The 844ins68 cystathionine beta-synthase and C677T MTHFR gene polymorphism and the vaso-occlusive event risk in sickle cell disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Calcium hydroxide and a corticosteroid-antibiotic association as dressings in cases of biopulpectomy. A comparative study in dogs' teeth.

The subject of this paper was to study the behavior of the periapical tissues of dogs' teeth after biopulpectomy and dressing with calcium hydroxide or a corticosteroid-antibiotic association, before root canal filling with zinc oxide eugenol (ZOE) or Sealapex sealers. The teeth were overinstrumented and dressed for 7 days before the root canal filling. The animals were sacrificed 180 days after treatment and the specimens were prepared for morphological analysis. Specimens treated with Sealapex presented a higher number of cases with biological closure than ZOE. When the root canals were filled with ZOE, better results were observed with the use of the Ca(OH)2 dressing.

Residual antibacterial activity of chlorhexidine digluconate and camphorated p-monochlorophenol in calcium hydroxide-based root canal dressings

The purpose of this study was to evaluate the residual antibacterial activity of several calcium hydroxide [Ca(OH) 2]-based pastes, placed in root canals of dogs' teeth with induced chronic periapical lesions. Root canals were instrumented with the ProFile rotary system and filled with 4 pastes: G1 (n=16): Ca(OH) 2 paste + anesthetic solution; G2 (n=20): Calen® paste + camphorated pmonochlorophenol (CMCP); G3 (n=18): Calen®; and G4 (n=18): Ca(OH) 2 paste + 2% chlorhexidine digluconate. After 21 days, the pastes were removed with size 60 K-files and placed on Petri plates with agar inoculated with Micrococcus luteus ATCC 9341. Pastes that were not placed into root canals served as control. After pre-diffusion, incubation and optimization, the inhibition zones of bacterial growth were measured and analyzed by Mann-Whitney U test at 5% significance level. All pastes showed residual antibacterial activity. The control samples had larger halos (p<0.05). The mean residual antibacterial activity halos in G1, G2, G3 and G4 were 7.6; 10.4; 17.7 and 21.4 mm, respectively. The zones of bacterial growth of G4 were significantly larger than those of G1 and G2 (p<0.05). In conclusion, regardless of the vehicle and antiseptic, all Ca(OH) 2-based pastes showed different degrees of measurable residual antibacterial activity. Furthermore, unlike CMCP, chlorhexidine increased significantly the antibacterial activity of Ca(OH) 2.

Combining xanthan and chitosan membranes to multipotent mesenchymal stromal cells as bioactive dressings for dermo-epidermal wounds

The association between tridimensional scaffolds to cells of interest has provided excellent perspectives for obtaining viable complex tissues in vitro, such as skin, resulting in impressive advances in the field of tissue engineering applied to regenerative therapies. The use of multipotent mesenchymal stromal cells in the treatment of dermo-epidermal wounds is particularly promising due to several relevant properties of these cells, such as high capacity of proliferation in culture, potential of differentiation in multiple skin cell types, important paracrine and immunomodulatory effects, among others. Membranes of chitosan complexed with xanthan may be potentially useful as scaffolds for multipotent mesenchymal stromal cells, given that they present suitable physico-chemical characteristics and have adequate tridimensional structure for the adhesion, growth, and maintenance of cell function. Therefore, the purpose of this work was to assess the applicability of bioactive dressings associating dense and porous chitosan-xanthan membranes to multipotent mesenchymal stromal cells for the treatment of skin wounds. The membranes showed to be non-mutagenic and allowed efficient adhesion and proliferation of the mesenchymal stromal cells in vitro. In vivo assays performed with mesenchymal stromal cells grown on the surface of the dense membranes showed acceleration of wound healing in Wistar rats, thus indicating that the use of this cell-scaffold association for tissue engineering purposes is feasible and attractive.

