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1.
Gastroenterol Hepatol ; 44(10): 687-695, 2021 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34023468

RESUMO

BACKGROUND: Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. OBJECTIVE: Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. METHODS: This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. RESULTS: ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.


Assuntos
Sistema Biliar/irrigação sanguínea , Corantes/farmacocinética , Verde de Indocianina/farmacocinética , Transplante de Fígado/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Traumatismo por Reperfusão/diagnóstico por imagem , Constrição Patológica/sangue , Constrição Patológica/diagnóstico por imagem , Feminino , Humanos , Imunossupressores/uso terapêutico , Isquemia/complicações , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Traumatismo por Reperfusão/sangue , Espectrofotometria , Esteroides/uso terapêutico , Fatores de Tempo
2.
PLoS One ; 16(3): e0247673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33647027

RESUMO

Infectious endocarditis is a life-threatening disease, and diagnostics are urgently needed to accurately diagnose this disease especially in the case of prosthetic valve endocarditis. We show here that maltohexaose conjugated to indocyanine green (MH-ICG) can detect Staphylococcus aureus (S. aureus) infection in a rat model of infective endocarditis. The affinity of MH-ICG to S. aureus was determined and had a Km and Vmax of 5.4 µM and 3.0 X 10-6 µmol/minutes/108 CFU, respectively. MH-ICG had no detectable toxicity to mammalian cells at concentrations as high as 100 µM. The in vivo efficiency of MH-ICG in rats was evaluated using a right heart endocarditis model, and the accumulation of MH-ICG in the bacterial vegetations was 2.5 ± 0.2 times higher than that in the control left ventricular wall. The biological half-life of MH-ICG in healthy rats was 14.0 ± 1.3 minutes, and approximately 50% of injected MH-ICG was excreted into the feces after 24 hours. These data demonstrate that MH-ICG was internalized by bacteria with high specificity and that MH-ICG specifically accumulated in bacterial vegetations in a rat model of endocarditis. These results demonstrate the potential efficacy of this agent in the detection of infective endocarditis.


Assuntos
Técnicas de Imagem Cardíaca/métodos , Endocardite Bacteriana/diagnóstico por imagem , Glicoconjugados/química , Verde de Indocianina/química , Oligossacarídeos/química , Infecções Estafilocócicas/diagnóstico por imagem , Animais , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Corantes/química , Corantes/farmacocinética , Cricetulus , Modelos Animais de Doenças , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/patologia , Glicoconjugados/farmacocinética , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/microbiologia , Ventrículos do Coração/patologia , Humanos , Verde de Indocianina/farmacocinética , Raios Infravermelhos , Masculino , Oligossacarídeos/farmacocinética , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade
3.
J Biomater Appl ; 35(9): 1109-1118, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33632005

RESUMO

Monoolein cubic phase immobilizing hydrophobically modified gelatin (HmGel) in its water channel was prepared by a melt-hydration method. The cubic phase was micronized into cubosomes by using hydrophobically modified quaternized cellulose nanofiber (HmQCNF) as a stabilizer. The phase transition temperature of the cubic phase was about 68-70 °C. Small angle X-ray diffraction revealed that HmGel-loaded cubosome stabilized with HmCNF was a diamond type of cubic phase. HmGel-loaded cubosomes stailized with HmQCNF were dependent on the pH value in terms of the release of their payload (i.e, methylene blue) much more strongly than HmGel-loaded cubosomes stabilized with Pluronic F127.


