RESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.
Asunto(s)
COVID-19 , Humanos , Adolescente , Persona de Mediana Edad , COVID-19/epidemiología , SARS-CoV-2 , Prevalencia , Estudios Retrospectivos , Radiografía , VacunaciónRESUMEN
BACKGROUND: To date, no study has investigated whether the neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) have a clinical value in Mycobacterium avium complex (MAC)-pulmonary disease (PD). METHODS: We aimed to assess whether the baseline NLR and MLR were different according to the severity of MAC-PD based on the radiologic classification by retrospectively analyzing 549 patients treated in a tertiary referral center in South Korea. RESULTS: Both NLR and MLR were significantly higher as 3.33 and 0.43 respectively in the fibrocavitary type, followed by 2.34 and 0.27 in the cavitary nodular bronchiectatic type and significantly lower as 1.88 and 0.23 in the non-cavitary nodular bronchiectatic type. CONCLUSION: The baseline NLR and MLR showed a distinct difference in accordance with the radiologic severity of MAC-PD.
Asunto(s)
Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/microbiología , Linfocitos , Monocitos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Neutrófilos , Estudios RetrospectivosRESUMEN
BACKGROUND: Phthalates can cause respiratory and immunological disorders. However, little is known about the role of serum periostin and YKL-40 levels in mediating the effects of phthalates. We investigated the mediating role of these biomarkers in the relationship between phthalates and airway dysfunction. METHODS: A total of 487 children (aged 10-12 years old) were examined. Four high-molecular-weight phthalate (HMWP) [Σ4 HMWP] metabolites and 3 low-molecular-weight phthalate (LMWP) [Σ3 LMWP] metabolites in urine samples were measured. Serum periostin and YKL-40 levels were measured. Airway function was measured using impulse oscillometry. A mediation model was used to quantify the mediating effects of periostin and YKL-40 on airway dysfunction. RESULTS: After adjustment for height, gender, BMI z-score, aeroallergen sensitization, secondary smoking, and vitamin D level, the level of urinary Σ3 LMWP metabolites was significantly associated with respiratory system resistance at 5 Hz (Rrs5; adjusted ß: 0.020, 95% CI: 0.005-0.034; p = .010). The levels of urinary Σ4 HMWP and Σ3 LMWP metabolites were significantly associated with periostin level, but not with YKL-40 level. In addition, the periostin level was associated with Rrs5 (adjusted ß: 0.048, 95% CI: 0.015-0.081; p = .005) and Rrs20-5 (adjusted ß: 0.040, 95% CI: 0.011-0.069; p = .007). Serum periostin level had a significant effect in mediating the relationship between Σ3 LMWP and Rrs5 (13.9%, 95% CI: 10.7-77.0; p < .001). CONCLUSION: Exposure to LMWPs was significantly associated with airway dysfunction, and this effect was partially attributable to increased serum periostin level.
Asunto(s)
Ácidos Ftálicos , Biomarcadores , Niño , Humanos , Pruebas de Función Respiratoria , Sistema RespiratorioRESUMEN
Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost-containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher-quality evidence for high single-dose rATG, and dose-rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target-attainment or on ideal-body-weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost-saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high-cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost-burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient-specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost-saving initiatives in the transplant population.
Asunto(s)
Trasplante de Riñón , Trasplantes , Suero Antilinfocítico/uso terapéutico , Rechazo de Injerto/prevención & control , Humanos , InmunosupresoresRESUMEN
BACKGROUND: Early aspirin (ASA) use after orthotopic heart transplantation (OHT) has been associated with lower rates of cardiac allograft vasculopathy (CAV). We hypothesized that the inverse association between ASA use and CAV incidence may be most pronounced in patients with allograft rejection. METHODS: Patients receiving OHT at a single center 2004-2010 (n = 120) were categorized by early ASA use post-transplant (ASA use for > 6 months in the first year) and the presence of biopsy-defined acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR) during 5-year follow-up. Propensity scores for ASA treatment were estimated using boosting models and applied by inverse probability of treatment weighting. The association between ASA use and time to moderate/severe CAV (ISHLT ≥ 2) was investigated. RESULTS: Among patients with ACR or AMR, ASA therapy was associated with significantly lower rates of CAV≥ 2 (3.3 vs. 30.1%; P = .001; HRadj .07; 95% CI .01-.52), whereas ASA therapy was not associated with lower rates of CAV in patients with no rejection (5.6 vs. 5.3%; P = .90; HRadj 1.26; 95% CI .08-20.30; pinteraction = .09). CONCLUSIONS: Early ASA use after OHT was associated with lower rates of moderate to severe CAV only in those patients with episodes of allograft rejection.
