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1.
PLoS One ; 13(12): e0208325, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521573

RESUMO

We examined the accumulation of polycyclic aromatic hydrocarbons (PAHs), alkyl PAHs, and toxic metals in soils by the roots of Echinacea purpurea (L.) Moench, in a 20-week greenhouse study and a 2-year field study. In the greenhouse study, inoculation by arbuscular mycorrhizal fungus (AMF), Rhizoglomus intraradices (N.C. Schenck & G.S. Sm.). increased the first order accumulation rates (k1) for PAHs by 10-fold, though had no effect on the bioaccumulation rates of toxic metals. In the greenhouse study, PAHs concentrations in soil increased over time with AMF inoculation, suggesting AMF promote 'solvent depletion' in soils by enhancing absorption of minerals and carbon by roots, concentrating the more hydrophobic PAHs in the residual soil. Under field conditions, contaminant concentrations in soils remained unchanged over the 2-year duration of the study. Despite this, all contaminants in E. purpurea roots increased significantly, as a result of a long term extraction of contaminants by plants from soil and a reduction in soil volume as a result of plant growth. First order accumulation rates by roots were inversely correlated to log Kow for the PAHs and alkyl PAHs, indicating that accumulation is inversely related to the compound's hydrophobicity. This study is the first to our knowledge to assess the accumulation of alkyl PAHs by roots, with implications for soil bioremediation by plants because alkyl PAHs are a major source of petrogenic contamination in soils.


Assuntos
Echinacea/metabolismo , Raízes de Plantas/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Monitoramento Ambiental , Micorrizas/metabolismo
2.
Int J Lab Hematol ; 37 Suppl 1: 31-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25976958

RESUMO

While we have understood the basic outline of the enzymes and reactions that make up the traditional blood coagulation cascade for many years, recently our appreciation of the complexity of these interactions has greatly increased. This has resulted in unofficial 'revisions' of the coagulation cascade to include new amplification pathways and connections between the standard coagulation cascade enzymes, as well as the identification of extensive connections between the immune system and the coagulation cascade. The discovery that polyphosphate is stored in platelet dense granules and is secreted during platelet activation has resulted in a recent burst of interest in the role of this ancient molecule in human biology. Here we review the increasingly complex role of platelet polyphosphate in hemostasis, thrombosis, and inflammation that has been uncovered in recent years, as well as novel therapeutics centered on modulating polyphosphate's roles in coagulation and inflammation.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Ativação Plaquetária/fisiologia , Polifosfatos/sangue , Hemostasia/fisiologia , Humanos , Inflamação/sangue , Inflamação/fisiopatologia , Modelos Biológicos , Trombose/sangue , Trombose/fisiopatologia
3.
Ophthalmologica ; 233(2): 61-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25503414

RESUMO

BACKGROUND/AIMS: The Age-Related Eye Disease Study (AREDS) showed that supplementation with their formula led to a significant decrease in progression of age-related macular degeneration (AMD). This study aims to assess the effect of different education protocols on concordance with the trial recommendations in two retinal clinics. METHODS: A prospective controlled survey of concordance with the AREDS recommendations in two retinal clinics was administered to 330 patients with AREDS category 3 or 4 AMD. The results were evaluated to assess the effect of differing levels of patient education. In clinic 1, there was a formal policy of giving the patient both verbal and written instructions and verbal repetition of these instructions from each staff member on each patient visit; in clinic 2, there was no specific education policy. RESULTS: Clinic 1 had a concordance rate of 81.6% and clinic 2 of 44.1%. There were no significant differences in the patient demographics between the two clinics. CONCLUSION: A high concordance rate can be achieved in clinical practice with rigorous patient education that includes a policy of having continual repetition of instructions.


Assuntos
Degeneração Macular/tratamento farmacológico , Cooperação do Paciente , Educação de Pacientes como Assunto/métodos , Vitaminas/administração & dosagem , Zinco/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/administração & dosagem , Suplementos Nutricionais , Progressão da Doença , Feminino , Guias como Assunto/normas , Humanos , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Centros de Atenção Terciária , Vitamina E/administração & dosagem , beta Caroteno/administração & dosagem
4.
Int J Obes (Lond) ; 39(5): 762-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25388403

RESUMO

BACKGROUND/OBJECTIVES: The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity. SUBJECTS/METHODS: Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35-55 years with waist circumferences in lean (<94 cm), overweight (94-102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture. RESULTS: Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants. CONCLUSIONS: This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of potential compensatory mechanisms that may work to counteract adipose tissue inflammation, possibly through an increased number of T-regulatory cells.


