Magnetic Resonance Imaging of Atherosclerotic Manifestations in Familial Hypercholesterolemia

Cardiovascular diseases (CVD) are, in developed countries, the leading cause of mortality. The majority of premature deaths and disability caused by CVD are due to atherosclerosis, a degenerating inflammatory disease affecting arterial walls. Early identification of lesions and initiation of treatment is crucial because the first manifestations quite often are major disabling cardiovascular events. Methods of finding individuals at high risk for these events are under development. Because magnetic resonance imaging (MRI) is an excellent non-invasive tool to study the structure and function of vascular system, we sought to discover whether existing MRI methods are able to show any difference in aortic and intracranial atherosclerotic lesions between patients at high risk for atherosclerosis and healthy controls. Our younger group (age 6-48) comprised 39 symptomless familial hypercholesterolemia (FH) patients and 25 healthy controls. Our older group (age 48-64) comprised 19 FH patients and 18 type 2 diabetes mellitus (DM) patients with coronary heart disease (CHD) and 29 healthy controls. Intracranial and aortic MRI was compared with carotid and femoral ultrasound (US). In neither age-group did MRI reveal any difference in the number of ischemic brain lesions or white matter hyperintensities (WMHIs) - possible signs of intracranial atherosclerosis - between patients and controls. Furthermore, MRI showed no difference in the structure or function of the aorta between FH patients and controls in either group. DM patients had lower compliance of the aorta than did controls, while no difference appeared between DM and FH patients. However, ultrasound showed greater plaque burden and increased thickness of carotid arterial walls in FH and DM patients in both age-groups, suggesting a more advanced atherosclerosis. The mortality of FH patients has decreased substantially after the late 1980´s when statin treatment became available. With statins, the progression of atherosclerotic lesions slows. We think that this, in concert with improvements in treatment of other risk factors, is one reason for the lack of differences between FH patients and controls in MRI measurements of the aorta and brain despite the more advanced disease of the carotid arteries assessed with US. Furthermore, whereas atherosclerotic lesions between different vascular territories correlate, differences might still exist in the extent and location of these lesions among different diseases. Small (<5 mm in diameter) WMHIs are more likely a phenomenon related to aging, but the larger ones may be the ones related to CVD and may be intermediate surrogates of stroke. The image quality in aortic imaging, although constantly improving, is not yet optimal and thus is a source of bias.

Wave propagation in a micropolar fluid contained in a visco-elastic membrane

The aim of the paper is to investigate the propagation of a pulse in a micropolar fluid contained in a visco-elastic membrane. It was undertaken with a view to study how closely we can approximate the flow of blood in arteries by the above model. We find that for large Reynolds number, the effect of micropolarity is hardly perceptible, whereas for small Reynolds numbers it is of considerable importance.

Cyclin dependent protein kinases as drug targets – potential in cardiovascular diseases