Assuntos
Corantes/farmacocinética , Gelatina/química , Nanofibras/química , Varredura Diferencial de Calorimetria , Celulose/química , Corantes/química , Portadores de Fármacos/química , Glicerídeos/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Azul de Metileno/química , Azul de Metileno/farmacocinética , Microscopia/métodos , Poloxâmero/química , Poloxâmero/farmacocinética , Espalhamento a Baixo Ângulo , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
4.
BJS Open ; 5(1)2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609394

RESUMO

BACKGROUND: Hepatectomy with extrahepatic bile duct resection is associated with a high risk of posthepatectomy liver failure (PHLF). However, the utility of the remnant liver volume (RLV) in cholangiocarcinoma has not been studied intensively. METHODS: Patients who underwent major hepatectomy with extrahepatic bile duct resection between 2002 and 2018 were reviewed. The RLV was divided by body surface area (BSA) to normalize individual physical differences. Risk factors for clinically relevant PHLF were evaluated with special reference to the RLV/BSA. RESULTS: A total of 289 patients were included. The optimal cut-off value for RLV/BSA was determined to be 300 ml/m2. Thirty-two patients (11.1 per cent) developed PHLF. PHLF was more frequent in patients with an RLV/BSA below 300 ml/m2 than in those with a value of 300 ml/m2 or greater: 19 of 87 (22 per cent) versus 13 of 202 (6.4 per cent) (P < 0.001). In multivariable analysis, RLV/BSA below 300 ml/m2 (P = 0.013), future liver remnant plasma clearance rate of indocyanine green less than 0.075 (P = 0.031), and serum albumin level below 3.5 g/dl (P = 0.015) were identified as independent risk factors for PHLF. Based on these risk factors, patients were classified into three subgroups with low (no factors), moderate (1-2 factors), and high (3 factors) risk of PHLF, with PHLF rates of 1.8, 14.8 and 63 per cent respectively (P < 0.001). CONCLUSION: An RLV/BSA of 300 ml/m2 is a simple predictor of PHLF in patients undergoing hepatectomy with extrahepatic bile duct resection.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Extra-Hepáticos/cirurgia , Corantes/farmacocinética , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Verde de Indocianina/farmacocinética , Falência Hepática/sangue , Falência Hepática/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Período Pós-Operatório , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
5.
ACS Appl Mater Interfaces ; 13(3): 3679-3693, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33464038

RESUMO

Hollow nanostructures have attracted significant research interest in drug delivery systems due to their high capacities for drug loading and unique physicochemical properties, showing great potential in specific biomedical applications. Herein, hollow porphyrinic metal-organic framework (H-PMOF) nanoparticles with a mesoporous spherical shell have been fabricated via a facile self-sacrificial ZIF-8 nanoparticle template strategy. The H-PMOF nanoplatform not only demonstrates a greatly enhanced photodynamic therapy efficacy compared with nonhollow porphyrinic MOF nanoparticles but also can be used as a superior drug carrier to co-load doxorubicin (DOX) and indocyanine green (ICG) with an ultrahigh drug-loading capacity of 635%. Furthermore, cancer cell membrane camouflage of the (DOX and ICG)@H-PMOF composite nanoparticles affords a biomimetic nanoplatform, that is, (DOX and ICG)@H-PMOF@mem (DIHPm for short), with an outstanding homologous tumor-targeting and immune-escaping ability. Interestingly, DIHPm shows both pH-controlled and near-infrared laser-triggered DOX release. Both in vitro and in vivo studies of DIHPm demonstrate an excellent imaging-guided synergistic photodynamic/photothermal/chemotherapy anticancer activity with negligible systemic toxicity. The development of the high-performance H-PMOF nanoplatform provides new insights into the design of MOF-based multifunctional nanomedicines for combination cancer therapy and precise theranostics.


