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1.
J Clin Imaging Sci ; 14: 20, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38975058

RESUMEN

Objectives: The objectives of this study were to clarify the pathological features of clinically significant prostate cancer (csPC) that is undetectable on multiparametric magnetic resonance imaging (mpMRI). Material and Methods: This single-center and retrospective study enrolled 33 men with prostate cancer (PC), encompassing 109 PC lesions, who underwent mpMRI before radical prostatectomy. Two radiologists independently assessed the mpMR images of all lesions and compared them with the pathological findings of PC. All PC lesions were marked on resected specimens using prostate imaging reporting and data system version 2.1 and classified into magnetic resonance imaging (MRI)-detectable and MRI-undetectable PC lesions. Each lesion was classified into csPC and clinically insignificant PC. Pathological characteristics were compared between MRI-detectable and MRI-undetectable csPC. Statistical analysis was performed to identify factors associated with MRI detectability. A logistic regression model was used to determine the factors associated with MRI-detectable and MRI-undetectable csPC. Results: Among 109 PC lesions, MRI-detectable and MRI-undetectable PCs accounted for 31% (34/109) and 69% (75/109) of lesions, respectively. All MRI-detectable PCs were csPC. MRI-undetectable PCs included 30 cases of csPC (40%). The detectability of csPC on mpMRI was 53% (34/64). The MRI-undetectable csPC group had a shorter major diameter (10.6 ± 6.6 mm vs. 19.0 ± 6.9 mm, P < 0.001), shorter minor diameter (5.7 ± 2.9 mm vs. 10.7 ± 3.4 mm, P < 0.001), and lower percentage of lesions with Gleason pattern 5 (17% vs. 71%, P < 0.001). Shorter minor diameter (odds ratio [OR], 2.62; P = 0.04) and lower percentage of Gleason pattern 5 (OR, 24; P = 0.01) were independent predictors of MRI-undetectable csPC. Conclusion: The pathological features of MRI-undetectable csPC included shorter minor diameter and lower percentage of Gleason pattern 5. csPC with shorter minor diameter may not be detected on mpMRI. Some MRI-undetectable csPC lesions exhibited sufficient size and Gleason pattern 5, emphasizing the need for further understanding of pathological factors contributing to MRI detectability.

2.
ACS Omega ; 9(6): 7123-7131, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38371820

RESUMEN

Substrate optimization is a time- and resource-consuming step in organic synthesis. Recent advances in chemo- and materials-informatics provide systematic and efficient procedures utilizing tools such as Bayesian optimization (BO). This study explores the possibility of reducing the required experiments further by utilizing computational Gibbs energy barriers. To thoroughly validate the impact of using computational Gibbs energy barriers in BO-assisted substrate optimization, this study employs a computational Gibbs energy barrier data set in the literature and performs an extensive numerical investigation virtually regarding the Gibbs energy barriers as virtual experimental results and those with systematic and random noises as virtual computational results. The present numerical investigation shows that even the computational reactivity affected by noises of as much as 20 kJ/mol helps reduce the number of required experiments.

3.
Acta Radiol Open ; 12(12): 20584601231220324, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38075408

RESUMEN

Background: The assessment of small metastatic liver tumours using dual-energy computed tomography (DECT) has not been fully established. Purpose: To assess the effect of low-keV virtual monochromatic imaging (VMI) with non-contrast and contrast-enhanced DECT on the qualitative and quantitative image parameters of small liver metastases. Material and methods: Two radiologists retrospectively evaluated 92 metastatic liver tumours (5-20 mm) in 32 patients. Non-contrast and contrast-enhanced VMI were reconstructed at seven energy levels (40-100 keV) with 10-keV intervals. Lesion boundary, lesion delineation, image noise, and overall image quality were evaluated using the visual analogue scale. A high subjective score indicates good overall image quality, clear nodal boundaries and delineation, and less noticeable image noise. Subjective scores were compared using the Kruskal-Wallis test. A quantitative analysis involving the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was performed. Results: The lesion boundary was highest at 40 keV and significantly improved during the non-contrast portal venous phase compared to that at higher keV (p < .005). The lesion delineation score was significantly higher at 40 keV and tended to decrease at higher keV. Image noise and overall image quality were rated low at low keV; however, those at 80, 90, and 100 keV were rated the highest (p < .005). The CNR and SNR were highest for non-contrast CT at 100 keV. During the portal venous phase, no significant differences were observed in CNR and SNR at each keV. Conclusion: Low-keV imaging using non-contrast and contrast-enhanced DECT is useful for delineating small hepatic metastatic tumours.

