The incidence of non-Hodgkins Lymphoma (NHL) or Malignant Lymphoma (ML) in dogs is reported to be more than 24 per 100,000. Advances in the diagnosis and treatment of ML in dogs not only improve the quality of life of animals but also enable better models in veterinary comparative oncology.

Thymidine kinase (TK) is an intracellular enzyme that plays an important role during pyrimidine synthesis. TK activity increases markedly in the G1-S phase, especially during cell division, and decreases rapidly in the G2 phase. Therefore, high extracellular TK activity reflects high DNA synthesis and cells that die during cell division. Hematopoietic system malignancies are characterized by high cell proliferation. Studies in the veterinary field have shown that serum Thymidine kinase activity is an important marker in the diagnosis, prognosis and monitoring of treatment efficacy in leukaemia, multiple myeloma and malignant lymphoma.

TK activity has been used for years in the diagnosis, prognosis and treatment follow-up of hematopoietic tumours in human oncology, and the first study in the veterinary field was conducted by Nakamura et al. conducted in 1997 in Lymphoma, leukaemia, non-hematopoietic tumours (breast tumour, mastocytoma, anal sac tumour, malignant histiocytosis) and healthy dogs. After the analysis, TC activity in dogs with Lymphoma and Leukemia was significantly increased compared to healthy dogs; in dogs with non-hematopoietic tumours, it was found to be at the same level as healthy dogs. Again in the same study, it was determined that TC Activity is important in the follow-up of the treatment in the analyzes performed before the treatment, at the stage of the disappearance of clinical symptoms, and at the relapse stage.

In another study conducted by Prof. Dr. Hendrik von EULER et al. in dogs diagnosed with ML between 1999-2003, it was reported that TK Activity can be used as a strong marker in the diagnosis of ML disease, especially in determining the prognosis and predicting clinical disease before a recurrence in dogs undergoing chemotherapy. Serum TK Activity was found to be 2 to 180 times higher in dogs with ML disease than in healthy dogs. It was determined that TC activity decreased to normal values ​​in dogs that responded to treatment and whose cancer symptoms disappeared (complete remission), and TC activity increased again before recurrence. In the same study, it was determined that TC activity was correlated with the clinical stages of the disease.

Similar studies have been carried out in cats in recent years, along with studies in dogs. The first study on cats was conducted on a total of 171 cats in the UK and Sweden, published in 2012 and also included in our partner laboratory, Dechra Specialist Laboratories. Of the cats included in the study, 49 were healthy, 33 had lymphoma, 55 had the inflammatory disease, and 34 had non-hematopoietic neoplasia. At the end of the study, it was determined that the serum TC activity was significantly higher in cats with lymphoma compared to the others, and it was reported that high TC activity would strengthen the diagnosis of lymphoma.

Thymidine kinase activity with recent studies;

• In the diagnosis of lymphoma and leukaemia together with other clinical and laboratory findings,
• In evaluating the prognosis,
• In the evaluation of chemotherapeutic success with analyzes performed before, during and after treatment,
• Monitoring chemotherapy and identifying relapse cases before they form,
• It has been used successfully in distinguishing clinical worsening in patients receiving chemotherapy treatment.

