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1.
Nat Genet ; 55(9): 1598-1607, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37550531

RESUMO

Several molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other phenotypic data directly from individuals exists. We developed PhenoScore: an open-source, artificial intelligence-based phenomics framework, combining facial recognition technology with Human Phenotype Ontology data analysis to quantify phenotypic similarity. Here we show PhenoScore's ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 37 of 40 investigated syndromes against clinical features observed in individuals with other neurodevelopmental disorders and show it is an improvement on existing approaches. PhenoScore provides predictions for individuals with variants of unknown significance and enables sophisticated genotype-phenotype studies by testing hypotheses on possible phenotypic (sub)groups. PhenoScore confirmed previously known phenotypic subgroups caused by variants in the same gene for SATB1, SETBP1 and DEAF1 and provides objective clinical evidence for two distinct ADNP-related phenotypes, already established functionally.


Assuntos
Inteligência Artificial , Proteínas de Ligação à Região de Interação com a Matriz , Humanos , Fenótipo , Algoritmos , Aprendizado de Máquina , Variação Biológica da População , Proteínas de Ligação a DNA , Fatores de Transcrição
2.
Transl Psychiatry ; 12(1): 421, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182950

RESUMO

CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype-phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furthermore, two unique inframe deletions, one larger deletion (exons 26-28), and one translocation were observed. Methylation analysis was performed for 13 patients, 11 of which showed the previously established episignature for IDDAM (85%) associated with CHD8 haploinsufficiency, one analysis was inconclusive, and one showing a possible gain-of-function signature instead of the expected haploinsufficiency signature was observed. Consistent with previous studies, phenotypical abnormalities affected multiple organ systems. Many neurological abnormalities, like intellectual disability (68%) and hypotonia (29%) were observed, as well as a wide variety of behavioural abnormalities (88%). Most frequently observed behavioural problems included autism spectrum disorder (76%), short attention span (32%), abnormal social behaviour (31%), sleep disturbance (29%) and impaired social interactions (28%). Furthermore, abnormalities in the digestive (53%), musculoskeletal (79%) and genitourinary systems (18%) were noted. Although no significant difference in severity was observed between males and females, individuals with a missense variant were less severely affected. Our study provides an extensive review of all phenotypic abnormalities in patients with IDDAM and provides clinical recommendations, which will be of significant value to individuals with a pathogenic variant in CHD8, their families, and clinicians as it gives a more refined insight into the clinical and molecular spectrum of IDDAM, which is essential for accurate care and counselling.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Deficiência Intelectual , Megalencefalia , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Proteínas de Ligação a DNA/genética , Feminino , Estudos de Associação Genética , Humanos , Deficiência Intelectual/genética , Masculino , Megalencefalia/genética , Fenótipo , Fatores de Transcrição/genética
3.
Am J Emerg Med ; 58: 175-185, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35696802

RESUMO

BACKGROUND: There is a lack of rapid, non-invasive tools that aid early prognostication in patients with return of spontaneous circulation (ROSC) after Out-of-Hospital Cardiac Arrest (OHCA). The shock index (SI) and modified shock index (MSI) have shown to be useful in several medical conditions, including myocardial infarction. In this study, we assessed the prognostic value of SI and MSI at Emergency Department (ED) triage on survival to discharge of OHCA patients. METHODS: A single-center retrospective observational cohort study. All OHCA patients with a period of ROSC between 2014 and 2019 were included. Data collection was based on the Utstein criteria. The SI and MSI at ED triage were calculated by dividing heart rate by systolic blood pressure or mean arterial pressure. Survival rates were compared between patients with a high and low SI and MSI. Subsequent Cox regression analysis was performed. MAIN RESULTS: A total of 403 patients were included, of which 46% survived until hospital discharge. An elevated SI and MSI was defined by SI ≥ 1.00 and MSI ≥ 1.30. Survival to discharge, 30-day- and one-year survival were significantly lower in patients with an elevated SI and MSI (p < 0.001). An elevated SI and MSI was also associated with a higher rate of recurrent loss of circulation in the ED (p < 0.001). The 30-day survival hazard ratio was 2.24 (1.56-3.22) for SI and 2.46 (1.71-3.53) for MSI; the one-year survival hazard ratio was 2.20 (1.54-3.15) for SI and 2.38 (1.66-3.40) for MSI. CONCLUSION: Survival to discharge and 30-day survival are lower in OHCA patients with an elevated SI and MSI at ED triage. Further studies are warranted to elucidate the causational mechanisms underlying the association between elevated SI or MSI and worse outcomes.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Choque , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Estudos Retrospectivos , Sobreviventes , Triagem
4.
Eur J Hum Genet ; 30(3): 271-281, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34521999

