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The tricyclic quinazoline alkaloid deoxyvasicinone (DOV, 1) was isolated from a marine-derived Streptomyces sp. CNQ-617, and its anti-melanogenic effects were investigated. Deoxyvasicinone was shown to decrease the melanin content of B16F10 and MNT-1 cells that have been stimulated by α-melanocyte-stimulating hormone (α-MSH). In addition, microscopic images of the cells showed that deoxyvasicinone attenuated melanocyte activation. Although, deoxyvasicinone did not directly inhibit tyrosinase (TYR) enzymatic activity, real-time PCR showed that it inhibited the mRNA expression of TYR, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). In the artificial 3D pigmented skin model MelanodermTM, deoxyvasicinone brightened the skin significantly, as confirmed by histological examination. In conclusion, this study demonstrated that the marine microbial natural product deoxyvascinone has an anti-melanogenic effect through downregulation of melanogenic enzymes.
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Melaninas/metabolismo , Quinazolinas/farmacología , Piel/efectos de los fármacos , Streptomyces/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Humanos , Melanocitos/efectos de los fármacos , Melanocitos/metabolismo , Melanoma/metabolismo , Melanoma Experimental/metabolismo , Ratones , Quinazolinas/aislamiento & purificación , Piel/metabolismoRESUMEN
CONTEXT: Traditionally, the root of Angelica gigas Nakai (Umbelliferae), has long been used to treat ischaemic diseases and is considered safe in humans. OBJECTIVE: To investigate the neuroprotective effects of a methanol extract of A. gigas root (AGmex) on the middle cerebral artery occlusion (MCAO)-induced brain injury in mice, and the underlying mechanisms. MATERIALS AND METHODS: Two hours of transient MCAO (tMCAO) was induced in C57BL/6 mice (MCAO control group and AGmex groups), AGmex was administered to the AGmex group at 300-3,000 mg/kg bw at 1, 1, and 24 h before tMCAO or at 1000 mg/kg bw at 1 h before and after tMCAO. Infarction volumes, tissue staining, and western blotting were used to investigate the mechanism underlying the neuroprotective effects of AGmex. RESULTS: The median effective dose (ED50) could not be measured because the AGmex treatment did not reduce the infarction volume caused by 2 h of tMCAO to within 50%; however, pre-treatment with AGmex twice at 1,000 mg/kg bw before tMCAO significantly reduced the infarction volumes. The proteins related to cell growth, differentiation, and death were upregulated by this treatment, and the major recovery mechanisms appeared to involve the attenuation of the mitochondrial function of Bcl-2/Bax and activation of the PI3K/AKT/mTOR and MAPK signalling pathways in ischaemic neurons. CONCLUSIONS: This study provides evidence supporting the use of A. gigas root against ischaemic stroke and suggests a novel developmental starting point for the treatment of ischaemic stroke.
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Angelica/química , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Animales , Lesiones Encefálicas/etiología , Lesiones Encefálicas/prevención & control , Relación Dosis-Respuesta a Droga , Infarto de la Arteria Cerebral Media , Accidente Cerebrovascular Isquémico/complicaciones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/aislamiento & purificación , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/administración & dosificación , Raíces de Plantas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Some species of Artemisia have been reported to induce apoptosis and autophagy, but little is known of the apoptotic and autophagic effects of the stems and leaves of Artemisia kruhsiana Bess. (AkB). This study was conducted to investigate the antioxidant and anti-autophagic effects of the methanol extracts of the stems (EAkBs) and leaves (EAkBl) of AkB on human prostate cancer PC-3 cells. The antioxidant effects of EAkBs and EAkBl were measured using in vitro total flavonoid and total phenolic assays and a free radical scavenging assay. The effects of EAkBl on cell viability, apoptosis, autophagy, intracellular reactive oxygen species (ROS) generation and protein expression levels were also investigated. EAkBl was found to induce apoptosis, autophagy, and intracellular ROS generation in PC-3 cells. In terms of protein levels, EAkBl reduced phospho (p)-protein kinase B (AKT)/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratios, and the activations of beclin 1/ß-actin and microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3 I ratios in PC-3 cells. The results of this study indicate EAkBl has antioxidant and anticancer effects on prostate cancer cells, and that these effects are associated with suppressions of p-AKT, p-mTOR, Bcl-2, and Bax, and the activations of beclin 1 and LC3. Our results indicate EAkBl has potential as a treatment for prostate cancer.
