Octreotide as medical therapy of idiopatic chylothorax in 3 cats after surgery

Idiopathic chylothorax is a rare disease that a ects cats. Dif- ferent therapeutical options both surgical and medical have been described without a clear standard protocol and posi- tive outcome. The use of Octreotide in cats have been described previ- ously (for the medical therapy of hyperinsulinemia in cats a ected by insulinomas, gastrinomas, acromegaly and acute pancreatitis) but its usefulness as de nitive treatment to cure chylothorax its unclear. This preliminary data describe the clinical features of three cats treated with Octreotide after a partial surgical resolution of idiopathic chylothorax. Three cats presenting a moderate amount of chylous e usion one week after surgical closure of thoracic duct with transdiaphragmatic approach were selected for our study. The Octreotide started seven days after surgery at the dose of 20 ug/kg/sc/tid (dose proposed in literature 10\u201320 ug/kg/ sc/tid for maximum 2\u20133 weeks). Standard clinical, radio- graphic and ultrasonographic evaluations were performed twice a month and together blood cell count, seroum bio- chemistry, cytological,chemical-physical evaluation of tho- racic e usion were performed at each control. Clinical, imaging and laboratory abnormalities were reported. The Octreotide administration was interrupted one month later by the end of the pleural collection and each patients was re-evaluated one year after surgery. Cat one: (DSH, 5 years old, neutered male) presented pleural e usion from day one to day 146 of therapy. Octreotide was interrupted at day 176. Cat two: (DSH, 6 years old, neutered male) presented pleural effusion from day one to day 143 of therapy. Octreotide was interrupted at day 173. Both cats were discharged with- out clinical symptoms and they were rechecked six month later without any clinical problems, except the di use pleural thickening observed at the ultrasonographic examination. Cat three: (DSH, 9 years old, neutered male) presented pleural effusion from day one to day 182 of octreotide ther- apy. At day 182 the cat was euthanised according to the owners due to respiratory insu ciency. Necropsy confirmed a severe constrictive pleuririts. In all the subject thoracentesis were performed during controls if necessary. No adverse e ects were observed even considering that this drug was used for 6 months therapy. In our experi- ence on three cats the use of Octreotide turned out useful and safe as complementary therapy of the idiopathic chylothorax

A dynamic distention protocol for whole-organ bladder decellularization: histological and biomechanical characterization of the acellular matrix

A combined physical\u2013chemical protocol for whole full-thickness bladder decellularization is proposed, based on organ cyclic distention through repeated infusion/withdrawal of the decellularization agents through the urethra. The dynamic decellularization was intended to enhance cell removal efficiency, facilitating the delivery of detergents within the inner layers of the tissue and the removal of cell debris. The use of mild chemical detergents (hypotonic solution and non-ionic detergent) was employed to limit adverse effects upon matrix 3D ultrastructure. Inspection of the presence of residual DNA and RNA was carried out on decellularized matrices to verify effective cell removal. Histological investigation was focused on assessing the retention of adequate structural and functional components that regulate the biomechanical behaviour of the acellular tissue. Biomechanical properties were evaluated through uniaxial tensile loading tests of tissue strips and through ex vivo filling cystometry to evaluate the whole-organ mechanical response to a physiological-like loading state. According to our results, a dynamic decellularization protocol of 17 h duration with a 5 ml/min detergent infusion flow rate revealed higher DNA removal efficiency than standard static decellularization, resulting in residual DNA content\u2009<\u200950 ng/mg dry tissue weight. Furthermore, the collagen network and elastic fibres distribution were preserved in the acellular ECM, which exhibited suitable biomechanical properties in the perspective of its future use as an implant for bladder augmentation

Reconstruction of ovine axonal cytoarchitecture enables more accurate models of brain biomechanics

There is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports a systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibres, namely the corpus callosum, the fornix and the corona radiata, with the specific aim to map different regions of the tissue and provide essential information for the development of accurate models of brain biomechanics. Ovine samples are imaged using scanning electron microscopy combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Focus is placed on the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. For each tract, a 3D reconstruction of relatively large volumes, including a significant number of axons, is performed and outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter are measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular axonal structures embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models using 3D volumes, either reconstructed directly from images or generated in silico using parameters extracted from the database of images, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue

Soluble receptor for advanced glycation end products : a protective molecule against intramyocardial lipid accumulation in obese Zucker rats?

