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1.
Heliyon ; 10(2): e24862, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312677

RESUMO

Although physical grids improve contrast in radiographic images by reducing scattered radiation, various artifacts such as grid shadow, moire, and cutoff result in increased patient doses. To overcome these problems, this study evaluates the applicability and usefulness of a material thickness-based scatter-correction technique for mammography. Specifically, this study aims to compare and evaluate the performance of mammography using the proposed software-based scatter correction framework and a physical grid. The proposed technique enables scatter correction based on pre-calculated parameters of a thickness-based scatter kernel at a water slab phantom and an empirical quantity of scatter components in a mammographic system. In the Monte Carlo simulation and experiment, the proposed framework displayed an intensity profile and full width at half maximum that closely approximated those seen in the physical grid. In addition, by applying the proposed framework to the ACR phantom, it was verified that all structures, including specks, were distinctly distinguished. The results demonstrate that the X-ray scatter-correction method with a software-based framework for mammography is applicable to the field of diagnostic imaging, as this approach yields image quality equivalent to that achieved with physical grids while also enabling a reduction in radiation doses for patients.

2.
J Clin Med ; 12(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37629320

RESUMO

Headaches are a common side effect of vaccination against the severe acute respiratory syndrome, coronavirus 2; however, it is usually not necessary to seek emergency medical attention or undergo brain imaging such as non-enhanced brain computed tomography (CT) for routine evaluation of vaccine-related headaches. This study aimed to demonstrate that brain CT is of no clinical benefit to patients presenting to the emergency department (ED) with post-coronavirus disease 2019 (COVID-19) vaccination headaches. This retrospective, single-center observational study used electronic medical record (EMR) data of patients who received the COVID-19 vaccination during the first year of the vaccination program. In total, 914 patients were analyzed, of whom 435 underwent CT (CT group, n = 435; no CT group, n = 475). More female patients visited the ED, and there was no significant sex difference between the CT and no-CT groups. The type of vaccine affected the clinical decision to perform brain CT, but the number of doses did not. The CT rate was relatively high for patients who had received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Johnson and Johnson Janssen (Jansen) vaccines (p = 0.004). Focal neurological deficits were present in all cases of abnormalities on non-enhanced brain CT in patients complaining of headaches. Two out of the 435 patients had abnormal brain CT findings (glioblastoma and Rathke's pouch cyst) at 35 and 32 days after vaccination, respectively. Non-enhanced brain CT should be performed cautiously in patients visiting the ED for post-vaccination headaches only.

3.
Int J Mol Sci ; 24(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37373260

RESUMO

Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.


Assuntos
Lipopolissacarídeos , Sepse , Humanos , Lipopolissacarídeos/metabolismo , Mitocôndrias/metabolismo , Sepse/metabolismo , Inflamação/metabolismo , Monócitos/metabolismo
4.
Medicine (Baltimore) ; 102(9): e33023, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36862896

RESUMO

Rosacea is a chronic erythematous disease with telangiectasia that affects the central area of the face. However, because of the ambiguity in the pathophysiology of rosacea, its treatment has not been clearly elucidated; therefore, new therapeutic options need to be developed. Gyejibokryeong-hwan (GBH) is widely used in clinical practice for various blood circulation disorders, including hot flushes. Therefore, we explored the potential pharmaceutical mechanism of GBH on rosacea and investigated the therapeutic points exclusive to GBH through comparative analysis with chemical drugs recommended in 4 guidelines for rosacea based on network analysis. The active compounds in GBH were identified, and the proteins targeted by these compounds and the genes related to rosacea were searched. Additionally, the proteins targeted by the guideline drugs were also searched to compare their effects. And the pathway/term analysis of common genes was conducted. Ten active compounds were obtained for rosacea. There were 14 rosacea-related genes targeted by GBH, with VEGFA, TNF, and IL-4, which were suggested as core genes. The pathway/term analysis of the 14 common genes revealed that GBH could potentially act on rosacea via 2 pathways: the "interleukin 17 signaling pathway" and the "neuroinflammatory response." Comparison and analysis of the protein targets between GBH and guideline drugs revealed that only GBH separately acts on the "vascular wound healing pathway." GBH has the potential to act on IL-17 signaling pathway, neuroinflammatory response and vascular wound healing pathway. Further studies are needed to determine the potential mechanism of GBH in rosacea.


