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Made available in DSpace on 2018-08-01T22:59:18Z (GMT). No. of bitstreams: 1 tese_6522_Tese Clarissa Loureiro Tonini.pdf: 3180565 bytes, checksum: 569dd647306b8509c99daff903fe8d06 (MD5) Previous issue date: 2013-03-27 Há décadas tem se estudado a relação entre a produção de espécies reativas de oxigênio e o desenvolvimento da aterosclerose. Sabe-se que todo processo inflamatório envolvido na progressão da placa acarreta em aumento da produção de radicais livres. Além disso, o envelhecimento é um fator que agrava a doença aterosclerótica e também a produção de espécies reativas de oxigênio, provavelmente pela perda da capacidade antioxidante que faz o balanceamento regular das espécies reativas de oxigênio. O camundongo Apolipoproteína E deficiente é um modelo amplamente utilizado no estudo da aterosclerose, no qual há elevada hipercolesterolemia o que acarreta em aumento da produção de espécies reativas de oxigênio na medula óssea, sangue e aorta. O envelhecimento por sua vez também leva ao aumento da produção das espécies reativas de oxigênio, entretanto quando cumulado com a hipercolesterolemia, o resultado desse fenômeno é a ocorrência de maior produção de espécies reativas de oxigênio e, consequentemente, níveis elevados de fragmentação oxidativa do DNA e apoptose celular. Neste sentido, com maior destaque está a análise das células de medula óssea que apresentaram neste estudo alta produção de ânions superóxido e de radicais de peróxido de hidrogênio, ou seja, a fonte de produção de células sanguíneas e células tronco para todo o organismo, que comumente apresenta ambiente com baixa tensão de oxigênio, é afetada pelo desequilíbrio oxidativo causado pelo envelhecimento e pela aterosclerose. Ainda, corroborando com estes dados, a análise da fragmentação do DNA, pelo ensaio do cometa, das células de medula revelaram altos índices de fragmentação nos animais ateroscleróticos e idosos. Ainda, as células de sangue e aorta dos animais ateroscleróticos e idosos também apresentaram alta produção de ânion superóxido. Entretanto, encontramos baixa produção de peróxido de hidrogênio nas células endoteliais de todos os grupos, sugerindo uma possível modulação tecido-específica dos efeitos de enzimas antioxidantes. Além disso, observamos que não há aumento da produção de peróxido de hidrogênio nas células sanguíneas de animais C57 idosos, ao contrário das células mononucleares de medula óssea, no qual observamos aumento. Por fim, pode-se destacar que, de modo geral, a aterosclerose aumenta a produção de espécies reativas de oxigênio assim como o envelhecimento, porém quando estes dois parâmetros são cumulados a tensão oxidativa é ainda maior. A análise da literatura científica sugere uma possível ativação da enzima NADPH oxidase, responsável pelo aumento da produção de espécies reativas de oxigênio, e downregulation de enzimas antioxidantes, que prejudica o balanceamento do estresse oxidativo nos tecidos analisados. PALAVRAS-CHAVE: ATEROSCLEROSE, CAMUNDONGO APOE-KO, ENVELHECIMENTO, ESTRESSE OXIDATIVO.

Information on the effects of early treatment of seizures on mortality is scarce. The authors assessed the survival of patients with a first generalised tonic-clonic seizure, randomised to immediate treatment (treated) versus treatment only in the event of seizure recurrence (untreated), over a 20-year period. METHODS: The authors followed 419 patients. The median follow-up was 19.7 years (range 0.2-21.5) for a total of 7867 person-years. RESULTS: 40 persons (9.6%) died during follow-up, 19 (8.9%) treated and 21 (10.3.%) untreated. The probability of surviving was 100% at 1 year, 97% (95% CI 95% to 99%) at 5 years, 94% (91-97) at 10 years and 91% (87-95) at 20 years in treated patients and 100%, 98% (95-100), 97% (94-99) and 89% (85-94), respectively, in untreated patients (p=0.7). After adjustment for treatment of first seizure and putative risk factors (gender, age, seizure type, previous uncertain seizures, family history of seizures, pre-, peri- and postnatal risk factors, remote aetiological factors for epilepsy, abnormal neurological examination, CT or MRI abnormalities, EEG abnormalities and acute treatment), only the presence of aetiological factors for epilepsy predicted a higher mortality (HR 3.4, 95% CI 2.5 to 4.3%; p

The spectro-photometric properties of galaxies in galaxy formation models are obtained by combining the predicted history of star formation and mass accretion with the physics of stellar evolution through stellar population models. In the recent literature, significant differences have emerged regarding the implementation of the Thermally-Pulsing Asymptotic Giant Branch phase of stellar evolution. The emission in the TP-AGB phase dominates the bolometric and near-IR spectrum of intermediate-age (~1 Gyr) stellar populations, hence it is crucial for the correct modeling of the galaxy luminosities and colours. In this paper for the first time, we incorporate a full prescription of the TP-AGB phase in a semi-analytic model of galaxy formation. We find that the inclusion of the TP-AGB in the model spectra dramatically alters the predicted colour-magnitude relation and its evolution with redshift. When the TP-AGB phase is active, the rest-frame V-K galaxy colours are redder by almost 2 magnitudes in the redshift range z~2-3 and by 1 magnitude at z~1. Very red colours are produced in disk galaxies, so that the V-K colour distributions of disk and spheroids are virtually undistinguishable at low redshifts. We also find that the galaxy K-band emission is more than 1 magnitude higher in the range z~1-3. This may alleviate the difficulties met by the hierarchical clustering scenario in predicting the red galaxy population at high redshifts. The comparison between simulations and observations have to be revisited in the light of our results., Comment: 6 pages, 4 figures. Accepted for publication on MNRAS Letters

Made available in DSpace on 2016-08-29T15:37:50Z (GMT). No. of bitstreams: 1 tese_2992_Dissertação Clarissa Loureiro Tonini.pdf: 1498941 bytes, checksum: 3fdb91f195aa56e06afb3bb897db0e1b (MD5) Previous issue date: 2008-08-04 As células tronco têm sido alvo de muitos estudos atualmente, muitos deles utilizando a terapia celular nas doenças cardiovasculares. Entretanto, pouco se sabe sobre os mecanismos que alteram a função e a mobilização das células tronco quando expostas a senescência e a aterosclerose. A análise das células tronco dos camundongos ApoE-KO mostrou que a aterosclerose aumenta o número de células tronco mesenquimais e hematopoéticas da medula óssea provavelmente através do aumento das divisões simétricas estimuladas pela progressão da placa aterosclerótica. Nos animais controle observamos aumento progressivo do número de células tronco hematopoéticas e diminuição do número de células tronco mesenquimais. Na análise de genotoxicidade das células da medula óssea observamos alto nível de fragmentação do DNA nas células mononucleares da medula óssea dos animais ateroscleróticos possivelmente pela ação dos radicais livres produzidos durante a progressão da placa aterosclerótica, o que também foi evidenciado pela senescência dos arcos aórticos analisados. Em contraste, o grupo C57 apresentou baixo nível de fragmentação do DNA e, portanto uma baixa senescência vascular, ou seja, o sistema de reparo é eficiente. Observamos também que o avanço da idade aumentou do número de células tronco hematopoéticas, ou seja, nessa linhagem de células não ocorre perda da capacidade proliferativa, o que não acontece com a linhagem mesenquimal. Palavras-chave: Aterosclerose. Células Tronco. Genotoxicidade

Journal of Mathematics and Science: Collaborative Explorations, 1998

Backgrounds/Aims: The World Health Organization estimates the annual worldwide incidence of death by drowning to be about 400,000. Deaths from drowning are more common in young children, representing 27% of deaths at 1–4 years from unintentional injury in the US.Drowning victims develop hypoxaemia related to the acute lung injury as a result of surfactant disruption. The severe lung dysfunction leads to alveolar collapse, atelectasis and intrapulmonary shunting and often progresses to acute respiratory distress syndrome (ARDS). Surfactant replacement therapy has been shown to reduce mortality and complications in prematures and neonates with severe respiratory distress syndrome(RDS). Administration of surfactant to adults with ARDS has received great attention and specific patients may benefit from surfactant treatement; however more studies are needed.This Case report describes our experience with a 18 months child affected by a severe ARDS from freshwater near-drowning and treated with a single dose of surfactant (Curosurf). Methods: While she was unatended, a little 18 months girl fell in a big basin full of freshwater. Her face remained under water for 3–5 min. Her parents rescued her and started a basic CPR. They transported her to the nearest hospital where she was intubated and ventilated. Medical staff continued CPR and started acidosis correction, noradrenaline infusion (0,1 mcg/kg/min), antibiotics and corticosteroids therapy. Finally both pupils reacted to light. The patient had severe combined acidosis whith pH 7.09, but normal electrolytes. On ICU admission, 270 min after the submersion, her GCS was 8, BP 100/60mmHg, HR 120. A chest X-Ray showed bilateral infiltrates, subatelectasis and an increased cardiothoracic ratio.The rectal temperature was almost normal.The pulse oximetry revealed a saturation 100% with FiO2 =1. After repeated suctioning and recruitment manoevres a 240 mg dose of Surfactant (Cursurf) in volume of 50 ml of normal saline was injected intratracheally during a fiberoptic broncoscopy (mg/5ml). The ET tube was connected to the pressure controlled ventilation. The patient was also treated with antibiotics (ceftriaxone and amikacin), corticosteroids (desametasone), ranitidine, phenobarbital, fluids therapy and rewarming. Results: The first blood gas 3 hours after surfactant administration showed PaO2/FiO2 ratio of blood gas analysis 0h (144) -3 h (407), 6h (431), 12h (471), -18h (474).and chest X-Rays were checked at 6–12-18 hours and revealed a rapid improvement of oxygenation and respiratory distress. Electroencephalography and neurological evaluation were normal. An Echocardiography revealed normal ventricular function and minor ventricular septal decreased contractility. Conclusions: The key pathophysiological feature in drowning is hypoxia. In our experience surfactant replacement had drammatically improved oxygenation. Prompt resuscitation is crucial for optimal survival: that means good neurological outcome.

Objective: We were aimed at evaluating the long-term impact of perinatal an omega-3 fatty acid-enriched diet on the mevalonate/cholesterol pathway in the brain of male offspring. Methods: Female rats were fed with standard or omega-3 fatty acid-enriched diet during pregnancy and lactation. Liver, brain and plasma were collected from infant, adolescent and adult male offspring for subsequent biochemical and morphological analyses. Results: The omega-3 enriched diet induced region-dependent changes of the 3-hydroxy 3-methylglutaryl Coenzyme A reductase in the brain and affected notably RhoA/CREB signaling and the nerve growth factor content in the hippocampus. Our data reveal a long-lasting impact of perinatal omega-3 fatty acid supplementation on hippocampal nerve growth factor levels mediated by reduced 3-hydroxy 3-methylglutaryl Coenzyme A reductase activation state and enhanced CREB signaling. Discussion: These data underline the importance of the perinatal omega-3 enriched diet for adult brain function and reveal a new pathway important for nerve growth factor regulation.

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.

Despite its undisputable role in the homeostatic regulation of the nervous system, the nerve growth factor (NGF) also governs the relevant cellular processes in other tissues and organs. In this study, we aimed at assessing the expression and the putative involvement of NGF signaling in skeletal muscle physiology. To reach this objective, we employed satellite cell-derived myoblasts as an in vitro culture model. In vivo experiments were performed on Tibialis anterior from wild-type mice and an mdx mouse model of Duchenne muscular dystrophy. Targets of interest were mainly assessed by means of morphological, Western blot and qRT-PCR analysis. The results show that proNGF is involved in myogenic differentiation. Importantly, the proNGF/p75NTR pathway orchestrates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain and that of oxidative markers. Concurrently, proNGF/p75NTR activation facilitates the induction of fast myosin heavy chain and of fast/glycolytic markers. Furthermore, we also provided evidence that the oxidative metabolism is impaired in mdx mice, and that these alterations are paralleled by a prominent buildup of proNGF and p75NTR. These findings underline that the proNGF/p75NTR pathway may play a crucial role in fiber type determination and suggest its prospective modulation as an innovative therapeutic approach to counteract muscle disorders.

Scope Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, the aim is to evaluate whether a diet rich in fat and fructose affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers of beta amyloid metabolism. Methods and results Middle aged rats are fed a high fat-high fructose (HFF) or a control diet for 4 weeks. Inflammatory markers and cholesterol levels significantly increase in hippocampus of HFF rats. A higher activation of 3-hydroxy 3-methylglutaryl coenzyme-A reductase, coupled with lower levels of apolipoprotein E, LXR-beta, and lipoproteins receptors is measured in hippocampus from HFF rats. The alteration of critical players of cholesterol homeostasis is associated with increased level of amyloid precursor protein, presenilin 1, and nicastrin, and decreased level of insulin degrading enzyme. Conclusions Overall these data show that a western diet is associated with perturbation of cholesterol homeostasis in middle aged rats, mostly in hippocampus. This might trigger molecular events involved in the onset of neurodegenerative diseases.

International audience; The mevalonate (MVA)/cholesterol pathway is crucial for central nervous system (CNS) development and function and consequently, any dysfunction of this fundamental metabolic pathway is likely to provoke pathologic changes in the brain. Mutations in genes directly involved in MVA/cholesterol metabolism cause a range of diseases, many of which present neurologic and psychiatric symptoms. This raises the question whether other diseases presenting similar symptoms are related albeit indirectly to the MVA/cholesterol pathway. Here, we summarized the current literature suggesting links between MVA/cholesterol dysregulation and specific diseases, namely autism spectrum disorder and Rett syndrome.

Highlights • In general surgery locoregional anaesthesia increased laparoscopy advantages. • 28 women submitted to gynaecological laparoscopy for benign adnexal conditions. • 13 patients under spinal anaesthesia, 15 under general anaesthesia. • Less postoperative pain and reduced need f opioids in the spinal anaesthesia arm. • Earlier mobilization and return of bowel function in the spinal anaesthesia arm., Background Laparoscopic gynaecological surgery is commonly performed under general anaesthesia with endotracheal intubation. In general surgery, locoregional anaesthesia was applied to laparoscopic procedures, increasing minimally invasive surgery advantages. Aims To assess and compare postoperative pain after laparoscopic adnexal procedures for benign conditions under spinal anaesthesia (SA) versus general anaesthesia (GA). Furthermore, anaesthesiologic, surgical and clinical data were evaluated in both groups. Materials and Methods This is a prospective cohort study performed in a tertiary level referral centre for minimally invasive gynaecological surgery (Gynaecology and Human Reproduction Physiopathology, University of Bologna). Women scheduled for adnexal laparoscopic surgery for benign conditions between February and May 2019 were assigned to receive either SA or GA with endotracheal intubation. A sample size of 13 women per group was needed to detect a 2-point difference in pain scores. Main findings 13 women were enrolled in the SA arm, 15 in the GA arm. In the SA cohort, the most common intraoperative adverse event was shoulder pain, reported by 3/12 women. At 1, 8, 12, 24 and 48 h after surgery pain was significantly lower in the SA arm (p < .05). Patients submitted to SA experienced no need for opioid drugs administration, unlike those receiving GA. Patients’ mobilization and return of bowel function were noted significantly earlier in the SA group (p < .05). Conclusions SA is a feasible, safe and effective anaesthesiologic technique for laparoscopic gynaecological procedures for benign conditions, allowing a better control of postoperative pain. Women undergoing SA achieve earlier mobilization and bowel canalization. During the Covid-19 pandemics, SA could be useful in reducing the need for invasive procedures on respiratory tract.