References

• Boyé, P. et al. (2019) ‘Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment  effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.’, Journal of veterinary internal medicine, 33(4), pp. 1728–1739. doi: https://doi.org/10.1111/jvim.15513.
• Bryan, J. N. (2016) ‘The Current State of Clinical Application of Serum Biomarkers for Canine Lymphoma.’, Frontiers in veterinary science, 3, p. 87. doi: https://doi.org/10.3389/fvets.2016.00087.
• von Euler, H. et al. (2004) ‘Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for  prognosis and monitoring the disease.’, Journal of veterinary internal medicine. United States, 18(5), pp. 696–702. doi: https://doi.org/10.1371/journal.pone.0137871.
• Kayar, A. et al. (2018) ‘Clinical features, haematologic parameters, blood serum biochemistry results and thymidine kinase activity of dogs affected by malignant lymphoma in Turkey’, Japanese Journal of Veterinary Research, 66(4), pp. 227–238. doi: https://doi.org/10.14943/jjvr.66.4.227.
• Larsdotter, S., Nostell, K. and von Euler, H. (2015) ‘Serum thymidine kinase activity in clinically healthy and diseased horses: a  potential marker for lymphoma.’, Veterinary journal (London, England : 1997). England, 205(2), pp. 313–316. doi: https://doi.org/10.1016/j.tvjl.2015.01.019.
• Nakamura, N. et al. (1997) ‘Plasma thymidine kinase activity in dogs with lymphoma and leukemia.’, The Journal of veterinary medical science. Japan, 59(10), pp. 957–960. doi: https://doi.org/10.1292/jvms.59.957.
• Selting, K. A. et al. (2016) ‘Thymidine Kinase Type 1 and C-Reactive Protein Concentrations in Dogs with  Spontaneously Occurring Cancer.’, Journal of veterinary internal medicine, 30(4), pp. 1159–1166. doi: https://doi.org/10.1111/jvim.13954.
• Taylor, S. S. et al. (2013) ‘Serum thymidine kinase activity in clinically healthy and diseased cats: a potential  biomarker for lymphoma.’, Journal of feline medicine and surgery. England, 15(2), pp. 142–147. doi: https://doi.org/10.1177/1098612X12463928.

Blood creatinine concentration is measured for purposes such as diagnosis of kidney failure, determination of its stage, follow-up of treatment, and evaluation of prognosis.

In addition, from time to time, urine creatinine concentration is measured and evaluated alone or in combination with other test parameters (such as protein). The only way to make these measurements is to use specific analytical methods. One of the commonly used methods is the Jaffe reaction. The creatinine concentration is determined from blood and urine samples by the Jaffe reaction, which is a colorimetric method¹.

132 years ago (1886) Max Jaffe (1841-1911) discovered that creatinine reacts with picric acid in an alkaline environment and explained this by publishing his article “Über den Niederschlag, welchen Pikrinsäure in normalem Harn erzeugt und über eine neue Reaction des Kreatinins”². The article describes this reaction and the nature of the precipitate formed. Jaffe’s discovery was a turning point. As a result of this study, the method of measuring creatinine concentration, which has become extremely popular and defied time, was born.

Over time, Jaffe’s name became synonymous with clinical creatinine testing, although his article later became the permanent method and the principle of further studies. At the beginning of the twentieth century, Otto Folin (1867-1934), taking up the research of Max Jaffe, developed a colorimetric method for measuring the concentration of creatinine in blood and urine³ and made it into modern biochemistry analysis.

Although there are more specific analytical methods⁴ today, this unique test is still used as the preferred method due to its simplicity of implementation, speed, compatibility with automated analyzers, and cost-effectiveness. Besides, the Jaffe reaction is the oldest test method used in clinical laboratories.

References

1. Delanghe JR, Speeckaert MM. Creatinine determination according to Jaffe – What does it stand for? NDT Plus. 2011;4(2):83-86. doi: http://doi.org/10.1093/ndtplus/sfq211
2. Jaffe M. Ueber den Niederschlag, welchen Pikrinsäure in normalem Harn erzeugt und über eine neue Reaction des Kreatinins. ZPhysiolChem. 1886. doi: https://doi.org/10.1515/BCHM1.1886.10.5.391
3. Folin O. Beitrag zur Chemie des Kreatinins und Kreatins im Harne. Hoppe Seylers Z Physiol Chem. 1904. doi: https://doi.org/10.1515/bchm2.1904.41.3.223
4. Panteghini M, IFCC. Enzymatic assays for creatinine: Time for action. Scand J Clin Lab Invest. 2008;46(4):567-572. doi: https://doi.org/10.1080/00365510802149978

Bisphenol A (BPA; IUPAC name: 2,2-bis(4-hydroxyphenyl) propane) is an organic synthetic compound that has a dysfunctional effect on the endocrine system.

Bisphenol A (BPA) causes random and systemic effects in living things without tissue separation. They can block the binding of natural ligands to their respective receptors. For example;

• Changes in the activity of gonadal hormones.
• Disturbances in thyroid hormone function; It is structurally similar to thyroid hormones and acts as a thyroid hormone receptor antagonist.
• Differences in central nervous system function.
• Suppression of the immune system.