Assuntos
Doenças Cardiovasculares , Rosácea , Humanos , Rosácea/tratamento farmacológico , Fogachos , Inflamação , Preparações Farmacêuticas
5.
Medicine (Baltimore) ; 102(12): e33323, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36961163

RESUMO

In this study, we used a network pharmacological method to explore the active ingredients of Hedyotis diffusa Willd (HDW) in the treatment of acne and elucidated the physiological mechanisms in the human body in which they are involved. We identified the active compounds of HDW that are expected to act effectively in the human body using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform and extracted potential interacting proteins for each active compound using the Swiss Target Prediction platform. Next, we analyzed the potential mechanisms of action of the protein targets shared by HDW and each standard drug on acne and assessed the possibility of spontaneous occurrence of the binding between proteins and active compounds through the molecular docking process. Seven active compounds were selected according to the oral bioavailability and drug-likeness criteria of the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Subsequently, 300 protein targets were collected from the Swiss Target Prediction. Using the Search Tool for the Retrieval of Interacting Genes/Proteins database, a protein-protein interaction network was constructed by analyzing the relationship between HDW, acne, and each standard drug. By analyzing the gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway, the "positive regulation of lipid metabolic process" was found to be the most involved pathway shared by HDW, acne, and isotretinoin. An analysis of the protein targets shared by the antibiotic agents with HDW and acne found that "cholesterol storage" in tetracycline, "icosacoid transport" in azithromycin, "steroid hydroxylase activity" in erythromycin, "positive regulation of leukocyte tethering or rolling" in clindamycin, "response to UV-A" in minocycline, "steroid 11-beta-monooxygenase activity" in doxycycline, and "neutrophil-mediated immunity" in trimethoprim were the most involved. Virtual molecular docking analysis showed that all proteins spontaneously bound to their corresponding active compounds. Our analysis suggests that HDW can, directly and indirectly, suppress sebum secretion and exert antiinflammatory effects on acne. Further, HDW may regulate free radicals and suppress apoptosis. Therefore, HDW can be used as an alternative or supplement to standard drugs for acne treatment in patients who cannot use standard treatments due to side effects.


Assuntos
Acne Vulgar , Medicamentos de Ervas Chinesas , Hedyotis , Humanos , Extratos Vegetais/farmacologia , Hedyotis/química , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Medicina Tradicional Chinesa , Acne Vulgar/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-36360621

RESUMO

This study aimed to improve the quality of ultrasound images by modeling an algorithm using a non-local means (NLM) noise-reduction approach to achieve precise quality control and accurate diagnosis of thyroid nodules. An ATS-539 multipurpose phantom was used to scan the dynamic range and gray-scale measurement regions, which are most closely related to the noise level. A convex-type 3.5-MHz frequency probe is used for scanning according to ATS regulations. In addition, ultrasound images of human thyroid nodules were obtained using a linear probe. An algorithm based on the NLM noise-reduction approach was modeled based on the intensity and relative distance of adjacent pixels in the image, and conventional filtering methods for image quality improvement were designed as a comparison group. When the NLM algorithm was applied to the image, the contrast-to-noise ratio and coefficient of variation values improved by 28.62% and 19.54 times, respectively, compared with those of the noisy images. In addition, the image improvement efficiency of the NLM algorithm was superior to that of conventional filtering methods. Finally, the applicability of the NLM algorithm to human thyroid images using a high-frequency linear probe was validated. We demonstrated the efficiency of the proposed algorithm in ultrasound images and the possibility of capturing improved images in the dynamic range and gray-scale region for quality control parameters.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Razão Sinal-Ruído , Nódulo da Glândula Tireoide/diagnóstico por imagem , Imagens de Fantasmas , Ultrassonografia , Algoritmos , Controle de Qualidade , Processamento de Imagem Assistida por Computador/métodos
8.
Int J Mol Sci ; 23(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35743025

RESUMO

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.


Assuntos
Lipopolissacarídeos , Sepse , Animais , Tolerância à Endotoxina , Interleucina-6 , Lactatos , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , NF-kappa B , Ratos , Espécies Reativas de Oxigênio , Sepse/patologia , Fator de Necrose Tumoral alfa
9.
Life (Basel) ; 12(3)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35330172

RESUMO

Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.

