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AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.
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Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacocinética , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Persona de Mediana Edad , Femenino , Anciano , Tasa de Filtración Glomerular/efectos de los fármacos , Glucemia/efectos de los fármacos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Glucósidos/farmacocinética , Glucósidos/uso terapéutico , Glucósidos/farmacología , Glucósidos/efectos adversos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiopatología , Adulto , Nefropatías Diabéticas/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Insuficiencia Renal/metabolismo , Transportador 2 de Sodio-Glucosa , Glucosuria/inducido químicamente , BenzofuranosRESUMEN
BACKGROUND: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy. METHODS: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection. RESULTS: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery. CONCLUSIONS: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period.
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Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias de la Tiroides , Humanos , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Puntaje de Propensión , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/cirugía , Disección del Cuello/efectos adversos , Disección del Cuello/métodos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios RetrospectivosRESUMEN
OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.
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Esomeprazol , Gastritis , Humanos , Esomeprazol/farmacocinética , Famotidina/farmacología , Voluntarios Sanos , Estudios Cruzados , Gastritis/diagnóstico , Gastritis/tratamiento farmacológicoRESUMEN
Glutathione (GSH) is necessary for maintaining physiological antioxidant function, which is responsible for maintaining free radicals derived from reactive oxygen species at low levels and is associated with improved cognitive performance after brain injury. GSH is produced by the linkage of tripeptides that consist of glutamic acid, cysteine, and glycine. The adequate supplementation of GSH has neuroprotective effects in several brain injuries such as cerebral ischemia, hypoglycemia, and traumatic brain injury. Brain injuries produce an excess of reactive oxygen species through complex biochemical cascades, which exacerbates primary neuronal damage. GSH concentrations are known to be closely correlated with the activities of certain genes such as excitatory amino acid carrier 1 (EAAC1), glutamate transporter-associated protein 3-18 (Gtrap3-18), and zinc transporter 3 (ZnT3). Following brain-injury-induced oxidative stress, EAAC1 function is negatively impacted, which then reduces cysteine absorption and impairs neuronal GSH synthesis. In these circumstances, vesicular zinc is also released into the synaptic cleft and then translocated into postsynaptic neurons. The excessive influx of zinc inhibits glutathione reductase, which inhibits GSH's antioxidant functions in neurons, resulting in neuronal damage and ultimately in the impairment of cognitive function. Therefore, in this review, we explore the overall relationship between zinc and GSH in terms of oxidative stress and neuronal cell death. Furthermore, we seek to understand how the modulation of zinc can rescue brain-insult-induced neuronal death after ischemia, hypoglycemia, and traumatic brain injury.
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Antioxidantes , Lesiones Traumáticas del Encéfalo , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Cisteína/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Zinc/farmacología , Zinc/metabolismo , Transportador 3 de Aminoácidos Excitadores/metabolismo , Glutatión/metabolismo , Estrés Oxidativo , Neuronas/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Muerte CelularRESUMEN
Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death.
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Lesiones Traumáticas del Encéfalo , Isquemia Encefálica , Canales de Potencial de Receptor Transitorio , Animales , Canales de Potencial de Receptor Transitorio/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Zinc/metabolismo , Mamíferos/metabolismoRESUMEN
Owing to the emergence and improvement of high-throughput technology and the associated reduction in costs, next-generation sequencing (NGS) technology has made large-scale sampling and sequencing possible. With the large volume of data produced, the processing and downstream analysis of data are important for ensuring meaningful results and interpretation. Problems in data analysis may be encountered if researchers have little experience in using programming languages, especially if they are clinicians and beginners in the field. A strategy for solving this problem involves ensuring easy access to commercial software and tools. Here, we observed the current status of free web-based tools for microbiome analysis that can help users analyze and handle microbiome data effortlessly. We limited our search to freely available web-based tools and identified MicrobiomeAnalyst, Mian, gcMeta, VAMPS, and Microbiome Toolbox. We also highlighted the various analyses that each web tool offers, how users can analyze their data using each web tool, and noted some of their limitations. From the abovementioned list, gcMeta, VAMPS, and Microbiome Toolbox had several issues that made the analysis more difficult. Over time, as more data are generated and accessed, more users will analyze microbiome data. Thus, the availability of free and easily accessible web tools can enable the easy use and analysis of microbiome data, especially for those users with less experience in using command-line interfaces.
