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BACKGROUND: During the process of managing suicide attempters in the emergency department (ED), the importance of hospitalization has been emphasized. Lethality and intent have been suggested as hospitalization determinants of suicide attempters, but their predictive values remain limited in adult and elderly populations. METHODS: Using prospectively collected the ED-based Suicide Registry, data from suicide attempters over 18 years old was retrospectively studied (2010-2020). The enrolled participants were divided into adult (N = 832) and elderly (>65 years, N = 378) groups. Suicide lethality and intent were assessed by the Risk-Rescue Rating Scale (RRRS) and Suicide Intent Scale (SIS), respectively. The moderating effects of age on the relationship between the psychological scales and hospitalization were examined by entering the interaction terms into a multivariable regression model. The predictive ability of each scale for hospitalization was evaluated in terms of performance and goodness-of-fit. RESULTS: Both scales' scores in both age groups were significantly higher in hospitalized patients than non-hospitalized patients. Interaction result indicated that only the odds of RRRS for hospitalization significantly differed by age group. Moreover, the predictive performance for hospitalization significantly differed by age group in RRRS but not SIS. In predicting hospitalization, the AUC of the RRRS was significantly higher than that of the SIS in the elderly group but not in the adult group. Comparing the two groups, the RRRS of the elderly group tended to have higher AUC than the adult group, whereas the AUC of the SIS was similar. The RRRS in both groups had a better overall fit compared to the SIS for hospitalization, but its best overall fit and strength with greater power were observed in the elderly group. CONCLUSIONS: The age-by-RRRS interaction is significantly associated with hospitalization, and the RRRS implementation as a hospitalization determinant is more useful and suitable for elderly suicide attempters than for adult suicide attempters in an emergency setting.
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Hospitalización/estadística & datos numéricos , Escalas de Valoración Psiquiátrica/normas , Intento de Suicidio/psicología , Adulto , Factores de Edad , Anciano , Servicio de Urgencia en Hospital/organización & administración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sistema de Registros , Estudios Retrospectivos , Sensibilidad y Especificidad , Intento de Suicidio/estadística & datos numéricosRESUMEN
BACKGROUND: Reduced cholesterol levels are associated with poor outcomes in critically ill patients. However, the effect of reduced cholesterol levels on the prognosis of patients with community-acquired pneumonia (CAP) is unclear. This study aimed to investigate the association between serum total cholesterol levels and the clinical outcomes of elderly patients with CAP. METHODS: This was a retrospective observational study that included elderly (≥65 years) CAP patients hospitalized through emergency department between January 2016 and December 2019. We collected their baseline characteristics and laboratory data, including total cholesterol levels at the time of admission. Univariate and multivariate analyses were performed to determine the association between total cholesterol levels and 14-day in-hospital mortality. RESULTS: A total of 380 patients were included. The overall 14-day in-hospital mortality rate was 12.37%. Survivors had higher total cholesterol levels than non-survivors (median, 125 mg/dL; interquartile range [IQR], 102-151 mg/dL versus median, 100 mg/dL; IQR, 83-126 mg/dL; p < 0.001). Multivariate analysis using a logistic regression model showed that a total cholesterol level of <97 mg/dL was independently associated with 14-day in-hospital mortality in patients with CAP (odds ratio, 2.93; 95% confidence interval, 1.13-7.599; p = 0.027). CONCLUSIONS: A decreased level of total cholesterol was associated with increased short-term mortality in elderly patients with CAP. Initial total cholesterol levels may be a useful biomarker to predict the outcome of patients with CAP.
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Colesterol/sangre , Infecciones Comunitarias Adquiridas/mortalidad , Servicio de Urgencia en Hospital , Neumonía/mortalidad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Puntuaciones en la Disfunción de Órganos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Phlegmonous gastritis (PG) is a rare and potentially fatal disease characterized by bacterial infection of the gastric wall. However, its clinical features are nonspecific, which may delay its diagnosis and treatment. CASE REPORT: We report a case of a previously healthy 53-year-old woman with localized PG complicated by subphrenic abscess formation who was treated successfully with antibiotics and percutaneous catheter drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early diagnosis and treatment initiation are important to improving outcomes. Emergency physicians should consider PG a differential diagnosis of acute abdomen.
