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No. of bitstreams: 2 Dissertação - Jordanna de Almeida e Silva.pdf: 1092808 bytes, checksum: 1a1858a05186289dd4e5c90b5d63a2d4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-02-28 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The objective of this research was to identify clinical and laboratory findings caused by the ingestion of calcium nitrate, encapsulated or conventional in different doses in cattle. Were used five bovines, cannulated, Nelore breed, male, with an average body weight of 500 kg were maintained during the entire experimental period in individual stalls with individual troughs for food and water. The experiment consisted of 75 days divided into five periods of 15 days. In each period the first 13 days were used for adaptation of the diet (Phase 1) followed by two days of collections (Phase 2). The experimental design was a latin square and the experimental groups were divided in the following way: not containing added nitrate in the diet (G1). 1.82% calcium nitrate and ammonium decahydrate without encapsulation in dry diet supplying 15% nitrogen (G2), 3.64% calcium nitrate and ammonium decahydrate without encapsulation in dry diet supplying 30% of nitrogen (G3), 2.58% calcium nitrate and ammonium decahydrate with encapsulation in dry diet providing 15% nitrogen (G4), 5.16% calcium nitrate and ammonium decahydrate with encapsulation in the dietary dry matter providing 30% nitrogen (G5). Data were analyzed using the R software (The R Development Core Team, 2010) in which was used the Tukey test by adopting a significance level of 5%. The animals were placed in contention tie stalls to perform physical examination. Then, were obtained blood samples for hemogram, fibrinogen, plasma protein, methemoglobin, nitrate and nitrite, blood biochemical, and ruminal fluid to measure pH, count protozoa and quantification of nitrite and nitrate. Changes in the hematological and biochemical examinations were nonspecific and punctual, while the methemoglobinemia was detected all livestock. The G3 group showed severe clinical signs requiring therapeutic intervention with methylene blue, which has been providing effective reductions in the levels of nitrate, nitrite and methemoglobin. Bovines to G2 and G4 groups have had similar clinical and laboratory results, not justifying the processing of nitrate font. The dose related to the G5 was efficient in preventing toxicosis nitrate / nitrite, however new research should be carried out to prove its cost / benefit. / O objetivo da presente pesquisa foi identificar alterações clínicas e laboratoriais ocasionadas pela ingestão de diferentes doses de nitrato de cálcio encapsulado ou convencional em diferentes doses em bovinos. Foram utilizados cinco bovinos fistulados, da raça Nelore, machos, com peso vivo médio de 500 kg, mantidos durante todo o período experimental em baias individuais com cochos individuais de água e comida. O experimento consistiu de 75 dias dividido em cinco períodos de 15 dias. Em cada período os primeiros 13 dias foram utilizados para adaptação da dieta (Fase 1) seguidos de dois dias de coletas (Fase 2). O delineamento experimental utilizado foi o quadrado latino e os grupos experimentais foram divididos da seguinte forma: sem adição de nitrato na dieta (G1); 1,82% de nitrato de cálcio e amônio decahidratado sem encapsulamento na matéria seca da dieta fornecendo 15% de nitrogênio (G2); 3,64% de nitrato de cálcio e amônio decahidratado sem encapsulamento na matéria seca da dieta fornecendo 30% de nitrogênio (G3); 2,58% de nitrato de cálcio e amônio decahidratado com encapsulamento na matéria seca da dieta fornecendo 15% de nitrogênio (G4); 5,16% de nitrato de cálcio e amônio decahidratado com encapsulamento na matéria seca da dieta fornecendo 30% de nitrogênio (G5). Os dados foram analisados pelo software R (The R Development Core Team, 2010) em que utilizou o teste Tukey adotando-se grau de significância de 5%. Os animais foram colocados em tronco de contenção para a realização de exame físico. Em seguida, foram obtidas amostras de sangue para a realização de hemograma, fibrinogênio, proteína plasmática, metemoglobina, nitrato e nitrito, bioquímicas sanguíneas, além de fluido ruminal para aferir ph, contagem de protozoários e quantificação do nitrito e nitrato. As alterações nos exames hematológicos e bioquímicos foram inespecíficas e pontuais, enquanto que a metemoglobinemia foi detectada em todos os animais. O grupo G3 apresentou sinais clínicos severos necessitando intervenção terapêutica com azul de metileno, que foi eficaz proporcionando reduções nos níveis de nitrato, nitrito e metemoglobina. Os bovinos dos grupos G2 e G4 tiveram resultados clínicos e laboratoriais semelhantes, não justificando o processamento da fonte de nitrato. A dose referente ao G5 foi eficiente na prevenção da toxicose de nitrato/nitrito, porem novas pesquisas devem ser realizadas para comprovar seu custo/benefício.

