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Additive manufacturing (AM) is the process of joining materials to create layer-by-layer three-dimensional objects using a 3D printer from a digital model. The great advantage of Additive Manufacturing is to allow a freer design than traditional processes. The development of additive manufacturing processes has permitted to optimize the production of the customized product through the modeling of the geometry and the knowledge of the morphometric parameters of the body structures. 3D printing has revolutionized the field of Regenerative Medicine because, starting from computerized tomography (CT) images and using traditional materials such as plastic and metals, it can provide customized prostheses for each patient, which adapt perfectly to the needs of the subject and act as structures support. 3D printing allows you to print three-dimensional porous scaffolds with a precise shape and chemical composition suitable for medical and veterinary use. Some of these scaffolds are biodegradable and appear to be ideal for bone tissue engineering. In fact, they are able to simulate extracellular matrix properties that allow mechanical support, favoring mechanical interactions and providing a model for cellular attachment and in vivo stimulation of bone tissue formation.

Paraganglioma is a rare neuroendocrine neoplasm originating from paraganglia and consisting of neuroendocrine cells of the sympathetic and parasympathetic nervous system. Extra-adrenal paraganglioma occurs with a low incidence in both humans and animals. This report presents the first case of paraganglioma in a cat with orbital primary location. An 18-year-old spayed female European domestic shorthair cat of 3.60 kg body weight was evaluated in a private veterinary clinic in Perugia, Italy, for a pronounced exophthalmos of the right eye. The cat underwent surgery for the enucleation of the right eye and of the mass. The biopsy samples of the removed tissue were fixed in 10% buffered neutral formalin for histological and immunohistochemical evaluations. Therefore, specific markers were used for immunohistochemical investigations, such as anti-neuron specific enolase (NSE), anti-synaptophysin, anti-glial fibrillary acid protein, anti-cytokeratin and anti-chromogranin. The results of these investigations allowed establishing the final diagnosis of ocular extra-adrenal paraganglioma of the cat.

Teratoma is a rare germ cell testicular cancer composed of cells that are not normally present in the site where it originates. These tumors are rarely described in horses, where they may develop due to cryptorchidism. Teratomas consist of cells originating from different germinal layers, arising from germinal multi-potential cells with differentiation defects, and can simultaneously contain several tissues from two or more embryonic layers. Testicular teratomas are described in horses, cats, dogs, wild boars, bulls, and humans. In the rare descriptions found in literature of testicular teratoma in stallions, they occur frequently in cryptorchid testicles, as a consequence of congenital neoplasm. To our knowledge there is no other report of a dentigerous equine teratoma in a stallion. We describe here a successful laparoscopic removal of a testicular teratoma and its clinic-pathological features.

Despite promising immunotherapy strategies in human melanoma, there are few studies on the immune environment of canine melanocytic tumors. In humans, the activation of immunosuppressive cell subpopulations, such as regulatory T cells (Tregs) that express forkhead box protein P3 (FoxP3), the engagement of immunosuppressive surface receptors like cytotoxic T lymphocyte antigen (CTLA-4), and the secretion of molecules inhibiting lymphocyte activation, such as indoleamine-pyrrole 2,3-dioxygenase (IDO), are recognized as immunoescape mechanisms that allow tumor growth and progression. The aim of our study was to investigate the expression of these immunosuppression markers in canine melanocytic tumors and to postulate their possible role in melanoma biology and progression. Fifty-five formalin-fixed, paraffin-embedded canine melanocytic tumors (25 oral melanomas; 20 cutaneous melanomas; 10 cutaneous melanocytomas) were selected to investigate the expression of FoxP3, CTLA-4, and IDO by immunohistochemistry and RT-qPCR (real-time quantitative polymerase chain reaction). All of the tested markers showed high gene and protein expression in oral melanomas and were differently expressed in cutaneous melanomas when compared to their benign counterpart. IDO expression was associated with an increased hazard of death both in univariable and multivariable analyses ( P < .05). FoxP3 protein expression >6.9 cells/HPF (high-power field) was an independent predictor of death ( P < .05). CTLA-4 gene and protein expressions were associated with a worse prognosis, but only in the univariable analysis ( P < .05). FoxP3, CTLA-4, and IDO likely play a role in canine melanoma immunoescape. Their expression, if supported by future studies, could represent a prognostic tool in canine melanoma and pave the way to future immunotherapeutic approaches in dogs.