Assuntos
Tecido Adiposo/metabolismo , Adiposidade/imunologia , Inflamação/metabolismo , Ativação Linfocitária , Macrófagos/metabolismo , Sobrepeso/metabolismo , Linfócitos T Reguladores/metabolismo , Adiposidade/fisiologia , Adulto , Composição Corporal , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real
6.
AIDS Care ; 20(6): 615-24, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18576163

RESUMO

Drawing on the Greater Involvement of People with HIV/AIDS (GIPA) principle, the HIV/AIDS movement began to "democratize" research in Canada in the mid-1990s. To date, there is little evidence about the success of the community-based research (CBR) movement in relation to the implementation of GIPA. We draw on findings from a larger study examining barriers and facilitating factors in relation to HIV-related CBR in Ontario, Canada. An online survey was completed by 39 senior managers in Ontario AIDS service organizations (ASOs). Twenty-five in-depth, semi-structured interviews were then conducted to further explore the survey findings. Survey respondents reported that, compared to researchers and frontline service providers, people living with HIV/AIDS (PLWHA) tended to be the least involved in all stages (input, process and outcome) of CBR projects. AIDS service organizations with a mandate that included serving rural and urban communities reported even lower levels of PLWHA involvement in CBR. Qualitative data reveal complex barriers that make meaningful PLWHA engagement in CBR difficult, including: HIV-related stigma; health-related challenges; "credentialism"; lack of capacity to engage in research; other issues taking priority; and mistrust of researchers. Facilitating factors included valuing lived experience; training and mentoring opportunities; financial compensation; trust building; and accommodating PLWHA's needs. While there is strong support for the GIPA principles in theory, practice lags far behind.


Assuntos
Serviços de Saúde Comunitária/normas , Infecções por HIV/psicologia , HIV-1 , Participação do Paciente , Desenvolvimento de Programas/métodos , Avaliação de Programas e Projetos de Saúde , Síndrome de Imunodeficiência Adquirida/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Ontário , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Preconceito , Projetos de Pesquisa , Pesquisadores/organização & administração , Revelação da Verdade
7.
Promot. educ ; 14(1): 6-11, 2007. ilus
Artigo em Inglês | CidSaúde - Cidades saudáveis | ID: cid-56828

RESUMO

An urban health research agenda for health promoters is presented. In Canada, urban issues are emerging as a major concern of policy makers. The voices raising these issues are from the non-health sectors, but many of these issues such as increasing income inequality and poverty, homelessness and housing insecurity, and social exclusion of youth, immigrants, and ethno-racial minorities have strong health implications as they are important social determinants of health. Emphasis on these and other social determinants of health and the policy decisions that strengthen or weaken them is timely as the quality of Canadian urban environments has become especially problematic. We argue for a participatory urban health research and action agenda with four components: (a) an emphasis on health promotion and the social determinants of health; (b) community-based participatory research; and (c) drawing on the lived experience of people to influence (d) policy analysis and policy change. Urban health researchers and promoters are urged to draw upon new developments in population health and community-based health promotion theory and research to identify and strengthen the roots of urban health through citizen action on public policy. (AU)


Assuntos
Promoção da Saúde , Participação da Comunidade , Formulação de Políticas , População Urbana , Pesquisa/métodos , Canadá
9.
J Clin Endocrinol Metab ; 90(7): 4051-6, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15827104

