Genotipificación de HLA-B en pacientes colombianos afectados por el síndrome Stevens-Johnson y la Necrólisis Epidérmica Tóxica

Las reacciones alérgicas a medicamentos cutáneas severas (RAM) como el Síndrome Stevens Johnson (SJS) y la Necrólisis Epidérmica Tóxica (NET),caracterizadas por exantema, erosión de la piel y las membranas mucosas, flictenas, desprendimiento de la piel secundario a la muerte de queratinocitos y compromiso ocular. Son infrecuentes en la población pero con elevada morbi-mortalidad, se presentan luego de la administración de diferentes fármacos. En Asia se ha asociado el alelo HLA-B*15:02 como marcador genético para SJS. En Colombia no hay datos de la incidencia de estas RAM, ni de la relación con medicamentos específicos o potenciales y tampoco estudios de aproximación genómica de genes de susceptibilidad.

Estudo da influência dos alelos do HLA classe I e II e do polimorfismo dos genes de citocinas na infecção pelo HTLV-1

INTRODUÇÃO: O vírus linfotrópico para células T humanas (HTLV-1) é o principal agente causador da Paraparesia Espástica Tropical / Mielopatia associada ao HTLV-1 (PET/MAH) e da Leucemia da célula T do Adulto (LTA). A maioria dos indivíduos infectados permanece assintomática, somente 2 a 5% irão desenvolver uma das duas doenças. Fatores da interação HTLV-1/ hospedeiro estão envolvidos no risco de desenvolver doença. A lesão neurológica na PET/MAH parece ser consequência de uma reação inflamatória, desencadeada pelo reconhecimento de células infectadas por linfócitos T citotóxicos, com consequente liberação de citocinas e lesão medular. OBJETIVO: Identificar marcadores genéticos, que possam ajudar no prognóstico e tratamento dos pacientes portadores do HTLV-1. MÉTODOS: Nas amostras de 117 portadores do HTLV-1 assintomáticos e 171 pacientes com acometimento neurológico em acompanhamento na cidade do Rio de Janeiro, foram realizadas as tipificações dos genes do HLA Classe I e II, dos polimorfismos dos genes das citocinas -308TNF-\03B1,-174IL-6, +874IFN-\03B3, códon 10 e 25TGF-\03B21 e -1082 - 819-592IL-10, e a quantificação da carga proviral. Os dados foram organizados em um banco de dados no programa SPSS. As frequências alélicas e genotípicas foram obtidas por contagem direta. O equilíbrio de Hardy-Weinberg foi avaliado para os polimorfismos das citocinas no sitio http://bioinfo.iconcologia.net/ubbweb/SNPStats_web, em relação ao HLA foram utilizadas as ferramentas disponíveis no sítio \201CLos Alamos HIV database tools\201D. As comparações entre os grupos foram realizadas através de tabelas de contingência 2x2 (quiquadrado, exato de Fisher e odds ratios), valores de p\22640,05 foram considerados significantes RESULTADOS E CONCLUSÕES: O alelo A*02 não influencia a condição clínica nem os níveis da carga proviral. Os alelos A*29 e B*44 foram mais frequentes entre os indivíduos assintomáticos e a sua presença influenciou os níveis da carga proviral sugerindo proteção ao desenvolvimento de doença neurológica. O alelo A*68 foi mais frequente entre os pacientes com doença neurológica, porém sua presença não influenciou nos níveis da carga proviral. O alelo C*04 foi mais frequente entre os portadores assintomáticos e não influenciou os níveis de carga proviral, já o alelo DRB1*03 predominou entre os pacientes com doença neurológica e a sua presença entre os indivíduos assintomáticos acarretou níveis mais elevados de carga proviral, sugerindo ser um possível fator de risco para o desenvolvimento de doença neurológica. Na análise do polimorfismo genético das citocinas, o polimorfismo de IL-10, com perfil fenotípico de baixo produtor da citocina foi mais frequente no grupo dos assintomáticos, enquanto que o fenótipo de produtor intermediário predominou entre os sintomáticos. O perfil fenotípico da população estudada foi caracterizado como: baixo produtor da citocina -308TNF-\03B1, intermediário a alto produtor para códon 10 e códon 25 TGF-\03B2, baixo a intermediário produtor para -1082,-819,- 592 IL-10, alto produtor para -174 IL-6 e baixo a intermediário produtor para +874IFN-\03B3

