Marcadores bioquímicos propuestos para el estudio de la sarcopenia / Proposed biochemical markers for the study of sarcopenia

La sarcopenia asociada a la edad es una condición clínica caracterizada por una disminución en la fuerza, calidad y cantidad de masa muscular así como también en la función muscular. Un biomarcador se define como una característica que es medible objetivamente y evaluable como indicador de un proceso biológico normal, patológico o respuesta terapéutica a una intervención farmacológica. Los marcadores bioquímicos propuestos para el estudio de la sarcopenia pueden ser categorizados en dos grupos. El primero de ellos evalúa el estatus musculoesquelético; este panel de marcadores está formado por miostatina/folistatina, procolágeno aminoterminal tipo III e índice de sarcopenia. El segundo grupo de marcadores bioquímicos evalúa factores causales, para lo cual se sugiere medir el factor de crecimiento insulino-símil tipo 1 (IGF-1), dehidroepiandrosterona (DHEAS), cortisol, facto-res inflamatorios [proteína C reactiva (PCR), interleuquina 6 (IL-6) y factor de necrosis tu-moral (TNF-a)]. Las recomendaciones realiza-das están basadas en la evidencia científica disponible en la actualidad y la disponibilidad de la metodología apropiada para cada uno de los biomarcadores. (AU)

Sarcopenia is a progressive and generalized skeletal muscle disorder defined by decrease in the strength, quality and quantity of muscle mass as well as in muscle function. A biomarker is defined as a feature objectively measured and evaluated as an indicator of a normal biologic process, a pathogenic process or a pharmacologic response to therapeutic intervention. The biochemical markers proposed for the study of sarcopenia may be classified in two groups. The first group evaluates the musculoskeletal status, made up by myostatin/follistatin, N-terminal Type III Procollagen and the sarcopenia index. The second evaluates causal factors, where the measurement of the following is suggested: hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate (DHEAS), cortisol, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)]. The recommendations made are based on scientific evidence currently available and the appropriate methodology availability for each biomarker. (AU)

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

Concentration of collagen fibers in the musculature of broiler chickens fed with cupuacu seed by-product / Concentração de fibras colágenas na musculatura de frangos alimentados com farinha de cupuaçu

In this essay, we quantify the concentration of collagen fibers in broiler chickens exposed to increasing concentrations of cupuacu seed by-product. Collection of material was carried out in five chickens per treatment at 70 days old in the groups: control, 5% and 10% inclusion of cupuacu seed by-product. Fragments of Thoracic Pectoralis (PT) and Iliotibial lateralis (ITL) muscles were prepared for light and electronic microscopy. The amount of collagen fibers in the muscle groups was 1.08±0.61% in the PTC group; 6.24±2.58% in PT5% and 7.30±2.75% in PT10%. In the Iliotibial Lateralis groups, the results were 6.96±3.14% in the ITLC; 7.43±4.22% in the ITL5% and 8.66±2.35% in ITL10%. The amount of collagen fibers in the ITL5% and ITL10% groups showed no significant statistical difference. However, when compared to the ILTC group, there was a significant statistical difference. The PT muscle responds to standard nutritional changes, unlike the ILT muscle, which requires a high-nutrient formulation. The use of 5% cupuacu seed by-product has proven to be a viable alternative source of animal feed, as it promotes an increase in the concentrations of collagen fibers in the musculature of broiler chickens and is possibly the determining factor in meat texture.(AU)

