Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 136
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Postgrad Med J ; 90(1061): 171-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24534711

RESUMO

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.

2.
Environ Technol ; : 1-11, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38190254

RESUMO

The uptake of sodium selenite (Se(IV)) and sodium selenate (Se(VI)) from aqueous medium by Lemna minor L. and the influence of different Se concentrations on its growth, morphological and ultrastructural characteristics were studied. L. minor was grown at different concentrations (1, 3, 5 and 10 mg L-1) of Se(IV) and Se(IV). The Se(IV) concentration in the plant tissue ranged between 77.7 (± 4.3) to 453 (± 0) mg kg-1 DW. The Se(VI) concentration in plant tissues ranged between 117 (± 11) to 417 (± 2) mg kg-1 DW. The highest bioconcentration factor for Se(VI) was 127 (± 7) at 3 mg/L, with a Se removal efficiency of 44%. For Se(IV), the highest bioconcentration factor was 77.7 (± 4.3) at 1 mg L-1, which had a Se removal efficiency of 23%. Growth of L. minor was suppressed at 10 mg L-1 Se in both forms. The addition of Se promoted the formation of starch granules in L. minor which occupied a chloroplast area of 74% for Se(IV) and 77% for Se(VI). The efficient uptake of both Se forms by L. minor indicates the potential application of this species for phytoremediation of Se laden wastewaters and its use as an alternative feedstock in biofuel production.

3.
Ann Rheum Dis ; 72(11): 1756-63, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23897772

RESUMO

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.


Assuntos
Biomarcadores/metabolismo , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Progressão da Doença , Humanos , Osteoartrite/patologia , Membrana Sinovial/metabolismo
4.
Psychol Rep ; 126(4): 2003-2026, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35234105

RESUMO

Individual preference for morning or evening activities (chronotype), affect, hardiness, and talent are associated with a variety of performance outcomes. This longitudinal study was designed to investigate the degree to which these variables are associated with academic, physical, and military performance. Self-reported measures of chronotype, affect, and hardiness were collected from 1149 cadets from the Class of 2016 upon entry to the United States Military Academy. Talent, a composite of academic, leadership, and physical fitness scores were drawn from cadet records. Academic, military, and physical performance measures were collected at graduation 4 years later. The results indicated that a morning orientation was associated with better physical and military performance. Higher talent scores, as well as lower levels of negative affect, were associated with better performance across all three performance measures. Hardiness was only associated with military performance. The findings suggest that a morning orientation and less negative affect may result in better performance overall within a challenging and structured military environment. Future studies of chronotype shifts may provide further insight into associated performance benefits.


Assuntos
Militares , Sono , Humanos , Ritmo Circadiano , Cronotipo , Estudos Longitudinais , Inquéritos e Questionários
5.
Osteoporos Int ; 21(6): 1031-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19813043

RESUMO

SUMMARY: From two randomised controlled trials, it is shown that 3-month changes in biochemical markers of bone formation (bone-specific alkaline phosphatase and C-terminal propeptide of type I procollagen) were associated with 3-year bone mineral density (BMD) changes, but not fracture incidence in patients treated with strontium ranelate. INTRODUCTION: The purpose of this study was to assess if short-term change in biochemical markers of bone remodelling is associated with long-term BMD change and fracture incidence observed during treatment with strontium ranelate. METHODS: From the SOTI and TROPOS trials, bone-specific alkaline phosphatase (BALP), C-terminal propeptide of type I procollagen (PICP), serum C-terminal telopeptides (S-CTX) and urine N-terminal telopeptides of type I collagen (U-NTX) were assessed at baseline and after 3 months. RESULTS: Two thousand three hundred seventy-three women were included in this study. Multiple regression analysis showed that 3-month changes in PICP and BALP but not s-CTX I nor s-NTX I were significantly (p < 0.001) associated with 3-year BMD changes at the lumbar spine and the femoral neck. Changes in s-CTX I, PICP and BALP were significantly associated with change in total proximal femur BMD. Changes in biochemical markers explain less than 8% of the BMD changes. The 3-month changes in BALP, PICP s-CTX I and s-NTX I were not significantly associated with fracture incidence. CONCLUSIONS: Short-term changes in biochemical markers of bone formation are associated with future BMD changes in patients treated with strontium ranelate, suggesting a bone-forming activity of this treatment, but are not appropriate to monitor the efficacy of strontium ranelate at the individual level.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Compostos Organometálicos/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Tiofenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/fisiologia , Feminino , Colo do Fêmur/fisiopatologia , Seguimentos , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Compostos Organometálicos/farmacologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/prevenção & controle , Tiofenos/farmacologia
6.
Osteoporos Int ; 21(2): 233-41, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19436941

