The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in ß-Cell Function in TODAY.

OBJECTIVE: Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired ß-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in ß-cell function. RESEARCH DESIGN AND METHODS: OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (△C30/△G30), and ß-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups. RESULTS: At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity. CONCLUSIONS: In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced ß-cell function and foretells increased glycemic failure rates with accelerated deterioration in ß-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.

Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell lines against β-amyloid: The involvement of GRP78 and CHOP

Objectives: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to β-amyloid-induced BV2 mouse microglial cells. Materials and Methods Cell viability was assessed by the MTT assay and Western blotting was also performed. Results: β-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with β-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in β-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against β-amyloid. Conclusions: This study reveals the protective effects of GE against β-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.

Avaliação das relações interdentárias na posição de relação cêntrica e em máxima intercuspidação habitual em modelos montados em articulador / Dental interarch relationship evaluation in centric relation and maximum intercuspation in articulator mounted models

A avaliação de modelos em gesso das arcadas dentárias montados em articulador na posição de RC (relação cêntrica), revela importantes detalhes muitas vezes não observados nos modelos de estudo ortodônticos tradicionais. O objetivo do presente estudo foi o de verificar possíveis diferenças entre RC e MIH (máxima intercuspidação habitual), em grupos sintomático e assintomático, avaliando-se as seguintes características oclusais: sobremordida, sobressaliência, desvio de linha média dentária inferior, classificação de Angle para molares e de caninos. A amostra foi composta por 77 participantes, de 19 a 30 anos, não desprogramados, divididos em um grupo sintomático, sendo 15 do gênero masculino e 20 do feminino, com média de idade de 22,8 anos, e outro, assintomático, de 42 indivíduos sendo 18 do gênero masculino e 24 do feminino, com média de idade de 23,6 anos. Todos os participantes assinaram o Termo de consentimento livre e esclarecido (n.82/05) aprovado pelo Comitê de Ética em Pesquisa da FOUSP e foram submetidos a anamnese, exame clínico, exame de palpação muscular e das ATM. O grupo sintomático foi caracterizado por sinais e sintomas de disfunção temporomandibular (DTM) de origem muscular, segundo Critérios Diagnósticos de Pesquisa em Distúrbio Temporomandibular (Dworkin e LeResche, 1992). Foram considerados assintomáticos indivíduos que apresentaram ausência de sinais e sintomas de DTM. Foram obtidos os registros de RC, de MIH e modelos superiores e inferiores em gesso, que foram montados em articulador semi-ajustável com registros de RC obtidos de acordo com a técnica power centric de Roth modificada. Para medições confiáveis, foi desenvolvido instrumento que manteve o plano oclusal inferior como referência nas duas posições avaliadas.

Para a análise estatística foram utilizados os testes ANOVA, ANOVA com medidas repetidas, Qui-Quadrado com correção de continuidade e teste não-paramétrico de McNemar-Bowker para dados pareados. Foram encontradas diferenças significativas entre RC e MIH em todas as variáveis examinadas, tanto no grupo sintomático como no assintomático, porém não foram encontradas diferenças entre os grupos. Foi observada sobressaliência significantemente maior (p<0,001), sobremordida significantemente menor (p<0,001) e desvio de linha média inferior maior (0,047) em RC que em MIH. O maior percentual de relação de Angle em MIH foi de Cl I, e em RC, de relação de Cl II, tanto para os caninos como para os molares. Foi observada associação significativa entre maior variação na sobremordida entre RC e MIH, e as mudanças da relação molar dos lados direito e relação de canino do lado esquerdo, com sobremordida maior em MIH. Foi encontrada associação significativa entre maior variação entre RC e MIH com sobressaliência maior em RC, com as variações da relação de canino do lado esquerdo. Observou-se também, associação significativa entre a alteração da relação molar do lado D, com maior desvio de linha média inferior em RC. Confirmou-se neste estudo que as maloclusões analisadas em RC são diferentes daquelas examinadas em MIH, o que pode modificar o diagnóstico e o plano de tratamento ortodônticos.