RESUMO

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Its encoded protein promotes pre-mRNA splicing of many genes essential for development. Whereas individual phenotypic traits have previously been linked to erroneous splicing of SON target genes, the phenotypic spectrum and the pathogenicity of missense variants have not been further evaluated. We present the phenotypic abnormalities in 52 individuals, including 17 individuals who have not been reported before. In total, loss-of-function variants were detected in 49 individuals (de novo in 47, inheritance unknown in 2), and in 3, a missense variant was observed (2 de novo, 1 inheritance unknown). Phenotypic abnormalities, systematically collected and analyzed in Human Phenotype Ontology, were found in all organ systems. Significant inter-individual phenotypic variability was observed, even in individuals with the same recurrent variant (n = 13). SON haploinsufficiency was previously shown to lead to downregulation of downstream genes, contributing to specific phenotypic features. Similar functional analysis for one missense variant, however, suggests a different mechanism than for heterozygous loss-of-function. Although small in numbers and while pathogenicity of these variants is not certain, these data allow for speculation whether de novo missense variants cause ZTTK syndrome via another mechanism, or a separate overlapping syndrome. In conclusion, heterozygous loss-of-function variants in SON define a recognizable syndrome, ZTTK, associated with a broad, severe phenotypic spectrum, characterized by a large inter-individual variability. These observations provide essential information for affected individuals, parents, and healthcare professionals to ensure appropriate clinical management.


Assuntos
Proteínas de Ligação a DNA , Deficiência Intelectual , Antígenos de Histocompatibilidade Menor , Proteínas de Ligação a DNA/genética , Humanos , Deficiência Intelectual/genética , Antígenos de Histocompatibilidade Menor/genética , Mutação de Sentido Incorreto , Fenótipo , Síndrome
5.
Phys Rev B ; 103(17)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-37588030

RESUMO

We report the magnetic ordering and structural distortion in PrFeAsO crystals, the basis compound for one of the oxypnictide superconductors, using high-resolution x-ray diffraction, neutron diffraction, and x-ray resonant magnetic scattering (XRMS). We find the structural tetragonal-to-orthorhombic phase transition at TS=147K, the AFM phase transition of the Fe moments at TFe=72K, and the Pr AFM phase transition at TPr=21K. Combined high-resolution neutron diffraction and XRMS show unambiguously that the Pr moments point parallel to the longer orthorhombic a axis and order antiferromagnetically along the a axis but ferromagnetically along the b and c directions in the stripelike AFM order. The temperature-dependent magnetic order parameter of the Pr moments shows no evidence for a reorientation of moments.

6.
Int J Mol Sci ; 21(8)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344752

RESUMO

Extracellular vesicles (EVs)-carrying biomolecules derived from parental cells have achieved substantial scientific interest for their potential use as drug nanocarriers. Ultrasound (US) in combination with microbubbles (MB) have been shown to trigger the release of EVs from cancer cells. In the current study, the use of microbubbles-assisted ultrasound (USMB) to generate EVs containing drug cargo was investigated. The model drug, CellTracker™ green fluorescent dye (CTG) or bovine serum albumin conjugated with fluorescein isothiocyanate (BSA FITC) was loaded into primary human endothelial cells in vitro using USMB. We found that USMB loaded CTG and BSA FITC into human endothelial cells (HUVECs) and triggered the release of EVs containing these compounds in the cell supernatant within 2 h after treatment. The amount of EV released seemed to be correlated with the increase of US acoustic pressure. Co-culturing these EVs resulted in uptake by the recipient tumour cells within 4 h. In conclusion, USMB was able to load the model drugs into endothelial cells and simultaneously trigger the release of EVs-carrying model drugs, highlighting the potential of EVs as drug nanocarriers for future drug delivery in cancer.


