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1.
Chemotherapy ; 67(2): 96-101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34839292

RESUMO

BACKGROUND: Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. OBJECTIVE: In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy. METHOD: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy. RESULTS: Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. CONCLUSION: Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Feminino , Humanos , Masculino , Cardiomiopatias , Carnitina/deficiência , Fadiga/etiologia , Hiperamonemia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Doenças Musculares , Inibidores de Proteínas Quinases/efeitos adversos
2.
Ther Drug Monit ; 42(1): 133-138, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31323015

RESUMO

BACKGROUND: Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As ABK has a narrow therapeutic concentration window, the dosage must be adjusted via therapeutic drug monitoring. However, the influence of the physiology of patients with FN on the pharmacokinetic (PK) parameters of ABK remains unclear. Therefore, we examined this influence on ABK PK parameters. METHOD: We performed a retrospective cohort study using data from patients with a hematologic malignancy who were ≥18 years and had been administered ABK. We excluded patients who did not receive therapeutic drug monitoring and had an estimated glomerular filtration rate (eGFR) of <30 mL/min, because clinically sufficient data would not be available. RESULT: Of the 99 enrolled patients, 25 did not have FN and 74 had FN. Arbekacin clearance (CLabk) was shown to correlate with eGFR in patients with FN (r = 0.32, P = 0.0062) and without FN (r = 0.50, P = 0.01). CLabk was higher in patients with FN than in those without FN. In addition, in the eGFR of <100 mL/min group (normal renal function), CLabk and CLabk/eGFR were also higher in patients with FN than in those without FN. CONCLUSIONS: CLabk was increased in patients with FN and normal renal function; therefore, we propose an increased ABK dose for patients with FN and normal renal function.


Assuntos
Anti-Infecciosos/farmacocinética , Dibecacina/análogos & derivados , Neutropenia Febril/metabolismo , Adulto , Idoso , Anti-Infecciosos/sangue , Estudos de Coortes , Dibecacina/sangue , Dibecacina/farmacocinética , Monitoramento de Medicamentos , Neutropenia Febril/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Rinsho Ketsueki ; 61(3): 245-250, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32224585

RESUMO

Nodal marginal zone lymphoma (NMZL) is a form of nodal B-cell lymphoma exhibiting proliferation of abnormal lymphocytes at the circumference of the mantle zone in the lymph nodes. Although the outcome of patients with this disease is often favorable, we recently encountered a patient with a CD5-positive NMZL who was resistant to chemotherapy. A 67-year-old woman complaining of systemic lymph node swelling was referred to our hospital. After biopsy of the neck lymph node, she was diagnosed with CD5-positive NMZL. Disease progression was revealed after 16 months, and she was initially treated with chemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP). However, this therapy was ineffective. Subsequent therapy with rituximab and bendamustine also failed to induce remission. A rebiopsy revealed that the NMZL had transformed into a diffuse large B-cell lymphoma. This patient died after 2 years from the initial diagnosis due to lymphoma progression. Cases of CD5-positive NMZL are rare; thus, it is difficult to study the clinical implications of CD5 expression in this disease. Here we describe the current understanding of CD5 expression in NMZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Idoso , Cloridrato de Bendamustina , Feminino , Humanos , Linfonodos , Rituximab
4.
Langmuir ; 35(44): 14222-14229, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31592666

RESUMO

The photoinduced reorientation of the side-chain mesogens in nematic liquid crystalline (LC) polymer thin films triggered by the axis-selective photo-Fries rearrangements of side-chain phenyl benzoate moieties is studied to understand the regulation of the anisotropic nanostructures supported by LC polymers. The influence of the substrate surface in anchoring the side-chain mesogens near the interfaces is examined by comparing the reorientation of 30- and 120-nm-thick films. Irradiation with linearly polarized ultraviolet (UV) light and subsequent annealing causes the side-chain mesogen reorientation to align perpendicular to the electric field of the incident UV light. The inplane order in the 30-nm-thick films is lower than that in the 120-nm ones. On the other hand, the annealing period required for mesogen alignment is independent of the film thickness. It is suggested that the substrate surfaces anchor the LC mesogens to fix their orientation, rather than slowing down the reorientational motion. In addition, it is demonstrated that small LC molecules miscible with the nematic LC polymer enhance photoinduced reorientation through cooperative molecular interaction with the side-chain mesogens, remarkably accelerating the orientation and improving the inplane order of the unidirectionally aligned mesogens.