Complications of atherosclerosis such as myocardial infarction and stroke are the primary cause of death in Western societies. The development of atherosclerotic lesions is a complex process, including endothelial cell dysfunction, inflammation, extracellular matrix alteration and vascular smooth muscle cell (VSMC) proliferation and migration. Various cell cycle regulatory proteins control VSMC proliferation. Protein kinases called cyclin dependent kinases (CDKs) play a major role in regulation of cell cycle progression. At specific phases of the cell cycle, CDKs pair with cyclins to become catalytically active and phosphorylate numerous substrates contributing to cell cycle progression. CDKs are also regulated by cyclin dependent kinase inhibitors, activating and inhibitory phosphorylation, proteolysis and transcription factors. This tight regulation of cell cycle is essential; thus its deregulation is connected to the development of cancer and other proliferative disorders such as atherosclerosis and restenosis as well as neurodegenerative diseases. Proteins of the cell cycle provide potential and attractive targets for drug development. Consequently, various low molecular weight CDK inhibitors have been identified and are in clinical development. Tylophorine is a phenanthroindolizidine alkaloid, which has been shown to inhibit the growth of several human cancer cell lines. It was used in Ayurvedic medicine to treat inflammatory disorders. The aim of this study was to investigate the effect of tylophorine on human umbilical vein smooth muscle cell (HUVSMC) proliferation, cell cycle progression and the expression of various cell cycle regulatory proteins in order to confirm the findings made with tylophorine in rat cells. We used several methods to determine our hypothesis, including cell proliferation assay, western blot and flow cytometric cell cycle distribution analysis. We demonstrated by cell proliferation assay that tylophorine inhibits HUVSMC proliferation dose-dependently with an IC50 value of 164 nM ± 50. Western blot analysis was used to determine the effect of tylophorine on expression of cell cycle regulatory proteins. Tylophorine downregulates cyclin D1 and p21 expression levels. The results of tylophorine’s effect on phosphorylation sites of p53 were not consistent. More sensitive methods are required in order to completely determine this effect. We used flow cytometric cell cycle analysis to investigate whether tylophorine interferes with cell cycle progression and arrests cells in a specific cell cycle phase. Tylophorine was shown to induce the accumulation of asynchronized HUVSMCs in S phase. Tylophorine has a significant effect on cell cycle, but its role as cell cycle regulator in treatment of vascular proliferative diseases and cancer requires more experiments in vitro and in vivo.

Mother-Infant Antibodies to Pneumococcal Polysaccharides and Proteins : Transfer and Persistence of Maternal Antibodies and Development of Vaccine-Induced and Naturally Acquired Antibodies in Infants

Symptomless nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is very common in young children. Occasionally the carriage proceeds into mild mucosal diseases, such as sinusitis or acute otitis media, or into serious life-threatening diseases, such as pneumonia, sepsis or meningitis. Each year, up to one million children less than five years of age worldwide die of invasive pneumococcal diseases (IPD). Especially in the low-income countries IPD is a leading health problem in infants; 75% of all IPD cases occur before one year of age. This stresses the need of increased protection against pneumococcus in infancy. Anti-pneumococcal antibodies form an important component in the defence against pneumococcal infection. Maternal immunisation and early infant immunisation are two possible ways by which potentially protective antibody concentrations against pneumococci could be achieved in early infancy. The aim of this thesis is to increase the knowledge of antibody mediated protection against pneumococcal disease in infants and young children. We investigated the transfer of maternal anti-pneumococcal antibodies from Filipino mothers to their infants, the persistence of the transferred antibodies in the infants, the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPV) in infants and the response of the children to a second dose of PPV at three years of age. We also investigated the development of antibodies to pneumococcal protein antigens in relation to culture-confirmed pneumococcal carriage in infants. Serum samples were collected from the mothers, the umbilical cords and from the infants at young age as well as at three years of age. The samples were used to determine the antibody concentrations to pneumococcal serotypes 1, 5, 6B, 14, 18C and 19F, as well as to the pneumococcal proteins PspA, PsaA, Ply, PspC, PhtD, PhtDC and LytC by the enzyme immunoassay. The findings of the present study confirm previously obtained results and add to the global knowledge of responses to PPV in young children. Immunising pregnant women with PPV provides the infants with increased concentrations of pneumococcal polysaccharide antibodies. Of the six serotypes examined, serotypes 1 and 5 were immunogenic already in infants. At three years of age, the children responded well to the second dose of PPV suggesting that maternal and early infant immunisations might not induce hyporesponsiveness to polysaccharide antigens after subsequent immunisations. The anti-protein antibody findings provide useful information for the development of pneumococcal protein vaccines. All six proteins studied were immunogenic in infancy and the development of anti-protein antibodies started early in life in relation to pneumococcal carriage.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

