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1.
Curr Osteoporos Rep ; 19(3): 318-326, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33876386

RESUMO

PURPOSE OF REVIEW: Bone matrix exhibits great complexity in its composition, structure and mechanics. Here, we provide a review of recent research articles and appraise the evidence that bone matrix quality is clinically important and possibly targetable for fracture prevention. RECENT FINDINGS: Deformation of mineralised collagen fibrils determines bone fracture mechanics. Slipping and separation at the mineral-fibril and fibril-fibril interfaces, respectively, are the structural mechanisms for plastic deformation and microcrack nucleation. Existing technologies for assessing bone tissue in vivo cannot measure matrix structure or fracture mechanics but have shown limited use in clinical settings for identifying fragility or following treatment outcomes based on composition. Matrix is biomechanically and clinically important, but the knowledge has not translated into clinical practice. The structural mechanisms by which a load is transferred from mineralised collagen fibrils to the whole bone via microcracking have been proven too complex to measure in vivo. The mineral-fibril or fibril-fibril interfaces might be suitable targets for diagnosing fragility or delivering molecules that reduce fracture risk by strengthening the mineral bonds while maintaining flexibility in the fibrils.


Assuntos
Matriz Óssea/fisiologia , Fraturas Ósseas/prevenção & controle , Fenômenos Biomecânicos , Colágeno/fisiologia , Módulo de Elasticidade , Humanos , Estresse Mecânico
2.
Semin Musculoskelet Radiol ; 24(3): 323-330, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32987429

RESUMO

No official data exist on the status of musculoskeletal (MSK) radiology in Europe. The Committee for National Societies conducted an international survey to understand the status of training, subspecialization, and local practice among the European Society of Musculoskeletal Radiology (ESSR) partner societies. This article reports the results of that survey. An online questionnaire was distributed to all 26 European national associations that act as official partner societies of the ESSR. The 24 questions were subdivided into six sections: society structure, relationship with the national radiological society, subspecialization, present radiology practice, MSK interventional procedures, and MSK ultrasound. The findings of our study show a lack of standardized training and/or accreditation methods in the field of MSK radiology at a national level. The European diploma in musculoskeletal radiology is directed to partly overcome this problem; however, this certification is still underrecognized. Using certification methods, a more homogeneous European landscape could be created in the future with a view to subspecialist training. MSK ultrasound and MSK interventional procedures should be performed by a health professional with a solid knowledge of the relevant imaging modalities and sufficient training in MSK radiology. Recognition of MSK radiology as an official subspecialty would make the field more attractive for younger colleagues as well as attracting the brightest and best, an important key to further development of both clinical and academic radiology. KEY POINTS: · Standardized training and/or accreditation methods in the field of MSK radiology is lacking at a national level.. · With certification methods, such as the European diploma in musculoskeletal radiology, a more homogeneous European landscape could be created in the future with a view to subspecialist training.. · Recognition of MSK radiology as an official subspecialty would make the field more attractive for younger colleagues as well as attracting the brightest and best, an important key to further development of both clinical and academic radiology..


Assuntos
Diagnóstico por Imagem/tendências , Doenças Musculoesqueléticas/diagnóstico por imagem , Europa (Continente) , Humanos , Sociedades Médicas
3.
J Shoulder Elbow Surg ; 29(10): 1981-1991, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32414612

