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1.
Braz. j. biol ; 84: e251970, 2024. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1345559

ABSTRACT

Abstract In order to better understand the ossification processes in anurans our study was carried out on tadpoles and adults of Lithobates catesbeianus. In this sense, we characterized the kinetic properties of alkaline phosphatase with p-nitrophenylphosphatase (pNPP) and pyrophosphate (PPi) and evaluated the activities of tartrate-resistant acid phosphatase and acid phosphatase. The enzyme extracts were obtained from tadpoles and adult femurs, which were divided into epiphysis and diaphysis. After homogenization, the samples were submitted to differential centrifugation to obtain cell membranes and, further, to phospholipase C (PIPLC) treatment, to remove membrane-bound proteins anchored by phosphatidylinositol. The average of specific activity for pNPP hydrolysis (at pH 10.5) by alkaline phosphatase released by phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus cereus among different bone regions at different animal ages was 1,142.57 U.mg-1, while for PPi hydrolysis (at pH 8.0), it was 1,433.82 U.mg-1. Among the compounds tested for enzymatic activity, the one that influenced the most was EDTA, with approximately 67% of inhibition for pNPPase activity and 77% for PPase activity. In the case of kinetic parameters, the enzyme showed a "Michaelian" behavior for pNPP and PPi hydrolysis. The Km value was around 0.6mM for pNPPase activity and ranged from 0.01 to 0.11mM for PPase activity, indicating that the enzyme has a higher affinity for this substrate. The study of pNPP and PPi hydrolysis by the enzyme revealed that the optimum pH of actuation for pNPP was 10.5, while for PPi, which is considered the true substrate of alkaline phosphatase, was 8.0, close to the physiological value. The results show that regardless of the ossification type that occurs, the same enzyme or isoenzymes act on the different bone regions and different life stages of anurans. The similarity of the results of studies with other vertebrates shows that anurans can be considered excellent animal models for the study of biological calcification.


Resumo Para melhor compreender o processo de ossificação em anuros, nosso estudo foi conduzido em girinos e adultos de Lithobates catesbeianus. Nesse sentido, as propriedades cinéticas da fosfatase alcalina com p-nitrofenilfosfato (pNPP) e pirofosfato (PPi) foram caracterizadas, e as atividades enzimáticas das fosfatases ácida e ácida tartarato resistente foram avaliadas. Os extratos enzimáticos foram obtidos de fêmur de girinos e adultos, divididos em epífise e diáfise. Após a homogeneização as amostras foram submetidas à centrifugação diferencial para obter membrana celular e, em seguida, ao tratamento com fosfolipase C (PIPLC), para remover as proteínas de membrana ancoradas por fosfatidilinositol. A média da atividade específica da fosfatase alcalina, liberada pela PIPLC de Bacillus cereus, para a hidrólise de pNPP (pH 10,5) nas diferentes regiões do fêmur e idades dos animais foi de 1.142,57 U.mg-1, enquanto para a hidrólise do PPi (pH 8,0) foi de 1.433,82 U.mg-1. Entre os compostos testados para a atividade enzimática, o de maior influência foi o EDTA, inibindo aproximadamente 67% e 77% das atividades de pNPPase e PPase, respectivamente. Quanto aos parâmetros cinéticos, a enzima apresentou comportamento Michaeliano para a hidrólise dos dois substratos. O valor de Km foi de 0,6 mM para a atividade de pNPPase e variou de 0,01 a 0,11 para a atividade de PPase, indicando uma maior afinidade por esse substrato. O estudo da hidrólise de pNPP e PPi revelou que o pH ótimo aparente de atuação foi de 10,5 para o pNPP e 8,0 para o PPi, próximo ao fisiológico, sendo que esse é considerado o substrato natural da fosfatase alcalina. Os resultados demonstram que, apesar do tipo de ossificação que ocorre, a mesma enzima ou isoenzimas, atuam nos diferentes locais do osso e estágios de vida dos anuros. A similaridade dos estudos com os realizados com outros vertebrados apontam que os anuros podem ser considerados excelentes modelos animais para o estudo da calcificação biológica.


Subject(s)
Animals , Osteogenesis , Alkaline Phosphatase/metabolism , Rana catesbeiana , Bone and Bones/metabolism , Kinetics
2.
Medicina (Ribeirao Preto, Online) ; 55(1)maio 2022. ilus, tab
Article in Portuguese | LILACS | ID: biblio-1410579

ABSTRACT

Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico (AU)


Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Osteoporosis , Bone Diseases, Metabolic , Alkaline Phosphatase , Chronic Pain , Fractures, Spontaneous , Hypophosphatasia/diagnosis
3.
Arch. argent. pediatr ; 120(1): e21-e24, feb 2022. tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1353741

ABSTRACT

La hipofosfatasia es un trastorno hereditario raro causado por mutaciones en el gen ALPL. Causa defectos en la mineralización ósea y dental, función respiratoria anormal, convulsiones, hipotonía, dolor óseo y nefrocalcinosis. Las formas clínicas se reconocen según la edad al diagnóstico y la gravedad. Presentamos el caso de una lactante con fontanela anterior agrandada, bóveda craneal blanda, fracturas, dificultad respiratoria y convulsiones. El análisis bioquímico mostró hipercalcemia, fosfato sérico normal y fosfatasa alcalina sérica baja. La radiografía mostró hipomineralización, fracturas y callos. La concentración plasmática de piridoxal-5'-fosfato era de 762 mg/l (intervalo normal: 5-50) y la concentración de fosfoetanolamina en orina era de 1015 mmol/l (intervalo normal: 15-341). El análisis del gen ALPL mostró dos mutaciones heterocigotas compuestas, una de las cuales es novedosa. El diagnóstico y tratamiento tempranos de la hipofosfatasia perinatal podría mejorar los resultados y tener un impacto positivo en la sobrevida.


