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Emerging evidence indicates that the immunomodulatory effect of mesenchymal stem cells (MSCs) is primarily attributed to the paracrine pathway. As a key paracrine effector, MSC-derived exosomes are small vesicles that play an important role in cell-to-cell communication by carrying bioactive substances. We previously found that exosomes derived from tonsil-derived mesenchymal stem cells (T-MSCs) were able to effectively attenuate inflammatory responses in mast cells. Here we investigated how T-MSC exosomes impact mast cells in steady state, and how exposure of T-MSCs to Toll-like receptors (TLRs) ligands changes this impact. Transcriptomic analysis of HMC-1 cells, a human mast cell line, using DNA microarrays showed that T-MSC exosomes broadly regulate genes involved in the normal physiology of mast cells. TLR3 or TLR4 primed T-MSC exosomes impacted fewer genes involved in specific functions in mast cells. This distinguishable regulation also was apparent in the analysis of related gene interactions. Our results suggest that MSC exosomes maintain immune homeostasis in normal physiology and impact the inflammatory state by modulating mast cell transcription.
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Exossomos , Células-Tronco Mesenquimais , Humanos , Mastócitos , Exossomos/genética , Exossomos/metabolismo , Comunicação Celular , Células-Tronco Mesenquimais/metabolismo , Expressão GênicaRESUMO
Introduction IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). This study evaluated the safety, pharmacokinetics, and pharmacodynamics of IMC-001 in patients with advanced solid tumors. Materials and Methods This open-labeled phase I study used a standard 3 + 3 dose-escalation design, with doses ranging from 2 to 20 mg/kg. IMC-001 was administered intravenously every 2 weeks until disease progression or unacceptable toxicity. The dose-limiting toxicity window was defined as 21 days from the first dose. Results Fifteen subjects were included in 5 dose-escalation cohorts. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common adverse events (AEs) were general weakness, decreased appetite, fever, and cough. No grade 4 or 5 treatment emergent AEs were reported during the study. One subject in the 2 mg/kg cohort showed grade 2 immune-induced thyroiditis and diabetes mellitus suspected to be related to IMC-001. Over the dose range of 2-20 mg/kg IMC-001, the AUC0-14d, AUC0-∞, and Cmax generally increased in a dose-proportional manner for each step of dose escalation. Of the 15 enrolled patients, 1 subject with rectal cancer showed a partial response, and the disease control rate was 33.3%. Conclusions IMC-001 demonstrated a favorable safety profile up to 20 mg/kg administered intravenously every 2 weeks and showed preliminary efficacy in patients with advanced solid tumors. Based on pharmacokinetic and pharmacodynamic data, 20 mg/kg was selected as the recommended phase II dose. Clinical trial identification NCT03644056 (date of registration: August 23, 2018).
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Anticorpos Monoclonais Humanizados , Antineoplásicos , Neoplasias , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Área Sob a Curva , Antígeno B7-H1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Dose Máxima Tolerável , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinéticaRESUMO
BACKGROUND: despite of the beneficial effects of fibroblast growth factor (FGF) 21 in several metabolic diseases, the association of plasma FGF21 with muscle mass and muscle strength is still unclear. METHODS: a total of 386 community-dwelling older adults aged 70-84 years were analysed. Appendicular skeletal muscle mass was measured using dual-energy X-ray absorptiometry and normalised to the square of height (ASM/ht2). Muscle strength was assessed using the hand grip strength (HGS) test. The definitions of low muscle mass (LMM) and low muscle strength (LMS) were based on the Asian Working Group for Sarcopenia. RESULTS: plasma FGF21 was significantly lower in participants with LMM than in those with normal muscle mass (289.7 [192.4-448.3] vs. 345.6 [238.6-503.2] pg/ml, P = 0.008). In contrast, the LMS group had a significantly higher plasma FGF21 level than the normal muscle strength group (369.7 [244.4-591.1] vs. 309.7 [205.3-444.8] pg/ml, P = 0.006). In the partial correlation analysis, following adjustment for age, sex and body mass index, FGF21 levels had no significant association with ASM/ht2, but were negatively associated with HGS (r = -0.112, P = 0.029). Furthermore, after multivariate adjustment for confounding variables, the odds ratio for the risk of LMS was 2.32 (95% confidence interval 1.20-4.46) when comparing the highest with the lowest FGF21 quartile. CONCLUSIONS: circulating FGF21 levels are negatively associated with muscle strength but are not independently correlated with muscle mass.
