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1.
Open Biol ; 6(2): 150202, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26842068

RESUMO

Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid ß (Aß) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro, contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming 'Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD)' clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Placa Amiloide/metabolismo , Agregação Patológica de Proteínas/metabolismo , Componente Amiloide P Sérico/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Angiopatia Amiloide Cerebral/metabolismo , Angiopatia Amiloide Cerebral/patologia , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Agregação Patológica de Proteínas/tratamento farmacológico , Componente Amiloide P Sérico/genética
2.
Proc Natl Acad Sci U S A ; 110(40): 16115-20, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23959890

RESUMO

Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.


Assuntos
Amiloide/metabolismo , Amiloidose/fisiopatologia , Inflamação/complicações , Proteína Amiloide A Sérica/metabolismo , Amiloidose/etiologia , Animais , Vermelho Congo , Primers do DNA/genética , Doxiciclina/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real
3.
J Immunol Methods ; 384(1-2): 92-102, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-22867744

RESUMO

The human pentraxin proteins, serum amyloid P component (SAP) and C-reactive protein (CRP) are important in routine clinical diagnosis, SAP for systemic amyloidosis and CRP for monitoring the non-specific acute phase response. They are also targets for novel therapies currently in development but their roles in health and disease are controversial. Thus, both for clinical use and to rigorously elucidate their functions, structurally and functionally intact, pharmaceutical grade preparations of the natural, authentic proteins are required. We report here the production from normal human donor plasma and the characterization of the first such preparations. Importantly, we demonstrate that, contrary to reports using recombinant proteins and less well characterized preparations, neither CRP nor SAP stimulate the release by human peripheral blood mononuclear cells in vitro of any TNFα, IL-6 or IL-8, nor does SAP cause release of IL-1ß or IL-10. Furthermore neither of our preparations was pro-inflammatory in mice in vivo.


Assuntos
Proteína C-Reativa/análise , Citocinas/metabolismo , Leucócitos Mononucleares/metabolismo , Componente Amiloide P Sérico/análise , Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/isolamento & purificação , Proteínas de Fase Aguda/farmacologia , Amiloidose/sangue , Animais , Proteína C-Reativa/isolamento & purificação , Proteína C-Reativa/farmacologia , Células Cultivadas , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Componente Amiloide P Sérico/isolamento & purificação , Componente Amiloide P Sérico/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Fator de Necrose Tumoral alfa/metabolismo
4.
Phytochemistry ; 74: 79-89, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22119077

RESUMO

In this study, an EST library (EH663598-EH666265) obtained from xylogenic tissue cultures of tobacco that had been previously generated was annotated. The library proved to be enriched in transcripts related to the synthesis and modification of secondary cell walls. The xylem-specific transcripts for most of the genes of the lignification and xylan pathways were identified and several full-length sequences obtained. Gene expression was determined in available tobacco lines down-regulated for enzymes of the phenylpropanoid pathway: CINNAMATE 4-HYDROXYLASE (sc4h), CINNAMOYL-COA REDUCTASE (asccr) and lignification-specific peroxidase (asprx). In addition, lines down-regulated in the nucleotide-sugar pathway to xylan formation through antisense expression of UDP-GLUCURONIC ACID DECARBOXYLASE (asuxs) were also analysed. It is shown herein that most transcripts were down-regulated for both lignin and xylan synthesis pathways in these lines, while CELLULOSE SYNTHASE A3 was up-regulated in lignin-modified lines. The analysis indicates the existence of interdependence between lignin and xylan pathways at the transcriptional level and also shows that levels of cellulose, xylan and lignin are not necessarily directly correlated to differences in transcription of the genes involved upstream, as shown by cell wall fractionation and sugar analysis. It is therefore suggested that cell wall biosynthesis regulation occurs at different levels, and not merely at the transcriptional level. In addition, all lines analyzed showed improved enzymic saccharification of secondary but not primary walls. Nevertheless, this demonstrates potential industrial applicability for the approach undertaken to improve biomass utility.


Assuntos
Parede Celular/metabolismo , Expressão Gênica , Genes de Plantas , Lignina/genética , Nicotiana/genética , Xilanos/genética , Xilema/genética , Celulose/biossíntese , Celulose/genética , Regulação da Expressão Gênica de Plantas , Biblioteca Gênica , Glucosiltransferases , Lignina/metabolismo , Células Vegetais/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Nicotiana/enzimologia , Transcrição Gênica , Xilanos/biossíntese , Xilema/metabolismo
5.
J Immunol Methods ; 371(1-2): 18-24, 2011 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-21708157