4.
Cardiovasc Intervent Radiol ; 46(11): 1632-1640, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37759091

RESUMEN

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.


Asunto(s)
Antibacterianos , Medios de Contraste , Humanos , Yopamidol , Cefazolina , Microesferas , Polímeros , Lidocaína , Analgésicos
5.
Radiol Oncol ; 57(2): 229-238, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37078697

RESUMEN

BACKGROUND: The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). PATIENTS AND METHODS: This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. RESULTS: Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). CONCLUSIONS: ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/epidemiología , Pulmón , Neumonitis por Radiación/etiología
6.
Med Dosim ; 47(1): 98-102, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34686403

RESUMEN

This study aimed to verify the accuracy of auto-contouring and auto-dose optimization for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT). Head computed tomography (CT) images of 15 patients were selected. The regions of interest, containing the brain, hippocampus, eyes, and lacrimal glands, were contoured manually and automatically on CT images. They were compared and evaluated for concordance rates using the Simpson coefficient. To verify the performance of dose optimization, auto-dose planning was compared with manual planning for 15 cases. All optimization plans were performed using the volumetric modulated arc therapy technique. The automatically contoured brain showed a very high concordance rate with the manually contoured brain; the Simpson coefficient was 0.990 ± 0.01. Contrastingly, the concordance rate of the hippocampal contour was low at 0.642 ± 0.15 (right) and 0.500 ± 0.16 (left); however, the rate improved to 0.871 ± 0.09 (right) and 0.852 ± 0.11 (left) with an additional 3-mm margin. For 2% of each planning target volume with the prescribed dose (D2%) and Dmean, there was no significant difference between the automatic and manual plans (35.50 Gy vs 35.23 Gy; p = 0.233 and 33.09 Gy vs 32.84 Gy; p = 0.073, respectively). The D98% was significantly better for the manual plan than for the automatic plan (25.49 Gy vs 26.11 Gy; p < 0.01). Dmax and D100% for the hippocampus did not show any significant difference between the automatic and manual plans (15.65, 16.09 Gy (right, left) vs 15.51, 15.80 Gy; p = 0.804, 0.233 and 8.08, 8.03 Gy vs 8.13, 8.01 Gy; p = 0.495, 1 respectively). The accuracy of auto-contouring for HA-WBRT can be guaranteed by providing an appropriate margin, and the precision of the auto-dose optimization was comparable to that of the manual plan.


Asunto(s)
Neoplasias Encefálicas , Radioterapia de Intensidad Modulada , Encéfalo , Irradiación Craneana , Hipocampo , Humanos , Tratamientos Conservadores del Órgano , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
7.
Mol Inform ; 41(3): e2100216, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34661976

RESUMEN

Theoretical reaction screening based on Gibbs energy barriers would be promising to accelerate chemical reactions mining. The number of quantum chemical calculations can be reduced by using an optimization algorithm such as genetic algorithm (GA) and Bayesian optimization (BO). The focus of this study is to generate a dataset of reaction barriers of size ∼100000. Such a dataset would be useful to quickly evaluate various implementations of an optimization algorithm such as GA and BO. The dataset includes Gibbs energy barriers of the Claisen rearrangement for ∼100000 molecules computed on the basis of a semiempirical theory PM7. After evaluating its chemical and numerical features, it is found that the dataset well reflects chemical trends of various substitutions and is useful in testing various implementations of an optimization algorithm. The dataset is available in the supplementary material of this paper.