5.
Toxicol Appl Pharmacol ; 345: 48-56, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29524502

RESUMO

Benzo[a]pyrene (BaP) is an environmental pollutant found in cigarette smoke and is implicated as a causative agent of tobacco-related diseases, such as arteriosclerosis. In contrast, vitamin D signaling, which is principally mediated by conversion of vitamin D to the active form, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], decreases cardiovascular disease risk. However, combined treatment with BaP and 1,25(OH)2D3 enhances BaP toxicity, including BaP-DNA adduct formation. We further investigated the cross-talk between BaP and 1,25(OH)2D3 signaling pathways, and found that combined treatment with these compounds induces mRNA and protein expression of plasminogen activator inhibitor 1 (PAI-1) in monocyte/macrophage-derived THP-1 and U937 cells. Protein synthesis inhibitor treatment did not inhibit induction of the PAI-1 gene (SERPINE1) in these cells. BaP plus 1,25(OH)2D3 induced differentiation markers, inhibited cellular proliferation, and induced apoptosis and oxidative stress in these cells. Reactive oxygen species scavenger treatment suppressed apoptosis but not SERPINE1 induction in cells treated with BaP plus 1,25(OH)2D3. Thus, combined treatment with BaP and 1,25(OH)2D3 induced SERPINE1 mRNA expression in these cells through a mechanism that does not require de novo protein synthesis or reactive oxygen species production. These findings suggest that induction of the proinflammatory factor PAI-1 plays a role in BaP toxicity. Interestingly, PAI-1 knockdown decreased expression of the cell surface antigen CD14, a monocytic differentiation marker, in THP-1 cells treated with BaP plus 1,25(OH)2D3. PAI-1 induction may also be related to a function of monocytes/macrophages in response to xenobiotic and vitamin D signaling.


Assuntos
Benzo(a)pireno/administração & dosagem , Colecalciferol/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Combinação de Medicamentos , Expressão Gênica , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Células THP-1/efeitos dos fármacos , Células THP-1/metabolismo , Células U937
6.
Langmuir ; 34(32): 9366-9375, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30039971

RESUMO

In UV nanoimprinting, the selection of monomers suitable for sub-15 nm patterning is difficult because the filling behavior of resin at this scale still remains scientifically unclear. We demonstrate sub-15 nm patterning by UV nanoimprinting using silica molds with 20, 15, and 7 nm diameter holes; however, the 7 nm diameter pillar patterns were not fabricated using hydroxy-containing monomers. The filling behavior into silica holes of around 10 nm depended on the chemical structure of the monomers. Resonance shear measurements revealed the following: (1) The viscosities of hydroxy-containing monomers confined between chlorodimethyl(3,3,3-trifluoropropyl)silane (FAS3-Cl)-modified surfaces began to increase at distances shorter than those of the monomers between unmodified surfaces. (2) The monomers confined between tridecafluoro-1,1,2,2-tetrahydrooctyltrimethoxysilane-modified surfaces were squeezed out when the surface-surface distance decreased at less than 7 nm. The measured viscosities between the FAS3-Cl-modified silica surfaces were correlated with the insufficient filling behavior into the silica holes of around 10 nm in UV nanoimprinting. Contact angle measurements provided an additional insight that a higher wettability of the monomers onto the antisticking chemisorbed monolayers resulted in imprinted patterns with higher aspect ratios. Considering the increase in the monomer viscosity in the nanospace and the wettability of monomers onto chemisorbed monolayers, we concluded that the monomer showing low viscosity under confinement and high wettability onto the mold surface was suitable for single-digit nanometer UV nanoimprinting.

