Pro-Inflammatory and Immunological Profile of Dogs with Myxomatous Mitral Valve Disease

Myxomatous mitral valve disease (MMVD) is a very frequently acquired cardiac disease in dog breeds and is responsible for congestive heart failure (CHF). The involvement of the immune system and pro-inflammatory cytokines in dogs with CHF due to mitral valve disease has not yet been extensively investigated. Here, we investigate the role of pro-inflammatory cytokines and the dysfunction of the immune system in dogs with different stages of severity through the blood assessment of CD4+FoxP3+regulatory T cells (Treg) cells, leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 pro-inflammatory cytokines, and immunological and echocardiographic parameters. A total of 36 cardiopathic dogs, 14 females and 22 males, with MMVD were included. Mean age and body weight (BW) at the time of enrollment were 10.7 ± 2.77 years and 10.9 ± 6.69 kg, respectively. For the comparison of the pro-inflammatory and immunological parameters, two groups of healthy dogs were also established. Control group 1 consisted of young animals (n. 11; 6 females and 5 males), whose age and mean weight were 4.1 ± 0.82 years and 13.8 ± 4.30 kg, respectively. Control group 2 consisted of elderly dogs (n. 12; 6 females and 6 males), whose age and BW were 9.6 ± 0.98 years and 14.8 ± 6.15 kg, respectively. Of particular interest, an increase in Treg cells was observed in the cohort of MMVD dogs, as compared to the healthy dogs, as Treg cells are involved in the maintenance of peripheral tolerance, and they are involved in etiopathogenetic and pathophysiological mechanisms in the dog. On the other hand, TNF-α, IL-1β, and IL-6 significantly increased according to the severity of the disease in MMVD dogs. Furthermore, the positive correlation between IL-6 and the left ventricle diastolic volume suggests that inflammatory activation may be involved in cardiac remodeling associated with the progressive volumetric overload in MMVD

Effect of a Weight Loss Program on Biochemical and Immunological Profile, Serum Leptin Levels, and Cardiovascular Parameters in Obese Dogs

This study aimed to investigate the effects of a weight loss program (WLP) on biochemical and immunological profile, and cardiovascular parameters in a cohort of dogs with naturally occurring obesity. Eleven obese dogs [body condition scoring (BCS), ≥7/9] were enrolled into the study and underwent clinical and cardiovascular examination, and blood testing before (T0) and after 6 months (T1) of WLP. Eleven normal weight (BCS, 4/5) healthy dogs were used as a control (CTR) group. Compared to the CTR group, at T0 obese dogs expressed higher serum leptin concentrations (p < 0.0005) that significantly decreased after weight loss (p < 0.005) but remained higher than the CTR group. Furthermore, obese dogs showed considerably lower levels (p < 0.0005) of regulatory T cell (Treg) compared to the CTR group, but they did not change after weight loss at T1. In obese dogs, tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were substantially reduced at T1 (p < 0.0001 and p < 0.005). Regarding the cardiovascular parameters, only one obese dog was hypertensive at T0, and systolic blood pressure values showed no significant differences at the end of the WLP. The ratio of interventricular septal thickness in diastole to left ventricle internal diameter in diastole (IVSd/LVIDd) was significantly greater in obese dogs at T0 than in the CTR group (p < 0.005). It decreased after weight loss (p < 0.05). In obese dogs, troponin I level significantly reduced with weight loss (p < 0.05), while endothelin-1 level did not differ statistically. The results suggest that the immune dysregulation in the presence of high leptin levels and reduced number of Treg could affect obese dogs as well as humans. Based on our findings, we may speculate that a more complete immune-regulation restore could be obtained by a greater reduction in fat mass and a longer-term WLP. Finally, left ventricular remodeling may occur in some obese dogs. However, in canine species, further studies are needed to investigate the impact of obesity and related WLP on cardiovascular system

Haematological and biochemical abnormalities in hunting dogs infected with Acanthocheilonema reconditum, associated risk factors, and a European overview

Acanthocheilonema reconditum is a filarial parasite transmitted by arthropods (fleas, lice, and ticks) that infect dogs. There is minimal published data available to date on potential haematological and biochemical changes associated with this parasitic infection. Study aims were (i) provide an overview of A. reconditum in Europe, (ii) define A. reconditum prevalence and risk factors in a specific dog population (hunting) from southern Italy, and (iii) assess the frequency of haemato-biochemical abnormalities associated with infection. Blood samples collected from 3020 dogs were tested by a modified Knott’s technique to count and identify microfilariae. Eighty-four dogs were infected by A. reconditum (2.78%; 95% CI 2.19–3.37%). Microfilariae ranged from 1 to 212/ml. Based on clinical examination, all but six dogs with non-specific symptoms were healthy. Haematological abnormalities included leucocytosis (n = 15), with eosinophilia (n = 14) and monocytosis (n = 13). Serum biochemical abnormalities included increased total serum proteins (n = 19), albumins (n = 7), total globulins (n = 14), ALT (n = 1), and ALP (n = 1); one dog was hypoalbuminemic, and BUN was mildly increased in 2 dogs. Risk factors included the province origin (Napoli, OR=5.4, 95%CI: 2.1–14.0; Caserta, OR=5.1, 95%CI: 2.5–10.6), hunting wild mammals (OR=2.8, 95% 95%CI: 1.6–4.8), and ectoparasite infestation (OR=1.9, 95%CI: 1.1–3.1). There was a negative correlation between microfilaraemic load and decreased albumin level (−0.37; p=0.021). Our results showed that A. reconditum circulates within the hunting dog population of southern Italy, with seemingly low pathogenic potential

