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1.
Nat Commun ; 14(1): 6099, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773161

RESUMO

Mitochondrial morphology, which is controlled by mitochondrial fission and fusion, is an important regulator of the thermogenic capacity of brown adipocytes. Adipose-specific peroxisome deficiency impairs thermogenesis by inhibiting cold-induced mitochondrial fission due to decreased mitochondrial membrane content of the peroxisome-derived lipids called plasmalogens. Here, we identify TMEM135 as a critical mediator of the peroxisomal regulation of mitochondrial fission and thermogenesis. Adipose-specific TMEM135 knockout in mice blocks mitochondrial fission, impairs thermogenesis, and increases diet-induced obesity and insulin resistance. Conversely, TMEM135 overexpression promotes mitochondrial division, counteracts obesity and insulin resistance, and rescues thermogenesis in peroxisome-deficient mice. Mechanistically, thermogenic stimuli promote association between peroxisomes and mitochondria and plasmalogen-dependent localization of TMEM135 in mitochondria, where it mediates PKA-dependent phosphorylation and mitochondrial retention of the fission factor Drp1. Together, these results reveal a previously unrecognized inter-organelle communication regulating mitochondrial fission and energy homeostasis and identify TMEM135 as a potential target for therapeutic activation of BAT.


Assuntos
Tecido Adiposo Marrom , Resistência à Insulina , Animais , Camundongos , Adipócitos Marrons , Tecido Adiposo Marrom/fisiologia , Homeostase , Camundongos Knockout , Dinâmica Mitocondrial , Obesidade , Peroxissomos , Termogênese
2.
Trends Endocrinol Metab ; 30(10): 710-723, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31422871

RESUMO

The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy expenditure represents one such approach. Brown adipocytes and the related beige adipocytes oxidize fatty acids and glucose to generate heat and are activated by cold exposure or consumption of high-calorie diets. Alternative, more practical means to activate thermogenic fat are needed. Here, we review emerging data suggesting new roles for lipids in activating thermogenesis that extend beyond their serving as a fuel source for heat generation. Lipids have also been implicated in mediating interorgan communication, crosstalk between organelles, and cellular signaling regulating thermogenesis. Understanding how lipids regulate thermogenesis could identify innovative therapeutic interventions for obesity.


Assuntos
Tecido Adiposo Bege/metabolismo , Termogênese/fisiologia , Animais , Humanos , Mitocôndrias/metabolismo , Obesidade/metabolismo , Plasmalogênios/metabolismo
3.
Pharmaceutics ; 11(6)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31159476

RESUMO

As caterpillars detect the presence of predators and secrete poison, herein, we show an innovative and highly effective cancer therapeutic system using biocompatible chitosan nanofiber (CNf) installed with a pH-responsive motif that senses tumor extracellular pH, pHe, prior to delivering dual-modal light-activatable materials for tumor reduction. The filamentous nanostructure of CNf is dynamic during cell interaction and durable in blood circulation. Due to its amine group, CNf uptakes a large amount of photothermal gold nanoparticles (AuNPs, >25 wt %) and photodynamic chlorin e6 (Ce6, >5 wt %). As the innovative CNf approaches tumors, cationic CNf effectively discharges AuNPs connected to the pH-responsive motif via electrostatic repulsion and selectively binds to tumor cells that are generally anionic, via the electrostatic attraction accompanied by CNf. We demonstrated via these actions that the endocytosed Ce6 (on CNf) and AuNPs (free from CNf) significantly elicited tumor cell death under light irradiation. As a result, the synergistic interplay of thermogenesis and photodynamic action was observed to switch on at the pHe, resulting in a striking reduction in tumor formation and growth rate upon light exposure.

4.
Carbohydr Polym ; 209: 282-290, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30732810

RESUMO

We report here the use of near-infrared fluorescent dye-labelled hyaluronate (HA) dot named HDFc for tumor imaging. We took advantage of the unique auto-quenching characteristic that occurs when the fluorescent dye molecules are in close proximity to one another under ordinary conditions. However, when the HDFc is located in tumor cells, the tumor cell-specific enzyme (e.g., hyaluronidase: HAase) affects the structure of the HDFc, followed by the transition from auto-quenched dye molecules to dequenched dye molecules, resulting in the identification of the tumor cells. For this purpose, HDFcs were synthesized, characterized, and exogenously treated with HAase to demonstrate the enzyme-dependent HDFc photoactivity. Specifically, confocal microscopy and flow cytometry confirmed the efficient cellular internalization and fluorescence production of HDFc in CD44+ and HAase-abundant tumor cells. Collectively, this study opens the door for utilizing polymeric dots to visualize tumor cells by introducing biocompatible HA and tumor cell-on photoluminescent dye.