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Fragilidade , Sarcopenia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Fatores de Crescimento de Fibroblastos , Força da Mão , Humanos , Força Muscular , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Músculos , República da Coreia/epidemiologia , Sarcopenia/diagnóstico por imagemRESUMO
OBJECTIVES: The prevalence of upper gastrointestinal disease is expected to change following advances in socioeconomic status and improved hygiene in Korea. The aim of this study was to investigate the recent trends in upper gastrointestinal diseases based on endoscopic findings and Helicobacter pylori (H. pylori) seroprevalence in subjects undergoing health check-up at tertiary centers in Korea. METHODS: A multicenter cross-sectional study was conducted at nine healthcare centers between September 2016 and June 2017. The subjects were evaluated using questionnaires, upper endoscopy and H. pylori serology tests. The results were compared with previous data in our study group obtained from eight tertiary healthcare centers in 2011 (n = 4023). RESULTS: In total, we prospectively enrolled 2504 subjects undergoing health check-up. The prevalence of reflux esophagitis (RE) was 9.7%, which showed an increasing but insignificant trend since 2011 (8.8%). The prevalence of active and healing-stage benign gastric ulcer and duodenal ulcer (DU) was 1.6% and 1.2%, respectively, which confirmed a significant decrease since 2011 (4.1%; p < .001 and 2.2%; p = .005, respectively). The prevalence of gastric cancer was 0.5%, representing an increasing trend since 2011 (0.12%; p = .003). H. pylori seroprevalence was 51.3%, which significantly decreased from 2011 (59.8%; p < .001). In multivariate analysis, H. pylori seropositivity was a significant risk factor for DU (p < .001), whereas a significant protective factor against RE (p < .001). CONCLUSIONS: The significant decrease of H. pylori seroprevalence in the past five years altered the incidence of upper gastrointestinal disease.
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Úlcera Duodenal/epidemiologia , Esofagite Péptica/epidemiologia , Infecções por Helicobacter/epidemiologia , Úlcera Péptica/epidemiologia , Neoplasias Gástricas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Gastroscopia , Infecções por Helicobacter/complicações , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
BACKGROUND: Muscle mass and muscle function are related to depressed mood in studies of adults. Like adults, Korean students are highly likely to suffer from decreased muscle mass due to social conditions. In this study, we evaluated the muscle mass status of Korean adolescents and assess the effect of muscle on depressive mood. METHODS: A total of 1,233 adolescent boys and girls participants from the Korea National Health and Nutrition Examination Survey were enrolled in our study. Participants underwent dual-energy X-ray absorptiometry for assessment of appendicular muscle mass and completed questionnaires regarding depressed mood, stress, suicidal ideations, and attempts. RESULTS: There was no difference in depressive mood according to muscle mass among boys (P = 0.634); girls with decreased muscle mass had a greater tendency for depressed mood compared to girls with optimal muscle mass (P = 0.023). After adjusting for age, waist circumference-to-height ratio, smoking status, alcohol consumption, frequency of physical activity, self-reported obesity, weight-loss efforts, and monthly household income, girls with low muscle mass (LMM) were 2.60 times more at risk of developing depression than girls with normal muscle mass (95% confidence interval [CI], 1.05-6.49; P = 0.040). This trend was similar for girls with LMM with obesity (95% CI, 1.00-11.97; P = 0.049). CONCLUSION: Adolescent girls who have insufficient muscle mass are more likely to report depressed mood than girls who have ideal muscle mass. Interventions for maintaining proper muscle mass are required.
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Transtornos do Humor/diagnóstico , Músculo Esquelético/fisiologia , Inquéritos Nutricionais , Absorciometria de Fóton , Adolescente , Composição Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Saúde Mental , Transtornos do Humor/epidemiologia , Músculo Esquelético/diagnóstico por imagem , Razão de Chances , República da Coreia/epidemiologia , Fatores de Risco , Autorrelato , Estresse Psicológico , Ideação Suicida , Inquéritos e QuestionáriosRESUMO
The mechanical, thermal, optical, electrical and morphological properties of cellulose, an excellent natural biomaterial, can be improved by organic-inorganic hybrid composite methods. Based on the pristine properties of cellulose, the preparation of cellulose-metal oxide hybrid nanocomposites using a dispersion process of nanoparticles into the cellulose host matrix by traditional methods, has limitations. Recently, the functionalized cellulose-polymer-based materials were considered to be an important class of high-performance materials, providing the synthesis of various functional hybrid nanocomposites using a sol-gel method. Transparent cellulose-POSS-amine-silica/titania hybrids were prepared by an in-situ sol-gel process in the presence of γ-aminopropyltrimethoxylsilane (γ-APTES). The methodology involves the formation of covalent bonding between the cellulose-POSS amine and SiO2/TiO2 hybrid nanocomposite material. An analysis of the synthesized hybrid material by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, differential thermal calorimetry, scanning electron microscopy, and transmission electron microscopy indicated that the silica/titania nanoparticles were bonded covalently and dispersed uniformly into the cellulose-POSS amine matrix. In addition, biological properties of the cellulose-POSS-silica/titania hybrid material were examined using an antimicrobial test against pathogenic bacteria, such as Bacillus cereus (F481072) and E. coli (ATCC35150) for the bacterial effect.