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Microbioma Gastrointestinal , Microbiota , Microbioma Gastrointestinal/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Microbiota/genética , ARN Ribosómico 16S/genética , Programas InformáticosRESUMEN
Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells. Under normal conditions, ceramide plays an important role in various physiological functions, such as differentiation and apoptosis. However, under pathological conditions, excessive ceramide production is toxic and activates the neuronal-death pathway. Therefore, we hypothesized that the inhibition of ASMase activity by imipramine would reduce ceramide formation and thus prevent TBI-induced neuronal death. To test our hypothesis, an ASMase inhibitor, imipramine (10 mg/kg, i.p.), was administrated to rats immediately after TBI. Based on the results of this study, we confirmed that imipramine significantly reduced ceramide formation, dendritic loss, oxidative stress, and neuronal death in the TBI-imipramine group compared with the TBI-vehicle group. Additionally, we validated that imipramine prevented TBI-induced cognitive dysfunction and the modified neurological severity score. Consequently, we suggest that ASMase inhibition may be a promising therapeutic strategy to reduce hippocampal neuronal death after TBI.
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Lesiones Traumáticas del Encéfalo , Imipramina , Animales , Ratas , Imipramina/farmacología , Imipramina/uso terapéutico , Esfingomielina Fosfodiesterasa/metabolismo , Ceramidas/metabolismo , Hipocampo/metabolismo , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Muerte Celular , ApoptosisRESUMEN
Organochlorine pesticides (OCPs) are widely used in certain countries. We determined atmospheric concentrations, distribution patterns, and seasonal variations of OCPs at four sites in South Korea for 1 year. Samples of 22 OCPs were collected using a high-volume air sampler, and measured via the isotope dilution method with HRGC/HRMS. In South Korea, pentachlorobenzene (PeCB), hexachlorocyclohexane (HCB), and endosulfan (EnSF) were dominant, accounting for > 87% of total OCPs. Spatial distributions showed significant differences and the highest levels were observed in Seosan (295.2 pg·m-3), indicating the compounding potential of diverse sources as Seosan has concentrated large-scale industrial complexes and agricultural activity (Seoul: 243.6 pg·m-3 > Jeju: 193.5 pg·m-3 > Baengnyeong: 178.2 pg·m-3). The isomeric ratios of OCPs in the South Korean atmosphere indicated that the dominant sources of HCB and dichlorodiphenyltrichloroethane were primarily used in the past; meanwhile, chlordane (CHL) and EnSFs were derived from recent material inputs. Seasonally, OCP concentrations largely peaked in summer with minimum values in winter. This apparent temperature dependence suggests the re-volatilization of accumulated chemicals into the atmosphere. Additionally, an air mass back trajectory indicated the influence of pollutants released from a reservoir through long-range atmospheric transport in the summer. In particular, restricted OCPs are primarily released into the atmosphere by inadvertent sources, such as industrial activities and volatilization from contaminated areas. Thus, severe OCP pollution in Korea is due to the mobile nature of the particles. These data can be useful for the continuous monitoring of long-range transported air pollutants that are transferred between countries.
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Contaminantes Atmosféricos , Hidrocarburos Clorados , Plaguicidas , Contaminantes Atmosféricos/análisis , Atmósfera/química , Monitoreo del Ambiente , Hidrocarburos Clorados/análisis , Plaguicidas/análisis , Estaciones del AñoRESUMEN
OBJECTIVE: Varenicline is an efficacious aid for smoking cessation. In this study, the pharmacokinetics and safety were compared between film-coated tablets of varenicline tartrate (reference drug) and the newly developed orally disintegrating films of varenicline salicylate (test drug), both of them contained 1 mg of varenicline. MATERIALS AND METHODS: A randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted in healthy male subjects. Serial blood samples were obtained for up to 72 hours in each period, with a washout period of 7 days or more. The pharmacokinetic parameters were calculated using the noncompartmental method. Safety profiles were assessed throughout the study. RESULTS: A total of 28 subjects completed the study. The plasma varenicline concentration-time profiles were similar for the two study drugs. The maximum plasma varenicline concentration (Cmax) was 5,768.95 ng/L (mean) and 5,780.55 ng/L for the test drug and reference drug, respectively. The areas under the concentration-time curve from time 0 to the last measurable time point (AUC0-t) were 94,086.30 h×ng/L and 89,958.55 h×ng/L for the test drug and reference drug, respectively. The geometric mean ratios (90% confidence intervals) of the test drug to the reference drug for Cmax and AUC0-t were 0.9955 (0.9488 - 1.0444) and 1.0449 (0.9848 - 1.1088), respectively, which fell within the bioequivalence range of 0.8 - 1.25. There was no difference in safety between the study drugs. CONCLUSION: The pharmacokinetics and safety profiles were similar between the two study drugs. The orally disintegrating film of varenicline salicylate can be an alternative to varenicline tartrate tablets.