Sydämen hypertrofian ja kroonisen vajaatoiminnan farmakologinen hoito

Sydämen krooninen vajaatoiminta on merkittävä maailmanlaajuinen ongelma. Se on erilaisten sydän- ja verisuonisairauksien aiheuttama monimuotoinen oireyhtymä. Sydämen vasemman kammion hypertrofia eli sydämen seinämien paksuuntuminen on yksi keskeinen tekijä, joka voi olla sydämen vajaatoiminnan taustalla. Kohonnut verenpaine on yleisin syy, joka johtaa sydänlihaksen paksuuntumiseen. Tämä johtaa sydämen pumppaustoiminnan häiriintymiseen, erilaisten neurohormonaalisten mekanismien aktivaatioon ja edelleen sydämen vajaatoimintaan. Sydämen vajaatoiminnan neurohormonaalisista mekanismeista tärkeimmät ovat reniini-angiotensiini-aldosteroni-järjestelmän ja sympaattisen hermoston aktivaatio, sydämen rakenteiden uudelleenmuovautuminen, sydänlihassolujen apoptoosi ja systeeminen tulehdustila. Sydämen hypertrofiaa ja sen syntymistä pyritään estämään kohonneen verenpaineen lääkehoidolla. Reniini-angiotensiini-aldosteronijärjestelmällä on keskeinen merkitys sydämen vajaatoiminnassa. Sydämen vajaatoiminnan ennusteeseen vaikuttavista lääkeaineista angiotensiinikonvertasin estäjät (ACEestäjät) ovat säilyttäneet johtoasemansa jo vuosikymmenten ajan. Angiotensiinireseptoreiden salpaajien (AT1-salpaajien) odotettiin syrjäyttävän ACE-estäjät sydämen vajaatoiminnan hoidossa, mutta toistaiseksi niitä pidetään vain vaihtoehtoisina lääkkeinä. Sympaattisen hermoston aktivaatiota vähentävät β-salpaajat ovat vakiinnuttaneet asemansa toiseksi tärkeimpänä lääkeryhmänä. Diureetit ovat paljon käytetty lääkeaineryhmä sydämen vajaatoiminnan hoidossa, mutta niistä ainoastaan aldosteroniantagonisteilla on tutkitusti ennustetta parantavaa vaikutusta. Kroonisen vajaatoiminnan hoidossa käytetään edelleen myös digoksiinia. Tulevaisuudessa sydämen vajaatoiminnan ennusteeseen vaikuttavia lääkeaineita voivat olla reniinin estäjät, neutraaliendopeptidaasin estäjät, vasopressiinin antagonistit tai inflammatroisiin sytokiineihin vaikuttavat molekyylit. Erikoistyön kokeellisessa osiossa tarkoituksena oli tutkia sydämen hypertrofian kehittymistä vatsa-aortta kuristetuilla rotilla ja kalsiumherkistäjä levosimendaanin sekä AT1-salpaaja valsartaanin vaikutuksia hypertrofian kehittymiseen. Kokeellisessa osiossa arvioitiin myös sydämen hypertrofian ja vajaatoiminnan jyrsijämallina käytetyn vatsa-aortan kuristuksen (koarktaation) toimivuutta ja vaikutuksia ultraäänen avulla määritettyihin kardiovaskulaarisiin parametreihin. Vatsa-aortta kuristettiin munuaisvaltimoiden yläpuolelta. Kuristus saa aikaan verenpaineen kohoamisen ja sydämen työtaakan lisääntymisen. Pitkittyessään tila johtaa sydänlihaksen hypertrofiaan ja vajaatoimintaan. 64 eläintä jaettiin ryhmiin, siten että jokaiseen ryhmään tuli kahdeksan eläintä. Ryhmistä kolmelle annettiin lääkeaineena levosimendaania kolmella eri päiväannoksella (0,01 mg/kg; 0,10 mg/kg; 1,00 mg/kg) ja kolmelle valsartaania kolmella eri päiväannoksella (0,10 mg/kg; 1,00 mg/kg; 10,00 mg/kg) juomaveden mukana. Lääkitys aloitettiin leikkauksen jälkeen ja jatkettiin kahdeksan viikon ajan. Kardiovaskulaariset parametrit, kuten isovolumetrinen relaksaatioaika (IVRT), vasemman kammion läpimitta systolessa ja diastolessa sekä seinämäpaksuudet, ejektiofraktio (EF), supistuvuusosuus (FS), minuuttitilavuus (CO) ja iskutilavuus (SV) määritettiin kahdeksan viikon kuluttua leikkauksesta ultraäänitutkimuksen avulla. Lisäksi määritettiin eläinten sydämen paino suhteessa ruumiin painoon. Tuloksia verrattiin ilman lääkehoitoa olleeseen koarktaatioryhmään. Eläinmallin toimivuutta arvioitiin vertaamalla koarktaatioryhmän tuloksia sham-operoidun ryhmän tuloksiin. Levosimendaanilla havaittiin työssä sydämen systolista toimintaa parantava vaikutus. Tämä näkyi tendenssinä parantaa ejektiofraktioita ja vasemman kammion supistuvuusosuuksia. Sydämen diastoliseen toimintaan ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Diastolista toimintaa arvioitiin isovolumetrisen relaksaatioajan muutoksilla. Sydämen hypertrofian kehittymiseen ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Eläinmallin todettiin mallintavan hyvin sydämen hypetrofiaa ihmisellä, mutta ei niinkään sydämen vajaatoimintaa.

