Teaching Schedule

Teaching Schedule / Attività didattica Dottorato SVA 2017-2018

Date Day Course Time Room Lecturer
15/12/2017 Friday Medical Statistic 3

09.00-13.00

310 Elisabetta Sala
20/12/2017 Wednesday Medical Statistic 3 09.00-13.00 310 Elisabetta Sala
01/02/2018 Thursday Medical Statistic 3 9.00-13.00 310 Elisabetta Sala

24/01/2018

Wednesday Communication 3 14.00-18.00   Ettore Galanti
07/02/2018 Wednesday

Communication 3

14.00-18.00   Ettore Galanti
21/02/2018 Wednesday Communication 3
14.00-18.00   Ettore Galanti

D'Urso / Stefanello

Elisa Silvia D’Urso, DVM, PhD student

Graduated in Veterinary Medicine in February 2014 with full marks and honor, with a dissertation concerning rabbit anaesthesia and analgesia entitled “Assessment of buprenorphine and ketorolac perioperative analgesia in desflurane anaesthetized rabbits undergoing ovariohysterectomy” (supervisor: Dr. Giuliano Ravasio, assistant supervisor: Dr. Alessandro Maria Pecile). After 5 months of post degree attendance at the Department of Veterinary Sciences and Public Health as part of the anaesthetist task group, she spent a 7-month post-degree practical training period at the veterinary hospital Gregorio VII in Rome, in order to develop a proper background in internal medicine, critical and intensive care, imaging and emergency care. During the same period, she participated to two workshops concerning general veterinary anaesthesia and hemodynamic evaluation (speakers: Dr. Enrico Stefanelli and Dr. Davide Gamba). Her main interests are veterinary anaesthesia in a variety of species and small animal critical and emergency care.


Damiano Stefanello, DVM, PhD in Comparative Veterinary Oncology, Ass. Professor DIVET, University of Milan

After graduating in Veterinary medicine with full marks and honor in 1999, he earned a PhD in Comparative Veterinary Oncology in 2004. Researcher since 2008, he carried out clinical and teaching activity as well as research at the Department of Veterinary Sciences and Public Health, focusing on clinical oncology and small animal surgery. Associate professor in veterinary clinical surgery. He founded and has been leading since 2009 the Veterinary Oncology Chemotherapy unit at the Veterinary Hospital and Experimental Animal Research and Application Centre, Lodi, Faculty of Veterinary Medicine. From 2007 to 2012, he was lecturer of the Veterinary Oncology Master at the University of Pisa. He is head chief of the Small Animal Pathology and Clinical Medicine School of Specialization at the Faculty of Veterinary Medicine, Milan. Member of SIONCOV, ESVONC and VSSO societies, he has been president of the Italian Veterinary Oncology Society (SIONCOV) from 2014 to 2017. Guest speaker at several Italian and international conventions concerning veterinary oncology, he is also author of more than 120 publications dealing with clinical oncology and small animal surgery, 42 of which on international peer-reviewed journals.


Research project: Ultrasound guided loco-regional anaesthesia in small animal practice

Peripheral and central nerve blocks play nowadays an important role in perioperative pain management both in human and in veterinary medicine; the injection of local anaesthetic around a nerve or a group of nerves determines a blockade in impulse conduction, causing temporary analgesia and loss of sensory and motor function. An effective nerve block thus allows to avoid supplementation of both general anaesthetic drugs and systemic opioids during surgery leading to a minor effect on the cardiovascular system and to a faster postoperative recovery for the veterinary and human patient. Ultrasonographic (US) guidance to perform peripheral nerve blocks is widely studied and standardized in human medicine, due to its remarkable advantages compared to the peripheral nerve stimulation (PNS) technique, while in veterinary medicine the description and validation of most US guidance nerve blocks is still scarce.
The purpose of this study is to assess and compare the efficacy of peripheral nerve stimulation technique, ultrasound guided technique and the combined technique in order to evaluate their suitability in veterinary medicine.

The study will be conducted in three years; during the first academic year, an ultrasonographic anatomical study on 20 dogs who underwent euthanasia for reasons not related to the study itself or died by natural causes will be carry out, in order to acknowledge proper ultra-sonographic landmarks for all the nerves and regions involved. Data collected should thus allow the creation of a complete database of images and landmarks, which is not currently present in veterinary medicine.

