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1.
J Phys Condens Matter ; 27(19): 194111, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25923112

RESUMO

We investigate the suitability of the local compressibility χ(z) as a measure of the solvophobicity or hydrophobicity of a substrate. Defining the local compressibility as the derivative of the local one-body density ρ(z) w.r.t. the chemical potential µ at fixed temperature T, we use density functional theory (DFT) to calculate χ(z) for a model fluid, close to bulk liquid-gas coexistence, at various planar substrates. These range from a 'neutral' substrate with a contact angle of θ≈90°, which favours neither the liquid nor the gas phase, to a very solvophobic, purely repulsive substrate which exhibits complete drying, i.e. θ = 180°. We find that the maximum in the local compressibility χ(z), which occurs within one-two molecular diameters of the substrate, and the integrated quantity χ(ex) (the surface excess compressibility, defined below) both increase rapidly as θ increases and the substrate becomes more solvophobic. χ(z) provides a more pronounced indicator of solvophobicity than the density depletion in the vicinity of the surface which increases only weakly with increasing θ. For the limiting case of drying, θ = 180°, we find lnχ(l) ∼ l, where l is the thickness of the intruding film of gas which diverges in the approach to bulk coexistence µ → µ(co). When the fluid is confined in a parallel slit with two identical solvophobic walls, or with competing solvophobic and solvophilic walls, χ(z) close to the solvophobic wall is altered little from that at the single substrate. We connect our results with simulation studies of water near to hydrophobic surfaces exploring the relationship between χ(z) and fluctuations in the local density and between χ(ex) and the mean-square fluctuation in the number of adsorbed molecules.

2.
Vet Comp Orthop Traumatol ; 28(2): 79-87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25632964

RESUMO

OBJECTIVES: To fully sequence and characterize equine aggrecan and confirm conservation of major aggrecanase, calpain and matrix metalloproteinase (MMP) cleavage sites. METHODS: Reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends were used to generate clones that encompassed the complete equine aggrecan sequence. Clones were sequenced and compared with the equine genome database to determine intron-exon boundaries. RESULTS: The aggrecan gene spans over 61 kb on chromosome 1 and is encoded by 17 exons. Two major variants of aggrecan were cloned; one containing 8187 bp (2728 amino acids) and a second sequence of 8061 nucleotides (2686 amino acids). The variation was due to a CS1 domain polymorphism. Both sequences are substantially larger than predicted by the genomic database; 11 CS1 repeat elements are absent in the database sequence. The equine amino acid sequence was compared with human, bovine and murine sequences. Globular domains 1, 2 and 3 are highly conserved (overall identity over 80%). Equine CS1 is considerably larger than in other species and, therefore, is the least conserved domain (an overall amino acid identity of 22%). Previously defined aggrecanase, calpain and MMP cleavage sites were identified. Western blotting of chondrocyte culture samples showed complex post-secretion processing. CLINICAL SIGNIFICANCE: The complete equine aggrecan sequence will support more in-depth research on aggrecan processing and degradation in equine articular cartilage and other musculoskeletal tissues.


Assuntos
Agrecanas/química , Agrecanas/genética , Cavalos/fisiologia , Sequência de Aminoácidos , Animais , Clonagem Molecular , Sequência Conservada , DNA Complementar , Endopeptidases/genética , Endopeptidases/metabolismo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária
3.
J Chem Phys ; 140(13): 134704, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24712805

