Oxidative stress in dogs with chronic inflammatory enteropathy treated with allogeneic mesenchymal stem cells.

The search for new biomarkers in patients with chronic inflammatory enteropathy (CIE) is ongoing in the human and veterinary medicine fields. Oxidative stress biomarkers (malondialdehyde [MDA], reduced glutathione [GSH], and albumin) have been studied in humans with chronic enteropathies, but among them, only albumin has been studied in dogs with CIE. Moreover, the effect of mesenchymal stem cell (MSCs) treatment with or without prednisone on these parameters has never been studied in dogs with CIE. These parameters were compared between healthy dogs (n = 12) and dogs with CIE, and before and 1, 3, 6, and 12 months after the treatment with MSCs alone (n = 9) or together with prednisone (n = 11). The relationship between the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) and oxidative stress was evaluated. Albumin was the only parameter that significantly differed between dogs with CIE and healthy dogs (p = 0,037). Differences were observed only in albumin values after combined treatment with MSCs and prednisone. No differences were observed in MDA and GSH after treatment with MSCs with or without prednisone. Albumin could help stage canine CIE, as well as its prognosis, as has already been demonstrated, although it is essential to evaluate this parameter for its antioxidant capacity, and therefore it could be a good biomarker of oxidative stress in this pathology. However, the treatment with MSCs seems unable to modify any of the analyzed oxidative stress parameters.

Urinary cystatin C and N-acetyl-beta-D-glucosaminidase (NAG) as early biomarkers for renal disease in dogs with leishmaniosis.

Canine leishmaniasis (CanL) is a disease caused by Leishmania infantum that can vary from a subclinical infection to a severe disease. Dogs affected with CanL present varying degrees of renal dysfunction. Unfortunately, traditional biomarkers such as urea and creatinine detect renal damage in advanced stages of the disease, so more accurate biomarkers are needed. Hence, we aimed to study how urinary cystatin C (CysC) and N-acetyl-beta-D-glucosaminidase (NAG), behave in dogs with CanL at different stages of the disease. Eighty-six CanL infected dogs were classified according to LeishVet stages: LI (16 dogs), LIIa (12 dogs), LIIb (12 dogs), LIII (16 dogs) and LIV (30 dogs); as a control, 17 healthy dogs were studied. Blood samples were collected for complete haematological and biochemistry analysis including plasma cystatin C. Urine analysis included urine specific gravity (USG), urine protein to creatinine ratio (UPC), CysC and NAG expressed as a ratio with creatinine uCysCc (µg/g) and uNAGc (IU/g). The haematological, biochemical and urinary analysis coincided with the LeishVet guidelines. The statistical study of the uCysCc ratio and the uNAGc, showed significant increase when compared against control starting from group LI (p < 0.05). Interestingly, when the cut-off values were calculated using the ROC curve, uCysCc (258.85 µg/g) and uNAGc (2.25 IU/g) 75 % of the dogs included in LI groups surpassed the threshold. Hence our study indicates that uCysCc and uNAGc, could help to detect early renal damage in CanL affected dogs.

Complete Blood Count-Derived Inflammatory Markers Changes in Dogs with Chronic Inflammatory Enteropathy Treated with Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (Ad-MSCs) exhibit anti-inflammatory and immunomodulatory activities. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been reported as novel biomarkers of the inflammatory state; however, they have never been examined in dogs with chronic inflammatory enteropathy (CIE) treated with Ad-MSCs. This study aimed to compare the clinical evolution and the changes in the NLR, PLR, and SII in dogs with CIE before and after cell therapy. Sixteen dogs with CIE were administered a single intravenous dose of Ad-MSCs. The canine chronic enteropathy clinical activity index (CCECAI), NLR, PLR, and SII were assessed before treatment (T0) and at 2 (T2) and 9 (T9) months post-treatment and compared over time and with the reference values obtained from a group of healthy dogs. NLR, PLR, and SII were significantly increased at T0 compared to the reference values, decreasing significantly over time. At T9, the NLR and SII did not differ from the reference values, but PLR remained above the reference values. A correlation was observed between CCECAI and the three markers. These findings show that the clinical improvement of dogs with CIE treated with Ad-MSCs is accompanied by a normalization of the inflammatory status.

