Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.

Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae)

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA A antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA A receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA A receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

Gender, race and socioeconomic influence on diagnosis and treatment of thyroid disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.

Effects of IL-10 and glucose on expression of OPG and RANKL in human periodontal ligament fibroblasts

The effects of interleukin-10 (IL-10) and glucose on mRNA and protein expression of osteoprotegerin (OPG), and its ligand, receptor activator of nuclear factor-κB ligand (RANKL), were investigated in human periodontal ligament fibroblasts (HPDLFs). Primary HPDLFs were treated with different concentrations of IL-10 (0, 1, 10, 25, 50, and 100 ng/mL) or glucose (0, 5.5, 10, 20, 30, and 40 mmol/L). Changes in mRNA and protein expression were examined using the reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. After IL-10 treatment, mRNA and protein levels of OPG were increased, while mRNA and protein levels of RANKL were decreased (P<0.05), both in a concentration-dependent manner. Glucose stimulation had the opposite concentration-dependent effect to that of IL-10 on OPG and RANKL expression. IL-10 upregulated OPG expression and downregulated RANKL expression, whereas high glucose upregulated RANKL and downregulated OPG in HDPLFs. Abnormal levels of IL-10 and glucose may contribute to the pathogenesis of periodontal disease.

Método de preparo das sementes de mamoneira (Ricinus communis L.) para o teste de tetrazólio

O teste de tetrazólio é um método rápido e eficaz para avaliar a viabilidade e o vigor de sementes. O presente trabalho teve por objetivo padronizar o método de preparo das sementes de mamoneira (Ricinus communis L.) para a avaliação do potencial fisiológico pelo teste de tetrazólio. Foram testados os seguintes métodos de preparo das sementes: corte longitudinal mediano através do tegumento, endosperma e embrião; corte longitudinal diagonal sem atingir o eixo embrionário; remoção do tegumento; remoção do tegumento com corte longitudinal mediano através do endosperma e embrião; e remoção do tegumento com corte longitudinal mediano, paralelo aos cotilédones, através do endosperma e embrião. Antes dos preparos, as sementes foram pré-condicionadas entre papel toalha umedecido por 18 horas a 30ºC, e após os preparos, as sementes foram imersas na solução de tetrazólio na concentração de 0,5% e mantidas em câmara escura a 35ºC para o desenvolvimento da coloração. Avaliou-se a uniformidade da coloração das sementes após cada preparo, por meio da comparação entre eles. Para a avaliação do potencial fisiológico das sementes de mamoneira pelo teste de tetrazólio o método indicado de preparo é a remoção do tegumento, com posterior corte longitudinal e mediano, no sentido do comprimento, através do endosperma e embrião.

Adequação do teste de tetrazólio para sementes de algodoeiro

O teste de tetrazólio destaca-se entre os demais testes devido à possibilidade de avaliar simultaneamente a viabilidade e o vigor de sementes. A recomendação existente para condução deste teste com sementes de algodoeiro é morosa, além de apresentar dificuldades na forma de preparo e avaliação. Diante do fato, este trabalho teve por objetivo a redução do tempo de preparo das sementes de algodoeiro para a execução do teste. Inicialmente foram realizados três ensaios: 1- corte distal seguido de corte longitudinal: após o pré-umedecimento em papel e imersão em água por seis, oito e 16 horas, respectivamente; 2- corte distal nas sementes secas: seguido de imersão direta em água por quatro, seis e oito horas e, em papel, por 16 horas; 3- imersão - corte - imersão: após duas horas de imersão, foi feito o corte na extremidade oposta ao eixo embrionário seguido de imersão em água por quatro, seis e oito horas a 25°C. O tratamento corte distal do lado oposto do embrião após duas horas de imersão, seguida de mais seis horas de embebição, reduziu o tempo e facilitou o preparo das sementes para condução do teste. Em seguida, foram testadas as concentrações de tetrazólio 0,1% e 0,075% e as temperaturas 30, 35 e 40ºC. Posteriormente, foi realizada a validação da metodologia proposta, com cinco lotes de sementes, em que foram comparados os resultados com os da germinação e primeira contagem. Conclui-se que, para as sementes de algodoeiro, o teste de tetrazólio deve ser executado da seguinte forma: imersão em água por duas horas, seguido de corte na extremidade oposta ao eixo embrionário e posterior imersão por mais seis horas em água, seguida da remoção do tegumento e da membrana interna e, por fim, as sementes devem ser colocadas em solução de tetrazólio a 0,075% e mantidas em estufa a 40ºC por 150 minutos.

Estado e economia na Coreia do Sul - do Estado desenvolvimentista à crise asiática e à recuperação posterior

The State and the economy in South Korea: from the developmentist state to the Asian crisis and later recovery. The article focuses on the institutions of South Korean capitalism and on the interactions between the state and the economy. The economic model in South Korea was characterized by a very interventionist state, which played a very active role in the process of industrialization. However, South Korea suffered a severe crisis in 1997, attributed by many authors to the distortions inherent to strong state intervention. The article shows that the crisis was a result of the combination between internal economic fragilities and a rapid process of financial deregulation, which undermined the state's capacity of control. The crisis, nevertheless, does not disqualify the role of the national institutions in the very successful process of industrialization. Despite the reforms, the Korean capitalism conserves much of the previous model of business organization and industrial relations. The state continues strong and played active role in the process of economic reforms. There are, nevertheless, doubts about the impacts of the reforms and the new configuration of Korean capitalism. They will depend on the current transformations in world economy and in the East Asian countries.