Vasomodulatory effect of novel peroxovanadate compounds on rat aorta: Role of rho kinase and nitric oxide/cGMP pathway

The present study was undertaken to assess the role of reactive oxygen species (ROS) in rat aortic ring vasoreactivity and integrity by using various peroxovanadate (pV) compounds. All the pV compounds (1 nM-300 mu M) used in the present study exerted concentration-dependent contractions on endothelium intact rat aortic rings. All compounds with an exception of DPV-asparagine (DPV-asn) significantly altered vascular integrity as shown by diminished KCl responses. Phenylephrine (PE)-mediated contractions (3 nM-300 mu M) were unaltered in the presence of these compounds. Acetylcholine (Ach)-mediated relaxation in PE (1 mu M) pre-contracted rings was significantly reduced in presence of diperoxovanadate (DPV), poly (sodium styrene sulfonate-co-maleate)-pV (PSS-CoM-pV) and poly (sodium styrene 4-sulfonate)-pV (PSS-pV). However, no significant change in Ach-mediated responses was observed in the presence of poly (acrylate)-pV (PM-pV) and DPV-asn. DPV-asn was thus chosen to further elucidate mechanism involved in peroxide mediated modulation of vasoreactivity. DPV-asn (30 nM-300 mu M) exerted significantly more stable contractions, that was found to be catalase (100 U/ml) resistant in comparison with H(2)O(2) (30 nM-300 mu M) in endothelium intact aortic rings. These contractile responses were found to be dependent on extracellular Ca(2+) and were significantly inhibited in presence of ROS scavenger N-acetylcysteine (100 mu M). Intracellular calcium chelation by BAPTA-AM (10 mu M) had no significant effect on DPV-asn (30 nM-300 mu M) mediated contraction. Pretreatment of aortic rings by rho-kinase inhibitor Y-27632 (10 mu M) significantly inhibited DPV-asn-mediated vasoconstriction indicating role of voltage-dependent Ca(2+) influx and downstream activation of rho-kinase. The small initial relaxant effect obtained on addition of DPV-asn (30 nM-1 mu M) in PE (1 mu M) pre-contracted endothelium intact rings, was prevented in the presence of guanylate cyclase inhibitor, methylene blue (10 mu M) and/or nitric oxide synthase (NOS) inhibitor, L-NAME (100 mu M) suggesting involvement of nitric oxide and cGMP. DPV-asn, like H(2)O(2), exerted a response of vasoconstriction in normal arteries and vasodilation at low concentrations (30 nM-1 mu M) in PE-pre contracted rings with overlapping mechanisms. These findings suggest usefulness of DPV-asn having low toxicity, in exploring the peroxide-mediated effects on various vascular beds. The present study also convincingly demonstrates role of H(2)O(2) in the modulation of vasoreactivity by using stable peroxide DPV-asn and warrants future studies on peroxide mediated signaling from a newer perspective. (C) 2011 Published by Elsevier Ltd.