RESUMO

We consider a simple fluid confined between two parallel walls (substrates), separated by a distance L. The walls exert competing surface fields so that one wall is attractive and may be completely wet by liquid (it is solvophilic) while the other is solvophobic. Such asymmetric confinement is sometimes termed a "Janus Interface." The second wall is: (i) purely repulsive and therefore completely dry (contact angle θ = 180°) or (ii) weakly attractive and partially dry (θ is typically in the range 160-170°). At low temperatures, but above the bulk triple point, we find using classical density functional theory (DFT) that the fluid is highly structured in the liquid part of the density profile. In case (i), a sequence of layering transitions occurs: as L is increased at fixed chemical potential µ close to bulk gas-liquid coexistence µco, new layers of liquid-like density develop discontinuously. In contrast to confinement between identical walls, the solvation force is repulsive for all wall separations and jumps discontinuously at each layering transition and the excess grand potential exhibits many metastable minima as a function of the adsorption. For a fixed temperature T = 0.56TC, where TC is the bulk critical temperature, we determine the transition lines in the L, µ plane. In case (ii), we do not find layering transitions and the solvation force oscillates about zero. We discuss how our mean-field DFT results might be altered by including effects of fluctuations and comment on how the phenomenology we have revealed might be relevant for experimental and simulation studies of water confined between hydrophilic and hydrophobic substrates, emphasizing it is important to distinguish between cases (i) and (ii).

4.
J Matern Fetal Neonatal Med ; 27(16): 1633-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24298956

RESUMO

UNLABELLED: Abstract Objective: To determine if high umbilical artery Doppler (UAD) pulsatility index (PI) is associated with cardio-vascular (CV) risk-factors in children at age 12 years. METHODS: We studied 195 children at age 12 years who had had in-utero UAD studies performed at 28 weeks' gestation. The children were grouped according to whether their umbilical Doppler PI was high (indicating poor feto-placental circulation) or normal. At age 12 years we assessed CV risk factors, including anthropometric measures, blood pressure, pulse wave velocity (a measure of arterial compliance), cardio-respiratory fitness, and homocysteine and cholesterol serum levels. RESULTS: Compared with children with a normal UAD PI (N = 88), the children (N = 107) with high UAD PI had higher resting pulse rate (p = 0.04), higher pulse wave velocity (p = 0.046), higher serum homocysteine levels (p = 0.032) and reduced arterial compliance (7.58 versus 8.50 m/s, p = 0.029) using univariate analysis. These differences were not present when adjusting for cofounders was modeled. CONCLUSION: High PI on UAD testing in-utero may be associated with increased likelihood of some CV risk factors at age 12-years but confounding variables may be as important. Our study raises possible long-term benefits of in-utero UAD measurements.


Assuntos
Doenças Cardiovasculares/etiologia , Artérias Umbilicais/diagnóstico por imagem , Criança , Feminino , Seguimentos , Hemodinâmica , Humanos , Masculino , Circulação Placentária , Gravidez , Fluxo Pulsátil , Fatores de Risco , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Artérias Umbilicais/fisiologia
5.
Vet Comp Orthop Traumatol ; 26(2): 100-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23172016

RESUMO

OBJECTIVE: To assess the ability of a contrast-enhanced magnetic resonance imaging (MRI) technique to quantitatively determine glycosaminoglycan content in canine articular cartilage. METHODS: Fifty-four full-thickness cartilage discs were collected from the femorotibial and scapulohumeral joints of three adult dogs immediately following euthanasia. One set of discs from each dog was analysed for glycosaminoglycan content using a colourimetric laboratory assay. The remaining position-matched set of discs from contralateral limbs underwent pre- and post-contrast gadolinium-enhanced MRI, using repeated saturation recovery pulse sequences which were used to generate calculated T1 maps of the cartilage discs. Linear regression analysis was then performed relating delayed gadolinium-enhanced MRI T1 calculated signal intensity to the cartilage glycosaminoglycan content normalized to DNA content. Repeatability of triplicate measurements was estimated by calculating the coefficient of variation. RESULTS: Mean coefficient of variation estimates for the gadolinium-enhanced MRI T1 signal intensity values for nine sampling sites from three dogs ranged from 5.9% to 7.5%. Gadolinium-enhanced MRI T1 signal intensity was significantly correlated (p <0.05) with normalized glycosaminoglycan content in two dogs (r = 0.79, p = 0.011; r = 0.78, p = 0.048), but not in the third dog (r = 0.53, p = 0.071). CLINICAL SIGNIFICANCE: Gadolinium-enhanced MRI assessment of cartilage may be predictive of glycosaminoglycan content and therefore offer an in vivo assessment of changes in cartilage characteristics over time. Additional studies appear indicated to determine the reliability and clinical applicability of gadolinium-enhanced MRI in detecting changes in cartilage over time.