Phenomenology is a critical component of autobiographical memory retrieval. Some memories are vivid and rich in sensory details whereas others are faded; some memories are experienced as emotionally intense whereas others are not. Sutin and Robins (2007) identified 10 dimensions in which a memory may vary—i.e., Vividness, Coherence, Accessibility, Sensory Details, Emotional Intensity, Visual Perspective, Time Perspective, Sharing, Distancing, and Valence—and developed a comprehensive psychometrically sound measure of memory phenomenology, the Memory Experiences Questionnaire (MEQ). Phenomenology has been linked to underlining stable dispositions—i.e. personality, as well as to a variety of positive/negative psychological outcomes—well-being and life satisfaction, depression and anxiety, among others. Using the MEQ, a cross-sectional and a longitudinal study were conducted on a large sample of American and Italian adults. In both studies, participants retrieved two ‘key’ personal memories, a Turning Point and a Childhood Memory, and rated the affect and phenomenology of each memory. Participants also completed self-reported measures of personality (i.e. Neuroticism and Conscientiousness), and measures of depression, well-being and life satisfaction. The present research showed that phenomenological ratings tend (a) to cross-sectionally increase across adulthood (Study 1), and (b) to be moderately stable over time, regardless the contents of the memories (Study 2). Interrelations among memory phenomenology, personality and psychological outcome variables were also examined (Study 1 and Study 2). In particular, autobiographical memory phenomenology was proposed as a dynamic expression of personality functioning that partially explains adaptive/maladaptive psychological outcomes. In fact, the findings partially supported the hypothesized mediating effect of phenomenology on the personality association with psychological outcomes. Implications of the findings are discussed proposing future lines of research. In particular, the need for more longitudinal studies is highlighted, along with the combined application of both self-report questionnaires and narrative measures.

Questo studio prospettico valuta l’efficacia e i vantaggi del sistema LigasureTM rispetto alle tecniche chirurgiche tradizionali, in quattro differenti procedure eseguite su 77 cani. I soggetti sono stati suddivisi in 4 gruppi, a seconda della chirurgia eseguita: Gruppo 1, 25 pazienti sottoposti a Splenectomia “aperta” semplice; Gruppo 2, 15 pazienti sottoposti a Splenectomia “aperta” complessa; Gruppo 3, 22 pazienti sottoposti ad Ovariectomia “aperta”. Gruppo 4: 18 pazienti sottoposti a Linfoadenectomia. Ciascun gruppo è stato a sua volta suddiviso in due sottogruppi: a (LigasureTM) e b (Tradizionale), a seconda della metodica utilizzata. Sono stati analizzati: il segnalamento, i parametri ematologici, le condizioni cliniche, le informazioni riguardanti l’intervento chirurgico e l’outcome. In tutti i gruppi il ricorso all’utilizzo di garze nonché dei fili da sutura sono risultati statisticamente inferiori nei pazienti operati con il sistema a radiofrequenza (Gruppo 1, P < 0.0001; Gruppo 2, P < 0,0014; Gruppo 3, P = 0,0001; Gruppo 4, P = 0,0148). Anche i tempi per la rimozione dell’organo sono significativamente ridotti in tutti i gruppi in cui è stato utilizzato il sistema LigasureTM (Gruppo 1 P < 0.0001; Gruppo 2 P < 0,0014; Gruppo 3 P = 0,0009; Gruppo 4 P = 0,0008), come i tempi chirurgici nei gruppi 1, 2 e 3 (P = 0,0287; P = 0,0064; e P = 0,0124) ed anestesiologici nei gruppi 1a e 2a (P = 0,0176; P = 0,0043). Tra le variabili analizzate, l’utilizzo del sistema di sintesi vascolare a radiofrequenza, è l’unico ad influenzare i tempi necessari per l’esecuzione della procedura. Questo studio dimostra, quindi, come il sistema LigasureTM sia sicuro ed efficace per le procedure chirurgiche esaminate, riducendo i tempi della chirurgia e limitando, quindi, i rischi per il paziente, indipendentemente dall’operatore, dall’esecuzione di altre procedure contemporanee e dalla natura della patologia splenica o linfonodale. / The purpose of