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1.
Endocr J ; 71(4): 383-393, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38369332

RESUMO

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.


Assuntos
Índice de Massa Corporal , Cistos , Bócio , Nódulo da Glândula Tireoide , Ultrassonografia , Humanos , Feminino , Adolescente , Masculino , Prevalência , Criança , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Japão/epidemiologia , Cistos/epidemiologia , Cistos/diagnóstico por imagem , Cistos/patologia , Pré-Escolar , Lactente , Adulto Jovem , Bócio/epidemiologia , Bócio/diagnóstico por imagem , Inquéritos Epidemiológicos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia
2.
J AOAC Int ; 107(2): 234-241, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070143

RESUMO

BACKGROUND: Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs. Introduction of a physicochemical assay for GmS is needed to help ensure its quality and quantity. OBJECTIVE: This study aimed to develop quality control measures for GmS that could be complementary to quantitative assays and purity tests specified in the JP. METHODS: For each gentamicin C component (C1, C2, and C1a), theoretical potencies were determined based on the quantitative relationship between purity and potency, as measured by quantitative 1H NMR and microbiological assays, respectively. Two lots of the JP reference standard (RS) were used as test samples, with the contents of each component and impurity (sisomicin and garamine) being determined using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). RESULTS: The ratios of theoretical potency for C1, C2, and C1a were 1.00, 1.21, and 1.80, respectively. The potencies of the GmS JP RSs, which were estimated based on the contents and theoretical potency of each C component, corresponded well with those determined through microbiological assays. Marked differences in impurities (%) between the two RS lots were highlighted by quantifying sisomicin and garamine. CONCLUSIONS: The developed analytical procedure enabled the characterization of two different JP RSs in terms of content ratio, potencies, and impurities. HIGHLIGHTS: Novel analytical procedures useful for routine quality control of GmS were developed using HILIC-MS/MS.


Assuntos
Gentamicinas , Espectrometria de Massas em Tandem , Japão , Padrões de Referência , Antibacterianos , Cromatografia Líquida , Sisomicina , Interações Hidrofóbicas e Hidrofílicas
3.
Clin Pediatr Endocrinol ; 32(1): 52-57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761492

RESUMO

We previously described the thyroid volume, which was calculated by measuring the thyroid width, thickness, and longitudinal length using ultrasonography, in children and adolescents. We have proposed a simplified method for quantitatively assessing the thyroid size, to overcome the inaccuracy and challenges in measuring the longitudinal length of the thyroid. Based on measurements of 317,847 (girls: 156,913, boys: 160,934) children and adolescents, we calculated sex-specific means and standard deviations of thyroid width and thickness, and of the cross-sectional area computed by multiplying them, for every age and 0.1 m2 of body surface area, after ensuring normal distribution with Box-Cox transformation. Multivariate regression analysis revealed that female sex, age, and body surface area were independently associated with areas of each thyroid lobe. Our novel method may be useful in quantitatively assessing the thyroid size, and appropriately diagnosing pathological conditions, such as hypoplasia, atrophy, and enlargement of the thyroid gland, in children and adolescents.

4.
Int J Mol Sci ; 24(3)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36768491

RESUMO

Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D2, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E3 (PGE3) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE3 and 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker. High PGE3 levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE3 levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Distrofias Musculares , Humanos , Distrofias Musculares/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/complicações , ortoaminobenzoatos/farmacologia , ortoaminobenzoatos/uso terapêutico , Cardiomiopatias/complicações , Biomarcadores , Canais de Cátion TRPV/metabolismo
5.
J Pharm Biomed Anal ; 219: 114940, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35882176

RESUMO

In recent years, cosmetics deemed equivalent to pharmaceutical products containing prostaglandin F2α (PGF2α) analogs have been distributed overseas in the form of eyelash serums that can be purchased via the internet. The purpose of this study was to investigate the presence or absence of PGF2α analogs in eyelash serums procured in Japan via the internet to elucidate the actual composition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement system was developed for the determination of 14 PGF2α analogs in cosmetic serums. In total, 64 eyelash serum samples were purchased from 34 websites. After pretreatment, eyelash serum samples were screened for PGF2α analogs using the LC-MS/MS system. Products containing PGF2α analogs were subjected to quantification of these compounds. Of the 64 products, four were found to contain bimatoprost, among which, three did not indicate their contents on their package labels. In contrast, no samples were found to contain latanoprost, travoprost, or tafluprost, which are prescribed for glaucoma treatment. Additionally, eight products contained other PGF2α analogs, which have not been used as pharmaceuticals. The ease of access to cosmetic serums containing PGF2α analogs via online purchases presents a risk of serious side effects, particularly when consumers are not informed of their contents on the packages. This issue requires serious consideration to avoid the incorporation of pharmaceutical substances into cosmetic products.