This study investigated the effects of a short-term administration of bovine colostrum (BC) in a TNBS model of induced colitis. Colitis was induced by TNBS treatment after seven days of BC (BC group, n = 12) or saline (control group, n = 12) administration in mice. Clinical signs, histopathological characteristics, expression levels of Toll-like receptor 4 (TLR4), pro- and anti-inflammatory cytokines, and microbial composition were assessed. BC was well tolerated and did not induce any histological damage or clinical symptoms. After TNBS treatment, the BC group showed a reduction in body weight (BW) loss compared to Control (p &lt, 0.05). Moreover, expression levels of TLR4 (p &lt, 0.01), Interleukin-1&beta, (IL-1&beta, p &lt, 0.001), Interleukin-8 (IL-8, 0.001), and Interleukin-10 (IL-10, 0.001) were lower in mice administered with BC. Finally, Escherichia coli were higher (p &lt, 0.05), while Enterococci (p &lt, 0.001), Lactobacillus spp. (p &lt, 0.001), and Bifidobacterium spp. (p &lt, 0.05) were lower in Control than BC group. This study confirms that pre-treatment with BC modulates the expression of genes and the count of microbes involved in the etiopathogenesis of colitis.

Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra-articular delivery of cells (including mesenchymal stromal cells), have been proposed. Among the many sources, the adipose tissue is considered very promising. We evaluated the safety, feasibility, and efficacy of a single intra-articular injection of autologous and micro-fragmented adipose tissue (MFAT) in 130 dogs with spontaneous OA. MFAT was obtained using a minimally invasive technique in a closed system and injected in the intra- and/or peri-articular space. Clinical outcomes were determined using orthopedic examination and owners’ scores for up to 6 months. In 78% of the dogs, improvement in the orthopedic score was registered 1 month after treatment and continued gradually up to 6 months when 88% of the dogs improved, 11% did not change, and 1% worsened compared with baseline. Considering the owners’ scores at 6 months, 92% of the dogs significantly improved, 6% improved only slightly, and 2% worsened compared with baseline. No local or systemic major adverse effects were recorded. The results of this study suggest that MFAT injection in dogs with OA is safe, feasible, and beneficial. The procedure is time sparing and cost-effective. Post injection cytological investigation, together with the clinical evidence, suggests a long-term pain control role of this treatment. The spontaneous OA dog model has a key role in developing successful treatments for translational medicine.

The aim of the present study was to evaluate: (1) the presence of nerve growth factor (NGF), neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR) in the rabbit uterus; and (2) the in vitro effects of NGF on PGF2α and PGE2 synthesis and on the PGE2-9-ketoreductase (PGE2-9-K) activity by the rabbit uterus. Nerve growth factor, NTRK1, and NGFR were immunolocalized in the luminal and glandular epithelium and stroma cells of the endometrium. reverse transcriptase polymerase chain reaction indicated the presence of messenger RNA for NGF, NTRK1, and NGFR in the uterus. Nerve growth factor increased (P < 0.01) in vitro secretions of PGF2α and PGE2 but coincubation with either NTRK1 or oxide nitric synthase (NOS) inhibitors reduced (P < 0.01) PGF2α production and blocked (P < 0.01) PGE2 secretion. Prostaglandins releases were lower (P < 0.01) than control when uterine samples were treated with NGF plus cyclooxygenase inhibitor. However, addition of NGFR inhibitor reduced (P < 0.01) PGF2α secretion less efficiently than NTRK1 or NOS inhibitors but had no effect on PGE2 yield. Nerve growth factor increased (P < 0.01) the activity of PGE2-9-K, whereas coincubation with NTRK1 or NOS inhibitors abolished (P < 0.01) this increase in PGE2-9-K activity. However, cotreatment with either cyclooxygenase or NGFR inhibitors had no effect on PGE2-9-K activity. This is the first study to document the distribution of NGF/NTRK1 and NGFR systems and their effects on prostaglandin synthesis in the rabbit uterus. NGF/NTRK1 increases PGF2α and PGE2 productions by upregulating NOS and PGE2-9-K activities, whereas NGF/NGFR augments only PGF2α secretion, through an intracellular mechanism that is still unknown.