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Antibacterianos , Celulose , Nanocompostos/química , Compostos de Organossilício , Dióxido de Silício , Titânio , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus cereus/crescimento & desenvolvimento , Celulose/química , Celulose/farmacologia , Escherichia coli/crescimento & desenvolvimento , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Titânio/química , Titânio/farmacologiaRESUMO
Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index ≥ 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age.
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Pneumopatias/epidemiologia , Pneumopatias/patologia , Obesidade/epidemiologia , Músculos Respiratórios/patologia , Sarcopenia/epidemiologia , Sarcopenia/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Obesidade/patologia , Tamanho do Órgão , Prevalência , Valores de Referência , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Testes de Função Respiratória , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por SexoRESUMO
PURPOSE: Spontaneous echo-contrast (SEC) appears on B-mode images as moving curls of smoke in the lumen of veins. The aims of this study were to investigate the prevalence and characteristics of internal jugular vein SEC among patients with stroke, in comparison with control subjects. METHODS: We enrolled 97 Korean patients with acute ischemic stroke and 50 controls. Both internal jugular veins were examined for the presence and severity of SEC and measurement of flow velocity. Venous samples were obtained for laboratory evaluation of hematologic factors. RESULTS: In 294 internal jugular veins, the prevalence of SEC was 81% in stroke patients and 68% in controls (odds ratio, 2.0; 95% confidence interval, 1.1-3.6; p = 0.013). Stroke patients were more likely to have SEC on the left (p = 0.025) than on the right (p = 0.184) internal jugular vein. Overall, the association between stroke and SEC remained significant after adjustment for other variables (odds ratio, 4.3; 95% confidence interval, 1.7-10.8; p = 0.002). CONCLUSIONS: Internal jugular vein SEC was found more frequently in stroke patients than in controls. However, local as well as systemic factors must be considered in the interpretation of this finding.
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Processamento de Imagem Assistida por Computador , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/fisiopatologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A-induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3ß1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2-mediated inhibition of vascular permeability involves an integrin α3ß1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3ß1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through "normalization" of vascular permeability in addition to previously described antiangiogenic effects.
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Permeabilidade Capilar/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-2/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Antígenos CD/metabolismo , Western Blotting , Caderinas/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citoesqueleto/metabolismo , Antagonismo de Drogas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Integrina alfa3beta1/genética , Integrina alfa3beta1/metabolismo , Isoquinolinas/farmacologia , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Mutação , Ligação Proteica/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 6/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Interferência de RNA , Sulfonamidas/farmacologia , Inibidor Tecidual de Metaloproteinase-2/genética , Vanadatos/farmacologiaRESUMO
BACKGROUND: The physiological effects of the non-anthocyanin fraction (NAF) in a black soybean seed coat extract on Aß-induced oxidative stress were investigated to confirm neuroprotection. In addition, we examined the preventive effect of NAF on cognitive defects induced by the intracerebroventricular (ICV) injection of Aß. METHODS: Levels of cellular oxidative stress were measured using 2',7'-dichlorofluorescein diacetate (DCF-DA). Neuronal cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. To investigate in vivo anti-amnesic effects of NAF by using Y-maze and passive avoidance tests, the learning and memory impairment in mice was induced by Aß. After in vivo assays, acetylcholinesterase (AChE) activity and