Assuntos
Portadores de Fármacos , Vesículas Extracelulares/metabolismo , Microbolhas , Nanopartículas , Ondas Ultrassônicas , Antineoplásicos/administração & dosagem , Biomarcadores , Sistemas de Liberação de Medicamentos , Humanos , Lisossomos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
7.
Cancers (Basel) ; 11(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600958

RESUMO

Tumor drug distribution and concentration are important factors for effective tumor treatment. A promising method to enhance the distribution and the concentration of the drug in the tumor is to encapsulate the drug in a temperature sensitive liposome. The aim of this study was to investigate the tumor drug distribution after treatment with various injected doses of different liposomal formulations of doxorubicin, ThermoDox (temperature sensitive liposomes) and DOXIL (non-temperature sensitive liposomes), and free doxorubicin at macroscopic and microscopic levels. Only ThermoDox treatment was combined with hyperthermia. Experiments were performed in mice bearing a human fibrosarcoma. At low and intermediate doses, the largest growth delay was obtained with ThermoDox, and at the largest dose, the largest growth delay was obtained with DOXIL. On histology, tumor areas with increased doxorubicin concentration correlated with decreased cell proliferation, and substantial variations in doxorubicin heterogeneity were observed. ThermoDox treatment resulted in higher tissue drug levels than DOXIL and free doxorubicin for the same dose. A relation with the distance to the vasculature was shown, but vessel perfusion was not always sufficient to determine doxorubicin delivery. Our results indicate that tumor drug distribution is an important factor for effective tumor treatment and that its dependence on delivery formulation merits further systemic investigation.

8.
Front Immunol ; 10: 1335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281310

RESUMO

Objectives: Considering the critical role of microRNAs (miRNAs) in regulation of cell activation, we investigated their role in circulating type-2 conventional dendritic cells (cDC2s) of patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from peripheral blood. A discovery cohort (15 pSS, 6 HC) was used to screen the expression of 758 miRNAs and a replication cohort (15 pSS, 11 HC) was used to confirm differential expression of 18 identified targets. Novel targets for two replicated miRNAs were identified by SILAC in HEK-293T cells and validated in primary cDC2s. Differences in cytokine production between pSS and HC cDC2s were evaluated by intracellular flow-cytometry. cDC2s were cultured in the presence of MSK1-inhibitors to investigate their effect on cytokine production. Results: Expression of miR-130a and miR-708 was significantly decreased in cDC2s from pSS patients compared to HC in both cohorts, and both miRNAs were downregulated upon stimulation via endosomal TLRs. Upstream mediator of cytokine production MSK1 was identified as a novel target of miR-130a and overexpression of miR-130a reduced MSK1 expression in cDC2s. pSS cDC2s showed higher MSK1 expression and an increased fraction of IL-12 and TNF-α-producing cells. MSK1-inhibition reduced cDC2 activation and production of IL-12, TNF-α, and IL-6. Conclusions: The decreased expression of miR-130a and miR-708 in pSS cDC2s seems to reflect cell activation. miR-130a targets MSK1, which regulates pro-inflammatory cytokine production, and we provide proof-of-concept for MSK1-inhibition as a therapeutic avenue to impede cDC2 activity in pSS.