Combining xanthan and chitosan membranes to multipotent mesenchymal stromal cells as bioactive dressings for dermo-epidermal wounds

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of intracanal dressings on repair and apical bridging of teeth with incomplete root formation

Periapical repair and apical bridging were studied in dog's teeth with incomplete root formation and induced chronic periapical lesions treated with different dressings. A total of 75 root canals from the upper and lower premolars of 4 dogs approximately 6 months of age were chemo-mechanically prepared and filled with the following dressings: antibacterial dressing consisting of a calcium hydroxide+camphorated p-monochlorophenol paste applied for 7 days and followed by monthly renewed calcium hydroxide paste as temporary dressing at 30, 60 and 90 days (Group A); antibacterial dressing consisting of camphorated p-monochlorophenol alone for 7 days, followed by temporary dressing with calcium hydroxide paste renewed at 30, 60 and 90 days (Group B). A control group (Group C) received no dressings. Ninety days after the last calcium hydroxide paste (Groups A, B) and after the last irrigation/aspiration (Group C), the animals were killed, the maxillae and mandibles were removed, and the material submitted to routine histological processing and examination. Both root canal dressings, were of fundamental importance for apical repair and bridging. The apical bridging was predominantly complete in Group A, incomplete in Group B, and absent in Group C. The calcium hydroxide+camphorated p-monochlorophenol combination gave better results than camphorated p-monochlorophenol alone.

Combining xanthan and chitosan membranes to multipotent mesenchymal stromal cells as bioactive dressings for dermo-epidermal wounds

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Response of mice connective tissue to intracanal dressings containing chlorhexidine

Substances containing chlorhexidine (CHX) have been studied as intracanal medicaments. The aim of the present study was to characterize the response of mouse subcutaneous connective tissue to CHX-containing medications by conventional optical microscopy. The tissue response was evaluated by implanting polyethylene tubes containing one of the substances evaluated: Calen paste + 0.5% CHX, Calen + 2% CHX, 2% CHX gel, and Calen paste (control). After experimental periods of 7, 21, and 63 days, the implants (n = 10) were removed along with the subcutaneous connective tissue. Tissue samples were subjected to histological processing, and sections were stained with hematoxylin and eosin. Qualitative and quantitative analyses of the number of inflammatory cells, blood vessels, and vascularized areas were performed. Results were analyzed by ANOVA and Tukey tests with the significance level set at 5%. We concluded that Calen + 0.5% CHX led to reparative tissue response in contrast with Calen + 2% CHX and 2% CHX gel, which induced persistent inflammatory response, pointing to the aggressive nature of this mixture. When Calen + 2% CHX and 2% CHX gel were compared, the latter induced more intense inflammatory response. Microsc. Res. Tech., 2012. (C) 2012 Wiley Periodicals, Inc.

Endovascular treatment for chronic atherosclerotic occlusive mesenteric disease: is stenting superior to balloon angioplasty?

Endovascular treatment is an increasingly used therapeutic option in patients with chronic atherosclerotic occlusive mesenteric disease. Purpose of this study was evaluation of patency and mortality in patients treated with visceral artery percutaneous transluminal angioplasty (PTA) or stenting including follow-up.

Gene and stem cell therapy in peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is a manifestation of systemic atherosclerosis strongly associated with a high risk of cardiovascular morbidity and mortality. In a considerable proportion of patients with PAOD, revascularization either by endovascular means or by open surgery combined with best possible risk factor modification does not achieve limb salvage or relief of ischaemic rest pain. As a consequence, novel therapeutic strategies have been developed over the last two decades aiming to promote neovascularization and remodelling of collaterals. Gene and stem cell therapy are the main directions for clinical investigation concepts. For both, preclinical studies have shown promising results using a wide variety of genes encoding for growth factors and populations of adult stem cells, respectively. As a consequence, clinical trials have been performed applying gene and stem cell-based concepts. However, it has become apparent that a straightforward translation into humans is not possible. While several trials reported relief of symptoms and functional improvement, other trials did not confirm this early promise of efficacy. Ongoing clinical trials with an improved study design are needed to confirm the potential that gene and cell therapy may have and to prevent the gaps in our scientific knowledge that will jeopardize the establishment of angiogenic therapy as an additional medical treatment of PAOD. This review summarizes the experimental background and presents the current status of clinical applications and future perspectives of the therapeutic use of gene and cell therapy strategies for PAOD.

MR angiography of infrapopliteal arteries in patients with peripheral arterial occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared with selective DSA

To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease.