RESUMO

UNLABELLED: Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Compostos Organometálicos/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Fraturas da Coluna Vertebral/prevenção & controle , Tiofenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Método Duplo-Cego , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento
7.
Plant Biol (Stuttg) ; 22(4): 745-749, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32141176

RESUMO

Dormancy cycling is a key mechanism that contributes to the maintenance of long-term persistent soil seed banks, but has not been recorded in long-lived woody shrub species from fire-prone environments. Such species rely on seed banks and dormancy break as important processes for post-fire recruitment and recovery. We used germination experiments with smoke treatments on fresh seeds and those buried for 1 year (retrieved in spring) and 1.5 years (retrieved the following late autumn) to investigate whether Asterolasia buxifolia, a shrub from fire-prone south-eastern Australia with physiologically dormant seeds, exhibited dormancy cycling. All seeds had an obligation for winter seasonal temperatures and smoke to promote germination, even after ageing in the soil. A high proportion of germination was recorded from fresh seeds. but germination after the first retrieval was significantly lower, despite high seed viability. After the second retrieval, germination returned to the initial level. This indicates a pattern of annual dormancy cycling; one of the few observations, to our knowledge, for a perennial species. Additionally, A. buxifolia's winter temperature and smoke requirements did not change over time, highlighting the potential for seeds to remain conditionally dormant (i.e. restricted to a narrow range of germination conditions) for long periods. For physiologically dormant species, such as A. buxifolia, we conclude that dormancy cycling is an important driver of successful regeneration, allowing seed bank persistence, sometimes for decades, during fire-free periods unsuitable for successful recruitment, while ensuring that a large proportion of seeds are available for recruitment when a fire occurs.


Assuntos
Incêndios , Dormência de Plantas , Rutaceae , Sementes , Germinação , Dormência de Plantas/fisiologia , Rutaceae/fisiologia , Sementes/fisiologia , Solo , Temperatura
8.
Osteoporos Int ; 20(7): 1157-66, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19011728

RESUMO

SUMMARY: The aim of this cross-sectional study was to determine and quantify some determinants associated to low bone mineral density (BMD) in elderly men. This study showed that ageing, a lower body mass index (BMI), a higher blood level of C-terminal cross-linking telopeptides of type I collagen (CTX-1), family history of osteoporosis, and/or fracture and prior fracture were associated with bone mineral density. INTRODUCTION: Our aims were to identify some determinants associated to low bone mineral density in men and to develop a simple algorithm to predict osteoporosis. METHODS: A sample of 1,004 men aged 60 years and older was recruited. Biometrical, serological, clinical, and lifestyle determinants were collected. Univariate, multivariate, and logistic regression analyses were performed. Receiver operating characteristic analysis was used to assess the discriminant performance of the algorithm. RESULTS: In the multiple regression analysis, only age, BMI, CTX-1, and family history of osteoporosis and/or fracture were able to predict the femoral neck T-score. When running the procedure with the total hip T-score, prior fracture also appeared to be significant. With the lumbar spine T-score, only age, BMI, and CTX-1 were retained. The best algorithm was based on age, BMI, family history, and CTX-1. A cut-off point of 0.25 yielded a sensibility of 78%, a specificity of 59% with an area under the curve of 0.73 in the development and validation cohorts. CONCLUSION: Ageing, a lower BMI, higher CTX-1, family history, and prior fracture were associated with T-score. Our algorithm is a simple approach to identify men at risk for osteoporosis.