RESUMO

CONTEXT: Alendronate (ALN) is a bisphosphonate compound that can be administered orally and has potential use in pediatric osteoporotic conditions. OBJECTIVE: The objective was to evaluate the pharmacokinetics and single-dose tolerability of ALN in children with osteogenesis imperfecta. DESIGN: ALN was administered iv and orally in a two-period, randomized crossover study, with doses separated by a 2-wk washout and follow-up carried out within 2 wk after the last ALN dose. SETTING: The study was conducted at the pediatric metabolic bone research unit at the Shriners Hospital for Children, Montréal, Canada. PATIENTS: Twenty-four children (aged 4-16 yr; eight girls) with osteogenesis imperfecta type I participated. INTERVENTIONS: All patients received iv ALN at a dose of 125 mug. In addition, patients weighing less than 40 kg received an oral dose of ALN 35 mg, whereas those weighing 40 kg or more received ALN 70 mg orally. MAIN OUTCOME MEASURES: Total urinary excretion and oral bioavailability of ALN, blood and urine safety parameters, and adverse events were the main outcome measures. RESULTS: The total urinary excretion of ALN after the iv dose was similar for both weight groups. The mean oral bioavailability (95% confidence interval) was 0.43% (0.28, 0.64%) for patients weighing less than 40 kg and 0.56% (0.36, 0.87%) for patients weighing 40 kg or more. Eighteen patients reported a total of 44 clinical adverse experiences, none of which were serious. The most common adverse experiences were mild to moderate headache (n = 7), nausea (n = 7), fever (n = 5), and abdominal pain (n = 6). Eighty percent of the adverse experiences (35 of 44) occurred within 48 h of medication administration, 91% (40 of 44) lasted less than 24 h, and 84% (37 of 44) were reported after oral dosing. Laboratory safety monitoring revealed a marginal decrease in absolute lymphocyte count and serum alkaline phosphatase after the study compared with baseline for both weight categories. CONCLUSIONS: The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies. Adverse experiences from single-dose ALN were minor, and the drug was generally well-tolerated.


Assuntos
Alendronato/farmacocinética , Osteogênese Imperfeita/tratamento farmacológico , Adolescente , Alendronato/efeitos adversos , Disponibilidade Biológica , Criança , Pré-Escolar , Estudos Cross-Over , Feminino , Humanos , Masculino , Comprimidos
10.
Am J Med Genet A ; 129A(1): 8-12, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15266607

RESUMO

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.


Assuntos
Doenças do Desenvolvimento Ósseo/patologia , Osso e Ossos/anormalidades , Crânio/patologia , Adolescente , Densidade Óssea , Doenças do Desenvolvimento Ósseo/complicações , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Feminino , Cefaleia/etiologia , Humanos , Osteosclerose/complicações , Osteosclerose/diagnóstico por imagem , Dor/etiologia , Radiografia , Crânio/diagnóstico por imagem
11.
Bone ; 34(5): 905-11, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15121023

RESUMO

Oncogenic hypophosphatemic osteomalacia (OHO) is an uncommon hypophosphatemic syndrome characterized by bone pain, proximal muscle weakness and rickets. It has been postulated that OHO results from overproduction of a humoral phosphaturic factor by an occult tumour. Recently, some OHO tumours have been shown to elaborate fibroblast growth factor-23 (FGF-23), which causes renal phosphate wasting when administered to mice. The purpose of this study was to undertake detailed investigations to confirm the diagnosis of OHO in a pediatric patient and to document the biochemical, radiographic and bone histological phenotype before and after tumour removal. We describe an 11-year-old, previously healthy girl with significant pain and functional disability associated with hypophosphatemic rickets. Circulating 1,25-(OH)(2) vitamin D was very low (14 pM; N: 40-140) while the FGF-23 serum level was markedly elevated [359.5 reference units (RU)/ml, N: 33-105]. An iliac bone biopsy revealed severe osteomalacia, but periosteocytic lesions, as are typical for X-linked hypophosphatemic rickets, were not seen. Sequence analyses of the PHEX and FGF23 genes were normal. A radiographic skeletal survey revealed a small exostosis of the left, distal ulnar metaphysis. A tumour was subsequently removed from this site and the pathology was consistent with benign, fibro-osseous tissue. Serum FGF-23 was normal when measured at 7 h post-operatively, while serum phosphate reached the low-normal range at 16 days following surgery. An iliac bone biopsy taken 5 months after the operation showed improvement, but not yet resolution, of the osteomalacia. Biochemical parameters of bone and mineral metabolism suggested that complete resolution of the osteomalacia was not achieved until 12 months following surgery. One year after tumour removal, the patient was pain-free and had resumed a normal level of activity. The rapid normalization of FGF-23 levels following removal of a benign tumour and the subsequent improvement in the biochemical and histological parameters of bone and mineral metabolism suggest that FGF-23 played a key role in this girl's disease.


