2_127/_pdf

C-Reactive Protein Concentration in Dogs with Various Diseases

Objective—To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs. Sample Population—Tumor specimens from 15 dogs with various tumors, including malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adenoma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon cancer (1), and osteosarcoma (3). Procedure—Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase- polymerase chain reaction and single-strand conformation polymorphism analysis, using 3 fragments that covered the entire open reading frame of the canine p53 gene, followed by nucleotide sequencing of the abnormal bands. Results—Point mutations, deletions, and insertions resulting in a number of amino acid substitutions of wild-type p53 were detected in 7 of the 15 tumor specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdomyosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberrations of the p53 gene on both allel...

Aberrations of the p53 tumor suppressor gene in various tumors in dogs.

To investigate the clinical utility of C-reactive protein (CRP) in idiopathic polyarthritis (IPA), its concentration was measured in dogs with IPA. The CRP concentration was markedly increased in all the IPA dogs at the time of diagnosis and decreased significantly in response to the initial corticosteroid treatment; this indicated that CRP can be used as an index for therapeutic response in IPA cases. Furthermore, at 6 months after the diagnosis, a significant association was observed between the CRP concentration at follow-up (6-13 days after the treatment was started) and the frequency of medication ("no or seldom-medicated (NSM)" groups or "continuing medication (CM)" groups). These results suggest that the initial response of CRP to corticosteroid treatment may be a prognostic factor of canine IPA.

C-Reactive Protein Concentration in Canine Idiopathic Polyarthritis

Telomeres are specific structures present at the end of liner chromosomes. DNA polymerase can not synthesize the end of liner DNA and, as a result, the telomeres become progressively shortened by successive cell divisions. To overcome the end replication problem, telomerase adds new telomeric sequences to the end of chromosomal DNA. The enzyme activity is undetectable in most normal human adult somatic cells, in which shortening of the telomere is thought to limit the somatic-cell life span. In contrast to normal somatic cells, many human tumors possess telomerase activity. The present study looked at whether telomerase activity might serve as a marker for canine tumors. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Normal dog somatic tissues showed little or no telomerase activity, while normal testis exhibited a high level of telomerase activity. We measured telomerase activity in tumor samples from 45 dogs; 21 mammary gland tumors, 16 tumors developed in the skin and oral cavity, 7 vascular tumors and 1 Sertoli cell tumor. Greater than 95% of the tumor samples contained telomerase activity (3-924 U/2 micrograms protein). The results obtained in this study indicated that telomerase should be a useful diagnostic marker for a variety of dog tumors, and it may serve as a target for antitumor chemotherapy.

Measurement of telomerase activity in dog tumors.

Transforming growth factor-β1 (TGF-β1), an inflammatory cytokine, plays a role in tissue fibrosis, such as glomerular sclerosis and tubulointerstitial fibrosis of the kidneys. In the present study, the urinary TGF-β1 level of cats diagnosed with chronic renal failure (CRF) was measured to investigate its relationship to the pathogenesis of feline CRF. Urinary TGF-β1 levels (TGF-β1/creatinine ratio) were significantly increased compared with healthy controls, whereas serum levels of TGF-β1 were not. These results indicate that TGF-β1 is expressed in the kidneys of CRF cats, and that it was reflected in the urinary TGF-β1 level. Therefore, TGF-β1 may play a role in feline CRF, and urinary TGF-β1 could be used as a clinical marker for renal fibrosis.

/pdf/urinary-transforming-growth-factor-b1-in-feline-chronic-19byfww26b.pdf

Asuka Setoguchi

Papers

C-Reactive Protein Concentration in Dogs with Various Diseases

Aberrations of the p53 tumor suppressor gene in various tumors in dogs.

C-Reactive Protein Concentration in Canine Idiopathic Polyarthritis

Measurement of telomerase activity in dog tumors.

Urinary Transforming Growth Factor-β1 in Feline Chronic Renal Failure