RESUMO
Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Mutação , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas B-raf , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Masculino , Adulto , Glioblastoma/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genéticaRESUMO
BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. OBJECTIVES: To investigate the drivers of EPC progression. METHODS: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient-derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. RESULTS: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer-relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen-activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient-derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR-directed therapy and immune checkpoint inhibition for more than 2 years. CONCLUSIONS: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC.
Assuntos
Porocarcinoma Écrino , Receptores ErbB , Sistema de Sinalização das MAP Quinases , Neoplasias das Glândulas Sudoríparas , Porocarcinoma Écrino/genética , Receptores ErbB/genética , Humanos , Terapia de Alvo Molecular , Mutação , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/genéticaRESUMO
The SPB/SFX instrument of the European XFEL provides unique possibilities for high-throughput serial femtosecond crystallography. This publication presents the liquid-jet sample delivery setup of this instrument. The setup is compatible with state-of-the-art gas dynamic virtual nozzle systems as well as high-viscosity extruders and provides space and flexibility for other liquid injection devices and future upgrades. The liquid jets are confined in a differentially pumped catcher assembly and can be replaced within a couple of minutes through a load-lock. A two-microscope imaging system allows visual control of the jets from two perspectives.
RESUMO
INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAFV600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor-pretreated compared with MAPK-inhibitor-naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1Bhigh cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. CONCLUSION: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.
Assuntos
Neoplasias Encefálicas/terapia , Resistencia a Medicamentos Antineoplásicos , Melanoma/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Tolerância a Radiação , Radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Ciclo Celular , Movimento Celular , Proliferação de Células , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. OBJECTIVES: To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. METHODS: Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. RESULTS: Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001). CONCLUSIONS: The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.
Assuntos
Adenocarcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias das Glândulas Sudoríparas/genética , Glândulas Sudoríparas/patologia , Adenocarcinoma Papilar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Dedos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Sudoríparas/patologia , Análise Serial de Tecidos , Regulação para CimaRESUMO
The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxΔC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxΔC21, the structure of the BimBH3 complex with BaxΔC displays a cavity surrounded by Bax α1, α2, α5 and α8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (α2-α5) and latch (α6-α8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.
Assuntos
Proteínas Reguladoras de Apoptose/química , Proteínas de Membrana/química , Fragmentos de Peptídeos/química , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas/química , Proteína X Associada a bcl-2/química , Sequência de Aminoácidos , Proteínas Reguladoras de Apoptose/genética , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/química , Proteína 11 Semelhante a Bcl-2 , Sítios de Ligação , Cristalografia por Raios X , Humanos , Proteínas de Membrana/genética , Mitocôndrias/química , Mitocôndrias/metabolismo , Modelos Moleculares , Mutagênese , Fragmentos de Peptídeos/genética , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Bak and Bax mediate apoptotic cell death by oligomerizing and forming a pore in the mitochondrial outer membrane. Both proteins anchor to the outer membrane via a C-terminal transmembrane domain, although its topology within the apoptotic pore is not known. Cysteine-scanning mutagenesis and hydrophilic labeling confirmed that in healthy mitochondria the Bak α9 segment traverses the outer membrane, with 11 central residues shielded from labeling. After pore formation those residues remained shielded, indicating that α9 does not line a pore. Bak (and Bax) activation allowed linkage of α9 to neighboring α9 segments, identifying an α9:α9 interface in Bak (and Bax) oligomers. Although the linkage pattern along α9 indicated a preferred packing surface, there was no evidence of a dimerization motif. Rather, the interface was invoked in part by Bak conformation change and in part by BH3:groove dimerization. The α9:α9 interaction may constitute a secondary interface in Bak oligomers, as it could link BH3:groove dimers to high-order oligomers. Moreover, as high-order oligomers were generated when α9:α9 linkage in the membrane was combined with α6:α6 linkage on the membrane surface, the α6-α9 region in oligomerized Bak is flexible. These findings provide the first view of Bak carboxy terminus (C terminus) membrane topology within the apoptotic pore.