Assuntos
Algoritmos , Densidade Óssea , Osteoporose/diagnóstico , Absorciometria de Fóton/métodos , Idoso , Envelhecimento , Bélgica/epidemiologia , Doenças Ósseas Metabólicas/epidemiologia , Colágeno Tipo I , Estudos Transversais , Colo do Fêmur/diagnóstico por imagem , Fraturas Ósseas/epidemiologia , França/epidemiologia , Articulação do Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/genética , Fragmentos de Peptídeos/sangue , Peptídeos , Pró-Colágeno/sangue , Curva ROC , Análise de Regressão , Fatores de Risco
9.
Osteoporos Int ; 20(10): 1663-73, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19153678

RESUMO

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/prevenção & controle , Fraturas da Coluna Vertebral/prevenção & controle , Tiofenos/uso terapêutico , Absorciometria de Fóton/métodos , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Qualidade de Vida , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Tiofenos/efeitos adversos , Resultado do Tratamento
10.
Science ; 208(4446): 807-12, 1980 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-17772803

RESUMO

Polymer science and technology has flourished as polymers with many new compositions have been, synthesized. The range of properties attainable has been continually extended, providing materials with higher strength, better reinforcing capabilities, and greater resistance to extreme thermal and corrosive environments. Examples of evolutionary developments in the polyamides, the fluorocarbon resins, and the aromatic engineering plastics are used to illustrate the trends. It is expected that this process will continue in order to meet changing needs and that emphasis will be put on selective polymer design for specific applications.

11.
Rev Med Liege ; 64(5-6): 248-52, 2009.
Artigo em Francês | MEDLINE | ID: mdl-19642453

RESUMO

In contrast to a polyclonal antiserum, a monoclonal antibody is specific to a single epitope on the surface of a complex antigen. In 1975, Kohler and Milstein produced the first monoclonal antibodies by using a method which rapidly became a key technology in immunology. By fusing activated antibody-forming cells (B cells) with myeloma cells, they obtained hybrid cells--the so-called hydridomas--which combine the ability of the activated B cells to secrete a single species of antibody and the immortality of the myeloma cell. The selected hybridomas proliferate continuously, their clonal progeny providing an unending supply of antibody with a single specificity. These antibodies have found many applications in basic research and in vitro diagnosis. In the clinical laboratory, monoclonal antibodies are used as reagents in immunoassays, often replacing traditional antisera. Many years of development and innovation were needed to humanize monoclonal antibodies in order to make them usable in human therapy.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/uso terapêutico , Biotecnologia/métodos , Humanos
12.
Rev Med Liege ; 64(5-6): 257-63, 2009.
Artigo em Francês | MEDLINE | ID: mdl-19642455

RESUMO

Immunoassays, or assays with antibodies as reagents, are widely used in medical laboratories. These assays are used to identify and quantify various substances in biological fluids, such as specific proteins (various tissue markers, markers of inflammation, hormones, coagulation factors...) or immunoglobulins (viral or bacterial antibodies, auto-antibodies...) and even both viral antigens and antibodies (HIV virology). The use of monoclonal antibodies allowed, through their specificity for a single epitope of the target molecule, the development of increasingly sophisticated immunoassays. In particular, the use of monoclonal antibodies with microarrays permits the simultaneous determination of various proteins (inflammatory profile, cardiac profile, specifics IgE...) quickly and accurately. Very important tools in the clinical laboratory, immunoassays techniques are, however, subject to various analytical interferences which may be responsible for significant changes in the test results.


Assuntos
Anticorpos Monoclonais/análise , Imunoensaio , Especificidade de Anticorpos , Humanos
13.
J Clin Invest ; 83(3): 1073-7, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2921317

RESUMO

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P less than 0.01) and strongly correlated (r = 0.72; P less than 0.001) with estrone circulating levels (E1). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean +/- SD = 30.9 +/- 9.9 micrograms/d) and 37 yr (mean +/- SD = 25.5 +/- 11.1 micrograms/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean +/- SD = 19.5 +/- 6.95 micrograms/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean +/- SD = 9.8 +/- 4 micrograms/d) (P less than 0.01). Because there is a strong relationship between E1 and PR (r = 0.64; P less than 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause-related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis.


Assuntos
Calcitonina/sangue , Estrona/sangue , Osteoporose/sangue , Adulto , Idoso , Calcitonina/metabolismo , Feminino , Humanos , Menopausa/sangue , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Análise de Regressão
14.
Ultramicroscopy ; 107(6-7): 431-44, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17258859

RESUMO

We have developed a new fast electron diffractometer working with high dynamic range and linearity for crystal structure determinations. Electron diffraction (ED) patterns can be scanned serially in front of a Faraday cage detector; the total measurement time for several hundred ED reflections can be tens of seconds having high statistical accuracy for all measured intensities (1-2%). This new tool can be installed to any type of TEM without any column modification and is linked to a specially developed electron beam precession "Spinning Star" system. Precession of the electron beam (Vincent-Midgley technique) reduces dynamical effects allowing also use of accurate intensities for crystal structure analysis. We describe the technical characteristics of this new tool together with the first experimental results. Accurate measurement of electron diffraction intensities by electron diffractometer opens new possibilities not only for revealing unknown structures, but also for electrostatic potential determination and chemical bonding investigation. As an example, we present detailed atomic bonding information of CaF(2) as revealed for the first time by precise electron diffractometry.