Neuroprotective activity of Wedelia calendulacea on cerebral ischemia/reperfusion induced oxidative stress in rats

Objective: This study was undertaken to evaluate the neuroprotective activity of Wedelia calendulacea against cerebral ischemia/reperfusion induced oxidative stress in the rats. Materials and Methods: The global cerebral ischemia was induced in male albino Wistar rats by occluding the bilateral carotid arteries for 30 min followed by 1 h and 4 h reperfusion. At various times of reperfusion, the histopathological changes and the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and hydrogen peroxide (H(2)O(2)) activity and brain water content were measured. Results: The ischemic changes were preceded by increase in concentration of MDA, hydrogen peroxide and followed by decreased GPx, GR, and GST activity. Treatment with W. calendulacea significantly attenuated ischemia-induced oxidative stress. W. calendulacea administration markedly reversed and restored to near normal level in the groups pre-treated with methanolic extract (250 and 500 mg/kg, given orally in single and double dose/day for 10 days) in dose-dependent way. Similarly, W. calendulacea reversed the brain water content in the ischemia reperfusion animals. The neurodegenaration also conformed by the histopathological changes in the cerebral-ischemic animals. Conclusion: The findings from the present investigation reveal that W. calendulacea protects neurons from global cerebral-ischemic injury in rat by attenuating oxidative stress.

Cerebroprotective activity of Wedelia calendulacea on global cerebral ischemia in rats

The present study was to investigate the effect of W. calendulacea on ischemia and reperfusion-induced cerebral injury. Cerebral ischemia was induced by occluding right and left common carotid arteries (global cerebral ischemia) for 30 min followed by reperfusion for 1 h and 4 h individually. Various biochemical alterations, produced subsequent to the application of bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO), hydrogen peroxide (H(2)O(2)), and decrease in reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), level in the brain tissue, Western blot analysis (Cu-Zn-SOD and CAT) and assessment of cerebral infarct size were measured. All those enzymes are markedly reversed and restored to near normal level in the groups pre-treated with W. calendulacea (250 and 500 mg/kg given orally in single and double dose/day for 10 days) in dose-dependent way. The effect of W. calendulacea had increased significantly the protein expression of copper/zinc superoxide dismutase (Cu-Zn-SOD) and CAT in cerebral ischemia. W. claendulacea was markedly decrease cerebral infarct damages but results are not statistically significant. It can be concluded that W. calendulacea possesses a neuroprotective activity against cerebral ischemia in rat.

Macromolecular Transport Through Porous Arterial Walls

Arteries are heterogeneous, composite structures that undergo large cyclic deformations during blood transport. Presence, build-up and consequent rupture of blockages in blood vessels, called atherosclerotic plaques, lead to disruption in the blood flow that can eventually be fatal. Abnormal lipid profile and hypertension are the main risk factors for plaque progression. Treatments span from pharmacological methods, to minimally invasive balloon angioplasty and stent procedures, and finally to surgical alternatives. There is a need to understand arterial disease progression and devise methods to detect, control, treat and manage arterial disease through early intervention. Local delivery through drug eluting stents also provide an attractive option for maintaining vessel integrity and restoring blood flow while releasing controlled amount of drug to reduce and alleviate symptoms. Development of drug eluting stents is hence interesting albeit challenging because it requires an integration of knowledge of mechanical properties with material transport of drug through the arterial wall to produce a desired biochemical effect. Although experimental models are useful in studying such complex multivariate phenomena, numerical models of mass transport in the vessel have proved immensely useful to understand and delineate complex interactions between chemical species, physical parameters and biological variables. The goals of this review are to summarize literature based on studies of mass transport involving low density lipoproteins in the arterial wall. We also discuss numerical models of drug elution from stents in layered and porous arterial walls that provide a unique platform that can be exploited for the design of novel drug eluting stents.

