Hospitalized women experiencing an episode of excessive oral anticoagulation had a higher bleeding risk than men.

OBJECTIVE: Overanticoagulated medical inpatients may be particularly prone to bleeding complications. Among medical inpatients with excessive oral anticoagulation (AC), we sought to identify patient and treatment factors associated with bleeding. METHODS: We prospectively identified consecutive patients receiving oral AC admitted to the medical ward of a university hospital (February-July 2006) who had at least one international normalized ratio (INR) value >3.0 during the hospital stay. We recorded patient characteristics, AC-related factors, and concomitant treatments (e.g., platelet inhibitors) that increase the bleeding risk. The outcome was overall bleeding, defined as the occurrence of major or minor bleeding during the hospital stay. We used logistic regression to explore patient and treatment factors associated with bleeding. RESULTS: Overall, 145 inpatients with excessive oral AC comprised our study sample. Atrial fibrillation (59%) and venous thromboembolism (28%) were the most common indications for AC. Twelve patients (8.3%) experienced a bleeding event. Of these, 8 had major bleeding. Women had a somewhat higher risk of major bleeding than men (12.5% vs 4.1%, p = 0.08). Multivariable analysis demonstrated that female gender was independently associated with bleeding (odds ratio [OR] 4.3, 95% confidence interval [95% C1] 1.1-17.8). Age, history of major bleeding, value of the index INR, and concomitant treatment with platelet inhibitors were not independent predictors of bleeding. CONCLUSIONS: We found that hospitalized women experiencing an episode of excessive oral AC have a 4-fold increased risk of bleeding compared with men. Whether overanticoagulated women require more aggressive measures of AC reversal must be examined in further studies.

In rats, oral oleoyl-DHEA is rapidly hydrolysed and converted to DHEA-sulphate

Background: Dehydroepiandrosterone (DHEA) released by adrenal glands may be converted to androgens and estrogens mainly in the gonadal, adipose, mammary, hepatic and nervous tissue. DHEA is also a key neurosteroid and has antiglucocorticoid activity. DHEA has been used for the treatment of a number of diseases, including obesity; its pharmacological effects depend on large oral doses, which effect rapidly wanes in part because of its short half-life in plasma. Since steroid hormone esters circulate for longer periods, we have studied here whether the administration of DHEA oleoyl ester may extend its pharmacologic availability by keeping high circulating levels. Results: Tritium-labelled oleoyl-DHEA was given to Wistar male and female rats by gastric tube. The kinetics of appearance of the label in plasma was unrelated to sex; the pattern being largely coincident with the levels of DHEA-sulfate only in females, and after 2 h undistinguishable from the results obtained using labelled DHEA gavages; in the short term, practically no lipophilic DHEA label was found in plasma. After 24 h only a small fraction of the label remained in the rat organs, with a different sex-related distribution pattern coincident for oleoyl- and free- DHEA gavages. The rapid conversion of oleoyl-DHEA into circulating DHEA-sulfate was investigated using stomach, liver and intestine homogenates; which hydrolysed oleoyl-DHEA optimally near pH 8. Duodenum and ileum contained the highest esterase activities. Pure hog pancreas cholesterol-esterase broke down oleoyl-DHEA at rates similar to those of oleoyl-cholesterol. The intestinal and liver esterases were differently activated by taurocholate and showed different pH-activity patterns than cholesterol esterase, suggesting that oleoyl-DHEA can be hydrolysed by a number of esterases in the lumen (e.g. cholesterol-esterase), in the intestinal wall and the liver. Conclusion: The esterase activities found may condition the pharmacological availability (and depot effect) of orally administered steroid hormone fatty acid esters such as oleoyl-DHEA. The oral administration of oleoyl-DHEA in order to extend DHEA plasma availability has not been proved effective, since the ester is rapidly hydrolysed, probably in the intestine itself, and mainly converted to DHEA-sulfate at least in females.

Oral pathogens in duwl's: risk of infection and strategies for their control

Water lines are an important source of potentíal contamination. Every dental unit is equipped with small-bore flexible plastic tubing to bring water to different hand pieces, such as the air/water syringe, the ultrasonic scaler or the high-speed hand piece. Most dental units are connected directly to municipal distribution systems for potable water and chlorinated or not, this water contains diverse...