Assuntos
Citocinas/imunologia , Células Dendríticas , MicroRNAs/imunologia , Proteínas Quinases S6 Ribossômicas 90-kDa/imunologia , Síndrome de Sjogren , Adulto , Idoso , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia
9.
Phys Rev B ; 100(1)2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38712019

RESUMO

Inelastic neutron scattering studies in single crystals of TbInO3 and TbIn0.95Mn0.05O3 with nearly triangular antiferromagnetic lattice are reported. At low energies, a broad and apparently gapless continuum of magnetic excitations, located at the triangular lattice (TL) Brillouin zone boundary, is observed. The data are well described by the uncorrelated nearest-neighbor valence bonds model. At higher energies, a broad excitation branch dispersing from the TL zone boundary is observed. No signs of static magnetic order are found down to the temperatures two orders of magnitude smaller than the effective interaction energy. The fluctuating magnetic moment exceeds two-thirds of the Tb3+ free-ion value and is confined to the TL plane. These observations are consistent with a TL-based spin liquid state in TbInO3.

10.
Front Med (Lausanne) ; 5: 301, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483505

RESUMO

Background: Atelectasis frequently develops in critically ill patients and may result in impaired gas exchange among other complications. The long-term effects of bronchoscopy on gas exchange and the effects on respiratory mechanics are largely unknown. Objective: To evaluate the effect of bronchoscopy on gas exchange and respiratory mechanics in intensive care unit (ICU) patients with atelectasis. Methods: A retrospective, single-center cohort study of patients with clinical indication for bronchoscopy because of atelectasis diagnosed on chest X-ray (CXR). Results: In total, 101 bronchoscopies were performed in 88 ICU patients. Bronchoscopy improved oxygenation (defined as an increase of PaO2/FiO2 ratio > 20 mmHg) and ventilation (defined as a decrease of > 2 mmHg in partial pressure of CO2 in arterial blood) in 76 and 59% of procedures, respectively, for at least 24 h. Patients with a low baseline value of PaO2/FiO2 ratio and a high baseline value of PaCO2 were most likely to benefit from bronchoscopy. In addition, in intubated and pressure control ventilated patients, respiratory mechanics improved after bronchoscopy for up to 24 h. Mild complications, and in particular desaturation between 80 and 90%, were reported in 13% of the patients. Conclusions: In selected critically ill patients with atelectasis, bronchoscopy improves oxygenation, ventilation, and respiratory mechanics for at least 24 h.

11.
Transplant Proc ; 50(8): 2426-2430, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30316371

RESUMO

INTRODUCTION: Kidneys from acute kidney injury (AKI) donors are used for kidney transplantation. However, different Acute Kidney Injury Network (AKIN) criteria may show varying results after transplantation. We investigated the clinical outcomes in kidney transplantation from deceased donors with AKI as defined by the AKIN criteria at a single center. METHODS: We retrospectively reviewed the medical records of 101 consecutive deceased donors and kidney transplantation recipients from March 2009 to June 2015 in a single center. Donor and recipient clinical characteristics with creatinine level, delayed graft function, estimated glomerular filtration rate (eGFR), rejection, and graft survival were investigated. RESULTS: Of the 101 deceased donor kidneys, AKI occurred in 64 (63.4%) deceased donors. No differences in eGFR and serum creatinine level were found according to AKIN criteria. However, the AKIN stage 3 group had a slightly decreased kidney function without statistical significance. In the older AKI donor group, creatinine level was significantly higher than in other groups at 1 month (P = .015). No differences were found between the 2 groups in patient survival, graft survival, or rejection-free survival (P = .359, P = .568, and P = .717, respectively). CONCLUSIONS: Kidney transplantation from deceased donors with AKI showed comparable outcomes despite high rates of delayed graft function. AKIN stage 3 donors and aged-deceased donors with AKI showed a slightly reduced renal function without statistical significance; hence, use from donors with AKI needs to be considered to expand donor pools, but caution should be taken for AKIN stage 3 donors and aged donors with AKI.


Assuntos
Injúria Renal Aguda , Sobrevivência de Enxerto , Transplante de Rim/métodos , Doadores de Tecidos , Injúria Renal Aguda/fisiopatologia , Adulto , Cadáver , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Transplant Proc ; 50(4): 1025-1028, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29678267

RESUMO

BACKGROUND: Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. METHODS: We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. RESULTS: Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P = .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. CONCLUSIONS: Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys.


