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1.
HIV Med ; 22(8): 662-673, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33964108

RESUMO

OBJECTIVES: Organ failure (OF), a leading cause of death in HIV-positive individuals, is common in patients undergoing liver transplantation (LT). We examined the impact of HIV infection on pre- and post-LT mortalities in cirrhotic patients stratified by the number and type of OFs. METHODS: We performed a cross-sectional study and a retrospective cohort study using the US National Inpatient Sample (NIS) and the United Network for Organ Sharing (UNOS) registry data, respectively. Patients who had not yet undergone LT from the NIS database (2010-2014) and patients undergoing LT from the UNOS database (2003-2016) were included in the study. RESULTS: Analysis of patients (201 348) from the NIS database showed that one [adjusted odds ratio (aOR) 1.531; 95% confidence interval (CI) 1.160-2.023], two (aOR 1.624; 95% CI 1.266-2.083) or three or more OFs (aOR 1.349; 95% CI 1.165-1.562) were associated with higher pre-LT mortality in HIV-infected patients compared with HIV-negative patients with the corresponding number of OFs. In patients without OF, HIV infection was not associated with increased pre-LT mortality. UNOS data for patients undergoing LT (38 942) showed that the presence of two or more OFs was associated with increased post-LT 1-year mortality in HIV-infected patients compared with non-HIV-infected patients with the corresponding number of OFs (aOR 2.342; 95% CI 1.576-3.480). However, in patients with no OF or only one OF, HIV infection was not associated with increased post-LT 1-year mortality (aOR 1.372; 95% CI 0.911-2.068). CONCLUSIONS: The results of this study emphasize the importance of preventing OF development, and justify LT for HIV-infected patients with no or only one OF.


Assuntos
Infecções por HIV , Transplante de Fígado , Estudos Transversais , Bases de Dados Factuais , Infecções por HIV/complicações , Humanos , Transplante de Fígado/métodos , Estudos Retrospectivos
2.
Br J Surg ; 108(8): 941-950, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-33693591

RESUMO

BACKGROUND: Quantifying the risks and benefits of revascularization for chronic limb-threatening ischaemia (CLTI) is important. The aim of this study was to create a risk prediction model for treatment outcomes 30 days after revascularization in patients with CLTI. METHODS: Consecutive patients with CLTI who had undergone revascularization between 2013 and 2016 were collected from the JAPAN Critical Limb Ischemia Database (JCLIMB). The cohort was divided into a development and a validation cohort. In the development cohort, multivariable risk models were constructed to predict major amputation and/or death and major adverse limb events using least absolute shrinkage and selection operator logistic regression. This developed model was applied to the validation cohort and its performance was evaluated using c-statistic and calibration plots. RESULTS: Some 2906 patients were included in the analysis. The major amputation and/or mortality rate within 30 days of arterial reconstruction was 5.0 per cent (144 of 2906), and strong predictors were abnormal white blood cell count, emergency procedure, congestive heart failure, body temperature of 38°C or above, and hemodialysis. Conversely, moderate, low or no risk in the Geriatric Nutritional Risk Index (GNRI) and ambulatory status were associated with improved results. The c-statistic value was 0.82 with high prediction accuracy. The rate of major adverse limb events was 6.4 per cent (185 of 2906), and strong predictors were abnormal white blood cell count and body temperature of 38°C or above. Moderate, low or no risk in the GNRI, and age greater than 84 years were associated with improved results. The c-statistic value was 0.79, with high prediction accuracy. CONCLUSION: This risk prediction model can help in deciding on the treatment strategy in patients with CLTI and serve as an index for evaluating the quality of each medical facility.


Assuntos
Isquemia Crônica Crítica de Membro/cirurgia , Procedimentos Endovasculares/métodos , Perna (Membro)/irrigação sanguínea , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
3.
Br J Surg ; 108(3): 286-295, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33793720

RESUMO

BACKGROUND: Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. METHODS: A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). RESULTS: Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P < 0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P = 0.093 and P =0.472 respectively). CONCLUSION: In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.