Assuntos
Cartilagem Articular/química , Cães , Glicosaminoglicanos/análise , Imageamento por Ressonância Magnética/veterinária , Animais , Cadáver , Colorimetria/veterinária , Meios de Contraste , Feminino , Gadolínio , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Projetos Piloto
6.
Phys Rev E Stat Nonlin Soft Matter Phys ; 86(3 Pt 1): 031601, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23030923

RESUMO

We consider a model fluid with long-range r(-6) (dispersion) interparticle potentials confined between competing parallel walls. One wall is solvophilic and would be completely wet at bulk liquid-gas coexistence µ(co)(-), whereas the other is solvophobic and would be completely dry at µ=µ(co)(+). When the wall separation L is large and the system is below the bulk critical temperature T(C) and close to bulk liquid-gas coexistence, a delocalized interface or soft-mode phase forms with a liquid-gas interface near the center of the slit; this interacts with the walls via the power-law tails of the interparticle potentials. We use a coarse-grained effective Hamiltonian approach to derive explicit scaling expressions for the Gibbs adsorption Γ, the surface tension γ, the solvation force f(s), and the total susceptibility χ. These quantities depend on the dimensionless scaling variable (L/σ)(3)ßδµ, where ß=(k(B)T)(-1), σ is the diameter of the fluid particles and δµ=µ-µ(co) is the chemical potential deviation from bulk coexistence. Using a nonlocal density functional theory, we calculate density profiles for the asymmetrically confined fluid at different chemical potentials and for sufficiently large L confirm the scaling predictions for the four thermodynamic quantities. Since the upper critical dimension for complete wetting with power-law potentials is less than 3, we argue that our (mean-field) scaling predictions should remain valid in treatments that incorporate the effects of interfacial fluctuations. As the wall separation L is decreased at µ(co), we predict a capillary evaporation transition from the delocalized interface phase to a dilute gas state with just a thin adsorbed film of liquidlike density next to the solvophilic wall. This transition is closely connected to the first-order prewetting transition that occurs at the solvophilic wall in the semi-infinite system. We compare the phase diagram for the competing walls system with the phase diagrams for the fluid confined between identical solvophilic and identical solvophobic walls. Comparisons are also made with earlier studies of asymmetric confinement for systems with short-range forces.

7.
Public Health ; 126(7): 561-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22607982

RESUMO

OBJECTIVE: To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight ≥10th centile). STUDY DESIGN: Controlled comparative study. METHODS: Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations. RESULTS: The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference. CONCLUSIONS: IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life.


Assuntos
Retardo do Crescimento Fetal , Hipertensão/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte/epidemiologia , Gravidez , Risco
8.
Arch Dis Child ; 96(3): 252-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20522466

RESUMO

OBJECTIVE: Interventions to reduce health inequalities for young children and their mothers are important: involving peers is recommended, but evidence of value for this approach is limited. The authors aimed to examine the effect of an innovative tailored peer-mentoring programme, based on perceived needs, for first-time mothers in socio-economically deprived communities. DESIGN: Randomised controlled trial; parallel qualitative study with purposive samples using semistructured interviews. SETTING: Socio-economically disadvantaged areas, Belfast. PARTICIPANTS: Primigravidae, aged 16-30 years, without significant co-morbidity. INTERVENTION: Peer-mentoring by a lay-worker fortnightly during pregnancy and monthly for the following year, tailored to participants' wishes (home visits/telephone contacts), additional to usual care. MAIN OUTCOME MEASURES: Infant psychomotor and mental development (Bayley Scales of Infant Development (BSID-II)) at 1 year, assessed by an observer blinded to group allocation. Mothers' health at 1 year postnatal (SF-36). RESULTS: Of 534 women invited, 343(64%) participated; 85%, with their children, completed outcome assessments (140 of 172 intervention; 152 of 171 controls). Intervention and control groups did not differ in BSID-II psychomotor (mean difference 1.64, 95% CI -0.94 to 4.21) or mental (-0.81, -2.78 to 1.16) scores, nor SF-36 physical functioning (-5.4, -11.6 to 0.7) or mental health (-1.8, -6.1 to 2.6). Women valued advice given in context of personal experience of child-rearing. Mentors gained health-related knowledge, personal skills and new employment opportunities. CONCLUSIONS: Despite possible longer-term social advantage, this peer-mentoring programme showed no benefit for infant development or maternal health at 1 year. Further rigorous evaluation of important outcomes of complex interventions promoting health for children in socially disadvantaged communities is warranted. TRIAL REGISTRATION NO: ISRCTN 55055030.