Assuntos
Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Verde de Indocianina/administração & dosagem , Estruturas Metalorgânicas/química , Porfirinas/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Corantes/administração & dosagem , Corantes/farmacocinética , Corantes/uso terapêutico , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Verde de Indocianina/farmacocinética , Verde de Indocianina/uso terapêutico , Camundongos Endogâmicos BALB C , Fotoquimioterapia
6.
J Surg Oncol ; 123(4): 1092-1098, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33333589

RESUMO

BACKGROUND AND OBJECTIVES: To compare the detection rates of sentinel lymph nodes after converting the tracer technique from blue dye to indocyanine green (ICG). METHODS: Patients with uterine or cervical cancer were enrolled for sentinel lymph node (SLN) dissection. A total of 109 consecutive patients were analyzed and compared to a historical cohort of 109 consecutive patients with the sentinel blue dye technique. SLNs were analyzed by ultrastaging. RESULTS: The bilateral mapping rate of sentinel nodes was significantly higher with the ICG (78%; n = 85) compared to the blue dye tracer (61%; n = 67; p = .006). Neither the mean number of SLN nor the rate of low volume metastases showed significant differences between both cohorts. In the subgroup of endometrial cancer patients, the number of systematic lymph node dissection (LND) was significantly lower in the ICG cohort compared to the blue dye cohort (9% vs. 28%, p = .001). CONCLUSIONS: ICG improved the detection rate of pelvic SLN compared to blue dye and may be considered as the superior technique. In clinical practice, the rate of systematic LND further decreased after incorporating SLN mapping with ICG. Reliable safety data are still pending.


Assuntos
Corantes/farmacocinética , Neoplasias dos Genitais Femininos/patologia , Verde de Indocianina/farmacocinética , Corantes de Rosanilina/farmacocinética , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Distribuição Tecidual
7.
J Cancer Res Clin Oncol ; 147(6): 1813-1823, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33230583

RESUMO

PURPOSE: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. METHODS: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. RESULTS: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. CONCLUSIONS: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/efeitos dos fármacos , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Corantes/análise , Corantes/farmacocinética , Diagnóstico por Imagem/instrumentação , Diagnóstico por Imagem/métodos , Feminino , Fluorescência , Humanos , Verde de Indocianina/análise , Verde de Indocianina/farmacocinética , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Linfonodo Sentinela/metabolismo , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/instrumentação , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/análise , Tecnécio/farmacocinética
8.
Int J Mol Sci ; 22(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379217

RESUMO

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.


Assuntos
Corantes/efeitos adversos , Exposição Dietética/efeitos adversos , Nanopartículas/efeitos adversos , Titânio/efeitos adversos , Animais , Corantes/química , Corantes/farmacocinética , Humanos , Nanopartículas/química , Titânio/química , Titânio/farmacocinética , Testes de Toxicidade
9.
J Mater Chem B ; 8(44): 10154-10161, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33094795

RESUMO

Two kinds of Bovine Serum Albumin (BSA)-loaded microspheres were prepared in water-organic bilayer systems using ultrasonic irradiation. The first method included an aqueous solution of BSA and water-soluble dye together, mixed with dodecane, that upon sonication formed a matrix system where the dye is concentrated in the protein shell. The other system included an aqueous solution of BSA mixed with octanol-soluble dye that, upon sonication, formed a reservoir system in which the dye filled the inner volume of the microspheres. Each of these microspheres was prepared with two different dyes and their leaching profiles into pure solvents were studied using UV-vis spectrometry. Fast leaching was observed at the beginning for both systems, which levelled-off after a certain time. For the matrix system, an equilibrium state was obtained after 100-200 hours, whereas for the reservoir system, leaching occurred much faster, within 1-3 hours. Such systems can serve as models for drug delivery agents.


Assuntos
Corantes/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Microesferas , Soroalbumina Bovina/farmacocinética , Animais , Bovinos , Corantes/administração & dosagem , Corantes/química , Vermelho Congo/administração & dosagem , Vermelho Congo/química , Vermelho Congo/farmacocinética , Liberação Controlada de Fármacos , Imageamento Tridimensional/métodos , Cinética , Oxazinas/administração & dosagem , Oxazinas/química , Oxazinas/farmacocinética , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/química
10.
Sci Rep ; 10(1): 17094, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051565