Assuntos
Cosméticos , Espectrometria de Massas em Tandem , Anti-Hipertensivos , Bimatoprost , Cromatografia Líquida , Prostaglandinas F/efeitos adversos , Espectrometria de Massas em Tandem/métodos , Travoprost
6.
Sci Adv ; 7(47): eabj6895, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34788088

RESUMO

Epithelial barriers that prevent dehydration and pathogen invasion are established by tight junctions (TJs), and their disruption leads to various inflammatory diseases and tissue destruction. However, a therapeutic strategy to overcome TJ disruption in diseases has not been established because of the lack of clinically applicable TJ-inducing molecules. Here, we found TJ-inducing peptides (JIPs) in mice and humans that corresponded to 35 to 42 residue peptides of the C terminus of alpha 1-antitrypsin (A1AT), an acute-phase anti-inflammatory protein. JIPs were inserted into the plasma membrane of epithelial cells, which promoted TJ formation by directly activating the heterotrimeric G protein G13. In a mouse intestinal epithelial injury model established by dextran sodium sulfate, mouse or human JIP administration restored TJ integrity and strongly prevented colitis. Our study has revealed TJ-inducing anti-inflammatory physiological peptides that play a critical role in tissue repair and proposes a previously unidentified therapeutic strategy for TJ-disrupted diseases.

7.
Anal Bioanal Chem ; 413(30): 7549-7558, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34671824

RESUMO

Staphylococcus epidermidis are gram-positive bacteria that form a biofilm around implanted devices and develop an infection into a chronic state. Recently, it has been revealed that microvesicles have important roles in biofilm formation and intercellular communication among bacteria. However, biofilm formation of Staphylococcus epidermidis, and its relation to microvesicle secretion, is poorly understood because of the difficulty required to preserve the delicate water-rich morphology of biofilm for high-resolution observations. Here, we successfully imaged the microvesicles secreted from Staphylococcus epidermidis and the subsequent process of their integration into biofilm using liquid-phase imaging using atmospheric scanning electron microscopy (ASEM). In the biofilm, cells were connected by nanotube-like structures attached by microvesicles, and surrounded by extracellular polymeric substances. Cells cultured in the ASEM specimen holder were aldehyde-fixed and stained using positively charged nanogold labelling and/or using National Center for Microscopy and Imaging Research method. The samples immersed in aqueous radical scavenger glucose buffer were imaged by the inverted SEM of ASEM. Information regarding the morphologies of microvesicles, nanotube-like fibrils, and biofilm formed by Staphylococcus epidermidis is expected to be useful to elucidate the biological mechanism of biofilm formation and to develop a medicine against biofilms and their associated infections.


Assuntos
Biofilmes , Microscopia Eletrônica de Varredura/métodos , Staphylococcus epidermidis/metabolismo , Nanotubos , Coloração e Rotulagem , Infecções Estafilocócicas/microbiologia
8.
Mater Sci Eng C Mater Biol Appl ; 121: 111718, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579506