Produção de micropartículas de alginato contendo Flavobacterium columnare inativada pelo método de emulsão para vacinação de peixes por via oral

Alginate microparticles were prepared by an emulsion method aiming oral controlled release of antigens to fish. The effects of emulsification temperature and impeller type on particle morphology, average diameter, and size distribution were evaluated. Microparticles contaning formalin-killed Flavobacterium columnare cells (a model antigen) were prepared and characterized regarding bacterial release and particle stability when exposed to Nile tilapia (Oreochromis niloticus) typical gastrointestinal conditions. This methodology allowed the production of microparticles containing up to 14.3 g/L of bacterin, stable at a pH range from 2.0 to 9.0 for 12 h and smaller than 35 μm.

Expression and distribution of connexin 32 in rat liver with experimentally induced fibrosis

The connexin 32 (Cx32) is a protein that forms the channels that promote the gap junction intercellular communication (GJIC) in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.

Analyse de la distribution des génotypes du virus du papillome humain dans les néoplasies anogénitales et de la tête et du cou en Afrique comparativement au reste du monde

Le virus du papillome humain (HPV) est l’infection sexuellement transmise la plus fréquente au monde. Plusieurs études ont établi son implication dans l’étiologie de pratiquement tous les cancers du col de l’utérus, une maladie qui constitue un problème de santé majeur dans les pays pauvres. Le HPV est également responsable de 90% des cancers de l’anus, 40-50% des cancers du pénis, de la vulve et du vagin, et 30% des cancers de la tête et du cou. L’objectif général de cette thèse est de combler les lacunes relatives aux connaissances sur la distribution génotypique du HPV dans les lésions néoplasiques cervicales utérines et de la tête et du cou, plus particulièrement en Afrique. Les objectifs spécifiques sont les suivants: 1) analyser la distribution génotypique du HPV dans les cancers du col de l’utérus et faire une analyse comparative de cette distribution dans cinq pays africains en fonction de la prévalence du VIH; 2) évaluer la présence du HPV dans les cancers de la tête et du cou au Sénégal; 3) faire une revue de la littérature et une méta-analyse sur la distribution du HPV dans les cancers de la tête et du cou dans toutes les régions du monde. Pour le premier et le second objectifs, qui découlent d’un large projet international coordonné par l’Institut Catalan d’Oncologie pour l’Organisation Mondiale de la Santé (OMS), une étude transversale multicentrique a été menée au Mali et au Sénégal pour collecter des blocs de paraffine de patientes diagnostiquées entre 2001 et 2010 du cancer invasif du col et des cancers de la tête et du cou. Pour le troisième objectif, une revue exhaustive de la littérature a permis d’identifier tous les articles qui ont été publiés sur les cancers de la tête et du cou dans tous les pays du monde et d’effectuer une méta-analyse sur la prévalence de l’ADN du HPV selon le site du cancer et la région géographique. Notre analyse montre que les principaux types de HPV ciblés dans les vaccins prophylactiques (HPV16/18) représentent la majorité des types de HPV détectés dans le cancer invasif du col de l’utérus en Afrique subsaharienne. Par contre, le HPV45 vient au second rang dans certains pays d’Afrique, dont le Mali et le Sénégal. Nos données suggèrent également que le VIH aurait un rôle dans la contribution relative du HPV18 et HPV45 dans le développement du cancer du col de l’utérus. Au Sénégal, notre étude montre que la prévalence du HPV dans les cancers de la tête et du cou est très faible et ne semble pas jouer un rôle important dans l’oncogenèse. Finalement, la méta-analyse a mesuré la prévalence des HPV dans les cancers de la cavité orale, de l’oropharynx, du larynx et de l’hypopharynx, et confirme l’importante contribution relative du HPV16 dans ces cancers. Globalement, cette thèse permet de mieux comprendre l’impact potentiel des vaccins prophylactiques sur l’incidence des cancers associés au HPV.

New grafted PLA-g-PEG polymeric nanoparticles used to improve bioavailability of oral drugs.