Assuntos
Apoptose/fisiologia , Membranas Mitocondriais/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Motivos de Aminoácidos , Animais , Humanos , Camundongos , Multimerização Proteica , Proteína X Associada a bcl-2/metabolismoRESUMO
The central role of the Bcl-2 family in regulating apoptotic cell death was first identified in the 1980s. Since then, significant in-roads have been made in identifying the multiple members of this family, characterizing their form and function and understanding how their interactions determine whether a cell lives or dies. In this review we focus on the recent progress made in characterizing the proapoptotic Bcl-2 family members, Bax and Bak. This progress has resolved longstanding controversies, but has also challenged established theories in the apoptosis field. We will discuss different models of how these two proteins become activated and different 'modes' by which they are inhibited by other Bcl-2 family members. We will also discuss novel conformation changes leading to Bak and Bax oligomerization and speculate how these oligomers might permeabilize the mitochondrial outer membrane.
Assuntos
Apoptose , Membranas Mitocondriais/metabolismo , Multimerização Proteica , Proteína Killer-Antagonista Homóloga a bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/química , Proteína X Associada a bcl-2/metabolismo , Humanos , Ligação ProteicaRESUMO
During apoptosis, Bak and Bax permeabilize the mitochondrial outer membrane by undergoing major conformational change and oligomerization. This activation process in Bak is reported to require dephosphorylation of tyrosine-108 close to an activation trigger site. To investigate how dephosphorylation of Bak contributes to its activation and conformational change, one-dimensional isoelectric focusing (1D-IEF) and mutagenesis was used to monitor Bak phosphorylation. On 1D-IEF, Bak extracted from a range of cell types migrated as a single band near the predicted isoelectric point of 5.6 both before and after phosphatase treatment, indicating that Bak is not significantly phosphorylated at any residue. In contrast, three engineered 'phosphotagged' Bak variants showed a second band at lower pI, indicating phosphorylation. Apoptosis induced by several stimuli failed to alter Bak pI, indicating little change in phosphorylation status. In addition, alanine substitution of tyrosine-108 and other putative phosphorylation sites failed to enhance Bak activation or pro-apoptotic function. In summary, Bak is not significantly phosphorylated at any residue, and Bak activation during apoptosis does not require dephosphorylation.
Assuntos
Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Focalização Isoelétrica , Ponto Isoelétrico , Células Jurkat , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Dados de Sequência Molecular , Fosforilação/efeitos dos fármacos , Proteínas Tirosina Fosfatases/metabolismo , Tirosina/química , Proteína Killer-Antagonista Homóloga a bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/genéticaRESUMO
The effects of centrifugal pumps on blood components other than erythrocytes, namely platelets and their interaction with the coagulation system, are not very well known. In a comparative study with three centrifugal pumps (BioMedicus BP-80, St. Jude Isoflow, and Sarns Delphin) and the Stockert roller pump hemolysis, platelet counts, thromboplastin and partial thromboplastin times, as well as resonance thrombography (RTG) parameters for the assessment of platelet and coagulation function were evaluated in vitro. Normalized indices of hemolysis (NIH) with ACD anticoagulation after 360 minutes were 0.008+/-0.004 (Isoflow), 0.018+/-0.017 (BP-80), 0.085+/-0.051 (Delphin), and 0.049+/-0.010 g/1001 (roller pump). Plasmatic coagulation was activated in all circuits. Platelet function was severely inhibited by the BP-80, indicated by increase in RTG platelet time to 358%+/-150% of initial values compared to 42%+/-29% (Isoflow), 40%+/-20% (Delphin), and 12%+/-10% (roller pump). Fibrin polymerization was affected similarly. The large surface area of the BP-80 leads to an extensive activation of platelets and plasminogen.
Assuntos
Coagulação Sanguínea , Eritrócitos/patologia , Circulação Extracorpórea/instrumentação , Coração Auxiliar , Agregação Plaquetária , Desenho de Equipamento , Segurança de Equipamentos , Estudos de Avaliação como Assunto , Estudos de Viabilidade , Coração Auxiliar/efeitos adversos , Hemólise , Humanos , Contagem de Plaquetas , Valores de ReferênciaRESUMO
DIABCARE Q-Net is a European project with a consortium of partners in healthcare, industry, and research, which has the overall target of improvement in diabetes care by aggregation, evaluation, and feedback of anonymized patient data with the tools of modern telematics, resulting from the initiative of the St. Vincent-Declaration, St. Vincent, Italy. Based on standardized tools for quality improvement in diabetes care, i.e., the Basic Information Sheet (BIS) and recently developed data entry and feedback software (DIABCARE Data for Windows), DIABCARE Q-Net as a part of the Telematics Applications Program of the European Commission will improve diabetes care and disease management by the implementation of a quality network. Therefore, the project implements regional, national, and central nodes for processing of diabetes quality indicators. All participating centers (GP's and clinics in Europe) get feedback by standardized benchmarking. The pilot testing and the state of implementation of our network confirm the importance of improving the quality of life of diabetic patients in all participating countries.