The evaluation of mounted models assembled in articulator on CR ( centric relation) position reveals important details that are often not observed in traditional orthodontic study dental casts. The objective of this study was to observe differences between CR and MIC (maximum intercuspation), evaluating the following occlusal characteristics: overbite, overjet, , inferior dental midline deviation, molar and canine Angles classification. The sample comprised 77 individuals, from 19 to 30 years old, divided into two groups: the symptomatic group (n=35) (mean age: 22.8 years, 15 men and 20 women) and the asymptomatic group (n=42) (mean age: 23.6 years, 18 men and 24 women). All individuals signed an informed consent agreeing with research procedures. Approval for the procedures of this research was obtained from the Ethics Committee of the University of São Paulo (Project Number 82/05). Based on data collected during anamnesis and clinical examination, the subjects were divided in two groups a symptomatic and an asymptomatic in accordance to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). From each subject, CR and MIC bite registrations were obtained. Models were mounted on an articulator, using CR records obtained by modified Roths power centric technique. For reliable measurements, an instrument was developed in order to maintain the inferior occlusal plane as a reference. ANOVA method, ANOVA method with repeated measurements, Chi-squared test with a continuity correction and non-parametric McNemar-Bowker test for two-related-samples were used for statistical analysis. A significantly greater overjet (p<0.001), a significantly less overbite (p<0.001), and a greater inferior midline deviation were observed (0.047) in CR compared with MIC. Significant differences between CR and MIC were also found for the Angle's classification of canines and molars. Class I was more prevalent in MIC and Class II was more prevalent in CR.

Condylar displacement between centric relation and maximum intercuspation in symptomatic and asymptomatic individuals.

OBJECTIVE: To measure condylar displacement between centric relation (CR) and maximum intercuspation (MIC) in symptomatic and asymptomatic subjects. MATERIALS AND METHODS: The sample comprised 70 non-deprogrammed individuals, divided equally into two groups, one symptomatic and the other asymptomatic, grouped according to the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Condylar displacement was measured in three dimensions with the condylar position indicator (CPI) device. Dahlberg's index, intraclass correlation coefficient, repeated measures analysis of variance, analysis of variance, and generalized estimating equations were used for statistical analysis. RESULTS: A greater magnitude of difference was observed on the vertical plane on the left side in both symptomatic and asymptomatic individuals (P = .033). The symptomatic group presented higher measurements on the transverse plane (P = .015). The percentage of displacement in the mesial direction was significantly higher in the asymptomatic group than in the symptomatic one (P = .049). Both groups presented a significantly higher percentage of mesial direction on the right side than on the left (P = .036). The presence of bilateral condylar displacement (left and right sides) in an inferior and distal direction was significantly greater in symptomatic individuals (P = .012). However, no statistical difference was noted between genders. CONCLUSION: Statistically significant differences between CR and MIC were quantifiable at the condylar level in asymptomatic and symptomatic individuals.

Estudo das relações interarcadas em modelos montados em artigulador panadent: comparação entre RC e MIH / Dental interarch relationship study on Panadent articulator mounting: comparison beteen CR and CO

Os tratamentos da oclusão levaram à escolha da relação cêntrica (RC) como posição de referência devido à sua reprodutibilidade, o que favorece maior precisão do diagnóstico. Este estudo prospectivo propôs-se a observar as diferenças entre RC e MIH (máxima intercuspidação habitual), avaliando-se as seguintes características inter-oclusais: sobressaliência, sobremordida, relação de molares, de caninos, desvio de linha média dentária inferior, e posição do primeiro contato oclusal em RC. A amostra foi de 30 participantes, dividida em grupo sintomático, caracterizado por sinais e sintomas de disfunção temporomandibular de origem muscular e outro assintomático ou controle. Foram obtidos registros de MIH e RC, sendo este último, obedienteà técnica power centric (Roth). Para as comparações entre os grupos sintomático e assintomático, foi utilizado o teste "t", e entre RC e MIH, o teste "t" pareado. O teste de McNemar avaliou as associações entre as variáveis estudadas. Em RC, comparada à MIH, observou-se sobressaliência significantemente maior (p<0,001), sobremordida significantemente menor (p<0,001), prevalência significantemente menor de relação de Classe I entre caninos direito e esquerdo, e molares do lado direito (p<0,05). Foi observada associação significativa entre maior variação na sobressaliência e variações da relação molar em ambos os lados. O primeiro contato dentário em RC localizou-se na maioria dos casos, no segundo molar permanente, unilateralmente. Não foram encontradas diferenças entre os grupos sintomático e assintomático quanto as variáveis estudadas. Conclui-se que as discrepâncias significativas entre RC e MIH modificam o diagnóstico, devendo ser consideradas sempre que visada a oclusão funcional como objetivo de tratamento.