During the second academic year, a clinical study will be conducted on two groups of 40 owned dogs each, submitted to the Faculty of Veterinary Medicine in order to undergo surgeries which require loco-regional anaesthesia as part of the analgesic protocol. In group 1, nerve block will be performed under ultrasonographic guidance. In group 2, nerve block will be performed with PNS technique. During the third academic year, nerve block will be performed on a third group of 40 owned dogs with the combined technique. In all patients, heart rate and invasive arterial blood pressure will be recorded during surgery in order to allow the assessment of intra-anaesthetic analgesic efficacy of the perineural nerve block. Rescue analgesia will be provided whenever needed and the number of rescue analgesic administration will be recorded as well. Data obtained from the clinical part of the study should allow to assess which technique is more suitable in small animal surgery to perform peripheral nerve block in a clinical setting in order to reduce failure rates and to minimize risks and side effects for the patient.

Manzoni / Gandolfi

PhD Student: Elena Franca Maria Manzoni graduated in Veterinary Biotechnology Master’s Degree at the University of Milan in July 2015 with the final mark of 110/110 cum laude. In 2012 she worked as an undergraduate student at the laboratory of Biomedical Sciences, University of Ulster under the supervision of Professor Colum Walsh on the epigenetic mechanisms regulating gene expression. In 2014 she worked as an intern at Genomnia srl where she learned next generation sequencing methods and bioinformatics analysis. This experience led to her graduation thesis entitled: ”Next Generation Sequencing analysis of human somatic cells exposed to 5-azacytidine:expression and methylation profiles“.


Tutor: Fulvio Gandolfi received his degree in Veterinary Medicine in 1982 at the University of Milan. He moved to the AFRC in Cambridge UK from 1985 to 1988 where he developed the first method for the in vitro culture of animal zygotes. He has been a visiting Professor at Monash University in Melbourne and at Adelaide University. At present he is Full Professor of Anatomy and Embryology at the Faculty of Veterinary Medicine in Milan (Italy). He works on the reproductive biology of farm animals and on the use of epigenetic mechanisms to direct and modify cell fate. He is Vice President of ICAR (International Congress of Animal Reproduction), a founding member of UNISTEM, the Centre for the Study of Stem Cells of the University of Milan, Member of the Board of Governors of the International Embryo Transfer Society. Since 2002 is Co-Editor in Chief of Theriogenology and he became Editor-in-Chief in 2013. An updated list of his research papers can be found on Google Scholar http://scholar.google.it/citations?user=9f9HZLAAAAAJ&hl=it
or SCOPUS
http://www.scopus.com/authid/detail.url?authorId=7007168713


Research Project: Molecular and cellular mechanisms regulating epigenetic cell conversion.

We have recently developed a protocol by which is possible to convert adult somatic cells into a different cell type using the epigenetic modifier 5-azacytidine (5-aza-CR).

This molecule is able to push the cells to a less committed state, increasing their plasticity. Once cells have entered into this higher plasticity window, they can easily be directed towards a different phenotype if they are exposed to specific differentiation stimuli.
This direct approach is highly efficient, it does not require any transgenic modification, it is patient-specific and therefore avoids allogeneic rejection. For all these reason cells derived with this approach (defined epiCC) may represent a very promising tool for the regenerative medicine of several and diverse degenerative diseases.

Aim of this project is to investigate the mechanisms that allowed the epigenetic erasing of cell phenotype and the acquisition of a high plasticity state. The expected results will expand our knowledge on the effect exerted by 5-aza-CR, further setting this technique as a robust and powerful tool for regenerative medicine and cell therapy.

A multidisciplinary approach will be used and will involve advanced techniques of stem cell culture, cell and molecular biology, methylation studies, immunofluorescence, electron and confocal microscopy, cellular mechanosensing, cell and exosome mediated interactions.