Comparative Histopathological Analysis of Human Pulps after Class I Cavity Preparation with a High-Speed Air-Turbine Handpiece or Er:YAG Laser

The purpose of this study was to comparatively evaluate the response of human pulps after cavity preparation with different devices. Deep class I cavities were prepared in sound mandibular premolars using either a high-speed air-turbine handpiece (Group 1) or an Er: YAG laser (Group 2). Following total acid etching and the application of an adhesive system, all cavities were restored with composite resin. Fifteen days after the clinical procedure, the teeth were extracted and processed for analysis under optical microscopy. In Group 1 in which the average for the remaining dentin thickness (RDT) between the cavity floor and the coronal pulp was 909.5 mu m, a discrete inflammatory response occurred in only one specimen with an RDT of 214 mu m. However, tissue disorganization occurred in most specimens. In Group 2 (average RDT = 935.2 mu m), the discrete inflammatory pulp response was observed in only one specimen (average RDT = 413 mu m). It may be concluded that the high-speed air-turbine handpiece caused greater structural alterations in the pulp, although without inducing inflammatory processes.

Evolution of class I cytokine receptors

Background
The Class I cytokine receptors have a wide range of actions, including a major role in the development and function of immune and blood cells. However, the evolution of the genes encoding them remains poorly understood. To address this we have used bioinformatics to analyze the Class I receptor repertoire in sea squirt (Ciona intestinalis) and zebrafish (Danio rerio).
Results
Only two Class I receptors were identified in sea squirt, one with homology to the archetypal GP130 receptor, and the other with high conservation with the divergent orphan receptor CLF-3. In contrast, 36 Class I cytokine receptors were present in zebrafish, including representative members for each of the five structural groups found in mammals. This allowed the identification of 27 core receptors belonging to the last common ancestor of teleosts and mammals.
Conclusion
This study suggests that the majority of diversification of this receptor family occurred after the divergence of urochordates and vertebrates approximately 794 million years ago (MYA), but before the divergence of ray-finned from lobe-finned fishes around 476 MYA. Since then, only relatively limited lineage-specific diversification within the different Class I receptor structural groups has occurred.

Evolution of class I cytokine receptor signalling

Cytokines are proteins that provide essential signals to blood and immune cells. The evolution of this system was determined from primitive organisms to humans and zebrafish. Analysis of zebrafish granulocyte colony-stimulating factor (GCSF) signalling revealed broad conservation of function with mammals and a novel role in white blood cell migration.

Recruitment of class I hydrophobins to the air : water interface initiates a multi-step process of functional amyloid formation

Class I fungal hydrophobins form amphipathic monolayers composed of amyloid rodlets. This is a remarkable case of functional amyloid formation in that a hydrophobic:hydrophilic interface is required to trigger the self-assembly of the proteins. The mechanism of rodlet formation and the role of the interface in this process have not been well understood. Here, we have studied the effect of a range of additives, including ionic liquids, alcohols, and detergents, on rodlet formation by two class I hydrophobins, EAS and DewA. Although the conformation of the hydrophobins in these different solutions is not altered, we observe that the rate of rodlet formation is slowed as the surface tension of the solution is decreased, regardless of the nature of the additive. These results suggest that interface properties are of critical importance for the recruitment, alignment, and structural rearrangement of the amphipathic hydrophobin monomers. This work gives insight into the forces that drive macromolecular assembly of this unique family of proteins and allows us to propose a three-stage model for the interface-driven formation of rodlets.

Prevalence of class-I, class-II and class-III obesity in Australian adults between 1995 and 2011-12

OBJECTIVE: To compare the prevalence of class-I, II and III obesity in Australian adults between 1995, 2007-08 and 2011-12. METHODS: Prevalence data for adults (aged 18+ years) were sourced from customised data from the nationally representative National Nutrition Survey (1995), the National Health Survey (2007-08), and the Australian Health Survey (2011-12) conducted by the Australian Bureau of Statistics. Obesity classifications were based on measured height and weight (class-I body mass index: 30.0-34.9kg/m(2), class-II: 35.0-39.9kg/m(2) and class-III: ≥40.0kg/m(2)). Severe obesity was defined as class-II or class-III obesity. RESULTS: Between 1995 and 2011-12, the prevalence of obesity (all classes combined) increased from 19.1% to 27.2%. During this 17 year period, relative increases in class I, II and III obesity were 1.3, 1.7 and 2.2-fold respectively. In 2011-12, the prevalence of class I, II and III obesity was 19.4, 5.9 and 2.0 per cent respectively in men, and 16.1, 6.9 and 4.2 per cent respectively in women. One in every ten people was severely obese, increasing from one in twenty in 1995, and women were disproportionally represented in this population. Obesity prevalence increased with increasing levels of area-level socioeconomic disadvantage, particularly for the more severely obese classes. Severe obesity affected 6.2% and 13.4% in the least and most disadvantaged quintiles respectively. CONCLUSION: Over the last two decades, there have been substantial increases in the prevalence of obesity, particularly the more severe levels of obesity. This study highlights high risk groups who warrant targeted weight gain prevention interventions.

The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of Ridge Inclination and Implant Localization on the Association of Mandibular Kennedy Class I Removable Partial Denture

The aim of this study was to evaluate the tendency of displacement of the supporting structures of the distal extension removable partial denture (DERPD) associated to the implant with different inclinations of alveolar ridge and implant localizations through a two-dimensional finite-element method. Sixteen mandibular models were fabricated, presenting horizontal, distally descending, distally ascending, or descending-ascending ridges. All models presented the left canine and were rehabilitated with conventional DERPD or implant-retained prosthesis with the ERA system. The models were obtained by the AutoCAD software and transferred to the finite-element software ANSYS 9.0 for analysis. A force of 50 N was applied on the cusp tips of the teeth, with 5 points of loading of 10 N. The results were visualized by displacement maps. For all ridge inclinations, the assembly of the DERPD with distal plate retained by an anterior implant exhibited the lowest requisition of the supporting structures. The highest tendency of displacement occurred in the model with distally ascending ridge with incisal rest. It was concluded that the association of the implant decreased the displacement of the DERPD, and the anterior positioning of the implant associated to the DERPD with the distal plate preserved the supporting structures for all ridges.

Influence of Implant Inclination Associated With Mandibular Class I Removable Partial Denture

The aim of this study was to use two-dimensional finite element method to evaluate the displacement and stress distribution transmitted by a distal extension removable partial denture (DERPD) associated with an implant placed at different inclinations (0, 5, 15, and 30 degrees) in the second molar region of the edentulous mandible ridge. Six hemimandibular models were created: model A, only with the presence of the natural tooth 33; model B, similar to model A, with the presence of a conventional DERPD replacing the missing teeth; model C, similar to the previous model, with a straight implant (0 degrees) in the distal region of the ridge, under the denture base; model D, similar to model C, with the implant angled at 5 degrees in the mesial direction; model E, similar to model C, with the implant angled at 15 degrees in the mesial direction; and model F, similar to ME, with the implant angled at 30 degrees in the mesial direction. The models were created with the use of the AutoCAD 2000 program (Autodesk, Inc, San Rafael, CA) and processed for finite element analysis by the ANSYS 8.0 program (Swanson Analysis Systems, Houston, PA). The force applied was vertical of 50 N on each cusp tip. The results showed that the introduction of the RPD overloaded the supporting structures of the RPD and that the introduction of the implant helped to relieve the stresses of the mucosa alveolar, cortical bone, and trabecular bone. The best stress distribution occurred in model D with the implant angled at 5 degrees. The use of an implant as a support decreased the displacement of alveolar mucosa for all inclinations simulated. The stress distribution transmitted by the DERPD to the supporting structures was improved by the use of straight or slightly inclined implants. According to the displacement analysis and von Mises stress, it could be expected that straight or slightly inclined implants do not represent biomechanical risks to use.

Evaluation of Bone Insertion Level of Support Teeth in Class I Mandibular Removable Partial Denture Associated With an Osseointegrated Implant: A Study Using Finite Element Analysis