RESUMO

Biofilm infections present a serious problem because antibacterial drugs are not effective against mature biofilms or biofilms formed by drug-resistant bacteria. To address this issue, we developed a drug delivery system based on metal-decorated polymeric particles. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) is an amphiphilic polymer used in biomedical formulations, while silver nanoparticles are widely acknowledged to have high antibacterial activity. We prepared silver-decorated Soluplus® micelle nanoparticles with high antibacterial activity using the emulsion solvent diffusion method. Decoration of Soluplus® micelles with silver nanoparticles was found to increase their antibacterial activity. Scanning transmission electron microscopy-cathodoluminescence (STEM-CL) spectroscopy allows imaging of the spatial distribution of labeled targets and the chemical identification of materials. However, STEM-CL spectroscopy of fragile polymer materials is challenging. We optimized the STEM-CL spectroscopy technique to determine the distribution of silver nanoparticles in Soluplus® micelles. Additionally, the surface plasmon properties of the silver nanoparticles were successfully characterized without deactivation. The developed silver-decorated Soluplus® nanoparticles were effective against biofilm infections and have the potential to be applied for other biofilm-related diseases. Additionally, the optimized STEM-CL spectroscopy technique is expected to contribute to the analysis and imaging of fragile polymer materials, as well as other soft materials such as cells and tissues.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Biofilmes , Microscopia Eletrônica de Transmissão e Varredura , Polietilenoglicóis , Polivinil , Análise Espectral
9.
Toxins (Basel) ; 11(7)2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277504

RESUMO

Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in Escherichia coli O157:H7 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. However, little is known about its inhibitory mechanism. In this study, we demonstrate that the ZorO localized in the inner membrane affects the plasma membrane integrity and potential when expressed in E. coli cells, which triggers the production of cytotoxic hydroxyl radicals. We further show that five internal amino acids (Ala-Leu-Leu-Arg-Leu; ALLRL) of ZorO are necessary for its toxicity. This result prompted us to address the potential of the synthetic ALLRL peptide as an antimicrobial. Exogenously-added ALLRL peptide to Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a fungus, Candida albicans, trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, E. coli. The ALLRL peptide retains its activity under the physiological salt concentrations, which is in contrast to natural antimicrobial peptides. Importantly, this peptide has no toxicity against mammalian cells. Taken together, an effective and short peptide, ALLRL, would be an attractive antimicrobial to Gram-positive bacteria and C. albicans.


Assuntos
Anti-Infecciosos/toxicidade , Bacillus subtilis/efeitos dos fármacos , Toxinas Bacterianas/química , Candida albicans/efeitos dos fármacos , Proteínas de Escherichia coli/química , Oligopeptídeos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Animais , Bacillus subtilis/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cricetinae , Escherichia coli , Staphylococcus aureus/crescimento & desenvolvimento
10.
BMJ Case Rep ; 12(1)2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30700467

RESUMO

Anticoagulants have recently been recognised as a cause of acute kidney injury (AKI). We describe the case of a 75-year-old man with IgA vasculitis and atrial fibrillation treated with rivaroxaban, who presented with macroscopic haematuria and an acute decline in renal function. Two months before referral, he noted palpable purpuric lesions and was diagnosed with IgA vasculitis based on skin biopsy findings; the skin lesion disappeared following treatment with a steroid external preparation. Renal biopsy revealed glomerular haemorrhage and red blood cell casts. Although rivaroxaban was withdrawn, his kidney function worsened and he was started on haemodialysis. His renal function did not recover. To the best of our knowledge, this is the first case of direct oral anticoagulant (DOAC)-related AKI in systemic vasculitis. During DOAC therapy, close monitoring of a patient's urinalysis results and their renal function may be required for patients with systemic vasculitis to avoid AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Vasculite/tratamento farmacológico , Injúria Renal Aguda/terapia , Idoso , Diagnóstico Diferencial , Humanos , Imunoglobulina A , Masculino , Diálise Renal
11.
Mater Sci Eng C Mater Biol Appl ; 97: 78-83, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678968

RESUMO

Ionic liquids (ILs) containing imidazolium cations have a number of useful properties, such as high permeability to cells, high antimicrobial activity, and good biocompatibility. With the aid of ILs, transdermal delivery, solubilization of poorly soluble drugs were developed and therapeutic effects were improved. In this work, 1­butyl­3­methylimidazolium hexafluorophosphate-incorporated, chitosan-modified, submicron-sized poly(dl­lactide­co­glycolide) (PLGA) nanoparticles (NPs) were prepared using the emulsion solvent diffusion method for the treatment of biofilm infections. Prepared IL-incorporated PLGA NPs using surfactants such as Tween-80 and poloxamer-188 showed a high antibacterial activity to the bacterial cells under the biofilm. Additionally, antibacterial mechanism of IL-incorporated PLGA NPs was revealed by annular dark field scanning transmission electron microscopy combined a simple sample pretreatment method. We established a drug delivery system using IL-incorporated PLGA NPs to enhance the potential of polymeric nanocarriers for treating biofilm infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Líquidos Iônicos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Imidazóis/química , Infecções/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Microscopia Eletrônica de Varredura , Nanopartículas/administração & dosagem , Poloxâmero/química , Polissorbatos/química , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/fisiologia , Tensoativos/química
12.
Biophys J ; 116(1): 92-103, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30580923