Over the past decades, stem cell technology has revolutionalized medical biotechnology due to the unlimited self-renewal ability and differentiation capacity of stem cells to generate cells and tissues of the entire human body. Many efforts have focused on providing cutting-edge stem cell therapies in order to repair or replace damaged cells or tissues, hoping to ultimately cure devastating diseases. Undoubtedly, this novel technology guarantees a serial entrepreneur’s confidence in the future prospects of stem cell-based products and services. Here, we describe the state of the art of several applications of adult stem cells, as well as of embryonic and induced pluripotent stem cells in biotechnology that represent entrepreneurial opportunities. Although the contribution of stem cells to medical research is enormous, several hurdles still have to be overcome, including ethical and regulatory issues, functional maturation of stem cell progenitors, stringent manufacturing guidelines, immune rejection, and tumorigenicity.

Fine needle aspiration and tissue biopsy samples were taken from a subcutaneous mass in the cranial stifle region of a 10-yr-old horse. Key cytologic features included numerous mildly to moderately pleomorphic histiocytic cells admixed with mononuclear inflammatory cells, occasional fibroblasts, multinucleated cells, and hemosiderin-laden macrophages. Based on these features, cytologic differentials included granulomatous inflammation with reactive fibroplasia, histiocytic sarcoma, giant cell tumor of soft parts (GCTSPs), and giant cell tumor of bone. The tissue biopsy supported a diagnosis of superficial GCTSPs. This neoplasm is of controversial origin but generally considered to be a soft tissue sarcoma and classified in the World Health Organization classification of tumors under fibrous histiocytic tumors as a giant cell tumor of soft tissue with low risk of malignancy. When found in the subcutis, this neoplasm rarely metastasizes in the horse and has a low rate of local reoccurrence. In this case, there was no local recurrence of the tumor after 6 mo, after which the horse was lost to follow-up.Keywords: Cytology, Equine, Giant cell tumor of soft parts, Histopathology.

// Barbara Chirullo 1 , Serena Ammendola 2 , Leonardo Leonardi 3 , Roberto Falcini 4 , Paola Petrucci 1 , Claudia Pistoia 1 , Silvia Vendetti 5 , Andrea Battistoni 2 , Paolo Pasquali 1 1 Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome 00161, Italy 2 Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy 3 Universita degli Studi di Perugia, Department of Veterinary Medicine, Perugia 06126, Italy 4 Veterinary Clinic, Rieti 02043, Italy 5 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Rome 00161, Italy Correspondence to: Barbara Chirullo, e-mail: barbara.chirullo@iss.it Paolo Pasquali, e-mail: paolo.pasquali@iss.it Keywords: bacterial therapy, cancer therapy, antitumor efficacy, attenuated-Salmonella, immune response Received: February 09, 2015 Accepted: April 24, 2015 Published: May 07, 2015 ABSTRACT Salmonella Typhimurium has been shown to be highly effective as antitumor agent. The aim of this study was to investigate the tumor targeting efficacy and the mechanism of action of a specific attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the whole operon coding for the high-affinity zinc transporter ZnuABC, which is required for bacterial growth in environments poor in zinc and for conferring full virulence to different Gram-negative pathogens. We showed that STM is able to penetrate and replicate into tumor cells in in vitro and in vivo models. The subcutaneous administration of STM in mammary adenocarcinoma mouse model led to both reduction of tumor growth and increase in life expectancy of STM treated mice. Moreover, investigating the potential mechanism behind the favorable clinical outcomes, we provide evidence that STM stimulates a potent inflammatory response and a specific immune pattern, recruiting a large number of innate and adaptive immune cells capable to contrast the immunosuppressive environment generated by tumors.

This paper reviews the composition of colostrum and the potential preventive and therapeutic use of this "first milk" for treating various gastrointestinal disorders in humans. Colostrum is a complex biological liquid that is richer in antimicrobial peptides, immune-regulating compounds and growth factors than the subsequent mature milk. The main functions of colostrum are to provide essential nutritional components, strengthen the natural defense system, modulate immune response, balance intestinal microbiota and enhance the growth and repair of several tissues. Several studies and clinical trials carried out both in vitro and in vivo on humans and animals suggest the clinical benefits of bovine colostrum (BC) supplementation in gastro-intestinal diseases. Despite the encouraging results, further well-designed studies are required in order to confirm these effects, the dose and duration of treatment. Colostrum is safe since there are no contraindications regarding high dose levels and few side effects of clinical relevance have been reported. In conclusion, in the near future, colostrum-based supplements may play a complementary role to synthetic drugs in the prevention and treatment of various gastrointestinal disorders.