Hypophosphatasia (HPP) is a rare inherited disorder caused by mutations in the ALPL gene. Mineralization defect in bones and teeth, abnormal respiratory function, seizures, hypotonia, bone pain, and nephrocalcinosis can be observed. Clinical forms are usually recognized based on age at diagnosis and severity of features. We present an infant with an enlarged anterior fontanelle, soft calvarium, fractures, respiratory distress, and seizures. Biochemical analysis showed hypercalcemia, normal serum phosphate, and low serum alkaline phosphatase (ALP) levels. X-ray showed hypomineralization, fractures, and callus formations. Plasma pyridoxal 5'-phosphate (PLP) was 762 mg/L (NV : 5-50) and urine phosphoethanolamine (PEA) was 1015 mmol/L (NV : 15-341) and ALPL gene analysis showed two compound heterozygous mutations, one of which is a novel one. Early diagnosis and treatment of perinatal HPP may improve outcomes and might have a positive impact on survival.


Subject(s)
Humans , Female , Pregnancy , Infant , Hypophosphatasia/diagnosis , Hypophosphatasia/genetics , Hypophosphatasia/drug therapy , Nephrocalcinosis , Seizures , Alkaline Phosphatase/genetics , Alkaline Phosphatase/therapeutic use , Mutation
4.
Article in Portuguese | LILACS | ID: biblio-1368967

ABSTRACT

RESUMO:Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico. (AU)


ABSTRACT: Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Osteoporosis , Alkaline Phosphatase , Fractures, Spontaneous , Hypophosphatasia/diagnosis
5.
Chinese Journal of Biotechnology ; (12): 1159-1172, 2022.
Article in Chinese | WPRIM | ID: wpr-927771

ABSTRACT

It is known that low-frequency pulsed electromagnetic fields (PEMFs) can promote the differentiation and maturation of rat calvarial osteoblasts (ROBs) cultured in vitro. However, the mechanism that how ROBs perceive the physical signals of PEMFs and initiate osteogenic differentiation remains unknown. In this study, we investigated the relationship between the promotion of osteogenic differentiation of ROBs by 0.6 mT 50 Hz PEMFs and the presence of polycystin2 (PC2) located on the primary cilia on the surface of ROBs. First, immunofluorescence staining was used to study whether PC2 is located in the primary cilia of ROBs, and then the changes of PC2 protein expression in ROBs upon treatment with PEMFs for different time were detected by Western blotting. Subsequently, we detected the expression of PC2 protein by Western blotting and the effect of PEMFs on the activity of alkaline phosphatase (ALP), as well as the expression of Runx-2, Bmp-2, Col-1 and Osx proteins and genes related to bone formation after pretreating ROBs with amiloride HCl (AMI), a PC2 blocker. Moreover, we detected the expression of genes related to bone formation after inhibiting the expression of PC2 in ROBs using RNA interference. The results showed that PC2 was localized on the primary cilia of ROBs, and PEMFs treatment increased the expression of PC2 protein. When PC2 was blocked by AMI, PEMFs could no longer increase PC2 protein expression and ALP activity, and the promotion effect of PEMFs on osteogenic related protein and gene expression was also offset. After inhibiting the expression of PC2 using RNA interference, PEMFs can no longer increase the expression of genes related to bone formation. The results showed that PC2, located on the surface of primary cilia of osteoblasts, plays an indispensable role in perceiving and transmitting the physical signals from PEMFs, and the promotion of osteogenic differentiation of ROBs by PEMFs depends on the existence of PC2. This study may help to elucidate the mechanism underlying the promotion of bone formation and osteoporosis treatment in low-frequency PEMFs.


Subject(s)
Animals , Rats , Alkaline Phosphatase/metabolism , Electromagnetic Fields , Osteoblasts/metabolism , Osteogenesis/genetics , TRPP Cation Channels/physiology
6.
São Paulo; s.n; s.n; 2022. 66 p. graf, ilus.
Thesis in English | LILACS | ID: biblio-1397067

ABSTRACT

Neutrophils are polymorphonuclear leukocytes that play a key role in the organism defense. These cells enroll in a range of actions to ensure pathogen elimination and orchestrate both innate and adaptative immune responses. The main physiological structures of neutrophils are their storage organelles that are essential since the cells activation and participate in all their functions. The storage organelles are divided into 2 types: granules and secretory vesicles. The granules are subdivided into azurophilic, specific and gelatinase. The granules are distinguished by their protein content, and since they play an important role on the neutrophil function, the knowledge of the proteins stored in these organelles can help to better understand these cells. Some proteins are present in high abundance and are used as markers for each storage organelle. These proteins are myeloperoxidase (MPO) for azurophil granules, neutrophil gelatinase associated with lipocalin-2 (NGAL) and lactoferrin (LTF) for specific granules, matrix metalloproteinase-9 (MMP9) for gelatinase granules and alkaline phosphatase (AP) for secretory vesicles. The isolation of neutrophils granules, however, is challenging and the existing procedures rely on large sample volumes, about 400 mL of peripheral blood or 3 x 108 neutrophils, not allowing for multiple biological and technical replicates. Therefore, the aim of this study was to develop a miniaturized neutrophil granules isolation method and to use biochemical assays, mass spectrometry-based proteomics and a machine learning approach to investigate the protein content of the neutrophils storage organelles. With that in mind, 40 mL of the peripheral blood of three apparently healthy volunteers were collected. The neutrophils were isolated, disrupted using nitrogen cavitation and organelles were fractionated with a discontinuous 3-layer Percoll density gradient. The presence of granules markers in each fraction was assessed using western blot , gelatin zymography and enzymatic assays. The isolation was proven successful and allowed for a reasonable separation of all neutrophils storage organelles in a gradient of less than 1 mL, about 37 times smaller than the methodsdescribed in the literature. Moreover, mass spectrometry-based proteomics identified 369 proteins in at least 3 of the 5 samples, and using a machine learning strategy, the localization of 140 proteins was predicted with confidence. Furthermore, this study was the first to investigate the proteome of neutrophil granules using technical and biological replicates, creating a reliable database for further studies. In conclusion, the developed miniaturized method is reproducible, cheaper, and reliable. In addition, it provides a resource for further studies exploring neutrophil granules protein content and mobilization during activation with different stimuli