Assuntos
Ácido Hialurônico/química , Ácido Hialurônico/metabolismo , Imagem Óptica/métodos , Endocitose , Humanos , Hialuronoglucosaminidase/metabolismo , Células MCF-7
5.
Pharmaceutics ; 11(2)2019 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-30691225

RESUMO

Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8⁺ T-cells for cancer therapy. MPLA and HA enabled HDEA@EVAT to interact with the toll-like receptor 4 and the CD44 receptor on DCs, followed by endosomal escape, owing to the protonation of pH-sensitive DEAP on the EV in conjunction with MUC1 release. The MUC1 was then processed and presented to DCs to activate CD8⁺ T-cells for additional anticancer-related immune reactions. Our findings support the anticancer vaccine activity by which HDEA@EVAT expedites the interaction between DCs and CD8⁺ T-cells by inducing DC-targeted maturation and by presenting the cancer-associated peptide MUC1.

6.
J Clin Invest ; 129(2): 694-711, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30511960

RESUMO

Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic coregulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity. Pex16 deficiency blocked cold-induced mitochondrial fission, decreased mitochondrial copy number, and caused mitochondrial dysfunction. Adipose-specific knockout of the peroxisomal ß-oxidation enzyme acyl-CoA oxidase 1 (Acox1-AKO) was not sufficient to affect adiposity, thermogenesis, or mitochondrial copy number, but knockdown of the plasmalogen synthetic enzyme glyceronephosphate O-acyltransferase (GNPAT) recapitulated the effects of Pex16 inactivation on mitochondrial morphology and function. Plasmalogens are present in mitochondria and decreased with Pex16 inactivation. Dietary supplementation with plasmalogens increased mitochondrial copy number, improved mitochondrial function, and rescued thermogenesis in Pex16-AKO mice. These findings support a surprising interaction between peroxisomes and mitochondria regulating mitochondrial dynamics and thermogenesis.


Assuntos
Tecido Adiposo/metabolismo , Temperatura Baixa , Lipídeos/biossíntese , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Peroxissomos/metabolismo , Termogênese , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Animais , Células COS , Chlorocebus aethiops , Células HEK293 , Humanos , Lipídeos/genética , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Peroxinas/genética , Peroxinas/metabolismo , Peroxissomos/genética , Plasmalogênios/farmacologia
7.
Carbohydr Polym ; 202: 323-333, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30287007

RESUMO

pH-Responsive drug vehicles targeting the specific extracellular pH of tumors have served as potent tools to overcome the limitation (e.g., low tumor seletivity) in antitumor drug delivery system. Here, we describe the advantage of pH-responsive extracellular vesicles (HDEA@EVs) containing the hyaluronic acid grafted with 3-(diethylamino)propylamine (HDEA) and a model antitumor drug, doxorubicin (DOX). We demonstrated their physicochemical characteristics through in vitro cell endocytosis, in vitro tumor cell toxicity, in vivo biodistribution, and in vivo tumor regression efficacy experiments. Because the HDEA@EVs efficiently responded to extracellular tumor pH (pH 6.5) and actively bound to CD44 receptors on HCT-116 tumor cells, the EVs selectively inhibited CD44+ tumor cell growth in vitro, and CD44+ tumor development in vivo. From these results, we conclude that HDEA@EVs can help in designing effective strategies for pharmacologic intervention in tumor therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Vesículas Extracelulares/química , Ácido Hialurônico/química , Animais , Antibióticos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HCT116 , Humanos , Receptores de Hialuronatos/antagonistas & inibidores , Receptores de Hialuronatos/metabolismo , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Tamanho da Partícula , Células Tumorais Cultivadas
8.
Int J Pharm ; 547(1-2): 377-384, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-29902507