RESUMO

Human serum amyloid P component (SAP) is of increasing interest for its possible pathogenic role in amyloidosis and Alzheimer's disease, and as a therapeutic target in these conditions. We have developed and validated a robust and reproducible immunoradiometric assay (IRMA) for human SAP in serum, plasma and cerebrospinal fluid, and characterized the notable stability of human SAP immunoreactivity during storage of undiluted serum at 4°C and 37°C as well as frozen at -30°C. SAP values were also stable after repeated freeze thawing of highly diluted serum samples. The 100 fold dynamic range of the assay, 0.5-50 µg/L, encompassed all values seen in blood and cerebrospinal fluid, when tested at suitable dilutions, from both normal healthy individuals and patients, including subjects receiving the SAP-depleting drug, CPHPC. Furthermore by comparing the IRMA values in the presence and absence of calcium, the new assay revealed interference due to the binding of CPHPC by SAP, which was markedly enhanced in heparinized plasma. It is therefore essential that SAP assays in samples from patients on CPHPC be conducted in the absence of free calcium, in order to completely abrogate interference and determine the actual total SAP concentration. Estimates by the IRMA of SAP concentration in 49 serum samples from amyloidosis patients corresponded closely with those obtained by the established standard electro-immunoassay method and by a newly developed commercial ELISA kit (Hycult Biotechnology).


Assuntos
Ensaio Imunorradiométrico/métodos , Componente Amiloide P Sérico/análise , Doença de Alzheimer/sangue , Doença de Alzheimer/tratamento farmacológico , Amiloidose/sangue , Amiloidose/tratamento farmacológico , Análise Química do Sangue/métodos , Ácidos Carboxílicos/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoensaio , Estabilidade Proteica , Pirrolidinas/farmacologia , Componente Amiloide P Sérico/antagonistas & inibidores
6.
Nature ; 468(7320): 93-7, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-20962779

RESUMO

Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.


Assuntos
Amiloide/efeitos dos fármacos , Amiloidose/prevenção & controle , Anticorpos/imunologia , Anticorpos/farmacologia , Componente Amiloide P Sérico/antagonistas & inibidores , Componente Amiloide P Sérico/imunologia , Amiloidose/terapia , Animais , Anticorpos/uso terapêutico , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Componente Amiloide P Sérico/genética
7.
Br J Haematol ; 148(5): 760-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20064157

RESUMO

Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their formation and/or persistence. We therefore developed CPHPC ((R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl]pyrrolidine-2 carboxylic acid), a novel bis(D-proline) drug, to specifically target SAP and report here a first, exploratory, open label proof of principle study in systemic amyloidosis. CPHPC produced sustained, >95% depletion of circulating SAP in all patients and c. 90% reduction in the SAP content of the two amyloidotic organs that became available. There were no significant adverse effects of either SAP depletion or CPHPC itself. No accumulation of amyloid was demonstrable by SAP scintigraphy in any patient on the drug. In hereditary fibrinogen amyloidosis, which is inexorably progressive, proteinuria was reduced in four of five patients receiving CPHPC and renal survival was prolonged compared to a historical control group. These promising clinical observations merit further study.


Assuntos
Amiloidose/tratamento farmacológico , Amiloidose/metabolismo , Ácidos Carboxílicos/uso terapêutico , Componente Amiloide P Sérico/efeitos dos fármacos , Componente Amiloide P Sérico/metabolismo , Adulto , Idoso , Amiloidose/sangue , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Ácidos Carboxílicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico
8.
Proteomics ; 9(9): 2355-72, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19402043

RESUMO

The utility of plant secondary cell wall biomass for industrial and biofuel purposes depends upon improving cellulose amount, availability and extractability. The possibility of engineering such biomass requires much more knowledge of the genes and proteins involved in the synthesis, modification and assembly of cellulose, lignin and xylans. Proteomic data are essential to aid gene annotation and understanding of polymer biosynthesis. Comparative proteomes were determined for secondary walls of stem xylem and transgenic xylogenic cells of tobacco and detected peroxidase, cellulase, chitinase, pectinesterase and a number of defence/cell death related proteins, but not marker proteins of primary walls such as xyloglucan endotransglycosidase and expansins. Only the corresponding detergent soluble proteome of secretory microsomes from the xylogenic cultured cells, subjected to ion-exchange chromatography, could be determined accurately since, xylem-specific membrane yields were of poor quality from stem tissue. Among the 109 proteins analysed, many of the protein markers of the ER such as BiP, HSP70, calreticulin and calnexin were identified, together with some of the biosynthetic enzymes and associated polypeptides involved in polymer synthesis. However 53% of these endomembrane proteins failed identification despite the use of two different MS methods, leaving considerable possibilities for future identification of novel proteins involved in secondary wall polymer synthesis once full genomic data are available.


