Fatal Pulmonary Hypertension and Right-Sided Congestive Heart Failure in a Kitten Infected with Aelurostrongylus abstrusus

Aelurostrongylus abstrusus is considered the most important respiratory nematode of domestic cats worldwide. This parasite inhabits the alveoli, alveolar ducts, and bronchioles and causes a subacute to chronic respiratory clinical disease. Clinical signs may occur in domestic cats of any age, though they are more often described in young animals. Physical examination, echocardiography, thoracic radiography, pulmonary and cardiac pathological findings, classical, and molecular parasitological analysis of a six-month-old kitten referred at the Veterinary Teaching Hospital of the University of Pisa (Italy) led to a diagnosis of parasitic bronchopneumonia caused by A. abstrusus, which was complicated by severe pulmonary hypertension (PH) and right-sided congestive heart failure (R-CHF) that caused the death of the animal. Cases of reversible PH associated with A. abstrusus infection have been seldom reported in cats. This is the first report of fatal PH and R-CHF in a kitten with clinical aelurostrongylosis

Effect of dietary supplementation of a mix of chestnut and quebracho tannins on intestinal morphology, bacterial load, Eimeria spp oocyst excretion and immune response after vaccination in rabbits

Among plant products, tannins exhibited a strong antioxidant activity and their employment was studied as food or feed addictive with positive effects. Nevertheless, their health-enhancing properties remain to be completely clarified, particularly in rabbits. The aim of the present study was to investigate the influence of a mix of chestnut and quebracho tannins as supplementation in rabbit diet on intestinal morphology, as well as bacterial loads and Eimeria spp coccidial oocyst excretion and humoral immune response after vaccination. Rabbits were fed four different diets: basal diet (negative control, group CN), basal diet with anticoccidial supplementation (positive control, group CP) and basal diet with tannins mix 0.3% (group T0.3) or 0.6% (group T0.6). Samples of intestine, liver, spleen thymus, mesenteric lymph nodes, kidney and heart were submitted to histopathologic investigations. Morphometric analyses were performed on portion of duodenum, jejunum and ileum. Intestinal contents were analyzed by flotation test for Eimeria spp. oocysts excretion and by microbiological assays for Clostridium perfringens and Escherichia coli. Rabbits belonging to the four experimental groups were vaccinated by means of a live attenuated myxomatosis virus and sera were collected individually at three time points to determine antibody response.The obtained results demonstratedthe absence of toxic effects of the tannin mix on examined organs, particularly on liver and kidney and any negative influence on the growth performance. A relevant anti-inflammatory effect on the intestinal tract, a reduction of Eimeria spp. oocysts excretion and a positive immunomodulatory and antibacterial effects were also observed. Diets supplemented with the tannins mix affected also the morphology of examined intestinal tracts, particularly duodenum and ileum

Cyclophilin A modulates bone marrow-derived CD117+ cells and enhances ischemia-induced angiogenesis via the SDF-1/CXCR4 axis

Abstract Background Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo . However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues. Methods and results Wild-type C57Bl/6j mice underwent acute hind-limb ischemia (HLI) and received a single intramuscular administration of recombinant CyPA or saline. Limb perfusion, capillary density and arteriole number in adductor muscles were significantly increased after CyPA treatment. Interestingly, BM-derived CD117 + cell recruitment was significantly higher in ischemic adductor tissue of mice treated with CyPA versus saline. Therefore, the effect of CyPA on isolated BM-derived CD117 + cells in vitro was evaluated. Low concentrations of CyPA stimulated CD117 + cell proliferation while high concentrations promoted cell death. Moreover, CyPA enhanced CD117 + cell adhesion and migration in a dose-dependent manner. Mechanistic studies revealed that CyPA up-regulated CXCR4 in CD117 + cells and in adductor muscles after ischemia. Additionally, SDF-1/CXCR4 axis inhibition by the CXCR4 antagonist AMD3100 decreased CyPA-mediated CD117 + cell recruitment in the ischemic limb. Conclusion CyPA induces neo-angiogenesis by recruiting BM-derived CD117 + cell into ischemic tissues, at least in part, through SDF-1/CXCR4 axis

Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil e ective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients' aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF- 1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients' TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine