Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Quantificação volumétrica da hiperplasia neointimal em artérias ilíacas após implante de suporte intravascular metálico

OBJETIVO: Quantificar a hiperplasia neointimal em artérias ilíacas após stent, correlacionando fatores clínicos, arteriais e materiais dos stents. MATERIAIS E MÉTODOS: De junho de 2003 a agosto de 2005, 60 pacientes realizaram angioplastia transluminal percutânea e stent. Desses, 30 foram reestudados com ultrassonografia intravascular. Os dados foram analisados no laboratório de análise quantitativa. RESULTA-DOS: Dezesseis pacientes eram do sexo masculino (53,3%) e 14 (46,7%), do sexo feminino. A média de idade foi de 60,3 anos. Apresentaram hipertensão arterial 22 pacientes (73,3%), tabagismo, 18 (62,1%), hiperlipidemia, 20 (66,7%), e diabetes, 9 (30%). Foram implantados 20 stents de nitinol (66,7%) e 10 de aço inoxidável (33,3%). Quatro pacientes eram TASC A (13,3%), 15 eram TASC B (50%) e 11, TASC C (36,7%). O volume da hiperplasia variou de 49,02 mm³ a 112,87 mm³ (média de 80,33 mm³). O percentual de obstrução intra-stent variou de 18% a 47% (média de 27,4%). Os resultados clínicos obtidos com stent se mantiveram até o reestudo. CONCLUSÃO: A hiperplasia neointimal sempre ocorre após a angioplastia transluminal percutânea e stent, porém os percentuais de obstrução não foram superiores a 50% em nenhum caso. Não houve diferença estatisticamente significante dos percentuais de obstrução intra-stent quanto aos materiais dos stents, aos fatores clínicos e aos fatores arteriais.

Utilização do índice de resistência vascular na diferenciação entre nódulos mamários benignos e malignos

OBJETIVO: O objetivo deste estudo foi avaliar o significado do Doppler espectral por meio da obtenção do índice de resistência vascular na diferenciação entre lesões mamárias benignas e malignas. MATERIAIS E MÉTODOS: Dezenove lesões malignas e 18 benignas, diagnosticadas por estudo histológico, foram submetidas previamente a análise de sua vascularização por meio do Doppler espectral para se obter o índice de resistência vascular. RESULTADOS: Observou-se diferença estatisticamente significante (p < 0,001) entre os valores médios do índice de resistência para os resultados benigno e maligno (0,62x 0,80, respectivamente), em nódulos maiores que 1 cm. Um índice de resistência 0,69 foi altamente associado a lesões malignas, com sensibilidade de 84,2%, especificidade de 88,9%, taxa de falso-positivo de 11,1% e taxa de falso-negativo de 15,8%. CONCLUSÃO: A análise do índice de resistência vascular pode fornecer grande auxílio na avaliação das lesões nodulares da mama maiores que 1 cm, em conjunto com as informações obtidas por meio da escala de cinzas, com elevada sensibilidade e especificidade.

Pathologies vasculaires lymphatiques: apport de la lympho-fluoroscopie [Lymphatic vascular pathologies: contribution of lympho-fluoroscopy].

Si l'examen clinique revêt une importance essentielle en lymphologie et exige des praticiens expérimentés, la lymphoscintigraphie et plus récemment la lympho-fluoroscopie au vert d'indocyanine constituent des moyens d'investigation précieux dans la prévention, le diagnostic et le traitement des pathologies vasculaires lymphatiques. L'intérêt de la lymphoscintigraphie réside dans l'analyse qualitative et quantitative de la migration des macromolécules par les vaisseaux lymphatiques et l'évaluation du secteur lymphatique profond. La lympho-fluoroscopie se distingue de la lymphoscintigraphie par l'obtention d'une cartographie détaillée des vaisseaux lymphatiques superficiels et d'images dynamiques en temps réel. Elle apporte à l'angiologue et au physiothérapeute des informations irremplaçables sur leur contractilité et la présence de dérivations compensatoires à privilégier lors du drainage lymphatique manuel. If clinical examination has an essential importance in lymphology disorders and requires experimented practitioners, lymphoscintigraphy and more recently green indocyanine lympho-fluoroscopy constitute precious complementary investigations in prevention, diagnosis, and treatment of lymphatic vascular pathologies. The lymphoscintigraphy interest lies in qualitative and quantitative analysis of macromolecules migration within lymphatic vessels and the deep lymphatic network. The lympho-fluoroscopy distinguishes itself from lymphoscintigraphy allowing real time superficial lymphatic vessels detailed mapping, gathering important information on their contractility, and the presence of compensatory derivations to be favored during manual lymphatic drainage to angiologist and physiotherapist.

Secondary growth of the Arabidopsis hypocotyl-vascular development in dimensions.

The secondary thickening of plant organs in extant dicotyledons is a massive growth process that constitutes the major carbon sink in perennial, woody plants. Yet, our understanding of its molecular genetic control has been mostly obtained by its analysis in an herbaceous annual model, Arabidopsis. Recent years have seen increased interest in this somewhat under-researched topic, and various (non-)cell autonomous factors that guide the extent and vascular patterning of secondary growth have been identified. Concomitantly, a more detailed understanding of vascular differentiation processes has been obtained through analyses of primary growth, mostly in the root meristem. A future challenge will be the integration of these patterning and differentiation modules together with cambial activity into the 4-dimensional frame of secondary thickening.

The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells

AIMS: Mitofusin-2 (Mfn2) expression is dysregulated in vascular proliferative disorders and its overexpression attenuates the proliferation of vascular smooth muscle cells (VSMCs) and neointimal lesion development after balloon angioplasty. We sought to gain insight into the mechanisms that control Mfn2 expression in VSMCs. METHODS AND RESULTS: We cloned and characterized 2 kb of the 5'-flanking region of the human Mfn2 gene. Its TATA-less promoter contains a CpG island. In keeping with this, 5'-rapid amplification of cDNA ends revealed six transcriptional start sites (TSSs), of which TSS2 and TSS5 were the most frequently used. The strong CpG island was found to be non-methylated under conditions characterized by large differences in Mfn2 gene expression. The proximal Mfn2 promoter contains six putative Sp1 motifs. Sp1 binds to the Mfn2 promoter and its overexpression activates the Mfn2 promoter in VSMCs. Chemical inhibition of Sp1 reduced Mfn2 expression, and Sp1 silencing reduced transcriptional activity of the Mfn2 promoter. In keeping with this view, Sp1 and Mfn2 mRNA levels were down-regulated in the aorta early after an atherogenic diet in apolipoprotein E-knockout mice or in VSMCs cultured in the presence of low serum. CONCLUSION: Sp1 is a key factor in maintaining basal Mfn2 transcription in VSMCs. Given the anti-proliferative actions of Mfn2, Sp1-induced Mfn2 transcription may represent a mechanism for prevention of VSMC proliferation and neointimal lesion and development.

The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells

AIMS: Mitofusin-2 (Mfn2) expression is dysregulated in vascular proliferative disorders and its overexpression attenuates the proliferation of vascular smooth muscle cells (VSMCs) and neointimal lesion development after balloon angioplasty. We sought to gain insight into the mechanisms that control Mfn2 expression in VSMCs. METHODS AND RESULTS: We cloned and characterized 2 kb of the 5'-flanking region of the human Mfn2 gene. Its TATA-less promoter contains a CpG island. In keeping with this, 5'-rapid amplification of cDNA ends revealed six transcriptional start sites (TSSs), of which TSS2 and TSS5 were the most frequently used. The strong CpG island was found to be non-methylated under conditions characterized by large differences in Mfn2 gene expression. The proximal Mfn2 promoter contains six putative Sp1 motifs. Sp1 binds to the Mfn2 promoter and its overexpression activates the Mfn2 promoter in VSMCs. Chemical inhibition of Sp1 reduced Mfn2 expression, and Sp1 silencing reduced transcriptional activity of the Mfn2 promoter. In keeping with this view, Sp1 and Mfn2 mRNA levels were down-regulated in the aorta early after an atherogenic diet in apolipoprotein E-knockout mice or in VSMCs cultured in the presence of low serum. CONCLUSION: Sp1 is a key factor in maintaining basal Mfn2 transcription in VSMCs. Given the anti-proliferative actions of Mfn2, Sp1-induced Mfn2 transcription may represent a mechanism for prevention of VSMC proliferation and neointimal lesion and development.

Notes breus (flora). Addicions i anotacions a la flora vascular de les illes Medes

Nota breu de flora relacionada amb la localització a les Illes Medes, d'una sèrie de tàxons que no figuren en el catàleg florístic de Bolòs & Vigo (1984)

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Corologia de la flora vascular d'interès de conservació al Parc Natural del Montseny

Presentem els resultats dels estudis realitzats des del 2009 al 2012, amb la finalitat de millorar la informació corològica disponibled'espècies de flora vascular considerades d'interès de conservació al Parc Natural del Montseny. S'han tingut en compte un total de 125tàxons. D'aquests, 3 corresponen a tàxons nous per la flora del massís (Aconitum vulparia, Botrychium matricariifolium i Polystichumlonchitis), 7 han estat retrobats i 13 corresponen a novetats per algun dels quadrats UTM 10 × 10 prospectats. Tot i les troballes, moltesespècies no han sigut localitzades durant el treball de camp. En alguns casos, atribuïm aquest fet a la reducció de les poblacions o fins i tota la desaparició, fet que afecta principalment a aquelles espècies vinculades majoritàriament a ambients oberts, que han patit una recessióimportant durant les darreres dècades. Aquest fenomen ha estat especialment rellevant al massís del turó de l'Home, sobretot a la vall deSanta Fe

Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Microestrutura e resistência à corrosão do Ti c.p. soldado a laser utilizando em prótese sobre implantes

Foram realizados estudos para avaliar a microestrutura, a dureza e a resistência à corrosão do titânio comercialmente puro-Ti c.p. soldado por laser e utilizado na confecção de prótese sobre implantes. Verificou-se que na soldagem a laser a microestrutura apresentou três regiões distintas: o cordão de solda, a zona afetada pelo calor - ZAC e o metal base. O Ti c.p. possui microestrutura granular, a microestrutura do cordão de solda é mais refinada e de maior dureza do que o metal base. A ZAC obtida por este processo de soldagem foi relativamente pequena quando comparada com o processo de soldagem por brasagem. Os ensaios eletroquímicos mostraram que a região da solda apresentou menor resistência à corrosão em meio de NaCl 0,15 molL-1 à temperatura ambiente.

Estudo microestrutural e resistência à corrosão de uma liga de Au soldada a laser, empregada em prótese sobre implantes

Investigou-se o comportamento de juntas soldadas de uma liga a base de ouro utilizada na confecção de próteses odontológicas sobre implantes antes e após ser submetida ao processo de soldagem a laser. Constatou-se que houve uma mudança estrutural na região da solda e esta apresentou uma microestrutura dendrítica refinada e o metal base uma microestrutura granular bifásica com maior dureza e presença de precipitados de Au. Os ensaios eletroquímicos, em meio aerado de NaCl 0,15 molL-1 à temperatura ambiente, que simula as condições do ambiente oral, demonstraram que a junta soldada apresentou melhor desempenho frente à corrosão quando comparada ao metal base; provavelmente devida a estrutura metalúrgica desta região.