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Artemisia , Muerte Celular Autofágica , Extractos Vegetales , Neoplasias de la Próstata , Apoptosis , Artemisia/química , Línea Celular Tumoral , Humanos , Masculino , Extractos Vegetales/farmacología , Hojas de la Planta/química , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patologíaRESUMEN
Dracocephalum palmatum Stephan is a medicinal plant traditionally used by nomadic people in Eastern Russia; however, research on this plant is currently limited. Recently, although studies have been conducted on the constituents of this plant and their antioxidant effects, data on its various pharmacological activities are still lacking. Thus, this study examined the anticancer potential of the dried leaves of D. palmatum S. (DpL) using human prostate cancer PC-3 cells. The antioxidant potential of DpL was evaluated by estimating the total flavonoid and total phenolic content (TFC and TPC, respectively). Additionally, we investigated the effects of the DpL ethyl acetate fraction (DpLE) on cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis, and cell cycle arrest in this cell line. The expression levels of superoxide dismutase (SOD)-1, SOD-2, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) ratio, phospho-protein kinase B (p-AKT), cleaved caspase-8, poly adenosine diphosphate (ADP) ribose polymerase (PARP), and cleaved-PARP were evaluated by western blotting. The results indicated that DpLE causes apoptosis and exerts intracellular ROS-independent anticancer effects on prostate cancer cells, associated with increased SOD-2, cleaved caspase-8, and cleaved-PARP expression and inhibited p-AKT signaling. Thus, DpLE may be a potential resource for the development of promising chemotherapeutic agents for prostate cancer.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 8/metabolismo , Lamiaceae/química , Extractos Vegetales/farmacología , Neoplasias de la Próstata/patología , Puntos de Control del Ciclo Celular , Humanos , Masculino , Células PC-3 , Neoplasias de la Próstata/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: The root of Angelica gigas Nakai (Apiaceae) has been traditionally used as an important herbal medicine to treat blood-deficiency-related disorders in Eastern Asian countries, and recently, it has been recognized as a potential candidate for improving cardiovascular diseases. METHODS: In this study, the neuroprotective effect of a methanol extract of A. gigas root (RAGE) was investigated in a mouse stroke model induced by a 90 min transient middle cerebral artery occlusion (tMCAO). Infarction volumes and morphological changes in brain tissues were measured using TTC, cresyl violet, and H&E staining. The neuroprotective mechanism of RAGE was elucidated through investigation of protein expression levels using western blotting, IHC, and ELISA assays. The plasma concentrations of decursin, a major compound in RAGE, were measured after oral administration of RAGE to SD rats. RESULTS: The infarction volumes in brain tissues were significantly reduced and the morphological deteriorations in the brain neuron cells were improved in tMCAO mice when pre-treated with RAGE at 1000 mg/(kg bw·d) for two consecutive days. The neuroprotective mechanism of RAGE was confirmed to attenuate ERK-related MAPK signaling pathways in the ipsilateral hippocampus hemisphere in mice. The concentrations of decursin in rat plasma samples showed peak absorption and elimination in vivo after oral administration of RAGE at 100 mg/rat. CONCLUSION: Mice administered RAGE before the tMCAO operation had less neuronal cell death than those that were not administered RAGE prior to the operation, and this study provides preclinical evidence for use of A. gigas in ischemic stroke.