Assuntos
Mentores , Mães/educação , Grupo Associado , Apoio Social , Adolescente , Adulto , Desenvolvimento Infantil , Feminino , Humanos , Recém-Nascido , Saúde Mental , Mentores/educação , Mães/psicologia , Avaliação de Resultados em Cuidados de Saúde , Poder Familiar , Áreas de Pobreza , Desempenho Psicomotor , Adulto Jovem
9.
Aust Vet J ; 88(4): 115-23, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20402698

RESUMO

OBJECTIVE: To present the technique for intra-articular catheter placement and report the clinical outcomes of 38 cases of equine synovial trauma and/or infection treated with broad-spectrum antimicrobials administered via an intrasynovial catheter (ISC). DESIGN: Retrospective study. PROCEDURE: Medical records of 38 horses treated for synovial trauma and sepsis with frequent antimicrobial administration through an ISC from 1995 to 2008 were reviewed. Follow-up information was obtained via clinical re-evaluation or telephone contact with the owners. RESULTS: The majority of horses (84%) received amikacin and Timentin(R) four times daily. In addition, synovial lavage through the ISC was carried out in 27 horses (71%). Only radiological evidence of osteolysis had a significant negative impact on both lameness at the time of hospital discharge and the long-term outcome. In total, 92% of horses treated with frequent antimicrobial administration through an ISC had clinical resolution of infection. Catheter obstruction occurred in three cases, necessitating replacement or removal, and two synovial fistulae developed at sites of open drainage. The majority of horses treated had a favourable outcome, with 86% being at least pasture sound and 43% returned to riding. CONCLUSION: Septic synovial structures treated with frequent antimicrobial administration through an ISC had a good prognosis for survival and 43% returned to riding, which is consistent with the results of other studies. The use of a simple ISC should be considered when broad-spectrum intrasynovial antimicrobial administration and lavage of a septic synovial structure are indicated.


Assuntos
Antibacterianos/administração & dosagem , Cateterismo/veterinária , Doenças dos Cavalos/tratamento farmacológico , Sinovite/veterinária , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Ácidos Clavulânicos/administração & dosagem , Ácidos Clavulânicos/uso terapêutico , Feminino , Cavalos , Injeções Intra-Articulares/veterinária , Masculino , Prognóstico , Estudos Retrospectivos , Sinovite/tratamento farmacológico , Irrigação Terapêutica/veterinária , Ticarcilina/administração & dosagem , Ticarcilina/uso terapêutico , Resultado do Tratamento
10.
Vet Comp Orthop Traumatol ; 20(3): 151-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17846679

RESUMO

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins.


Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Cartilagem Articular/fisiologia , Proteínas Morfogenéticas Ósseas/uso terapêutico , Cartilagem Articular/lesões , Homeostase/fisiologia , Humanos , Transdução de Sinais/fisiologia
11.
Vet Comp Orthop Traumatol ; 20(3): 185-91, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17846684

RESUMO

Articular chondrocytes are phenotypically unique cells that are responsible for the maintenance of articular cartilage. The articular chondrocytic phenotype is influenced by a range of soluble factors. In particular, members of the bone morphogenetic protein (BMP) family support the articular chondrocytic phenotype and stimulate synthesis of cartilaginous matrix. This study was carried out to determine the importance of BMPs in supporting the differentiated phenotype of articular chondrocytes in vitro. Exogenous BMP-2 supported expression of collagen type II and aggrecan in monolayer chondrocyte cultures, slowing the dedifferentiation process that occurs under these conditions. In contrast, BMP-2 had little effect on expression of these genes in three-dimensional aggregate cultures. Endogenous BMP-2 expression was lost in monolayer cultures, coincident with the down-regulation of collagen type II and aggrecan mRNAs, whereas BMP-2 mRNA levels were stable in aggregate cultures. Antagonism of endogenous BMP activity in aggregate cultures by Noggin or a soluble form of the BMP receptor resulted in reduced expression of collagen type II and aggrecan mRNAs, reduced collagen type II protein and sulfated glycosaminoglycan (GAG) deposition into the aggregate matrices and reduced secretion of GAGs into the culture media. These results indicate that endogenous BMPs are required for maintenance of the differentiated articular chondrocytic phenotype in vitro. These findings are of importance to cell-based strategies designed to repair articular cartilage. Articular chondrocytes require conditions that will support endogenous expression of BMPs to maintain the specialized phenotype of these cells.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Animais , Northern Blotting , Técnicas de Cultura , Cavalos , Fenótipo , RNA Mensageiro/análise
12.
Osteoarthritis Cartilage ; 14(4): 392-402, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16406703

RESUMO

OBJECTIVE: Aggrecan degradation by aggrecanases [a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) 1, 4, 5, 8, 9, 15] is considered to initiate much of the cartilage pathology seen in human arthritis, however, the proteinase responsible and its mode of control is unclear. The present work was done to examine mechanisms of aggrecanase control in a novel murine epiphyseal cell system and to determine whether ADAMTS5 alone is responsible for aggrecanolysis by these cells. METHODS: Epiphyseal cells from 4-day-old mice (wild type, TS-5 (-/-), CD44(-/-), syndecan-1(-/-), membrane type-4 matrix metalloproteinase [MT4MMP(-/-)]) were maintained in non-adherent aggregate cultures and aggrecanolysis studied by biochemical and histochemical methods. Confocal immunolocalization analyses were done with specific probes for ADAMTS5, hyaluronan (HA) and aggrecanase-generated fragments of aggrecan. RESULTS: Aggrecanolysis by these cells was specifically aggrecanase-mediated and it occurred spontaneously without the need for addition of catabolic stimulators. Chondrocytes from ADAMTS5-null mice were aggrecanase-inactive whereas all other mutant cells behaved as wild type in this regard suggesting that ADAMTS5 activity is not controlled by CD44, syndecan-1 or MT4MMP in this system. Immunohistochemical analysis supported the central role for ADAMTS5 in the degradative pathway and indicated that aggrecanolysis occurs primarily in the HA-poor pericellular region in these cultures. CONCLUSION: These findings are consistent with published in vivo studies showing that single-gene ADAMTS5 ablation confers significant protection on cartilage in murine arthritis. We propose that this culture system and the analytical approaches described provide a valuable framework to further delineate the expression, activity and control of ADAMTS-mediated aggrecanolysis in human arthritis.


Assuntos
Condrócitos/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Lâmina de Crescimento/metabolismo , Lectinas Tipo C/metabolismo , Proteínas ADAM , Agrecanas , Animais , Lâmina de Crescimento/patologia , Receptores de Hialuronatos/metabolismo , Metaloproteinases da Matriz/metabolismo , Metaloproteinases da Matriz Associadas à Membrana , Glicoproteínas de Membrana/metabolismo , Camundongos , Proteoglicanas/metabolismo , Sindecana-1 , Sindecanas
13.
Phys Rev E Stat Nonlin Soft Matter Phys ; 71(1 Pt 1): 011602, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15697613