Distribution and risk factors of canine haemotropic mycoplasmas in hunting dogs from southern Italy

Mycoplasma haemocanis (Mhc) and “Candidatus Mycoplasma haematoparvum” (CMhp) are the main haemoplasma species known to infect dogs. The aim of this study was to determine the prevalence of haemoplasma species infections in hunting dogs from southern Italy and assess related risk factors. 1,433 hunting dogs living in Campania region were tested by qPCR assay. The prevalence was 19.9 %; 13.1 % for Mhc and 11.4 % for CMhp; 4.6 % showed a coinfection with both haemoplasma species. Statistical analysis revealed living in Salerno province (Mhc: OR 3.72; CMhp: OR 2.74), hound (Mhc: OR 5.26; CMhp: OR 8.46) and mixed breed (Mhc: OR 3.38; CMhp: OR 2.80), rural environment (Mhc: OR 12.58; CMhp: OR 10.38), wild mammal hunting (Mhc: OR 8.73; CMhp: OR 8.32), cohabitation with other animals (Mhc: OR 2.82; CMhp: OR 2.78) and large pack size (Mhc: OR 2.96; CMhp: OR 1.61) as risk factors for haemoplasmas. Male gender (OR 1.44) and tick infestation history (OR 1.40) represented risk factors only for Mhc, while adult age (2 7 years - OR 2.01; > 7 years - OR 1.84) and large body size (OR 1.48) were associated only to CMhp. Mhc infection was significantly associated to Babesia vogeli (p < 0.05) and Hepatozoon canis (p < 0.001), while CMhp with H. canis (p < 0.001). This study adds information on haemoplasma species distribution in hunting dogs in southern Italy. Outdoor lifestyle and contact with wild fauna, through greater exposure to tick infestation, or possibly wounds acquired during hunting or fighting, could be factors contributing to haemoplasma infections

Hepatozoon canis in hunting dogs from Southern Italy: distribution and risk factors

Hepatozoon canis is a hemoprotozoan organism that infects domestic and wild carnivores throughout much of Europe. The parasite is mainly transmitted through the ingestion of infected ticks containing mature oocysts. The aims of the present survey were to determine the prevalence of H. canis in hunting dogs living in Southern Italy and to assess potential infection risk factors. DNA extracted from whole blood samples, collected from 1433 apparently healthy dogs living in the Napoli, Avellino, and Salerno provinces of Campania region (Southern Italy), was tested by a quantitative real-time polymerase chain reaction (qPCR) assay to amplify H. canis. Furthermore, the investigated dog population was also screened by qPCR for the presence of Ehrlichia canis, a major tick-borne pathogen in Southern Italy, in order to assess possible co-infections. Two hundred dogs were H. canis PCR-positive, resulting in an overall prevalence of 14.0% (CI 12.2–15.9). Breed category (P &lt; 0.0001), hair coat length (P = 0.015), and province of residence (P &lt; 0.0001) represented significant risk factors for H. canis infection. The presence ofH. canis DNA was also significantly associated with E. canis PCR positivity (P &lt; 0.0001). Hunting dogs in Campania region (Southern Italy) are frequently exposed to H. canis, and the infection is potentially associated with close contact with wildlife. Further studies are needed to assess the pathogenic potential of H. canis, as well as the epidemiological relationships between hunting dogs and wild animal populations sharing the same habitats in Southern Italy

H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.

H-Prune hydrolyzes short-chain polyphosphates (PPase activity) together with an hitherto cAMP-phosphodiesterase (PDE), the latest influencing different human cancers by its overexpression. H-Prune promotes cell migration in cooperation with glycogen synthase kinase-3 (Gsk-3β). Gsk-3β is a negative regulator of canonical WNT/β-catenin signaling. Here, we investigate the role of Gsk-3β/h-Prune complex in the regulation of WNT/β-catenin signaling, demonstrating the h-Prune capability to activate WNT signaling also in a paracrine manner, through Wnt3a secretion. In vivo study demonstrates that h-Prune silencing inhibits lung metastasis formation, increasing mouse survival. We assessed h-Prune levels in peripheral blood of lung cancer patients using ELISA assay, showing that h-Prune is an early diagnostic marker for lung cancer. Our study dissects out the mechanism of action of h-Prune in tumorigenic cells and also sheds light on the identification of a new therapeutic target in non-small-cell lung cancer