Neste estudo, foram quantificadas as concentrações de fibras colágenas de frangos expostos a crescentes concentrações de farinha de cupuaçu. A coleta de material foi realizada em cinco animais por tratamento, aos 70 dias de idade, nos grupos: controle, inclusão de 5% e de 10% de farinha de cupuaçu. Fragmentos dos músculos peitoral torácico (PT) e iliotibial lateral (ITL) foram preparados para microscopia de luz e eletrônica. A quantidade de fibras colágenas nos grupos foi: 1,08±0,61% no grupo PTC; 6,24±2,58% em PT5% e 7,30±2,75% em PT10%. Nos grupos iliotibial lateral, os resultados foram: 6,96±3,14% no ITLC; 7,43±4,22% no ITL5% e 8,66±2,35% em ITL10%. A quantidade de fibras colágenas nos grupos ITL5% e ITL10% não apresentou diferença estatística significativa. No entanto, quando comparados ao grupo ILTC, houve diferença estatística significativa. O músculo PT responde a mudanças nutricionais padrão, ao contrário do músculo ILT, que requer alta formulação nutricional. O uso de 5% de farinha de cupuaçu provou ser uma fonte alternativa viável de alimentação animal, pois promove um aumento nas concentrações de fibras de colágeno na musculatura de frangos de corte e é possivelmente um fator determinante na textura da carne.(AU)

Biomarcadores de fibrosis y función ventricular derecha en maratonistas con distinto grado de entrenamiento: estudio en la maratón de Santiago / Fibrosis and right ventricular function biomarkers in marathon runners: a study at the Santiago, Chile marathon

Resumen: Introducción: Atletas altamente entrenados muestran cambios cardíacos estructurales como adaptación a la sobrecarga, producto del ejercicio repetitivo y extenuante. Se han evidenciado elevación de biomarcadores de remodelado y fibrosis miocárdica posterior al ejercicio intenso en atletas. Sin embargo, el comportamiento de estos biomarcadores según el nivel de entrenamiento previo no se ha evaluado. Objetivo: Investigar biomarcadores de fibrosis y función ventricular derecha en maratonistas con distinto nivel de entrenamiento previo. Métodos: Se incluyeron 36 maratonistas hombres, sanos, que completaron 42 km en la maratón de Santiago. Se dividieron según entrenamiento previo en dos grupos, Grupo 1 (G1): ≥100 km/semana y Grupo 2 (G2): <100 km/semana. Se realizó ecocardiografía transtorácica y se evaluaron niveles plasmáticos de galectina-3 y del propéptido amino terminal del procolágeno tipo III (PIIINP) en la semana previa a la carrera e inmediatamente posterior a ésta. Resultados: Posterior a la maratón, la función sistólica del ventrículo derecho disminuyó en el grupo G2 junto con un aumento significativo de los niveles plasmáticos de PIIIPNP (61±16 a 94±24 ng/mL, p=0,01). Estos cambios no se observaron en el grupo G1 (65 ± 11 a 90±29 ng/mL, p=0,10). Los niveles plasmáticos de galectina-3 aumentaron significativamente en ambos grupos posterior al ejercicio (6,8±2,2 a 19,7±4,9 ng/mL, p 0,012 y 6,0±1,1 a 19,4 ± 5,9 ng/mL, p 0,01) en los grupos G1 y G2, respectivamente). Conclusiones: Atletas con menor grado de entrenamiento, presentan posterior a una maratón un significativo aumento de productos de degradación del colágeno (PIIIPNP) asociado a disminución de la función del ventrículo derecho. Los niveles de galectina-3 plasmática aumentan significativamente en ambos grupos post-esfuerzo independiente del entrenamiento previo.

Abstracts: Introduction: Highly trained athletes show structural cardiac changes as adaptation to overload. Rise in remodeling biomarkers and myocardial fibrosis after intense exercise in athletes has been evidenced; however, the behavior of these biomarkers according to pre-competition training level has not been evaluated. Objective: To evaluate fibrosis biomarkers levels and right ventricle function in marathon runners according to their previous training level, in the period prior to a marathon race and immediately after it. Methods: Thirty-six healthy male marathon runners were included. Subjects were grouped according to their previous training level: Group 1 (G1): ≥100 km/week and Group 2 (G2): <100 km/week. Transthoracic echocardiography along with plasmatic levels of galectin-3 and amino terminal propeptide of type III procollagen (PIIINP) were measured one week previous and immediately after the marathon. Results: Post-effort right ventricle systolic function decreased in G2, together with a significant elevation of PIIIPNP (61±16 to 94±24 ng/mL, p=0.01). These changes were not observed in G1 (from 65±11 to 90±29 ng/mL, p=0.10). Plasma galectin-3 increased significantly in both groups immediately post-exercise (6.8±2.2 to 19.7±4.9 ng/mL, p=0.012, and 6.0±1.1 to 19.4±5.9 ng/mL, p=0.01, in G1 and G2. respectively). Conclusion: Less trained athletes evidenced higher post marathon levels of PIIIPNP which is associated with a decreased global right ventricle function. Plasma galectin-3 levels increased significantly after intense exertion regardless of the intensity of previous training.