RESUMO

This work was aimed at the synthesis of a hybrid (STpe-AgNP), obtained by impregnation of silver nanoparticles (AgNP) onto Solanum tuberosum peel (STpe), for the ultrasonic assisted adsorption of bromophenol blue (BB) dye. SEM, FTIR, XRD, EDX, TGA and BET techniques were used to characterize the adsorbents. The XRD, SEM and EDX confirmed successful impregnation of AgNPs onto STpe to form the hybrid. The AgNPs impregnated onto the hybrid were found to be water stable at various pH values of 2.0-9.0. Chi-square (χ2 < 0.024) and linear regression (R2 > 0.996) showed that the Freundlich model was best fitted among the isotherm models, corroborated by the oriented site model. Kinetic analysis conformed to the intraparticle diffusion and pseudo-first-order rate equations, while thermodynamics displayed a physical, spontaneous and endothermic adsorption process. The presence of competing Pb(II), Ni(II), Cd(II) and Zn(II) metal ions in solution interfered with the adsorption of BB onto the biosorbents. In terms of reusability, STpe and STpe-AgNP showed BB desorption of 91.3% and 88.5% respectively, using NaOH as eluent. Ultra-sonication significantly enhanced the adsorption of BB by both adsorbents, but the impregnation of AgNPs only slightly improved adsorption of the dye from the simulated wastewater. This study also illustrated that pristine STpe biomass waste is a cheap viable option for the decontamination of BB from water.


Assuntos
Azul de Bromofenol/farmacocinética , Corantes/farmacocinética , Nanopartículas Metálicas , Tubérculos/metabolismo , Solanum tuberosum/metabolismo , Poluentes Químicos da Água/farmacocinética , Purificação da Água/métodos , Adsorção , Azul de Bromofenol/análise , Corantes/análise , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Prata , Espectroscopia de Infravermelho com Transformada de Fourier , Ultrassom , Poluentes Químicos da Água/análise , Difração de Raios X
11.
Regul Toxicol Pharmacol ; 115: 104719, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32565410

RESUMO

Experimental data of all 143 organic pigments registered with the European Chemicals Agency, of which 88 were listed in a nanomaterial inventory, was retrieved from the registered substance fact sheets. Availability of the data was 93% for solubility, 82% for bacterial mutagenicity, 79% for acute oral toxicity, 75% for irritation, 59% for skin sensitisation, 36% for repeated dose toxicity and 34% for each clastogenicity and mutagenicity in mammalian cells and 23% for toxicity to reproduction. Pigments mostly had a water and octanol solubility of significantly below 0.1 mg/L, but fourteen were found to be of higher solubility. None were irritating to skin and eyes. Except for the metal salt and the ß-naphthol pigments, none of the insoluble pigments showed adverse effects up to limit doses indicating that poor solubility prevents systemic uptake of toxicologically relevant amounts. The few available toxicokinetic data shows absence of metabolism or significant uptake and is in support of this. Occasional effects observed on bacterial mutagenicity and skin sensitisation are attributed to impurities. There is no indication that for organic pigments other particle characteristics such as surface area or morphology have an impact on the investigated toxicological endpoints.


Assuntos
Corantes/farmacocinética , Corantes/toxicidade , Animais , Disponibilidade Biológica , Corantes/química , Humanos , Solubilidade , Testes de Toxicidade
12.
Int J Mol Sci ; 21(9)2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32397373