RESUMO

BACKGROUND: The high incidence of scapular notching in reverse total shoulder arthroplasty (RTSA) has spurred several methods to minimize bone loss. However, up to 93% of RTSAs accompanying scapular notching have been reported to maintain good implant stability for over 10 years. This study was conducted to investigate the relationship between scapular notching and glenoid fixation in RTSA. METHODS: Cadaveric testing was performed to measure the notch-induced variations in strain on the scapular surface and micromotion at the bone-prosthesis interface during arm abductions of 30°, 60°, and 90°. Finite element analysis was used to further study the bone and screw stresses as well as the bone-prosthesis micromotion in cases with a grade 4 notch during complicated arm motions. RESULTS: The notch resulted in an apparent increase in inferior screw stress in the root of the screw cap and at the notch-screw conjunction. However, the maximum stress (172 MPa) along the screw after notching is still much less than the fatigue strength of the titanium screw (600 MPa) under cyclic loading. The bone-prosthesis micromotion results did not present significant notch-induced variations. CONCLUSIONS: Scapular notching will lead to few impacts on the stability of an RTSA on the glenoid side. This finding may explain the long-term longevity of RTSA in cases of severe scapular notching. The relationship between scapular notching and weak regions along the inferior screw may explain why fractures of the inferior screw are sometimes reported in patients with RTSA clinically.


Assuntos
Artroplastia do Ombro , Parafusos Ósseos , Escápula/patologia , Idoso , Artroplastia do Ombro/métodos , Fenômenos Biomecânicos , Cadáver , Feminino , Análise de Elementos Finitos , Humanos , Masculino , Falha de Prótese , Escápula/cirurgia , Articulação do Ombro/cirurgia , Prótese de Ombro , Estresse Mecânico
4.
J Shoulder Elbow Surg ; 29(5): 1019-1029, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31948834

RESUMO

BACKGROUND: Hemiarthroplasty has clear advantages over alternative procedures and is used in 20% of all shoulder joint replacements. Because of cartilage wear, the clinical outcome of hemiarthroplasty is unreliable and controversial. This paper suggests that the optimal choice of prosthetic material may reduce cartilage degeneration and improve the reliability of the procedure. The specific objectives were to assess 3 materials and assess how the severity of arthritis might affect the choice of prosthetic material. METHODS: A CoCr alloy, an AL2O3 ceramic, and a polycarbonate urethane polymer (PCU) were mechanically tested against 5 levels of human osteoarthritic cartilage (from intact to severely arthritic, n = 45). A high friction coefficient, a decrease in Young's modulus, an increase in permeability, a decrease in relaxation time, an increase in surface roughness, and a disrupted appearance of the cartilage after testing were used as measures of cartilage damage. The biomaterial that caused minimal cartilage damage was defined as superior. RESULTS: The CoCr caused the most damage. This was followed by the AL2O3 ceramic, whereas the PCU caused the least amount of damage. Although the degree of arthritis had an effect on the results, it did not change the trend that CoCr performed worst and PCU the best. DISCUSSION AND CONCLUSION: This study indicates that ceramic implants may be a better choice than metals, and the articulating surface should be as smooth as possible. Although our results indicate that the degree of arthritis should not affect the choice of prosthetic material, this suggestion needs to be further investigated.


Assuntos
Cartilagem Articular/lesões , Hemiartroplastia/efeitos adversos , Hemiartroplastia/instrumentação , Prótese de Ombro/efeitos adversos , Materiais Biocompatíveis/efeitos adversos , Cerâmica/efeitos adversos , Ligas de Cromo/efeitos adversos , Módulo de Elasticidade , Fricção , Humanos , Teste de Materiais , Osteoartrite/diagnóstico por imagem , Poliuretanos/efeitos adversos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
5.
Knee Surg Sports Traumatol Arthrosc ; 27(1): 206-214, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30097687