RESUMO

Sec14, the major yeast phosphatidylcholine (PC)/phosphatidylinositol (PI) transfer protein (PITP), coordinates PC and PI metabolism to facilitate an appropriate and essential lipid signaling environment for membrane trafficking from trans-Golgi membranes. The Sec14 PI/PC exchange cycle is essential for its essential biological activity, but fundamental aspects of how this PITP executes its lipid transfer cycle remain unknown. To address some of these outstanding issues, we applied time-resolved small-angle neutron scattering for the determination of protein-mediated intervesicular movement of deuterated and hydrogenated phospholipids in vitro. Quantitative analysis by small-angle neutron scattering revealed that Sec14 PI- and PC-exchange activities were sensitive to both the lipid composition and curvature of membranes. Moreover, we report that these two parameters regulate lipid exchange activity via distinct mechanisms. Increased membrane curvature promoted both membrane binding and lipid exchange properties of Sec14, indicating that this PITP preferentially acts on the membrane site with a convexly curved face. This biophysical property likely constitutes part of a mechanism by which spatial specificity of Sec14 function is determined in cells. Finally, wild-type Sec14, but not a mixture of Sec14 proteins specifically deficient in either PC- or PI-binding activity, was able to effect a net transfer of PI or PC down opposing concentration gradients in vitro.


Assuntos
Fosfatidilcolinas/metabolismo , Fosfatidilinositóis/metabolismo , Proteínas de Transferência de Fosfolipídeos/química , Proteínas de Saccharomyces cerevisiae/química , Difração de Nêutrons , Fosfatidilcolinas/química , Fosfatidilinositóis/química , Proteínas de Transferência de Fosfolipídeos/metabolismo , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/metabolismo , Espalhamento a Baixo Ângulo , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo
13.
J Biomed Mater Res B Appl Biomater ; 106(3): 1280-1285, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28636123

RESUMO

In the medical biology, it is essential to understand not only biological morphology but also the interaction between biological materials and agents. To study these, electron microscopy (EM) is often utilized. However, sample preparation techniques for EM require a high level of skill and a considerable time. Here, we conducted EM using a simple technique employing a conductive liquid, BEL-1, and compared the results with another simple technique employing an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ]). BEL-1 was used for sample pretreatment, and the morphologies of the mouse RAW 264.7 cell line, Porphyromonas gingivalis, and the RAW 264.7 cell line were stimulated via co-incubation with P. gingivalis and observed using field emission scanning EM (FE-SEM). In the present study, the inflammation-induced system of P. gingivalis was successfully established. FE-SEM results revealed the fine morphology of the RAW 264.7 cell line and P. gingivalis and confirmed a morphological change in the RAW 264.7 cell line caused by P. gingivalis stimulation. Using the developed sample preparation technique employing BEL-1, high-contrast and high-resolution observations of deformable biological materials were conducted without any difficulty or the necessity for complicated technique. This morphological information and the developed techniques can contribute to reveal the interaction between biological materials and agents and thereby accelerate drug formulation and disease treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1280-1285, 2018.