level of malondialdehyde (MDA) in the mouse brain were determined to confirm the cognitive effect. Individual phenolics of NAF were qualitatively analyzed by using an ultra-performance liquid chromatography (UPLC) Accurate-Mass Quadrupole Time of-Flight (Q-TOF) UPLC/MS. RESULTS: A NAF showed cell protective effects against oxidative stress-induced cytotoxicity. Intracellular ROS accumulated through Aß1-40 treatment was significantly reduced in comparison to cells only treated with Aß1-40. In MTT and LDH assay, the NAF also presented neuroprotective effects on Aß1-40-treated cytotoxicity. Finally, the administration of this NAF in mice significantly reversed the Aß1-40-induced cognitive defects in in vivo behavioral tests. After behavioral tests, the mice brains were collected in order to examine lipid peroxidation and AChE activity. AChE, preparation was inhibited by NAF in a dose-dependent manner. MDA generation in the brain homogenate of mice treated with the NAF was decreased. Q-TOF UPLC/MS analyses revealed three major phenolics from the non-anthocyanin fraction; epicatechin, procyanidin B1, and procyanidin B2. CONCLUSIONS: The results suggest that the NAF in black soybean seed coat extracts may improve the cytotoxicity of Aß in PC12 cells, possibly by reducing oxidative stress, and also have an anti-amnesic effect on the in vivo learning and memory deficits caused by Aß. Q-TOF UPLC/MS analyses showed three major phenolics; (-)-epicatechin, procyanidin B1, and procyanidin B2. Above results suggest that (-)-epicatechins are the major components, and contributors to the anti-amnesic effect of the NAF from black soybean seed coat.
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Encéfalo/efeitos dos fármacos , Glycine max/química , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/efeitos adversos , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biflavonoides/análise , Biflavonoides/farmacologia , Biflavonoides/uso terapêutico , Encéfalo/metabolismo , Catequina/análise , Catequina/farmacologia , Catequina/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/metabolismo , Aprendizagem/efeitos dos fármacos , Deficiências da Aprendizagem/tratamento farmacológico , Deficiências da Aprendizagem/metabolismo , Masculino , Transtornos da Memória/metabolismo , Camundongos Endogâmicos ICR , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polifenóis/análise , Polifenóis/uso terapêutico , Proantocianidinas/análise , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Ratos , SementesRESUMO
Background/Aims: Well-known risk factors for gallbladder polyps include metabolic syndrome, age, and dyslipidemia. Jeju Island is approximately 80 km from the Korean peninsula and is divided into two administrative regions (Jeju City and Seogwipo City), with Mount Halla intervening in the center. Jeju City has higher employment and birth rates than Seogwipo City. Age and alcohol consumption differ between the two regions, and these factors may affect the prevalence of gallbladder polyps (GBPs). Therefore, we investigated the prevalence of GBPs and compared various factors, including alcohol consumption habits and age, associated with GBPs among residents in the two regions. Methods: This study included 21,734 residents who visited the Health Screening and Promotion Center of Jeju National University Hospital between January 2009 and December 2019. We investigated the prevalence and associated factors of GBPs among residents of Jeju City and Seogwipo City. Results: The prevalence of GBPs in Jeju City and Seogwipo City was 9.8% and 8.9% (p = 0.043), respectively. The mean age and rate of high-risk alcohol intake were higher in Seogwipo City. The mean body mass index and levels of fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase were lower in Jeju City. Conclusions: This study demonstrated a significant difference in GBP prevalence between the two regions of Jeju Island. Age and alcohol consumption might contribute to this difference; however, further prospective cohort studies are warranted to confirm our findings.
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OBJECTIVE: Non-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. METHODS: Between January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications. RESULTS: The median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased. CONCLUSIONS: Despite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.