Asunto(s)
Teorema de Bayes
8.
Biol Pharm Bull ; 44(12): 1866-1871, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34853269

RESUMEN

In this study, we focused on a nuclear localization signal (NLS)-based versatile peptide vector, designed by us, combined with electroporation (EP) to establish an efficient gene delivery system to non-dividing or slow growing dendritic cells. We determined the intranuclear transport, gene expression, and cell viability in JAWS II mouse dendritic cells transfected with the green fluorescent protein (GFP) expression plasmid DNA alone (naked pEGFP); positive charged complex of NLS derivative STR-CH2SV40H2C, and pEGFP (binary complex); or negative charged complex of the binary complex with a biocompatible polyanion, γ-polyglutamic acid (ternary complex) combined with or without EP application. Although the binary complex showed higher nuclear transport and GFP expression in the absence of EP than those for naked pEGFP, the combination of EP significantly decreased the cell viability and did not improve the efficiency of compared gene expression. However, in the ternary complex, the intranuclear transport and GFP expression efficiency were significantly higher than those of naked pEGFP and the binary complex when combined with EP, and there was no decrease in cell viability. The results suggest that polyanion-coated ternary complex with EP is useful for non-viral gene delivery system into non-dividing cells for ex vivo gene/cell therapy.


Asunto(s)
Núcleo Celular , Células Dendríticas , Electroporación , Técnicas de Transferencia de Gen , Terapia Genética , Señales de Localización Nuclear , Polímeros , Animales , Antígenos Transformadores de Poliomavirus , Supervivencia Celular , ADN , Expresión Génica , Vectores Genéticos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Inmunoterapia , Ratones , Neoplasias/terapia , Oligopéptidos , Plásmidos , Ácido Poliglutámico/análogos & derivados , Transfección
9.
Rinsho Shinkeigaku ; 61(12): 856-861, 2021 Dec 22.
Artículo en Japonés | MEDLINE | ID: mdl-34789630

RESUMEN

An 82-year-old man presented with subacute bilateral lower limb paralysis, deep sensory disturbance, and vesico-rectal disturbance. MRI of the spinal cord revealed a large gray matter-dominant lesion extending from the medulla oblongata to the lower thoracic spinal cord. The patient was treated with steroid-pulse therapy for myelitis, but without symptomatic improvement. A spinal cord biopsy was performed for treatment-resistant myelopathy, and histopathology revealed a diffuse large B-cell lymphoma, that was diagnosed as a primary intramedullary spinal cord lymphoma because systemic examination didn't show any other findings suggestive of malignant lymphoma. A spinal cord biopsy is necessary for the definitive diagnosis of this disease, but in the case of poor response to treatment and a progressive course, intramedullary malignant lymphoma should be considered if there is a persistent elevation of CSF IL-10 or a prolonged contrast effect.


Asunto(s)
Linfoma de Células B Grandes Difuso , Enfermedades de la Médula Espinal , Neoplasias de la Médula Espinal , Anciano de 80 o más Años , Biopsia , Gadolinio , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Médula Espinal , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/etiología , Neoplasias de la Médula Espinal/diagnóstico por imagen
10.
Mol Pharm ; 18(3): 1038-1047, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395310

RESUMEN

Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin: the stratum corneum (SC) and tight junctions. We have previously reported that atopic dermatitis of skin without the SC can be efficiently treated by the intradermal administration of trans-activator of transcription (Tat) peptide and AT1002 (tight junction opening peptide). However, novel drug delivery systems are needed for effective SC penetration. Therefore, in the present study, we aimed to develop a lyotropic liquid crystalline (LC) system containing Tat and AT1002 for effective siRNA penetration through the SC. An LC formulation was prepared using selachyl alcohol and purified water, and its skin penetration ability was evaluated. No fluorescence was observed in mouse skin treated with a siRNA solution, as there was no intradermal localization of siRNA from naked siRNA. However, intradermal delivery of siRNA was remarkable and extensive with the LC formulation containing both Tat and AT1002. Semiquantitative analysis by brightness measurement revealed that the LC formulation containing both Tat and AT1002 had significantly enhanced intact skin permeability than other formulations. These results show that the functional peptides in the LC formulation increased SC penetration and intradermal delivery in the healthy skin. Therefore, this novel LC system may be useful in the treatment of various skin diseases.