Assuntos
Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Cadáver , Isquemia Fria/efeitos adversos , Função Retardada do Enxerto/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos/provisão & distribuição , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
13.
Nanoscale ; 10(16): 7511-7518, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29637946

RESUMO

DNA has emerged as a biocompatible biomaterial that may be considered for various applications. Here, we report tumor cell-specific aptamer-modified DNA nanostructures for the specific recognition and delivery of therapeutic chemicals to cancer cells. Protein tyrosine kinase (PTK)7-specific DNA aptamer sequences were linked to 15 consecutive guanines. The resulting aptamer-modified product, AptG15, self-assembled into a Y-shaped structure. The presence of a G-quadruplex at AptG15 was confirmed by circular dichroism and Raman spectroscopy. The utility of AptG15 as a nanocarrier of therapeutics was tested by loading the photosensitizer, methylene blue (MB), to the G-quadruplex as a model drug. The generated MB-loaded AptG15 (MB/AptG15) showed specific and enhanced uptake to CCRF-CEM cells, which overexpress PTK7, compared with Ramos cells, which lack PTK7, or CCRF-CEM cells treated with a PTK7-specific siRNA. The therapeutic activity of MB/AptG15 was tested by triggering its photodynamic effects. Upon 660 nm light irradiation, MB/AptG15 showed greater reactive oxygen species generation and anticancer activity in PTK7-overexpressing cells compared to cells treated with MB alone, those treated with AptG15, and other comparison groups. AptG15 stemmed DNA nanostructures have significant potential for the cell-type-specific delivery of therapeutics, and possibly for the molecular imaging of target cells.


Assuntos
Aptâmeros de Nucleotídeos , DNA/química , Nanoestruturas/química , Fármacos Fotossensibilizantes/administração & dosagem , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Quadruplex G , Técnicas de Silenciamento de Genes , Humanos , Azul de Metileno/administração & dosagem , Fotoquimioterapia , Espécies Reativas de Oxigênio/química , Receptores Proteína Tirosina Quinases/genética
14.
Transplant Proc ; 49(9): 2050-2054, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29149959

RESUMO

BACKGROUND: Recently, urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT). METHODS: This is a single-center, prospective, observational study. We enrolled 74 patients who underwent KT between August 2013 and December 2016. Urine sample were collected immediately after the operation. The primary outcome was development of DGF as defined by need for dialysis of more than 1 session within 7 days of KT. RESULTS: Twenty-three patients (31%) were diagnosed with DGF. In univariate analysis, kidneys from expanded criteria donors, higher donor serum creatinine, lower donor estimated glomerular filtration rate, antithymoglobulin exposure, neutrophil gelatinase associated lipocalin, and urinary [TIMP-2]·[IGFBP7] were significantly different between early graft function and DGF. However, in multivariate analysis adjusting other factors, deceased donor and urinary [TIMP-2]·[IGFBP7] at 0 hours post-transplantation could predict the development of DGF. The receiver operating characteristic curve for prediction of DGF showed an area under the curve of 0.867 (sensitivity 0.86, specificity 0.71) for a cutoff value of 1.39. CONCLUSIONS: Our results indicate that urine [TIMP-2]·[IGFBP7] immediately after transplantation could be an early, predictive biomarker of DGF in kidney transplantation.


Assuntos
Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/diagnóstico , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Transplante de Rim , Inibidor Tecidual de Metaloproteinase-2/sangue , Adulto , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Lipocalina-2/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Diálise Renal , Doadores de Tecidos
15.
Transplant Proc ; 49(1): 88-91, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28104166