Les nanoparticules (NPs) de polymère ont montré des résultats prometteurs pour leur utilisation comme système de transport de médicaments pour une libération contrôlée du médicament, ainsi que pour du ciblage. La biodisponibilité des médicaments administrés oralement pourrait être limitée par un processus de sécrétion intestinale, qui pourrait par la suite être concilié par la glycoprotéine P (P-gp). La dispersion de la Famotidine (modèle de médicament) à l’intérieur des nanoparticules (NPs) pegylées a été évaluée afin d’augmenter la biodisponibilité avec du polyéthylène glycol (PEG), qui est connu comme un inhibiteur de P-gp. L’hypothèse de cette étude est que l’encapsulation de la Famotidine (un substrat de P-gp) à l’intérieur des NPs préparées à partir de PEG-g-PLA pourrait inhiber la fonction P-gp. La première partie de cette étude avait pour but de synthétiser quatre copolymères de PEG greffés sur un acide polylactide (PLA) et sur un squelette de polymère (PLA-g-PEG), avec des ratios de 1% et 5% (ratio molaire de PEG vs acide lactique monomère) de soit 750, soit 2000 Da de masse moléculaire. Ces polymères ont été employés afin de préparer des NPs chargés de Famotidine qui possède une faible perméabilité et une solubilité aqueuse relativement basse. Les NPs préparées ont été analysées pour leur principaux paramètres physicochimiques tels que la taille et la distribution de la taille, la charge de surface (Potentiel Zeta), la morphologie, l’efficacité d’encapsulation, le pourcentage résiduel en alcool polyvinylique (PVA) adsorbé à la surface des NPs, les propriétés thermiques, la structure cristalline et la libération du médicament. De même, les formules de NPs ont été testées in vitro sur des cellules CaCo-2 afin dʼévaluer la perméabilité bidirectionnelle de la Famotidine. Généralement, les NPs préparées à partir de polymères greffés PLA-g-5%PEG ont montré une augmentation de la perméabilité du médicament, ce par l’inhibition de l’efflux de P-gp de la Famotidine dans le modèle CaCo-2 in vitro. Les résultats ont montré une baisse significative de la sécrétion de la Famotidine de la membrane basolatéral à apical lorsque la Famotidine était encapsulée dans des NPs préparées à partir de greffes de 5% PEG de 750 ou 2000 Da, de même que pour d’autres combinaisons de mélanges physiques contenant du PEG5%. La deuxième partie de cette étude est à propos de ces NPs chargées qui démontrent des résultats prometteurs en termes de perméabilité et d’inhibition d’efflux de P-gp, et qui ont été choises pour développer une forme orale solide. La granulation sèche a été employée pour densifier les NPs, afin de développer des comprimés des deux formules sélectionnées de NPs. Les comprimés à base de NPs ont démontré un temps de désintégration rapide (moins d’une minute) et une libération similaire à la Famotidine trouvée sur le marché. Les résultats de l’étude du transport de comprimés à base de NPs étaient cohérents avec les résultats des formules de NPs en termes d’inhibition de P-gp, ce qui explique pourquoi le processus de fabrication du comprimé n’a pas eu d’effet sur les NPs. Mis ensemble, ces résultats montrent que l’encapsulation dans une NP de polymère pegylé pourrait être une stratégie prometteuse pour l’amélioration de la biodisponibilité des substrats de P-gp.

Influence of Post and Resin Cement on Stress Distribution of Maxillary Central Incisors Restored with Direct Resin Composite

The current study evaluated the influence of two endodontic post systems and the elastic modulus and film thickness of resin cement on stress distribution in a maxillary central incisor (MCI) restored with direct resin composite using finite element analysis (FEA). A three-dimensional model of an MCI with a coronary fracture and supporting structures was performed. A static chewing pressure of 2.16 N/mm(2) was applied to two areas on the palatal surface of the composite restoration. Zirconia ceramic (ZC) and glass fiber (GF) posts were considered. The stress distribution was analyzed in the post, dentin and cement layer when ZC and GF posts were fixed to the root canals using resin cements of different elastic moduli (7.0 and 18.6 GPa) and different layer thicknesses (70 and 200 mu m). The different post materials presented a significant influence on stress distribution with lesser stress concentration when using the GF post. The higher elastic modulus cement created higher stress levels within itself. The cement thicknesses did not present significant changes.

Oral health in transition: the case of Indigenous peoples from Brazil

The objective of this paper is to summarise epidemiological information about the distribution of dental caries among Indigenous peoples in Brazil. The authors also present a case study of a specific group of Xavante Indians, one of the most numerous of Brazil`s Indigenous peoples, describing how their oral health has deteriorated over recent decades, and showing how an oral health programme is attempting to reverse the present trend of increase in caries. The programme at Etenheritipa Xavante village incorporated three principal components: educational, preventive, and clinical. From the beginning, the programme included epidemiological record keeping for monitoring the level of caries in the population. Transversal studies of the condition of oral health among the Xavante of Etenheritipa were undertaken in 1999, 2004, and 2007. In the period from 2004 to 2007 the DMFS values in the 11-15 age cohort had a significant reduction in caries experience. The mean DMFS score fell from 4.95 in 2004 to 2.39 in 2007 (p<0.01). An increase in the percent of individuals who were free from caries was also noted: in 1999, 20% of adolescents 11-15 had no caries; in 2007, the proportion had risen to 47%. The Xavante case is a prime example of the transition in oral health that is taking place among the Indigenous peoples of the Americas, and it highlights the importance of oral health promotion through preventive measures such as access to fluoridation and basic care in reducing the inequality between Indians and non-Indians.