Síndrome de la esclerótica azul: manejo perinatal en un hospital especializado / Blue sclera syndrome: perinatal management in a specialized hospital

RESUMEN La Osteogénesis Imperfecta (OI) se presenta en 1 de cada 20.000 a 1 de cada 60.000 nacimientos. Se trata de un grupo heterogéneo de trastornos, caracterizados por anomalías del colágeno tipo I que interfieren en el proceso normal de osificación del hueso. Debido a lo complejo del manejo del manejo de un niño con OI es recomendable manejar dicho diagnóstico en la etapa fetal de manera a estar preparados tanto los padres como los profesionales para el cuidado y seguimiento, de ahí la importancia de los estudios ecográficos, más los antecedentes genéticos y otros estudios ideales durante el control prenatal de la madre. El ultrasonido es el procedimiento menos invasivo para el diagnóstico prenatal y por lo tanto comporta un menor riesgo utilizarlo. El médico puede examinar el esqueleto del feto buscando curvaturas (torceduras de los huesos de la pierna o el brazo), fracturas, acortamientos o cualquier otra anormalidad ósea que pueda indicar la presencia de OI.Se presenta un caso de OI del Hospital Distrital de Lambaré.

ABSTRACT Osteogenesis Imperfecta (OI) occurs in 1 in 20,000 to 1 in 60,000 births. It is a heterogeneous group of disorders characterized by abnormalities of type I collagen that interfere with the normal process of bone ossification. Due to the complexity of handling the management of a child with OI is advisable to handle that diagnosis in the fetal stage so be prepared both parents and professionals for the care and monitoring, hence the importance of ultrasound studies plus genetic background and other ideals studies during antenatal mother. The ultrasound is less invasive procedure for prenatal diagnosis and therefore is less risky use. The doctor can examine the fetal skeleton looking curvatures (sprained bones of the leg or arm), fractures, bone shortening or other abnormalities that may indicate the presence of OI. A case OI District Hospital of Lambaré is presented.

Correlation Between Radiographic Area and Immunolocation of MMP-2 and MMP-9 in Unilocular Radiographic Lesions

Unilocular bone cysts are the most common entities affecting the maxillofacial region. The mechanism of proliferation and expansion remains unclear. Metalloproteinases (MMPs) are associated to diverse pathological conditions. The aim of the present study was to correlate the radiographic aspect (area) and the presence of MMP-2 and MMP-9 in dentigerous cysts, radicular cysts and keratocystic odontogenic tumors. The radiographic area of each lesion was calculated using the mathematical formula of the ellipse area. All specimens were subjected to immunohistochemical analysis for these enzymes. The average radiographic area was 284.17 mm2, 235.81 mm2 and 381.81 mm2, respectively. Statistical analyses revealed no association between the immunoreactivity of MMPs and radiographic area of the lesions in all pathologies studied, except for MMP-2 and radicular cysts, for which smaller lesions had increased immunostaining for this enzyme. The results demonstrate that quantities of MMP-2 and MMP-9 are especially involved with dentigerous and radicular cysts in expansion, whereas these enzymes seem to be related to the biological behavior of keratocystic odontogenic tumors, indicating invasion and cell proliferation. Moreover, there is an inverse association between MMP-2 and MMP-9 in keratocystic odontogenic tumors (p=0.03; rs=-0.660), indicating activity in different regions.