Assuntos
Neoplasias Ósseas/cirurgia , Fatores de Crescimento de Fibroblastos/biossíntese , Hipofosfatemia Familiar/terapia , Ulna/patologia , Sequência de Bases , Neoplasias Ósseas/complicações , Neoplasias Ósseas/metabolismo , Criança , Primers do DNA , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipofosfatemia Familiar/etiologia
12.
Bone ; 34(1): 134-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14751570

RESUMO

X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia and arises from mutations in the Phex and PHEX genes in mice (Hyp) and humans, respectively. The present study was undertaken to examine the effect of gene dose on the skeletal phenotype using a histomorphometric approach. Metrical traits (vertebral length, growth plate thickness, cancellous osteoid volume per bone volume, and cancellous, endocortical, and periosteal osteoid thickness) were compared in caudal vertebrae of mutant female (Hyp/+, Hyp/Hyp) and male (Hyp/Y) mice and their normal female (+/+) and male (+/Y) littermates. Mutant animals had trait values that differed significantly from those of normal animals. However, with the exception of vertebral length and cancellous osteoid thickness, values were not significantly different between the three mutant genotypes. We also examined the effect of gamete-of-origin on histomorphometric parameters in obligate Hyp/+ females derived from male or female transmitting parents. The metrical trait values in both groups of Hyp/+ mice were similar, with the exception of vertebral length and cancellous osteoid volume per bone volume. In summary, we demonstrate that the amount of osteoid per bone volume is similar in the three mutant genotypes and conclude that the extent and magnitude of the mineralization defect is fully dominant and likely not affected by gene dose. The differences in vertebral length in the mutants suggest that rickets and osteomalacia are not the only causes of decreased vertebral growth in Hyp mice and that Phex protein may influence bone growth and mineralization by distinct pathways.


Assuntos
Osso e Ossos/patologia , Dosagem de Genes , Doenças Genéticas Ligadas ao Cromossomo X/genética , Hipofosfatemia Familiar/genética , Hipofosfatemia Familiar/patologia , Proteínas/genética , Proteínas/metabolismo , Animais , Osso e Ossos/metabolismo , Cruzamento , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Genótipo , Hipofosfatemia Familiar/sangue , Hipofosfatemia Familiar/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Mutação/genética , Endopeptidase Neutra Reguladora de Fosfato PHEX , Fosfatos/sangue , Cromossomo X/genética
13.
Bone ; 31(1): 12-8, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12110406

RESUMO

Osteogenesis imperfecta (OI) is a heritable disease of bone with low bone mass and bone fragility. The disease is generally classified into four types based on clinical features and disease severity, although recently fifth and sixth forms have also been reported. Most forms of OI are autosomal dominant. Rarely, autosomal recessive disease has been described. We report the clinical, radiological, and histological features of four children (age 3.9-8.6 years at last follow-up; all girls) and four adults (age 28-33 years; two women) with a novel form of autosomal recessive OI living in an isolated First Nations community in northern Quebec. In keeping with the established numeric classification for OI forms, we have called this form of the disease OI type VII. The phenotype is moderate to severe, characterized by fractures at birth, bluish sclerae, early deformity of the lower extremities, coxa vara, and osteopenia. Rhizomelia is a prominent clinical feature. Histomorphometric analyses of iliac crest bone samples revealed findings similar to OI type I, with decreased cortical width and trabecular number, increased bone turnover, and preservation of the birefringent pattern of lamellar bone. The disease has subsequently been localized to chromosome 3p22-24.1, which is outside the loci for type I collagen genes. The underlying genetic basis for the disease remains to be determined.