Most of the obesity-related complications are due to ectopic fat accumulation. Recently, the activation of the cell-surface receptor for advanced glycation end products (RAGE) has been associated with lipid accumulation in different organs. Nevertheless, the role of RAGE and sRAGE, the soluble form that prevents ligands to activate RAGE, in intramyocardial lipid accumulation is presently unknown. To this aim, we analyzed whether, in obesity, intramyocardial lipid accumulation and lipid metabolism-related transcriptome are related to RAGE and sRAGE. Heart and serum samples were collected from 10 lean (L) and 10 obese (OB) Zucker rats. Oil red staining was used to detect lipids on frozen heart sections. The lipid metabolism-related transcriptome (84 genes) was analyzed by a specific PCR array. Heart RAGE expression was explored by real-time RT-PCR and Western blot analyses. Serum levels of sRAGE (total and endogenous secretory form (esRAGE)) were quantified by ELISA. Genes promoting fatty acid transport, activation, and oxidation in mitochondria/peroxisomes were upregulated in OB hearts. Intramyocardial lipid content did not differ between OB and L rats, as well as RAGE expression. A slight increase in epicardial adipose tissue was observed in OB hearts. Total sRAGE and esRAGE concentrations were significantly higher in OB rats. sRAGE may protect against obesity-induced intramyocardial lipid accumulation by preventing RAGE hyperexpression, therefore allowing lipids to be metabolized. EAT also played a protective role by working as a buffering system that protects the myocardium against exposure to excessively high levels of fatty acids. These observations reinforce the potential role of RAGE pathway as an interesting therapeutic target for obesity-related complications, at least at the cardiovascular level

Morphometric study of the ventricular indexes in healthy ovine BRAIN using MRI.

BACKGROUND: Sheep (Ovis aries) have been largely used as animal models in a multitude of specialties in biomedical research. The similarity to human brain anatomy in terms of brain size, skull features, and gyrification index, gives to ovine as a large animal model a better translational value than small animal models in neuroscience. Despite this evidence and the availability of advanced imaging techniques, morphometric brain studies are lacking. We herein present the morphometric ovine brain indexes and anatomical measures developed by two observers in a double-blinded study and validated via an intra- and inter-observer analysis. RESULTS: For this retrospective study, T1-weighted Magnetic Resonance Imaging (MRI) scans were performed at 1.5 T on 15 sheep, under general anaesthesia. The animals were female Ovis aries, in the age of 18-24 months. Two observers assessed the scans, twice time each. The statistical analysis of intra-observer and inter-observer agreement was obtained via the Bland-Altman plot and Spearman rank correlation test. The results are as follows (mean ± Standard deviation): Indexes: Bifrontal 0,338 ± 0,032 cm; Bicaudate 0,080 ± 0,012 cm; Evans' 0,218 ± 0,035 cm; Ventricular 0,241 ± 0,039 cm; Huckman 1693 ± 0,174 cm; Cella Media 0,096 ± 0,037 cm; Third ventricle ratio 0,040 ± 0,007 cm. Anatomical measures: Fourth ventricle length 0,295 ± 0,073 cm; Fourth ventricle width 0,344 ± 0,074 cm; Left lateral ventricle 4175 ± 0,275 cm; Right lateral ventricle 4182 ± 0,269 cm; Frontal horn length 1795 ± 0,303 cm; Interventricular foramen left 1794 ± 0,301 cm; Interventricular foramen right 1,78 ± 0,317 cm. CONCLUSIONS: The present study provides baseline values of linear indexes of the ventricles in the ovine models. The acquisition of these data contributes to filling the knowledge void on important anatomical and morphological features of the sheep brain

In vivo Diffusion Tensor Magnetic Resonance Tractography of the Sheep Brain : An Atlas of the Ovine White Matter Fiber Bundles