Assuntos
Aneurisma Infectado/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma Ilíaco/cirurgia , Fatores Etários , Idoso , Aneurisma Infectado/mortalidade , Aneurisma da Aorta Abdominal/mortalidade , Prótese Vascular , Estudos de Coortes , Procedimentos Endovasculares , Feminino , Seguimentos , Humanos , Hipoalbuminemia/mortalidade , Aneurisma Ilíaco/mortalidade , Japão/epidemiologia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Choque/mortalidade
4.
Clin Radiol ; 76(2): 155.e15-155.e23, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33220941

RESUMO

AIM: To assess the image quality of deep-learning image reconstruction (DLIR) of chest computed tomography (CT) images on a mediastinal window setting in comparison to an adaptive statistical iterative reconstruction (ASiR-V). MATERIALS AND METHODS: Thirty-six patients were evaluated retrospectively. All patients underwent contrast-enhanced chest CT and thin-section images were reconstructed using filtered back projection (FBP); ASiR-V (60% and 100% blending setting); and DLIR (low, medium, and high settings). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated objectively. Two independent radiologists evaluated ASiR-V 60% and DLIR subjectively, in comparison with FBP, on a five-point scale in terms of noise, streak artefact, lymph nodes, small vessels, and overall image quality on a mediastinal window setting (width 400 HU, level 60 HU). In addition, image texture of ASiR-Vs (60% and 100%) and DLIR-high was analysed subjectively. RESULTS: Compared with ASiR-V 60%, DLIR-med and DLIR-high showed significantly less noise, higher SNR, and higher CNR (p<0.0001). DLIR-high and ASiR-V 100% were not significantly different regarding noise (p=0.2918) and CNR (p=0.0642). At a higher DLIR setting, noise was lower and SNR and CNR were higher (p<0.0001). DLIR-high showed the best subjective scores for noise, streak artefact, and overall image quality (p<0.0001). Compared with ASiR-V 60%, DLIR-med and DLIR-high scored worse in the assessment of small vessels (p<0.0001). The image texture of DLIR-high was significantly finer than that of ASIR-Vs (p<0.0001). CONCLUSIONS: DLIR-high improved the objective parameters and subjective image quality by reducing noise and streak artefacts and providing finer image texture.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Torácica/métodos , Doenças Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Colorectal Dis ; 22(1): 62-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344314

RESUMO

AIM: Patient body composition is an important indicator of metabolic status and is associated with cancer progression. Because body composition varies between men and women, we aimed to examine the difference in clinical impact of preoperative body composition according to sex. METHOD: We used an integrated dataset of 559 colorectal cancer (CRC) patients. The association between preoperative body composition indices [body mass index (BMI), visceral to subcutaneous fat area ratio (VSR) and skeletal muscle index (SMI)] and patient outcome, clinicopathological factors and preoperative inflammation and nutritional status was analysed, comparing men and women. RESULTS: Preoperative low BMI and low SMI in men was significantly associated with unfavourable overall survival (OS) [BMI: hazard ratio (HR) 2.22, 95% CI 1.28-4.14, P = 0.004; SMI: HR 2.54, 95% CI 1.61-4.07, P < 0.001] and high VSR in women was significantly associated with unfavourable OS (HR 1.79, 95% CI 1.03-3.02, P = 0.040). Additionally, low SMI in men was significantly associated with deeper tumour invasion and greater distant metastasis and high VSR in women was significantly associated with advanced age, right-sided tumour, lower total lymphocyte count and lower albumin levels. Interestingly, low BMI in men was significantly associated with deeper tumour invasion, but also with favourable inflammation and nutritional status (lower C-reactive protein and higher albumin). CONCLUSION: The clinical impact of preoperative body composition differed between men and women: SMI in men and VSR in women were good prognosticators. Our findings may provide a novel insight for CRC treatment strategies.