RESUMO

We examine the interfacial properties of a hard spherical cavity, radius R , immersed in a solvent in which the fluid-fluid interaction potential contains both a hard-sphere repulsive part and an attractive - r(-6) component. Near to liquid-gas coexistence where the chemical potential deviation deltamu identical withmu- mu(co) (T) --> 0(+) complete wetting by the gas (drying) occurs and a coarse-grained effective Hamiltonian approach shows that the wall/liquid surface tension has a term in R(-2/3) , i.e., a leading-order power-law nonanalyticity in the curvature ( R-1 ) in the large cavity limit. For states sufficiently well removed from coexistence the surface tension can be expanded in integer powers of the curvature R-1 , provided R> R(c) with the length scale given by R(c) =2 gamma(gl) (infinity) / (Deltarhodeltamu) , where gamma(gl) (infinity) is the planar liquid/gas surface tension and Deltarho is the difference between the coexisting densities. However, even in these circumstances there are additional R-2 ln R contributions to the surface tension arising from the dispersion forces. An exact statistical mechanical sum rule is used to relate the density of the fluid at the point of contact with the cavity, rho ( R+ ,mu) , to the pressure of the reservoir and the surface tension. This predicts that rho ( R+ ,mu) acquires a term in R(-5/3) in the regime R< R(c) . Numerical results obtained by applying classical density functional theory to this model confirm all the predictions from the coarse-grained approach for both the surface tension and the contact density. We argue that our results for leading-order nonanalytic contributions are exact, i.e., they should remain valid in the presence of interface fluctuations, and we discuss briefly the repercussions for solvation phenomena and for other wetting situations.

17.
J Orthop Res ; 19(2): 171-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11347687

RESUMO

Aseptic loosening is the most common cause of orthopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result, 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation. Skeletally mature, adult mice (4-16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening.


Assuntos
Envelhecimento/fisiologia , Osteólise/fisiopatologia , Osso Parietal/efeitos dos fármacos , Osso Parietal/fisiopatologia , Titânio/efeitos adversos , Cicatrização , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Osteólise/patologia , Osso Parietal/patologia , Fatores de Tempo
18.
Endocrinology ; 141(12): 4552-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11108267

RESUMO

A growing body of evidence suggests that systemic hormones and peptide growth factors may exert their effects on cell growth and differentiation in part through regulation of the cell division cycle. We hypothesized that thyroid hormone regulates terminal differentiation of growth plate chondrocytes in part through controlling cell cycle progression at the G1/S restriction point. Our results support this hypothesis by demonstrating that treatment of epiphyseal chondrocytes with thyroid hormone under chemically defined conditions results in the arrest of DNA synthesis and the onset of terminal differentiation, indicating that thyroid hormone is one factor capable of regulating the transition between cell growth and differentiation in these cells. This terminal differentiation process is associated with induction of the cyclin/cyclin-dependent kinase inhibitors p21(cip-1 waf-1) and p27kip1, suggesting that thyroid hormone may regulate terminal differentiation in part by arresting cell cycle progression through induction of cyclin-dependent kinase inhibitors.


Assuntos
Proteínas de Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores Enzimáticos , Expressão Gênica , Lâmina de Crescimento/metabolismo , Hormônios Tireóideos/farmacologia , Proteínas Supressoras de Tumor , Animais , Animais Recém-Nascidos , Proteínas de Transporte/genética , Divisão Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/genética , Lâmina de Crescimento/citologia , Proteínas Associadas aos Microtúbulos/genética , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Tiroxina/farmacologia , Tri-Iodotironina/farmacologia
19.
J Bone Miner Res ; 15(1): 166-74, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10646126