RESUMO

PURPOSE: To analyse the stress distribution through longitudinal and radial meniscal tears in three tear locations in weight-bearing conditions and use it to ascertain the impact of tear location and type on the potential for healing of meniscal tears. METHODS: Subject-specific finite-element models of a healthy knee under static loading at 0°, 20°, and 30° knee flexion were developed from unloaded magnetic resonance images and weight-bearing, contrast-enhanced computed tomography images. Simulations were then run after introducing tears into the anterior, posterior, and midsections of the menisci. RESULTS: Absolute differences between the displacements of anterior and posterior segments modelled in the intact state and those quantified from in vivo weight-bearing images were less than 0.5 mm. There were tear-location-dependent differences between hoop stress distributions along the inner and outer surfaces of longitudinal tears; the longitudinal tear surfaces were compressed together to the greatest degree in the lateral meniscus and were most consistently in compression on the midsections of both menisci. Radial tears resulted in an increase in stress at the tear apex and in a consistent small compression of the tear surfaces throughout the flexion range when in the posterior segment of the lateral meniscus. CONCLUSIONS: Both the type of meniscal tear and its location within the meniscus influenced the stresses on the tear surfaces under weight bearing. Results agree with clinical observations and suggest reasons for the inverse correlation between longitudinal tear length and healing, the inferior healing ability of medial compared with lateral menisci, and the superior healing ability of radial tears in the posterior segment of the lateral meniscus compared with other radial tears. This study has shown that meniscal tear location in addition to type likely plays a crucial role in dictating the success of non-operative treatment of the menisci. This may be used in decision making regarding conservative or surgical management.


Assuntos
Análise de Elementos Finitos , Articulação do Joelho/fisiologia , Meniscos Tibiais/fisiopatologia , Modelos Biológicos , Lesões do Menisco Tibial/fisiopatologia , Adulto , Artroscopia , Humanos , Joelho , Traumatismos do Joelho , Imageamento por Ressonância Magnética , Masculino , Pressão , Amplitude de Movimento Articular , Tomografia Computadorizada por Raios X , Suporte de Carga , Cicatrização
6.
Biochim Biophys Acta ; 1860(4): 648-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26777880

RESUMO

BACKGROUND: Natural mutations of R218 in human serum albumin (HSA) result in an increased affinity for L-thyroxine and lead to the autosomal dominant condition of familial dysalbuminemic hyperthyroxinemia. METHODS: Binding was studied by equilibrium dialysis and computer modeling. RESULTS: Ten of 32 other isoforms tested had modified high-affinity hormone binding. L-thyroxine has been reported to bind to four sites (Tr) in HSA; Tr1 and Tr4 are placed in the N-terminal and C-terminal part of the protein, respectively. Site-directed mutagenesis gave new information about all the sites. CONCLUSIONS: It is widely assumed that Tr1 is the primary hormone site, and that this site, on a modified form, is responsible for the above syndrome, but the binding experiments with the genetic variants and displacement studies with marker ligands indicated that the primary site is Tr4. This new assignment of the high-affinity site was strongly supported by results of MM-PBSA analyses and by molecular docking performed on relaxed protein structure. However, dockings also revealed that mutating R218 for a smaller amino acid increases the affinity of Tr1 to such an extent that it can become the high-affinity site. GENERAL SIGNIFICANCE: Placing the high-affinity binding site (Tr4) and the one which can result in familial dysalbuminemic hyperthyroxinemia (Tr1) in two very different parts of HSA is not trivial, because in this way persons with and without the syndrome can have different types of interactions, and thereby complications, when given albumin-bound drugs. The molecular information is also useful when designing drugs based on L-thyroxine analogues.


Assuntos
Hipertireoxinemia Disalbuminêmica Familiar , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Albumina Sérica/química , Tiroxina/química , Sítios de Ligação , Albumina Sérica/genética , Albumina Sérica/metabolismo , Tiroxina/metabolismo
7.
Clin Rev Bone Miner Metab ; 14(3): 150-160, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27683260

RESUMO

Bone is a complex hierarchical structure, and its principal function is to resist mechanical forces and fracture. Bone strength depends not only on the quantity of bone tissue but also on the shape and hierarchical structure. The hierarchical levels are interrelated, especially the micro-architecture, collagen and mineral components; hence, analysis of their specific roles in bone strength and stiffness is difficult. Synchrotron imaging technologies including micro-CT and small/wide angle X-ray scattering/diffraction are becoming increasingly popular for studying bone because the images can resolve deformations in the micro-architecture and collagen-mineral matrix under in situ mechanical loading. Synchrotron cannot be directly applied in vivo due to the high radiation dose but will allow researchers to carry out systematic multifaceted studies of bone ex vivo. Identifying characteristics of aging and disease will underpin future efforts to generate novel devices and interventional therapies for assessing and promoting healthy aging. With our own research work as examples, this paper introduces how synchrotron imaging technology can be used with in situ testing in bone research.