Assuntos
Composição Corporal/fisiologia , Índice de Massa Corporal , Neoplasias Colorretais/fisiopatologia , Indicadores Básicos de Saúde , Fatores Sexuais , Tecido Adiposo/fisiopatologia , Idoso , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
6.
Colorectal Dis ; 21(1): 100-109, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30230148

RESUMO

AIM: Preoperative anaemia is associated with adverse outcomes in colorectal cancer (CRC). To clarify the reason for this we aimed to comprehensively assess the association of preoperative anaemia with tumour characteristics, host systemic inflammation and nutrition status, and perioperative blood transfusion. METHOD: We used an integrated database of 592 CRC patients. The association of preoperative anaemic subtype, calculated from haemoglobin and erythrocyte mean corpuscular volume levels, with patient outcome, preoperative serum data relating to systemic inflammation and nutrition and perioperative blood transfusion was analysed. RESULTS: Preoperative anaemia was significantly associated with poorer overall survival and relapse-free survival (RFS); in particular microcytic anaemia had a trend to poorer RFS than other forms of anaemia (P = 0.0648). In addition, preoperative anaemia was significantly correlated with right-sided tumours, greater depth of tumour invasion, use of neoadjuvant chemotherapy, poorer prognostic nutritional index and higher modified Glasgow Prognostic Score (mGPS). Microcytic anaemia in particular had a strong association with a greater depth of tumour invasion (P = 0.0072) and higher mGPS (P = 0.0058) than other causes of anaemia. Perioperative blood transfusion for CRC patients with anaemia was associated with adverse outcomes. CONCLUSIONS: Preoperative anaemia, especially microcytic anaemia, was associated with poor patient outcomes, possibly due to poor systemic inflammatory and nutritional status, and it was not improved by perioperative blood transfusion. Our data suggest that preoperative anaemia and the anaemic subtype may serve as an easily available predictor of outcome in CRC.


Assuntos
Anemia/epidemiologia , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/classificação , Anemia/metabolismo , Anemia Macrocítica/epidemiologia , Anemia Macrocítica/metabolismo , Transfusão de Sangue , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Índices de Eritrócitos , Feminino , Hemoglobinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Avaliação Nutricional , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Albumina Sérica/metabolismo , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
7.
Insect Mol Biol ; 27(2): 154-165, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29096051

RESUMO

Despite possessing a limited number of neurones compared to vertebrates, honeybees show remarkable learning and memory performance, an example being 'dance communication'. In this phenomenon, foraging honeybees learn the location of a newly discovered food source and transmit the information to nestmates by symbolic abdomen vibrating behaviour, leading to navigation of nestmates to the new food source. As an initial step toward understanding the detailed molecular mechanisms underlying the sophisticated learning and memory performance of the honeybee, we focused on the neural immediate early genes (IEGs), which are specific genes quickly transcribed after neural activity without de novo protein synthesis. Although these have been reported to play an essential role in learning and memory processes in vertebrates, far fewer studies have been performed in insects in this regard. From RNA-sequencing analysis and subsequent assays, we identified three genes, Src homology 3 (SH3) domain binding kinase, family with sequence similarity 46 and GB47136, as novel neural IEGs in the honeybee. Foragers and/or orientating bees, which fly around their hives to memorize the positional information, showed induced expression of these IEGs in the mushroom body, a higher-order centre essential for learning and memory, indicating a possible role for the novel IEGs in foraging-related learning and memory processes in the honeybee.


Assuntos
Abelhas/fisiologia , Genes Precoces/genética , Proteínas de Insetos/genética , Memória , Animais , Abelhas/genética , Comportamento Alimentar , Proteínas de Insetos/metabolismo , Aprendizagem
8.
Insect Mol Biol ; 25(1): 16-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26471013

RESUMO

Ticks are obligate haematophagous arthropods that feed on vertebrate blood containing high levels of iron. The host-derived iron reacts to oxygen in the tick's body, and then high levels of reactive oxygen species, including hydrogen peroxide (H(2)O(2)), may be generated. High levels of H(2)O(2) cause oxidative stress to aerobic organisms. Therefore, antioxidant responses are necessary to control H(2)O(2). We focused on peroxiredoxins (Prxs), H(2)O(2) -scavenging enzymes. The sequence of Haemaphysalis longicornis 2-Cys Prx (HlPrx2) was identified from fat body cDNA libraries of this tick and recombinant HlPrx2 was then prepared using Escherichia coli. By comparison with the 2-Cys Prxs of other organisms, we found two conserved cysteines in HlPrx2, Cys51 and Cys172. We examined the antioxidant activity of HlPrx2 and mutant proteins produced by a single base substitution, converting one or both of these cysteines into serines. The assays revealed that proteins containing Cys51 showed antioxidant activity when H(2)O(2) was removed. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and size-exclusion chromatography demonstrated that only the wild-type HlPrx2 formed homodimers and that all of the proteins that we made had a high molecular weight peak. These results indicate that both Cys51 and Cys172 are essential for the dimerization of HlPrx2, whereas only the Cys51 residue is necessary for antioxidant activity.