Asunto(s)
Aspirina , Trasplante de Corazón , Aloinjertos , Aspirina/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Trasplante de Corazón/efectos adversos , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Low body mass index (BMI) is an important prognostic factor in chronic obstructive pulmonary disease (COPD). However, the prognostic value of longitudinal BMI change in COPD has not been well studied. OBJECTIVE: We aimed to evaluate the association between longitudinal change of BMI and prognosis of COPD in Korean COPD cohort. METHODS: This study was conducted in a prospective Korean Obstructive Lung Disease (KOLD) cohort where COPD patients were recruited on an outpatient basis at 17 hospitals in South Korea. Annual BMI was measured over a period of 3 years or more. All patients were categorized into underweight (UW), normal weight (NW), and overweight (OW) groups by BMI. Clinical characteristics and outcomes including exacerbation and mortality were compared based on initial BMI grade and longitudinal change of BMI. RESULTS: This analysis included 537 COPD patients (mean age = 67.4 ± 7.9 years, male = 97.0%, mean BMI = 23.0 ± 3.1) of KOLD cohort. The proportions of UW, NW, and OW groups were 6.9% (n = 37), 68.9% (n = 370), and 24.2% (n = 130) respectively. The UW group showed lower forced expiratory volume in 1 s (FEV1) (p < 0.001), shorter 6-minute walk distance (p < 0.001), higher modified Medical Research Council score (p = 0.002), higher St. George Respiratory Questionnaire score (p < 0.001), higher emphysema index (p < 0.001) and air-trapping index (p < 0.001), and more frequent (p < 0.001) and severe exacerbations (p = 0.003). Multivariable analyses demonstrated that decrease of BMI (hazard ratio [HR] = 0.786, p = 0.038) and the descent of BMI group (HR = 3.167, p = 0.016) at 3-year follow-up along with age, initial BMI, post-bronchodilator FEV1, and severe exacerbations were significantly associated with mortality. CONCLUSIONS: This study demonstrated that BMI decrease during follow-up was independently associated with exacerbation and higher mortality of COPD, suggesting BMI reduction in COPD should be carefully managed.
Asunto(s)
Índice de Masa Corporal , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Delgadez/fisiopatología , Pérdida de Peso/fisiología , Anciano , Pueblo Asiatico , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , República de Corea , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
The larva of Allomyrina dichotoma (family Scarabaeidae) is an edible insect that is registered in the Korean Food Standards Codex as a food resource. The chemical study on the larvae of A. dichotoma resulted in the isolation of three new tetrahydroquinolines, allomyrinaines A-C (1-3), one new dopamine derivative, allomyrinamide A (4), and four known compounds (5-8). The structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) and MS spectroscopic data analysis. Allomyrinaines A-C (1-3) possessed three stereogenic centers at C-2, C-3, and C-4, whose relative configurations were determined by analyses of the coupling constants and the nuclear Overhauser enhancement spectroscopy (NOESY) data, as well as DP4+ calculation. The anti-inflammatory effects of compounds 1-4 were evaluated in human endothelial cells. Allomyrinaines A-C (1-3) could stabilize vascular barrier integrity on lipopolysaccharide (LPS)-induced vascular inflammation via inhibition of the nuclear factor-κB (NF-κB) pathway. The physiologically relevant concentration was confirmed by Q-TOF-MS-based quantitative analysis on allomyrinaines A-C in crude extract. This study suggests that allomyrinaines A-C (1-3) are bioactive constituents of A. dichotoma to treat vascular inflammatory disorder.