15.
ACS Omega ; 2(3): 1222-1231, 2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-31457499

RESUMO

N-Alkylation of 2-azidobenzenesulfonamide with 5-bromopent-1-ene gave an N-pentenyl sulfonamide, which underwent intramolecular aminohydroxylation to give an N-(2-azidoaryl)sulfonyl prolinol, a precursor for the synthesis of a pyrrolobenzothiadiazepine. The attempted N-alkylation of 2-azidobenzamide gave a separable mixture (∼1:1) of a benzotriazinone and a quinazolinone in a 72% combined yield. Other primary alkyl halides (3 examples) gave similar mixtures of benzotriazinones and quinazolinones. Benzylic, allylic, and secondary and tertiary alkyl halides (5 examples) gave only benzotriazinones in moderate yields. The results of mechanistic studies show the likely involvement of nitrene intermediates in the quinazolinone pathway and a second pathway involving a dimethylsulfoxide or dimethylsulfide-mediated conversion of 2-azidobenzamide into benzotriazinones.

16.
Curr Med Chem ; 13(13): 1585-90, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16787205

RESUMO

In vitro, strontium ranelate increases collagen and non-collagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated rat osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. In a phase II dose ranging trial Strontium ranelate (500 mg, 1000 mg, 2000 mg/day) or placebo were given to 353 postmenopausal women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving 2000 mg of strontium ranelate was + 7.3%, a significant increase in bone alkaline phosphatase, over a 6-month period and a significant decrease in N-telopeptide crosslinks throughout the 2-year period were seen. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patient experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture by 16% in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture by 36% was also demonstrated in the patients at high risk of hip fracture (age > or =74 years and Femoral Neck T score < or = -2.4 according to NHANES normative value). All these results suggest that strontium ranelate is a new, effective and safe treatment of vertebral and non-vertebral osteoporosis, with a unique mode of action.


Assuntos
Compostos Organometálicos/farmacologia , Osteoporose/tratamento farmacológico , Tiofenos/farmacologia , Animais , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Tiofenos/farmacocinética , Tiofenos/uso terapêutico
17.
Cancer Res ; 46(7): 3728-33, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3486713

RESUMO

The frequency of gross cystic breast disease in premenopausal women and its possible association with increased breast cancer risk emphasize the importance of investigations relating to breast cyst fluid composition. In order to contribute to a better analysis of this medium, we have measured four proteins the presence of which in human milk was well documented. Breast cyst fluid specimens from 266 breast cyst disease patients were assayed and compared as to concentrations of alpha-lactalbumin, gross cystic disease fluid protein (GCDFP-15), epidermal growth factor (EGF), and epithelial membrane antigen (EMA). All the analyzed cyst fluids contained GCDFP-15, EMA, and EGF whereas alpha-lactalbumin was detected in only 14.2% of fluids assayed. Positive correlations were observed between GCDFP-15 and EMA concentrations (P less than 0.005), as well as GCDFP-15 and EGF concentrations (P less than 0.0005). The cyst fluid GCDFP-15 and EGF levels were higher when alpha-lactalbumin concentrations were below detection limits. This association was statistically significant for GCDFP-15 (P less than 0.03) and for EGF (P less than 0.001). These results suggest that GCDFP-15 and EMA could be the biochemical expression of apocrine metaplasia and epithelial hyperplasia, respectively, two histopathological features which characterize breast cystic disease. On the other hand, the occasional presence of alpha-lactalbumin in the cyst fluid would reflect the persistence of differentiated cells in the epithelium surrounding the cyst and would be inversely proportional to the degree of cellular proliferation. The omnipresence of EGF in the cyst fluid argues for the hypothesis of its production by the mammary gland. The highly significant relationship between GCDFP-15 and EGF levels in the medium remains to be elucidated but may be related to an androgen sensitivity in the breast epithelium surrounding the cyst.