Assuntos
Ixodidae/enzimologia , Peroxirredoxinas/metabolismo , Sequência de Aminoácidos , Animais , Antioxidantes/metabolismo , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Cromatografia em Gel , Dimerização , Peróxido de Hidrogênio , Ixodidae/genética , Dados de Sequência Molecular , Proteínas Recombinantes/metabolismo
9.
Eur J Vasc Endovasc Surg ; 48(3): 316-24, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24980076

RESUMO

OBJECTIVE: To evaluate the outcomes of surgical revascularization for critical limb ischemia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: From 2004 to 2010, 184 patients with 213 critically ischaemic limbs caused by arteriosclerosis were admitted to The University of Tokyo Hospital. The outcomes of primarily surgical revascularization-based treatments were retrospectively compared in patients with ESRD (ESRD group: 79 patients, 101 limbs) and without ESRD (non-ESRD group: 105 patients, 112 limbs) during the same period. RESULTS: Arterial reconstruction was performed on 56 limbs in 46 patients in the ESRD group and 78 limbs in 73 patients in the non-ESRD group (55% vs. 70%; p = .03). Major amputation was performed in 6 of 48 limbs with patent grafts in the ESRD group because of uncontrolled infection or progression of necrosis. The limb salvage rate after arterial reconstruction was significantly lower in the ESRD group than in the non-ESRD group (p = .0019). The postoperative survival rate was lower in the ESRD group than in the non-ESRD group, although this difference was not significant (p = .052). Associated cardiovascular disease and systemic infection were the most frequent causes of death in the ESRD group. There was no significant difference in graft patency between the two groups after distal bypass surgery; however, the limb salvage rate was significantly lower in the ESRD group than in the non-ESRD group (p = .03). CONCLUSIONS: Critical limb ischemia associated with ESRD has a poor prognosis. Infection control is particularly important for achievement of good treatment outcomes.


Assuntos
Isquemia/etiologia , Isquemia/cirurgia , Falência Renal Crônica/complicações , Perna (Membro)/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Grau de Desobstrução Vascular
10.
Pol J Vet Sci ; 26(2): 307-309, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37389419

RESUMO

A separate, cat-specific hospitalization room away from dogs is recommended to reduce stress in cats; however, this can be difficult for some hospitals to provide. In such cases, measures are undertaken to reduce the cat's stress by providing a place to hide. However, inability to observe the cat's condition may be an obstacle to providing veterinary care. The use of a one-way mirror to create a sheltered environment while allowing observation of the cats was assessed. Five healthy cats were assessed using the Cat Stress Score (CSS) while in a cage with either a transparent panel or a one-way mirror. No significant differences in the CSS between the transparent panel and one-way mirror were observed. Variations in the CSS scores depended on the cat's personality, with friendlier and more sociable cats showing a lower CSS with the one-way mirror. A one-way mirror may be useful to reduce stress in hospitalized cats.


Assuntos
Doenças do Gato , Doenças do Cão , Gatos , Animais , Cães , Hospitalização , Doenças do Gato/terapia
11.
Sci Rep ; 13(1): 5122, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36991136

RESUMO

Microwave sintering of fly ash samples with large amounts of unburned carbon and CaCO3 was examined in this study. To this end, CaCO3 was mixed with fly ash sintered body to fix CO2. The decomposition of CaCO3 was observed when the raw material was heated to 1000 °C using microwave irradiation; however, a sintered body containing aragonite was obtained when the raw material was heated to 1000 °C with added water. Further, carbides in the fly ash could be selectively heated by controlling the microwave irradiation. The microwave magnetic field created a temperature gradient of 100 °C in a narrow region of 2.7 µm or less in the sintered body, and it helped suppress the CaCO3 decomposition in the mixture during sintering. By storing water in the gas phase before spreading, CaCO3, which is difficult to sinter using conventional heating, can be sintered without decomposing.