Assuntos
Parede Celular/química , Nicotiana/química , Proteínas de Plantas/análise , Caules de Planta/química , Proteoma/análise , Xilema/química , Linhagem Celular , Parede Celular/metabolismo , Espectrometria de Massas , Microssomos/química , Microssomos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Caules de Planta/metabolismo , Nicotiana/enzimologia , Nicotiana/metabolismo , Xilema/metabolismo
9.
Phytochemistry ; 68(11): 1497-509, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17509629

RESUMO

Understanding regulation of phenolic metabolism underpins attempts to engineer plants for diverse properties such as increased levels of antioxidant flavonoids for dietary improvements or reduction of lignin for improvements to fibre resources for industrial use. Previous attempts to alter phenolic metabolism at the level of the second enzyme of the pathway, cinnamate 4-hydroxylase have employed antisense expression of heterologous sequences in tobacco. The present study describes the consequences of homologous sense expression of tomato CYP73A24 on the lignin content of stems and the flavonoid content of fruits. An extensive number of lines were produced and displayed four developmental variants besides a normal phenotype. These aberrant phenotypes were classified as dwarf plants, plants with distorted (curly) leaves, plants with long internodes and plants with thickened waxy leaves. Nevertheless, some of the lines showed the desired increase in the level of rutin and naringenin in fruit in a normal phenotype background. However this could not be correlated directly to increased levels of PAL and C4H expression as other lines showed less accumulation, although all lines tested showed increases in leaf chlorogenic acid which is typical of Solanaceous plants when engineered in the phenylpropanoid pathway. Almost all transgenic lines analysed showed a considerable reduction in stem lignin and in the lines that were specifically examined, this was correlated with partial sense suppression of C4H. Although not the primary purpose of the study, these reductions in lignin were amongst the greatest seen in plants modified for lignin by manipulation of structural genes. The lignin showed higher syringyl to coniferyl monomeric content contrary to that previously seen in tobacco engineered for downregulation of cinnamate 4-hydroxylase. These outcomes are consistent with placing CYP73A24 more in the lignin pathway and having a role in flux control, while more complex regulatory processes are likely to be involved in flavonoid and chlorogenic acid accumulation.


Assuntos
Flavonoides/metabolismo , Lignina/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , Solanum lycopersicum/genética , Transcinamato 4-Mono-Oxigenase/genética , Sequência de Aminoácidos , Frutas/genética , Frutas/metabolismo , Inativação Gênica , Dados de Sequência Molecular , Fenóis/metabolismo , Fenótipo , Proteínas de Plantas/metabolismo , Caules de Planta/genética , Caules de Planta/metabolismo , Plantas Geneticamente Modificadas/anatomia & histologia , Alinhamento de Sequência , Transcinamato 4-Mono-Oxigenase/metabolismo , Transformação Genética
10.
Phytochemistry ; 67(16): 1750-7, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16616263

RESUMO

Plant secondary metabolism is highly regulated within the major pathways to terpenoids, phenolics and alkaloids. Such regulation can occur at multiple levels from transcription through to the compartmentation of the product. However, the possibility exists for cross-talk between these pathways, the regulation of which is largely unknown at present. Such phenomena are important to understand in the application of plant breeding, where unintended effects of transgenesis or mutation can have an impact on the environment or human health. In an effort to improve dietary antioxidant content of crop plants, the tomato has been a major focus of effort for engineering both lipophilic antioxidants such as carotenoids and hydrophilic antioxidants such as flavonoid glycosides. In this study, a panel of transgenic and mutant tomato lines has been subjected to metabolite profiling in comparison with wild type Ailsa Craig for both carotenoids and phenolics. A range of mutants and transgenic lines were selected showing a range of phenotypes varying from down-regulation through to increased levels of lycopene and beta-carotene. All mutants altered in structural genes for carotenoid biosynthesis showed that perturbations in carotenoid biosynthesis do not generally alter phenolic or flavonoids content significantly even when devoid of carotenoids. Reciprocally, the down-regulation of ferulate 5-hydroxylase had no effect on carotenoid content. In contrast mutants defective in light perception such as the high pigment (hp-1) and LA3771 possess elevated chlorogenic acid and rutin as well as increased carotenoid content. These lines can act as the hosts for further genetic manipulation for increased antioxidant content.


Assuntos
Antioxidantes/metabolismo , Carotenoides/metabolismo , Fenóis/metabolismo , Solanum lycopersicum/metabolismo , Cromatografia Líquida de Alta Pressão , Plantas Geneticamente Modificadas , Terpenos/metabolismo
11.
FEBS Lett ; 580(6): 1541-6, 2006 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-16480721

RESUMO

A 42kDa chitin-binding proline-rich protein (PRP) from French bean has been previously characterised through its involvement in plant-pathogen interactions. It is located at the plasmalemma-wall interface, intercellular spaces and binds to the pathogen Colletotrichum lindemuthianum in vitro and in planta. It is also present in cell wall appositions formed in response to an hrp mutant of Xanthomonas campestris. We now show that the 42kDa protein is composed of two components, a 25kDa polypeptide member of the PRP family of legumes and a 6.8kDa cysteine-rich peptide with high similarity to snakin-2 from potato. Snakins bind to pathogens and are antimicrobial. Molecular cloning of the longest PRP corresponding to the N-terminal sequence of the purified protein and the 6.8kDa component is reported. The cognate mRNAs show coordinate expression. The two-component protein complex has already been shown to be involved in binding and immobilising pathogens through oxidative cross-linking of the PRP components but could also function as a two-component chitin-receptor involved in plant-pathogen interactions through antimicrobial activity and/or signalling.