Diffusion Tensor Magnetic Resonance Imaging (DTI) allows to decode the mobility of water molecules in cerebral tissue, which is highly directional along myelinated fibers. By integrating the direction of highest water diffusion through the tissue, DTI Tractography enables a non-invasive dissection of brain fiber bundles. As such, this technique is a unique probe for in vivo characterization of white matter architecture. Unraveling the principal brain texture features of preclinical models that are advantageously exploited in experimental neuroscience is crucial to correctly evaluate investigational findings and to correlate them with real clinical scenarios. Although structurally similar to the human brain, the gyrencephalic ovine model has not yet been characterized by a systematic DTI study. Here we present the first in vivo sheep (ovis aries) tractography atlas, where the course of the main white matter fiber bundles of the ovine brain has been reconstructed. In the context of the EU's Horizon EDEN2020 project, in vivo brain MRI protocol for ovine animal models was optimized on a 1.5T scanner. High resolution conventional MRI scans and DTI sequences (b-value = 1,000 s/mm2, 15 directions) were acquired on ten anesthetized sheep o. aries, in order to define the diffusion features of normal adult ovine brain tissue. Topography of the ovine cortex was studied and DTI maps were derived, to perform DTI tractography reconstruction of the corticospinal tract, corpus callosum, fornix, visual pathway, and occipitofrontal fascicle, bilaterally for all the animals. Binary masks of the tracts were then coregistered and reported in the space of a standard stereotaxic ovine reference system, to demonstrate the consistency of the fiber bundles and the minimal inter-subject variability in a unique tractography atlas. Our results determine the feasibility of a protocol to perform in vivo DTI tractography of the sheep, providing a reliable reconstruction and 3D rendering of major ovine fiber tracts underlying different neurological functions. Estimation of fiber directions and interactions would lead to a more comprehensive understanding of the sheep's brain anatomy, potentially exploitable in preclinical experiments, thus representing a precious tool for veterinaries and researchers

Tracheal tissue regeneration

Tracheal circumferential defects involving more than half of the tracheal wall still represent an unsolved problem. Several studies have developed different methods to help repair cartilage and improve healing but a suitable tracheal reconstruction or replacement has not been achieved yet. Novel bioengineering technologies seem to be the new answer to this serious problem. This chapter briefly describes the fundamentals of the anatomical and physiological tracheal functions and provides a review of trachea tissue engineering. Then it describes the project and development by means of electrospinning of a biodegradable tubular tracheal scaffold with an in vitro and in vivo preliminary experimental approach

A study of mutations in the c-kit gene of 32 dogs with mastocytoma

Mutations in the intracellular juxtamembrane domain of the c-kit gene in 32 dogs with different grades of histologically confirmed mastocytoma were studied. Transcript RNAs extracted from neoplastic tissue surgically collected from dogs of different breeds and from a negative control were reverse transcribed into complementary DNA and amplified by polymerase chain reaction. The region corresponding to the c-kit juxtamembrane domain was sequenced and compared with GenBank sequences. Two different types of mutations were identified within exon 11: a previously underscribed single-nucleotide substitution and a 6-bp deletion. The c-kit juxtamembrane domain sequences of all dogs were grouped in 3 clusters. No mutations were detected in tissues constitutively expressing c-kit (cerebellum and spleen), obtained from dogs not affected by mastocytoma (controls). All the substitutions were found in dogs bearing grade I or II mast cell tumors; the deletion was detected in 1 dog with grade II mastocytoma

Mesenchymal Stem Cell Therapy for Airway Restoration Following Surgery

Post-resectional bronchopleural fistula is a pathological connection between the airway (bronchus) and the pleural space that may develop after lung resection; it may be caused by incomplete bronchial closure, impediment of bronchial stump wound healing, or stump destruction by residual neoplastic tissue. The clinical effect of impaired bronchial stump healing after anatomic lung resection may culminate in a life-threatening septic and ventilatory catastrophe. Stem cells can be used to repair defects in the airway wall, resulting from tumors, trauma, and diseases associated with epithelial damage; two groups of stem cells can be used for this purpose: endogenous progenitor cells present in the respiratory tract or exogenous stem cells derived from other tissues in the body; in this second group of stem cells there are embryonic stem cells, induced pluripotent stem cells, amniotic fluid stem cells, and fat-derived or bone marrow-derived mesenchymal stem cells (MSCs). Experimental and clinical evidence exists regarding MSC efficacy in airway defects restoration; although clinical MSC use\u2014in the daily practice\u2014is not yet reached for airway diseases, we can argue that MSC do not represent any more merely an experimental approach to airway tissue defects restoration but they can considered as a \u201csalvage\u201d therapeutic tool in very selected patients and diseases