Savarese / Brambilla

Alice Savarese, DVM, PhD Student

She graduated in March 2009 in Medical Biotechnologies at the University of Milan (104/110), with a thesis entitled “Study of the levels of methylation of the telomerase gene promoter in steel workers exposed to particulate matter” (Supervisor: Prof. Andrea Baccarelli). After graduating, she obtained a short scholarship at the Epidemiology Laboratory of the Ospedale Maggiore - Policlinico of Milan. But then she decided to change perspective and start a career in Veterinary Medicine. She graduated in March 2015 at the University of Milan (110/110 cum laude) with a thesis entitled “Cardiorenal syndrome – anemia complex in dogs suffering from mitral valve disease: a retrospective study” (Supervisor: Prof. Paola Brambilla). During her career, she spent one year in Spain, at the Veterinary Faculty of Santiago de Compostela, attending the Veterinary Hospital and, especially, the cardiology unit. After graduating and once acquired the professional license, she started a traineeship in a private clinic. At the same time, she continued to attend the Cardiology Unit of the Department of Veterinary Science and Public Health, where she has the opportunity to acquire more skills about cardiology and internal medicine.
Her main research interests are in echocardiography, electrocardiography, small animal internal medicine (cardiology and nephrology), clinical pathology and the analytical validation of innovative diagnostic markers for cardiac diseases and renal injuries.


Paola Brambilla, DVM, PhD

Paola Brambilla is an associate Professor of Veterinary Clinical Epidemiology at the Department of Veterinary Sciences and Public Health, University of Milan and Associate Professor in Small Animal Cardiology at School of Specialization in Clinic and Pathology of Companion Animals, University of Milan.

She graduated with honour at the University of Milan and then obtained a PhD in Large Animal Internal Medicine. She is actually in charge with the Cardiology Unit of Small Animals at the Department of Veterinary Sciences and Public Health, University of Milan.
Paola G. Brambilla is a member of the Commissione Malattie Cardiovascolari – Fondazione Salute Animale [Commission of Cardiovascular Disease - Animal Health Foundation], and of the Italian Society of Veterinary Cardiology (SICARV).
The research interests are focused on the cardiovascular diseases in dog and cat:
• No-invasive echocardiographic and color-Doppler techniques to assess the mitral valve regurgitation (flow mapping of vena contracta)
• No-invasive advanced echocardiographic techniques (speckle-tracking echocardiography) focused on strain and strain rate in the longitudinal, circumferential and radial planes of left and right ventricle
• Survival studies and analysis on prognostic factors in dogs affected by different heart disease, and using different therapeutic approach.
• Cardiac biomarkers (troponine I)
• Diagnosis and therapy of congenital heart disease in dog (Pulmonic Stenosis, Patent Ductus Arteriosus)
• Cardio-Renal Syndrome in dog: study of the survival time and the prognostic indicator
In addition to the expertise in canine and feline cardiology, Prof. Paola G. Brambilla was involved in studies on canine X-linked muscular dystrophy and primary hypertrophic cardiomyopathy in Main Coon.


RESEARCH PROJECT

“CARDIORENAL SYNDROME-ANEMIA” COMPLEX IN SMALL ANIMAL MEDICINE: RESEARCH IN DIAGNOSTIC

Cardiorenal syndrome (CRS) can be defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of one organ may induce acute or chronic dysfunction of the other. CRS includes a vast array of interrelated disorders, and stress the bidirectional nature of heart-kidney interactions. In human medicine, CRS is classified in five subtypes that reflect the pathophysiology, the time frame, and the nature of concomitant cardiac and renal dysfunction.
CRS type 2 is the most common in canine patients, and it comprises chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive chronic kidney disease. The most common acquired heart disease affecting old dogs and leading to congestive heart failure is chronic mitral valve disease (MVD), also known as myxomatous mitral valve degeneration. The MVD cause systolic regurgitation from left ventricle to left atrium, and decrease in stroke volume. The worsening of the cardiac performance, and the consequent reduction of the renal perfusion contribute to the development of renal insufficiency in the setting of hearth failure (CRS type 2).
In cats, the most common CRS are type 2, as in dogs, and type 4, in which chronic kidney failure leads to chronic heart failure. Unlike that in dogs, in cats the most common cardiac disease is hypertrophic cardiomyopathy (HCM), a primary myocardial disorder characterized by increased cardiac mass and a hypertrophied, not dilated, left ventricle.
Anemia is often associated with heart failure and renal insufficiency, and this unfavorable triad of conditions has been called “CRS-anemia” complex. CRS-anemia complex is well known in human patients: anemia has been recognized as an important comorbidity factor in subjects affected by heart disease, and it appears to be related to bad outcomes in subjects with both heart failure and chronic kidney disease.