Asunto(s)
Escarabajos/química , Insectos Comestibles/química , Inflamación/prevención & control , Quinolinas/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Citocinas/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos , Espectroscopía de Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , Estructura Molecular , FN-kappa B/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Quinolinas/químicaRESUMEN
OBJECTIVES: Curative resection is not indicated for non-small cell lung cancer (NSCLC) with pleural seeding, which is classified as stage IV (M1a) disease. However, some patients with a presumably resectable main tumor are diagnosed with localized pleural seeding during surgery. METHODS: A retrospective analysis was performed of 3,975 patients who underwent surgery for NSCLC from 2000 to 2011. Among these cases, 78 (2.0%) patients had unexpected pleural seeding detected during surgery. Exploration with pleural biopsy was performed in 42 of these patients (exploration-only group) and pulmonary resection, including for the main tumor, was performed in 36 cases (resection group; sublobar resection in 12, lobectomy in 21, and pneumonectomy in 3 patients). Survival and cancer progression rates were estimated using the Kaplan-Meier method. Cox proportional hazard regression was used to evaluate prognostic factors associated with survival. RESULTS: Adenocarcinoma was the predominant histological type in both the exploration and resection groups (88.1 and 86.1%, respectively). Epidermal growth factor receptor expression was detected in 22 (52.4%) patients of the exploration group and 21 (58.3%) patients of the resection group. Baseline characteristics including age, sex, comorbidity, pulmonary function, and clinical T/N status were not significantly different between the two groups. There were no postoperative deaths in either group but postoperative complications occurred in two (4.8%) patients of the exploration group and three (8.3%) patients of the resection group. The overall 3- and 5-year survival rates in the exploration group were 41.1 and 15.2%, respectively, with a median survival time (MST) of 33 months, whereas they were 66.7 and 42.7%, respectively, in the resection group, with a 52-month MST (p = 0.012). Local and regional progression-free rates were significantly different (p < 0.001 and p = 0.029, respectively) between groups, whereas no difference was seen in the distant metastasis rates (p = 0.957). In multivariate survival analysis, surgical resection was the only significant prognostic factor (p = 0.01). CONCLUSIONS: Pulmonary resection including the main tumor, regardless of resection extent, may increase long-term survival for NSCLC patients with localized pleural seeding first detected during surgery, without a significant increase in hospital mortality or morbidity.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias Pleurales/cirugía , Neumonectomía , Anciano , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/secundario , Neumonectomía/efectos adversos , Neumonectomía/métodos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To assess if color measurement with intraoral scanner correlates with digital colorimeter and to evaluate the possibility of application of a digital scanner for shade selection. MATERIALS AND METHODS: The L*a*b* values of the five shade tabs (A1, A2, A3, A3.5, and A4) were obtained with an intraoral scanner (TRIOS Pod) and a colorimeter (ShadeEye). Both devices were calibrated according to the manufacturer's instructions before measurements. Color measurement values were compared with paired t-test, and a Pearson's correlation analysis was performed to evaluate the relationship of two methods. RESULTS: The L*a*b* values of the colorimeter were significantly different from those of the digital scanner (p < 0.001). The L* and b* values of both methods were strongly correlated with each other (both p < 0.05). The device repeatability in both methods were reported to be excellent (p < 0.05). Within the limitations of this study, color measurements with digital intraoral scanners and computer-assisted image analysis were in accordance with those of the colorimeter with respect to L* and b* values; however, all the coordinates of shade tabs were significantly different between two methods. CONCLUSIONS: The digital intraoral scanner may not be used as the primary method of color selection in clinical practices, considering significant differences in color parameters with colorimeter. The scanner's capability in shade selection should be further evaluated.
Asunto(s)
Colorimetría/instrumentación , Diseño de Prótesis Dental , Procesamiento de Imagen Asistido por Computador , Coloración de Prótesis/métodos , HumanosRESUMEN
Protaetia brevitarsis seulensis (Kolbe) has been temporarily registered as a food material by the Ministry of Food and Drug Safety of Korea (MFDS). The current study aimed to discover small antithrombotic molecules from this edible insect. Five indole alkaloids, 5-hydroxyindolin-2-one (1), (1R,3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (2), (1S,3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (3), (3S)-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (4) and L-tryptophan (5), were isolated from the insect. Among them, compounds 1 and 2 prolonged aPTT and PT and impaired thrombin and FXa generation on HUVEC surface. Moreover, these compounds inhibited platelet aggregation. Antithrombotic effects of compounds 1 and 2 were further confirmed in pre-clinical models of pulmonary embolism and arterial thrombosis. Collectively, these results demonstrated that compounds 1 and 2 could be effective antithrombotic agents and serve as new scaffolds for the development of antithrombotic drug.
Asunto(s)
Alcaloides Indólicos/farmacología , Agregación Plaquetaria/efectos de los fármacos , Trombosis/tratamiento farmacológico , Animales , Escarabajos/química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/aislamiento & purificación , Insectos/química , Trombosis/patologíaRESUMEN
Recently, we reported that Lumbricusin, an antimicrobial peptide isolated from earthworm Lumbricus terrestris, enhanced neuronal proliferation and ameliorated motor dysfunction and dopaminergic neurodegeneration. Accumulating evidence suggests that neurodegeneration is the primary pathological feature of acute or chronic inflammation mediated by microglia, the resident macrophage of the central nervous system. Therefore, microglial activation inhibitors may be useful as therapeutic agents for neurodegenerative diseases. To determine whether Lumbricusin ameliorates neuroinflammation through inhibition of microglial activation by lipopolysaccharides (LPS), we newly synthesized 9-mer Lumbricusin analogues based on the amino acid sequence of Lumbricusin. One of these, Lumbricusin Analogue 5 (LumA5; QLICWRRFR-NH2), markedly reduced expression of enzymes (COX-2, iNOS), cytokines (IL-6, IL-1ß, TNF-α), and signal transduction factors (AKT, MAPKs, NF-κB) involved in inflammation triggered by LPS in vitro and in vivo. In addition, LumA5 inhibited the cytotoxicity of conditioned medium prepared by LPS-activated BV-2 microglia to neuronal SH-SY5Y cells and improved cell viability. These results indicate that LumA5 may be a potential therapeutic agent for the treatment of various neuroinflammatory conditions.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Proteínas del Helminto/química , Proteínas del Helminto/farmacología , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Animales , Antiinflamatorios/uso terapéutico , Línea Celular , Citocinas/inmunología , Proteínas del Helminto/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Microglía/inmunología , Microglía/patología , Proteínas Quinasas Activadas por Mitógenos/inmunología , Fármacos Neuroprotectores/uso terapéutico , Oligoquetos/química , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal/efectos de los fármacosAsunto(s)
Antagonistas de los Receptores Histamínicos , Rinitis Alérgica , Humanos , Antagonistas de los Receptores Histamínicos/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Administración Intranasal , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. METHODS: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. RESULTS: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza. CONCLUSIONS: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.
Asunto(s)
Gripe Humana/mortalidad , Infecciones por Virus Sincitial Respiratorio/mortalidad , Adulto , Hospitales de Enseñanza , Humanos , Estudios RetrospectivosRESUMEN
Despite the increasing interest in insect-based bioactive products, the biological activities of these products are rarely studied adequately. Larvae of Tenebrio molitor, the yellow mealworm, have been eaten as a traditional food and provide many health benefits. Therefore, we hypothesized that T. molitor larvae might influence adipogenesis and obesity-related disorders. In the present study, we investigated the anti-adipogenic and antiobesity effects of T. molitor larvae in vitro and in vivo. The lipid accumulation and triglyceride content in mature adipocytes was reduced significantly (up to 90%) upon exposure to an ethanol extract of T. molitor larvae, without a reduction in cell viability. Exposure also resulted in key adipogenic and lipogenic transcription factors. Additionally, in adipogenic differentiation medium the extract induced phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and mitogen-activated protein kinases. Daily oral administration of T. molitor larvae powder to obese mice fed high-fat diet attenuated body weight gain. We also found that the powder efficiently reduced hepatic steatosis as well as aspartate and alanine transaminase enzyme levels in mice fed a high-fat diet. Our results suggest that T. molitor larvae extract has an antiobesity effect when administered as a food supplement and has potential as a therapeutic agent for obesity.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Productos Biológicos/administración & dosificación , Larva , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Obesidad/metabolismo , Transducción de Señal/efectos de los fármacos , Tenebrio , Células 3T3-L1 , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipogénesis/genética , Tejido Adiposo/anatomía & histología , Tejido Adiposo/efectos de los fármacos , Animales , Fármacos Antiobesidad/administración & dosificación , Peso Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Dieta Alta en Grasa , Suplementos Dietéticos , Modelos Animales de Enfermedad , Hígado Graso/tratamiento farmacológico , Hígado Graso/etiología , Hígado Graso/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/etiología , Fosforilación , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The CopA3 dimer peptide is a coprisin analog that has an anticancer effect against human cancer cells in vitro. In this study, we investigated the anticancer activity of the enantiomeric CopA3 dimer peptide in human gastric cancer cell lines as well as in an in vivo tumor xenograft model. Enantiomeric CopA3 reduced gastric cancer cell viability and exhibited cytotoxicity against cancer cells. Enantiomeric CopA3-induced cell death was mediated by specific interactions with phosphatidylserine and phosphatidylcholine, membrane components that are enriched in cancer cells, in a calcein leakage assay. Moreover, acridine orange/ethidium bromide staining, flow cytometric analysis, and Western blot analysis showed that enantiomeric CopA3 induced apoptotic and necrotic gastric cancer cell death. The antitumor effect was also observed in a mouse tumor xenograft model in which intratumoral inoculation of the peptide resulted in a significant decrease in the SNU-668 gastric cancer tumor volume. In addition, periodic acid-Schiff and hematoxylin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed apoptotic and necrotic cell death in tumor masses treated with greater than 150 µg CopA3. Collectively, these results indicate that the enantiomeric CopA3 dimer peptide induces apoptosis and necrosis of gastric cancer cells in vitro and in vivo, indicating that the peptide is a potential candidate for the treatment of gastric cancer, which is a common cause of cancer and cancer deaths worldwide.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Proteínas de Insectos/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Secuencia de Aminoácidos , Animales , Péptidos Catiónicos Antimicrobianos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Caspasas/metabolismo , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Proteínas de Insectos/química , Ratones Endogámicos BALB C , Ratones Desnudos , Multimerización de Proteína , Transducción de Señal/efectos de los fármacos , Estereoisomerismo , Neoplasias Gástricas/patología , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: The cytomegalovirus (CMV) donor-positive/recipient-positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate-risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head-to-head analysis, to our knowledge, comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs 900 mg/day for 3 months in D+/R+ RTR. METHODS: A multicenter, retrospective analysis evaluated 478 adult RTR between January 2008 and October 2011. Study participants received VGCV 450 mg/day (Group 1; n=398) or 900 mg/day (Group 2; n=89)×3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study-approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months. RESULTS: The rates of graft loss, patient survival, T-cell and/or antibody-mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups. CONCLUSION: The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs 3.4%; P=1.000). Log-rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P=.939).
Asunto(s)
Profilaxis Antibiótica/métodos , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Citomegalovirus/aislamiento & purificación , Ganciclovir/análogos & derivados , Trasplante de Riñón/efectos adversos , Adulto , Aloinjertos/virología , Antivirales/administración & dosificación , Antivirales/efectos adversos , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/virología , Femenino , Estudios de Seguimiento , Ganciclovir/administración & dosificación , Ganciclovir/efectos adversos , Ganciclovir/uso terapéutico , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Humanos , Terapia de Inmunosupresión/métodos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/epidemiología , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Pruebas Serológicas , Receptores de Trasplantes , Resultado del Tratamiento , ValganciclovirRESUMEN
STATEMENT OF PROBLEM: Conventional impression-making methods are being replaced by intraoral digital scanning. How long dental professionals take to master the new technologies is unknown. PURPOSE: The purpose of this human subject study was to compare the experience curves of 2 intraoral scanners among dental hygienists and determine whether repeated scanning experience could change the scan time (ST). MATERIAL AND METHODS: A total of 29 dental hygienists with more than 3 years of working experience were recruited (group 1: 3-5 years; group 2: >6 years of clinical experience) to learn the iTero and Trios systems. All learners scanned the oral cavities of 4 human participants (participants A, B, C, and D) 10 times (T1-T10) throughout the learning sessions and the experimental dentoform model twice at the beginning and end of the 10 sessions. ST was measured, and changes in ST were compared between the 2 devices. RESULTS: The average ST for 10 sessions was greater with iTero than with Trios, but the decrease in the measured ST was greater for iTero than for Trios. Baseline and postexperience STs with iTero showed statistically significant differences, with a decrease in time related to the clinical experience levels of the dental hygienists (group 1: T2 and T4, P<.01; group 2: T2 and T5, P<.01). The experience curve with iTero was not influenced by the human participant's intraoral characteristics, and greater ST was shown for participants B and C than for participants A and D with Trios. CONCLUSIONS: Although the learning rate of iTero was rapid, the average ST for iTero was longer than Trios, and clinical experience levels influenced the operator's ability to manipulate the device. In contrast, the learning rate of Trios was slow, and measured ST was shorter than iTero, and was not influenced by clinical experience.
Asunto(s)
Higienistas Dentales , Técnica de Impresión Dental/instrumentación , Procesamiento de Imagen Asistido por Computador , Curva de Aprendizaje , Modelos Dentales , Tomógrafos Computarizados por Rayos X , Competencia Clínica , Simulación por Computador , HumanosRESUMEN
BACKGROUND: S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. METHODS: Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027Ax2192;G and -1608Tx2192;C were genotyped. RESULTS: Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). CONCLUSION: S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.