Cistos ósseos uniloculares são as entidades mais comuns que afetam a região maxilofacial. O mecanismo de proliferação e expansão permanece obscuro. As metaloproteinases (MMPs) estão associadas a diversas condições patológicas. O objetivo do presente estudo foi correlacionar o aspecto radiográfico (área) e a presença de MMP-2 e MMP-9 em cistos dentígeros, cistos radiculares e tumores odontogênicos queratocísticos. A área radiográfica de cada lesão foi calculada usando a fórmula matemática da área de elipse. Todas as amostras foram submetidas à análise imunoistoquímica para estas enzimas. A área radiográfica média foi de 284,17 mm2, 235,81 mm2 e 381,81 mm2, respectivamente. As análises estatísticas não mostraram associação entre a imunorreatividade de MMPs e área radiográfica das lesões em todas as patologias estudadas, exceto para MMP-2 e cistos radiculares, nas quais as lesões menores tinham maior imunomarcação para esta enzima. Os resultados demonstraram que a quantidade de imunomarcação da MMP-2 e MMP-9 estão envolvidos com cistos dentígeros e radiculares na expansão óssea, ao passo que estas enzimas parecem estar relacionados com o comportamento biológico dos tumores odontogénicos queratocísticos, indicando invasão e proliferação celular. Além disso, há uma relação inversa entre a MMP-2 e MMP-9 em tumores odontogénicos queratocísticos (p=0,03; rs= -0,660), indicando atividade em diferentes regiões.

Supresión temprana a los 3 meses del propéptido amino terminal del procolágeno tipo 1 (P1NP) durante el tratamiento con risedronato 150 mg/mensuales en osteoporosis posmenopáusica / Early at 3 months of amino terminal propeptide of procollagen type 1 (P1NP) suppression during treatment with risedronate 150 mg / month in postmenopausal osteoporosis

Objetivo: Evaluar la respuesta temprana del uso de risedronato 150 mg/mensuales sobre el propéptido amino terminal del procolágeno, un marcador óseo altamente específico de la formación ósea y su correlación con otro marcador altamente específico de la resorción ósea, C telopéptido. Estas dos mediciones han sido sugeridas por la IOF y la IFCC como marcadores óseos confiables, específicos y reproductibles. Métodos: Propéptido amino terminal del procolágeno tipo I y C telopéptido (Beta-CrossLaps. CTx) séricos fueron evaluados en 80 mujeres venezolanas posmenopáusicas con baja masa ósea (T-score menor a -1,5) en columna lumbar o cuello de fémur. Propéptido amino terminal del procolágeno y CTx fueron dosificados en un equipo automatizado cobas e 411 de Roche Diagnóstica (analizador de inmunoensayo por electroquimioluminiscencia). Resultados: La edad promedio fue 59,8 ± 8,3 años, la edad de menopausia fue 46,8±6,3, 26 % habían recibido THR durante un promedio de 2,99 años. DMO en la columna lumbar y el cuello de fémur fueron T-scores -2,34 y -1,95. P1NP disminuyó 46,3 %, de 59,06 ± 22.3 a 31,01 ± 17,8 ng/mL, P< 0,000. El CTx disminuyó 48 %, de 0,45 ± 0,18 a 0,21 ± 0,14 ng/mL, P< 0,000. La correlación entre P1NP y CTx fue altamente significativa antes de la terapia r=638, P<0,000 y luego de 3 meses, r=0,538, P<0,000. Igualmente la correlación entre P1NP inicial y a los 3 meses de terapia fue altamente significativa, r=0,693, P<0,000. La supresión del remodelado óseo estimado por una disminución mayor al 10 % de los valores iniciales de P1NP fue alcanzada en 94,7 % de las pacientes Conclusión: El uso de risedronato 150 mg/mensuales suprime el remodelado óseo alcanzando valores premenopáusicos a los 3 meses de su uso , disminuyendo los valores de P1NP en 46,3 % y los de CTC en 48 %. P1NP disminuyó más del 10 % en 94,7 % de las pacientes.