8.
Biochim Biophys Acta ; 1840(9): 2806-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24769178

RESUMO

BACKGROUND: Sodium octanoate (Oct) and N-acetyl-l-tryptophan (N-AcTrp) are widely used as stabilizers during pasteurization and storage of albumin products. However, exposure to light photo-degrades N-AcTrp with the formation of potentially toxic compounds. Therefore, we have examined the usefulness of N-acetyl-l-methionine (N-AcMet) in comparison with N-AcTrp for long-term stability, including photo stability, of albumin products. METHODS: Recombinant human serum albumin (rHSA) with and without additives was photo-irradiated for 4weeks. The capability of the different stabilizers to scavenge reactive oxygen species (ROS) was examined by ESR spectrometry. Carbonyl contents were assessed by a spectrophotometric method using fluoresceinamine and Western blotting, whereas the structure of rHSA was examined by SDS-PAGE, far-UV circular dichroism and differential scanning calorimetry. Binding was determined by ultrafiltration. RESULTS: N-AcMet was found to be a superior ROS scavenger both before and after photo-irradiation. The number of carbonyl groups formed was lowest in the presence of N-AcMet. According to SDS-PAGE, N-AcMet stabilizes the monomeric form of rHSA, whereas N-AcTrp induces degradation of rHSA during photo-irradiation. The decrease in α-helical content of rHSA was the smallest in the presence of Oct, without or with N-AcMet. Photo-irradiation did not affect the denaturation temperature or calorimetric enthalpy of rHSA, when N-AcMet was present. CONCLUSION: The weakly bound N-AcMet is a superior protectant of albumin, because it is a better ROS-protector and structural stabilizer than N-AcTrp, and it is probable and also useful for other protein preparations. GENERAL SIGNIFICANCE: N-AcMet is an effective stabilizer of albumin during photo-irradiation, while N-Ac-Trp promotes photo-oxidative damage to albumin.


Assuntos
Sequestradores de Radicais Livres/química , Metionina/análogos & derivados , Espécies Reativas de Oxigênio/química , Albumina Sérica/química , Triptofano/análogos & derivados , Humanos , Metionina/química , Oxirredução , Processos Fotoquímicos , Estabilidade Proteica , Triptofano/química
9.
Biochem Biophys Res Commun ; 465(3): 481-7, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26277392

RESUMO

Peroxynitrite, the reaction product of superoxide [Formula: see text] and nitric oxide (NO), nitrates tyrosine residues, unsaturated fatty acids, cyclic guanosine monophosphate and other phenolics. We report herein that indoxyl sulfate (IS) is also nitrated by peroxynitrite in vitro and forms 2-nitro-IS, as determined from spectral characteristics and (1)H-NMR. IS is one of the very important uremic toxins that accelerate the progression of chronic kidney disease via various mechanisms. However, cell viability experiments with human proximal tubular cells show that the cytotoxicity of 2-nitro-IS is several-fold higher than that of IS. The explanation for this finding seems to be that 2-nitro-IS induces a much more pronounced generation of intracellular reactive oxygen species (ROS) than IS. Results with inhibitors revealed that an organic anion transporter, several intracellular enzymes and nonprotein-bound iron ions are reasons for this finding. Most importantly, however, as detected by immunofluorescence and Western blotting, 2-nitro-IS induces the expression of heme oxygenase-1 and thereby the formation of ROS; most probably through the Fenton reaction. The final result of the increased amounts of ROS is death of the kidney cells. Thus, nitration of uremic toxins by peroxynitrite may help us to understand the initiation and progress of chronic kidney diseases.