RESUMO

In this study, we report pH-responsive liposomes consisting of hydrogenated soy phosphatidylcholine (HSPC) as a lipid, hyaluronic acid (HA) grafted with functional 3-diethylaminopropyl (DEAP) groups (hereafter denoted as HA-g-DEAP) as a pH-responsive polymer, and docetaxel (DTX) as an antitumor drug. DTX-loaded HSPC liposomes were prepared via a conventional liposome manufacturing procedure and then were decorated with HA-g-DEAP (HA-g-DEAP0.15, HA-g-DEAP0.25, and HA-g-DEAP0.40, according to the molar conjugate ratio of DEAP to HA) in an aqueous solution (pH 7.4), by sonication. The liposomes with HA-g-DEAP0.40 allowed the efficient release of the encapsulated DTX content when the pH of the solution decreased to 6.5 (i.e., endosomal pH), owing to the acidic pH-induced protonation of the DEAP anchored to the vesicular lipid bilayers. These hyaluronated liposomes were effective at entering the human colon carcinoma HCT-116 cells with a CD44 receptor overexpression. In an in vitro tumor cell cytotoxicity test, the DTX-loaded liposomes caused a significant increase in HCT-116 tumor cell death, revealing their pharmaceutical potential in tumor therapy.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Taxoides/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Química Farmacêutica/métodos , Neoplasias do Colo/patologia , Docetaxel , Portadores de Fármacos/química , Feminino , Células HCT116 , Humanos , Concentração de Íons de Hidrogênio , Células KB , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilcolinas/química , Glycine max/química , Taxoides/farmacologia
9.
Cell Rep ; 20(12): 2766-2774, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28930673

RESUMO

How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme. Notably, PexRAP interacts with importin-ß1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARγ, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARγ complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Desidrogenase do Álcool de Açúcar/metabolismo , Termogênese/genética , Fatores de Transcrição/metabolismo , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Sequência de Bases , Núcleo Celular/metabolismo , Perfilação da Expressão Gênica , Marcação por Isótopo , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR gama/metabolismo , Ligação Proteica , Transporte Proteico , Gordura Subcutânea/metabolismo , Desidrogenase do Álcool de Açúcar/genética , Transcrição Gênica
10.
PLoS One ; 12(1): e0170017, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28081262

RESUMO

Chronic kidney disease (CKD) represents a major medical challenge and frequently coexists with cardiovascular disease (CVD), which can be treated by statin trerapy. However, whether statin treatment affects renal progression and outcomes in CKD patients remains unclear. We retrospectively reviewed CKD patients at Gachon University Gil Medical Center from 2003-2013. From a total of 14,497 CKD patients, 858 statin users were paired with non-users and analyze with propensity score matching was performed. The outcomes of this study were creatinine doubling, renal death, all-cause mortality, and interactive factors for composite outcomes. Statins were prescribed to 13.5% of the study subjects. Hazard ratios (HRs) [95% confidence intervals (CIs)] for statin treatment for the doubling of serum creatinine levels were significant only in CKD patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and were 0.744 (0.635-0.873) in the unmatched cohort and 0.767 (0.596-0.986) in the matched cohort. In analyses of secondary outcomes, the HRs (95% CIs) for all-cause mortality were 0.655 (0.502-0.855) in the unmatched cohort and 0.537 (0.297-0.973) in the matched cohort. The HRs (95% CIs) for statin therapy for composite outcomes among patients with and without an eGFR ≥30 mL/min/1.73 m2 were 0.764 (0.613-0.952) and 1.232 (0.894-1.697), respectively (P for interaction, 0.017). Thus, statin treatment may have beneficial effects on renal progression and all-cause mortality only for the patients with early- stage CKD.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento
11.
Ann Surg Treat Res ; 92(1): 42-46, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28090505