Neutrófilos são leucócitos polimorfonucleares que possuem papel fundamental na defesa do organismo. Essas células desempenham diversas ações a fim de assegurar a eliminação de um patógeno e, além disso, orquestram a resposta imune inata e adaptativa. O conjunto composto pelos grânulos de armazenamento e as vesículas secretórias compõe a principal estrutura fisiológica dos neutrófilos. Estes componentes são essenciais desde a ativação celular, participando de todas as funcionalidades desta célula. Os grânulos são subdivididos em azurófilos, específicos e gelatinase. Eles podem ser distinguidos por meio de seu conteúdo proteico e, como são importantes na funcionalidade dos neutrófilos, identificar quais proteínas são armazenadas nestas organelas é imprescindível para entender melhor essa célula como um todo. Algumas proteínas, estão presentes de forma abundante e, portanto, são utilizadas como marcadores dos grânulos. Tais proteínas são mieloperoxidase (MPO) para os grânulos azurófilos, gelatinase de neutrófilo associada a lipocalina (NGAL) e lactoferrina (LTF) para os específicos, metaloproteinase de matrix 9 (MMP9) para os grânulos de gelatinase e fosfatase alcalina (AP) para as vesículas secretórias. Isolar estas estruturas, no entanto, é desafiador visto que os protocolos existentes na literatura utilizam grandes volumes de amostra, cerca de 400 mL de sangue ou 3 x 108 neutrófilos, para apenas um isolamento, impedindo a realização de replicatas técnicas e biológicas. Desta forma, o objetivo do presente estudo foi desenvolver um protocolo miniaturizado de isolamento dos grânulos neutrofílicos e utilizar métodos bioquímicos, de proteômica e machine learning para investigar o conteúdo proteico destas estruturas celulares. Para isto, 40 mL de sangue periférico de três voluntários aparentemente saudáveis foi coletado. Os neutrófilos foram então isolados, lisados com cavitação de nitrogênio e o fracionamento subcelular foi realizado baseado em um gradiente descontínuo de 3 camadas de Percoll. O método de isolamento foi avaliado através da investigação dos marcadores utilizando western blotting (WB), zimografia de gelatina e ensaios enzimáticos em cada fração coletada. O isolamento demonstrou-se eficiente e permitiu uma ótima separação dos grânulosem um gradiente menor que 1 mL, cerca de 37 vezes menor que os métodos atualmente descritos na literatura. Além disso, a análise proteômica foi capaz de identificar 369 proteínas presentes em pelo menos 3 das 5 réplicas investigadas e, utilizando ferramentas de machine learning, 140 proteínas foram classificadas como pertencentes a um dos tipos de grânulos ou vesícula secretória com alto nível de confiabilidade. Por fim, o presente estudo foi o primeiro a investigar o proteoma dos grânulos utilizando replicatas técnicas e biológicas, criando e fornecendo uma base de dados robusta que poderá ser utilizada em estudos futuros. Conclui-se, portanto, que a metodologia miniaturizada desenvolvida é eficaz, reprodutível e mais barata, além de permitir estudos mais complexos e profundos sobre o proteoma dos grânulos dos neutrófilos em diferentes momentos celulares, tais como quando ativados via estímulos distintos


Subject(s)
Proteomics/instrumentation , Methodology as a Subject , Neutrophils/classification , Mass Spectrometry/methods , Cavitation , Blotting, Western/instrumentation , Gelatinases/analysis , Alkaline Phosphatase/adverse effects , Machine Learning/classification
7.
Braz. dent. sci ; 25(1): 1-6, 2022. tab, ilus
Article in English | LILACS, BBO | ID: biblio-1361486

ABSTRACT

Objetivo: A progressão da cicatrização de um alvéolo após uma extração é geralmente analisada por meio de exame clínico e investigação radiográfica. Embora a cicatrização do tecido mole geralmente seja mantida bem, a progressão da cicatrização do tecido duro é mais difícil de prever e gerenciar, com problemas como alvéolo seco ou má união do osso subjacente. Biomarcadores séricos para progressão da cicatrização óssea, como a Fosfatase Alcalina (FAL), podem ser úteis como ferramenta diagnóstica para intervenção precoce. Material e Métodos:Vinte indivíduos saudáveis de 18-30 anos de idade que deveriam extrair dentes do siso inferiores impactados foram incluídos. Foram coletados 2 ml de sangue, antes do tratamento e 48 horas depois, as amostras seguintes foram coletadas 1 mês, 2 meses e 3 meses após o procedimento. As radiografias intraorais foram realizadas no final dos três meses. Resultados: Houve uma correlação obtida com a cura e os níveis de FAL em intervalos de tempo de 1, 2 e 3 meses (p <0,05), onde 17 pacientes que tiveram um aumento substancial nos níveis de FAL também tiveram cura satisfatória após três meses. Três indivíduos que não apresentaram aumento no nível de FAL não tiveram cura satisfatória. Conclusão: FAL é um biomarcador suplementar útil para a consolidação óssea (AU)


Objective: The progression of a healing socket following an extraction is usually analysed through clinical examination and radiographic investigation. Whilst soft tissue healing is usually maintained well, healing progression of hard tissue is more challenging to predict and manage, with issues such as a dry socket or mal-union of the underlying bone. Serum biomarkers for bone healing progression, such as alkaline phosphatase (ALP), could prove helpful as a diagnostic tool for early intervention. Material and Methods: Twenty healthy 18-30-year-old individuals who were to extract lower impacted wisdom teeth were included. 2ml of blood was collected before treatment, 48 hours after then following samples were collected 1 month, 2 months and 3 months after the procedure. Intra-oral radiographs were taken at the end of the three months. Results: There was a significant correlation elicited with the healing and ALP levels at 1,2 & 3 months' time intervals (p<0.05), where 17 patients who had a substantial increase in the levels of ALP also had satisfactory healing after three months. Three individuals who did not show any increase in ALP level did not have satisfactory healing. Conclusion:ALP is a useful supplementary biomarker for bone healing.(AU)


Subject(s)
Humans , Adult , Surgery, Oral , Tooth Extraction , Wound Healing , Alkaline Phosphatase
8.
Rev. bras. ortop ; 56(6): 796-803, Nov.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1357140