Assuntos
Anticoagulantes , Oclusão Vascular Mesentérica , Veias Mesentéricas , Trombose Venosa , Vitamina K , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Idoso , Vitamina K/antagonistas & inibidores , Trombose Venosa/tratamento farmacológico , Trombose Venosa/diagnóstico por imagem , Resultado do Tratamento , Estudos Retrospectivos , Veias Mesentéricas/diagnóstico por imagem , Administração Oral , Oclusão Vascular Mesentérica/tratamento farmacológico , Oclusão Vascular Mesentérica/diagnóstico por imagem , Recidiva , Hemorragia/induzido quimicamente , Fatores de Tempo , Fatores de RiscoRESUMO
BACKGROUND: In vitro antioxidant activities and neuron-like PC12 cell protective effects of solvent fractions from aged garlic extracts were investigated to evaluate their anti-amnesic functions. Ethyl acetate fractions of aged garlic had higher total phenolics than other fractions. METHODS: Antioxidant activities of ethyl acetate fractions from aged garlic were examined using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) and malondialdehyde (MDA) inhibitory effect using mouse whole brain homogenates. Levels of cellular oxidative stress as reactive oxygen species (ROS) accumulation were measured using 2',7'-dichlorofluorescein diacetate (DCF-DA). PC12 cell viability was investigated by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydtrogenase (LDH) assay. The learning and memory impairment in institute of cancer research (ICR) mice was induced by neurotoxic amyloid beta protein (Aß) to investigate in vivo anti-amnesic effects of aged garlic extracts by using Y-maze and passive avoidance tests. RESULTS: We discovered that ethyl acetate fractions showed the highest ABTS radical scavenging activity and MDA inhibitory effect. Intracellular ROS accumulation resulting from Aß treatment in PC12 cells was significantly reduced when ethyl acetate fractions were presented in the medium compare to PC12 cells which was only treated with Aß only. Ethyl acetate fractions from aged garlic extracts showed protection against Aß-induced neurotoxicity. Pre-administration with aged garlic extracts attenuated Aß-induced learning and memory deficits in both in vivo tests. CONCLUSIONS: Our findings suggest that aged garlic extracts with antioxidant activities may improve cognitive impairment against Aß-induced neuronal deficit, and possess a wide range of beneficial activities for neurodegenerative disorders, notably Alzheimer's disease (AD).
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Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Cognição/efeitos dos fármacos , Alho/química , Extratos Vegetais/administração & dosagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Animais , Sobrevivência Celular , Humanos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
To describe long-term follow-up of 25 patients who presented with subarachnoid hemorrhages due to blood blister-like aneurysms (BBAs) treated with direct clipping or clip reinforcement with or without direct neck repair. Between June 1993 and July 2009, 25 consecutive patients with ruptured BBAs of the supraclinoid internal carotid artery were retrospectively reviewed. The mean age of patients was 39.5 ± 11.3 years. The mean duration of clinical follow-up was 128.9 months (range, 85-196 months). All aneurysms were located in the supraclinoid portion of the internal carotid artery. The mean aneurysm diameter was 4.04 ± 1.3 mm on intra-operative microscopic field. Tearing of the aneurysmal neck during dissection occurred in 8 (32%) patients. Six of 7 patients with neck tearing underwent direct neck repair. Surgeons treated aneurysms via direct clipping with a Bemsheet® in 5 (20%) patients or by clip reinforcement with a silicone sheet in 20 (80%) patients. Clinical outcomes were favorable (modified Rankin Scale [mRS]: 0-2) in 21 (84%) of 25 patients. Four (16%) patients had an unfavorable outcome (mRS: 3-6). The patient with severe disability (mRS: 4) was treated with clip reinforcement and direct neck repair. Mild stenosis, moderate stenosis, and total occlusion of the parent artery were confirmed in 10 (40%) patients, 6 (24%) patients, and 1 (4%) patient, respectively. Although surgical treatment of BBAs was associated with varying degrees of parent vessel patency loss, long-term follow-up results for more than 10 years showed that direct surgical clipping or clip reinforcement with a silicone sheet appeared to be a curative surgery.
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Aneurisma Roto , Aneurisma Intracraniano , Humanos , Adulto , Pessoa de Meia-Idade , Artéria Carótida Interna/cirurgia , Seguimentos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Constrição Patológica , Aneurisma Roto/cirurgia , Angiografia Cerebral , Resultado do TratamentoRESUMO
Considering the recent advancements in endovascular management of aortoiliac aneurysms, the use of an iliac branch device (IBD) to preserve pelvic blood flow and reduce complications caused by embolization of the internal iliac artery (IIA) is recommended by various guidelines. Although the outcomes reported following IBD placement are mainly positive and durable, IBD-specific complications such as a type Ic endoleak and associated reintervention may occur. Moreover, only one IBD device and one type of balloon-expandable bridging stent graft for IIA are currently available on the domestic market. Here we present two cases of type Ic endoleak following IBD placement. In both cases, IIA diameter was slightly larger than the basic instructions for use. Notably, the initial procedures were considered successful; however, type Ic endoleaks were detected on 1-month follow-up imaging. This finding emphasizes the need for a precise preoperative evaluation, intraoperative manipulation, and postoperative follow-up.