Assuntos
Teste de Materiais/métodos , Porphyromonas gingivalis , Células RAW 264.7/ultraestrutura , Animais , Tamanho Celular , Citocinas/biossíntese , Gengivite/microbiologia , Gengivite/patologia , Líquidos Iônicos , Camundongos , Microscopia Eletrônica de Varredura
14.
Eur J Pharm Sci ; 111: 205-214, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28893625

RESUMO

The aim of this study was to prepare and characterize solid dispersion particles with a novel amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, as a water-soluble carrier. Solid dispersion particles were prepared by hot-melt extrusion and spray drying. Indomethacin (IMC) was used as a model comprising drugs with low solubility in water and d-mannitol (MAN) was used as an excipient. The physicochemical properties of prepared particles were characterized by scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, FTIR spectra analysis, and drug release studies. Stability studies were also conducted under stress conditions at 40°C, 75% relative humidity. We found that dissolution behavior of the original drug crystal could be improved by solid dispersion with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. The PXRD pattern and thermal analysis indicated that the solid dispersion prepared with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC was in an amorphous state. FTIR spectra analysis indicated that the interaction manner between the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC may differ with the preparation method and formulation of solid dispersions. Stability studies proved that the amorphous state of IMC in solid dispersion particles was preserved under stress conditions for more than two weeks.


Assuntos
Indometacina/química , Manitol/química , Polietilenoglicóis/química , Polivinil/química , Simulação por Computador , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Microscopia Eletrônica de Varredura , Modelos Químicos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Int J Pharm ; 531(2): 588-594, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28663084

RESUMO

The crystal structure of an inclusion complex of ß-cyclodextrin (ß-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two ß-CD, and several water molecules. ß-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (ß-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of ß-CD and one guest molecule. Fentanyl is totally contained within the ß-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the ß-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations.


Assuntos
Fentanila/química , beta-Ciclodextrinas/química , Química Farmacêutica , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares
16.
Mater Sci Eng C Mater Biol Appl ; 76: 1066-1074, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28482470

RESUMO

In drug delivery systems employing polymeric nanoparticles, accurate delivery of drugs to target sites such as bacterial cells, cell tissues, and organelles is essential. In particular, when designing drug delivery systems for the treatment of the biofilm infections, evaluation of the interaction between polymeric nanoparticles and biofilm or bacterial cells using a simple technique is of significant importance. Here we develop two types of novel techniques for the biological imaging of the intracellular behavior of two types of polymeric nanoparticles, biodegradable chitosan-modified poly (dl-lactide-co-glycolide) (PLGA) nanoparticles and chitosan-modified polyvinyl caprolactam - polyvinyl acetate -polyethylene glycol graft copolymer (Soluplus®, Sol) nanoparticles, within a Staphylococcus epidermidis biofilm. As the first technique, Raman imaging of unstained biological materials using slit-scanning confocal Raman microscopy (unstained Raman imaging) was performed, and as the second, field-emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analysis of biological materials labeled with quantum dots (SEM-QD imaging) was demonstrated. These analyses revealed differing localization of the respective nanoparticles within the biofilm in accordance with the specific interactions of PLGA nanoparticles and Sol nanoparticles with the biofilm. These novel techniques open the door to biological imaging and analyses with high spatial resolution, which will help to understand the efficacy of drug delivery to target materials.


Assuntos
Nanopartículas , Biofilmes , Ácido Láctico , Microscopia Confocal , Microscopia Eletrônica de Varredura , Ácido Poliglicólico , Análise Espectral , Staphylococcus epidermidis , Raios X
17.
Yakugaku Zasshi ; 137(4): 477-484, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28381726

RESUMO

Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients with surgically untreatable malignant tumors. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. To overcome these problems, we modified the formulation of Mohs paste by excluding starch, which is the cause of physical changes, and investigated the base. In the modified Mohs paste using the macrogol ointment for the base, no marked change with time was noted in the hardness, malleability, or elongation property, and the water-absorbing properties were equivalent to those of Mohs paste immediately after preparation. The hardness did not decrease even after absorbing water. The drug release rate increased 1.5 times with the modified Mohs paste. Based on these findings, the risk of liquefaction-associated damage of the surrounding skin decreased on using the modified Mohs paste, and preparing in advance became possible. These results suggest that the modified Mohs paste using the macrogol ointment for the base exhibits an equivalent effect for control of exudate and a high effect for tissue fixation.