Effects of Allogeneic Mesenchymal Stem Cell Transplantation in Dogs with Inflammatory Bowel Disease Treated with and without Corticosteroids.

Mesenchymal stem cells have proven to be a promising alternative to conventional steroids to treat canine inflammatory bowel disease (IBD). However, their administration requires a washout period of immunosuppressive drugs that can lead to an exacerbation of the symptoms. Therefore, the feasibility and effects of the combined application of stem cells and prednisone in IBD-dogs without adequate response to corticosteroids was evaluated for the first time in this study over a long- term follow up. Two groups of dogs with IBD, one without treatment and another with prednisone treatment, received a single infusion of stem cells. The clinical indices, albumin and cobalamin were determined prior to the infusion and after one, three, six and 12 months. In both groups, all parameters significantly improved at each time point. In parallel, the steroid dosage was gradually reduced until it was suppressed in all patients a year after the cell therapy. Therefore, cell therapy can significantly and safely improve the disease condition in dogs with IBD receiving or not receiving prednisone. Furthermore, the steroid dosage can be significantly reduced or cancelled after the stem cell infusion. Their beneficial effects are stable over time and are long lasting.

Effects of Sedation with Medetomidine and Dexmedetomidine on Doppler Measurements of Ovarian Artery Blood Flow in Bitches.

The aim was to evaluate if medetomidine and dexmedetomidine affected arterial ovarian blood flow in dogs. The dogs were randomly assigned to two different groups. In Group 1, medetomidine (10 µg/kg) was administered intramuscularly and, in Group 2, dexmedetomidine (5 µg/kg) was used. After a preliminary exam, arterial blood pressure (BP) was measured and a duplex Doppler ultrasonographic examination of both ovarian arteries was performed. Twenty minutes after the administration of medetomidine or dexmedetomidine, BP and ovarian Doppler ultrasonography were repeated. High quality tracings of ovarian artery flow velocity were obtained in all dogs and Doppler parameters: Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV) and Resistive Index (RI) were measured before and after drug administration in the left (LO) and right (RO) ovaries. PSV and EDV values decreased significantly after drug administration (p < 0.05) compared to the non-sedated values, but no differences were found between the LO and RO (p > 0.05). The RI was not affected by drugs administration in neither of the groups studied (p > 0.05). In conclusion, the administration of medetomidine or dexmedetomidine causes a decrease in blood flow velocity in the ovarian artery and may be a good choice to avoid excessive bleeding prior surgeries in which ovariectomy.

Comparison of N-terminal proB-type natriuretic peptide levels at different stages of visceral leishmaniosis and in patients with chronic kidney disease.

N-terminal proB-type natriuretic peptide (NT-proBNP) may be a useful marker in canine leishmaniosis (CanL). The aim was to compare NT-proBNP in dogs at different LeishVet stages of CanL and with idiopathic chronic kidney disease (CKD). Dogs diagnosed with CanL or CKD and a group of healthy dogs were included (group A, five normal dogs; group B, six dogs LeishVet 1-2; group C, 13 dogs LeishVet 3-4; group D, six dogs with CKD). NT-proBNP was higher (P<0.001) in group C (7.616 pmol/l, interquartile range (IQR) 3537-10,000 pmol/l) than in group A (293 pmol/l, IQR 257-373), group B (388.5 pmol/l, IQR 324-793) and group D (740 pmol/l, IQR 557-962 pmol/l). International Renal Interest Society (IRIS) kidney stage was not different between groups C and D or between groups A and B, but was different within all the rest of the group comparisons (P<0.001). In group C all dogs had echocardiographic increase in left ventricular mass index. NT-proBNP had negative correlation with haematocrit (P<0.001, r=0.749) and positive correlation with systemic blood pressure (P<0.001, r=0.728). NT-proBNP is consistently elevated in dogs with advanced CanL and is strongly correlated with the degree of systemic hypertension and anaemia. Moreover, dogs with advanced CanL exhibit increase in left ventricular mass. NT-proBNP may however be a less desirable cardiac marker as unlike cardiac troponin I it is often not elevated at earlier stages of CanL.