10.
Diagnostics (Basel) ; 12(2)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35204429

RESUMO

The purpose of this study was to investigate the viability of the proposed method in preventing the loss of metallic components including the clip and coil in cerebral computed tomography angiography (CTA). Forty patients undergoing surgery for aneurysms carried metallic materials. The proposed method is based on conventional bone subtraction CTA (BS-CTA) system. Briefly, the position of metal components was determined using the threshold value and a region of interest (ROI). An appropriate threshold was used to separate the background from the target materials based on the Otsu method. A three-dimensional (3D) rendering was performed from the proposed BS-CTA data carrying the extracted target information. The accuracy of clip and coil region measured using the dice similarity coefficient (DSC) and bidirectional Hausdorff distance (HD) is reported. The metallic components of the proposed BS-CTA were significantly visualized in various patient cases. Quantitative evaluation using the proposed method is based on the mean DSC of 0.93 with a standard deviation (SD) of ±0.05 (e.g., maximum value = 0.99, minimum value = 0.75, 95% confidence interval (CI) = 0.91 to 0.95, and all p < 0.05). The mean HD was 1.50 voxels with an SD of ± 0.58 (e.g., maximum value = 5.95, minimum value = 0.12, 95% CI = 1.10 to 1.90, and all p < 0.05). The proposed method demonstrates effective segmentation of the metallic component and application to the existing conventional BS-CTA system.

11.
Sci Rep ; 12(1): 2852, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181715

RESUMO

Hair loss is one of the most common skin problems experienced by more than half of the world's population. In East Asia, medicinal herbs have been used widely in clinical practice to treat hair loss. Recent studies, including systematic literature reviews, indicate that medicinal herbs may demonstrate potential effects for hair loss treatment. In a previous study, we identified medical herbs used frequently for alopecia treatment. Herein, we explored the potential novel therapeutic mechanisms of 20 vital medicinal herbs for alopecia treatment that could distinguish them from known mechanisms of conventional drugs using network pharmacology analysis methods. We determined the herb-ingredient-target protein networks and ingredient-associated protein (gene)-associated pathway networks and calculated the weighted degree centrality to define the strength of the connections. Data showed that 20 vital medicinal herbs could exert therapeutic effects on alopecia mainly mediated via regulation of various target genes and proteins, including acetylcholinesterase (AChE), phospholipase A2 (PLA2) subtypes, ecto-5-nucleotidase (NTE5), folate receptor (FR), nicotinamide N-methyltransferase (NNMT), and quinolinate phosphoribosyltransferase (QPRT). Findings regarding target genes/proteins and pathways of medicinal herbs associated with alopecia treatment offer insights for further research to better understand the pathogenesis and therapeutic mechanism of medicinal herbs for alopecia treatment with traditional herbal medicine.


Assuntos
Alopecia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Farmacologia em Rede , Plantas Medicinais , Acetilcolinesterase/genética , Alopecia/genética , Alopecia/prevenção & controle , Ásia Oriental , Receptor 1 de Folato/genética , Humanos , Medicina Tradicional Chinesa , Nicotinamida N-Metiltransferase/genética , Nucleotidases/genética , Pentosiltransferases/genética , Fosfolipases A2/genética , Fitoterapia , Preparações de Plantas/química , Preparações de Plantas/uso terapêutico
12.
BMC Complement Med Ther ; 20(1): 230, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689985

RESUMO

BACKGROUND: The human placenta (HP) is a complex organ used to alleviate tiredness and promote wound healing. Previous research showed the hair growth-promoting effect of HP. However, no reports have addressed the effects of HP on hair regrowth in chemotherapy-induced alopecia. In this study, we investigated the effects of HP on the apoptosis and proliferation of hair follicles in chemotherapy-induced alopecia. METHODS: Male C57BL/6 mice in telogen were depilated to enter anagen. After 9 days, dystrophic catagen was induced by the intraperitoneal injection of 150 mg/kg cyclophosphamide. During 9 to 16 days, 0.1 and 1 mg/mL HP were topically applied to depilated dorsal skin. RESULTS: Dystrophic hair follicles by cyclophosphamide were recovered by HP treatment. New hair shafts containing hair fibers appeared to be straight after HP treatment. Immunohistological staining revealed a significant increase of Ki67-positive cells in hair follicles treated with 1 mg/mL HP. Topical HP treatment increased the ratio of Bcl-2/Bax, while it attenuated the expression of pro-apoptotic Bax, p53, and cytochrome c with caspase-9 and -3. In addition, the expression of KGF and the phosphorylation of AKT were upregulated by HP treatment. CONCLUSION: These results suggest that HP treatment induced hair growth by inhibiting apoptosis and promoting the proliferation of hair follicles. HP may be useful for treating chemotherapy-induced alopecia.