7.
J Infect Chemother ; 24(7): 544-548, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29627326

RESUMO

A central venous catheter (CVC) is a catheter placed into a large vein, and is used for chemotherapy administration. However, there is little confirmatory data on which antiseptic-such as chlorhexidine or povidone-iodine (PI) -is more protective against CVC-related infectious complications in patients receiving intensive chemotherapy. We aimed to compare the effectiveness of 1% chlorhexidine gluconate in 70% alcohol (CH) vs. PI for skin disinfection before CVC insertion in patients receiving intensive chemotherapy. Methods We used either CH or 10% PI as skin antiseptics before CVC insertion, and assessed which agent was more protective against CVC-related infection. The participants were 112 patients with haematologic malignancies who underwent chemotherapy; a total of 292 CVCs were inserted over this period. Blood cultures were obtained when febrile neutropenia occurred. The CVC was removed and the catheter-tip qualitatively cultured when catheter-related infection was suspected. The cumulative incidence of febrile neutropenia, microbial growth from blood or catheter-tip culture, and catheter-related blood stream infection (CRBSI) was evaluated retrospectively. A univariate Cox proportional hazards model showed that CH significantly alleviated infectious complications. Notably, no case of CRBSI occurred in the CH group. Multivariate analysis, adjusted for prolonged neutropenia (>15 days) and older age (>52 years), also showed significant reduction in the cumulative incidence of microbial growth from catheter-tips in the CH group (hazard ratio = 0.146, 95% confidence interval: 0.023-0.502, p = 0.0008). Disinfection using CH, compared with PI, can potentially decrease catheter-related infection without causing adverse skin reactions in patients with haematologic malignancies.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/microbiologia , Clorexidina/análogos & derivados , Neoplasias Hematológicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Cateterismo Venoso Central , Cateteres Venosos Centrais/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/sangue , Neutropenia Febril Induzida por Quimioterapia/microbiologia , Clorexidina/uso terapêutico , Desinfecção/métodos , Contaminação de Equipamentos , Etanol , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povidona-Iodo/uso terapêutico , Estudos Retrospectivos , Pele/microbiologia
8.
Rinsho Ketsueki ; 59(4): 395-400, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29743398

RESUMO

An 80-year-old man presented to our hospital with a thoracic vertebrae compression fracture. He was diagnosed with IgG-λ myeloma (International Staging System stage II, Durie-Salmon stage IIIA). Since melphalan-prednisolone (MP) was not effective, we treated him with lenalidomide and low-dose dexamethasone (DEX) (Ld), achieving a partial response. As DEX provoked edema and psychiatric symptoms, the patient disagreed with its use, and pomalidomide (POM) monotherapy was initiated. Although the POM dosage was reduced to 1-2 mg/day due to somnolence, which was reported as an adverse event, stringent complete response (sCR) was achieved and sustained for 10 months following 11 cycles of low-dose POM monotherapy. It is assumed that sCR was achieved with low-dose POM monotherapy due to its early introduction as well as there being no high-risk chromosomal abnormalities. Even though adverse events develop with a standard dose, a continuation of low-dose POM is considered more important than discontinuation.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Masculino , Talidomida/uso terapêutico
10.
Langmuir ; 31(14): 4188-95, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25793911

RESUMO

We used fluorescence microscopy to show that low adsorption of resin components by a mold surface was necessary for continuous ultraviolet (UV) nanoimprinting, as well as generation of a low release energy on detachment of a cured resin from a template mold. This is because with low mold pollution, fracture on demolding occurred at the interface between the mold and cured resin surfaces rather than at the outermost part of the cured resin. To achieve low mold pollution, we investigated the radical photopolymerization behaviors of fluorescent UV-curable resins and the mechanical properties (fracture toughness, surface hardness, and release energy) of the cured resin films for six types of di(meth)acrylate-based monomers with similar chemical structures, in which polar hydroxy and aromatic bulky bisphenol moieties and methacryloyl or acryloyl reactive groups were present or absent. As a result, we selected bisphenol A glycerolate dimethacrylate (BPAGDM), which contains hydroxy, bisphenol, and methacryloyl moieties, which give good mechanical properties, monomer bulkiness, and mild reactivity, respectively, as a suitable base monomer for UV nanoimprinting under an easily condensable alternative chlorofluorocarbon (HFC-245fa) atmosphere. The fluorescent UV-curable BPAGDM resin was used for UV nanoimprinting and lithographic reactive ion etching of a silicon surface with 32 nm line-and-space patterns without a hard metal layer.