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Effect of abutment's height and framework alloy on the load distribution of mandibular cantilevered implant-supported prosthesis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of cantilever length and framework alloy on the stress distribution of mandibular-cantilevered implant-supported prostheses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Photoelastic Analysis of the Influence of Platform Switching on Stress Distribution in Implants

The aim of this study was to evaluate the stress distribution of platform switching implants using a photoelastic method. Three models were constructed of the photoelastic resin PL-2, with a single implant and a screw-retained implant-supported prosthesis. These models were Model A, platform 5.0 mm/abutment 4.1 mm; Model B, platform 4.1 mm/abutment 4.1 mm; and Model C, platform 5.00 mm/abutment 5.00 mm. Axial and oblique (45 degrees) loads of 100 N were applied using a Universal Testing Machine (EMIC DL 3000). Images were photographed with a digital camera and visualized with software (AdobePhotoshop) to facilitate the qualitative analysis. The highest stress concentrations were observed at the apical third of the 3 models. With the oblique load, the highest stress concentrations were located at the implant apex, opposite the load application. Stress concentrations decreased in the cervical region of Model A (platform switching), and Models A (platform switching) and C (conventional/wide-diameter) displayed similar stress magnitudes. Finally, Model B (conventional/regular diameter) displayed the highest stress concentrations of the models tested.

Comparison of stress distribution between complete denture and implant-retained overdenture-2D FEA

The aim of this study was to compare the stress distribution induced by posterior functional loads on conventional complete dentures and implant-retained overdentures with different attachment systems using a two-dimentional Finite Element Analysis (FEA-2D). Three models representative of edentulous mandible were constructed on AutoCAD software; Group A (control), a model of edentulous mandible supporting a complete denture; Group B, a model of edentulous mandible supporting an overdenture over two splinted implants connected with the bar-clip system; Group C, a model of edentuluos mandible supporting an overdenture over two unsplinted impants with the O-ring system. Evaluation was conducted on Ansys software, with a vertical force of 100 N applied on the mandibular left first molar. When the stress was evaluated in supporting tissues, groups B (51.0 MPa) and C (52.6 MPa) demonstrated higher stress values than group A (10.1 MPa). Within the limits of this study, it may be conclued that the use of an attachment system increased stress values; furthermore, the use of splinted implants associated with the bar-clip attachment system favoured a lower stress distribution over the supporting tissue than the unsplinted implants with an O-ring abutment to retain the manibular overdenture.

Effect of Metal-Ceramic or All-Ceramic Superstructure Materials on Stress Distribution in a Single Implant-Supported Prosthesis: Three-Dimensional Finite Element Analysis

Purpose: This three-dimensional finite element analysis study evaluated the effect of different material combinations on stress distribution within metal-ceramic and all-ceramic single implant-supported prostheses. Materials and Methods: Three-dimensional finite element models reproducing a segment of the maxilla with a missing left first premolar were created. Five groups were established to represent different superstructure materials: GP, porcelain fused to gold alloy; GR, modified composite resin fused to gold alloy; TP, porcelain fused to titanium; TR, modified composite resin fused to titanium; and ZP, porcelain fused to zirconia. A 100-N vertical force was applied to the contact points of the crowns. All models were fixed in the superior region of bone tissue and in the mesial and distal faces of the maxilla section. Stress maps were generated by processing with finite element software. Results: Stress distribution and stress values of supporting bone were similar for the GP, GR, TP, and ZP models (1,574.3 MPa, 1,574.3 MPa, 1,574.3 MPa, and 1,574.2 MPa, respectively) and different for the TR model (1,838.3 MPa). The ZP model transferred less stress to the retention screw (785 MPa) than the other groups (939 MPa for GP, 961 MPa for GR, 1,010 MPa for TP, and 1,037 MPa for TR). Conclusion: The use of different materials to fabricate a superstructure for a single implant-supported prosthesis did not affect the stress distribution in the supporting bone. The retention screw received less stress when a combination of porcelain and zirconia was used. Int J Oral Maxillofac Implants 2011;26:1202-1209