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Popliteal artery entrapment syndrome (PAES) is a rare vascular disorder characterized by the compression of the popliteal artery behind the knee, primarily affecting physically active individuals. This is a case of a 36-year-old man who presented with a 1-week history of sudden-onset left leg pain. Diagnostic evaluation, including physical examination, color duplex ultrasonography, computed tomography, and magnetic resonance imaging, revealed a popliteal artery pseudoaneurysm caused by type 5 PAES. The patient underwent surgical exploration to release the entrapment, followed by an interposition graft with the ipsilateral great saphenous vein. Patient postoperative recovery was uneventful, with significant symptomatic improvement. This case underscores the significance of considering PAES as a differential diagnosis in young patients with popliteal artery aneurysms and highlights the necessity for prompt diagnosis and treatment to prevent limb-threatening complications.
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One of the most affected aspects of the aging process is immunity, with age-related immune system decline being responsible for an increase in susceptibility to infectious diseases and cancer risk. On the other hand, the aging process is accompanied with low-grade pro-inflammatory status. This condition involves a persistent rise in cytokine levels that can activate both innate and adaptive immune systems. Finally, despite the fact that immunological responses to antigenic stimulations decrease with age, the incidence and prevalence of many common autoimmune diseases increase in the elderly population. Overall, the co-existence of a prolonged, low-grade inflammatory status and declining immune activity appears to be a paradoxical phenomenon. This study characterized skin inflammation in mouse dermatitis model of various ages to monitor possible changes of inflammatory responses during aging.
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Persistent sciatic artery (PSA) is a rare congenital anomaly considered an embryologic remnant of the internal iliac artery. Traditionally, the classification systems categorized PSA based on the completeness of PSA and superficial femoral artery (SFA) alongside the origin of PSA. The most common class has been known as type 2a in Pillet-Gauffre classification, meaning complete PSA with incomplete SFA. The mainstay of these patients with limb ischemia has been surgical bypass alongside excision or ligation of PSA aneurysm if present. However, the current PSA classification system does not account for collateral blood flow. Herein, we described two cases of type 2a PSA with distal embolization and explored therapeutic choices for PSA based on collateral presence. The first patient was treated with thromboembolectomy and patch angioplasty, and the second with conservative management. Despite distal embolization in both patients, bypass surgery was avoided, and distal circulation was maintained via collaterals from deep and superficial femoral arteries without increased risk of recurrent embolization. Thus, carefully examining collateral circulation and customized strategy is essential for managing PSA.
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Purpose: This study aimed to investigate the clinical outcomes of internal iliac artery (IIA) interruption during endovascular aneurysm repair (EVAR) and to identify the risk factors for ischemic complications. Materials and Methods: Endovascular treatment was performed in 316 patients with aneurysms or pseudoaneurysms of the abdominal aorta or iliac arteries between March 2006 and January 2022. Medical records and radiological imaging studies were retrospectively reviewed. The incidences of buttock claudication, ischemic colitis, and spinal cord ischemia after IIA interruption were investigated as clinical outcomes. Binary logistic regression analysis were performed to identify the risk factors. Results: IIA embolization was performed in 78 patients. Among the 42 patients who underwent IIA flow preservation procedures, the one-month computed tomography detected early failure in five patients. The origin of the IIA was covered with an endograft in ten patients who did not undergo embolization. Eventually, interruption of the IIA by EVAR was observed in 93 patients. Considering preoperative IIA occlusion, there was a total of six patients who did not have at least one IIA patency. Buttock claudication occurred in 32.6% of the patients, and none of the patients had ischemic colitis or spinal cord ischemia. In multivariable analysis, age ≤80 years and isolated iliac artery aneurysm were associated with the development of postoperative buttock claudication. Conclusion: The most common complication after IIA interruption is buttock claudication; however, critical complications such as ischemic colitis or spinal cord ischemia are rare, even in bilateral IIA occlusion. Adjunctive procedures to preserve bilateral IIA perfusion should be adopted selectively.
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Although hepatic artery aneurysms (HAAs) are uncommon, they are associated with risk of rupture. HAAs >2 cm in diameter require endovascular or open surgical repairs. For HAAs involving the proper hepatic artery or gastroduodenal artery, which is a collateral artery from the superior mesenteric artery, hepatic arterial reconstruction is especially important to avoid ischemic liver injury. In this study, right gastroepiploic artery transposition was performed in a 53-year-old man after a 4 cm common hepatic artery and proper hepatic artery aneurysm was identified. The patient was discharged without any complications on postoperative day 8.