this prospective study was to compare the efficacy and the advantages of the LigasureTM device with the conventional surgical technique (Ligation tecnique, in four different surgical procedures in 77 dogs. All subjects were assigned into four groups, according to the surgical procedure performed: Group 1, 25 patients having “open” simple splenectomy; Group 2, 15 patients having “open” complex splenectomy; Group 3: 22 dogs having “open” ovariectomy; Group 4: 18 dogs having lymphadenectomy. For each group, patients were randomly assigned into two subgroups: a (LigasureTM)and b (Traditional), depending on surgical technique. Data collected for each dog included: signalment, complete blood count, biochemistry,urinalysis, clinical status, surgical records and outcome. For all groups, gauzes number used was statistically lower in vessels sealing device group (Group 1, P < 0.0001; Group 2, P < 0,0014; Group 3, P = 0,0001; Group 4, P = 0,0148), likewise suture material consumption. Moreover, even time for tissue/organ removal was shorter when LigasureTM was used for all the procedures (Group 1, P < 0.0001; Gruop 2, P < 0,0014; Gruop 3, P = 0,0009; Group 4, P = 0,0008). As regards the assessment of operative times, these were also significantly lower in Group 1, 2 and 3 (respectively P = 0,0287, P = 0,0064 and P = 0,0124), meanwhile anesthesiological time were lower in Group 1 and 2 (P = 0,0176 and P = 0,0043). The incidence of postoperative complications was similar regardless of the surgical technique used. This study shows how LigasureTM is safe and effective for performing splenectomy,ovariectomy and limphadenectomy in dog, reducing mean operative time and so,potentially decreasing risk to the patient. This was true despite the experience/training of the surgeon, the performance of other surgical procedures, and histopathologic nature of the splenic or lymph node disease.

The general aim of this dissertation was to uncover the association between psychosocial factors and rehabilitation outcome after stroke. METHOD. A sample of patients with stroke (n=40) and their caregivers (n=36) were assessed at admission to and six months after discharge from rehabilitation hospital, using the following instruments: Structured Clinical Interview for DSM-IV, structured interview based on Diagnostic Criteria for Psychosomatic Research, Symptom Questionnaire, Psychosocial Index, Psychological Well-Being Scales, and Family Assessment Device. 40 subjects from the general population underwent the same psychological assessment. In addition, patients' functional status was measured using the Functional Independence Measure. RESULTS. Stroke survivors reported lower education and higher alcohol consumption than controls. No significant differences emerged between the two groups in the prevalence of psychiatric diagnoses or psychosomatic syndromes, however patients reported significantly higher levels of anxiety, depression, somatic symptoms, and lower autonomy than controls. Caregivers reported significantly higher scores in anxiety, depression, and somatic symptoms compared to normative data, while no impairments emerged in psychological well-being and family functioning. At six-month follow-up, in patients a significant decrease in smoking habit and an increase in DSM diagnoses were reported. Both stroke survivors and caregivers showed significant reductions in anxiety, with patients displaying also a decrease in somatic symptoms, an increase in stress and a deterioration in quality of life. Significant deteriorations in several aspects of family functioning was perceived only by patients. An association between patients' functional recovery in the cognitive domain and family behavior control emerged. For caregivers, family functioning significantly predicted hostility and somatic symptoms were associated with family affective involvement. CONCLUSIONS. These data highlight the utility in the Italian setting of the adoption of a psychosocial assessment and a family-systems approach in stroke rehabilitation, in order to development interventions properly targeted to the characteristics of patients and their family members.