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INTRODUCTION: Physicians and other prescribing clinicians use opioids as the primary method of pain management after traumatic injury, despite growing recognition of the major risks associated with usage for chronic pain. Placebos given after repeated administration of active treatments can acquire medication-like effects based on learning mechanisms. This study hypothesises that dose-extending placebos can be an effective treatment in relieving clinical acute pain in trauma patients who take opioids. METHODS AND ANALYSIS: The relieving acute pain is a proof-of-concept randomised, placebo-controlled, double-blinded, single-site study enrolling 159 participants aged from 18 to 65 years with one or more traumatic injuries treated with opioids. Participants will be randomly assigned to three different arms. Arm 1 will receive the full dose of opioids with non-steroidal anti-inflammatory drugs (NSAIDs). Arm 2 will receive the 50% overall reduction in opioid dosage, dose-extending placebos and NSAIDs. Arm 3 (control) will receive NSAIDs and placebos. The trial length will be 3 days of hospitalisation (phase I) and 2-week, 1-month, 3-month and 6-month follow-ups (exploratory phase II). Primary and secondary outcomes include feasibility and acceptability of the study. Pain intensity, functional pain, emotional distress, rates of rescue therapy requests and patient-initiated medication denials will be collected. ETHICS AND DISSEMINATION: All activities associated with this protocol are conducted in full compliance with the Institutional Review Board policies and federal regulations. Publishing this study protocol will enable researchers and funding bodies to stay up to date in their fields by providing exposure to research activity that may not otherwise be widely publicised. DATE AND PROTOCOL VERSION IDENTIFIER: 3/6/2019 (HP-00078742). TRIAL REGISTRATION NUMBER: NCT03426137.
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Dolor Agudo/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto JovenRESUMEN
Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up- or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.
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Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa/efectos adversos , Ephedra sinica , Hiperlipidemias/tratamiento farmacológico , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Animales , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Hiperlipidemias/inducido químicamente , Hiperlipidemias/genética , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Metanol , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Triglicéridos/sangreRESUMEN
Ischemia followed by reperfusion of cerebral blood flow after a stroke leads to the death of nerve cells and loss of brain tissue. The most commonly used animal model for studying stroke is the middle cerebral artery occlusion (MCAO) model. Previous research studies have reported different infarct sizes even when the same experimental animal species was used under similar MCAO conditions. Therefore, we developed an improved experimental method to address this discrepancy. Mice were subjected to MCAO using a filament as the occlusion material to mimic human stroke conditions and filament thickness was optimized to establish more reproducible infarction volume. Mice treated with a methanol extract of Glycyrrhizae Radix et Rhizome (GRex) following stroke induction showed a significantly decreased total infarction volume and increased number of surviving cells relative to the untreated control group. This modified experimental protocol successfully and reproducibly demonstrated the beneficial effect of GRex on ischemic stroke.
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Glycyrrhiza/clasificación , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Rizoma/químicaRESUMEN
BACKGROUND: Forsythiae Fructus (FF) is a well-known medicinal herb derived from the dried fruits of Forsythia suspensa (Thunb.) Vahl. (Oleaceae). Recently, bioactive compounds isolated from hydrophobic solvent fractions of FF have been reported to have anti-oxidant, antibacterial, and anti-cancer effects. OBJECTIVE: Almost all herbal medicines are derived from water extracts, which suggests different extraction methods might enhance the practical efficacies of herbal medicines. In this study, the authors further investigated the most potential anti-cancer fraction, that is, the hexane fraction (FFH) of the methanol extract (FFM) of the dried fruits of Forsythia suspensa. MATERIALS AND METHODS: FFH was investigated by measuring its effects on the viability and apoptotic death of PC-3 cells (a prostate cancer cell line), on the expression levels of Bcl-2, Bax, cytochrome c, procaspase-9, procaspase-3 and PARP, and caspase-3 activity. RESULTS: FFH significantly accelerated apoptotic cell death and decreased the protein levels of Bcl-2, procaspase-9, and procaspase-3. CONCLUSION: FFH can act as a pro-oxidative agent and induce the apoptosis of prostate cancer cells. SUMMARY: Hexane fraction of the methanol extract of Forsythiae Fructus (FFH) at a concentration more than 50 µg/mL significantly reduced PC-3 cell viabilityFFH time and dose dependently elevated intracellular ROS levels and increased the proportion of cells arrested in the G0/G1 phaseFFH significantly accelerated apoptotic cell death and diminished the protein expression levels of Bcl-2, procaspase-9, and procaspase-3The protein expression levels of Bax, cytochrome c, and cleaved PARP were increased by FFH, and so was the caspase-3 activity. Abbreviations used: FF: Forsythiae Fructus; FFM: Methanol extract of Forsythiae Fructus; FFH: Hexane fraction of the methanol extract; DCFH-DA: 2',7'-dichlorodihydro-fluorescein diacetate.