RESUMO

BACKGROUND: The Kidney Donor Risk Index (KDRI) scoring system for deceased donors has been widely introduced for postoperative evaluation of graft function. We analyzed the usefulness of the KDRI in deceased donors with acute kidney injury (AKI). METHODS: Forty-nine recipients from deceased donors with AKI between January 2009 and December 2014 were reviewed retrospectively. Data collected from donor medical records included age, height, weight, hypertension or diabetes history, cause of death, serum creatinine (sCr), and donation after cardiac death. Graft function data including sCr, estimated glomerular filtration rate (eGFR), and acute rejection episodes were monitored for 1 year. Correlations between KDRI score and factors indicating graft function were analyzed. A cutoff value for KDRI score was calculated using a receiver operating characteristic (ROC) curve for significant graft function. RESULTS: The mean ages of donors and recipients were 46.81 ± 13.13 and 47.69 ± 11.43, respectively. The mean KDRI score was 1.24 ± 0.40. Univariable analysis of KDRI score and factors indicating graft function indicated that sCr at 6 to 12 months, eGFR at 1 year, and slow graft function (SGF) had statistical significance. The ROC curve of KDRI score for SGF showed an optimal cutoff value of 1.20, with sensitivity of 69.2% and specificity of 69.4% (area under the curve = 0.75) in deceased donors with AKI. CONCLUSIONS: KDRI score in deceased donors with AKI was correlated with postoperative graft values including eGFR and SGF. KDRI could be used as a predictor for the short-term clinical outcome after kidney transplant from deceased donor with AKI.


Assuntos
Injúria Renal Aguda , Transplante de Rim/métodos , Doadores de Tecidos , Transplantes/fisiopatologia , Injúria Renal Aguda/fisiopatologia , Adulto , Cadáver , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos/provisão & distribuição
16.
J Mater Chem B ; 5(32): 6666-6675, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32264429

RESUMO

Signal regulatory protein alpha (SIRPα) is highly expressed in macrophages of the reticuloendothelial system and in tumor-associated macrophages, whereas tumor cells express the surface membrane protein, CD47, which interacts with SIRPα to negatively regulate phagocytosis. In this study, we modified the surfaces of graphene oxide (GO) nanosheets with a CD47-like SIRPα-binding peptide (SP). The presence of SP on GO nanosheets reduced the macrophage uptake to a greater extent than the PEGylation of such nanosheets. This reduced uptake was found to be mediated by the activation of Src homology region 2 domain-containing phosphatase 1 (SHP-1) and the downstream inhibition of myosin assembly, which is necessary for phagosome formation. Unlike SP-coated GO nanosheets, PEGylated GO nanosheets did not affect myosin assembly or phagocytosis. After in vivo systemic administration, the clearance of SP-coated GO nanosheets was slower than that of PEGylated GO nanosheets, and this difference increased with repeated administration. Finally, SP-coated GO nanosheets showed a higher distribution to tumor tissues than PEGylated GO nanosheets or a physical mixture of SP and GO nanosheets. Our findings indicate that immune-camouflaged GO nanosheets with natural CD47-like SIRPα-binding molecules can reduce the nonspecific loss of such nanosheets through macrophage uptake, thereby enhancing their blood circulation and tumor delivery after multiple injections.

17.
Int J Cosmet Sci ; 38(3): 286-93, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26564311

RESUMO

OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mm KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R(2) ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics.


Assuntos
Adenosina/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Cosméticos , Preparações Clareadoras de Pele , Limite de Detecção , Solubilidade , Espectrofotometria Ultravioleta/métodos , Água
18.
Transplant Proc ; 47(4): 1096-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26036528