Emotional intelligence (EI) represents an attribute of contemporary attractiveness for the scientific psychology community. Of particular interest for the present thesis are the conundrum related to the representation of this construct conceptualized as a trait (i.e., trait EI), which are in turn reflected in the current lack of agreement upon its constituent elements, posing significant challenges to research and clinical progress. Trait EI is defined as an umbrella personality-alike construct reflecting emotion-related dispositions and self-perceptions. The Trait Emotional Intelligence Questionnaire (TEIQue) was chosen as main measure, given its strong theoretical and psychometrical basis, including superior predictive validity when compared to other trait EI measures. Studies 1 and 2 aimed at validating the Italian 153-items forms of the TEIQue devoted to adolescents and adults. Analyses were done to investigate the structure of the questionnaire, its internal consistencies and gender differences at the facets, factor, and global level of both versions. Despite some low reliabilities, results from Studies 1 and 2 confirm the four-factor structure of the TEIQue. Study 3 investigated the utility of trait EI in a sample of adolescents over internalizing conditions (i.e., symptoms of anxiety and depression) and academic performance (grades at math and Italian language/literacy). Beyond trait EI, concurrent effects of demographic variables, higher order personality dimensions and non-verbal cognitive ability were controlled for. Study 4a and Study 4b addressed analogue research questions, through a meta-analysis and new data in on adults. In the latter case, effects of demographics, emotion regulation strategies, and the Big Five were controlled. Overall, these studies showed the incremental utility of the TEIQue in different domains beyond relevant predictors. Analyses performed at the level of the four-TEIQue factors consistently indicated that its predictive effects were mainly due to the factor Well-Being. Findings are discussed with reference to potential implication for theory and practice.

L’approccio chirurgico agli adenomi ipofisari ACTH secernenti è la terapia d’elezione nell’uomo. L’ipofisectomia transfenoidale è invece una tecnica poco diffusa in ambito veterinario. La terapia più diffusa nel cane con ipercortisolismo ipofisi dipendente (PDH) è di tipo medico e prevede la somministrazione di farmaci inibitori della sintesi del cortisolo. Gli adenomi ipofisari possono aumentare di volume e determinare una conseguente sintomatologia neurologica; in questi casi le uniche opzioni terapeutiche sono rappresentate dall’asportazione chirurgica della neoplasia e dalla radioterapia. Nella presente tesi vengono descritti 8 interventi di ipofisectomia transfenoidale effettuati su 7 cani con macroadenoma ipofisario presso il Dipartimento di Scienze Mediche Veterinarie dell’Università di Bologna. La difficoltà maggiore per il chirurgo è rappresentata dalla localizzazione della fossa ipofisaria rispetto ai punti di repere visibile in tomografia computerizzata o in risonanza magnetica nucleare, oltre ai problemi di sanguinamento durante la rimozione della neoplasia. Nel periodo post-operatorio maggiori complicazioni si riscontrano in soggetti con adenomi ipofisari di maggiori dimensioni. Al contrario, in presenza di adenomi di dimensioni più contenute, la ripresa post-operatoria risulta più rapida e il tasso di successo maggiore. Al fine di poter eseguire nel cane l’exeresi mirata della sola neoplasia ipofisaria, al pari di quanto avviene nell’uomo, è stato condotto uno studio sulla tomografia computerizzata (TC) in 86 cani con PDH. Il protocollo TC non ha tuttavia permesso di individuare con precisione la posizione della neoplasia per guidare il chirurgo nella sua rimozione. In due casi riportati nel presente lavoro si è verificata una recidiva della neoplasia ipofisaria. In un soggetto si è optato per il reintervento, mentre nell’altro caso per la radioterapia. Entrambe le opzioni hanno garantito una buona qualità di vita per più di un anno