Assuntos
Alopecia/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Placenta , Administração Tópica , Alopecia/induzido quimicamente , Animais , Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez
13.
Med Phys ; 46(12): 5833-5847, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621917

RESUMO

PURPOSE: The purpose of this study was to investigate the feasibility of two-dimensional (2D) dose distribution deconvolution using convolutional neural networks (CNNs) instead of an analytical approach for an in-house scintillation detector that has a detector-interface artifact in the penumbra region. METHODS: Datasets of 2D dose distributions were acquired from a medical linear accelerator of Novalis Tx. The datasets comprise two different sizes of square radiation fields and 13 clinical intensity-modulated radiation treatment (IMRT) plans. These datasets were divided into two datasets (training and test) to train and validate the developed network, called PenumbraNet, which is a shallow linear CNN. The PenumbraNet was trained to transform the measured dose distribution [M(x, y)] to calculated distribution [D(x, y)] by the treatment planning system. After training of the PenumbraNet was completed, the performance was evaluated using test data, which were 10 × 10 cm2 open field and ten clinical IMRT cases. The corrected dose distribution [C(x, y)] was evaluated against D(x, y) with 2%/2 mm and 3%/3 mm criteria of the gamma index for each field. The M(x, y) and deconvolved dose distribution with the analytically obtained kernel using Wiener filtering [A(x, y)] were also evaluated for comparison. In addition, we compared the performance of the shallow depth of linear PenumbraNet with that of nonlinear PenumbraNet and a deep nonlinear PenumbraNet within the same training epoch. RESULTS: The mean gamma passing rates were 84.77% and 95.81% with 3%/3 mm gamma criteria for A(x, y) and C(x, y) of the PenumbraNet, respectively. The mean gamma pass rates of nonlinear PenumbraNet and the deep depth of nonlinear PenumbraNet were 96.62%, 93.42% with 3%/3 mm gamma criteria, respectively. CONCLUSIONS: We demonstrated the feasibility of the PenumbraNets for 2D dose distribution deconvolution. The nonlinear PenumbraNet which has the best performance improved the gamma passing rate by 11.85% from the M(x, y) at 3%/3 mm gamma criteria.


Assuntos
Redes Neurais de Computação , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos de Viabilidade , Humanos , Radiometria , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada
14.
J Surg Res ; 206(2): 427-434, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27884339

RESUMO

BACKGROUND: The cecal slurry model was introduced as an alternative method for creating an animal sepsis model. This study was performed to evaluate dose-dependent mortality and organ injury in a sepsis model of cecal slurry peritonitis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 5.0, 7.5, 10, or 15 mL/kg groups, according to the volume of cecal slurry administered into the peritoneal cavity. In the survival study, rats were observed for 14 d after sepsis induction. In the second experiment, blood and tissue were harvested to measure organ injury and the 2', 7'-dichlorofluorescein diacetate concentrations. RESULTS: All rats in the 5.0 mL/kg group survived for 14 d, whereas all rats in the 15 mL/kg group died within 24 h. The survival rates in the 7.5 mL/kg and 10 mL/kg groups were 60% and 30%, respectively. In the arterial blood gas analysis, lactate concentrations increased and HCO3- decreased in a dose-dependent manner across the groups. Alanine aminotransferase and blood urea nitrogen concentrations increased as the dose of cecal slurry increased. 2', 7'-Dichlorofluorescein diacetate concentrations also increased in a dose-dependent manner. CONCLUSIONS: The cecal slurry model of sepsis evaluated in this study demonstrates dose-dependent mortality, metabolic acidosis, liver and kidney injuries, and reactive oxygen species production, and it could be used for subsequent sepsis experiments, considering the severity of sepsis induced.


Assuntos
Modelos Animais de Doenças , Insuficiência de Múltiplos Órgãos/etiologia , Peritonite/mortalidade , Ratos Sprague-Dawley , Sepse/mortalidade , Animais , Ceco , Estimativa de Kaplan-Meier , Masculino , Insuficiência de Múltiplos Órgãos/diagnóstico , Peritonite/etiologia , Peritonite/fisiopatologia , Distribuição Aleatória , Ratos , Sepse/etiologia , Sepse/fisiopatologia , Índice de Gravidade de Doença
15.
Biomacromolecules ; 17(11): 3632-3639, 2016 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-27739685