Purpose: This study evaluated the influence of distal extension removable partial denture associated with implant in cases of different bone level of abutment tooth, using 2D finite element analysis.Materials and Methods: Eight hemiarch models were simulated: model A-presenting tooth 33 and distal extension removable partial denture replacing others teeth, using distal rest connection and no bone lost; model B-similar to model A but presenting distal guide plate connection; model C-similar to model A but presenting osseointegrated implant with ERA retention system associated under prosthetic base; model D-similar to model B but presenting osseointegrated implant as described in model C; models E, F, G, and H were similar to models A, B, C, and D but presenting reduced periodontal support around tooth 33. Using ANSYS 9.0 software, the models were loaded vertically with 50 N on each cusp tip. For results, von Mises Stress Maps were plotted.Results: Maximum stress value was encountered in model G (201.023 MPa). Stress distribution was concentrated on implant and retention system. The implant/removable partial denture association decreases stress levels on alveolar mucosa for all models.Conclusions: Use of implant and ERA system decreased stress concentrations on supporting structures in all models. Use of distal guide plate decreased stress levels on abutment tooth and cortical and trabecular bone. Tooth apex of models with reduced periodontal support presented increased stress when using distal rest. (Implant Dent 2011;20:192-201)

Comparative Histopathological Analysis of Human Pulps after Class I Cavity Preparation with a High-Speed Air-Turbine Handpiece or Er:YAG Laser

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of Conventional and Resin-modified Glass-Ionomer Liner on Dentin Adhesive Interface of Class I Cavity Walls After Thermocycling

Objective: The aim of this in vitro study was to analyze the effect of glass-ionomer cement as a liner on the dentin/resin adhesive interface of lateral walls of occlusal restorations after thermocycling.Materials and Methods: Occlusal cavities were prepared in 60 human molars, divided into six groups: no liner (1 and 4); glass-ionomer cement (GIC, Ketac Molar Easymix, 3M ESPE) (2 and 5); and resin-modified glass-ionomer cement (RMGIC, Vitrebond, 3M ESPE) (3 and 6). Resin composite (Filtek Z250, 3M ESPE) was placed after application of an adhesive system (Adper Single Bond 2, 3M ESPE) that was mixed with a fluorescent reagent (Rhodamine B) to allow confocal microscopy analysis. Specimens of groups 4, 5 and 6 were thermocycled (5 degrees C-55 degrees C) with a dwell time of 30 seconds for 5000 cycles. After this period, teeth were sectioned in approximately 0.8-mm slices. One slice of each tooth was randomly selected for confocal microscopy analysis. The other slices were sectioned into 0.8 nun x 0.8 mm beams, which were submitted to microtensile testing (MPa). Data were analyzed using two-way ANOVA and Tukey test (p < 0.05).Results: There was no detectedstatistical difference on bond strength among groups (alpha < 0.05). Confocal microscopy analysis showed a higher mean gap size in group 4(12.5 mu m) and a higher percentage of marginal gaps in the thermocycled groups. The RNIGIC liner groups showed the lowest percentage of marginal gaps.Conclusions: Lining with RMGIC resulted in less gap formation at the dentin/resin adhesive interface after artificial aging. RMGIC or GIC liners did not alter the microtensile bond strength of adhesive system/resin composite to dentin on the lateral walls of Class I restorations.

Longitudinal study of mandibular behavior in Class I subjects with vertical and horizontal growth

OBJETIVO: avaliar as possíveis diferenças no comportamento mandibular em indivíduos Classe I com crescimento vertical e horizontal. MÉTODOS: a amostra desse estudo consistiu de 20 indivíduos Classe I não tratados, sendo o grupo 1 composto por 10 indivíduos com padrão de crescimento vertical e o grupo 2 por 10 indivíduos com padrão de crescimento horizontal, pertencentes aos arquivos do Burlington Growth Center, University of Toronto, no Canadá, acompanhados radiograficamente nas idade de 9, 12 e 21 anos. Determinou-se, por meio de telerradiografias cefalométricas, em norma lateral, os valores médios para a avaliação longitudinal do comportamento da mandíbula utilizando as medidas SNB, Co-Gn, SN.GoMe, altura facial anterior e altura facial posterior. RESULTADOS: o valor de SNB e Co-Gn foram maiores no grupo com crescimento horizontal em todas as idades. A medida Sn.GoMe foi significativamente menor no grupo com crescimento horizontal, a altura facial anterior (AFH) apresentou valores menores nos indivíduos com padrão de crescimento horizontal, e a altura facial posterior (PFH) apresentou valores menores nos indivíduos com crescimento vertical. CONCLUSÃO: as comparações longitudinais das tendências de crescimento de indivíduos Classe I indicam que existe diferenças significativas entre os dois grupos. A mandíbula apresentou tendência à rotação horária no grupo 1. O grupo 2 exibiu tendência à característica de indivíduos braquicefálicos, na forma facial, devido ao déficit no desenvolvimento vertical na altura facial anterior.