In veterinary medicine very few data exists on CRS-anemia complex in small animals, and the investigation of the CRS-anemia complex might be worthy, as the geriatric population of companion animals increases and reaches advanced disease stages.
The aims of the study are:
1) determine the prevalence of CRS - Anemia complex in a clinical population of dogs affected by heart diseases, especially MVD, at different severity stages of heart failure (ACVIM classification - American College of Veterinary Internal Medicine’s Board) and renal failure (IRIS classification – International Renal Interest Society)
2) determine the prevalence of CRS - anemia complex in a clinical population of cats affected by cardiac diseases, especially HCM, at different severity stages, and by CKD, at different severity stages (according to the IRIS classification)
3) describe the patterns of anemia based on red blood cells indices (MCV, MCH, MCHC), reticulocyte production index (IR), and red blood cell distribution width (RDW)
4) monitor the progression of renal and cardiac diseases through the evaluation of biomarkers, useful to identify the stages of organ damage in patients affected by CRS - anemia complex. In human medicine in fact, one of the cornerstones of CRS management is the early identification of patients at risk for worsening kidney and heart function, with the use of imaging technique as well as renal and cardiac biomarkers. Diagnostic and prognostic biomarkers of myocardial and renal injury useful in stadiation of CRS type 2 and type 4 in dog and cat can be:
- Doppler echocardiographic indices
- Blood and urine biomarkers, like for example serum Cystatin C and/or urinary Cystatin C, symmetric dimetylarginine (SDMA), Neutrophil gelatinase-associated lipocalin (NGAL), NT-pro-BNP, selected interleukins and cytokines of generalized inflammation (TNF-α, IL-1, IL2, IL-6, IL-7, IL-8), Troponine I (cTRI), Asymmetric dimethylarginine (ADMA), Pentraxine-3, Galectine-3 and ST2, Paroxonase
- Haematological and blood chemistry parameters, like for example C-reactive protein, Homocysteine, Uric Acid, Serum iron profile, Vitamin B12 and folate.
- Epigenetic biomarkers (methylation of CpG sites, histone methylation, miRNA). Methylation is a process by which methyl groups are added to DNA or histone modifying gene expression, while microRNAs (miRNAs) are single-stranded RNAs of ~22 nt that operate as post-transcriptional gene regulators by base pairing with target mRNAs, and leading to mRNA destruction in the RNA-induced silencing complex through argonaute-catalysed cleavage.

The goal of epigenetic biomarker development is to design experimental assays that produce relevant information for diagnosis, prognosis and therapy optimization in routine clinical treatment of a multifactorial syndrome, such as CRS. Furthermore, epigenetic biomarkers show lower susceptibility to short – term fluctuations.

All the biomarkers listed above have strong bibliographic references in human medicine, but little is known about the use of some of them in small animal medicine: one of our purpose is trying to identify which fits better with veterinary medicine and clinical practice, testing them in our patients and performing statistical analysis. For some of them, validation process could be necessary.

5) Evaluate the effects of selected factors on the survival of these patients to predict the risk of death/worsening renal and cardiac function (e.g. ACVIM/IRIS class vs red blood cells indices, RI, RDW, serum creatinine, uremia, etc.)

The descriptive analysis of the enrolled population of patients will be performed first, and then the biomarkers concentration will be determined in the different ACVIM and IRIS class of patients. The influence on quality of life and survival time of prognostic selected factor using Kaplan Meyer curves and Cox proportional hazards will be executed.
The identification of the stage of the organ damage and the effects of prognostic factors may contribute to a better definition of prognosis, and could also provide new opportunities for novel therapeutic strategies in these patients.

Curone / Vigo

Ph.D. Student: Giulio Curone

Graduated in Veterinary Medicine at the University of Milan in July 2015 with the evaluation of 110/110 cum laude. He is author of the thesis “PTX3 in the goat mastitis caused by Staphylococcus Aureus, biomarker candidate?”. His main interest fields are the animal physiology (in particular reproduction, milk production, energetic metabolism and immune system) and biodiversity. His work is now focused on the physiological characterization of the Italian autochthonous cattle breeds in comparison with the cosmopolitan cattle breeds (Holstein and Brown).