ABSTRACT

Abstract Objective To evaluate the role of serum alkaline phosphatase (ALP) and ultrasonography (USG) in monitoring the progress of treatment in diaphyseal non-unions. Methods This prospective observational cohort study included adult patients with diaphyseal fractures of major long bones previously treated with internal fixation and eventually resulting in non-union. Following the definitive treatment for non-union, the patients were followed-up periodically for six months, and serial monitoring of the levels of ALP and USG were performed along with radiographs (X-rays) to ascertain the status of the union. Results After an initial rise at seven weeks, ALP levels declined to normal values in fractures which united, whereas they remained high in cases of persistent non-union. Similarly, after an elevation of the vascular resistive index (RI) at around 12 weeks in all the patients, it decreased in cases progressing to union, while it remained persistently high even at 24 weeks in fractures failing to unite. Cases of persistent non-union continued to show hypoechogenic callus at 24 weeks instead of converting into hyperechogenic callus, as observed in cases which progressed to union. Conclusion Significant changes suggestive of union appeared simultaneously on the X-rays, USG and ALP levels during the follow-up. However, a serial examination of the ALP levels and USG during the follow-up gave a hint of the direction of progress in the healing process of fracture non-union. Their role in monitoring the outcome of nonunion is more complimentary than supplementary to the X-rays.


Resumo Objetivo Avaliar o papel da concentração sérica de fosfatase alcalina (FA) e da ultrassonografia no monitoramento do progresso do tratamento da ausência de consolidação em fraturas diafisárias. Métodos Este estudo de coorte observacional prospectivo incluiu pacientes adultos com fraturas diafisárias dos principais ossos longos previamente submetidas a fixação interna sem consolidação. Após o tratamento definitivo, os pacientes foram avaliados periodicamente por seis meses, com realização seriada de ultrassonografia, determinação da concentração de FA e radiografias para verificar a presença de consolidação. Resultados Após um aumento inicial em sete semanas, os níveis de FA voltaram ao valor normal em pacientes com fraturas consolidadas, mas continuaram elevados nos casos de ausência de consolidação. Da mesma forma, após uma elevação do índice de resistência (IR) vascular em cerca de 12 semanas em todos os pacientes, o IR diminuiu nos casos que progrediram para consolidação, mas continuou alto até as 24 semanas em fraturas não consolidadas. Os casos com ausência de consolidação ainda apresentavam calo hipoecogênico às 24 semanas, que não se converteu no calo hiperecogênico observado nos casos que progrediram para consolidação. Conclusão Alterações significativas sugestivas de consolidação foram simultaneamente observadas nas radiografias, na ultrassonografia e na concentração de FA durante o período de acompanhamento. No entanto, a realização seriada de exames da concentração de FA e de ultrassonografia durante o acompanhamento indicou o progresso da consolidação da fratura. Seu papel no monitoramento da ausência de consolidação é mais complementar do que suplementar à radiografia.


Subject(s)
Humans , Male , Female , Bony Callus , Ultrasonography , Outcome Assessment, Health Care , Alkaline Phosphatase , Fractures, Bone/therapy , Fractures, Ununited
9.
Rev. bras. med. esporte ; 27(3): 335-337, July-Sept. 2021. tab
Article in English | LILACS | ID: biblio-1288579

ABSTRACT

ABSTRACT Introduction One of the evaluation factors of human health is bone health, and an evaluation index of bone health is osteoporosis. Sports are an effective way to improve the human body. Objective The paper discusses the effects of different exercise intensities on human bone health. Methods The thesis selected 51 female college students, designed different exercise intensities of fitness running intervention programs, and conducted a 12-month exercise intervention. We divide female college students into three groups. The subjects' bone mineral density (BMD), serum alkaline phosphatase (ALP), and serum osteocalcin (BGP) were tested before and after the experiment. Results The differences in femoral BMD, serum ALP, serum BGP, and lumbar spine BMD of the three groups of volunteers were significant (P<0.05), while the differences in ulna and radius BMD were not significant. Conclusions Sports can promote human bone health. At the same time, the effect of fitness running on human BMD is site-specific. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Introdução Um dos fatores de avaliação da saúde humana é a saúde óssea, e um índice de avaliação da saúde óssea é a osteoporose. Os esportes são uma forma eficaz de melhorar o corpo humano. Objetivo o artigo discute os efeitos de diferentes intensidades de exercício na saúde óssea humana. Métodos A tese selecionou 51 universitárias, elaborou diferentes intensidades de exercícios em programas de intervenção de corrida de aptidão e conduziu uma intervenção de exercícios de 12 meses. Dividimos as universitárias em três grupos. A densidade mineral óssea (BMD), fosfatase alcalina sérica (ALP) e osteocalcina sérica (BGP) dos indivíduos foram testadas antes e depois do experimento. Resultados As diferenças na DMO femoral, ALP sérica, BGP sérica e DMO da coluna lombar dos três grupos de voluntários foram significativas (P <0,05), enquanto as diferenças na DMO da ulna e rádio não foram significativas. Conclusão O esporte pode promover a saúde óssea humana. Ao mesmo tempo, o efeito da corrida adaptativa na DMO humana é específico do local. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción Uno de los factores de evaluación de la salud humana es la salud ósea y un índice de evaluación de la salud ósea es la osteoporosis. Los deportes son una forma eficaz de mejorar el cuerpo humano. Objetivo El artículo analiza los efectos de diferentes intensidades de ejercicio en la salud ósea humana. Métodos La tesis seleccionó a 51 estudiantes universitarias, diseñó diferentes intensidades de ejercicio de programas de intervención para correr y realizó una intervención de ejercicio de 12 meses. Dividimos a las estudiantes universitarias en tres grupos. La densidad mineral ósea (DMO), la fosfatasa alcalina sérica (ALP) y la osteocalcina sérica (BGP) de los sujetos se analizaron antes y después del experimento. Resultados Las diferencias en la DMO femoral, la ALP sérica, la BGP sérica y la DMO de la columna lumbar de los tres grupos de voluntarios fueron significativas (P <0,05), mientras que las diferencias en la DMO del cúbito y del radio no fueron significativas. Conclusión Los deportes pueden promover la salud ósea humana. Al mismo tiempo, el efecto de la actividad física en la DMO humana es específico del sitio. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.