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Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis. The responses to PAR2-AP were initial and sustained contractions, depending on time. The maximum contraction of the initial phase occurred at 60 s. The PAR2-AP-induced contraction was mediated by Gαi1, Gαi3, and Gαq protein activation, leading to phospholipase-c (PLC) and myosin light chain kinase (MLCK) activation. 20 kDa myosin light chain (MLC20) was phosphorylated by PAR2-AP. Rho kinase-2 (ROCK-2), an activator of 17 kDa C-kinase potentiated Protein phosphatase-1 Inhibitor (CPI-17), was increased by PAR2 receptor activation. In conclusion, PAR2-AP produced an initial contraction mediated by Gαi1, Gαi3, and Gαq protein activation, resulting in PLC and MLCK activation. The sustained contraction by PAR2-AP was mediated by the Rho/Rho kinase-dependent pathway.
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Esófago/citología , Contracción Muscular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Oligopéptidos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , GatosRESUMEN
Purpose. To investigate the effect of tear protein deposition on the change in oxygen permeability (Dk) of soft contact lenses (SCL). Methods. Three hydrogel lenses (polymacon, nelfilcon A, and etafilcon A) and two silicon hydrogel lenses (lotrafilcon A and balafilcon A) were investigated. Etafilcon A lenses were incubated in artificial tear solution for 1, 6, 12, and 48 h, whereas the other SCL were incubated for 1, 3, 7, and 14 days. Oxygen permeability was measured using the polarographic method, and lenses were stacked in four layers to correct the boundary effect. Results. The Dk of all investigated SCL was decreased by the protein deposition. Silicone hydrogel lenses showed a smaller deposition of artificial tear proteins than conventional hydrogel lenses. However, their Dk was reduced twofold than those of 3 conventional hydrogel lenses when compared at the same level of protein deposition. Despite a large amount of total deposited protein in etafilcon A lenses, their Dk was more stable than other SCL. Conclusions. From the results, it was revealed that the Dk of SCL is different from the value provided by manufacturers because of the tear protein deposition on surface and/or in pore of SCL; however, the degree of Dk change in SCL was not simply correlated with the amount of tear protein deposition. Thus, it is considered that the correlation between tear protein deposition and properties of lens materials affects Dk change.
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Quercetin-3-O-ß-D-glucuronopyranoside (QGC) is a flavonoid glucoside extracted from Rumex Aquaticus. Recent studies have shown that QGC exhibits anti-inflammatory, anti-oxidateve effect in vivo and cytoprotective effect in vitro. Reactive oxygen species (ROS), at low concentration, play role as a primary signal or second messenger, however, at high concentration, ROS are cytotoxic. In this study, we investigated the protective mechanism of QGC in H2O2-induced injury of Feline Esophageal Epithelial Cells. Primary-cultured feline esophagus cells were identified by an indirect immunofluorescent staining method using a cytokeratin monoclonal antibody. Cell viability was determined by the conventional MTT reduction assay. Western blot analysis was performed with specific antibodies to investigate the activation of MAPKs, NF-κB, and IκB-α, and the expression of COX-2. When the cells were exposed to 600 µM H2O2 medium for 24 h, cell viability decreased to 54 %. However, when cells were pretreated with 50-150 µM QGC for 12 h, the viability of cells exposed to H2O2 significantly increased in the dose dependent manner. QGC (50 µM, 12 h) also inhibited the expression of COX-2 induced by 10 µM H2O2 for 24 h. We found that treatment of H2O2 activated p38 MAPK and JNK, but not ERK. However QGC inhibited the H2O2-induced p38 MAPK and JNK phosphorylation. In addition, NF-κB was activated by H2O2 and translocated into the nucleus, but QGC inhibited the activation of NF-κB by blocking degradation of IκB. These data suggest that QGC reduces H2O2-induced COX-2 production by modulating the p38 MAPK, JNK, NF-κB signal pathway in feline esophageal epithelial cells.