Assuntos
Redes de Comunicação de Computadores , Diabetes Mellitus/terapia , Qualidade da Assistência à Saúde , Humanos , Desenvolvimento de ProgramasRESUMO
The EU regulatory statute for the acute hazard identification of chemicals requires selection of the two most appropriate routes of administration. Testing employing the oral route is mandatory, whereas selection of the dermal or inhalation route requires expert judgement, i.e. considerations of structural alerts with regard to the inherent acute inhalation toxicity as well as the likelihood of dermal and inhalation exposure, respectively. Currently, testing of chemicals requires acute inhalation exposure of 4-h and 1-h durations according the EU classification and labelling and UN Transport Guidelines, respectively. The analysis made revealed that 1-h exposures appear to add little knowledge in addition to existing 4-h LC50 values and a default value of 4 should be used for conversion of 4-h to 1-h LC50 values, independently of the physical state of the chemical. Therefore, also the unit of concentration of exposure atmospheres should be independent of nominal features of the test substance. Hence, the preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking into account the overall variability of acute toxicity data the recommendations given are classification into the following groups of 4-h LC50 values: < or = 0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made concerning vapours and aerosols with regard to units and conversion factors from 4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable. Further differentiation of classification is not indicated due to technical variability of acute inhalation testing and resolution of the acute bioassay.
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Testes de Toxicidade/métodos , Toxicologia/legislação & jurisprudência , Administração por Inalação , Animais , União Europeia , Dose Letal Mediana , Preparações Farmacêuticas/classificaçãoRESUMO
Confluent skin fibroblasts from normal humans were incubated in serum free medium with up to 100 nmole/mL eicosapentaenoic acid (EPA; bound to albumin in a 4.6:1 ratio) and compared with cells incubated with oleic acid (OA) at similar concentrations. The rate of [14C]OA incorporation into triacylglycerol (TG) (nmol/mg/h) was approximately 5-fold greater than that of [14C]EPA. The mass of TG formed after incubation of fibroblasts with EPA was also significantly lower than that formed with OA (43.2 +/- 9.3 vs. 59.5 +/- 6.6 micrograms/mg cell protein, respectively, P = 0.006). The addition of excess, unlabeled EPA reduced the rate of incorporation of [14C]OA into TG whereas unlabeled OA stimulated incorporation of [14C]EPA into TG. When the cells were preincubated with human serum basic proteins (BP I, II and III), the mass of TG formed (compared to baseline) was significantly higher with the basic proteins whether OA or EPA was studied. Only BP I significantly stimulated the mass of cell phospholipids, an effect that occurred with either OA or EPA in the medium. The results suggest that in cultured normal human fibroblasts, OA is a better substrate for TG synthesis than EPA and that this effect may be accentuated by the presence of the basis proteins.
Assuntos
Ácido Eicosapentaenoico/metabolismo , Fibroblastos/metabolismo , Lipídeos/biossíntese , Ácidos Oleicos/metabolismo , Ligação Competitiva , Proteínas Sanguíneas/farmacologia , Células Cultivadas , Humanos , Ácido Oleico , Triglicerídeos/biossínteseRESUMO
Since artificial heart valve related complications such as thrombus formation, hemolysis and calcification are considered related to flow disturbances caused by the inserted valve, a thorough hemodynamic characterization of heart valve prostheses is essential. In a pulsatile flow model, fluid velocities were measured one diameter downstream of a Hancock Porcine (HAPO) and a Ionescu-Shiley Pericardial Standard (ISPS) aortic valve. Hot-film anemometry (HFA) was used for velocity measurements at 41 points in the cross-sectional area of the ascending aorta. Three-dimensional visualization of the velocity profiles, at 100 different instants during one mean pump cycle, was performed. Turbulence analysis was performed as a function of time by calculating the axial turbulence energy within 50 ms overlapping time windows during the systole. The turbulent shear stresses were estimated by using the correlation equation between Reynolds normal stress and turbulent (Reynolds) shear stress. The turbulent shear stress distribution was visualized by two-dimensional color-mapping at different instants during one mean pump cycle. Based on the velocity profiles and the turbulent shear stress distribution, a relative blood damage index (RBDI) was calculated. It has the feature of combining the magnitude and exposure time of the estimated shear stresses in one index, covering the entire cross-sectional area. The HAPO valve showed a skewed jet-type velocity profile with the highest velocities towards the left posterior aortic wall. The ISPS valve revealed a more parabolic-shaped velocity profile during systole. The turbulent shear stresses were highest in areas of high or rapidly changing velocity gradients. For the HAPO valve the maximum estimated turbulent shear stress was 194 N m-2 and for the ISPS valve 154 Nm-2. The RBDI was the same for the two valves. The turbulent shear stresses had magnitudes and exposure times that might cause endothelial damage and sublethal or lethal damage to blood corpuscules. The RBDI makes comparison between different heart valves easier and may prove important when making correlation with clinical observations.