RESUMO

Numerous in vitro culture models have been developed for the investigation of chondrocyte and cartilage biology. In this study, we investigated the stability of the chondrocytic phenotype in monolayer, aggregate, pellet, and explant culture models and assessed the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) and serum supplementation on the phenotype in each model. Phenotypic effects were assessed by analyses of procollagen type II, aggrecan, (V + C)- fibronectin, and procollagen type I messenger RNA expression. In monolayer cultures, we noted a characteristic loss of procollagen type II and induction of procollagen type I expression. The aggregate and pellet culture models supported matrix protein gene expression profiles more reflective of in vivo levels. In explant cultures, expression of matrix protein genes was consistently depressed. Treatment with rhBMP-2 significantly increased the expression of procollagen type II and aggrecan in monolayer cultures; however, other models showed comparatively little response. Similarly, serum supplementation significantly down-regulated procollagen type II and aggrecan expression in monolayer cultures but had less effect on gene expression in the other models. Serum supplementation increased procollagen type I expression in monolayer and aggregate cultures. These results suggest that the influence of exogenous BMP-2 and serum on expression of chondrocyte-specific matrix protein genes is influenced by aspects of substrate attachments, cellular morphology, and/or cytoskeletal organization. Finally, the analyses of fibronectin expression suggest that V and C region alternative splicing in chondrocytes is linked to the establishment of a three-dimensional multicellular complex.


Assuntos
Sangue , Proteínas Morfogenéticas Ósseas/farmacologia , Cartilagem Articular/citologia , Condrócitos/citologia , Proteínas da Matriz Extracelular , Fator de Crescimento Transformador beta , Agrecanas , Animais , Sequência de Bases , Proteína Morfogenética Óssea 2 , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Primers do DNA , Fibronectinas/genética , Fibronectinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cavalos , Humanos , Lectinas Tipo C , Modelos Biológicos , Fenótipo , Pró-Colágeno/genética , Pró-Colágeno/metabolismo , Proteoglicanas/genética , Proteoglicanas/metabolismo , RNA Mensageiro/genética , Proteínas Recombinantes/farmacologia
20.
Pediatr Res ; 45(6): 799-802, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10367768

RESUMO

Respiratory viruses are an extremely common cause of childhood morbidity. However, the current seroprevalence of viruses in infant populations is difficult to establish because invasive venipuncture may be technically and ethically unacceptable. This prospective study aimed to establish the seroprevalence of respiratory viruses in an infant population by use of a novel multiantigen fluorescence immunoassay against common respiratory viruses, using heel-prick blood samples collected on filter paper. Mothers and babies were recruited in the immediate peripartum period in the Royal Maternity Hospital, Belfast. Cord blood samples at birth and heel-prick filter paper blood samples at 7 mo were collected for measurement of virus-specific IgG to respiratory syncytial virus, influenza A virus, adenovirus, and parainfluenza virus type 1, type 2, and type 3 by indirect immunofluorescence using a multiviral assay developed for this purpose. Of 386 mothers approached, 325 (84%) permitted follow-up at 7 mo, and of these, 256 (79%) agreed to the heel prick. From 234 paired samples, 125 infections were documented. Adenovirus infections were commonest, 53 (22.6%), followed by respiratory syncytial virus, 32 (13.7%); influenza A virus, 22 (9.4%); parainfluenza virus type 3, 14 (6%); parainfluenza virus type 1, 2 (0.85%); and parainfluenza virus type 2, 2 (0.85%). These results demonstrate the seroprevalence of a range of respiratory viruses in an infant population, using a novel multiviral immunoassay. The filter paper collection of blood samples and multiantigen assay format has implications for easy, widespread viral serodiagnosis in both seroepidemiology studies and in the diagnosis of pediatric viral illnesses. Filter paper permits recovery of respiratory virus-specific IgG and can be used as a simple and acceptable epidemiologic and diagnostic tool.


Assuntos
Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Viroses/epidemiologia , Viroses/imunologia , Antígenos Virais , Coleta de Amostras Sanguíneas/métodos , Feminino , Sangue Fetal/imunologia , Fluorimunoensaio/métodos , Humanos , Lactente , Recém-Nascido , Masculino , Irlanda do Norte/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Estudos Soroepidemiológicos
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