RESUMO

Functional hyperbranched polyglycerols (PGs) have recently garnered considerable interest due to their potential in biomedical applications. Here, we present a one-pot synthesis of hyperbranched PGs possessing amine functionality using a novel amino glycidyl ether monomer. A Boc-protected butanolamine glycidyl ether (BBAG) monomer was designed and polymerized with glycidol (G) through anionic ring-opening multibranching polymerization to yield a series of hyperbranched P(G-co-BBAG) with controlled molecular weights (4800-16700 g/mol) and relatively low molecular weight distributions (1.2-1.6). The copolymerization and subsequent deprotection chemistry allow the incorporation of an adjustable fraction of primary amine moieties (typically, 5-20% monomer ratio) within the hyperbranched PG backbones, thus providing potentials for varying charge densities and functionality in PGs. The copolymerization kinetics of G and BBAG was also evaluated using a quantitative in situ 13C NMR spectroscopic analysis, which revealed gradient copolymerization between the comonomers. The free amine groups within the deprotected P(G-co-BAG) copolymer were further utilized for a facile conjugation chemistry with a model molecule in a quantitative manner. Furthermore, the superior biocompatibility of the prepared P(G-co-BAG) polymers was demonstrated via cell viability assays, outperforming many existing polyamines possessing relatively high cytotoxicity. Taken together, the biocompatibility with facile conjugation chemistry of free amine groups sheathed within the framework of hyperbranched PGs holds the prospect of advancing biological and biomedical applications.


Assuntos
Materiais Biocompatíveis/química , Glicerol/química , Poliaminas/química , Polímeros/química , Materiais Biocompatíveis/síntese química , Compostos de Epóxi/química , Éteres/química , Glicerol/síntese química , Poliaminas/síntese química , Polimerização , Polímeros/síntese química , Propanóis/química
16.
J Ethnopharmacol ; 180: 12-7, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26778605

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Spirodela polyrhiza has been used as a traditional remedy for the treatment of urticarial, acute nephritis, inflammation, as well as skin disease. AIM OF STUDY: Atopic dermatitis (AD) is characterized hyperplasia of skin lesion and increase of serum immunoglobulin E (IgE) level. In this study, the topical effects of S. polyrhiza (SP) on 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice model were investigated by several experiments. MATERIALS AND METHODS: BALB/c mice were randomly divided into five groups as NOR, CON, DEX, SP 1, and SP 100 groups (n=5, respectively). To induce atopic dermatitis-like skin lesions, DNCB had been applied on shaved dorsal skin. SP was topically treated to DNCB-induced mice as 1 and 100mg/mL concentrations. Histological changes were showed by hematoxylin and eosin (H&E) staining and the infiltration of mast cells was detected by toluidine blue staining. In addition, the level of IgE and each cytokines were measured and expressions of inflammatory signaling factors were analyzed by western blotting assay. RESULTS: SP treatment improved a hyperplasia of epidermis and dermis in DNCB-induced AD-like skin lesion. The infiltration of mast cells was also decreased by treatment of SP. In addition, SP reduced the level of IgE in serum and attenuated the secretion of cytokines such as interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Treatment of SP also inhibited the expressions of pro-inflammatory mediators including nuclear factor-κB (NF-κB), phosphor-IκB-α, and mitogen-activated protein kinase (MAPK)s. CONCLUSIONS: From these data, we propose that SP ameliorates AD via modulation of pro-inflammatory mediators. SP may have the potential to be used as an alternative for treatment of AD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Araceae , Dermatite Atópica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Tópica , Animais , Anti-Inflamatórios/farmacologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno , Feminino , Imunoglobulina E/sangue , Mastócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
17.
Clin Exp Emerg Med ; 2(2): 123-129, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27752583

RESUMO

OBJECTIVE: Use of computed tomography (CT) continues to increase, but the relatively high radiation doses associated with CT have raised health concerns such as future risk of cancer. We investigated the level of awareness regarding radiation doses and possible risks associated with CT in medical personnel (MP). METHODS: This study was conducted from April to May 2012 and included physicians and nurses who worked in the emergency department of 17 training hospitals. The questionnaire included measurement of the effect of CT or radiography on health using a 10-point numerical rating scale, estimation of the radiation dose of one abdominal CT scan compared with one chest radiograph, and perception of the increased lifetime risk of cancer associated with CT. RESULTS: A total of 354 MP participated in this study: 142 nurses, 87 interns, 86 residents, and 39 specialists. Interns were less aware of the effects of CT or radiography on health than other physicians or nurses (mean±SD of 4.8±2.7, 5.9±2.7, 6.1±2.7, and 6.0±2.2 for interns, residents, specialists, and nurses, respectively; P<0.05). There was a significant difference in knowledge about the relative radiation dose of one abdominal CT scan compared with one chest radiograph between physicians and nurses (48.6% vs. 28.9% for physicians vs. nurses, P<0.05). MP perceived an increased risk of cancer from radiation associated with CT. CONCLUSION: MP perceive the risk of radiation associated with CT, but their level of knowledge seems to be insufficient.