11.
Langmuir ; 30(24): 7127-33, 2014 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-24892792

RESUMO

We investigated reactive fluorinated (meth)acrylate monomers and macromonomers that caused segregation at the cured resin surface of a viscous hydroxy-containing monomer, glycerol 1,3-diglycerolate diacrylate (GDD), and decreased the demolding energy in ultraviolet (UV) nanoimprinting with spin-coated films under a condensable alternative chlorofluorocarbon gas atmosphere. The X-ray photoelectron spectroscopy and contact angle measurements used to determine the surface free energy suggested that a nonvolatile silicone-based methacrylate macromonomer with fluorinated alkyl groups segregated at the GDD-based cured resin surface and decreased the surface free energy, while fluorinated acrylate monomers hardly decreased the surface free energy because of their evaporation during the annealing of the spin-coated films. The average demolding energy of GDD-based cured resins with the macromonomer having fluorinated alkyl groups was smaller than that with the macromonomer having hydrocarbon alkyl groups. The fluorinated alkyl groups were responsible for decreasing the demolding energy rather than the polysiloxane main chains. We demonstrated that the GDD-based UV-curable resin with the fluorinated silicone-based macromonomer was suitable for step-and-repeat UV nanoimprinting with a bare silica mold, in addition to silica molds treated by chemical vapor surface modification with trifluoro-1,1,2,2-tetrahydropropyltrimethoxysilane (FAS3) and tridecafluoro-1,1,2,2-tetrahydrooctyltrimethoxysilane (FAS13).

12.
J Phys Chem Lett ; 15(2): 659-664, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38206160

RESUMO

Diversity in structures of water endowed by a hydrogen-bonding network plays crucial roles in wide varieties of phenomena in nature. Chiral ordering of water molecules is an intriguing phenomenon from the viewpoint of bimolecular functions. However, experimental reports on chiral ordering have been limited to the water molecules interacting with biomolecules on the molecular scale. It remains unclear whether pure liquid water forms long-range chiral ordering without any interaction with biomolecules. Here, we show that chiral anisotropy can be observed in the macro/mesoscopic network pattern of an unknown water layer formed via spinodal phase separation-like dynamics at the interface between water and ice III with a chiral crystal structure. We named this unknown water homoimmiscible water. Our observations infer that the unknown water is a chiral liquid crystal. This possibility opens new avenues for a wide variety of research fields such as liquid polymorphism, biology, earth and planetary science, and so forth from the perspective of chirality.

13.
J Phys Chem Lett ; 15(6): 1564-1571, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38316420

RESUMO

Studies on chiral spectroscopy have recently demonstrated strong enhancement of chiral light-matter interaction in the chiral near-field of Mie resonance in high-refractive-index dielectric nanostructures by studies on chiral spectroscopy. This situation has motivated researchers to demonstrate effective chiral photosynthesis under a chiral near-field beyond circularly polarized light (CPL) as a chiral source. However, the effectivity of the chiral near-field of Mie resonance for chiral photosynthesis has not been clearly demonstrated. One major challenge is the experimental difficulty in evaluating enantiomeric excess of a trace amount of chiral products synthesized in the near-field. Here, by adopting sodium chlorate chiral crystallization as a phenomenon that includes both synthesis and the amplification of chiral products, we show that crystallization on a Mie-resonant silicon metasurface excited by CPL yields a statistically significant large crystal enantiomeric excess of ∼18%, which cannot be achieved merely by CPL. This result provides implications for efficient chiral photosynthesis in a chiral near-field.

14.
Biomedicines ; 12(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38927484

RESUMO

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.

15.
Sci Rep ; 13(1): 16227, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821508

RESUMO

Experimentally demonstrating the existence of waters with local structures unlike that of common water is critical for understanding both the origin of the mysterious properties of water and liquid polymorphism in single component liquids. At the interfaces between water and ices Ih, III, and VI grown/melted under pressure, we previously discovered low- and high-density unknown waters, that are immiscible with the surrounding water. Here, we show, by in-situ optical microscopy, that an unknown water appears at the ice V-water interface via spinodal-like dynamics. The dewetting dynamics of the unknown water indicate that its characteristic velocity is ~ 90 m/s. The time evolution of the characteristic length of the spinodal-like undulation suggests that the dynamics may be described by a common model for spinodal decomposition of an immiscible liquid mixture. Spinodal-like dewetting dynamics of the unknown water transiently showed anisotropy, implying the property of a liquid crystal.