Assuntos
Heme Oxigenase-1/metabolismo , Indicã/administração & dosagem , Indicã/química , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/fisiologia , Ácido Peroxinitroso/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Túbulos Renais Proximais/efeitos dos fármacos , Nitrocompostos/administração & dosagem , Nitrocompostos/síntese química
10.
Nature ; 457(7227): 301-4, 2009 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-19148097

RESUMO

Turbulent rotating convection controls many observed features of stars and planets, such as magnetic fields, atmospheric jets and emitted heat flux patterns. It has long been argued that the influence of rotation on turbulent convection dynamics is governed by the ratio of the relevant global-scale forces: the Coriolis force and the buoyancy force. Here, however, we present results from laboratory and numerical experiments which exhibit transitions between rotationally dominated and non-rotating behaviour that are not determined by this global force balance. Instead, the transition is controlled by the relative thicknesses of the thermal (non-rotating) and Ekman (rotating) boundary layers. We formulate a predictive description of the transition between the two regimes on the basis of the competition between these two boundary layers. This transition scaling theory unifies the disparate results of an extensive array of previous experiments, and is broadly applicable to natural convection systems.

12.
Knee Surg Sports Traumatol Arthrosc ; 23(8): 2230-2236, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24770381

RESUMO

PURPOSE: Radiolucencies are commonly observed in unicompartmental knee arthroplasty (UKA) patients within 1 year of arthroplasty. The objective of the study was to identify how the bone mineral density (BMD) changes up to 1 year post-arthroplasty. METHODS: Dual X-ray absorptiometry scans were obtained from 11 UKA patients at 10 days and 3, 6, and 12 months post-surgery. Patients were scanned in both anteroposterior and lateral knee orientations. RESULTS: Most subjects saw a large decline in BMD in the first 6 months following surgery, followed by some recovery in bone mass. The biggest change occurred under the tibial intercondylar eminence, which decreased significantly by an average of 18 % at 6 months and was 15 % at 1 year. The average bone loss under the tibial tray was low; however, the bone loss at the anterior portion was higher with a significant average decrease of 14 %. There was no change in BMD under the tibial keel. There was significant bone loss of 13 % under the femoral component; the regions anterior and posterior to the central femoral implant peg both had significant bone loss of 14 %. The bone response between patients was very variable, with some patients losing bone steadily, and others gaining it rapidly after an early fall. CONCLUSIONS: While the overall reduction in BMD under both components was low, it was significant and there was substantial individual variation superimposed on this. Improving our understanding of this response to surgery may impact on prosthesis survival. LEVEL OF EVIDENCE: Therapeutic study: case series with no comparison group, Level IV.


Assuntos
Artroplastia do Joelho/efeitos adversos , Densidade Óssea , Reabsorção Óssea/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Idoso , Reabsorção Óssea/etiologia , Feminino , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Tíbia/cirurgia
13.
Biochim Biophys Acta ; 1830(12): 5535-44, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23528895

RESUMO

BACKGROUND: Human serum albumin and some of its ligand complexes possess enzymatic properties which are useful both in vivo and in vitro. SCOPE OF REVIEW: This review summarizes present knowledge about molecular aspects, practical applications and potentials of these properties. MAJOR CONCLUSIONS: The most pronounced activities of the protein are different types of hydrolysis. Key examples are esterase-like activities involving Tyr411 or Lys199 and the thioesterase activity of Cys34. In the first case, hydrolysis involves water and both products are released, whereas in the latter cases one of the products is set free, and the other stays covalently bound to the protein. However, the modified Cys34 can be converted back to its reduced form by another compound/enzymatic system. Among the other activities are glucuronidase, phosphatase and amidase as well as isomerase and dehydration properties. The protein has great impact on the metabolism of, for example, eicosanoids and xenobiotics. Albumin with a metal ion-containing complex is capable of facilitating reactions involving reactive oxygen and nitrogen species. GENERAL SIGNIFICANCE: Albumin is useful in detoxification reactions, for activating prodrugs, and for binding and activating drug conjugates. The protein can be used to construct smart nanotubes with enzymatic properties useful for biomedical applications. Binding of organic compounds with a metal ion often results in metalloenzymes or can be used for nanoparticle formation. Because any compound acting as cofactor and/or the protein can be modified, enzymes can be constructed which are not naturally found and therefore can increase, often stereospecifically, the number of catalytic reactions. This article is part of a Special Issue entitled Serum Albumin.