Tutor: Daniele Vigo, DVM, PhD

Full Professor at the Faculty of Veterinary Medicine of Milan for the SSD 02 Vet Veterinary Physiology.

2015 - Techincal member of table 4 in “The Milan Charter” – Expo 2015
2015- Expo 2015 – Honorary speaker in the “Sustainable agriculture forum”

Scientific and professional associations
1985- Member of the professional veterinary order of Pavia
1985- Member of the Società Italiana di Scienze Veterinarie (SISVet)
1985- Member of the Società Italiana di Patologia ed Allevamento Suino (SIPAS)
1986- Member of the Società Italiana di Buiatria
1986- Member of the International Pig Veterinary Society (IPVS)
2008- Member of the Controlled Release Society (CRS)

Research interests
- Veterinary physiology, endocrinology, reproduction and lactation in domestics animals
- Animal welfare, stress and lactation
- 3D cellular culture system, neorgans and pseudorgans
- Controlled release technology, biotechnology and nanotechnology

Publications
- Author of 50 publications in international journals indexed in PubMed
- Author of 300 pubblication
- Author of 9 patents
- Author of four book chapters
- h index: 13 (Scopus)


ABSTRACT

The theme of biodiversity in recent years is becoming increasingly important and the United Nations General Assembly declared the 2011-2020 period as the United Nations Decade on Biodiversity.

In the last century the dairy livestock sector has undergone a considerable reduction of biodiversity caused by a very thrust selection with the only goal of the milk production increase. The preservation and rational use of autochthonous cattle breeds plays a key role in the maintenance of the biodiversity. These breeds have unique and peculiar features resulting from the interaction of its genetic background and the environmental conditions where they live.

[Figure 1. Italian autochthonous cattle breeds]

The animal husbandry of the 21st century has brought a decline in biodiversity of bovine breeds, due to the abandonment of autochthonous cows in favor of more productive cosmopolitan breeds (Holstein, Brown and Jersey) only following the milk production increase goal.

This mono-aptitude selective criterion has caused a decline in several aspects, the main ones being reproductive performances, quality of products and disease resistance. Moreover, the cost of their diets, which are based on starch and protein meals, has dramatically increased and there are great investments to cure recurring diseases. This situation have to change in the future, because the European Union requires for the next 50 years the reduction of the energy level of the ration (less cereals and more forage) and water consume and the reduction of the antibiotic consumption. In this light, the autochthonous cows, characterized by good food conversion and disease resistance, are the perfect model to address these challenges.

[Figure 2. Milk fat globules (green) and casein micelles (brown)]

In this project we will focus on the study of North Italian autochthonous cattle breeds (figure 1). In literature there are few studies on these breeds and are focused mainly on the genetics characterization in order to understand the link between the Italian native bovine population. The proposed study will focus on the characterization of the autochthonous dairy breeds of Northern Italy based on physiological parameters and their relation to adaptive capability:
• Metabolic physiology
we will study the metabolic balance during the open days period using many parameters such as ketone bodies in milk, blood concentration of 1- and 3-metylhistidine, thickness variation of the subcutaneous tissues and longissimus dorsi and hair cortisol concentration.
• Reproduction physiology
in order to investigate the reproductive efficiency we will monitor the open days period and the progesterone milk concentration.
• Production physiology
we will characterize the milk quality using the percentage of fat and protein, the dimensions of the fat milk globules and the fat acid composition of the fat milk globules (figure 2).
• Immune system physiology
in order to understand if the Italian autochthonous breeds could be predisposed or resistant to pathologies, we will study the white blood cell count, the leukocyte formula, the milk lysozyme activity and the PTX3 expression levels in the milk fat globules and milk somatic cells.
We will monitor this parameter, at specific time points, in the Holstein and at least 4 autochthonous breeds (Varzese, Bianca Val Padana, Cabannina, Reggiana), reared in same environmental conditions (i.e. same herd and same feeding conditions).
Finally, using these results, we could understand what kind of physiological error have been done in the Italian dairy cattle. Only with an accurate analysis of those errors we will be able to modulate the decisions for future innovation in the dairy production and industry. Moreover, the better knowledge of the autochthonous Italian breeds will allow an increase of their use, answering to the UE requirement of antibiotic reduction, energy food and water consumption.