Subject(s)
Humans , Female , Bone and Bones/physiology , Bone Density , Osteocalcin/blood , Alkaline Phosphatase/blood , High-Intensity Interval Training
10.
Arch. endocrinol. metab. (Online) ; 65(3): 289-294, May-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1285157

ABSTRACT

ABSTRACT Objectives: Alkaline phosphatase (ALP) is the main laboratory marker of hypophosphatasia (HPP), a rare disease unknown to most physicians. The prevalence of HPP has been widely discussed in the literature due to the diverse phenotypes of HPP. The purpose of this study was to search for patients with hypophosphatasemia based on previous biochemistry tests and reevaluate them to confirm the diagnosis of HPP. Subjects and methods: A total of 289,247 biochemical tests for ALP in adults were performed from 2015 to 2019 in two tertiary hospitals in Rio de Janeiro were reviewed (Clementino Fraga Filho University Hospital - HUCFF - and Bonsucesso Federal Hospital - BFH). Results: A total of 1,049 patients were identified with ALP levels below 40 U/L, and 410 patients had hypophosphatasemia confirmed by at least two exams. After the active search of medical reports and/or interviews based on structured questionnaires, 398 subjects were excluded due to secondary causes of reduced ALP. The remaining 12 patients were invited to attend the medical consultation at HUCFF, accompanied by at least one first-degree relative. None of the patients or their relatives had a history or clinical manifestations consistent with HPP. Serum ALP was within reference values in all relatives, but persistently low in further laboratory evaluation in all the 12 patients, in whom secondary causes were ruled out. Thus, we cannot exclude the possibility that they might carry the mutations associated with HPP. Conclusion: Further image evaluations and genetic testing would be appropriate to confirm this asymptomatic adult form of HPP.


Subject(s)
Humans , Adult , Alkaline Phosphatase/blood , Hypophosphatasia/diagnosis , Brazil
11.
Rev. bras. ortop ; 56(3): 351-355, May-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1288681

ABSTRACT

Abstract Objective To compare the serum levels of vitamin D and minerals in children with or without isolated distal radius fractures. Methods The present prospective clinical study included 50 children (aged between 5 and 15 years) with isolated distal radius fractures who were admitted to our emergency unit between February and May 2018 as the study group (group A), and 50 healthy children with no history of fracture as the control group (group B). Peripheral venous blood samples were obtained and analyzed for measurements of 25-hydroxyvitamin D (25(OH)D), calcium (Ca), magnesium (Mg), phosphorus (P), alkaline phosphatase (ALP), and parathyroid hormone (PTH) in both groups. Patient characteristics and peripheral venous blood samples were compared between the groups. Results The mean age, height, weight, body mass index (BMI) and gender distribution were similar in both groups. There were no statistical differences in the blood analyses, including Ca, Mg, P, ALP, and PTH. However, the serum levels of 25(OH)D were statistically lower in group A when compared to group B (p < 0.001), and the number of patients with 25(OH)D insufficiency was statistically higher in group A than in group B (p = 0.012). Conclusion Children with isolated distal radius fracture should be informed about vitamin D deficiency, and, in children with low levels of vitamin D, supplementation may be considered.


Resumo Objetivo Comparar os níveis séricos de vitamina D e minerais de crianças com ou sem fraturas isoladas da extremidade distal do rádio. Métodos Este estudo clínico prospectivo incluiu 50 crianças (com idade entre 5 e 15 anos) com fratura isolada distal do rádio que deram entrada em nossa unidade de emergência entre fevereiro e maio de 2018 como grupo de estudo (grupo A), e 50 crianças saudáveis sem histórico de fratura como grupo controle (grupo B). Foram obtidas e analisadas amostras de sangue venoso periférico para medições de 25-hidroxivitamina D (25(OH)D), Cálcio (Ca), Magnésio (Mg), Fósforo (P), fosfatase alcalina (FA) e hormônio da paratireoide (HPT) em ambos os grupos. As características dos pacientes e as amostras de sangue venoso periférico foram comparadas entre os grupos. Resultados A média de idade, altura, peso, índice de massa corporal (IMC) e distribuição de gênero foram semelhantes em ambos os grupos. Não houve diferenças estatísticas nas análises sanguíneas, incluindo Ca, Mg, P, FA e HPT. No entanto, os níveis séricos de 25(OH)D foram estatisticamente menores no grupo A do que no grupo B (p < 0,001), e o número de pacientes com insuficiência de 25(OH)D foi estatisticamente maior no grupo A do que no grupo B (p = 0,012). Conclusão Crianças com fratura isolada distal do rádio devem ser informadas sobre deficiência de vitamina D, e, em crianças com baixos níveis de vitamina D, a suplementação pode ser considerada.


Subject(s)
Humans , Child , Parathyroid Hormone , Radius Fractures , Vitamin D , Vitamin D Deficiency , Body Weight , Body Mass Index , Calcium , Alkaline Phosphatase
12.
Article in Chinese | WPRIM | ID: wpr-879608

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature.@*METHODS@#Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software.@*RESULTS@#The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.


Subject(s)
Child , Female , Humans , Alkaline Phosphatase , Genomics , High-Throughput Nucleotide Sequencing , Hypophosphatasia/genetics , Mutation , Exome Sequencing
13.
Article in English | WPRIM | ID: wpr-962186

ABSTRACT

ABSTRACT@#The goal of this study was to investigate differences in alkaline phosphatase (ALP) levels in young and old rabbits after administering the soybean isoflavone genistein during orthodontic tooth movement. Twelve rabbits were used and assigned to four groups (n = 3); OG (old rabbits), OGS (old rabbits + soybean), YG (young rabbits), and YGS (young rabbits + soybean). The rabbit mandibulary incisors were distalised using a nickel-titanium open coil spring (50 g force). Genistein was administered from the initial orthodontic force delivery until day 21, at a dose of 1.2 mg/kg BW once a day. ALP levels (U/mg) were measured on days 1, 7, 14, 21 after orthodontic force delivery using a UV-Vis 6300 spectrophotometer at a 405 nm wavelength. The results were analysed by one-way analysis of variance followed by Tukey’s Honest Significant Difference (HSD) test (p < 0.05). The ALP levels between the young and old age groups were significantly different. ALP levels were highest in the YGS group, and significantly lowest in the OG group (p < 0.05). Moreover, the ALP level of the OGS group was significantly higher than that in the OG group (p < 0.05). In conclusion, daily consumption of soybean isoflavone genistein could enhance ALP levels during orthodontic tooth movement, particularly in older rabbits.