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Salicilatos , Administración Oral , Área Bajo la Curva , Estudios Cruzados , Voluntarios Sanos , Humanos , Masculino , Comprimidos , Equivalencia Terapéutica , Vareniclina/efectos adversosRESUMEN
Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.
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Lesiones Traumáticas del Encéfalo/patología , Muerte Celular/efectos de los fármacos , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Compuestos Nitrosos/farmacología , Pirimidinas/farmacología , Animales , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/fisiopatología , Recuento de Células , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Neuronas/patología , Neuronas/fisiología , Compuestos Nitrosos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Pirimidinas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Canales Catiónicos TRPC/antagonistas & inhibidores , Zinc/metabolismoRESUMEN
Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium-hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions. During the ischemic state, excessive sodium ions enter neurons and inappropriately activate the sodium-calcium exchanger (NCX). Zinc can also enter neurons through voltage-gated calcium channels and NCX. Here, we tested the hypothesis that zinc enters the intracellular space through NCX and the subsequent zinc accumulation induces neuronal cell death after global cerebral ischemia (GCI). Thus, we conducted the present study to confirm whether inhibition of NHE-1 by amiloride attenuates zinc accumulation and subsequent hippocampus neuronal death following GCI. Mice were subjected to GCI by bilateral common carotid artery (BCCA) occlusion for 30 min, followed by restoration of blood flow and resuscitation. Amiloride (10 mg/kg, intraperitoneally (i.p.)) was immediately injected, which reduced zinc accumulation and neuronal death after GCI. Therefore, the present study demonstrates that amiloride attenuates GCI-induced neuronal injury, likely via the prevention of intracellular zinc accumulation. Consequently, we suggest that amiloride may have a high therapeutic potential for the prevention of GCI-induced neuronal death.
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Acidosis/prevención & control , Amilorida/administración & dosificación , Isquemia Encefálica/tratamiento farmacológico , Bloqueadores del Canal de Sodio Epitelial/administración & dosificación , Hipocampo/metabolismo , Zinc/metabolismo , Acidosis/etiología , Acidosis/metabolismo , Amilorida/farmacología , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Muerte Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Bloqueadores del Canal de Sodio Epitelial/farmacología , Hipocampo/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood-brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.
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Compuestos de Boro/administración & dosificación , Cimenos/administración & dosificación , Neuronas/metabolismo , Convulsiones/prevención & control , Canales Catiónicos TRPM/metabolismo , Zinc/metabolismo , Animales , Transporte Biológico , Barrera Hematoencefálica/metabolismo , Compuestos de Boro/farmacología , Cimenos/farmacología , Modelos Animales de Enfermedad , Masculino , Neuronas/efectos de los fármacos , Pilocarpina/efectos adversos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Canales Catiónicos TRPM/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage. Several previous studies have shown that TRPM2 channel activation contributes to neuroinflammation and neurodegeneration cascades. Therefore, we examined whether anti-oxidant treatment, such as with N-acetyl-l-cysteine (NAC), provides neuroprotection via regulation of TRPM2, following global cerebral ischemia (GCI). Experimental animals were then immediately injected with NAC (150 mg/kg/day) for 3 and 7 days, before sacrifice. We demonstrated that NAC administration reduced activation of GCI-induced neuronal death cascades, such as lipid peroxidation, microglia and astroglia activation, free zinc accumulation, and TRPM2 over-activation. Therefore, modulation of the TRPM2 channel can be a potential therapeutic target to prevent ischemia-induced neuronal death.