Objective: Evaluate early response of risedronate 150 mg once-a-month on N-terminal propeptide of procollagen, a highly specific marker of bone formation and its correlation with another high specific marker of bone resorption, C telopeptide. This two measurements has been suggested by IOF and IFCC as a reliable, specific and reproductible bone markers. Methods: N-terminal propeptide of procollagen type I and serum Beta-CrossLaps (CTx) were evaluated in 80 postmenopausic Venezuelan women with low bone mass (T-score below -1.5) either at lumbar spine or femoral neck. N-terminal propeptide of procollagen and CTx were measured on fully automated cobas e411, Roche Diagnóstica (Electro-chemiluminescent immunoassay analyzer). Results: Mean age was 59.8 ± 8.3, age of menopause 46.8±6.3, 26 % had received HRT for a mean of 2.99 years. BMD at lumbar spine and femoral neck were T-scores -2.34 and -1.95. P1NP decreased 46.3.%, from 59.06 ± 22.3 to 31.01 ± 17.8 ng/mL, P< 0.000. CTx decreased 48 %, from 0.45 ± 0.18 to 0.21 ± 0.14 ng/mL, P< 0.000. Correlation between P1NP and CTx were highly significant before therapy r=638, P<0.000 and after 3 months r=0.538, P<0.000, Initial and 3 months P1NP were also highly correlated r=0.693, P<0.000. Suppression of bone remodeling (more than 10 % decrease in serum P1NP) was achieved in 94.7 of the patients. Conclusion: Risedronate 150 mg once-a-month suppressed bone remodeling into normal premenopausal reference range at 3 months, measured by 46.3 % reduction on P1NP and 48 % on serum CTx. P1NP decreased more than 10 % in 94.7 % of patients.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

The effects of discontinuing long term alendronate therapy in a clinical practice setting / Efeitos da retirada do uso prolongado de alendronato na prática clínica

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7 percent) in G1 and one (5.2 percent) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

OBJETIVO: Avaliar a evolução dos marcadores de metabolismo ósseo (MMO) e da densidade mineral óssea (DMO) após cinco anos de uso de alendronato em mulheres osteoporóticas na pós-menopausa. SUJEITOS E MÉTODOS: 40 pacientes (pct) osteoporóticas, na pós-menopausa, em uso de alendronato (10 mg/dia) por pelo menos 5 anos (Grupo 1 − G1) tiveram o uso do bisfosfonato suspenso. O grupo 2 (G2): 25 mulheres na pós-menopausa, em uso de alendronato (10 mg/dia) há pelo menos 1 ano. Grupo 3 (G3): 23 pct osteoporóticas, controles ainda sem tratamento. G1 e G2 submeteram-se à avaliação da DMO por DXA (basal e após 12 meses de seguimento). Todas as pct colheram amostras basais de CTX e P1NP, e G1 e G2 submeteram-se a coletas trimestrais de CTX e P1NP durante 1 ano. Resultados foram analisados por ANOVA on ranks e Mann-Whitney. RESULTADOS: Níveis médios de DMO não variaram em G1 ou G2 durante o estudo; no entanto, 16 pct (45,7 por cento) no G1 e 1 pct (5,2 por cento) no G2 apresentaram redução clinicamente significativa de DMO (P < 0,001). Níveis basais de CTX e P1NP não diferiram entre G1 e G2, com ambos inferiores aos níveis de G3. Em G1, observou-se elevação significativa de CTX e P1NP após 3 meses. Os níveis de CTX e P1NP em G2 permaneceram estáveis durante todo o seguimento. CONCLUSÃO: Não parece haver supressão excessiva do metabolismo ósseo na prática clínica. A suspensão temporária do alendronato após seu uso prolongado pode não ser segura.