dall’intervento terapeutico. Questi casi clinici dimostrano come il reintervento e la radioterapia possano essere considerate valide opzioni in caso di recidiva. / Surgical excision of pituitary adenomas represents the first line treatment in humans with pituitary-dependent hypercortisolism (PDH). Transsphenoidal hypophysectomy in dogs is a surgical technique available in few veterinary centres. The most common treatment for PDH in dogs is the medical therapy with inhibitors of cortisol secretion. Pituitary adenomas can enlarge, reaching considerable size with subsequent neurological symptoms, in these cases the surgical removal of the tumor or radiotherapy are the only therapeutic options. A wide collaboration between different specialists is needed in case of transsphenoidal hypophysectomy. In this thesis 8 cases of transsphenoidal hypophysectomy in 7 dogs operated at the Department of Veterinary Medical Sciences, University of Bologna, are described. The main intraoperative difficulties for the surgeon were the localization of the pituitary fossa in relationship with the surgical landmarks visible in computed tomography (CT) or magnetic resonance imaging, besides bleeding problems during the removal of the mass. In the post-operative period major complication were encountered in patients with the most enlarged pituitary glands, together with a higher failure rate. On the contrary in cases of smaller tumor, the post-operative recovery was faster and with a higher success rate. In order to reach the targeted removal of the neoplasia, as in humans, a CT study has been conducted on 86 dogs with PDH. Unfortunately the CT protocol didn’t permit to identify precisely the location of the tumor and to guide the surgeon in its removal. In two cases reported in the present work, the pituitary tumor recurred. In one case reoperation was decided, while in the other dog radiotherapy was chosen. Both therapeutic options allowed a good quality of life for more than one year. These cases demonstrate that both reoperation and radiotherapy can be considered valid options in case of recurrence.

Abstract Background: Turner syndrome (TS) is a chromosomal abnormality (total or partial absence of one of the sexual chromosomes in some or all cells of the body), which affects approximately 1:2000 female. Principal characteristics are short stature and gonadal disgenesis. Clinical management consist of Growth Hormone (GH) treatment and oestrogen replacement therapy (HRT), to induce development of secondary characteristics and to avoid the sequelae of oestrogen deficiency. Aim of the study: To assess clinical management, quality of life (QoL) and general psychosocial adjustment of women with TS. Population: 70 adult Caucasian females with TS (mean age: 27.8, ± 7.6; range 18-48 y.). Setting: Specialist service for Rare Disease care, University Hospital. Methods: Subjects were required to fill in questionnaires collecting ASR, WHOQOL, and 8 open questions. Data were compared with those of the Italian population or to those collected in a comparison group (70 healthy females, mean age: 27.9, ±7.3, range 21-48 y.). Results: Women with TS are educated as well as the Italian Population, but they have a less successful professional life. They show good QoL in general, but they appeared less satisfied in social area. They had statistically higher scores than the comparison group for depression, anxiety and withdrawal. Are less involved in a love relationship. Diagnosis communication was mostly performed by doctors or parents, satisfaction was higher when information was given by parents. Main preoccupation about TS are infertility, feeling of being different and future health problem. Conclusions: Italian people with TS were generally well adapted and have a good QoL, but lived more often with parents and show impaired sentimental and sexual life. They have higher degree of psychological distress compared to a comparison group. Psychological intervention should firstly address parents in order to encourage an open communication on diagnosis issues and on sexual education.