Subject(s)
Rabbits , Alkaline Phosphatase , Tooth Movement Techniques
14.
Article in Chinese | WPRIM | ID: wpr-921907

ABSTRACT

OBJECTIVE@#To explore effect of tobramycin (TOB) on healing of femoral fractures in rats.@*METHODS@#Totally 32 male sprague-dawley (SD) rats were selected and randomly divided into sham group (group A), fracture group (group B), fracture with TOB group (group C) and fracture + TOB + IWR-1 group (group D), 8 rats in each group. Close femoral fracture model in rats were established in group B, C and D, group A was sham operation without otherwise process. Group D was intraperitoneal injected 100 μl (8 μM) of Wnt pathway inhibitor IWR-1-endo (IWR-1) before molding at 1 day. At 1 day after molding, 100 μl (100 μM) of TOB was intraperitoneally injected into group C and D at once a day for 7 days. At 7 weeks after modling, fracture healing of group B, C and D were observed by X-ray, Western blotting was appilied to detect alkaline phosphatase(ALP) and Runt related transcription factor 2 (RUNX2) and β-catenin of Wnt passway.@*RESULTS@#X-ray results showed fracture line disappeared, callus formation and fracture healing well in group C compared with begning of molding; while a little fracture line, callus formation and fracture malunion in group B and d could be seen. Western blotting results showed ALP, RUNX2 and expression of β-catenin in group B, C and D were higher than that of group A (@*CONCLUSION@#Tobramycin could promote osteoblast differentiation and fracture healing by stimulating Wnt / β-catenin signaling pathway, up regulating expression of ALP and RUNX2.


Subject(s)
Animals , Male , Rats , Alkaline Phosphatase , Cell Differentiation , Core Binding Factor Alpha 1 Subunit/genetics , Femoral Fractures , Fracture Healing , Osteogenesis , Tobramycin , Wnt Signaling Pathway , beta Catenin/metabolism
15.
Hepatología ; 2(2): 392-397, 2021. ilus, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1396515

ABSTRACT

La manifestación paraneoplásica conocida como síndrome de Stauffer tiene una presentación atípica, caracterizada por ictericia y colestasis intrahepática. Presentamos el caso de un paciente de 53 años de edad, con antecedente de una masa renal derecha en plan de resección quirúrgica programada, con cuadro de evolución de dolor abdominal en hipocondrio derecho e ictericia. A su ingreso se documentó hepatoesplenomegalia, elevación de bilirrubinas a expensas de la directa, y de fosfatasa alcalina junto con elevación de transaminasas. Se descartaron causas obstructivas a nivel de vía biliar intra y extrahepática. No se documentaron metástasis o lesiones focales a nivel de parénquima, ni lesiones de etiología vascular que explicaran el cuadro. También se descartó hepatitis B, C e infección por VIH, por lo cual se consideró un probable síndrome de Stauffer. Fue llevado a nefrectomía intrahospitalaria, con posterior diagnóstico patológico compatible con carcinoma de células claras. Luego del procedimiento se normalizó la bioquímica hepática y se corrigió la ictericia. Es importante reconocer que la afectación hepática en el contexto de neoplasias, no es solo atribuida a metástasis a distancia, sino también a la existencia de síndromes paraneoplásicos como condicionantes.


The paraneoplastic manifestation known as Stauffer syndrome has an atypical presentation, characterized by jaundice and intrahepatic cholestasis. We present the case of a 53-year-old patient, with a history of a right renal mass with a planned surgical resection, who developed abdominal pain in the right upper quadrant and jaundice. Upon admission, hepatosplenomegaly, elevated bilirubin, at the expense of direct bilirubin, alkaline phosphatase and elevated transaminases were documented. Intra- and extrahepatic bile ducts obstruction were ruled out. There were no documented metastases or focal lesions at the level of the parenchyma, or lesions of vascular etiology that could explain the condition. Hepatitis B, C and HIV infection were also ruled out, and a probable Stauffer syndrome was considered. In-hospital nephrectomy was performed, with subsequent pathology compatible with clear cell carcinoma. After the procedure, liver biochemistry was normalized and jaundice was corrected. It is important to recognize that liver involvement in the context of neoplasms is not only attributed to distant metastases but to the existence of paraneoplastic syndromes as determining factors.


Subject(s)
Humans , Male , Middle Aged , Paraneoplastic Syndromes/etiology , Carcinoma, Renal Cell/complications , Paraneoplastic Syndromes/diagnosis , Carcinoma, Renal Cell/diagnosis , Cholestasis, Intrahepatic/diagnosis , Alkaline Phosphatase/analysis , Transaminases/analysis , Jaundice/diagnosis
16.
An. Fac. Cienc. Méd. (Asunción) ; 54(2): 145-150, 2021.
Article in Spanish | LILACS | ID: biblio-1281112

ABSTRACT

Paciente de sexo femenino de 60 años de edad, con antecedente de carcinoma ductal de mama izquierda, presentó dolor agudo en epigastrio que se acompaña de 6 meses de dispepsia, saciedad precoz y pirosis; con una pérdida de 9 kilogramos en 2 meses. Refirió coluria, negó ictericia y acolia. Las pruebas de función hepática mostraron un patrón de colestasis con elevación de gama glutamiltrasferasa (GGT) y fosfatasa alcalina (FA). Fue diagnosticada con un Colangiocarcinoma perihiliar basado en hallazgos abdominales de tomografía y resonancia, con un nódulo parenquimatoso en el segmento 8 del hígado como un tumor infiltrante periductal. El diagnóstico presuntivo fue el de Tumor de Klatskin, pero la anatomía patológica fue compatible con metástasis de carcinoma ductal de mama (CK7 + / GATA3 +). El informe complementario mostró HER-2 negativo y estrógeno negativo (ER) y progesterona (PR) por lo que el inmunofenotipo final fue ER- / PR-; HER2- con índice de proliferación Ki67 <5%, una metástasis de cáncer de mama triple negativo.