Assuntos
Colágeno Tipo I , Genes Recessivos , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Densidade Óssea/genética , Criança , Pré-Escolar , Colágeno/genética , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Humanos , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Linhagem , Radiografia
14.
Bone ; 31(1): 85-9, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12110417

RESUMO

We have previously shown that idiopathic juvenile osteoporosis (IJO) is characterized by a decreased cancellous bone volume and a very low bone formation rate on cancellous surfaces. Whether IJO similarly affects cortical bone is unknown. We therefore compared tetracycline double-labeled transfixing iliac-crest bone biopsies from eight children with typical clinical features of IJO (six girls; age 10-12 years) and from nine children (four girls; age 9-12 years) without metabolic bone disease. No differences in intracortical remodeling activity were detected. Both structural parameters reflecting intracortical remodeling (cortical porosity, active canal diameter, and quiescent canal diameter) and bone surface-based metabolic parameters (osteoid, osteoblast, mineralizing, osteoclast and eroded surfaces, and bone formation rate) were similar in IJO patients and controls (p > 0.2 each, t-test). Although the internal cortex of the biopsy was thinner in IJO patients than in controls (660 +/- 170 microm vs. 980 +/- 320 microm; p = 0.02), there was no difference in the width of the external cortex (p = 0.36). In growing children, both cortices exhibit an external modeling drift. Therefore, the difference in internal cortical width point to a decreased modeling activity on the endocortical surface of the internal cortex. In fact, bone formation rate on this surface was 48% lower in IJO patients than in controls (82 +/- 45 microm(3)/microm(2) per year vs. 159 +/- 162 microm(3)/microm(2) per year). However, this difference did not achieve statistical significance (p = 0.21) due to the high variability of bone formation rate on modeling surfaces. The disturbance of bone remodeling in IJO is limited to cancellous bone, but there may be a modeling defect affecting the internal cortex. Thus, the process causing IJO appears to mainly affect bone surfaces that are in contact with the bone marrow cavity.


Assuntos
Osteogênese/fisiologia , Osteoporose/patologia , Remodelação Óssea/fisiologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Criança , Feminino , Humanos , Masculino , Osteoporose/fisiopatologia , Estatísticas não Paramétricas
15.
Bone ; 30(6): 823-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12052448

RESUMO

Quantitative data on metaphyseal bone histology during early human development are scarce. In the present study the proximal femoral metaphysis of 35 fetuses and newborns (gestational age 16-35 weeks) was analyzed by histomorphometry. Averaged over the entire metaphyseal area, the relative amount of bone and cartilage was higher in the third compared to the second trimester. Osteoid thickness increased with gestational age, whereas indices of bone resorption decreased. The relative amount of cartilage decreased with increasing distance from the growth plate, whereas the relative amount of bone increased. This was due to trabecular thickening, which occurred at an estimated rate of 3 microm/day in areas close to the growth plate. Despite this rapid rate of net bone gain, osteoid indices were relatively low, indicating that mineralization occurred very rapidly after bone deposition. These observations suggest that modeling, not remodeling, is the predominant mechanism responsible for the development of femoral metaphyseal cancellous bone in utero.


Assuntos
Desenvolvimento Ósseo/fisiologia , Fêmur/embriologia , Fêmur/crescimento & desenvolvimento , Análise de Variância , Remodelação Óssea/fisiologia , Fêmur/fisiologia , Feto/embriologia , Feto/fisiologia , Humanos , Recém-Nascido
16.
Bone ; 27(4): 487-94, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11033443

RESUMO

Normal postnatal bone growth is essential for the health of adults as well as children but has never been studied histologically in human subjects. Accordingly, we analyzed iliac bone histomorphometric data from 58 healthy white subjects, aged 1.5-23 years, 33 females and 25 males, of whom 48 had undergone double tetracycline labeling. The results were compared with similar data from 109 healthy white women, aged 20-76 years, including both young adult reference ranges and regressions on age. There was a significant increase with age in core width, with corresponding increases in both cortical width and cancellous width. In cancellous bone there were increases in bone volume and trabecular thickness, but not trabecular number, wall thickness, interstitial thickness, and inferred erosion depth. Mineral apposition rates declined on the periosteal envelope and on all subdivisions of the endosteal envelope. Because of the concomitant increase in wall thickness, active osteoblast lifespan increased substantially. Bone formation rate was almost eight times higher on the outer than on the inner periosteum, and more than four times higher on the inner than on the outer endocortical surface. On the cancellous surface, bone formation rate and activation frequency declined in accordance with a fifth order polynomial that matched previously published biochemical indices of bone turnover. The analysis suggested the following conclusions: (1) Between 2 and 20 years the ilium grows in width by periosteal apposition (3.8 mm) and endocortical resorption (3.2 mm) on the outer cortex, and net periosteal resorption (0.4 mm) and net endocortical formation (1.0 mm) on the inner cortex. (2) Cortical width increases from 0.52 mm at age 2 years to 1.14 mm by age 20 years. To attain adult values there must be further endocortical apposition of 0.25 mm by age 30 years, at a time when cancellous bone mass is declining. (3) Lateral modeling drift of the outer cortex enlarges the marrow cavity; the new trabeculae filling this space arise from unresorbed cortical bone and represent cortical cancelization; (4) Lateral modeling drift of the inner cortex encroaches on the marrow cavity; some trabeculae are incorporated into the expanding cortex by compaction. (5) The net addition of 37 microm of new bone on each side of a trabecular plate results from a <5% difference between wall thickness and erosion depth and between bone formation and bone resorption rates; these small differences on the same surface are characteristic of bone remodeling. (6) Because the amount of bone added by each cycle of remodeling is so small, the rate of bone remodeling during growth must be high to accomplish the necessary trabecular hypertrophy.