18.
CJEM ; 17(1): 54-61, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25781384

RESUMO

OBJECTIVE: To determine the influence of early pain relief for patients with suspected appendicitis on the diagnostic performance of surgical residents. METHODS: A prospective randomized, double-blind, placebo-controlled trial was conducted for patients with suspected appendicitis. The patients were randomized to receive placebo (normal saline intravenous [IV]) infusions over 5 minutes or the study drug (morphine 5 mg IV). All of the clinical evaluations by surgical residents were performed 30 minutes after administration of the study drug or placebo. After obtaining the clinical probability of appendicitis, as determined by the surgical residents, abdominal computed tomography was performed. The primary objective was to compare the influence of IV morphine on the ability of surgical residents to diagnose appendicitis. RESULTS: A total of 213 patients with suspected appendicitis were enrolled. Of these patients, 107 patients received morphine, and 106 patients received placebo saline. The negative appendectomy percentages in each group were similar (3.8% in the placebo group and 3.2% in the pain control group, p=0.62). The perforation rates in each group were also similar (18.9% in the placebo group and 14.3% in the pain control group, p=0.75). Receiver operating characteristic analysis revealed that the overall diagnostic accuracy in each group was similar (the area under the curve of the placebo group and the pain control group was 0.63 v. 0.61, respectively, p=0.81). CONCLUSIONS: Early pain control in patients with suspected appendicitis does not affect the diagnostic performance of surgical residents.


Assuntos
Dor Abdominal/tratamento farmacológico , Apendicite/diagnóstico , Educação Médica Continuada/métodos , Cirurgia Geral/educação , Internato e Residência , Morfina/administração & dosagem , Manejo da Dor/normas , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Doença Aguda , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Apendicite/complicações , Diagnóstico Diferencial , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
J Trauma Acute Care Surg ; 78(2): 370-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25757124

RESUMO

BACKGROUND: The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock. METHODS: Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes. After the hemorrhagic shock period, rats were randomly allocated to one of three groups as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group) or normal saline for the control group was administered via tail vein for 10 minutes, and shed blood was transfused for 15 minutes. For the survival study, animals were observed for up to 9 hours, and their survival time was recorded until death. Separate experiments were performed to examine the effect of CsA on inflammatory responses and liver injury. Rats were sacrificed at 210 minutes after the shock period, and blood and liver tissues were harvested. RESULTS: Survival times were shown to be significantly longer in the CsA-treated groups (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin-6 and thiobarbituric acid-reactive substances were significantly lower in the CsA50 group than in the control group and phosphorylation of Akt, GSK-3ß, and Bad were significantly increased in the CsA-treated groups compared with the control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic cytochrome C were significantly decreased in the CsA-treated groups compared with the control group. Although histologic liver injury was not significantly different among the groups, ultrastructural changes of mitochondria were more prominent in the control group than in the CsA-treated groups. CONCLUSION: CsA increased survival time, decreased proinflammatory cytokine and lipid peroxidation, and augmented Akt survival pathways in rats subjected to pressure-controlled hemorrhagic shock.


Assuntos
Ciclosporina/farmacologia , Choque Hemorrágico/tratamento farmacológico , Animais , Gasometria , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Hemodinâmica , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Masculino , Microscopia Eletrônica , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Análise de Sobrevida , Fatores de Tempo
20.
J Trauma Acute Care Surg ; 76(3): 771-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24553547

RESUMO

BACKGROUND: Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock. METHODS: Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats. RESULTS: All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1ß, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05). CONCLUSION: Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.


Assuntos
Pressão Sanguínea/fisiologia , Ressuscitação/métodos , Choque Hemorrágico/terapia , Alanina Transaminase/sangue , Animais , Gasometria , Interleucina-1beta/análise , Interleucina-6/análise , Ácido Láctico/sangue , Fígado/química , Fígado/patologia , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/análise , Reperfusão/métodos , Choque Hemorrágico/patologia , Choque Hemorrágico/fisiopatologia
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