Ateneo - UPO

Biochemistry of hormonal regulation; neuro-endocrine regulation and hypothalamic factors: catecholamines and biogenic amines, hormones of the posterior and intermediate pituitary gland. Hormones of the anterior pituitary gland, hypothalamic-pituitary axes and their peripheral targets
- Regulation of energy metabolism and its dysfunctions in the metabolic syndrome
The regulation of catabolic and anabolic processes; signaling pathway of PI3K / AKT / mTOR, AMPK, sirtuins. The insulin signaling pathway and systemic metabolic effects. Transcriptional control of energy metabolism. Endocrine role of adipose tissue. Molecular basis of the metabolic syndrome. Alterations in insulin signaling pathways and in the homeostasis of glucose and lipid metabolism
- Protein biomarkers (inflammatory, tumor markers). Enzyme biomarkers: main enzymes used in the clinical laboratory.

Antonozzi-Gulletta
Medicina di Laboratorio Logica e Patologia Clinica, Third edition, Piccin

Understanding how metabolic, protein and genetic markers can be used as diagnostic, predictive and therapeutic indicators.
Understanding how biochemical and molecular biology techniques are used in diagnostics
Understanding the informative value of the enzymatic and metabolic markers in the evaluation of organ functionality and in the diagnosis of metabolic disorders.
To gain an overview on the regulation of metabolic processes in different organs and tissues and to understand how single alterations in the intracellular signaling pathways can compromise the homeostasis not only of the cell or of the tissue, but of the whole organism

Basic knowledge of metabolic pathways and their regulation, signal transduction and regulation of gene expression. Good knowledge of cell biology

Frontal lessons with slides presentation. Execution of problems, quizzes and exposition of cases in the classroom to show precise molecular diagnostic problems and guide the student to their resolution.
Running problems, quizzes and case resolution at home using the moodle platform.
For the preparation of the exam students can use the material provided by the teacher (a pdf copy of the slides projected in class, of handouts prepared by the teacher and of some articles taken from scientific journals on the topics discussed during the course) and on the recommended textbook

A pdf copy of the projected slides, the in-depth material and all the information regarding the course and the methods of examination will be made available on the moodle DIR (https://www.dir.uniupo.it/)

The aim of the exam consists in verifying the level of knowledge skills developed by the student concerning the course program topics. The exam will consist in a written test including 40 questions related to all the topics of the course program divided into: quizzes with multiple choice answers or true / false and open question that require the resolution of problems concerning the determination of characteristics of a laboratory test (sensitivity, specificity and predictive values) or a short discussion of specific arguments treated during the course. The evaluation is expressed in thirtieths (minimum mark 18). During the written test it is not allowed to consult any kind of material. The calculator is allowed. The exam allows to evaluate the theoretical knowledge, the critical sense, the ability to understand the text (exercises with a request to make a choice between different alternatives) and the ability to apply the acquired knowledge to practical circumstances (numerical exercises).
The syllabus and exam modality will be available on the moodle DIR platform

1_Biochemistry of hormonal regulation
Neuro-hormonal regulation and hypothalamic factors
SNS and SNP signaling mechanisms. Catecholamines: structure, mechanism of action and peripheral metabolic effects
Biogenic amines (dopamine and serotonin): structure, mechanism of action and peripheral metabolic effects
Posterior pituitary hormones
- Vasopressin and oxytocin: structure, mechanism of action and peripheral metabolic effects
Intermediate pituitary hormones
- The derivatives of pro-opiomelanocortin: melanocortins, endorphins, lipotropins. Structure, mechanism of action and metabolic effects.
Hormones of the anterior pituitary, hypothalamic-pituitary axes and their peripheral targets
- CRH / ACTH axis. GRH, ACTH, cortical adrenal hormones, glucorticoids and mineralocorticoids: synthesis, structure, mechanism of action and metabolic effects. Pathological changes.
- GnRH / LH-FSH / sex hormones axis. General information on gonadotropic hormones. Regulation, structure, receptors and function. Sex hormones. Progesterone, estrogens, androgens (cholesterol biosynthesis and regulation of pituitary hormone synthesis, structure and function).
- Axis TRH / TSH / Thyroid hormones: regulation, synthesis, structure, mechanism of action and metabolic effects. Hypothyroidism and hyperthyroidism: metabolic consequences
- GHRH / GH / IGF1 axis: mechanism of action and metabolic effects. Pathological changes.