RESUMO

PURPOSE: Directional atherectomy (DA) was introduced for the management of infrainguinal arterial stenosis or occlusive lesions. The procedure success rate in the DEFINITIVE LE study was determined using radiologic imaging. The aim of our study was to determine the usefulness of intraoperative ultrasonography (USG) during DA for evaluating the early results of this procedure. METHODS: Patients who underwent DA from January to December 2014 were reviewed retrospectively. Twenty lesions from 14 patients with femoral artery stenosis (>70% stenosis) with short segment occlusive lesions (<2 cm in length) were treated. Among 20 lesions, 3 were treated with the TurboHawk system with a protective device due to lesion calcification. The percentage of stenosis during and after DA was determined with USG. RESULTS: Median follow-up was 5.1 months, and the procedural success rate (<30% stenosis at the end of the procedure) was 100% on angiography, but only 30% on intraoperative USG. On USG, median residual stenosis was 40% (range, 28%-42%) at the end of DA, 40% (range, 30%-55%) at 1 month, 55% (range, 35%-85%) at 6 months, and 64% (range, 60%-100%) at 1 year. There was one dissection, but no cases of perforation, pseudoaneurysm, or thrombosis. Primary patency, which was defined as a peak systolic velocity ratio ≤3.5 with no reintervention at 6 months, was found in 18 lesions (90%), and 11 of 14 patients (78.6%) were free of ischemic symptoms such as claudication at 6 months. CONCLUSION: Our results demonstrated that DA with intraoperative USG is an effective treatment option for short segment occlusive lesions of the femoral artery.

12.
PLoS One ; 10(10): e0141172, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26488294

RESUMO

Cancer stem cells (CSCs) are a small subset of cancer cells responsible for maintenance and progression of several types of cancer. Isolation, propagation, and the differentiation of CSCs in the proper stem niches expose the intrinsic difficulties for further studies. Here we show that induced cancer like stem cells (iCLSCs) can be generated by in vitro oncogenic manipulation of mouse embryonic stem cells (mESCs) with well-defined oncogenic elements; SV40 LTg and HrasV12 by using a mouse stem virus long terminal repeat (MSCV-LTR)-based retroviral system. The reprogrammed mESCs using both oncogenes were characterized through their oncogenic gene expression, the enhancement of proliferation, and unhampered maintenance of stem properties in vitro and in vivo. In addition, these transformed cells resulted in the formation of malignant, immature ovarian teratomas in vivo. To successfully further expand these properties to other organs and species, more research needs to be done to fully understand the role of a tumor- favorable microenvironment. Our current study has provided a novel approach to generate induced cancer like stem cells through in vitro oncogenic reprogramming and successfully initiated organ-specific malignant tumor formation in an orthotopic small animal cancer model.


Assuntos
Células-Tronco Neoplásicas/fisiologia , Animais , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oncogenes/fisiologia , Retroviridae/metabolismo , Sequências Repetidas Terminais/genética , Microambiente Tumoral/fisiologia
13.
Biomaterials ; 73: 32-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26398307

RESUMO

Thermogenic program (also known as browning) is a promising and attractive anti-obesity approach. Islet amyloid polypeptide (IAPP) and irisin have emerged as potential browning hormones that hold high potential to treat obesity. Here, we have constructed a dual browning gene system containing both IAPP and irisin (derived from fibronectin type III domain containing 5; FNDC5) combined with 2A and furin self-cleavage sites. Intraperitoneal administration of the construct complexed with a linear polyethylenimine into diet-induced obese mice demonstrated the elevation of anti-obesogenic effects characterized as the decreased body weight, adiposity, and levels of glucose and insulin. In addition, the construct delivery increased energy expenditure and the expression of core molecular determinants associated with browning. The additional advantages of the dual browning gene construct delivery compared to both single gene construct delivery and dual peptide delivery can be emphasized on efficacy and practicability. Hence, we have concluded that dual browning gene delivery makes it therapeutically attractive for diet-induced obesity treatment.


Assuntos
Dieta Hiperlipídica , Fibronectinas/genética , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Obesidade/genética , Obesidade/terapia , Termogênese/genética , Tecido Adiposo/patologia , Adiposidade , Administração Oral , Animais , Composição Corporal , Peso Corporal , Calorimetria , Fibronectinas/química , Furina/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Células HEK293 , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Fases de Leitura Aberta , Peptídeos/química , Plasmídeos/metabolismo , Polietilenoimina/química
14.
J Control Release ; 207: 154-62, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-25817008

RESUMO

The combinatorial peptidergic therapy of islet amyloid polypeptide (IAPP) and leptin (LEP) analogues was once an optimistic option in treating obese animals and patients. However, the need for frequent administrations and its negative side effects prevent it from being a viable choice. Here, we developed a combinatorial gene therapy of IAPP and LEP, where two genes are inserted into a single plasmid with self-cleaving furin and 2A sites to treat diet-induced obese (DIO) mice. The developed plasmid DNA (pDNA) individually produced both IAPP and LEP peptides in vitro and in vivo. The pDNA was delivered with a non-viral polymeric carrier, and its once-a-week administrations demonstrated a synergistic loss of body weight and significant reductions of fat mass, blood glucose, and lipid levels in DIO mice. The results suggest that the combinatorial gene therapy would have higher potential than the peptidergic approach for future translation due to its improved practicability.