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Acetilcisteína/farmacología , Antioxidantes/farmacología , Isquemia Encefálica/tratamiento farmacológico , Neuronas/efectos de los fármacos , Canales Catiónicos TRPM/metabolismo , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Peroxidación de Lípido/efectos de los fármacos , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Neuroglía/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , Canales Catiónicos TRPM/antagonistas & inhibidores , Zinc/metabolismoRESUMEN
We herein propose a multiwalled carbon nanotube (MWCNT) doping method into liquid crystal (LC) alignment polyimides (PIs) with low resistivity for resolving both issues of voltage holding and image sticking in low-frequency-driven fringe-field switching (FFS) LC modes using negative dielectric LCs (n-LCs). By utilizing strong ion trapping ability of MWCNTs, the FFS n-LC cell aligned by low resistivity PIs with 0.05 wt% MWCNT doping exhibited an excellent voltage holding ratio of 99% under an extremely low operation frequency of 0.5 Hz and approximately 23.6 times better surface discharging property than that aligned by high resistivity PIs.
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BACKGROUND: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. RESULTS: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. CONCLUSION: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles.
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Encéfalo/metabolismo , Hígado/metabolismo , Nanopartículas/análisis , Placenta/metabolismo , Titanio/farmacocinética , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Exposición Materna , Nanopartículas/química , Especificidad de Órganos , Embarazo , Ratas , Distribución Tisular , Titanio/químicaRESUMEN
BACKGROUND: Minimally invasive aesthetic procedures of the neck are becoming more popular. However, anatomical studies on the venous structures of the neck in relation to these procedures are lacking. OBJECTIVE: The aims of this study were to identify the locations and communication patterns of the anterior jugular vein and external jugular vein (AJV and EJV) and the communicating vein (CV) based on superficial anatomical landmarks and to determine dangerous areas for dermal filler injections into the neck. MATERIALS AND METHODS: Thirty sides of the neck from Korean adult cadavers were dissected for this study. RESULTS: Four anatomical variants were identified. In Type Ia, the CV ran along the anterior border of the sternocleidomastoid muscle (SCM) (33.4%); in Type Ib, a single vein was observed connecting the CV and the EJV at the level of laryngeal prominence (23.3%); in Type Ic, the CV proceeded separately from the medial side of the anterior border of the SCM (13.3%); and in Type II, the CV was absent while the EJV and AJV were observed (30%). CONCLUSION: Given the 4 anatomical variants identified in this study, the authors recommend exerting caution when performing dermal filler injections approximately 10, 30, and 60 mm lateral to the midsagittal line to avoid iatrogenic side effects.
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Rellenos Dérmicos/administración & dosificación , Cuello/irrigación sanguínea , Venas/anatomía & histología , Anciano , Puntos Anatómicos de Referencia , Variación Anatómica , Cadáver , Femenino , Humanos , Inyecciones , Venas Yugulares/anatomía & histología , Masculino , República de CoreaRESUMEN
Siloxanes have been used as chemical additives in various products since the 1940s. They are known to have potentially toxic effects, to be environmentally persistent, and to be bioaccumulative. Previous studies have reported high levels of siloxanes in various environmental matrices. In this study, 6 cyclic siloxanes (D4-D9) and 13 linear siloxanes (L3-L15) in coastal sediment collected from southeastern bays adjacent to industrial zones in South Korea (Busan, Ulsan, Jinhae, and Gwangyang) were analyzed. The contamination levels and spatial distribution of siloxanes in the coastal sediment samples were investigated, with the hazard quotients (HQs) for siloxanes evaluated using Monte Carlo simulation. Across all samples, the total concentration (Σ19) of siloxanes was in the range of 11.6-3877 (mean: 305; median: 133) ng/g dry weight (dw). The highest average concentration of Σ19 siloxanes was found in Busan (mean: 580; median: 233â¯ng/g dw), followed by Ulsan (mean: 316; median: 209â¯ng/g dw), Jinhae (mean: 266; median: 125â¯ng/g dw), and Gwangyang (mean: 33; median: 27â¯ng/g dw), all of which are suggested to be affected by both industrial and domestic activities. The highest contributions were from D5 (18%) and D6 (34%), followed by D9 (7.3%) and L11 (5.8%). The HQs for siloxanes were less than 1, indicating that there was no risk to benthic organisms in the study areas; however, further monitoring of various environmental matrices is required to fully assess the potential ecological risks.