Influence of hemostatic agents upon the outcome of periapical surgery: dressings with anesthetic and vasoconstrictor or aluminum chloride

OBJECTIVE To evaluate the effects of different hemostatic agents upon the outcome of periapical surgery. DESIGN A retrospective study was made of patients subjected to periapical surgery between 2006-2009 with the ultrasound technique and using MTA as retrograde filler material. We included patients with a minimum follow-up of 12 months, divided into two groups according to the hemostatic agent used: A) dressings impregnated in anesthetic solution with adrenalin; or B) aluminum chloride paste (Expasyl). Radiological controls were made after 6 and 12 months, and on the last visit. The global evolution scale proposed by von Arx and Kurt (1999) was used to establish the outcome of periapical surgery. RESULTS A total of 96 patients (42 males and 54 females) with a mean age of 40.7 years were included. There were 50 patients in the aluminum chloride group and 46 patients in the anesthetic solution with vasoconstrictor group. No significant differences were observed between the two groups in terms of outcome after 12 months - the success rate being 58.6% and 61.7% in the anesthetic solution with vasoconstrictor and aluminum chloride groups, respectively (p > 0.05). CONCLUSION The outcome after 12 months of follow-up was better in the aluminum chloride group than in the anesthetic solution with vasoconstrictor group, though the difference was not significant.

Smooth Muscle Hyperplasia due to ACTA2/MYH11 Mutations: Identification of Novel Pathology and Pathways Leading to Aneurysms and Diverse Vascular Occlusive Diseases

Missense mutations in smooth muscle cell (SMC) specific ACTA2 (á-actin) and MYH11 (â-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs and myofibroblasts were assessed and found to not form á-actin filaments whereas control cells did, suggesting a dominant negative effect of ACTA2 mutations on filament formation. A loss of á-actin filaments would be predicted to cause decreased SMC contractility. Histological examination of vascular tissues from patients revealed SMC hyperplasia leading to arterial stenosis and occlusion, supporting a gain of function associated with the mutant gene. Furthermore, ACTA2 mutant SMCs and myofibroblasts proliferated more rapidly in static culture than control cells (p<0.05). We also determined that Acta2-/- mice have ascending aortic aneurysms. Histological examination revealed aortic medial SMC hyperplasia, but minimal features of medial degeneration. Acta2-/- SMCs proliferated more rapidly in culture than wildtype (p<0.05), and microarray analysis of Acta2-/- SMCs revealed increased expression of Actg2, 15 collagen genes, and multiple focal adhesion genes. Acta2-/- SMCs showed altered localization of vinculin and zyxin and increased phosphorylated focal adhesion kinase (FAK) in focal adhesions. A specific FAK inhibitor decreased Acta2-/- SMC proliferation to levels equal to wildtype SMCs (p<0.05), suggesting that FAK activation leads to the increased proliferation. We have described a unique pathology associated with ACTA2 and MYH11 mutations, as well as an aneurysm phenotype in Acta2-/- mice. Additionally, we identified a novel pathogenic pathway for vascular occlusive disease due to loss of SMC contractile filaments, alterations in focal adhesions, and activation of FAK signaling in SMCs with ACTA2 mutations.

Re: "The enigma of lesion morphology in peripheral arterial occlusive disease".

no abstract available

Non-invasive and non-occlusive blood pressure estimation via a chest sensor

The clinical demand for a device to monitor Blood Pressure (BP) in ambulatory scenarios with minimal use of inflation cuffs is increasing. Based on the so-called Pulse Wave Velocity (PWV) principle, this paper introduces and evaluates a novel concept of BP monitor that can be fully integrated within a chest sensor. After a preliminary calibration, the sensor provides non-occlusive beat-by-beat estimations of Mean Arterial Pressure (MAP) by measuring the Pulse Transit Time (PTT) of arterial pressure pulses travelling from the ascending aorta towards the subcutaneous vasculature of the chest. In a cohort of 15 healthy male subjects, a total of 462 simultaneous readings consisting of reference MAP and chest PTT were acquired. Each subject was recorded at three different days: D, D+3 and D+14. Overall, the implemented protocol induced MAP values to range from 80 ± 6 mmHg in baseline, to 107 ± 9 mmHg during isometric handgrip maneuvers. Agreement between reference and chest-sensor MAP values was tested by using intraclass correlation coefficient (ICC = 0.78) and Bland-Altman analysis (mean error = 0.7 mmHg, standard deviation = 5.1 mmHg). The cumulative percentage of MAP values provided by the chest sensor falling within a range of ±5 mmHg compared to reference MAP readings was of 70%, within ±10 mmHg was of 91%, and within ±15mmHg was of 98%. These results point at the fact that the chest sensor complies with the British Hypertension Society (BHS) requirements of Grade A BP monitors, when applied to MAP readings. Grade A performance was maintained even two weeks after having performed the initial subject-dependent calibration. In conclusion, this paper introduces a sensor and a calibration strategy to perform MAP measurements at the chest. The encouraging performance of the presented technique paves the way towards an ambulatory-compliant, continuous and non-occlusive BP monitoring system.