Assuntos
Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Modelos Cardiovasculares , Velocidade do Fluxo Sanguíneo/fisiologia , Plaquetas/fisiologia , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Cor , Hemodinâmica/fisiologia , Humanos , Ativação Plaquetária/fisiologia , Desenho de Prótese , Fluxo Pulsátil , Fluxo Sanguíneo Regional/fisiologia , Reologia , Estresse MecânicoRESUMO
Two electrical conductivity methods of hematocrit (H) measurement, Coulter Counter (CCH) and lonometer (IH), were compared to the microhematocrit (MH) with two different anticoagulants, Li Heparin (Li) and EDTA. The results showed MH-Li is higher than MH-EDTA (mean difference 1.7 vol%). The IH-Li is 1.8 vol% higher than CC H-EDTA. These differences are attributed to osmotic shrinking of red cells by EDTA. The MH-Li and IH-Li correlate very closely (r = .992), and are considered to provide the truest hematocrit values.
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Eritropoetina/administração & dosagem , Hematócrito/instrumentação , Proteínas Recombinantes/administração & dosagem , Volume de Eritrócitos/efeitos dos fármacos , Humanos , Potenciais da Membrana/efeitos dos fármacos , Valores de ReferênciaRESUMO
A closed loop Na kinetic model is developed which permits 1) prescription of precise profiles of Na removal from its extracellular volume of distribution ((dVeCe)/dt), while 2) assuring that the total interdialytic accumulation of Na is removed during each dialysis. The model requires precise continuous measurement of Na flux in the dialysate stream, and a device to accomplish this (Ionflow) was developed and evaluated. In vivo studies showed that changes in body content of Na agreed to +/- 40 mEq, with total Na flux measured by Ionoflow. This agreement is excellent, considering that +/- 1 mEq/L in blood Na represents approximately 40 mEq in the average patient. The Ionoflow is considered accurate to +/- 10 to 20 mEq Na over a dialysis. The Ionoflow fulfills monitoring requirements necessary to implement clinical trials of closed loop Na modeling.
Assuntos
Rins Artificiais , Monitorização Fisiológica/instrumentação , Sistemas On-Line/instrumentação , Potássio/sangue , Sódio/sangue , Soluções para Diálise/análise , Humanos , Computação MatemáticaRESUMO
Measuring turbulent shear stresses is of major importance in artificial heart valve evaluation. Bi- and unidirectional fluid velocity measurements enable calculation of Reynolds shear stress [formula: see text] and Reynolds normal stress [formula: see text]. tau is important due to the relation to hemolysis and thrombus formation, but sigma is the only obtainable parameter in vivo. Therefore, determination of a correlation factor between tau and sigma is pertinent. In a pulsatile flow model, laser Doppler (LDA) and hot-film (HFA) anemometry were used for simultaneous bi- and unidirectional fluid velocity measurements downstream of a Hall Kaster and a Hancock Porcine aortic valve. Velocities were registered in two flow field locations and at four cardiac outputs. The velocity signals were subjected to analog signal processing prior to digital turbulence analysis, as a basis for calculation of tau and sigma. A correlation factor of 0.5 with a correlation coefficient of 0.97 was found between the maximum Reynolds shear stress and Reynolds normal stress, implying [formula: see text]. In vitro estimation of turbulent shear stresses downstream of artificial aortic valves, based on the axial velocity component alone, seems possible.