12.
Diabetologia ; 55(3): 845-54, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22143324

RESUMO

AIMS/HYPOTHESIS: Methylglyoxal (MG) is an important precursor for AGEs. Normally, MG is detoxified by the glyoxalase (GLO) enzyme system (including component enzymes GLO1 and GLO2). Enhanced glycolytic metabolism in many cells during diabetes may overpower detoxification capacity and lead to AGE-related pathology. Using a transgenic rat model that overexpresses GLO1, we investigated if this enzyme can inhibit retinal AGE formation and prevent key lesions of diabetic retinopathy. METHODS: Transgenic rats were developed by overexpression of full length GLO1. Diabetes was induced in wild-type (WT) and GLO1 rats and the animals were killed after 12 or 24 weeks of hyperglycaemia. N ε)-(Carboxyethyl)lysine (CEL), N(ε)-(carboxymethyl)lysine (CML) and MG-derived-hydroimidazalone-1 (MG-H1) were determined by immunohistochemistry and by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS). Müller glia dysfunction was determined by glial fibrillary acidic protein (GFAP) immunoreactivity and by spatial localisation of the potassium channel Kir4.1. Acellular capillaries were quantified in retinal flat mounts. RESULTS: GLO1 overexpression prevented CEL and MG-H1 accumulation in the diabetic retina when compared with WT diabetic counterparts (p < 0.01). Diabetes-related increases in Müller glial GFAP levels and loss of Kir4.1 at the vascular end-feet were significantly prevented by GLO1 overexpression (p < 0.05) at both 12- and 24-week time points. GLO1 diabetic animals showed fewer acellular capillaries than WT diabetic animals (p < 0.001) at 24 weeks' diabetes. CONCLUSIONS/INTERPRETATION: Detoxification of MG reduces AGE adduct accumulation, which, in turn, can prevent formation of key retinal neuroglial and vascular lesions as diabetes progresses. MG-derived AGEs play an important role in diabetic retinopathy.


Assuntos
Retinopatia Diabética/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Lactoilglutationa Liase/biossíntese , Neuroglia/metabolismo , Retina/metabolismo , Vasos Retinianos/metabolismo , Animais , Retinopatia Diabética/sangue , Retinopatia Diabética/patologia , Retinopatia Diabética/prevenção & controle , Humanos , Hiperglicemia/metabolismo , Imuno-Histoquímica , Isoenzimas/genética , Isoenzimas/metabolismo , Lactoilglutationa Liase/genética , Microvasos/metabolismo , Microvasos/patologia , Terapia de Alvo Molecular , Neuroglia/patologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Aldeído Pirúvico , Ratos , Ratos Transgênicos , Proteínas Recombinantes/biossíntese , Retina/enzimologia , Retina/patologia , Vasos Retinianos/patologia , Fatores de Tempo
13.
Gene Ther ; 19(1): 61-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21654819

RESUMO

Gene therapy is expected to open a new strategy for the treatment of refractory vascular diseases, so the development of appropriate gene vectors for vascular lesions is needed. To realize this requirement with a non-viral approach, cyclo(RGDfK) peptide (cRGD) was introduced to block copolymer, poly(ethylene glycol)-block-polycation carrying ethylenediamine units (PEG-PAsp(DET)). cRGD recognizes α(v)ß(3) and α(v)ß(5) integrins, which are abundantly expressed in vascular lesions. cRGD-conjugated PEG-PAsp(DET) (cRGD-PEG-PAsp(DET)) formed polyplex micelles through complexation with plasmid DNA (pDNA) and the cRGD-PEG-PAsp(DET) micelles achieved significantly more efficient gene expression and cellular uptake as compared with PEG-PAsp(DET) micelles in endothelial cells and vascular smooth muscle cells. Intracellular tracking of pDNA showed that cRGD-PEG-PAsp(DET) micelles were internalized via caveolae-mediated endocytosis, which is associated with a pathway avoiding lysosomal degradation and that, PEG-PAsp(DET) micelles were transported to acidic endosomes and lysosomes via clathrin-mediated endocytosis. Further, in vivo evaluation in rat carotid artery with a neointimal lesion revealed that cRGD-PEG-PAsp(DET) micelles realized sustained gene expression, whereas PEG-PAsp(DET) micelles facilitated rapid, but transient gene expression. These findings suggest that introduction of cRGD to polyplex micelles might create novel and useful functions for gene transfer and contribute to the establishment of efficient gene therapy for vascular diseases.