Assuntos
Esterases/metabolismo , Albumina Sérica/metabolismo , Esterases/química , Humanos , Ligantes , Conformação Proteica , Albumina Sérica/química
14.
Biochim Biophys Acta ; 1830(12): 5405-17, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23558059

RESUMO

BACKGROUND: At present, 67 different genetic variants of human serum albumin and proalbumin have been molecularly characterized at the protein and/or gene level. SCOPE OF REVIEW: This review summarizes present knowledge about genetic and molecular aspects, functional consequences and potential uses of the variants. MAJOR CONCLUSIONS: The frequency of bisalbuminemia in the general population is probably about 1:1000, but it can be much higher in isolated populations. Mutations are often due to hypermutable CpG dinucleotides, and in addition to single-amino acid substitutions, glycosylated variants and C-terminally modified alloalbumins have been found. Some mutants show altered stability in vivo and/or in vitro. High-affinity binding of Ni(++) and Cu(++) is blocked, or almost so, by amino acid changes at the N-terminus. In contrast, substitution of Leu90 and Arg242 leads to strong binding of triiodothyronine and l-thyroxine, respectively, resulting in two clinically important syndromes. Variants often have modified plasma half-lives and organ uptakes when studied in mice. GENERAL SIGNIFICANCE: Because alloalbumins do not seem to be associated with disease, they can be used as markers of migration and provide a model for study of neutral molecular evolution. They can also give valuable molecular information about albumins binding sites, antioxidant and enzymatic properties, as well as stability. Mutants with increased affinity for endogenous or exogenous ligands could be therapeutically relevant as antidotes, both for in vivo and extracorporeal treatment. Variants with modified biodistribution could be used for drug targeting. In most cases, the desired function can be further elaborated by producing site-directed, recombinant mutants. This article is part of a Special Issue entitled Serum Albumin.


Assuntos
Isoformas de Proteínas/fisiologia , Albumina Sérica/fisiologia , Humanos , Modelos Moleculares , Conformação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Albumina Sérica/química , Albumina Sérica/genética
15.
Biochim Biophys Acta ; 1830(12): 5494-502, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23612153

RESUMO

BACKGROUND: DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA). SCOPE OF REVIEW: To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. MAJOR CONCLUSIONS: CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. GENERAL SIGNIFICANCE: Study of the defects in the ALB resulting in CAA allows the identification of "hot spot" regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Albumina Sérica/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Humanos , Mutação
16.
Biochim Biophys Acta ; 1830(4): 2917-23, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23328494

RESUMO

BACKGROUND: 4Z,15Z-bilirubin-IXα (BR), an endogenous toxic compound that is sparingly soluble in water, binds human serum albumin (HSA) with high affinity in a flexible manner. Our previous findings suggest that both Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of BR, and especially Lys199 in stand-alone domain II plays a prominent role in the renal elimination of BR. Our hypothesis is that HSA-domain II with high BR binding would be a useful therapeutic agent to treat hyperbilirubinemia in patients with impaired liver function. METHODS: Unbound BR concentrations were determined using a modified HRP assay. To evaluate the effect of pan3_3-13 domain II mutant in promoting urinary BR excretion, the serum concentration and urinary excretion amount of BR were determined using bile duct ligation mice. RESULTS: After three or six rounds of panning, pan3_3-13 and pan6_4 were found to have a significantly higher affinity for BR than wild-type domain II. Administration of pan3_3-13 significantly reduced serum BR level and increased its urinary excretion in the disease model mice as compared to wild-type domain II treatment. CONCLUSIONS: These results suggest that pan3_3-13 has great potential as a therapeutic agent that promotes urinary BR excretion in hyperbilirubinemia. GENERAL SIGNIFICANCE: This is the first study to be applied to other HSA bound toxic compounds that are responsible for the progression of disease, thereby paving the way for the development of non-invasive and cost effective blood purification treatment methods.