RESUMO

Antimicrobial resistance, an ever-growing global crisis, is strongly linked to the swine production industry. In previous studies, Melaleuca alternifolia and Rosmarinus officinalis essential oils have been evaluated for toxicity on porcine spermatozoa and for antimicrobial capabilities in artificial insemination doses, with the future perspective of their use as antibiotic alternatives. The aim of the present research was to develop and validate in vitro and ex vivo models of porcine uterine mucosa for the evaluation of mucosal toxicity of essential oils. The in vitro model assessed the toxicity of a wider range of concentrations of both essential oils (from 0.2 to 500 mg/mL) on sections of uterine tissue, while the ex vivo model was achieved by filling the uterine horns. The damage induced by the oils was assessed by Evans Blue (EB) permeability assay and histologically. The expression of ZO-1, a protein involved in the composition of tight junctions, was assessed through immunohistochemical and immunofluorescence analysis. The results showed that low concentrations (0.2-0.4 mg/mL) of both essential oils, already identified as non-spermicidal but still antimicrobial, did not alter the structure and permeability of the swine uterine mucosa. Overall, these findings strengthen the hypothesis of a safe use of essential oils in inseminating doses of boar to replace antibiotics.


Assuntos
Anti-Infecciosos/toxicidade , Melaleuca/química , Mucosa/efeitos dos fármacos , Óleos Voláteis/toxicidade , Rosmarinus/química , Óleo de Melaleuca/toxicidade , Útero/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Corantes/farmacocinética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Epitélio/efeitos dos fármacos , Epitélio/ultraestrutura , Azul Evans/farmacocinética , Feminino , Inseminação Artificial/veterinária , Masculino , Microscopia de Fluorescência , Óleos Voláteis/farmacologia , Permeabilidade/efeitos dos fármacos , Preservação do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Suínos , Óleo de Melaleuca/farmacologia , Junções Íntimas/efeitos dos fármacos , Útero/ultraestrutura , Proteína da Zônula de Oclusão-1/análise
13.
Biomater Sci ; 8(12): 3443-3453, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32412569

RESUMO

Reliable diagnosis and efficient targeted therapy are important and may lead to the effective treatment of laryngeal carcinoma. Multifunctional nano-theranostic agents demonstrate great potential in tumor theranostic applications. Thus, herein, we report novel targeting multifunctional theranostic nanoparticles, internalized RGD (iRGD)-modified indocyanine green (ICG) encapsulated liposomes (iLIPICG), for imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) for the treatment of laryngeal carcinoma. The iRGD-PEG-DSPE lipid endowed iLIPICG with high affinity for tumor vascular targeting, tumor-penetration and tumor cell targeting. The in vivo results showed that iLIPICG exhibited excellent blood circulation and tumor accumulation. iLIPICG could be spatially and temporally controlled, simultaneously producing hyperthermia and reactive oxygen species as well as a fluorescence-guided effect through ICG to ablate laryngeal carcinoma cells under irradiation from an 808 nm laser. iLIPICG generated synergistic photodynamic-photothermal cytotoxicity against Hep-2 cells, resulting in the efficient ablation of laryngeal carcinoma. Thus, the iLIPICG system provides a promising strategy to improve the precision imaging and effective phototherapy for the treatment of laryngeal carcinoma.


Assuntos
Corantes/administração & dosagem , Verde de Indocianina/administração & dosagem , Neoplasias Laríngeas/terapia , Oligopeptídeos/administração & dosagem , Fototerapia , Animais , Linhagem Celular Tumoral , Corantes/química , Corantes/farmacocinética , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Lasers , Lipossomos , Masculino , Camundongos SCID , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Imagem Óptica , Fosfatidiletanolaminas/administração & dosagem , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/farmacocinética , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Espécies Reativas de Oxigênio/metabolismo
14.
Jpn J Radiol ; 38(10): 997-1003, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32458127