Assuntos
Desenvolvimento Ósseo , Adolescente , Adulto , Envelhecimento/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valores de Referência
17.
J Bone Miner Res ; 15(9): 1650-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10976985

RESUMO

Osteogenesis imperfecta (OI) is commonly subdivided into four clinical types. Among these, OI type IV clearly represents a heterogeneous group of disorders. Here we describe 7 OI patients (3 girls), who would typically be classified as having OI type IV but who can be distinguished from other type IV patients. We propose to call this disease entity OI type V. These children had a history of moderate to severe increased fragility of long bones and vertebral bodies. Four patients had experienced at least one episode of hyperplastic callus formation. The family history was positive for OI in 3 patients, with an autosomal dominant pattern of inheritance. All type V patients had limitations in the range of pronation/supination in one or both forearms, associated with a radiologically apparent calcification of the interosseous membrane. Three patients had anterior dislocation of the radial head. A radiodense metaphyseal band immediately adjacent to the growth plate was a constant feature in growing patients. Lumbar spine bone mineral density was low and similar to age-matched patients with OI type IV. None of the type V patients presented blue sclerae or dentinogenesis imperfecta, but ligamentous laxity was similar to that in patients with OI type IV. Levels of biochemical markers of bone metabolism generally were within the reference range, but serum alkaline phosphatase and urinary collagen type I N-telopeptide excretion increased markedly during periods of active hyperplastic callus formation. Qualitative histology of iliac biopsy specimens showed that lamellae were arranged in an irregular fashion or had a meshlike appearance. Quantitative histomorphometry revealed decreased amounts of cortical and cancellous bone, like in OI type IV. However, in contrast to OI type IV, parameters that reflect remodeling activation on cancellous bone were mostly normal in OI type V, while parameters reflecting bone formation processes in individual remodeling sites were clearly decreased. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations affecting glycine codons or splice sites. In conclusion, OI type V is a new form of autosomal dominant OI, which does not appear to be associated with collagen type I mutations. The genetic defect underlying this disease remains to be elucidated.


Assuntos
Osso e Ossos/patologia , Osteogênese Imperfeita/classificação , Osteogênese Imperfeita/patologia , Adolescente , Fosfatase Alcalina/sangue , Biomarcadores , Peso ao Nascer , Peso Corporal , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Fibroblastos , Genes Dominantes , Humanos , Hiperplasia/patologia , Recém-Nascido , Cariotipagem , Masculino , Mutação , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/genética , Radiografia , Terminologia como Assunto
18.
Bone ; 27(3): 453-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10962359

RESUMO

The Ilizarov method of limb lengthening makes use of the fact that osteogenesis is induced at an osteotomy site when distraction is applied. It is unknown at present how the mechanical forces created by distraction are translated into biological signals. Because bone morphogenetic proteins (BMPs) are potent inducers of osteogenesis in many experimental systems, they are obvious candidates for playing a role in this process. In this study, we investigated the temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week consolidation phase. Each week after osteotomy one rabbit was killed for immunohistochemical studies. Staining for BMP-2, -4, and -7 was evident before distraction was applied and was mainly localized to mesenchymal cells and osteoblastic cells in the periosteal region. After distraction was started, the typical fibrous interzone developed between the osteotomy fragments, where both intramembranous and endochondral ossification were noted. In this area, cells resembling fibroblasts and chondrocytes, but not mature osteoblasts, showed intense staining for all three BMPs. This high level of expression was maintained during the entire distraction phase and then gradually disappeared during the consolidation phase. These results are compatible with the hypothesis that BMPs play an important role in the signaling pathways that link the mechanical forces created by distraction to biological responses.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Osso e Ossos/metabolismo , Osteogênese por Distração , Fator de Crescimento Transformador beta , Animais , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 4 , Proteína Morfogenética Óssea 7 , Imuno-Histoquímica , Masculino , Coelhos , Tíbia/metabolismo , Tíbia/cirurgia , Fatores de Tempo
19.
J Clin Endocrinol Metab ; 85(5): 1846-50, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10843163