Asunto(s)
Cristales Líquidos/química , ARN Interferente Pequeño/administración & dosificación , Piel/efectos de los fármacos , Piel/metabolismo , Animales , Dermatitis Atópica/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Epidermis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Oligopéptidos/administración & dosificación , Péptidos/administración & dosificación , Permeabilidad , Calidad de Vida , Absorción Cutánea/fisiología , Uniones Estrechas/efectos de los fármacos
11.
Interv Radiol (Higashimatsuyama) ; 6(1): 4-8, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35910525

RESUMEN

We report the usefulness of cone-beam computed tomography angiography (CBCTA) and automated vessel detection (AVD) software in transcatheter arterial embolization in two cases of obscure ascending colonic diverticular hemorrhage after unsuccessful endoscopic clipping. Arteriography of the superior mesenteric artery demonstrated no active bleeding. Considering the positional relationship of the clips, we could narrow the responsible vessel down to two candidates but could not definitively identify the responsible vessel. We performed CBCTA at the marginal artery of the right colic artery, and the responsible branch was identified using AVD. The responsible vessel could be embolized, and hemostasis was achieved with no ischemic complications. CBCTA and AVD software for colonic diverticular hemorrhage after endoscopic clipping were useful for identifying the responsible vessel and in performing selective embolization.

12.
Int J Hematol ; 112(4): 544-552, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32572828

RESUMEN

Although patients with cancer and immunosuppression are at a risk of functional hyposplenism, how to detect it promptly remains unclear. Since hyposplenism allows erythrocytes with nuclear remnants (Howell-Jolly bodies [HJBs]) to appear in the peripheral blood, HJB detection by a routine microscopic examination may help identify patients with functional hyposplenism. This prospective study was thus performed to determine the underlying diseases in patients who presented with HJBs. Of 100 consecutive patients presenting with HJBs, 73 had a history of splenectomy. The remaining 27 had hematologic cancer (n = 6, 22%), non-hematologic cancer (n = 8, 30%), hepatic disorders (n = 4, 15%), premature neonates (n = 3, 11%), hemolytic anemia (n = 2, 7%), autoimmune disorders (n = 2, 7%) and miscellaneous diseases (n = 2, 7%), and their prior treatments included chemotherapy (n = 8, 30%), steroids (n = 7, 26%) and molecular-targeted therapy (n = 3, 11%). Among the 27 patients, 22 had computed tomography scans available: 3 (14%) had underlying diseases in the spleen, and the remaining 19 (86%) were all found to have a decreased splenic volume, including 11 (50%) with more than 50% of the ideal value. The present findings suggest that HJB detection identifies patients with potentially functional hyposplenism who should receive appropriate interventional treatment, such as vaccination and prophylactic antibiotics.


Asunto(s)
Inclusiones Eritrocíticas/patología , Inclusiones Eritrocíticas/ultraestructura , Eritrocitos/citología , Eritrocitos/patología , Enfermedades del Bazo/sangre , Enfermedades del Bazo/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades del Bazo/etiología , Adulto Joven
13.
Eur J Pharm Biopharm ; 152: 85-94, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32387702

RESUMEN

We previously developed a nose-to-brain delivery system using poly(ethylene glycol)-polycaprolactone block polymeric micelles modified by a cell-penetrating peptide, Tat (PEG-PCL-Tat). This system showed excellent delivery of the anti-cancer drug camptothecin to the brain and improved therapeutic efficacy in a brain tumor model. However, improvements are necessary to selectively deliver drugs to tumor sites once they enter the brain, and avoid toxic side effects to normal brain tissue. In this study, to develop tumor-selective novel polymeric micelles, mixed micelles consisting of Tat-conjugated polymer micelles and stearoyl-modified bombesin (Bom/PEG-PCL-Tat) were designed. The GRPR selectivity, cellular uptake, and cytotoxicity in C6 glioma cells as well as the intracerebral drug distribution and therapeutic efficacy of Bom/PEG-PCL-Tat mixed micelles after intranasal administration in C6 glioma orthotropic grafted rats were evaluated. Selective cellular uptake and marked cytotoxic effects against GRPR-expressing C6 glioma cells were observed, as well as C6 tumor tissue-specific accumulation in vivo. Rats treated with camptothecin subsequent to a brain tumor graft survived longer when the drug was delivered by Bom/PEG-PCL-Tat mixed micelles than by PEG-PCL-Tat micelles.