Assuntos
Proteínas de Transporte/metabolismo , Quitina/química , Peptídeos/metabolismo , Phaseolus/metabolismo , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Proteínas de Transporte/química , Proteínas de Transporte/genética , Clonagem Molecular , Cisteína/química , DNA Complementar/genética , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/genética , Phaseolus/química , Proteínas de Plantas/química , Proteínas de Plantas/genética , Domínios Proteicos Ricos em Prolina , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Transcrição Gênica
12.
Kidney Int Suppl ; (88): S94-9, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14870882

RESUMO

UNLABELLED: The in vitro biocompatibility performance of a 25 mmol/L bicarbonate/10 mmol/L lactate-buffered peritoneal dialysis fluid. BACKGROUND: The biocompatibility profile of a new peritoneal dialysis (PD) solution (Physioneal 35) was determined using a selection of in vitro assay systems. Physioneal 35 is buffered by a combination of 25 mmol/L bicarbonate and 10 mmol/L lactate, thereby providing a solution with a total of 35 mmol/L of alkali to complement the currently available 25 mmol/L bicarbonate and 15 mmol/L lactate combination solution, Physioneal 40. In addition, the new solution contains a calcium concentration of 1.75 mmol/L rather than 1.25 mmol/L present in Physioneal 40. Physioneal 35 and 40 are manufactured in double chamber bag systems that permit separation of glucose from the buffer during sterilization. When the two chambers are mixed just before patient use, the resulting solution has a neutral pH and reduced glucose degradation content. Physioneal 35 was evaluated for its cytotoxicity potential using a murine fibroblast assay, its acute effect on human neutrophil and human peritoneal mesothelial cell function, and its in vitro potential to form advanced glycation end products (AGE). The biocompatibility characteristics of this new formulation were compared with that of a conventional, lactate-based solution and to that of its parent formulation, Physioneal 40. METHODS: Proliferation of murine fibroblasts was determined after exposure to dialysis fluids for 72 hours. Cell viability was assayed by the ability to take up neutral red dye. Human neutrophils were exposed for 15 minutes to dialysis fluids, and their ATP content and phorbol 12-myristate 13-acetate (PMA) stimulated chemiluminescence response was determined as a measure of viability and respiratory burst activity, respectively. Cellular interleukin (IL)-1beta-driven IL-8 synthesis by human mesothelial cells following acute exposure to dialysis fluids was also assessed. Advanced glycation end product formation in the dialysis fluids was measured after 5 and 20 days of incubation with human serum albumin (HSA) as the model protein. RESULTS: In all assays employed, the biocompatibility profile of Physioneal 35 was similar to that of the Physioneal 40 parent formulation. Physioneal 35 showed a significant improvement in biocompatibility performance compared to a pH neutralized conventional lactate-buffered peritoneal dialysis solution in the murine fibroblast assay. In the acute exposure assays, human neutrophil viability and respiratory burst were significantly improved compared with the acidic, conventional solution; however, no statistically significant improvement were seen in mesothelial cells. AGE formation, which is thought to be an important mechanism by which glucose and glucose degradation products cause structural and functional changes of the peritoneal membrane, was significantly lower in Physioneal 35 compared with the conventional dialysis solution. CONCLUSION: The biocompatibility profile of Physioneal 35 was similar to that of the original Physioneal 40 bicarbonate/ lactate-buffered dialysis solution, confirming that differences in both buffer content and calcium concentration do not affect biocompatibility performance. Both bicarbonate/lactate formulations (Physioneal 35 and Physioneal 40) were more biocompatible than a conventional lactate-buffered dialysis solution in this in vitro biocompatibility assessment.


Assuntos
Bicarbonatos/administração & dosagem , Materiais Biocompatíveis/química , Soluções para Diálise/química , Ácido Láctico/administração & dosagem , Teste de Materiais , Trifosfato de Adenosina/metabolismo , Animais , Materiais Biocompatíveis/normas , Sobrevivência Celular/efeitos dos fármacos , Soluções para Diálise/normas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Interleucina-8/metabolismo , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Compostos Orgânicos , Peritônio/citologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Explosão Respiratória/efeitos dos fármacos
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