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis

Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled 48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NF kappa B pathway. Ectopic overexpression and silencing experiments revealed that glioma-secreted MCSF has no role in autocrine functions and M2 polarization of macrophages. In contrast, silencing expression of MCSF in glioma cells prevented tube formation of human umbilical vein endothelial cells elicited by the supernatant from monocytes/microglial cells treated with conditioned medium from glioma cells. Quantitative proteomics based on stable isotope labeling by amino acids in cell culture showed that glioma-derived MCSF induces changes in microglial secretome and identified insulin-like growth factor-binding protein 1 (IGFBP1) as one of the MCSF-regulated proteins secreted by microglia. Silencing IGFBP1 expression in microglial cells or its neutralization by an antibody reduced the ability of supernatants derived from microglial cells treated with glioma cell-conditioned medium to induce angiogenesis. In conclusion, this study shows up-regulation of MCSF in GBM via a SYK-PI3K-NF kappa B-dependent mechanism and identifies IGFBP1 released by microglial cells as a novel mediator of MCSF-induced angiogenesis, of potential interest for developing targeted therapy to prevent GBM progression.

The hemodynamic effects of in-tandem carotid artery stenosis: implications for carotid endarterectomy.

OBJECTIVES: It remains controversial whether patients with severe disease of the internal carotid artery and a coexisting stenotic lesion downstream would benefit from a carotid endarterectomy (CEA) of the proximal lesion. The aim of this study was to simulate the hemodynamic and wall shear effects of in-tandem internal carotid artery stenosis using a computational fluid dynamic (CFD) idealized model to give insight into the possible consequences of CEA on these lesions. METHODS: A CFD model of steady viscous flow in a rigid tube with two asymmetric stenoses was introduced to simulate blood flow in arteries with multiple constrictions. The effect of varying the distance between the two stenoses, and the severity of the upstream stenosis on the pressure and wall shear stress (WSS) distributions on the second plaque, was investigated. The influence of the relative positions of the two stenoses was also assessed. RESULTS: The distance between the plaques was found to have minimal influence on the overall hemodynamic effect except for the presence of a zone of low WSS (range -20 to 30 dyne/cm2) adjacent to both lesions when the two stenoses were sufficiently close (<4 times the arterial diameter). The upstream stenosis was protective if it was larger than the downstream stenosis. The relative positions of the stenoses were found to influence the WSS but not the pressure distribution. CONCLUSIONS: The geometry and positions of the lesions need to be considered when considering the hemodynamic effects of an in-tandem stenosis. Low WSS is thought to cause endothelial dysfunction and initiate atheroma formation. The fact that there was a flow recirculation zone with low WSS in between the two stenoses may demonstrate how two closely positioned plaques may merge into one larger lesion. Decision making for CEA may need to take into account the hemodynamic situation when an in-tandem stenosis is found. CFD may aid in the risk stratification of patients with this problem.

Prudentia Iuris, 2007, n° 62-63 (número completo)