Asunto(s)
Antineoplásicos/administración & dosificación , Encéfalo/efectos de los fármacos , Péptidos de Penetración Celular/química , Glioma/tratamiento farmacológico , Nanopartículas/química , Nariz/efectos de los fármacos , Polímeros/química , Administración Intranasal , Animales , Antineoplásicos/química , Bombesina , Neoplasias Encefálicas/tratamiento farmacológico , Camptotecina , Línea Celular Tumoral , Portadores de Fármacos/química , Ligandos , Masculino , Micelas , Tamaño de la Partícula , Poliésteres/química , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley
14.
Sci Data ; 7(1): 103, 2020 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-32218461

RESUMEN

As the most abundant animals on earth, nematodes are a dominant component of the soil community. They play critical roles in regulating biogeochemical cycles and vegetation dynamics within and across landscapes and are an indicator of soil biological activity. Here, we present a comprehensive global dataset of soil nematode abundance and functional group composition. This dataset includes 6,825 georeferenced soil samples from all continents and biomes. For geospatial mapping purposes these samples are aggregated into 1,933 unique 1-km pixels, each of which is linked to 73 global environmental covariate data layers. Altogether, this dataset can help to gain insight into the spatial distribution patterns of soil nematode abundance and community composition, and the environmental drivers shaping these patterns.


Asunto(s)
Distribución Animal , Nematodos/clasificación , Animales , Ecosistema , Suelo
15.
Nature ; 572(7768): 194-198, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31341281

RESUMEN

Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 1020 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.


Asunto(s)
Mapeo Geográfico , Nematodos/clasificación , Nematodos/aislamiento & purificación , Suelo/parasitología , Animales , Biomasa , Carbono/metabolismo , Nematodos/química , Filogeografía , Reproducibilidad de los Resultados , Incertidumbre
16.
Rinsho Shinkeigaku ; 59(3): 157-159, 2019 Mar 28.
Artículo en Japonés | MEDLINE | ID: mdl-30814446

RESUMEN

A 64-year-old man was diagnosed with spinal and bulbar muscular atrophy (SBMA) in 2014, and began gait training with the hybrid assistive limb (HAL) in 2017. We conducted 2 courses of HAL-based gait training and temporary improvement was confirmed both before and after intervention based on evaluation of the 2-minute walking distance, walking speed, and the Timed Up and Go test. HAL-based gait training may be effective for improving and maintaining walking ability in SBMA. However, long-term observation of this patient will be performed.


Asunto(s)
Atrofia Bulboespinal Ligada al X/rehabilitación , Terapia por Ejercicio/instrumentación , Dispositivo Exoesqueleto , Marcha/fisiología , Rehabilitación Neurológica/instrumentación , Acondicionamiento Físico Humano/instrumentación , Modalidades de Fisioterapia/instrumentación , Caminata/fisiología , Atrofia Bulboespinal Ligada al X/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
17.
Int J Pharm ; 542(1-2): 213-220, 2018 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-29551748

RESUMEN

Nucleic acid-based targeting of nuclear factor kappaB (NF-κB) is gaining attention as a treatment option for skin diseases like atopic dermatitis (AD). Transdermal administration improves patient quality of life because of non-invasive; however, siRNA delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of siRNA for topical skin application using functional peptides. We previously reported that combined treatment with a cytoplasm-responsive stearylated-arginine-rich peptide (STR-CH2R4H2C) and a tight junction opening peptide (AT1002) showed high siRNA permeability in the skin of AD-induced and normal mice. Here, we used murine macrophage RAW264.7 cells to examine siRNA permeation and the therapeutic effect of anti-NF-κB (RelA) siRNA (siRelA) complexed with STR-CH2R4H2C and AT1002 for AD-induced mice. We showed that significantly higher siRNA cellular uptake occurs after this treatment as well as decreased TNF-α and IL-6 expression. Additionally, we showed that effective siRNA transdermal delivery occurs with the suppression of the tight junction protein ZO-1. Moreover, topical skin application of siRelA with STR-CH2R4H2C and AT1002 improved AD-like symptoms in model mice. Thus, the combined treatment of STR-CH2R4H2C and AT1002 could serve as an effective transdermal siRNA therapeutic system for AD.