Assuntos
Bilirrubina/metabolismo , Hiperbilirrubinemia/tratamento farmacológico , Albumina Sérica/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Camundongos , Camundongos Endogâmicos ICR , Dados de Sequência Molecular , Mutação , Estrutura Terciária de Proteína , Albumina Sérica/química , Ressonância de Plasmônio de Superfície
17.
Acta Orthop ; 85(1): 91-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24286563

RESUMO

BACKGROUND AND PURPOSE: It is difficult to evaluate glenoid component periprosthetic radiolucencies in total shoulder arthroplasties (TSAs) using plain radiographs. This study was performed to evaluate whether computed tomography (CT) using a specific patient position in the CT scanner provides a better method for assessing radiolucencies in TSA. METHODS: Following TSA, 11 patients were CT scanned in a lateral decubitus position with maximum forward flexion, which aligns the glenoid orientation with the axis of the CT scanner. Follow-up CT scanning is part of our routine patient care. Glenoid component periprosthetic lucency was assessed according to the Molé score and it was compared to routine plain radiographs by 5 observers. RESULTS: The protocol almost completely eliminated metal artifacts in the CT images and allowed accurate assessment of periprosthetic lucency of the glenoid fixation. Positioning of the patient within the CT scanner as described was possible for all 11 patients. A radiolucent line was identified in 54 of the 55 observed CT scans and osteolysis was identified in 25 observations. The average radiolucent line Molé score was 3.4 (SD 2.7) points with plain radiographs and 9.5 (SD 0.8) points with CT scans (p = 0.001). The mean intra-observer variance was lower in the CT scan group than in the plain radiograph group (p = 0.001). INTERPRETATION: The CT scan protocol we used is of clinical value in routine assessment of glenoid periprosthetic lucency after TSA. The technique improves the ability to detect and monitor radiolucent lines and, therefore, possibly implant loosening also.


Assuntos
Artroplastia de Substituição/efeitos adversos , Prótese Articular , Falha de Prótese , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artefatos , Protocolos Clínicos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Osteólise/etiologia , Posicionamento do Paciente/métodos , Articulação do Ombro/fisiopatologia , Tomografia Computadorizada por Raios X/métodos
18.
Nitric Oxide ; 30: 36-42, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23402724

RESUMO

S-Nitrosated human serum albumin (SNO-HSA) is useful in preventing liver ischemia/reperfusion injury, and SNO-HSA should thus be able to prevent cell injury during liver transplantation. However, the potential protective effect of SNO-HSA on a combination of cold and warm ischemia, which is obligatory when performing liver transplantation, has not been examined. Therefore, we evaluated the protective effect of SNO-HSA added to University of Wisconsin (UW) solution during cold or/and warm ischemia in situ and in vitro. First, we observed that apoptotic and necrotic cell death were increased during cold and warm ischemia, respectively. SNO-HSA, which possesses anti-apoptosis activity at low NO concentrations, can inhibit cold ischemia injury both in situ and in vitro. In contrast, SNO-HSA had no significant effect on warm liver ischemia injury which, however, can be reduced by UW solution. We also demonstrated that the cellular uptake of NO from SNO-HSA can occur during cold ischemia resulting in induction of heme oxygenase-1 within 3h of cold ischemia. Our results indicate that treatment with SNO-HSA or UW solution alone is not sufficient to inhibit liver injury during a period of both cold and warm ischemia. However, a combination of SNO-HSA and UW solution can be used to prevent the two types of ischemia. SNO-HSA-added UW solution could be very useful in transplantation, because the previously imposed constraints on preservation time can be removed. This is a great advantage in a situation as the present one with increased utilization of scarce donor organs for more recipients.