BPA is a chemical used in the manufacture of many household items. It is frequently used in food and beverage packaging materials; polycarbonate plastics (plastic bottles, storage containers…), and epoxy resins (metal cans, soft drink cans, aluminum containers, tin containers…). Today, the production volume of BPA in the world is expressed in trillions of dollars annually and this volume is increasing every year.

Due to the faulty production of containers containing BPA, BPA is migrated to the food and it is taken into the body with the consumption of this food. Considering its negative impact on living things and its widespread use, its importance emerges and it draws attention, especially in packaging products that come into contact with canned food. Due to its negative effects on human health, many countries, especially the United States, the European Union, and the Republic of Turkey (Turkish Food Codex Communiqué on Plastic Substances and Materials in Contact with Food; No: 2013/34), have limited the use of BPA and set migration limits. In addition, its use is completely prohibited, especially in some products; such as polycarbonate baby bottles, pacifiers, and bottle caps. It is seen that these legal regulations and many studies are completely focused on human health.

Bisphenol A and Pets

It is known that cats and dogs are mostly fed commercial foods. However, the BPA content of these foods is questionable. Regarding BPA exposure, studies on the packaging of pet foods (especially cans) and food migration, the level of BPA exposure in pet animals, and potential health consequences are limited.

In a study, different concentrations of BPA were detected in 15 different commercial cat foods and 11 different commercial dog foods (Kang and Kondo, 2002).

In a study comparing cats with hyperthyroidism and cats with normal thyroid function, it was determined that feeding canned food poses a higher risk for hyperthyroidism than feeding other types of packaged food. It has been hypothesized that this situation may be related to the BPA content of canned foods (especially aluminum-composition tin containers) (Edinboro et al., 2004; Köhler et al., 2016).

In a recent study on dogs (Koestel et al. 2017), the BPA content in commercial dog foods was determined and the effects on the exposure level and health status of animals were investigated after consumption of these foods in a short time period (two weeks). For this purpose, a two-week feeding program was applied, one using packaged commercial food specified as BPA-free and the other commercial food without such an indication. The serum BPA concentrations of the animals were compared with the hematological tests, serum biochemistry, cortisol, DNA methylation, and intestinal microbiome changes in the samples (blood, feces) taken before the diet and two weeks later. As a result of the study, it was determined that serum BPA concentrations increased 3 times in dogs fed with both foods. It was determined that this increase was accompanied by changes in serum biochemistry and microbiome. It has been determined that the increase in serum BPA level decreases the bacterial species in the microbiome. One of the interesting findings of the study was the detection of measurable levels of BPA, even in foods specified as BPA-free.

BPA can bioaccumulate in terrestrial and aquatic resources, thus posing the risk of continued exposure to animals and humans. In a world where humans and animals live together, we cannot separate human and animal health. The principle of “One Health” should always be adopted, the issue of BPA should be approached from this perspective and more studies on the subject are needed.

References

• Edinboro CH, Scott-Moncrieff JC, Janovitz E, Thacker HL, Glickman LT, (2004). Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats. J Am Vet Med Assoc., 224(6):879-886. https://doi.org/10.2460/javma.2004.224.879
• Kang JH, Kondo F, (2002). Determination of bisphenol A in canned pet foods. Res Vet Sci., 73(2):177-182. https://doi.org/10.1016/s0034-5288(02)00102-9
• Koestel ZL, Backus RC, Tsuruta K, Spollen WG, Johnson SA, Javurek AB, Ellersieck MR, Wiedmeyer CE, Kannan K, Xue J, Bivens NJ, Givan SA, Rosenfeld CS, (2017). Bisphenol A (BPA) in the serum of pet dogs following short-term consumption of canned dog food and potential health consequences of exposure to BPA. Sci Total Environ., 579:1804-1814. https://doi.org/10.1016/j.scitotenv.2016.11.162
• Köhler I, Ballhausen BD, Stockhaus C, Hartmann K, Wehner A, (2016). Prevalence of and risk factors for feline hyperthyroidism among a clinic population in Southern Germany. Tierarztl Prax Ausg K Kleintiere Heimtiere., 44(3):149-157. https://doi.org/10.15654/tpk-150590
• Er B, SarımehmetoğluB, (2011). Gıdalarda bisfenol A varlığının değerlendirilmesi. Vet. Hekim Der Derg., 82(1):69-74.