RESUMO

Indocyanine green (ICG) excretory defect is characterized by an ICG retention rate of more than 50% at 15 min without any other abnormal liver functions. The incidence of ICG excretory defect is 0.007% in the Japanese population. Due to its rarity, the imaging characteristics associated with ICG excretory defect remain unclear. Herein, we present three cases of ICG excretory defect, which showed impaired lesion detectability on gadoxetic acid-enhanced MR imaging (EOB-MRI). In the hepatobiliary phase (HBP) of EOB-MRI, diminished enhancement of the liver parenchyma, prolonged intravascular enhancement, and attenuated gadoxetic acid excretion to the bile duct were observed. Our study also investigated the expression level of organic anion transporting polypeptide (OATP) 1B3 and OATP1B1/1B3, which is related to the uptake of ICG and gadoxetic acid into hepatocytes. All cases showed decreased expression of OATP1B3, which was assumed to be characteristic of ICG excretory defect. The present study indicates that, when patients with ICG excretory defect are evaluated using EOB-MRI, attention should be paid to the impaired lesion detectability in the HBP due to the attenuated gadoxetic acid uptake into the liver parenchyma.


Assuntos
Corantes/farmacocinética , Gadolínio DTPA , Verde de Indocianina/farmacocinética , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Idoso , Ductos Biliares/diagnóstico por imagem , Meios de Contraste , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo
15.
PLoS One ; 15(4): e0230970, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287318

RESUMO

The ability to predict when an individual will die can be extremely useful for many research problems in aging. A technique for predicting death in the model organism, Drosophila melanogaster, has been proposed which relies on an increase in the permeability of the fly intestinal system, allowing dyes from the diet to permeate the body of the fly shortly before death. In this study we sought to verify this claim in a large cohort study using different populations of D. melanogaster and different dyes. We found that only about 50% of the individuals showed a visible distribution of dye before death. This number did not vary substantially with the dye used. Most flies that did turn a blue color before death did so within 24 hours of death. There was also a measurable effect of the dye on the fly mean longevity. These results would tend to limit the utility of this method depending on the application the method was intended for.


Assuntos
Drosophila melanogaster/fisiologia , Intestinos/fisiologia , Longevidade/fisiologia , Envelhecimento/fisiologia , Animais , Corantes/administração & dosagem , Corantes/farmacocinética , Corantes/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Feminino , Longevidade/efeitos dos fármacos , Masculino , Modelos Biológicos , Permeabilidade
16.
World J Surg Oncol ; 18(1): 79, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326968

RESUMO

BACKGROUND: Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. METHODS: Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. RESULTS: Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. CONCLUSIONS: CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.


Assuntos
Carcinoma Hepatocelular/complicações , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/complicações , Índice de Gravidade de Doença , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Corantes/administração & dosagem , Corantes/farmacocinética , Estudos de Viabilidade , Feminino , Hepatectomia , Eliminação Hepatobiliar , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/farmacocinética , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prognóstico , Curva ROC , Estudos Retrospectivos
17.
J Med Chem ; 63(9): 4896-4907, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32267685

RESUMO

Development of new photosensitizers (PSs) with high photodynamic efficacy and minimal side effects is of great interest in photodynamic therapy (PDT). In this work, we reported several pyridine-embedded phenothiazinium (pyridophenothiazinium) dyes, which could be conveniently synthesized in a few short steps and acted as highly efficient and potent PSs to selectively localize to lysosomes and photosensitively kill cancer cells. Among them, compound 5, which possessed the ability of promoting intracellular reactive oxygen species (ROS) upon light irradiation by almost 40-fold higher than that of methylene blue (MB, a general phenothiazinium-based PS), exhibited a remarkable phototherapeutic index (PI = 53.8) against HT29 cancer cells, leading to eradication of large solid tumors (∼300 mm3) in a xenograft mouse model without apparent side effects. These results suggest that the pyridophenothiazinium dyes developed herein, especially compound 5, may serve as promising lysosome-targeted PSs for efficient photodynamic antitumor therapy.