RESUMO

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation has been the fundamental treatment and has shown significant results in selected patients diagnosed with type 1 diabetes with renal insufficiency. Most pancreas transplantations are dependent on deceased donors, yet the waiting time for SPK transplantation from deceased donors is significantly long in Asian countries. METHODS: In 3 cases, living-donor SPK transplantation was performed with the use of hand-assisted laparoscopic donor surgery (HALS). Three cases of patients who underwent SPK transplantation from living donors (LDSPK) with the use of HALS at Korea University Anam Hospital from 2012 to 2013 were retrospectively reviewed regarding patient characteristics and clinical outcomes of donors and recipients. For the donors, the pancreas and renal function had been well preserved postoperatively. RESULTS: One donor had a pancreatic fistula, which was controlled with conservative management. Of the 3 cases of recipient operation, 1 case was performed by ABO incompatibility donor. The levels of creatinine, serum insulin, and C-peptide of recipients were normalized and remained stable at the last follow-up. CONCLUSIONS: LDSPK can be an efficient alternative in cases in which the deceased donor is not present at the proper time, depending on the degree of completion in the operator's skill.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Laparoscopia Assistida com a Mão/métodos , Transplante de Rim/métodos , Doadores Vivos , Transplante de Pâncreas/métodos , Seleção de Pacientes , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento
19.
Bone Marrow Transplant ; 50(4): 523-30, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25581410

RESUMO

Trial outcomes comparing cytokine agents for PBSC mobilization in autologous hematopoietic transplant patients have been controversial. We performed a systematic review and meta-analysis of evidence available on pegfilgrastim vs filgrastim in chemo-cytokine mobilization. Electronic literature searches of PubMed, EMBASE and CENTRAL identified nine articles eligible for qualitative analysis with one randomized controlled trial. Eight articles involving 719 patients were included in the meta-analysis. Results showed similar CD34+ cell collection yields for pegfilgrastim and filgrastim (SDM -0.08, 95% CI: -0.388 to 0.228). On comparison with filgrastim, pegfilgrastim showed a significantly earlier apheresis onset time (SDM: -0.512, 95% CI: -0.973 to -0.050) and reduction in required apheresis procedures (SDM -0.260, 95% CI: -0.466 to -0.054). Times to leukocyte (⩾1.0 × 10(9)/L) and platelet (⩾20 × 10(9)/L) recovery were similar between groups (SDM: 0.015, 95% CI: -0.41 to 0.44 and SDM: 0.309, 95% CI: -0.11 to 0.72, respectively). Both agents were well tolerated and mild bone pain was the most frequently reported adverse event. Pegfilgrastim may be a convenient alternative to filgrastim in PBSC mobilization for multiple myeloma and lymphoma patients, but further studies are required to clarify effects of cytokine dosage and previous cytotoxic exposure in specific subpopulations.


Assuntos
Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Feminino , Humanos , Masculino , Polietilenoglicóis , Proteínas Recombinantes/uso terapêutico
20.
Clin Otolaryngol ; 40(3): 183-90, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25346100

RESUMO

OBJECTIVES: To compare the recovery rates of patients with idiopathic sudden sensorineural hearing loss (ISSHL) treated with oral systemic steroids (PO) or intratympanic steroid injection (IT) or both. DESIGN: A retrospective observational study. SETTING: Tertiary referral centre. PARTICIPANTS: Eight hundred and forty-four patients diagnosed with ISSHL within 14 days of the onset of symptoms. The patients were divided into three groups by treatment modality. MAIN OUTCOME MEASURES: Threshold of pure-tone tests, age, accompanying symptoms and underlying diseases were compared. The level of final hearing recovery was evaluated by the application of the results of the pure-tone test that was performed at least 3 months after the completion of each treatment. RESULTS: Final hearing recovery rate differed significantly by the type of treatment (P = 0.031). Recovery rates in the PO and combined groups were significantly higher in patients with mild (85.1% and 88.6%, respectively) than with profound (52.8% and 69.0%, respectively) hearing loss (P < 0.05). In contrast, severity and recovery rate were not significantly correlated in the IT group (P > 0.05). Combined treatment yielded significantly higher recovery rates than other treatment modalities in patients without hypertension (HTN) and diabetes mellitus (DM) (P = 0.021). CONCLUSION: In the group treated with combined therapy, better hearing improvement was obtained than in the groups treated with systemic steroid only or with intratympanic steroid injection only without complications. These findings suggest that the combination of systemic administration and intratympanic injection may improve patient prognosis.


Assuntos
Dexametasona/administração & dosagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Audição/fisiologia , Administração Oral , Audiometria de Tons Puros , Feminino , Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Súbita/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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