2_Regulation of energy metabolism and its dysfunctions in the metabolic syndrome
The regulation of catabolic and anabolic processes
- PI3K / AKT / mTOR signaling route
- AMPK signaling route
- The sirtuins
- The insulin signaling pathway and systemic metabolic effects. Transcriptional control of energy metabolism
- Endocrine role of adipose tissue
Molecular basis of the metabolic syndrome
- Alterations in insulin signaling pathways and in the homeostasis of glucose and lipid metabolism
- Notes on caloric restriction and aging
The biomarkers
1_Finality and significance of biomarkers
- Proteomic, metabolomic and genomic biomarkers
- Diagnostic, predictive, prognostic, efficacy, evolution biomarkers
2_Biomarkers of proteins
Inflammatory markers
Tumor markers
Proteomics
Enzyme biomarkers
- Selection criteria for enzymatic biomarkers in the clinical laboratory. Methods for determining enzymatic activities. General factors affecting the levels of different enzymes in the blood in health and disease conditions. Factors that influence the diagnostic utility of enzymes
- Main enzymes used as clinical biomarkers: biologic function in normal conditions and biological rationale for their use as disease markers. Definition and diagnostic value of isoenzymes. Organ enzymatic expression and diseases conditions with increases or decreases in transaminases, creatine kinase, lactic dehydrogenase, alkaline phosphatase, gamma glutamyl transferase, amylase, lipase, trypsin, cholinesterase. Biochemical and functional characteristics of markers of myocardial pathology: myoglobin and troponins
3_ Metabolic biomarkers: clinical applications of metabolomic analysis
Introduction to metabolomic analysis
Congenital alterations of metabolism
- “Biochemical” classification of laboratory markers used in the diagnosis of congenital alterations of metabolism
- Investigations of the metabolome: diagnostic significance of the profile of free fatty acids, organic acids and amino acids.
- Investigations of the proteome and enzymatic assays: fields of application and limits. Definition of diagnostic screening and its applications.
- Examples of congenital alterations of metabolism investigated or potentially investigated by neonatal screening: phenylketonuria, tyrosinemias, cystinuria, congenital hypothyroidism, biotinidase defect, adrenogenital syndrome, galactosemia, branched-chain organic acidemia (Maple Syrup Urine Disease / MSUD), aciduria isovaleric, propionic aciduria, methylmalonic aciduria. Urea cycle alterations, Medium-Chain Acyl-CoA dehydrogenase (MCAD) deficiency, congenital hyperplasia of the adrenal gland
4_Genomic biomarkers: clinical applications of molecular biology
Introduction
- Classification and functional consequences of genetic alterations investigated in molecular diagnostics
- Potential and limits of molecular tests. The choice of the starting biological material, according to the type of investigation and the purpose of the molecular test to be carried out. Sensitivity and specificity of molecular tests
- Main techniques used in molecular diagnostics
Molecular diagnostics in oncology
- Molecular diagnostics of colon cancer
- Molecular diagnostics of breast cancer
- Molecular diagnostics of lung cancer

Being able to independently assess how the pre-analytical and analytical conditions contribute to define the quality and the informative value of a laboratory result and to choose the most adequate molecular test according to test chemical-physical properties to the characteristics of the marker investigated.
To know the main biochemical (protein and metabolic) markers used in laboratory diagnostics to investigate organ function (mainly kidney and liver) and for the diagnosis of inborn metabolic diseases.
To know the main signaling pathways downstream of hormones, growth factors and cytokines.
Understanding how various pathological conditions may be characterized by alterations in energy metabolism and how knowledge of these alterations can be used to identify new therapeutic targets.