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Gastritis , Absceso Subfrénico , Enfermedad Aguda , Antibacterianos/uso terapéutico , Femenino , Gastritis/complicaciones , Gastritis/diagnóstico , Humanos , Persona de Mediana Edad , Absceso Subfrénico/tratamiento farmacológicoRESUMEN
BACKGROUND: The purpose of this study was to evaluate the psychological scales reflecting lethality and intent as predictors of suicide attempter's hospitalization. METHODS: Data of suicide attempters aged over 15years, who visited the ED from January 2013 to June 2016, were retrospectively collected and they were divided into the hospitalization and discharge groups. We evaluated the Risk-Rescue Rating Scale (RRRS) and Self-Inflicted Injury Severity Form (SIISF) for lethality and Suicide Intent Scale (SIS) for intent, respectively. The predictive abilities of these scales for hospitalization were compared in terms of performance (AUCs) and goodness-of-fit (the Bayesian information criterion [BIC]). RESULTS: A total of 382 suicide attempters were enrolled, of which 233 (61%) were hospitalized. The scores of all psychological scales were significantly higher in the hospitalization group and all scales were identified as independent predictors of hospitalization. The AUC of the RRRS tended to be higher than those of the SIS and SIISF; similarly, the RRRS demonstrated the best overall fit (the lowest BIC). The AUC of combined the RRRS and SIS was superior to that of any of the individual scales alone. While the AUC of combined the SIISF and SIS was superior to that of either individual scale, it was comparable to that of the RRRS. CONCLUSIONS: The psychological scales can be helpful for predicting suicide attempter's hospitalization in emergency settings. Especially, the RRRS seemed to have a superior predictive ability. Moreover, combining the scales had significantly better predictive performance than use of the individual scale alone did.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Escalas de Valoración Psiquiátrica , Intento de Suicidio/psicología , Adulto , Teorema de Bayes , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: To investigate whether 48 hours of therapeutic hypothermia is more effective to attenuate brain apoptosis than 24 hours and to determine whether the antiapoptotic effects of therapeutic hypothermia are associated with the suppressions of the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Male domestic pigs (n = 24). INTERVENTIONS: After 6 minutes of no-flow time that was induced by ventricular fibrillation, cardiopulmonary resuscitation was provided, and the return of spontaneous circulation was achieved. The animals were randomly assigned to the following groups: sham, normothermia, 24 hours of therapeutic hypothermia, or 48 hours of therapeutic hypothermia. Therapeutic hypothermia (core temperature, 32-34°C) was maintained for 24 or 48 hours post return of spontaneous circulation, and the animals were rewarmed for 8 hours. At 60 hours post return of spontaneous circulation, the animals were killed, and brain tissues were harvested. MEASUREMENTS AND MAIN RESULTS: We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in the hippocampus. The 48 hours of therapeutic hypothermia attenuated cellular apoptosis and neuronal damage when compared with normothermia. There was also a decrease in the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3. However, 24 hours of therapeutic hypothermia did not significantly attenuate cellular apoptosis or neuronal damage. CONCLUSIONS: We found that 48 hours of therapeutic hypothermia was more effective in attenuating brain apoptosis than 24 hours of therapeutic hypothermia. We also found that the antiapoptotic effects of therapeutic hypothermia were associated with the suppressions of the cleavage of protein kinase C-δ, the cytosolic release of cytochrome c, and the cleavage of caspase 3.
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Apoptosis , Encéfalo/patología , Paro Cardíaco/prevención & control , Hipotermia Inducida/métodos , Animales , Masculino , Porcinos , Factores de TiempoRESUMEN
OBJECTIVE: This study investigated the associations between paraspinal muscle measurements on chest computed tomography and clinical outcomes of elderly patients with community-acquired pneumonia (CAP). METHODS: This single-center, retrospective, observational study analyzed elderly patients (≥65 years) with CAP hospitalized through an emergency department between March 2020 and December 2022. We collected their baseline characteristics and laboratory data at the time of admission. The paraspinal muscle index and attenuation were calculated at the level of the 12th thoracic vertebra using chest computed tomography taken within 48 hours before or after admission. Univariable and multivariable logistic regression analyses were conducted to evaluate the association between paraspinal muscle measurements and 28-day mortality. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to evaluate the prognostic predictive power. RESULTS: Of the 338 enrolled patients, 60 (17.8%) died within 28 days after admission. A high paraspinal muscle index was associated with low 28-day mortality in elderly patients with CAP (adjusted odds ratio, 0.994; 95% confidence interval, 0.992-0.997). The area under the ROC curve for the muscle index was 0.75, which outperformed the pneumonia severity index and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65 years) metric, both of which showed an AUC of 0.64 in predicting mortality. CONCLUSION: A high paraspinal muscle index was associated with low 28-day mortality in patients aged 65 years or older with CAP.
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OBJECTIVES: To determine whether niacin attenuates brain injury and improves neurological outcome after cardiac arrest in rats and if its therapeutic benefits are associated with suppression of the mitogen-activated protein kinase pathway. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats (n=77). INTERVENTIONS: After 6 minutes of no flow time induced by ventricular fibrillation, cardiopulmonary resuscitation was provided and return of spontaneous circulation was achieved. Animals were then administered vehicle, single low dose (360 mg/kg; at 1 hr postreturn of spontaneous circulation), single high dose (1080 mg/kg; at 1 hr), or repeated low dose of niacin (360 mg/kg/d for 3 d; at 1, 24, and 48 hr) through an orogastric tube. MEASUREMENTS AND MAIN RESULTS: Neurologic deficit scales were scored at 24 hours, 72 hours, and 7 days postreturn of spontaneous circulation. Single high dose of niacin improved neurologic deficit scales at 48 hours and 7 days, and repeated low dose of niacin improved neurologic deficit scales at 7 days. Then, a separate set of animals were killed at 72 hours postreturn of spontaneous circulation, and brain tissues were harvested. Single high dose and repeated low dose of niacin attenuated cellular apoptosis and neuronal damage in hippocampal cornu ammonis 1 and decreased axonal injury and microglial activation in corpus callosum. They increased nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate and reduced glutathione levels, and decreased malondialdehyde level in brain tissues. Furthermore, they suppressed the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3. However, they failed to enhance extracellular signal-regulated kinases 1/2 phosphorylation. CONCLUSIONS: Single high dose and repeated low dose of niacin attenuated brain injury and improved neurological outcome after cardiac arrest in rats. Their therapeutic benefits were associated with suppressions of the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3.
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Lesiones Encefálicas/prevención & control , Paro Cardíaco/complicaciones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Niacina/farmacología , Vasodilatadores/farmacología , Animales , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Niacina/administración & dosificación , Fosforilación , Estudios Prospectivos , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Spontaneous spinal epidural hematoma (SEH) is a rare disease. Furthermore, Brown-Séquard syndrome due to spontaneous SEH has been rarely reported. Early detection of spontaneous SEH is not easy because early symptoms are often atypical and neurologic findings are often absent in the early stage. Early diagnosis and urgent surgical management are needed to prevent permanent neurologic deficits. We report a case of a 30-year-old patient who presented with Brown-Séquard syndrome due to spontaneous SEH. The patient has recovered successfully without any complications through surgical decompression within 12 hours of onset.
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Síndrome de Brown-Séquard/diagnóstico , Hematoma Espinal Epidural/diagnóstico , Adulto , Síndrome de Brown-Séquard/etiología , Síndrome de Brown-Séquard/cirugía , Hematoma Espinal Epidural/complicaciones , Hematoma Espinal Epidural/cirugía , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with community-acquired pneumonia (CAP) has not been evaluated. The aim of the present study was to investigate whether NT-proBNP level could predict mortality in hospitalised CAP patients. METHODS: We performed a structured medical record review of all hospitalised CAP patients from May 2003 to October 2006, and classified patients into the 30-day survival and non-survival group. Data included demographic and clinical characteristics, and laboratory findings including NT-proBNP levels. The APACHE II scores, PSI (pneumonia severity index) and CURB65 (confusion, urea, respiratory rate, blood pressure and aged 65 or more) scores were calculated. Comparisons between survivors and non-survivors were made with χ(2), non-parametric tests and logistic regression and ROC analysis were used to compare the ability of NT-proBNP (adjusted for age, heart failure and creatinine), APACHE II, PSI and CURB65 to predict mortality. RESULTS: Of 502 patients, 61 (12.2%) died within 30 days. NT-proBNP levels were measured in 167 patients and were significantly higher in non-survivors compared to survivors (median 841.7 (IQR 267.1-3137.3) pg/ml vs 3658.0 (1863.0-7025.0) pg/ml, p=0.019). NT-proBNP was an independent predictor of mortality (adjusted OR 1.53; 95% CI 1.16 to 2.02, p=0.002). The AUC for NT-proBNP was 0.712 (95% CI, 0.613 to 0.812), which was comparable to those of PSI (0.749, p=0.531) and CURB65 (0.698, p=0.693), but inferior to that of APACHE II (0.831, p=0.037). Adding NT-proBNP to APACHE II, PSI and CURB65 did not significantly increase the AUCs, respectively. CONCLUSIONS: NT-proBNP level is an independent predictor of mortality in hospitalised CAP patients. The performance of NT-proBNP level is comparable to those of PSI and CURB65 in predicting mortality.
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Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Neumonía/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/terapia , Servicio de Urgencia en Hospital , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Neumonía/mortalidad , Neumonía/terapia , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The relationship between body mass index (BMI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been fully investigated in patients with community-acquired pneumonia (CAP). METHODS: This prospective observational study examined 510 consecutive patients hospitalized for CAP. NT-proBNP, BMI, and the pneumonia severity index (PSI) were determined for all participants. The moderating effects of BMI on the relationship between NT-proBNP and CAP mortality were examined using interaction terms in a multivariable regression model. The ability of NT-proBNP to predict mortality was evaluated using the area under the curve (AUC). RESULTS: A significant inverse relationship was observed between BMI and NT-proBNP. After multivariable adjustment including BMI, NT-proBNP remained a significant predictor of CAP mortality. The AUC of the fully adjusted (including BMI) NT-proBNP model was significantly higher than that excluding BMI (p = 0.021) and that of PSI (p = 0.038), respectively. The predictive performance of NT-proBNP for mortality significantly differed by BMI group, with the NT-proBNP of the overweight and obesity group having a significantly higher AUC than that of the underweight and normal-weight group. The AUC of NT-proBNP was significantly higher and tended to be higher than that of PSI in the overweight group (p = 0.013) and the obesity group (p = 0.113), respectively. CONCLUSIONS: BMI significantly strengthens the prognostic performance of NT-proBNP in CAP patients. The BMI-NT-proBNP interaction is significantly associated with CAP mortality, but as a prognostic determinant for CAP, NT-proBNP seems to be more useful for overweight and obese patients than for underweight and normal-weight patients.
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Insuficiencia Cardíaca , Neumonía , Biomarcadores , Índice de Masa Corporal , Humanos , Péptido Natriurético Encefálico , Fragmentos de Péptidos , PronósticoRESUMEN
AIM: We sought to investigate whether the Geriatric Nutritional Risk Index is associated with systemic organ dysfunction among older patients who present with cholecystitis to the emergency department. METHODS: This was an observational retrospective study among consecutive older patients with cholecystitis in the emergency department from 2012 to 2018. We collected baseline characteristics and laboratory data, and re-categorized the Geriatric Nutritional Risk Index into three risk groups. We carried out univariate and multivariate analyses to identify factors associated with systemic organ dysfunction. Logistic regression was used for statistical analysis. RESULTS: A total of 303 patients were included in this study. The median age of participants was 74 years (interquartile range 68-79 years). The overall proportion of systemic organ dysfunction was 26.4%. The Geriatric Nutritional Risk Index was stratified as: ≥98 (n = 183, systemic organ dysfunction 15.3%), 87 to <98 (n = 90, systemic organ dysfunction 38.9%) and <87 (n = 30, systemic organ dysfunction 56.7%). Multivariate analysis using a logistic regression model showed that age, respiratory rate, temperature, geriatric nutritional risk index and quick Sepsis-related Organ Failure Assessment score in the emergency department were independently associated with systemic organ dysfunction in patients with cholecystitis. CONCLUSIONS: The Geriatric Nutritional Risk Index was recognized as an independent factor associated with systemic organ dysfunction in older patients in the emergency department who presented with cholecystitis. This index might be helpful in screening patient risk and deciding whether to carry out further tests. Geriatr Gerontol Int 2020; 20: 455-460.
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Colecistitis/diagnóstico , Evaluación Geriátrica/métodos , Estado Nutricional , Anciano , Anciano de 80 o más Años , Colecistitis/complicaciones , Servicio de Urgencia en Hospital , Femenino , Humanos , Modelos Logísticos , Masculino , Insuficiencia Multiorgánica/complicaciones , Insuficiencia Multiorgánica/diagnóstico , Puntuaciones en la Disfunción de Órganos , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sepsis/diagnósticoRESUMEN
BACKGROUND: The older population (≥65 years) has rapidly increased in size in recent years. Among them, the middle-to-oldest-old (≥75 years) tend to have a poor health status. Therefore, subdivision and evaluation of older patients with traumatic injury are required. We focused on the risk of femoral intertrochanteric fractures occurring in older adults due to minor falls and compared young-old and middle-to-oldest-old populations. METHODS: The medical records of patients who visited the emergency center due to hip injuries between March 2017 and March 2019 were retrospectively analyzed. Patients were divided into older adult (≥65 years) and non-older (age 18-64 years) groups; the older adult group was subdivided into young-old (65-74 years), middle-old (75-84 years), and oldest-old (≥85 years) groups. This study investigated the occurrence rate of femoral intertrochanteric fractures and related factors. RESULTS: The older adult group had a higher incidence of femoral intertrochanteric fractures than that in the non-older adult group (95.3% vs. 4.7%, p<0.001). However, there was no significant difference between young-old and non-older groups (58.8% vs. 41.2%, p=0.145). Middle-old to oldest-old age and osteoporosis were associated with an increased incidence of femoral intertrochanteric fractures (p<0.001, p=0.004). CONCLUSION: A higher incidence of femoral intertrochanteric fractures from minor falls was found among middle-old to oldest-old patients compared to that in young-old patients. Therefore, physicians should perform more thorough physical examinations and radiograph reading in middle-old to oldest-old patients even if the patients do not complain of pain.
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This paper describes the fabrication and evaluation of phase-change material (PCM) nanoparticles containing chlorin e6 (Ce6) and nanodiamonds (NDs) for photodynamic and photothermal approaches for tumor therapy, respectively. The temperature of the PCM nanoparticles containing NDs (ND/PCM, 0.5mg/mL in water) is increased to 45°C during laser exposure for 5min. The singlet oxygen generation intensity of PCM nanoparticles containing Ce6 and NDs (Ce6/ND/PCM) is gradually increased with respect to the laser exposure time. Also, the release of Ce6 from Ce6/ND/PCM can be controlled in an on-and-off manner using laser. Cell ablation tests reveal that Ce6/ND/PCM greatly ablates KB cells upon laser exposure, which is attributed to both the temperature increase in the media and singlet oxygen generation by the released Ce6. In an animal model, tumor volume is notably reduced over time after the intratumoral injection of Ce6/ND/PCM and subsequent laser exposure with a higher efficiency compared to ND/PCM. The Ce6/ND/PCM can be a promising nanomedicine for tumor therapy.
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Rayos Láser , Nanopartículas/administración & dosificación , Neoplasias/terapia , Fototerapia , Porfirinas/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Clorofilidas , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Neoplasias/patología , Porfirinas/química , Fármacos Sensibilizantes a Radiaciones/química , Oxígeno Singlete/químicaRESUMEN
This paper describes the design of alendronate-conjugated nanodiamonds (Alen-NDs) and evaluation of their feasibility for bone-targeted delivery. Alen-NDs exhibited a high affinity to hydroxyapatite (HAp, the mineral component of bone) due to the presence of Alen. Unlike NDs (without Alen), Alen-NDs were preferentially taken up by MC3T3-E1 osteoblast-like cells, compared to NIH3T3 and HepG2 cells, suggesting their cellular specificity. In addition, NDs itself increased ALP activity of MC3T3-E1 cells, compared to control group (osteogenic medium) and Alen-NDs exhibited more enhanced ALP activity. In addition, an in vivo study revealed that Alen-NDs effectively accumulated in bone tissues after intravenous tail vein injection. These results confirm the superior properties of Alen-NDs with advantages of high HAp affinity, specific uptake for MC3T3-E1 cells, positive synergistic effect for ALP activity, and in vivo bone targeting ability. The Alen-NDs can potentially be employed for osteoporosis treatment by delivering both NDs and Alen to bone tissue.
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Alendronato/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanodiamantes/administración & dosificación , Alendronato/química , Alendronato/farmacocinética , Fosfatasa Alcalina/metabolismo , Animales , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacocinética , Huesos/metabolismo , Línea Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Durapatita/química , Femenino , Células Hep G2 , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanodiamantes/química , Osteoporosis/tratamiento farmacológicoRESUMEN
BACKGROUND: The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats. METHODS: HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6, and IL-8 levels in the serum. RESULTS: The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione-glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-κB pathway; suppressed TNF-α, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage. CONCLUSION: A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species-dependent NF-κB pathway.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Niacina/uso terapéutico , Choque Hemorrágico/complicaciones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Animales , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , FN-kappa B/metabolismo , Niacina/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVES: The aim of this study is to investigate whether glutamine (GLN) enhances heat shock protein-25 (Hsp-25) and heat shock protein-72 (Hsp-72) expressions and attenuates cerebral ischaemic injury in rat cardiac arrest model. METHODS: Rats survived from cardiac arrest model were randomly assigned to CPR+GLN group (0.75 g/kg of alanyl-glutamine, n=6) or CPR group (same volume of 0.9% saline, n=6). Additional 6 rats were used for SHAM group. For the outcome measures, neurologic deficit score (NDS, 0-80) was checked at 24h and 72 h after cardiac arrest. At 72 h after cardiac arrest, rats were euthanised and the brain was harvested. Then, right hemisphere was used for cresyl-violet and TUNEL staining. Left hemisphere was used for Western blot analysis of phosphorylated heat shock factor-1 (p-HSF-1), Hsp-25, Hsp-72, and cleaved caspase-3. Kruskal-Wallis test and Mann-Whitney U post hoc test with Bonferroni correction were used for the analysis. RESULTS: Resuscitation variables were not different between CPR and CPR+GLN. NDS in CPR+GLN was higher than that in CPR (p<0.017) and lower than that in SHAM (p<0.017) at both 24h and 72 h. p-HSF-1, Hsp-25 and Hsp-72 expressions in CPR+GLN were significantly enhanced (p<0.017) than those in other groups. Cleaved caspase-3 expression in CPR was significantly higher (p<0.017) than in SHAM and CPR+GLN. Ischaemic and TUNEL-positive neurons were more frequently observed in CPR than in CPR+GLN. CONCLUSIONS: Glutamine attenuates cerebral ischaemic injury in cardiac arrest model of rats and this is associated with the enhancement of Hsp-25 and Hsp-72 expressions.
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Isquemia Encefálica/patología , Encéfalo/efectos de los fármacos , Reanimación Cardiopulmonar/métodos , Glutamina/farmacología , Paro Cardíaco/terapia , Proteínas de Choque Térmico/análisis , Animales , Western Blotting , Encéfalo/patología , Isquemia Encefálica/prevención & control , Modelos Animales de Enfermedad , Proteínas del Choque Térmico HSP72/análisis , Paro Cardíaco/patología , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/análisis , Masculino , Proteínas Serina-Treonina Quinasas/análisis , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Estadísticas no Paramétricas , Recolección de Tejidos y ÓrganosRESUMEN
Replacement of glycine 227 in the fifth WD40 motif of α-COP/Ret1p/Soo1p by charged or aromatic amino acids is responsible for the temperature-dependent osmo-sensitivity of Saccharomyces cerevisiae, while truncations of WD40 motifs exerted a reduction in cell growth rate and impairment in assembly of cell-wall associated proteins such as enolase and Gas1p. Yeast two-hybrid analysis revealed that the ret1-1/soo1-1 mutation of α-COP abolished the interaction with ß- and É-COP, respectively, and that the interaction between α-COP and ß-COP relied on the WD40 domain of α-COP. Furthermore, although the WD40 domain is dispensable for interaction of α-COP with É-COP, structural alterations in the WD40 domain could impair the interaction.
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Proteína Coat de Complejo I/metabolismo , Proteína Coatómero/genética , Mutación , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteína Coat de Complejo I/química , Proteína Coat de Complejo I/genética , Proteína Coatómero/química , Proteína Coatómero/metabolismo , Unión Proteica , Multimerización de Proteína , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
CONTEXT: Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. OBJECTIVE: To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. MATERIALS AND METHODS: Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 µg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. RESULTS: GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869). CONCLUSION: Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Antioxidantes/farmacología , Herbicidas/envenenamiento , Paraquat/envenenamiento , Selenio/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/fisiopatología , Animales , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Congenital nystagmus (CN) is an ocular oscillation that usually manifests during early infancy. Typical features of CN include bilateral, conjugate, uniplanar, and usually horizontal eye movements, a null position, increased oscillation during fixation, and decreased amplitude during convergence. Our purposes were description and analysis of clinical and oculomotor findings of patients with X-linked familial CN. METHODS: We describe the clinical and oculographic features of five patients from three families with X-linked CN. Three-dimensional video-oculography disclosed various patterns of CN and variable degrees of gaze-holding deficits and visual impairments. RESULTS: The features of CN varied even in patients from the same family. Head tilt, strabismus, reversal of optokinetic nystagmus, and impairments of the vestibulo-ocular reflex, smooth pursuits, and saccades were frequent findings. CONCLUSIONS: The intra- and interfamilial diversities imply that heredity plays a secondary role in determining the clinical phenotypes and waveforms of CN.