A 60-year-old female, with a medical history of a ductal carcinoma of the left breast, presented with sharp pain in epigastrium with 6 months of dyspepsia, early satiety and pyrosis and with the loss of 9 kilograms in 2 months. She referred choluria and denied jaundice and acholia. Liver function tests showed a cholestasis pattern with only elevated Gama Glutamyl Teransferase and alkaline phosphatase. She was diagnosed with a hilar cholangiocarcinoma based on abdominal CT and MRI findings, with a parenchymal nodule in segment 8 of the liver as a periductal infiltrating tumor. The presumed diagnosis was Klatskin Tumor, but the biopsied site was compatible with breast ductal carcinoma metastasis (CK7 + / GATA3 +). The complementary report showed negative HER-2 and negative estrogen (ER) and progesterone (PR) so the final immunophenotype is ER- / PR-; HER2- with proliferation index Ki67 <5%, a triple-negative breast cancer metastasis.


Subject(s)
Carcinoma , Cholestasis , Carcinoma, Ductal, Breast , Dyspepsia , Alkaline Phosphatase , Acute Pain , Anatomy
17.
Arch. endocrinol. metab. (Online) ; 65(5): 609-616, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345206

ABSTRACT

ABSTRACT Objective: To evaluate whether there is a relationship between diet quality and bone health in a group of elderly Brazilian women. Subjects and methods: A cross-sectional study was performed with 105 elderly women. Participants were evaluated regarding diet quality (good, needing improvement, and poor) and its relationship with bone mineral density (BMD), bone-specific alkaline phosphatase (BSAP), and C-telopeptide (CTX). Results: Fifty eight participants (55.2%) presented a poor-quality diet and 47 (44.8%) required dietary improvements, while no subjects presented a good quality diet. The group requiring dietary improvements had lower CTX [0.35 (0.05;1.09) vs. 0.52 (0.10;1.45); p = 0.03)] and BSAP (38.7 ± 12.9 U/L vs. 46.10 ± 15.2 U/L; p < 0.01) levels than the poor-quality diet group. Groups did not differ in terms of BMD. Conclusion: In this group of elderly Brazilian women, there was a relationship between diet quality and bone health, where worse diet quality was associated with higher levels of bone remodelling markers.


Subject(s)
Humans , Female , Aged , Bone and Bones , Bone Density , Biomarkers , Cross-Sectional Studies , Diet , Alkaline Phosphatase
18.
Braz. dent. j ; 31(6): 617-622, Nov.-Dec. 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132349

ABSTRACT

Abstract Recent studies suggest that osteoporosis, in addition to the damage caused in long bones, may cause deterioration in the jaws, especially in alveolar bone sites, with effects in the progress of periodontal disease as well as in bone healing. The aim of this study was to evaluate the effect of osteoporosis in the metabolism of rat alveolar bone osteoblasts. There were used 10 female rats divided in two experimental groups (Sham and OVX), which were ovariectomized and after 8 weeks euthanized to collect mandibular bone samples in order to isolate osteoblastic cells. The cells were cultured in 24-well plates to perform the in vitro experiments. After 7, 10 and 14 days, there were evaluated cell proliferation by MTT assay, in situ detection of alkaline phosphatase (ALP) as well as mineralized nodules and expression of genes associated to bone remodeling. Results showed that at 7, 10 and 14 days cell proliferation was lower for OVX group. In situ detection of ALP was higher at 7 days and lower at 10 and 14 days in OVX group. At 17 and 21 days, OVX group had a significative decrease of mineralization nodules. There was a downregulation in the expression of Alp, Bglap and Runx2 genes and an upregulation of Opg in OVX group, whereas Opn and Rankl modulation was similar between the evaluated groups. Our results suggest that osteoporosis has a deleterious effect on alveolar bone cells from ovariectomized rats, which might affect the treatment of diseases associated to the jaw bones.


Resumo Estudos recentes sugerem que a osteoporose, além dos danos provocados em ossos longos, pode causar deterioração dos ossos maxilares, especialmente na região do osso alveolar, com efeitos na progressão da doença periodontal assim como no reparo ósseo. O objetivo deste estudo foi avaliar o efeito da osteoporose no metabolismo de osteoblastos do osso alveolar mandibular de ratos. Foram utilizadas 10 ratas fêmeas divididas em dois grupos experimentais (Sham e OVX), que foram ovariectomizadas e após 8 semanas, eutanasiadas para coletar amostras do osso mandibular e isolar as células osteoblásticas. As células foram cultivadas em placas de cultura de 24 poços para serem realizados os experimentos in vitro. Após 7, 10 e 14 dias foram avaliados a proliferação celular pelo ensaio de MTT, detecção in situ de fosfatase alcalina (ALP) assim como de nódulos mineralizados e expressão quantitativa de genes associados à remodelação óssea. Os resultados mostraram que aos 7, 10 e 14 dias a proliferação celular foi menor para o grupo OVX. A detecção in situ de ALP foi maior aos 7 dias e menor aos 10 e 14 dias no grupo OVX. Aos 17 e 21 dias o grupo OVX apresentou uma diminuição dos nódulos mineralizados. Houve uma repressão na expressão dos genes Alp, Bglap e Runx2 e uma indução do gene Opg no grupo OVX, enquanto que a modulação dos genes Opn e Rankl foi similar entre os grupos experimentais. Nossos resultados sugerem que a osteoporose tem um efeito deletério no metabolismo de células do osso alveolar em ratas ovariectomizadas, o que pode afetar o tratamento de doenças associadas aos ossos maxilares