RESUMO

Severe osteogenesis imperfecta (OI) is a hereditary disorder characterized by increased bone fragility and progressive bone deformity. Cyclical pamidronate infusions improve clinical outcome in children older than 3 yr of age with severe OI. Because earlier treatment may have potential to prevent deformities and improve functional prognosis in young children, we studied nine severely affected OI patients under 2 yr of age (2.3-20.7 months at entry) for a period of 12 months. Pamidronate was administered i.v. in cycles of 3 consecutive days. Patients received four to eight cycles during the treatment period, with cumulative doses averaging 12.4 mg/kg. Clinical changes were evaluated regularly during treatment, and radiological changes were assessed after 6-12 months of treatment. The control group consisted of six age-matched, severely affected OI patients, who had not received pamidronate treatment. During treatment bone mineral density (BMD) increased between 86-227%. The deviation from normal, as indicated by the z-score, diminished from -6.5 +/- 2.1 to -3.0 +/- 2.1 (P < 0.001). In the control group the BMD z-score worsened significantly. Vertebral coronal area increased in all treated patients (11.4 +/- 3.4 to 14.9 +/- 1.8 cm2; P < 0.001), but decreased in the untreated group (P < 0.05). In the treated patients, fracture rate was lower than in control patients (2.6 +/- 2.5 vs. 6.3 +/- 1.6 fractures/year; P < 0.01). No adverse side-effects were noted, apart from the well known acute phase reaction during the first infusion cycle. Pamidronate treatment in severely affected OI patients under 3 yr of age is safe, increases BMD, and decreases fracture rate.


Assuntos
Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Osteogênese Imperfeita/tratamento farmacológico , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Lactente , Vértebras Lombares/diagnóstico por imagem , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/fisiopatologia , Pamidronato , Radiografia
20.
Endocrinology ; 141(7): 2658-66, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10875271

RESUMO

The 25-hydroxyvitamin D-24-hydroxylase enzyme (24-OHase) is responsible for the catabolic breakdown of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D. The 24-OHase enzyme can also act on the 25-hydroxyvitamin D substrate to generate 24,25-dihydroxyvitamin D, a metabolite whose physiological importance remains unclear. We report that mice with a targeted inactivating mutation of the 24-OHase gene had impaired 1,25(OH)2D catabolism. Surprisingly, complete absence of 24-OHase activity during development leads to impaired intramembranous bone mineralization. This phenotype was rescued by crossing the 24-OHase mutant mice to mice harboring a targeted mutation in the vitamin D receptor gene, confirming that the elevated 1,25(OH)2D levels, acting through the vitamin D receptor, were responsible for the observed accumulation of osteoid. Our results confirm the physiological importance of the 24-OHase enzyme for maintaining vitamin D homeostasis, and they reveal that 24,25-dihydroxyvitamin D is a dispensable metabolite during bone development.


Assuntos
24,25-Di-Hidroxivitamina D 3/deficiência , Densidade Óssea , Calcitriol/metabolismo , Sistema Enzimático do Citocromo P-450/deficiência , Receptores de Calcitriol/deficiência , Esteroide Hidroxilases/deficiência , Alelos , Animais , Calcitriol/sangue , Calcitriol/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Feminino , Hibridização Genética , Rim/efeitos dos fármacos , Rim/patologia , Camundongos , Camundongos Knockout/genética , Mutação/fisiologia , Fenótipo , Ratos , Receptores de Calcitriol/genética , Esteroide Hidroxilases/genética , Vitamina D3 24-Hidroxilase
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