Asunto(s)
Bahías/química , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Siloxanos/análisis , Contaminantes Químicos del Agua/análisis , Desarrollo Industrial , República de CoreaRESUMEN
Paddy soil contamination is directly linked to human dietary exposure to toxic chemicals via crop consumption. In Korea, rice paddy fields are often located around industrial complexes, a major anthropogenic source of metals. In this study, rice paddy soils were collected from 50 sites in three industrial cities to investigate the contamination characteristics and ecological risk of metals in the soils. The cities studied and their major industries are as follows: Ulsan (petrochemical, nonferrous, automobile, and shipbuilding), Pohang (iron and steel), and Gwangyang (iron and steel, nonmetallic, and petrochemical). Thirteen metals (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn) were analyzed using inductively coupled plasma-optical emission spectrometry (ICP-OES). The mean concentration of Cd (1.98 mg/kg) exceeded the soil quality guideline of Canada (1.4 mg/kg), whereas concentrations of other metals were under the standards of both Korea and Canada. Generally, levels of metal concentrations decreased with increasing distance from industrial complexes. Among the three cities, Pohang showed high concentrations of Zn (142.2 mg/kg), and Ulsan and Gwangyang showed high concentrations of Cr (33.9 mg/kg) and Ba (126.4 mg/kg), respectively. These contamination patterns were influenced by the different major industries of each city, which was clearly demonstrated by the principal component analysis results. Pollution indices suggested that As, Cd, Pb, and Zn were enriched in the paddy soils via anthropogenic activities. Comprehensive potential ecological risk indices were at considerable levels for most sites, especially because of major contributions from As and Cd, which can pose potential ecological threats.
Asunto(s)
Arsénico/análisis , Monitoreo del Ambiente , Industrias , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Suelo/química , Ciudades , Humanos , Oryza/crecimiento & desarrollo , República de Corea , Suelo/normasRESUMEN
Arsenic contamination in marine environments is a serious issue because some arsenicals are very toxic, increasing the health risks associated with the consumption of marine products. This study describes the development of an improved rapid method for the quantification of arsenic species, including arsenite (AsIII), arsenate (AsV), arsenocholine (AsC), arsenobetaine (AsB), dimethylarsinic acid (DMA), and monomethyl arsonic acid (MMA), in seaweed, sediment, and seawater samples using high-performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). ICP-MS based on dynamic reaction cells was used to eliminate spectral interference. Ammonium nitrate- and phosphate-based eluents were used as the mobile phases for HPLC analysis, leading to shorter overall retention time (6 min) and improved peak separation. Arsenicals were extracted with a 1% HNO3 solution that required no clean-up process and exhibited reasonable sensitivity and peak resolution. The optimized method was verified by applying it to hijiki seaweed certified reference material (CRM, NMIJ 7405-a) and to spiked blank samples of sediment and seawater. The proposed method measured the concentration of AsV in the CRM as 9.6 ± 0.6 µg/kg dry weight (dw), which is close to the certified concentration (10.1 ± 0.5 µg/kg dw). The recovery of the six arsenicals was 87-113% for the sediment and 99-101% for the seawater. In the analysis of real samples, AsV was the most abundant arsenical in hijiki and gulfweed, whereas AsB was dominant in other seaweed species. The two inorganic arsenicals (AsIII and AsV) and AsV were the most dominant in the sediment and seawater samples, respectively.
Asunto(s)
Arsenicales/análisis , Cromatografía Líquida de Alta Presión/métodos , Monitoreo del Ambiente/métodos , Espectrometría de Masas/métodos , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/instrumentación , Sedimentos Geológicos/química , República de Corea , Agua de Mar/química , Algas Marinas/químicaRESUMEN
We demonstrated a 2D/3D switchable mobile display using a polarization-dependent switching liquid crystalline polymeric (LCP) lens array film. In spite of short viewing distance and enough viewing window conditions provided by a small f-number lens for mobile displays, the 3D images when switched to the multi-view 3D mode showed a low crosstalk property owing to the improved lens aberration, as applying an aspherical lens curvature interface between the planar-convex LCP layer and the concave-planar isotropic polymer layer. Both 2D and 3D images were demonstrated based on a 5.5-inch quad high definition mobile display panel, where the binocular crosstalk of the 3D mode was 3.3%.