Assuntos
Dieta Hiperlipídica , Técnicas de Transferência de Genes , Terapia Genética/métodos , Leptina/biossíntese , Obesidade/terapia , Polímeros/química , Adiposidade , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos , Células HEK293 , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/biossíntese , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Leptina/genética , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/genética , Plasmídeos/genética , Plasmídeos/metabolismo , Fatores de Tempo , Transfecção , Redução de Peso
15.
Surg Today ; 42(10): 950-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22535018

RESUMO

PURPOSE: To investigate the clinical course of patients with venous malformation (VM) treated conservatively. METHODS: We reviewed retrospectively the database of our Congenital Vascular Malformation clinic and interviewed 207 patients with VM, who had been managed only conservatively. The questionnaires asked about changes in size (no change, increase in proportion to growth, increase greater than in proportion to growth, decrease) and changes in symptoms (markedly worse, moderately worse, no change, moderately improved, markedly much improved). Progression of VMs was defined as an increase greater than in proportion to growth or worsening symptoms. RESULTS: Fifty patients (24 %) reported an increase in size greater than in proportion to growth and 25 patients (12 %) reported symptoms worsening from their initial symptoms. Overall, sixty-six (32 %) of the patients reported evidence of progression of their VM. A binary logistic regression model identified VM combined with capillary malformation (CM) or lymphatic malformation (LM) as an independent predictor of VM progression (OR 2.67, 95 % CI 1.29-5.53). CONCLUSIONS: Based on responses to the questionnaire, the size and symptoms of VM progressed in 32 % of patients over the course of their life. VMs combined with CM or LM were the only independent predictor of progression of a VM after conservative management.


Assuntos
Progressão da Doença , Malformações Vasculares/terapia , Anormalidades Múltiplas , Adolescente , Adulto , Idoso , Capilares/anormalidades , Criança , Pré-Escolar , Bandagens Compressivas , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Anormalidades Linfáticas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Malformações Vasculares/patologia , Conduta Expectante , Adulto Jovem
16.
Ann Vasc Surg ; 26(5): 643-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22266239

RESUMO

BACKGROUND: Hand arteriovenous malformations (AVMs) are difficult to treat because of the necessity to maintain function and the high complication rate of treatment. The purpose of this study was to review the treatment of hand AVMs with embolo/sclerotherapy and the surgical procedures at a single institute. MATERIAL AND METHODS: We retrospectively reviewed the medical records and identified the patients who were referred to the vascular division owing to hand AVMs between 1995 and 2009. The lesions were classified according to their affected areas. The treatments used at the clinic included conservative treatment, amputation, and embolo/sclerotherapy. We investigated the clinical data and assessed the treatment results. RESULTS: Sixty-four patients were involved in this study. The median follow-up duration was 26.9 months (range: 3.5-141.8 months). The median age of the patients was 31.5 years (range: 0.3-75.0 years). All of the lesions were of the extratruncal (ET) form, and 37 cases (57.8%) were of the infiltrating type. Sixteen patients were treated conservatively. Primary amputation was performed in seven cases with previous complications such as ulcer, bleeding, or functional limitations. Embolo/sclerotherapy with ethanol was performed in 41 patients. Sixteen (39.0%) of them showed clinical improvement. The treatment of 20 (48.8%) of the 41 patients was interrupted owing to a variety of complications, and 2 (4.9%) of these patients failed with embolo/sclerotherapy. Skin necrosis was the major complication, and this occurred in 17 patients treated with embolo/sclerotherapy--14 of these cases were small and the skin necrosis healed with conservative treatment; 1 patient had autoamputation owing to necrosis; and 2 patients underwent amputation surgery owing to gangrene. The risk for skin necrosis was higher for the AVMs that involved the subcutaneous layer and the AVMs that extended diffusely (P = 0.021, P = 0.011). Seven neuropathic complications developed after embolo/sclerotherapy, and all of them were transient. CONCLUSIONS: The symptoms and characteristics of the lesions are important factors in devising a treatment plan for AVMs. AVM treatment, and especially embolo/sclerotherapy, is a long-term prospect, and it carries a potential risk for serious complications. After every treatment, the lesions must be reevaluated and new treatment plans must be made by the members of a multidisciplinary team.