La prima parte del nostro studio riguarda la tecnica LAMP (Loop-mediated isothermal amplification), una tecnica di amplificazione isotermica recentemente inventata (Notomi et al., 2000). Essa presenta notevoli vantaggi rispetto alle tradizionali PCR: non necessita di strumentazioni sofisticate come i termociclatori, può essere eseguita da personale non specializzato, è una tecnica altamente sensibile e specifica ed è molto tollerante agli inibitori. Tutte queste caratteristiche fanno sì che essa possa essere utilizzata al di fuori dei laboratori diagnostici, come POCT (Point of care testing), con il vantaggio di non dover gestire la spedizione del campione e di avere in tempi molto brevi risultati paragonabili a quelli ottenuti con la tradizionale PCR. Sono state prese in considerazione malattie infettive sostenute da batteri che richiedono tempi molto lunghi per la coltivazione o che non sono addirittura coltivabili. Sono stati disegnati dei saggi per la diagnosi di patologie virali che necessitano di diagnosi tempestiva. Altri test messi a punto riguardano malattie genetiche del cane e due batteri d’interesse agro-alimentare. Tutte le prove sono state condotte con tecnica real-time per diminuire il rischio di cross-contaminazione pur riuscendo a comprendere in maniera approfondita l’andamento delle reazioni. Infine è stato messo a punto un metodo di visualizzazione colorimetrico utilizzabile con tutti i saggi messi a punto, che svincola completamente la reazione LAMP dall’esecuzione in un laboratorio specializzato. Il secondo capitolo riguarda lo studio dal punto di vista molecolare di un soggetto che presenza totale assenza di attività mieloperossidasica all’analisi di citochimica automatica (ADVIA® 2120 Hematology System). Lo studio è stato condotto attraverso amplificazione e confronto dei prodotti di PCR ottenuti sul soggetto patologico e su due soggetti con fenotipo wild-type. Si è poi provveduto al sequenziamento dei prodotti di PCR su sequenziatore automatico al fine di ricercare la mutazione responsabile della carenza di MPO nel soggetto indicato. / The first part of the present study concerns the LAMP technique (Loop-Mediated Isothermal Amplification), an isothermal amplification technique recently developed (Notomi et al., 2000). LAMP has many advantages over traditional PCR: it doesn’t require sophisticated instruments like thermal cyclers, it can be performed by unskilled staff, it is a highly sensitive and specific technique and it is very tolerant to inhibitors. All these characteristics make it suitable to be used outside diagnostic laboratories, as POCT (Point-of-care testing), with the advantage of not having to send the sample and obtaining results as accurate as PCR tests and in very short times. We designed and optimized assays to detect bacteria that require a very long time for cultivation or that are not even cultivable. We drew assays for the diagnosis of viral diseases that require to be diagnosed as soon as possible. We developed a test to assess two genetic diseases of the dog and two food contaminating bacteria. All tests were carried out using real-time technique to decrease the risk of cross-contamination. Finally, we developed a colorimetric method for showing results which can be applied to all of the assays we optimized. The second section presents the molecular study of a subject who had myeloperoxidase deficiency at the automated cytochemistry analysis (ADVIA ® 2120 Hematology System). The study was conducted through amplification and comparison of the PCR products obtained from the pathological subject and on two subjects with wild-type phenotype. The products were sequenced using an automated sequencer in order to find the responsible mutation for the MPO deficiency in the indicated subject.

Disorders of the somatosensory system causing neuropathic pain (NP) are common in people. In small animals medicine, this condition remains underestimated probably due to the lack of standardized assessment methods and studies focused on the description of structures playing a key role in developing and maintaining neuropathic pain, such as dorsal root ganglia (DRG). Hence, the aims of the present research project, structured in three different studies, were: a) investigate the possible effects of the reduction in radicular blood flow on the vascular density, ganglionic and endoneurial ischemia and shift in neuronal metabolism, in fifteen L7-DRG from a total of eight dogs suffering from painful compressed spinal L7 nerve roots (NRs) and DRG; b) perform a preliminary characterization of the expression of substance P, calcitonin gene-related peptide, calbindin D-28k, neuronal nitric oxide synthase and the colocalization of those molecules in lumbosacral DRG neurons of three neurologically normal dogs; c) Investigate the prevalence, risk factors and owners’ perception of their pets quality of life of the Phantom Complex (PC) in a client-owned population of 107 dogs with limb amputation through an online survey. Main results were: a) Our findings highlight a significant neuronal distress in compressed DRG. Despite the similarity of vascular density between controls and compressed L7-DRG, we found a significant increased in neuronal immunoreactivity for hypoxia-related markers and for markers related to glycolytic cellular metabolism. b) The wide variability of CGRP-, SP-, CALB-, and nNOS-immunoreactivity among different species was confirmed. Further studies are required in order to better define the characterization of those markers in canine DRG. c) Our study demonstrates for the first time the presence of PC.Significant risk factors associated with the frequency of post-amputation pain episodes are duration of pain before amputation and time between diagnosis and amputation.