Estudo in vitro da produção de quimiocinas e pró-colágeno I por fibroblastos de gengiva, ligamento periodontal e polpa dental humanos / In vitro study of chemokines and procollagen I by human gingival, periodontal ligament and dental pulp fibroblasts

Fibroblastos são as células mais numerosas encontradas nos tecidos orais como gengiva, ligamento periodontal e polpa dental. Além de exercerem função estrutural, estas células também desempenham papel importante na resposta imune destes tecidos através do reconhecimento de antígenos e produção de mediadores inflamatórios e citocinas. Evidências apontam ainda para o fato de que fibroblastos não constituem um grupo único de células. Sendo assim, os objetivos deste estudo foram: (I) avaliar a produção diferencial de fibroblastos de gengiva, ligamento periodontal e polpa dental de dentes permanentes e decíduos quanto à produção das quimiocinas CCL3 e CXCL12; (II) avaliar a produção de pró-colágeno I pelas células de polpa e (III) avaliar a expressão diferencial dos fibroblastos quanto a microRNAs. Dentes recentemente extraídos (terceiros molares hígidos) e fragmentos de gengivas saudáveis de três pacientes adultos foram obtidos no Laboratório de Farmacologia e Fisiologia Clínica da Faculdade de Odontologia de Bauru. Caninos decíduos de dois pacientes com indicação para extração por motivos ortodônticos foram obtidos na Clínica de Odontopediatria da mesma unidade. Culturas primárias de fibroblastos de gengiva (n=3), ligamento periodontal (n=3) e polpa de dente permanente (n=3) e polpa dental de dente decíduo (n=2) foram estabelecidas a partir de tecidos humanos por meio de técnica de explant. Após a quarta passagem, a produção de CCL3 e de CXCL12 foi avaliada após estímulo com concentrações crescentes (0 10 µg/mL) de ácido lipoteicóico de Enterococcus faecalis (EfLTA), lipopolissacarídeo de Porphyromonas gingivalis (PgLPS) ou LPS de Escherichia coli (EcLPS) por ELISA após 1, 6 e 24 h. O RNAm para as quimiocinas no grupo estimulado com EcLPS por 24 h foi avaliado por transcrição reversa seguida de reação em cadeia da polimerase quantitativa. A produção de pró-colágeno I por células de polpa estimuladas com EfLTA e PgLPS foi avaliada por imunofluorescência. O perfil...

Fibroblasts are the dominant cells within oral tissues such as gingiva, periodontal ligament and dental pulp. Besides the architectural maintenance of the connective tissues, fibroblasts are also involved in connective tissue immune response through antigen recognition and production of inflammatory mediators and cytokines. Recent studies also demonstrated that fibroblasts do not constitute a unique group of cells. Taken this togeter, the objectives of the present study were: (I) to evaluate the production of the chemokines CCL3 and CXCL12 by human gingival, periodontal ligament as well as permanent and deciduous dental pulp fibroblasts; (II) to evaluate the production of procollagen I by dental pulp fibroblasts and (III) to evaluate the differential pattern of expression of microRNAs by the oral fibroblasts. Recently extracted teeth (non-carious third molars) and fragments of healthy gingiva from three adults were obtained at the Laboratory for Clinical Pharmacology and Physiology at Dental School of Bauru. Deciduous canines from two patients with orthodontic indication for extraction were obtained at Pediatrics Clinics of Dental School of Bauru. Primary cultures of fibroblasts from gingiva (n=3), periodontal ligament (n=3) as well as permanent pulp (n=3) and deciduous pulp (n=2) were established through an explant technique. After the fourth passage, fibroblasts were challenged with increasing concentrations (0 10 µg/mL) of Enterococcus faecalis lipoteichoic acid (EfLTA), Porphyromonas gingivalis lipopolysaccharide (PgLPS) or Escherichia coli LPS (EcLPS) for 1, 6 and 24 h. The chemokines were assessed through ELISA while the mRNA for CCL3 and CXCL12 (EcLPS at 24 h) were assessed through reverse transcription followed by quantitative polymerase chain reaction. The expression of microRNAs was screened through a microarray assay. The production of CCL3 on cell supernatants was detected in all cellular groups, with higher amounts at gingival fibroblasts...