Subject(s)
Humans , Animals , Female , Rats , Osteoporosis/genetics , Osteoblasts , Bone and Bones , Ovariectomy , Bone Density , Alkaline Phosphatase
19.
Int. j. morphol ; 38(5): 1496-1507, oct. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1134467

ABSTRACT

RESUMEN: En la enfermedad hepática crónica el trasplante ortotópico es la única alternativa terapéutica actual pero es limitada por falta de donantes. Ensayos con células madre adultas en daño hepático agudo evidencian promisorios resultados. El objetivo de este trabajo fue evaluar en ratas con daño hepático crónico la efectividad de la infusión de células madre adiposas humanas (CMAd-h). Ratas con fibrosis hepática inducida por tioacetamida fueron agrupadas en: grupo I control que no recibió tioacetamida ni células madre, grupo II recibió tioacetamida y suero fisiológico i.v., grupo III recibió tioacetamida y células madre adiposas 1 x 106/kg i.v. vía vena de la cola. La regeneración hepática histológica se evaluó por el index METAVIR, mientras las Macrophagocytus stellatus, células estrelladas a- SMA+ y células colágeno I+ por inmunohistoquímica; el daño funcional se evaluó por los niveles sanguíneos de los analitos Aspartato Aminotransferasa (AST), Alanina Aminotransferasa (ALT), Fosfatasa Alcalina (ALP), úrea y nitrógeno ureico (BUN) y hemograma. Los resultados muestran atenuación del daño estructural hepático evidenciado por disminución de los nódulos, del grado de lesión histológica en el score Metavir, y disminución de Macrophagocytus stellatus, células a-SMA+ y células colágeno tipo I+; funcionalmente hay reducción moderada de AST, ALT, urea, BUN y disminución moderada de células blancas pero efecto favorable sobre el volumen corpuscular media y la hemoglobina corpuscular media. Ocho semanas después de la infusión hay escasa población de CMAd-h en el hígado. En conclusión la infusión intravenosa de CMAd-h en ratas disminuye el daño funcional y estructural de la fibrosis hepática con escasa persistencia de CMAd-h en el parénquima hepático. A nuestro conocimiento este es el primer trabajo que evalúa el efecto de las CMAd-h en el modelo daño hepático crónico murino y la persistencia de las células trasplantadas.


SUMMARY: In chronic liver disease, orthotopic transplantation is the only current therapeutic alternative but it is limited due to lack of donors. Trials with adult stem cells in acute liver damage show promising results. The aim of this work was to evaluate the effectiveness of human adipose stem cell (h-ASC) infusion in rats with chronic liver damage. Rats with thioacetamide- induced liver fibrosis were grouped into: group I control that did not receive thioacetamide and h-ASC, group II received thioacetamide and saline i.v., group III received thioacetamide and h-ASC 1 x 106/ kg i.v. via tail vein. Histological liver regeneration was evaluated by METAVIR index, while Macrophagocytus stellatus (Kupffer cells), stellate cells a-SMA+ and collagen I+ cells by immunohistochemistry; functional damage was evaluated by blood levels of the analytes Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Urea and Blood Urea Nitrogen (BUN) and hemogram. The results show attenuation of structural liver damage evidenced by decreased nodules, degree of histologic injury on Metavir score, and decreased Macrophagocytus stellatus, a-SMA+ cells and type I+ collagen cells; functionally there is moderate reduction of AST, ALT, urea, BUN and moderate decrease of white cells but favorable effect on mean corpuscular volume and mean corpuscular hemoglobin. Eight weeks after infusion there is a small population of h-ASC in the liver. In conclusion, intravenous infusion of h-ASC in rats reduces functional and structural damage of hepatic fibrosis with low persistence of h- ASC in the liver parenchyma. To our knowledge this is the first work that evaluates the effect of h-SC in the model of chronic murine liver damage and the persistence of transplanted cells.


Subject(s)
Animals , Female , Rats , Mesenchymal Stem Cell Transplantation/methods , Liver Cirrhosis, Experimental/therapy , Aspartate Aminotransferases/analysis , Immunohistochemistry , Treatment Outcome , Alanine Transaminase/analysis , Disease Models, Animal , Alkaline Phosphatase/analysis , Cell- and Tissue-Based Therapy/methods , Liver Cirrhosis, Experimental/pathology
20.
Arch. endocrinol. metab. (Online) ; 64(5): 623-629, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131137

ABSTRACT

SUMMARY Hypophosphatasia (HPP) is a rare disease with a high mortality rate in its severe forms. It is caused by mutations within the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme responsible for bone mineralization. In 2015, the Food and Drug Administration approved the use of asfotase alfa, the first medication showing benefit in the treatment of HPP. We describe a case with a 2-year follow-up of the first Brazilian child treated with asfotase alfa. A 5-year-old boy, born to consanguineous parents, was diagnosed with HPP at the age of 20 months. During prenatal ultrasonography, polyhydramnios and shortening of long bones were detected. After birth, he presented delayed motor development, repeated respiratory infections, and bone deformities. At the age of 2 years and 8 months, he started walking and had already lost his primary teeth. He had reduced levels of alkaline phosphatase (ALP), elevated levels of pyridoxal 5'-phosphate (PLP), and a p.Ala33Val (c.98C>T) missense mutation in homozygosis in the TNSALP gene. His parents and sister also had reduced ALP levels, high PLP levels, and the same mutation in heterozygosis. His father and sister were healthy, and his mother was diagnosed with rickets in childhood, which resulted in short physical stature and lower limb deformities. The patient was started on asfotase alfa at the age of 2 years and 10 months. After 2 years of treatment, he improved his motor skills, had no further episodes of severe respiratory infection, and showed improved radiological findings of rickets, without any severe side effect.


Subject(s)
Humans , Male , Infant, Newborn , Child, Preschool , Child , Alkaline Phosphatase , Hypophosphatasia/genetics , Hypophosphatasia/drug therapy , Hypophosphatasia/diagnostic imaging , United States , Recombinant Fusion Proteins , Brazil , Immunoglobulin G , Follow-Up Studies , Enzyme Replacement Therapy
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