L’avvento della terapia antiretrovirale ha trasformato l’infezione da HIV in una patologia di tipo cronico, rendendo possibile la manifestazione di comorbidità HIV-relate. Particolare importanza rivestono le lesioni a carico del compartimento osseo, infatti i soggetti sieropositivi hanno un rischio maggiore di sviluppare osteopenia e osteoporosi, rispetto alla popolazione sana. Numerosi lavori hanno dimostrato come sia il virus HIV che la terapia antivirale siano in grado di determinare l’alterazione di questo bilancia, attraverso un’azione negativa diretta sulle cellule della linea osteoblastica. Per quanto riguarda il compartimento osteoclastico, invece, le indicazioni presenti in letteratura sono poche e spesso contrastanti. La prima parte di questo elaborato si è quindi focalizzata sullo studio dell’effetto indotto dal virus e dalla terapia antiretrovirale sulle cellule della linea osteoclastica in un modello sperimentale in vitro. I risultati ottenuti mostrano che in presenza del virus e della terapia si osserva un’intensificazione dell’attività osteoclastica, con conseguente riduzione della densità di massa ossea. Tuttavia, nonostante gli indubbi successi della cART la terapia non si è dimostrata in grado di eradicare l’infezione. Questo scenario ha aperto la strada allo sviluppo di nuove molecole ad azione antiretrovirale in grado di bloccare l’ingresso del virus attraverso il contatto sessuale: in particolare, alcuni studi si sono focalizzati sull’utilizzo di composti da impiegare a livello delle mucose genitali, con lo scopo di contrastare, o almeno ridurre, la trasmissione di HIV-1. In tal senso si è indirizzata la seconda parte della tesi, volta a valutare l’efficacia di una molecola di nuova concezione, un mini CD4 chiamato M48U1, da solo o in combinazione con farmaci tradizionali, nel ridurre o prevenire l’infezione di HIV-1. Dai dati emersi è possibile osservare una consistente riduzione della trasmissione dell’infezione sia su un modello in vitro che su un modello ex vivo. / Several studies have shown that HIV infection and treatment with antiretroviral drugs can induce a significant increase in cases of osteopenia / osteoporosis in HIV-infected patients. The loss of bone mass density (BMD) is related to the functional loss of balance of bone forming unit (BFU) that is characterized by fine adjustment that normally elapses between the trophic action of osteoblasts and bone resorption action of osteoclasts. In the first part of this work we evaluate the effect of HIV, specific viral proteins and some conditioned medium on the differentiation of osteoclasts. The achieved results show the contribute of the therapy and the viral protein on the osteoclast differentiation, with a consequent higher bone resorption and a decrease of Bone Mass Density. In the second part of this work, we analysed the antiviral activity of mini CD4 M48U1 peptide formulated in HEC on activated peripheral blood mononuclear cells (PBMCs) infected by R5 and X4–tropic HIV strains. The results demonstrated that M48U1 prevented the HIV-1BaL and HIV-1IIIB infection in activated PBMCs with the half maximal effective concentration (EC50) determined at 30 and 20.3 nM, respectively. In addition, M48U1 was tested in association with Tenofovir in HEC and these two antiretroviral drugs synergized for the HIV inhibition. It is noteworthy that M48U1 alone or in combination with Tenofovir in HEC hydrogel strongly inhibited HIV replication in an organ-like structure of human cervico-vaginal tissue without any induction of significant tissue toxicity.