Centric relation (CR) is considered a reference position for treatments of the occlusion due to its reproducibility, what favors accuracy for diagnosis. The objective of this prospective study was to observe differences between CR and CO (maxim intercuspation), evaluating the following occlusal characteristics: overjet, overbite, molar and canine Angle S classification,inferior dental midline and initial premature occlusal contact in CR. Thirty individuals, from 19 to 30 years old, with no gender distinction, were divided into symptomatic group- characterized by signs and symptoms of TMD (temporomandibular disfunction) of muscular origin, and another group, asymptomatic or control. CR and C0 bite registrations were obtained,being this last, according Roth Spower centric technique. For comparisons between the symptomatic and asymptomatic groups, and between CR and CO, test t and paired t were used, respectively. The test of McNemar evaluated the associations between the variables studied. A statistically significant difference in the measurements was found, when comparing CR to CO, relatedto overjet increase (p<0,001) and overbite decrease (p<0,001). A significant smaller prevalence of C1 I was found on right and left canines, and right molars (p<0,05). Significant association was observed between greater overjet changes and molar relation changes, on both sides, rigth and left. The initial premature contact in CR was detected, in most of the cases, on the second permanent molar, unilaterally. There were not found differences between the symptomatic and asymptomatic groups for the variables studied. It is concluded that the significant discrepancies between CR and C0 mod-fl the diagnosis, therefore, it should always be considered when functional occlusion is related as a treatment goal.

Comparação dos registros de RC obtidos pelos métodos de manipulação uni e bimanual - estudo preliminar / Comparing CR records achieved through one hand and bimanual manipulation - a preliminary study

O correto registro da relação cêntrica constitui procedimento essencial para o diagnóstico ortodôntico e depende, entre outros aspectos, de adequada manipulação mandibular. Roth adotou a manipulação unimanual (Método I) e Dawson, a bimanual (Método II). Este estudo comparou ambos os métodos. A amostra foi de 30 participantes, sem distinção de gênero, com idades entre 19 e 30 anos, dividida em grupo sintomático - caracterizado pela presença de dor muscular espontânea, a palpação ou durante os movimentos mandibulares, com ou sem estalidos nas ATM - e outro, assintomático ou controle. De cada participante foram obtidos dois registros de RC segundo a técnica power centric, manipulando-se a mandíbula segundo os Métodos I e 11. Para comparação dos mesmos, empregaram-se modelos de gesso montados em articulador e o indicador de posição axial Panadent. As diferenças entre os dois métodos foram medidas nos três plaiios do espaço, em gráficos correspondentes aoslados direito, esquerdo e transversal, analisadas pelos testes "t" e "t" pareado. A comparação entre os métodos uni e bimanual, nos grupos sintomático e assintomático, separadamente, não revelou diferença estatisticamente significante (p > 0,05 em todas as comparações), o que permitiu a unificação destes últimos. As diferenças entre os Métodos I e II, medidas em milímetros, foram em média, de 0,05 (p = 0,474) e -0,076 (p = 0,440) no sentido horizontal dos lados direito e esquerdo, respectivamente. No sentido vertical, a diferença entre eles foi de 0,066 (p = 0,411) do lado direito, e de 0,086 (p = 0,406) no lado esquerdo. No transversal, a diferença média foi de 0,023 (p = 0,716). Estas medidas não caracterizaram diferenças estatisticamente significantes entre os métodos estudados, em nenhum dos planos considerados. Conclui-se que, nas condições experimentais desteestudo, os métodos de manipulação uni e bimanual mostraram-se estatisticamente equivalentes. Também, não foram encontradasdiferenças...

The precise registration of centric relation (CR) constitutes an essential procedure for the correct orthodontic diagnosis and it depends among other things on appropriate mandibular manipulation technique. Roth advocated one hand manipulation (Method I) and Dawson, himanual (Method II). This study compared the two methods. Thirty participants, 19 to 30 years old with no gender distinction, were divided into symptomatic (TMD) group-characterized by spontaneous muscular pain through jaw movements or palpation, with or without clicking - and another group, asymptomatic or control. From each subject it was taken two CR bite registration according to the power centric technique (Roth), and the jaw manipulated according to Methods I and II. Comparing both method, mounted models in articulator were used, in addition to the Panadent axial position indicator. The differences between the two methods were measured on the three-spatial planes, on corresponding graphs of transverse, right and left side, and analyzed by the tests t and paired t. The comparison between the uni- and bi-manual methods, in the symptomatic and asymptomatic groups, applied separately, didn't reveal significant statistical differences (p>0.05 in all of the comparisons), which allowed the unification of the groups. On the horizontal plane the mean were 0,05 on the rigth side (p=0,474) and -0,07(p=0,440) on the left. On the vertical plane the mean were -0,066 (p=0,411) on the right side and 0,086(p=0,406) on the left. The mean on the transversal plane was 0,023 (p=0,716). No significant difference between Methods I and II was found, nor between the rigth and left sides. It is, therefore, concluded that, in the experimental terms of this study, the one hand and bimanual manipulation methods revealed statistical equivalence.