Assuntos
Cloretos , Composição de Medicamentos/métodos , Compostos de Zinco , Óxido de Zinco , Fenômenos Químicos , Bases para Pomadas , Pomadas , Polietilenoglicóis , Amido
18.
Med Mol Morphol ; 50(1): 9-16, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27119723

RESUMO

In this study, we developed a drug delivery system (DDS) using polymeric nanocarriers for the treatment of biofilm infection disease. Clarithromycin (CAM)-encapsulated and chitosan (CS) modified polymeric nanoparticles (NPs) were prepared using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) (Sol) and poly-(DL-lactide-co-glycolide), respectively. To understand the availability of the prepared NPs, we made morphological observations of the antibacterial activity derived from the NPs toward the bacterial cells within the biofilm using scanning electron microscopy and transmission electron microscopy measurements. These results revealed different antibacterial activities for the two types of drug carriers. In the case of CAM-encapsulated + CS-modified Sol micelles treatment, NPs can exert their antibacterial activity not only by the surfactant, CAM and CS effects but also by intrusion into the bacterial cells. Thereby, CAM-encapsulated + CS-modified Sol micelles had a higher antibacterial activity. The morphological information is useful to design suitable NPs for the treatment against biofilm infections.


Assuntos
Biofilmes/efeitos dos fármacos , Claritromicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Antibacterianos/farmacologia , Quitosana/química , Contagem de Colônia Microbiana , Ácido Láctico/química , Micelas , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Eletricidade Estática
19.
J Biomed Mater Res B Appl Biomater ; 105(6): 1432-1437, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27086715

RESUMO

In this study, we developed a scanning transmission electron microscopy (STEM) method for imaging the antibacterial activity of organic polymeric nanoparticles (NPs) toward biofilms formed by Staphylococcus epidermidis bacterial cells, for optimizing NPs to treat biofilm infections. The combination of sample preparation method using a hydrophilic ionic liquid (IL) and STEM observation using the cooling holder eliminates the need for specialized equipment and techniques for biological sample preparation. The annular dark-field STEM results indicated that the two types of biodegradable poly-(DL-lactide-co-glycolide) (PLGA) NPs: PLGA modified with chitosan (CS), and clarithromycin (CAM)-loaded + CS-modified PLGA, prepared by emulsion solvent diffusion exhibited different antibacterial activities in nanoscale. To confirm damage to the sample during STEM observation, we observed the PLGA NPs and the biofilm treated with PLGA NPs by both the conventional method and the newly developed method. The optimized method allows microstructure of the biofilm treated with PLGA NPs to be maintained for 25 min at a current flow of 40 pA. The developed simple sample preparation method would be helpful to understand the interaction of drugs with target materials. In addition, this technique could contribute to the visualization of other deformable composite materials at the nanoscale level. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1432-1437, 2017.


Assuntos
Antibacterianos , Biofilmes/efeitos dos fármacos , Líquidos Iônicos , Microscopia Eletrônica de Transmissão e Varredura , Nanopartículas/química , Staphylococcus epidermidis , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Quitosana/farmacologia , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Nanopartículas/ultraestrutura , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Staphylococcus epidermidis/fisiologia , Staphylococcus epidermidis/ultraestrutura
20.
Mater Sci Eng C Mater Biol Appl ; 72: 143-149, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28024570

RESUMO

Understanding of self-protection activity of the bacteria and interaction with drug substances has significant importance for designing of effective drug delivery system for treatment of biofilm infections. Recently silver nanoparticle has attracted attention as antibacterial substance for drug delivery system because of its high antibacterial activity. Here, efflux of silver nanoparticles obtained from within the prepared silver-decorated poly (DL-lactide-co-glycolide) (Ag PLGA) nanoparticles derived from Staphylococcus epidermidis bacterial cell was successfully visualized using scanning transmission electron microscopy (STEM). We also revealed the interaction between prepared Ag PLGA nanoparticles and the bacterial cells at the nanoscale level using field emission scanning electron microscopy and STEM, after a pretreatment process by an ionic liquid. This finding is significant to understand a fundamental function of S. epidermidis bacterial cells, which is not explored previously. The results suggest that Ag PLGA nanoparticles could demonstrate high efficacy against biofilm infections.


Assuntos
Ácido Láctico/química , Nanopartículas Metálicas/química , Ácido Poliglicólico/química , Prata/química , Staphylococcus epidermidis/fisiologia , Biofilmes/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/toxicidade , Microscopia Eletrônica de Varredura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
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