Assuntos
Lesões das Artérias Carótidas/terapia , Técnicas de Transferência de Genes , Micelas , Peptídeos Cíclicos/administração & dosagem , Polietilenoglicóis/metabolismo , Proteínas/metabolismo , Animais , Artérias Carótidas , Lesões das Artérias Carótidas/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Terapia Genética , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Ligantes , Modelos Animais , Peptídeos Cíclicos/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Polietilenoglicóis/administração & dosagem , Proteínas/administração & dosagem , Ratos , Receptores de Vitronectina/metabolismo
14.
Ann Oncol ; 23(12): 3151-3155, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22843420

RESUMO

BACKGROUND: Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. MATERIALS: In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. RESULTS: In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. CONCLUSIONS: To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.


Assuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Descoberta de Drogas , Antineoplásicos , Aprovação de Drogas , Humanos , Japão , Políticas , Pesquisadores
15.
Osteoporos Int ; 23(6): 1673-81, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21901479

RESUMO

UNLABELLED: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. INTRODUCTION: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. METHODS: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). RESULTS: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI (ß = -0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles (P < 0.01). CONCLUSION: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality.


Assuntos
Calcâneo/diagnóstico por imagem , Produtos Finais de Glicação Avançada/metabolismo , Pele/metabolismo , Adulto , Povo Asiático , Densidade Óssea , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Pele/química , Ultrassonografia
16.
Diabet Med ; 29(4): 492-500, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21916970

RESUMO

AIMS: Skin autofluorescence, a non-invasive measure of the accumulation for advanced glycation end products, has been reported to be a useful marker for diabetic vascular risks in the Caucasian population. The aim of this study was to evaluate associations between skin autofluorescence and vascular complications in non-Caucasian patients with Type 2 diabetes. METHODS: Subjects in this cross-sectional study comprised 130 Japanese patients with Type 2 diabetes. Skin advanced glycation end products were assessed by skin autofluorescence using an autofluorescence reader. Association between skin autofluorescence and severity of vascular complications was evaluated. RESULTS: Of the 130 patients, 60 (46.2%) had microvascular complications such as diabetic retinopathy, neuropathy and nephropathy, 10 (7.7%) had macrovascular complications and 63 (48.5%) had micro- and/or macrovascular complications. Skin autofluorescence increased with severity of vascular complications. Independent determinants of skin autofluorescence were age (ß = 0.24, P < 0.01), mean HbA(1c) in previous year (ß = 0.17, P = 0.03), microvascular complications (ß = 0.44, P < 0.01) and macrovascular complications (ß = 0.27, P < 0.01). Multiple logistic regression analysis revealed that diabetes duration (odds ratio 1.15, P < 0.01), systolic blood pressure (odds ratio 1.04, P = 0.01), skin autofluorescence (odds ratio 3.62, P = 0.01) and serum albumin (odds ratio 0.84, P < 0.01) were independent factors for the presence of vascular complications in these patients. CONCLUSIONS: Skin autofluorescence had independent effects on vascular complications in Japanese patients with Type 2 diabetes. This indicates that skin advanced glycation end products are a surrogate marker for vascular risk and a non-invasive autofluorescence reader may be a useful tool to detect high-risk cases in non-Caucasian patients with diabetes.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Fluorescência , Produtos Finais de Glicação Avançada/metabolismo , Pele/metabolismo , Fumar/efeitos adversos , Idoso , Povo Asiático , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/metabolismo , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco
17.
Eur J Vasc Endovasc Surg ; 43(3): 257-61, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22230600