Editorial -- Las Segundas Jornadas sobre Ley Natural llevadas a cabo en la Facultad de Derecho de la Pontificia Universidad Católica Argentina -- Presentación y estudio preliminar / Gabriel Limodio -- Habermas / Eduardo Martín Quesada -- Iusnaturalismo vs. iuspositivismo (un alegato iusnaturalista) / Rodolfo L. Vigo -- Derecho Natural y Ciencia Jurídica / Carlos I. Massini Correas -- Ley natural y pluralismo cultural / Félix Adolfo Lamas -- La laicidad del derecho y la Encíclica “Deus caritas est” / Carlos Raúl Sanz -- Universalismo de derechos y asimilacionismo / Juan Cianciardo -- Ley natural y multiculturalismo: verdad y diálogo / Daniel Alejandro Herrera -- La falacia del Particularismo: sobre las condiciones de posibilidad de una Ética Global / Raúl Madrid Ramírez -- Homenaje a la Dra. María Josefa Méndez Costa. Encuentro Interuniversitario de Derecho de Familia. “Familia y Matrimonio hoy” -- Matrimonio y familia / Gabriel Limodio -- Palabras de la homenajeada / María Josefa Méndez Costa -- El concepto jurídico de familia. Matrimonio y familia / Catalina Elsa Arias de Ronchietto -- El principio jurídico de matrimonialidad y las políticas públicas. La familia: cordón umbilical de la humanidad / Catalina Elsa Arias de Ronchietto -- El concepto de familia, su juricidad y la querida profesora María Josefa Méndez Costa. Insinuaciones jurídicas de una tarde inolvidable / Úrsula Basset -- El consentimiento matrimonial sobre la necesidad de que sea prestado por un hombre y una mujer / Eduardo Sambrizzi -- Familia, matrimonio y la legislación sobre educación / Jorge Nicolás Lafferriere -- I Congreso de evangelización de la cultura -- Católicos y vida pública en América Latina / Guzmán M. Carriquiry Lecour -- Nota bibliográfica

Depresión y calcificación en la raíz aórtica y arterias coronarias

Resumen: Se estudia, en adultos de ambos sexos, la asociación entre la depresión y la presencia simultánea de calcificación en las arterias coronarias y la raíz aórtica por un lado, y entre la depresión y la presencia de calcificación coronaria, por otro lado. Estudio transversal. Participaron mayores de 21 años, asintomáticos, sin antecedentes coronarios, que se realizaron una angiotomografía cardíaca por indicación del médico tratante y que fueron evaluados para la depresión. La presencia de calcificación se evaluó mediante angiotomografía cardíaca. La depresión se evaluó mediante un test psicológico. Resultados: 60 adultos, 30 hombres y 30 mujeres, media de 51 ± 5 años. Encontramos una asociación de mayor fortaleza entre la depresión y la calcificación en dos ubicaciones (calcificación coronaria y aórtica) que en un solo lugar (calcificación coronaria). Las personas con calcificación coronaria y aórtica puntuaron más alto en las pruebas de depresión que las personas con calcificación coronaria únicamente. El presente estudio tiene limitaciones debido al tamaño de la muestra y el diseño utilizado. Sin embargo, los resultados sugieren que podría ser interesante estudiar una muestra más grande, con un diseño prospectivo, teniendo en cuenta otras variables intervinientes. Los resultados del presente trabajo confirmaron la presencia simultánea de la depresión y las lesiones ateroscleróticas. Se sugieren dos preguntas: si el tratamiento de la depresión podría modificar el proceso de evolución de las lesiones, y viceversa, y si una intervención terapéutica en ambos (enfermedad aterosclerótica y la depresión), sería más acertada que sólo realizar el tratamiento de la enfermedad aterosclerótica.

A Proteomic Study on Cell Cycle Progression of Endothelium Exposed to Tumor Conditioned Medium and the Possible Role of Cyclin D-1/E

This study was designed to comprehensively analyze the differential expression of proteins from human umbilical vein endothelial cells (HUVECs) exposed to tumor conditioned medium (TCM) and to identify the key regulator in the cell cycle progression. The HUVECs were exposed to TCM from breast carcinoma cell line MDA-MB-231, then their cell cycle distribution was measured by flow cytometer (FCM). The role of protein in cell cycle progression was detected via two-dimensional polyacrylamide gel electrophoresis (2-DE) and western blotting. Following the stimulation of TCM, HUVECs showed a more cells in the S phase than did the negative control group (ECGF-free medium with 20% FBS), but the HUVECs' level was similar to the positive control group (medium with 25 mug/ml ECGF and 20% FBS). Increased expression of cyclin D-1/E and some changes in other related proteins occurred after incubation with TCM. From our results, we can conclude that breast carcinoma cell line MDA-MB-231 may secrete soluble pro-angiogenic factors that induce the HUVEC angiogenic switch, during which the expression of cell cycle regulator cyclin D-1/E increases and related proteins play an important role in this process.