Assuntos
Malformações Arteriovenosas/terapia , Embolização Terapêutica , Mãos/irrigação sanguínea , Escleroterapia , Procedimentos Cirúrgicos Vasculares , Adolescente , Adulto , Idoso , Amputação Cirúrgica , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Radiografia , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Escleroterapia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto Jovem
17.
J Microbiol Methods ; 84(1): 41-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20971135

RESUMO

The primary goal of this study was to develop a new strategy to inactivate bacterial biofilms using the thermal stress derived from superparamagnetic iron oxide nanoparticles (SPIONs) in an alternating current (AC) magnetic field. A large number of studies have examined the inactivation of bacterial biofilms using antimicrobial agents; however, there have been no attempts to inactivate biofilms by hyperthermia using SPIONs. In this study, a SPION solution was added to Pseudomonas aeruginosa (P. aeruginosa) PA01 biofilm, and heat was generated by placing the nanoparticle-containing biofilm in an AC magnetic field. The heating temperature was dependent on the concentration of the added SPION solution. More than 4 log inactivation of the PA01 biofilm was obtained using a 60 mg mL(-1) SPION solution in 8 min, and this resulted in a dramatic disintegration of the bacterial cell membrane in the biofilm. This inactivation was largely due to the thermal effect. Local heating of a specific area is also possible using this method, and the heating temperature can be easily adjusted by controlling the concentration of the SPION solution. Therefore, hyperthermia using magnetic nanoparticles holds promise as an effective tool for inactivating the bacterial biofilm.


Assuntos
Biofilmes/efeitos da radiação , Magnetismo , Nanopartículas Metálicas , Viabilidade Microbiana/efeitos da radiação , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/efeitos da radiação , Desinfecção/métodos , Compostos Férricos , Temperatura Alta
18.
Int J Stem Cells ; 4(2): 88-98, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24298340

RESUMO

BACKGROUND AND OBJECTIVES: The clinical benefits of stem cell therapy have been reported in patients with peripheral arterial occlusive disease. However, those studies had no standard reporting system to assess the outcomes, so we made a scoring system and assessed the outcomes of the limbs that underwent whole bone marrow stem cell (WBMSC) therapy. METHODS AND RESULTS: Between July 4 and June 2009, 90 limbs of 67 patients with symptomatic thromboangiitis obliterans (TAO) were enrolled. Autologous whole bone marrow was implanted into the limb by intramuscular injections. The primary outcomes were defined by the clinical and angiographic improvement in all the limbs and the secondary outcomes were the clinical improvement and the amputation-free rates in the critical ischemic limbs (CILs). Clinical improvement and angiographic improvement was observed in 55.6% and 43.2% of all the limbs and in 50% and 50%of the CILs, respectively. The 1, 3 and 5-year amputation-free rates were 91.9%, 88.5% and 84.6% for all the limbs, respectively, and 83.9%, 77.5% and 70.4% for the CILs, respectively. A history of sympathectomy/sympathetic block was shown to be a negative prognostic factor for clinical improvement in all the limbs and in the CILs. In addition, a history of sympathetic block/sympathectomy and the smoking state were the major predictors of amputation for the CILs. CONCLUSIONS: This study indicated that autologous WMBSC therapy improves the clinical status and reduces amputation factors in the limbs with symptomatic TAO and a history of sympathetic block/sympathectomy and the smoking state are useful prognostic factors.

19.
Nanotechnology ; 21(16): 165102, 2010 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-20351408

RESUMO

A microheater was established by embedding magnetic nanoparticles into PDMS (MNP-PDMS). MNP-PDMS generated heat under an AC magnetic field and the temperature was controlled by varying the magnetic particle content and the magnetic field intensity. In this study, the MNP-PDMS chip was demonstrated to amplify the target DNA (732 bp) with > 90% efficiency compared to the conventional PCR thermocycler, and exhibited good performance in regards to temperature control. This system holds great promise for reliably controlling the temperature of thermal processes on an integrated microchip platform for biochemical applications.


Assuntos
Dimetilpolisiloxanos/química , Calefação/instrumentação , Magnetismo/instrumentação , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanotecnologia/instrumentação , Campos Eletromagnéticos , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização
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