Assuntos
Antineoplásicos/uso terapêutico , Corantes/uso terapêutico , Lisossomos/metabolismo , Neoplasias/tratamento farmacológico , Fenotiazinas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Corantes/síntese química , Corantes/farmacocinética , Corantes/efeitos da radiação , Feminino , Humanos , Luz , Masculino , Camundongos Endogâmicos BALB C , Fenotiazinas/síntese química , Fenotiazinas/farmacocinética , Fenotiazinas/efeitos da radiação , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/efeitos da radiação , Piridinas/síntese química , Piridinas/farmacocinética , Piridinas/efeitos da radiação , Piridinas/uso terapêutico , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Arch Toxicol ; 94(2): 357-369, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32030457

RESUMO

The continuous increase in the popularity of tattoos and permanent make-up (PMU) has led to substantial changes in their societal perception. Besides a better understanding of pathological conditions associated with the injection of highly diverse substances into subepidermal layers of the skin, their regulation has occupied regulatory bodies around the globe. In that sense, current regulatory progress in the European Union is an exemplary initiative for improving the safety of tattooing. On one hand, the compilation of market surveillance data has provided knowledge on hazardous substances present in tattoo inks. On the other hand, clinical data gathered from patients enabled correlation of adverse reactions with certain substances. Nevertheless, the assessment of risks remains a challenge due to knowledge gaps on the biokinetics of highly complex inks and their degradation products. This review article examines the strategies for regulating substances in tattoo inks and PMU in light of their potential future restriction in the frame of the REACH regulation. Substance categories are discussed in terms of their risk assessment and proposed concentration limits.


Assuntos
Corantes/farmacocinética , Tatuagem/efeitos adversos , Tatuagem/legislação & jurisprudência , Desinfetantes/uso terapêutico , Humanos , Tinta , Distribuição Tecidual
19.
HPB (Oxford) ; 22(2): 258-264, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31326264

RESUMO

BACKGROUND: Multidisciplinary treatment for colorectal liver metastases (CLMs) often includes major hepatectomy for preoperative chemotherapy-related hepatic injury, although the safety limit for resection extent is unclear. We investigated this parameter using the estimated indocyanine green clearance rate (ICG-K) of liver remnants, focusing on postoperative subclinical hepatic insufficiency (PHI). METHODS: Altogether, 225 patients who underwent resection of CLMs were studied. The predictive power of estimated ICG-K of liver remnant (ICG-Krem) for subclinical PHI (peak bilirubin ≥3 mg/dL or refractory ascites) was compared with those of other potential predictors. The suggested safety limit of ICG-Krem ≥0.05 was also assessed. RESULTS: Receiver-operating curve analysis revealed that ICG-Krem [area under the curve (AUC) 0.752, cutoff 0.102] was the best predictor of subclinical PHI (AUC range for others was 0.632-0.668). Makuuchi's criteria corresponded to ICG-Krem 0.10. Subclinical PHI incidence was significantly elevated at ICG-Krem <0.10 (26% vs 8%, p = 0.002), while potentially fatal PHI (peak bilirubin >7 mg/dL) was not observed until down to ICG-Krem of 0.05. CONCLUSIONS: ICG-Krem sensitively predicts subclinical PHI. Liver failure-related death could be avoided so long as ICG-Krem remains at ≥0.05. However, patients with ICG-Krem 0.05-0.10 are at high risk of subclinical PHI and require intensive care postoperatively.


Assuntos
Neoplasias Colorretais/patologia , Corantes/farmacocinética , Insuficiência Hepática/diagnóstico , Verde de Indocianina/farmacocinética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Feminino , Hepatectomia , Insuficiência Hepática/etiologia , Insuficiência Hepática/metabolismo , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/secundário , Masculino , Metastasectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos
20.
Cancer Med ; 9(1): 62-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31701652

RESUMO

PURPOSE: The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression-free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. RESULTS: For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple-drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). CONCLUSIONS: The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Corantes/farmacocinética , Verde de Indocianina/farmacocinética , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Corantes/administração & dosagem , Relação Dose-Resposta a Droga , Óleo Etiodado/administração & dosagem , Feminino , Eliminação Hepatobiliar , Humanos , Verde de Indocianina/administração & dosagem , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos
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