16.
Leuk Lymphoma ; 64(1): 171-177, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36222572

RESUMO

We investigated the incidence, risk factors, and clinical outcomes of cytomegalovirus (CMV) disease in patients with B-cell lymphoma treated with a bendamustine-containing regimen. The incidence of CMV disease was analyzed after starting treatment with 139 regimens in 126 patients. Clinically significant CMV disease was observed in seven patients. The median duration between bendamustine initiation and the diagnosis of CMV disease was 69 d (range, 40-233), and the median of cycles completed at onset was 2 (range, 1-6). Furthermore, the incidence of CMV disease was significantly higher in the elderly patients than that in the younger patients. The target organs of CMV disease were the liver, gastrointestinal tract, lungs, and retinas. Antiviral therapy was administered to all patients. However, the recurrence of CMV disease was observed in two patients. This study provides information that could contribute to clinicians' decision-making on lymphoma therapy using bendamustine.


Assuntos
Infecções por Citomegalovirus , Linfoma , Humanos , Idoso , Cloridrato de Bendamustina/efeitos adversos , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Fatores de Risco , Antivirais/efeitos adversos , Estudos Retrospectivos
17.
Case Rep Oncol ; 16(1): 338-346, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37384208

RESUMO

Pulmonary veno-occlusive disease (PVOD) is an extremely rare condition in oncology practice. Although PVOD is clinically similar to pulmonary arterial hypertension, the conditions differ in terms of pathophysiology, management, and prognosis. This report discusses the case of a 47-year-old woman who developed dyspnea and fatigue after high-dose cyclophosphamide chemotherapy and autologous hematopoietic stem cell transplantation for relapsed lymphoma. The patient exhibited tachycardia, tachypnea, and hypotension, but other findings in the physical examination were unremarkable. The imaging studies showed no evidence of pulmonary embolism, but multiple ground-glass opacities and bilateral pleural effusions were observed on chest high-resolution computed tomography scans. In the right heart catheterization study, the mean pulmonary artery pressure and pulmonary vascular resistance were 35 mm Hg and 5.93 Wood units, respectively, with a normal pulmonary capillary wedge pressure of 10 mm Hg. Pulmonary function tests revealed a remarkable reduction in the percentage predicted value of diffusing capacity of the lungs for carbon monoxide to 31%. Lymphoma progression, collagen diseases, infectious diseases such as human immunodeficiency virus or parasitic infections, portal hypertension, and congenital heart disease were carefully excluded as these are also capable of causing pulmonary arterial hypertension. Thereafter, we reached a final diagnosis of PVOD. The patient was treated with supplemental oxygen and a diuretic during 1 month of hospitalization, which relieved her right heart overload symptoms. Herein, we present the patient's clinical course and diagnostic workup because misdiagnosis or inappropriate treatment can lead to unfavorable outcomes in patients with PVOD.