Use of the plasma CTX for assessing the bone activity of the mandible among osteopenic and osteoporotic patients

The aim of this study was to determine whether the plasma CTX bone remodeling marker is useful for indicating the bone metabolic activity level of the mandible. Thirty-six patients were selected; all were postmenopausal and aged 50 years or over. In accordance with the WHO criteria for osteoporosis, a control group was set up (n = 10) in which the T-score was greater than -1 and a diseased group with T-score less than -1. Using MDP-99mTc samples, the radioisotope uptake in the femoral neck (R2) and mandibular body (R1) was analyzed. A third examination was performed using the plasma CTX biochemical bone-modeling marker. The inferential results for the diseased group showed that Ln(R1) presented a statistically significant linear relationship with Ln(CTx) (p = 0.067) and with the T-score (p = 0.018). The plasma CTX bone remodeling marker is useful for monitoring the bone metabolic activity of the mandible.

Naturally supraorganized collagen increases axonal regeneration after tubulization repair

After axotomy, regeneration can be enhanced by bridging the transected nerve with a biocompatible tube, and the effect of trophic substances or molecules from the extracellular matrix can be investigated by filling the prosthesis. In this study, we assessed the importance of the molecular organization and aggregational state of collagen type I in axonal regeneration and guidance. Two types of collagen were used, namely, a collagen gel derived from bovine tendon that displays supraorganization after extrusion, and collagen from rat tail which does not self-organize under such conditions. Adult male Wistar rats were divided into four groups. In the first group (n=3), the polyethylene tube was filled with bovine collagen, while in the second (n=3), the prosthesis was filled with rat-derived collagen. In the third group (n=3), the tube was left empty, and the fourth group (n=3), consisted of unoperated rats. Six weeks after tubulization, the number of axons was significantly higher with bovine collagen than with rat collagen (7,661 ± 1,018 versus 4,110 ± 1,027, p<0.05), as was the degree of implant absorption. These results support the hypothesis that the use of extracellular matrix substances that self-assembly in an organized pattern can enhance nerve regeneration.

Concentração sérica de procolágeno amino-terminal tipo III como marcador de fibrose hepática em lactentes com hepatopatia crônica / Serum concentration of type III aminoterminal procollagen as a marker of hepatic fibrosis in infants with chronic hepatitis

Objetivo: avaliar comparativamente os níveis séricos de PIIP com estudo histológico de lactentes hepatopatas. Foram avaliados 38 pacientes, com idade entre 5 e 104 semanas, com hepatopatia crônica de diferentes causas. A análise histológica foi feita segundo escore de Knodell, demonstrando 4 pacientes com escore 0, 11 com escore 1, 20 com escore 2 e três com escore 4...

Sensibilidad de los marcadores del remodelamiento óseo: su modificación en la menopausia, ante la terapia estrogénica de reemplazo y ante una enfermedad metabólica generalizada / Markers of bone turnover, their sensibility to bone remodeling: changes in menopause, in hormone replacement therapy and in a metabolic bone disease