Asunto(s)
Dermatitis Atópica/terapia , FN-kappa B/genética , Oligopéptidos/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Administración Cutánea , Animales , Dermatitis Atópica/genética , Dermatitis Atópica/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismo , Proteína de la Zonula Occludens-1/metabolismo
18.
Rinsho Shinkeigaku ; 57(8): 436-440, 2017 08 31.
Artículo en Japonés | MEDLINE | ID: mdl-28740064

RESUMEN

A 78-year old woman who presented with akinetic mutism was admitted to our hospital. Brain MRI showed multifocal increased T2/FLAIR signal with extensive cortical-subcortical involvement. We suspected autoimmune encephalitis and the patient received methylprednisolone pulse. Her conscious level gradually recovered, but later relapsed again and presented with refractory status epilepticus. We treated her with intravenous immunoglobulin, plasma exchange and pulsed cyclophosphamide, with satisfactory response. A brain biopsy showed perivascular lymphocytic infiltrates and reactive gliosis. Anti-gamma aminobutyric acid (GABA)A receptor antibodies test came back to be positive after her recovery, and the diagnosis of anti-GABAA receptor antibody-positive encephalitis was made. This is a very rare case where brain biopsies were performed in a patient with anti-GABAA receptor antibody-positive encephalitis.


Asunto(s)
Anticuerpos Monoclonales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encefalitis/inmunología , Encefalitis/terapia , Inmunoterapia/métodos , Receptores de GABA-A/inmunología , Anciano , Ciclofosfamida/administración & dosificación , Encefalitis/complicaciones , Encefalitis/diagnóstico por imagen , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Linfocitos/patología , Imagen por Resonancia Magnética , Prednisolona/administración & dosificación , Quimioterapia por Pulso , Índice de Severidad de la Enfermedad , Estado Epiléptico/etiología , Resultado del Tratamiento
19.
Molecules ; 21(10)2016 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-27669207

RESUMEN

As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients' quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.


Asunto(s)
Técnicas de Transferencia de Gen , Péptidos/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Piel/metabolismo , Uniones Estrechas/metabolismo , Administración Tópica , Adsorción , Animales , Citoplasma/metabolismo , Dermatitis Atópica , Sistemas de Liberación de Medicamentos , Queratinocitos/metabolismo , Masculino , Ratones , Péptidos/química , Permeabilidad , ARN Interferente Pequeño/química
20.
Intern Med ; 55(14): 1911-6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27432102

RESUMEN

A 58-year-old woman with a 1-month history of right hand clumsiness and speaking difficulty was admitted to our hospital. A neurological examination revealed sensory aphasia and right hemiparesis. Her laboratory tests showed elevated serum levels of IgG and IgG4, pancytopenia, and liver dysfunction. The results of the imaging studies of her abdomen were compatible with sclerosing cholangitis. Brain MRI showed extensive signal abnormalities in the left hemisphere on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, extending from left internal capsule to the cerebral peduncle with an irregularly enhancing lesion in the left parietal lobe. A brain biopsy revealed lymphocyte and plasma cell infiltration and reactive gliosis. Most of the plasma cells were IgG positive; however, IgG4-positive plasma cells were sparsely observed. After the initiation of betamethasone treatment, her symptoms and the brain MRI abnormalities showed significant improvement. The brain biopsy results did not meet the current criteria of IgG4-related disease. This is the first reported case of a tumefactive lesion of the brain parenchyma with serum IgG4 elevation, which was responsive to steroid treatment. The accumulation of a greater number of reports on the pathological investigation of cases of possible IgG4-related disease may help to elucidate the exact role of IgG4 in IgG4-related disorders.


Asunto(s)
Encefalopatías/complicaciones , Granuloma de Células Plasmáticas/complicaciones , Hipergammaglobulinemia/complicaciones , Inmunoglobulina G/sangre , Biopsia , Encefalopatías/diagnóstico , Colangitis Esclerosante/diagnóstico por imagen , Femenino , Granuloma de Células Plasmáticas/diagnóstico , Humanos , Hepatopatías/complicaciones , Imagen por Resonancia Magnética , Persona de Mediana Edad
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