RESUMO

OBJECTIVE: We retrospectively analysed surgically treated abdominal aortic aneurysm (AAA) in patients with massive atheroma in the aneurysmal neck and compared the outcomes of endovascular aneurysm repair (EVAR) and open surgery (OS) to determine an appropriate strategy for massive neck atheroma cases. METHODS: A retrospective study was performed in 326 consecutive patients who underwent EVAR and in 247 patients who underwent OS. We defined massive neck atheromas if the following characteristics were observed: (1) thickness ≥ 5 mm; (2) the circumference of the infrarenal aorta ≥ 75%; and (3) length ≥ 5 mm. Twenty-eight patients (8.5%) in the EVAR group and 22 (8.9%) in the OS group met these criteria. We modified the previously published reporting standards on the basis of the selection of systemic and embolisation-related complications. RESULTS: Patients in the EVAR group had less intra-operative blood loss, shorter operation time, and shorter hospital stays after the operation (P < 0.01). No perioperative deaths were observed in either group. Major complications were categorised as early (in-hospital) or late (outpatient, within 6 months). Five and three patients in the OS and EVAR groups had early complications, but the difference was not statistically significant. In contrast, 7 patients in the EVAR group had late complications, compared to no patients in the OS group (P = 0.01). Kaplan-Meier analysis revealed a significantly higher survival rate in the OS group (P = 0.011). Two of the 4 patients with suprarenal clamping developed major complications. Mild eosinophilia was observed in 10 patients in the EVAR group. Proteinuria occurred or worsened in 5 EVAR patients and 1 OS patient. CONCLUSION: Compared to OS patients, EVAR patients with massive neck atheroma tend to develop late-phase complications possibly related to cholesterol crystal embolisation. The clinical features of massive neck atheroma patients receiving EVAR should be carefully monitored even after hospital discharge.


Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares , Placa Aterosclerótica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/mortalidade , Prótese Vascular , Causalidade , Comorbidade , Contraindicações , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pescoço/cirurgia , Placa Aterosclerótica/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Grau de Desobstrução Vascular
19.
AJNR Am J Neuroradiol ; 43(6): 893-898, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35550283

RESUMO

BACKGROUND AND PURPOSE: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment. RESULTS: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10-6 mm2/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10-6 mm2/s. The mean ADC threshold was 520 × 10-6 mm2/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (P < .0001). CONCLUSIONS: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10-6 mm2/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Imagem de Difusão por Ressonância Magnética , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia
20.
Eur J Vasc Endovasc Surg ; 42(4): 517-22, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21550267

RESUMO

OBJECTIVES: Aneurysms associated with congenital vascular malformation (CVM) comprise critical complication. We review our experience with extracranial CVM-associated aneurysms and attempt to clarify their clinical features. PATIENTS AND METHODS: The prevalence, site, size and morphology of the accompanying aneurysms of 48 consecutive CVM patients, who were managed at our hospital from 1999 to 2008, were evaluated. After diagnosis or treatment, the patients were followed up, and the recurrence of aneurysms and patient survival were assessed. RESULTS: CVM-associated aneurysms were found in 14 patients (29%). CVMs were classified according to the Hamburg classification. The patients were classified into groups as follows: four (31%), in the 'predominantly arteriovenous (AV) shunting defect type'; eight (47%), 'combined vascular defects + predominantly AV shunting defects type'; and two (11%), 'combined vascular defects type'. All aneurysms except one situated at the CVM were saccular, whereas nine were fusiform aneurysms; all the ruptured aneurysms and seven out of the nine enlarging aneurysms were saccular. Surgical treatment was performed 8 times in six patients. During the postoperative follow-up period, recurrence and an aneurysm rupture were encountered in one patient each. CONCLUSION: Aneurysm is not a rare complication of CVM. It is important to treat CVM before the emergency presents. In addition to the treatment for malformation, regular screening for and proper management of the aneurysms in CVM patients are indispensable.


Assuntos
Aneurisma/cirurgia , Malformações Vasculares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma/complicações , Aneurisma/diagnóstico , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico , Aneurisma Roto/cirurgia , Criança , Pré-Escolar , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Malformações Vasculares/complicações , Malformações Vasculares/diagnóstico , Adulto Jovem
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