Evalua una batería de marcadores bioquímicos específicos y sensibles para predecir cambios en la velocidad del remodelamiento óseo. Se estudió a mujeres sanas pre y postmenospáusicas y en estas últimas a su vez se evaluó los cambios producidos después de 90 días de una terapia hormonal de reemplazo. Respecto de los marcadores bioquímicos de formación, la FA total aumentó en las postmenospáusicas respecto del grupo premenospáusico (P < 0,0001), al igual que la BGP (1 < 0,01); en cambio, la FA ósea no registró cambios significativos. Luego de la terapia hormonal de reemplazo ninguno de estos marcadores registraron cambios significativos. Todos los marcadores de resorción aumentaron en als mujeres postmenospáusicas. Los convencionales tales como el calcio urinario/creatinina y la hidroxiprolina con un p < 0,01 y p < 0,006 respectivamente. Los nuevos marcadores de resorción presentaron los siguientes cambios: Pyr p < 0,001; 72 por ciento; D-Pyr p < 0,003, 27 por ciento y Crosslaps p < 0,003, 70 por ciento de aumento respectivamente. Ante la terapia estrogénica, si bien los marcadores convencionales no mostraron diferencias significativas respecto del nivel basal, la Pyr disminuyó significativamente en un 15 por ciento (p < 0,03), la D-Pyr en un 15 por ciento (p < 0,04) y los Crosslaps en un 39 por ciento (p < 0,001). También se investigó la precisión diagnóstica de los marcadores bioquímicos en pacientes con un remodelamiento óseo aumentado, como es el caso de enfermedades celíacas. Estas se compararon con los normales que presentaban igual estado estrogénico observándose distintos comportamientos entre pre y postmenospáusicas. La BGP aumentó sólo en las celíacas premenospáusicas (p < 0,003). La FA total en los dos grupos estrogénicos (p < 0,0001 y p < 0,005 respectivamente), al igual que la FA ósea (p < 0,0003 y p< 0,0004, respectivamente). El marcador de resorción D-Pyr no presentó diferencias significativas en ninguno de los dos grupos, la Pyr sílo en las premenopáusicas (p < 0,01). La hidroxiprolina aumentó en ambos (p < 0,04 y p < 0,004, respectivamente), al igual que los Crosslaps (p < 0,001 para los dos grupos estrogénicos)

Serum type III procollagen peptides in patients with hepatointestinal and compensated hepatoesplenic schistosomiasis forms

Os níveis dos peptídios séricos do procolágeno tipo III (PSPC III) foram determinados em 35 indivíduos: 25 esquistossomóticos näo tratados da parasitose, sendo 16 da forma hepatointestinal (HI) e nove da hepatoesplênica compensada (HEC) e dez sadios. Para a dosagem dos PSPC III foram utilizados kits de radioimunoensaio. Procurou-se demonstrar a correlaçäo entre os níveis dos PSPC III e as atividades séricas das enzimas aminotransferase da alanina (ALT), aminotransferase do aspartato (AST), fosfatase alcalina (FA) e gamaglutamiltranspeptidase (GGTP). As médias dos valores dos PSPC III nas formas HI (13 ng/ml) e HEC (17 ng/ml) foram significantemente maiores do que as do grupo controle (9,0 ng/ml) (p < 0,05). Näo se observou diferença significante quanto aos valores dos PSPC III entre os grupos de pacientes das formas HI e HEC. Näo houve correlaçäo entre os aumentos dos PSPC III e os da atividade sérica da ALT, AST, FA e GGPT. Os autores discutem aspectos sobre eventual aplicabilidade da determinaçäo dos PSPC III em pacientes com esquistossomose

Serum type III procollagen peptides in patients with schistosomiasis mansoni before and after the treatment with oxamniquine

A fibrose pode ter importância significativa na hepatopatia esquistossomótica. O tratamento específico atual da esquistossomose pode proporcionar bons resultados, com regressäo de algumas alteraçöes hepáticas e, eventualmente, da fibrose. Os peptídios séricos dos procolágeno tipo III (PSPC III) poderiam, segundo alguns autores, estar correlacionados com o grau de fibrose, com a atividade fibrogênica, entre outros significados. A determinaçäo dos PSPCIII tem sido considerada útil no estudo evolutivo de algumas doenças hepáticas. Foram estudados 19 esquistossomóticos, 16 da forma clínica hepatointestinal (HI) e três da forma hepatoesplênica compensada (HEC) e um grupo controle, cosntituído de 10 indivíduos sadios. Os pacientes foram submetidos à avaliaçäo clínico-laboratorial antes e aproximadamente seis meses após o tratamento com oxamniquine. Para a dosagem dos PSPCIII, utilizaram-se kits de radioimunoensaio. Näo houve diferença estatisticamente significante quando se comapraram as médias dos valores séricos dos PSPCIII antes (13,6ng/ml e após (11,3ng/ml) o tratamento com oxamniquine. Os autores comentam a respeito das dificuldades para interpretaçäo dos resultados