Assuntos
Apolipoproteínas , Proteínas de Transporte , Fator de Crescimento Epidérmico/análise , Doença da Mama Fibrocística/análise , Glicoproteínas/análise , Lactalbumina/análise , Proteínas de Membrana/análise , Proteínas de Membrana Transportadoras , Apolipoproteínas D , Líquidos Corporais/análise , Feminino , Humanos , Imunoensaio , Mucina-1
19.
Oncogene ; 17(16): 2059-71, 1998 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-9798677

RESUMO

Fibroblast Growth Factors 3 (FGF-3) and 4 (FGF-4) were compared for the effects they each exert on EF43 mouse cells. This non-transformed mammary cell line appears to be myoepithelial mainly because it expresses alpha-smooth muscle actin. The EF43 cells were infected with similar vectors that carry either the short fgf-3 sequence (the product of which goes into the secretory pathway), fgf-4 or the selection gene only as control. In syngeneic animals, EF43.fgf-3 cells were tumorigenic only when orthotopically implanted whereas EF43.fgf-4 cells invariably gave rise to aggressive tumors. However, both tumor types were metastatic as evidenced by the blue micrometastases observed when the implanted cells expressed lacZ. In vitro, the FGF-3 producing cells were strongly invasive in matrigel coated chambers whereas the EF43.fgf-4 cells only were invasive in type I-collagen gels. Interestingly, FGF-3 production greatly stimulated the synthesis of pro-MMP-9 (Matrix Metalloprotease-9) and, to a lesser extent, that of pro-MMP-2. FGF-3 also up-regulated the production of plasminogen activators. In contrast, FGF-4 had no effect on these secretions and the medium conditioned by the EF43.fgf-4 cells displayed the largest plasminogen activator-inhibitor activity. These results show that FGF-3 and FGF-4 have distinct mechanisms of action on myoepithelial cells.


Assuntos
Transformação Celular Neoplásica , Fatores de Crescimento de Fibroblastos/fisiologia , Glândulas Mamárias Animais/patologia , Proteínas Proto-Oncogênicas/fisiologia , Animais , Linhagem Celular , Colagenases/metabolismo , Células Epiteliais , Feminino , Fator 3 de Crescimento de Fibroblastos , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/genética , Gelatinases/metabolismo , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Transplante de Neoplasias , Inativadores de Plasminogênio/metabolismo , Proteínas Proto-Oncogênicas/genética , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
20.
J Sports Med Phys Fitness ; 55(9): 953-61, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24947814

RESUMO

AIM: Jumper's knee is a frequent chronic overuse syndrome of the proximal part of the patellar tendon. Platelets contain lots of growth factors which could enhance the healing process of tendons. The aim of this study was to clarify the possible efficacy of one injection of Platelet-rich plasma (PRP) in cases of rebel jumper's knees. METHODS: Twenty patients with chronic proximal patellar tendinopathy were enrolled. Assessments were made before infiltration of PRP, and 6 weeks and 3 months after the infiltration, using a 10-point visual analogic scale of pain, clinical examinations with a pressure algometer, algofunctional scores (IKDC and VISA-P), functional assessments (isokinetic and optojump evaluations) and imagery (ultrasounds and MRI). The PRP was obtained with an apheresis system (COMTEC®, Fresenius-Kabi, Bad Homburg, Germany). Six millilitres of PRP were injected without local anesthetic. One week after infiltration, patients started a standardized sub-maximal eccentric reeducation. RESULTS: During daily activities pain significantly decreased with time. At functional evaluation, it decreased as well, but without significant functional improvement. No improvements in the imagery measurements were observed. Younger patients seemed to be more susceptible to have an improvement of pain by the PRP infiltration. CONCLUSION: This study demonstrates that a local infiltration of PRP associated with a submaximal eccentric protocol can improve symptoms of chronic jumper's knee in patients non-responsive to classical conservative treatments.


Assuntos
Articulação do Joelho/fisiopatologia , Plasma Rico em Plaquetas , Tendinopatia/terapia , Adulto , Doença Crônica , Feminino , Humanos , Injeções Intra-Articulares , Articulação do Joelho/diagnóstico por imagem , Masculino , Tendinopatia/fisiopatologia , Escala Visual Analógica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA