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1.
Proc Natl Acad Sci U S A ; 119(50): e2209586119, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36469787

RESUMEN

Liquid mobility is ubiquitous in nature, with droplets emerging at all size scales, and artificial surfaces have been designed to mimic such mobility over the past few decades. Meanwhile, millimeter-sized droplets are frequently used for wettability characterization, even with facial mask applications, although these applications have a droplet-size target range that spans from millimeters to aerosols measuring less than a few micrometers. Unlike large droplets, microdroplets can interact sensitively with the fibers they contact with and are prone to evaporation. However, wetting behaviors at the single-microfiber level remain poorly understood. Herein, we characterized the wettability of fibrous layers, which revealed that a multiscale landscape of droplets ranged from the millimeter to the micrometer scale. The contact angle (CA) values of small droplets on pristine fibrous media showed sudden decrements, especially on a single microfiber, owing to the lack of air cushions for the tiny droplets. Moreover, droplets easily adhered to the pristine layer during droplet impact tests and then yielding widespread areas of contamination on the microfibers. To resolve this, we carved nanowalls on the pristine fibers by plasma etching, which effectively suppressed such wetting phenomena. Significantly, the resulting topographies of the microfibers managed the dynamic wettability of droplets at the multiscale, which reduced the probability of contamination with impact droplets and suppressed the wetting transition upon evaporation. These findings for the dynamic wettability of fibrous media will be useful in the fight against infectious droplets.


Asunto(s)
Máscaras , Humectabilidad , Fenómenos Físicos
2.
Arch Toxicol ; 98(7): 2185-2197, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38607375

RESUMEN

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.


Asunto(s)
Vacunas contra la COVID-19 , Pruebas de Micronúcleos , Ratas Sprague-Dawley , SARS-CoV-2 , Animales , Perros , Vacunas contra la COVID-19/toxicidad , Ratas , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/efectos de los fármacos , COVID-19/prevención & control , Femenino , Daño del ADN/efectos de los fármacos , Ensayo Cometa , Vesiculovirus/efectos de los fármacos , Vacunas Sintéticas/inmunología , Temperatura Corporal/efectos de los fármacos
3.
Clin Immunol ; 257: 109819, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37918467

RESUMEN

Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monocytogenes infection, DRG2-/- mice showed delayed recruitment of neutrophils and monocytes into the peritoneal cavity, which led to elevated bacterial burden, inflammatory cytokine production at a late infection time point, and liver micro-abscesses. DRG2 deficiency decreased the transcriptional activity of NF-κB and impaired the inflammatory response of both bone marrow-derived and peritoneal macrophages upon L. monocytogenes stimulation. Our findings reveal that DRG2 in macrophages is critical for the initial inflammatory response and protection against L. monocytogenes infection.


Asunto(s)
Proteínas de Unión al GTP , Listeria monocytogenes , Listeriosis , Macrófagos , Animales , Ratones , Inmunidad Innata , Listeriosis/inmunología , Macrófagos/inmunología , Ratones Noqueados , Monocitos , Proteínas de Unión al GTP/metabolismo
4.
Arch Toxicol ; 97(9): 2429-2440, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37491472

RESUMEN

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Masculino , Humanos , Ratas , Conejos , Animales , Perros , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , SARS-CoV-2 , Modelos Animales , Adyuvantes Inmunológicos , Vacunas de Subunidad
5.
Medicina (Kaunas) ; 59(3)2023 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-36984461

RESUMEN

Tension pneumothorax is a relatively rare complication after anesthetic induction that requires prompt diagnosis and treatment. Several handling errors related to intubation procedures or equipment and vigorous positive pressure ventilation are potentially important etiologies of tension pneumothorax in patients with underlying lung disease or in mechanically ventilated patients. We describe a case of tension pneumothorax observed after double-lumen tube (DLT) insertion followed by single-lumen tube replacement using an airway exchanger catheter in a mechanically ventilated patient. An 84-year-old female on mechanical ventilation underwent minimally invasive cardiac surgery under general anesthesia. Immediately after left-sided DLT insertion using an airway exchanger catheter, oxygen saturation decreased to 89%, peak airway pressure increased to 35 cm H2O with inadequate tidal volume, and blood pressure gradually dropped to 69/41 mmHg. Breath sounds from the right hemithorax were significantly reduced. Severe collapse of the right lung, a flattened diaphragm, and compressed abdominal organs were identified on chest radiography. Therefore, a tube thoracotomy was performed based on the findings of a tension pneumothorax. Then, oxygen saturation, peak airway pressure with adequate tidal volume, and blood pressure improved, and the distended abdomen normalized. After the pneumothorax resolved, a bronchoscopy was performed. Slight redness was noted in the right bronchus, indicating that the DLT was incorrectly inserted into the right side. In conclusion, the possibility of a tension pneumothorax should be considered during DLT intubation or endotracheal tube replacement with an airway exchange catheter.


Asunto(s)
Neumotórax , Edema Pulmonar , Femenino , Humanos , Anciano de 80 o más Años , Neumotórax/etiología , Neumotórax/terapia , Intubación Intratraqueal/efectos adversos , Pulmón , Respiración Artificial
6.
J Cell Mol Med ; 25(22): 10430-10440, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34651412

RESUMEN

Hypoxic-ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin-preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells (th-hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th-hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th-hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague-Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th-hWJMSCs on the growth of newborn babies. Our results suggest that th-hWJMSCs are non-toxic and non-tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.


Asunto(s)
Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Trombina/metabolismo , Gelatina de Wharton/citología , Animales , Animales Recién Nacidos , Biomarcadores , Transformación Celular Neoplásica , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Humanos , Hipoxia-Isquemia Encefálica/etiología , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Ratas , Trombina/farmacología
7.
J Arthroplasty ; 36(8): 2759-2764, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33906786

RESUMEN

BACKGROUND: The purpose of the present study was to compare the functional outcomes of medial unicompartmental knee arthroplasty (UKA) between patients with lateral meniscal abnormalities (LM [+] group) on the preoperative magnetic resonance imaging and those without lateral meniscal pathology (LM [-] group) and to evaluate the effect of a lateral meniscus lesion on functional outcomes after minimal 5 year follow-ups of medial UKA. METHODS: The outcomes of 66 knees (LM (+) group) were compared with the outcomes of 59 knees (LM (-) group) with a mean follow-up period of 75 months (range 60-93 months). The clinical outcomes were examined including the KS object/function score, Knee Injury and Osteoarthritis Outcome score, lateral side pain, and squatting ability at the last follow-up. The radiological parameters (mechanical axis and component position) were compared at the final follow-up visit. RESULT: No significant intergroup difference was found in terms of the KS object/function score, Knee Injury and Osteoarthritis Outcome score, presence of lateral side pain, and squatting ability. On the radiographic evaluation, there was no statistical difference in the position of the implant and mechanical axis between the two groups. After the surgery, the LM (+) group showed a tendency of slight varus alignment in the postoperative radiography. CONCLUSION: The results of UKA for medial unicompartmental knee osteoarthritis were excellent regardless of preoperative lateral meniscal pathology in the magnetic resonance imaging, if the patients had no symptoms related to the lateral meniscus lesion.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Imagen por Resonancia Magnética , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
8.
Sensors (Basel) ; 20(14)2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32664426

RESUMEN

A Lamb wave in a plate with a finite width has both thickness and width modes, whereas only thickness modes exist in an infinitely wide plate. The thickness and width modes are numerously formed in a finite-width plate, and they all have different cut-off frequencies, wave velocities, and wave structures. These different characteristics can be utilized in various applications, but a selective generation method for a particular Lamb wave mode in a finite-width plate has not been sufficiently studied, and only a method using multiple elements has been reported. This paper presents the selective generation of a certain Lamb wave mode in a finite-width plate by an angle-beam excitation method using single or dual wedges. In the proposed generation method, a specially designed wedge with grooves or a patch having insulation layers is employed for partial acoustic insulation of the ultrasonic energy incident into the plate. The feasibility of the proposed method was investigated through finite element method (FEM) simulations for Lamb wave excitation and propagation, and then experimentally demonstrated by the measurement of Lamb wave propagation using a laser scanning vibrometer.

9.
Int J Mol Sci ; 21(2)2020 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-31963761

RESUMEN

The demyelinating diseases of the central nervous system involve myelin abnormalities, oligodendrocyte damage, and consequent glia activation. Neurotoxicant cuprizone (CPZ) was used to establish a mouse model of demyelination. However, the effects of CPZ on microRNA (miRNA) expression and behavior have not been clearly reported. We analyzed the behavior of mice administered a diet containing 0.2% CPZ for 6 weeks, followed by 6 weeks of recovery. Rotarod analysis demonstrated that the treated group had poorer motor coordination than control animals. This effect was reversed after 6 weeks of CPZ withdrawal. Open-field tests showed that CPZ-treated mice exhibited significantly increased anxiety and decreased exploratory behavior. CPZ-induced demyelination was observed to be alleviated after 4 weeks of CPZ treatment, according to luxol fast blue (LFB) staining and myelin basic protein (MBP) expression. miRNA expression profiling showed that the expression of 240 miRNAs was significantly changed in CPZ-fed mice compared with controls. Furthermore, miR-155-5p and miR-20a-5p upregulations enhanced NgR induction through Smad 2 and Smad 4 suppression in demyelination. Taken together, our results demonstrate that CPZ-mediated demyelination induces behavioral deficits with apparent alterations in miRNA expression, suggesting that differences in miRNA expression in vivo may be new potential therapeutic targets for remyelination.


Asunto(s)
Cuprizona/efectos adversos , Enfermedades Desmielinizantes/psicología , Conducta Exploratoria/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Animales , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/genética , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/efectos de los fármacos , MicroARNs/genética , Prueba de Desempeño de Rotación con Aceleración Constante
10.
Regul Toxicol Pharmacol ; 92: 83-93, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29155077

RESUMEN

Ginseng is a major herbal remedy used in Asian countries for thousands of years and known to restore and enhance vital energy. Korean red ginseng, which is processed by steaming and drying fresh Panax ginseng, is most popular and contains unique ginsenosides, which have anticancer and anti-inflammatory properties. The present study was carried out to evaluate the repeated oral dose toxicity of Korean red ginseng extract. The test article was administered orally once a day to male and female Sprague-Dawley rats at dose levels of 0, 500, 1000, or 2000 mg/kg/day for 13 consecutive weeks (15 animals/sex/group in the vehicle control and 2000 mg/kg/day groups, and 10 animals/sex/group in the 500 and 1000 mg/kg/day groups). Ten animals per group were sacrificed at the end of the 13-week treatment period, and the remaining rats were sacrificed after a 4-week recovery period. Administration of Korean red ginseng extract did not result in any toxicologically significant changes in mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights, or histopathology. It was established that the no observed adverse effect level (NOAEL) of the test article was 2000 mg/kg/day for both sexes in this study.


Asunto(s)
Panax/efectos adversos , Extractos Vegetales/efectos adversos , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Ginsenósidos/efectos adversos , Corea (Geográfico) , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
11.
Paediatr Anaesth ; 28(8): 739-744, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30004624

RESUMEN

BACKGROUND: Emergence delirium is a common complication of sevoflurane anesthesia in children. AIMS: We examined the effects of maintaining remifentanil infusion during the recovery period on the incidence of emergence delirium in preschool-age children undergoing strabismus surgery under sevoflurane anesthesia. METHODS: Eighty children (aged 3-7 years) were randomly assigned to either the control group (group C; intraoperative remifentanil infusion) or the intervention group (group R; intraoperative remifentanil infusion followed by remifentanil maintenance during the recovery phase). Intraoperative remifentanil infusion (0.2 µg/kg/min) was discontinued upon surgery completion in the group C, and was maintained until the discharge criteria were met at a dose of 0.05 µg/kg/min in the group R. The incidence of emergence delirium was assessed using a five-point agitation scale and the Pediatric Anesthesia Emergence Delirium scale after arrival in the postanesthesia care unit. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale. RESULTS: The incidence of emergence delirium according to the five-point agitation scale (scores ≥ 4) was lower in the group R (33.3%) compared to the group C (68.3%) (odds ratio 0.206; 95% CI 0.080 to 0.531; P = 0.002). Similar results were obtained using the Pediatric Anesthesia Emergence Delirium scale (scores > 12), with an incidence of 5.1% in the group R and 34.0% in the control group (odds ratio 0.104; 95% CI 0.022 to 0.497; P = 0.001). The Children's Hospital of Eastern Ontario Pain Scale scores and occurrence of postoperative adverse events including laryngospasm, desaturation, nausea, and vomiting were similar between the two groups. CONCLUSION: Maintaining a low dose of remifentanil (0.05 µg/kg/min) throughout the recovery phase attenuated the incidence of emergence delirium in children undergoing strabismus surgery under sevoflurane anesthesia.


Asunto(s)
Delirio del Despertar/inducido químicamente , Delirio del Despertar/tratamiento farmacológico , Remifentanilo/administración & dosificación , Sevoflurano/efectos adversos , Analgésicos Opioides/administración & dosificación , Periodo de Recuperación de la Anestesia , Anestésicos/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Niño , Preescolar , Monitores de Conciencia , Femenino , Humanos , Masculino , Atención Perioperativa/métodos , Cuidados Posoperatorios/métodos , Estrabismo/cirugía , Resultado del Tratamiento
12.
J Korean Med Sci ; 33(5): e33, 2018 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-29349943

RESUMEN

BACKGROUND: Industrial pollution may affect the heavy metal body burden of people living near industrial complexes. We determined the average concentrations of atmospheric heavy metals in areas close to and distant from industrial complexes in Korea, and the body concentrations of these heavy metals in residents living near and distant from these facilities. METHODS: The atmospheric data of heavy metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan. We recruited 1,148 participants, 872 who lived near an industrial complex ("exposed" group) and 276 who lived distant from industrial complexes ("non-exposed" group), and measured their concentrations of blood lead, urinary cadmium, and urinary total mercury. RESULTS: The results showed that atmospheric and human concentrations of heavy metals were higher in areas near industrial complexes. In addition, residents living near industrial complexes had higher individual and combined concentrations (cadmium + lead + mercury) of heavy metals. CONCLUSION: We conclude that residents living near industrial complexes are exposed to high concentrations of heavy metals, and should be carefully monitored.


Asunto(s)
Metales Pesados/sangre , Adulto , Anciano , Contaminantes Atmosféricos/sangre , Contaminantes Atmosféricos/orina , Cadmio/orina , Exposición a Riesgos Ambientales , Femenino , Humanos , Plomo/sangre , Modelos Logísticos , Masculino , Mercurio/orina , Persona de Mediana Edad , República de Corea , Fumar , Adulto Joven
13.
J Biochem Mol Toxicol ; 31(3)2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27870266

RESUMEN

The anticancer-drug cyclophosphamide (CP) is known to have nephrotoxicity. The aim of this study was to identify urinary biomarkers indicating CP-induced nephrotoxicity. We investigated the urine metabolic profiles using nuclear magnetic resonance spectrometry of rats administered with single high-doses of CP (0, 30, and 100 mg/kg body weight) and daily low-doses over a 4-week period (0, 1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2-oxoglutarate, citrate, hippurate, formate, valine, and alanine for short-term and 2-oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and lysine for long-term were selected as potential biomarkers. Pathway-enrichment analysis suggested that the urinary metabolism of CP is related to valine, leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate, and glutamate metabolism, with high pathway impact. The potential biomarkers obtained in this study could be used to monitor CP-induced nephrotoxicity relative to dose and treatment time.


Asunto(s)
Biomarcadores/orina , Ciclofosfamida/efectos adversos , Riñón/efectos de los fármacos , Metabolómica , Neoplasias/orina , Animales , Ciclofosfamida/administración & dosificación , Humanos , Isoleucina/orina , Riñón/patología , Leucina/orina , Espectroscopía de Resonancia Magnética , Redes y Vías Metabólicas/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Ratas , Taurina/análogos & derivados , Taurina/orina , Valina/orina
14.
Arch Toxicol ; 91(1): 453-464, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27017489

RESUMEN

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.


Asunto(s)
Encéfalo/efectos de los fármacos , Epidídimo/efectos de los fármacos , Riñón/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Testículo/efectos de los fármacos , alfa-Clorhidrina/toxicidad , Administración Oral , Animales , Encéfalo/citología , Pruebas de Carcinogenicidad , Cruzamientos Genéticos , Epidídimo/citología , Femenino , Humanos , Riñón/citología , Masculino , Ratones Endogámicos BALB C , Ratones Transgénicos , Neuronas/citología , Neuronas/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Distribución Aleatoria , Organismos Libres de Patógenos Específicos , Médula Espinal/citología , Análisis de Supervivencia , Testículo/citología , Vacuolas/efectos de los fármacos , alfa-Clorhidrina/administración & dosificación
15.
J Korean Med Sci ; 31(8): 1190-6, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27478327

RESUMEN

Diagnosis of scrub typhus is challenging due to its more than twenty serotypes and the similar clinical symptoms with other acute febrile illnesses including leptospirosis, murine typhus and hemorrhagic fever with renal syndrome. Accuracy and rapidity of a diagnostic test to Orientia tsutsugamushi is an important step to diagnose this disease. To discriminate scrub typhus from other diseases, the improved ImmuneMed Scrub Typhus Rapid Diagnostic Test (RDT) was evaluated in Korea and Sri Lanka. The sensitivity at the base of each IgM and IgG indirect immunofluorescent assay (IFA) in Korean patients was 98.6% and 97.1%, and the specificity was 98.2% and 97.7% respectively. The sensitivity and specificity for retrospective diagnosis at the base of IFA in Sri Lanka was 92.1% and 96.1%. ImmuneMed RDT was not reactive to any serum from seventeen diseases including hemorrhagic fever with renal syndrome (n = 48), leptospirosis (n = 23), and murine typhus (n = 48). ImmuneMed RDT shows superior sensitivity (98.6% and 97.1%) compared with SD Bioline RDT (84.4% at IgM and 83.3% at IgG) in Korea. The retrospective diagnosis of ImmuneMed RDT exhibits 94.0% identity with enzyme-linked Immunosorbent assay (ELISA) using South India patient serum samples. These results suggest that this RDT can replace other diagnostic tests and is applicable for global diagnosis of scrub typhus. This rapid and accurate diagnosis will be beneficial for diagnosing and managing scrub typhus.


Asunto(s)
Tifus por Ácaros/diagnóstico , Anticuerpos Antibacterianos/sangre , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Orientia tsutsugamushi/inmunología , Juego de Reactivos para Diagnóstico , Estudios Retrospectivos , Tifus por Ácaros/microbiología , Sensibilidad y Especificidad
16.
Chembiochem ; 16(5): 854-60, 2015 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-25703680

RESUMEN

Triterpenoids with desired glycosylation patterns have attracted considerable attention as potential therapeutics for inflammatory diseases and various types of cancer. Sugar-hydrolyzing enzymes with high substrate specificity would be far more efficient than other methods for the synthesis of such specialty triterpenoids, but they are yet to be developed. Here we present a strategy to rationally design a ß-glycosidase with high regiospecificity for triterpenoids. A ß-glycosidase with broad substrate specificity was isolated, and its crystal structure was determined at 2.0 Å resolution. Based on the product profiles and substrate docking simulations, we modeled the substrate binding modes of the enzyme. From the model, the substrate binding cleft of the enzyme was redesigned in a manner that preferentially hydrolyzes glycans at specific glycosylation sites of triterpenoids. The designed mutants were shown to produce a variety of specialty triterpenoids with high purity.


Asunto(s)
Biocatálisis , Triterpenos/metabolismo , beta-Glucosidasa/química , beta-Glucosidasa/metabolismo , Actinomycetales/enzimología , Actinomycetales/genética , Modelos Moleculares , Conformación Molecular , Mutación , Especificidad por Sustrato , Triterpenos/química , beta-Glucosidasa/genética , beta-Glucosidasa/aislamiento & purificación
17.
J Surg Res ; 195(1): 37-43, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25659616

RESUMEN

BACKGROUND: Although there is a possibility of cross talk between opioid and adenosine signaling pathways in the ischemic-reperfused myocardium, it is not clear that an ultra-short-acting opioid receptor agonist remifentanil-induced postconditioning (RPostC) has cross talk with adenosine receptor (ADR). The purpose of this study was to determine whether there is cross talk with ADR in RPostC. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. RPostC was induced by 100 ng/mL of remifentanil perfusion, 5 min before reperfusion, followed by 5 min of reperfusion. The nonspecific opioid receptor antagonist naloxone (NAL) and the nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (8-SPT) were perfused for a 20-min period, 10 min before RPostC to the end of RPostC. Western blot analysis was performed to detect phospho-ERK1/2 in cultured cardiomyocytes. RESULTS: In cultured cardiomyocytes, remifentanil incubation significantly increased the phosphorylation of ERK1/2 and this effect was blocked by both NAL and 8-SPT (P < 0.01 and P < 0.05, respectively). RPostC significantly reduced infarct size over ischemic area at risk from 34.1 ± 10.5% to 16.6 ± 7.5% (P < 0.05 versus control). The infarct-limitation effect of RPostC was reversed by both NAL (33.8 ± 13.0%, P < 0.05) and 8-SPT (35.7 ± 14.5%, P < 0.01). CONCLUSIONS: This study strongly implies that the intracellular signaling pathways of cardioprotection by RPostC has cross talk with ADR in the ischemic-reperfused myocardium.


Asunto(s)
Analgésicos Opioides/farmacología , Circulación Coronaria , Poscondicionamiento Isquémico , Piperidinas/farmacología , Receptores Purinérgicos P1/efectos de los fármacos , Animales , Biometría , Western Blotting , Células Cultivadas , Pruebas de Función Cardíaca , Técnicas In Vitro , Masculino , Infarto del Miocardio/patología , Miocardio/patología , Agonistas del Receptor Purinérgico P1/farmacología , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor Cross-Talk , Remifentanilo , Daño por Reperfusión/patología
18.
Anesth Analg ; 121(3): 778-784, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26176357

RESUMEN

BACKGROUND: The anxiolytic efficacy of video watching, in the absence of parents, during the mask induction of anesthesia in young children with high separation anxiety has not been clearly established. We performed this study to determine whether the effect of video distraction on alleviating preoperative anxiety is independent of parental presence and whether a combination of both interventions is more effective than either single intervention in alleviating preoperative anxiety and postoperative behavioral disturbance in preschool children. METHODS: In this prospective trial, 117 children aged 2 to 7 years scheduled for elective minor surgery were randomly allocated to 1 of 3 groups, a video distraction group (group V), a parental presence group (group P), or a combination of video distraction plus parental presence group (group VP) during induction of sevoflurane anesthesia. The Modified Yale Preoperative Anxiety Scale (mYPAS) was used to assess anxiety in the preoperative holding area (baseline), immediately after entry to the operating room, and during mask induction. Compliance during induction, emergence delirium during recovery, and negative behavioral changes at 1 day and 2 weeks postoperatively were also assessed. RESULTS: The mYPAS scores were comparable (P = 0.558), and the number of children exhibiting baseline anxiety (an mYPAS score > 30) were not different among the 3 groups in the preoperative holding area (P = 0.824). After intervention, the changes in mYPAS scores from baseline to induction were not different among the 3 groups (P = 0.049). The proportion of children with increased mYPAS scores was higher in group P compared with group V from baseline to operating room entry (Bonferroni-adjusted 95% confidence interval for difference, 2 to 49) but similar from baseline to induction in all 3 groups. Although children in group V were more cooperative during mask induction than those in the other 2 groups (P < 0.001 versus group P and P = 0.001 versus group VP), no significant intergroup differences were observed in the incidence of emergence delirium or new-onset negative behavioral change after surgery. CONCLUSIONS: Video distraction, parental presence, or their combination showed similar effects on preoperative anxiety during inhaled induction of anesthesia and postoperative behavioral outcomes in preschool children having surgery.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/psicología , Ansiedad/psicología , Padres/psicología , Complicaciones Posoperatorias/psicología , Cuidados Preoperatorios/psicología , Juegos de Video/psicología , Procedimientos Quirúrgicos Ambulatorios/métodos , Ansiedad/diagnóstico , Ansiedad/prevención & control , Niño , Preescolar , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Estudios Prospectivos
19.
J Anesth ; 29(5): 666-71, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25808345

RESUMEN

PURPOSE: The additional administration of remifentanil during inhalation induction with sevoflurane could provide better conditions for laryngeal mask airway (LMA) insertion than sevoflurane alone. This study was designed to evaluate the 50 % effective bolus dose (ED50) and 95 % effective bolus dose (ED95) of remifentanil required for LMA insertion in children during inhalation induction with sevoflurane. METHODS: Pediatric patients aged 3-12 years requiring general anesthesia were recruited. A predetermined dose of remifentanil was injected over 30 s after the induction of general anesthesia with sevoflurane. LMA insertion was attempted 60 s after remifentanil injection. The dose of remifentanil was determined using the Dixon's up-and-down method, starting from 0.5 µg/kg (step size of 0.05 µg/kg). RESULTS: The study was conducted until seven cross-over points and 29 children were collected. The ED50 of remifentanil for successful LMA insertion during sevoflurane inhalation induction in children was 0.168 ± 0.035 µg/kg using Dixon's method. In addition, the ED50 and ED95 of remifentanil from the probit analysis were 0.176 µg/kg (95 % confidence limits, 0.102-0.216 µg/kg) and 0.268 µg/kg (95 % confidence limits, 0.223-0.659 µg/kg), respectively. CONCLUSION: The ED50 and ED95 of remifentanil for successful LMA insertion in children were estimated to be 0.176 (0.168) and 0.268 µg/kg during inhalation induction with 2.1 % sevoflurane.


Asunto(s)
Anestesia General/métodos , Máscaras Laríngeas , Éteres Metílicos/administración & dosificación , Piperidinas/administración & dosificación , Anestésicos por Inhalación/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Masculino , Remifentanilo , Sevoflurano
20.
Psychooncology ; 23(1): 35-9, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24038620

RESUMEN

OBJECTIVE: Population-based data on the epidemiology of psychiatric disorders in patients with breast cancer are lacking. Because the National Health Insurance (NHI) Program in South Korea is a compulsory social insurance system covering the entire Korean population, the NHI is a good source of information for epidemiological studies. In the present study, we examined the incidence of psychiatric disorders among Korean women newly diagnosed with breast cancer using the NHI Corporation (NHIC) database. METHODS: Data were collected for adult women newly diagnosed with breast cancer using the claim database and cancer registration files of the NHIC from 2005 to 2008. We analysed data for women diagnosed with psychiatric disorders over a 5-year period, from 2004 (at least 1 year before the cancer registration date) to 2009 (at least 1 year after the cancer registration date). RESULTS: We identified 6536 patients with psychiatric disorders among 42 190 women with breast cancer. The most prevalent psychiatric disorder was anxiety disorder (N = 2518). The incidence rates of anxiety disorders, depressive disorders, sleep disorders and adjustment disorders were 27.08, 22.41, 10.57 and 4.35 cases per 1000 person-year, respectively. CONCLUSION: The incidence rates of psychiatric disorders in Korean women with breast cancer from the nationwide database were much lower than found by previous reports using screening tools. The finding implicates that psychiatric disorders among breast cancer patients tend to be underdiagnosed and undertreated in actual clinical practice. Our epidemiological findings provide important information for establishing a national strategy of cancer care to detect and manage psychiatric problems.


Asunto(s)
Neoplasias de la Mama/psicología , Trastornos Mentales/epidemiología , Trastornos de Adaptación/complicaciones , Trastornos de Adaptación/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/epidemiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Comorbilidad , Trastorno Depresivo/complicaciones , Trastorno Depresivo/epidemiología , Femenino , Humanos , Incidencia , Trastornos Mentales/complicaciones , Persona de Mediana Edad , Sistema de Registros/estadística & datos numéricos , República de Corea/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Adulto Joven
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