18.
Acc Chem Res ; 44(10): 1080-93, 2011 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-21786832

RESUMO

Recent advances in nanotechnology, materials science, and biotechnology have led to innovations in the field of nanomedicine. Improvements in the diagnosis and treatment of cancer are urgently needed, and it may now be possible to achieve marked improvements in both of these areas using nanomedicine. Lipid-coated nanoparticles containing diagnostic or therapeutic agents have been developed and studied for biomedical applications and provide a nanomedicine strategy with great potential. Lipid nanoparticles have cationic headgroups on their surfaces that bind anionic nucleic acids and contain hydrophobic drugs at the lipid membrane and hydrophilic drugs inside the hollow space in the interior. Moreover, researchers can design nanoparticles to work in combination with external stimuli such as magnetic field, light, and ionizing radiation, which adds further utility in biomedical applications. In this Account, we review several examples of lipid-based nanoparticles and describe their potential for cancer treatment and diagnosis. (1) The development of a lipid-based nanoparticle that included a promoter-enhancer and transcriptional activator greatly improved gene therapy. (2) The addition of a radiosensitive promoter to lipid nanoparticles was sufficient to confer radioisotope-activated expression of the genes delivered by the nanoparticles. (3) We successfully tailored lipid nanoparticle composition to increase gene transduction in scirrhous gastric cancer cells. (4) When lipophilic photosensitizing molecules were incorporated into lipid nanoparticles, those particles showed an increased photodynamic cytotoxic effect on the target cancer. (5) Coating an Fe(3)O(4) nanocrystal with lipids proved to be an efficient strategy for magnetically guided gene-silencing in tumor tissues. (6) An Fe(16)N(2)/lipid nanocomposite displayed effective magnetism and gene delivery in cancer cells. (7) Lipid-coated magnetic hollow capsules carried aqueous anticancer drugs and delivered them in response to a magnetic field. (8) Fluorescent lipid-coated and antibody-conjugated magnetic nanoparticles detected cancer-associated antigen in a microfluidic channel. We believe that the continuing development of lipid-based nanomedicine will lead to the sensitive minimally invasive treatment of cancer. Moreover, the fusion of different scientific fields is accelerating these developments, and we expect these interdisciplinary efforts to have considerable ripple effects on various fields of research.


Assuntos
Portadores de Fármacos/química , Monitoramento de Medicamentos/métodos , Lipídeos/química , Nanomedicina/métodos , Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/uso terapêutico , Humanos , Imãs/química , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética
19.
Cytokine ; 60(3): 694-700, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22929411

RESUMO

Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic-uremic syndrome (HUS). We assessed the kinetics of the release of cytokines such as neopterin, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α and the soluble forms of type I and II TNF receptors during EHEC O111-induced HUS (EHEC O111/HUS). Fourteen patients with EHEC O111/HUS were enrolled in this study. Serum concentrations of all cytokines other than TNF-α were significantly elevated in patients with severe HUS compared with those in patients with mild HUS. Although serum concentrations of TNF-α were not significantly higher in patients with severe HUS, most patients with acute encephalopathy showed elevated TNF-α levels. Serum concentrations of these cytokines rapidly and markedly increased, and massive hypercytokinaemia developed 1 day before the diagnosis of HUS in patients with severe HUS. Changes in the number of white blood cells and concentration of serum lactate dehydrogenase were significantly larger between the onset of hemorrhagic colitis and the time of the diagnosis of HUS in patients with severe HUS compared with those in patients with mild HUS. Proinflammatory cytokines play an important role in the pathogenesis of EHEC infection and development of severe complications, including HUS and encephalopathy. Monitoring the cytokine profile may be useful for assessing disease activity of EHEC O111 infections.


Assuntos
Citocinas/sangue , Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli/complicações , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/etiologia , Adolescente , Adulto , Criança , Infecções por Escherichia coli/microbiologia , Feminino , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Lactente , Interleucina-6/sangue , Interleucina-8/sangue , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Masculino , Neopterina/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
20.
Langmuir ; 28(31): 11646-53, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22780225

RESUMO

We describe the selective electrodeposition of submicrometer gold (Au) patterns achieved by a thin film resist layer of polystyrene (PS) that was exposed to ultraviolet (UV) light on a photoreactive monolayer of a benzophenone-containing alkylthiol formed on a Au-plated substrate and patterned by thermal nanoimprint lithography. The presence of a PS graft layer caused by the benzophenone monolayer photochemistry at an interface between the PS resist layer and photoreactive monolayer played the important role of suppressing the unfavorable growth of tiny Au grains in regions masked with the PS resist layer, resulting in the selective Au electrodeposition in aperture regions of PS resist patterns. The suppressive effect on selective Au electrodeposition depended on the molecular weight of PS used as a resist material. Among unimodal PSs having weight-average molecular weights (M(w)'s) of 2100, 10,900, and 106,000 g mol(-1), the PS of M(w) = 10,900 g mol(-1) functioned most effectively as the resist layer. Au electrodeposition at a low current density allowed the preparation of Au lines having widths of submicrometers and a uniform height independent of line widths in resist aperture regions. Submicrometer bump structures of Au lines could be fabricated on transparent silica substrates by the subsequent wet etching of a Au electrode layer and then a chromium adhesive layer.

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