Assuntos
Apoptose/efeitos dos fármacos , Hepatopatias/prevenção & controle , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Compostos Nitrosos/farmacologia , Soluções para Preservação de Órgãos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Albumina Sérica/farmacologia , Adenosina/química , Adenosina/farmacologia , Alopurinol/química , Alopurinol/farmacologia , Análise de Variância , Animais , Glutationa/química , Glutationa/farmacologia , Células Hep G2 , Humanos , Insulina/química , Insulina/farmacologia , Fígado/citologia , Fígado/efeitos dos fármacos , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Masculino , Necrose , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Compostos Nitrosos/química , Soluções para Preservação de Órgãos/química , Rafinose/química , Rafinose/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Albumina Sérica/química , Albumina Sérica Humana
19.
Clin Biomech (Bristol, Avon) ; 107: 106032, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37348206

RESUMO

BACKGROUND: In vivo evaluation of ankle joint biomechanics is key to investigating the effect of injuries on the mechanics of the joint and evaluating the effectiveness of treatments. The objectives of this study were to 1) investigate the kinematics and contact strains of the ankle joint and 2) to investigate the correlation between the tibiotalar joint contact strains and the prevalence of osteochondral lesions of the talus distribution. METHODS: Eight healthy human ankle joints were subjected to compressive load and 3 T MRIs were obtained before and after applying load. The MR images in combination with digital volume correlation enabled non-invasive measurement of ankle joint kinematics and tibiotalar joint contact strains in three dimensions. FINDINGS: The total translation of the calcaneus was smaller (0.48 ± 0.15 mm, p < 0.05) than the distal tibia (0.93 ± 0.16 mm) and the talus (1.03 ± 0.26 mm). These movements can produce compressive and shear joint contact strains (approaching 9%), which can cause development of lesions on joints. 87.5% of peak tensile, compressive, and shear strains in the tibiotalar joint took place in the medial and lateral zones. INTERPRETATION: The findings suggested that ankle bones translate independently from each other, and in some cases in opposite directions. These findings help explain the distribution of osteochondral lesions of the talus which have previously been observed to be in medial and lateral regions of the talar dome in 90% of cases. They also provide a reason for the central region of talar dome being less susceptible to developing osteochondral lesions.


Assuntos
Articulação do Tornozelo , Tálus , Humanos , Articulação do Tornozelo/diagnóstico por imagem , Tornozelo , Fenômenos Biomecânicos , Tálus/diagnóstico por imagem , Imageamento por Ressonância Magnética
20.
JSES Int ; 7(3): 493-498, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37266168

RESUMO

Background: Glenoid loosening remains a concern in anatomical total shoulder replacement. Preoperative planning software allows optimization of the component positioning, but the target orientation remains unclear due to conflicting optimization priorities. Commonly, the component is aligned to the prescribed version and inclination that reflect the population's average anatomy. The freehand technique attempts to secure strong fixation by aiming to preserve the subchondral bone. This study compared the state of the subchondral plate after reaming and compared the results of these two techniques. Methods: Two groups of shoulder computed tomography scans were assessed, 34 normal and 34 osteoarthritic. Preoperative planning software was used to place the glenoid component in prescribed adjusted angles, with neutral (0o,0o), retroverted (-10o,0o) and inclined alignment (0o,10o). The computed tomography Hounsfield values at the virtually reamed surface were assessed to determine the percentage of the intended component-bone interface consisting of cortical bone, here termed "cortical bone seating". This was then compared to positioning the component using a freehand technique. Results: The freehand technique improved cortical bone seating in the osteoarthritic group with a mean (standard deviation) of 53.3% (14.3), while neutral alignment resulted in 36.7% (10.8), retroversion 40.4% (13.1), and inclination 39.3% (13.5), P < .001. A similar trend was observed in the normal group. Conclusions: The freehand method resulted in significantly improved cortical bone seating compared to the prescribed adjusted angles. These findings question the use of a one-size-fits-all-orientation and suggest that applying a technique that aims for maximum cortical fixation (freehand) may reduce the risk of aseptic loosening.

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