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Mucosa Esofágica/efectos de los fármacos , Mucosa Esofágica/lesiones , Peróxido de Hidrógeno/toxicidad , Quercetina/análogos & derivados , Animales , Gatos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Mucosa Esofágica/metabolismo , Femenino , Masculino , Técnicas de Cultivo de Órganos , Sustancias Protectoras/farmacología , Quercetina/farmacologíaRESUMEN
BACKGROUND: The dried fruit of Forsythia suspensa (Thunb.) Vahl. (Oleaceae) are better known by their herbal name Forsythiae Fructus, and have a bitter taste, slightly pungent smell, and cold habit. FF has been widely used to treat symptoms associated with the lung, heart, and small intestine. Recently, bioactive compounds isolated from hydrophobic solvent fractions of FF have been reported to have anti-oxidant, anti-bacterial, and anti-cancer effects. Traditionally, almost all herbal medicines are water extracts, and thus, extraction methods should be developed to optimize the practical efficacies of herbal medicines. MATERIALS AND METHODS: In this study, the anti-inflammatory effects of the ethyl acetate fraction of the methanol extract of FF (FFE) were assessed by measuring NO and PGE2 production by and intracellular ROS and protein levels of iNOS and COX-2 in RAW 264.7 cells. RESULTS: FFE inhibited COX-2 expression in LPS-stimulated RAW 264.7 cells. CONCLUSION: In summary, FFE effectively reduced intracellular ROS and NO levels and inhibited PGE2 production by down-regulating COX-2 levels. Abbreviations: FF, of Forsythiae Fructus; NO, nitric oxide; iNOS, inducible NO synthase; COX-2, cyclooxygenase-2; ROS, reactive oxygen species; PGE2, prostaglandin E2.
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Acetatos/farmacología , Antiinflamatorios/farmacología , Forsythia/química , Metanol/química , Extractos Vegetales/química , Animales , Ciclooxigenasa 2/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/metabolismo , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
AIM: To determine the effect of pH, osmolality, and buffering system on the oxygen permeability (Dk) of soft contact lenses. METHODS: Two hydrogel lenses (nelfilcon A and etafilcon A) and 2 silicone hydrogel lenses (lotrafilcon A and balafilcon A) were used in the study. These lenses were incubated in phosphate-buffered saline (PBS) and borate-buffered saline (BBS) solutions adjusted by 0.8 pH increments to a pH in the range of 5.8-9.0 or in hypotonic (280 mOsmol/kg), isotonic (310 mOsmol/kg) and hypertonic (380 mOsmol/kg) PBS solutions. Polarographic method was used for measuring the Dk and lenses were stacked as 4 layers to correct the boundary effect. RESULTS: Dk values of all contact lenses measured in BBS solutions were more stable than those in PBS solutions. Especially the etafilcon A lens showed a relative big change compared with other types of contact lenses at the same conditions. When the osmolality of PBS solution increased from hypotonic to hypertonic, Dk of all contact lenses decreased. Variations in Dk existed depending on lens materials, etafilcon A lens was the most affected and nelfilcon A was the least affected by osmolality. CONCLUSION: From the result obtained, it is revealed that Dk of contact lenses is changed by the pH, osmolality, and buffering condition of tear. Thus, Dk of contact lens can be varied by the lens wearers' physiological and/or pathological conditions.
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FSGS is the second most common cause of idiopathic NS in children. It often progresses to ESRD and commonly recurs after KT. To investigate the risk factors and the prognosis of recurrence in pediatric idiopathic FSGS in Korea, retrospective review of 43 KT in 38 children with idiopathic FSGS of last two decades was conducted. The patients presented at the median age of 5.1 yr (range 1.1-13.8 yr) and received KT 5.7 yr later (range 1.3-17.6 yr). FSGS recurred in 20 allografts immediately after transplantation, only in those who presented with NS but not in those who presented with AUA. The risk factors for recurrence were age of onset >5 yr and progression to ESRD within six yr but not sooner than 18 months. CR was achieved in 13 patients with FSGS recurrence and sustained in nine without subsequent relapse over a median of six and a half yr (0.6-20.7 yr). Pediatric idiopathic FSGS presenting with NS recurred in more than half of patients after transplantation. Interestingly, more rapid progression within less than 18 months did not predict recurrence. To identify high-risk patients of recurrence, an international cooperative study would be necessary.
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Glomeruloesclerosis Focal y Segmentaria/cirugía , Trasplante de Riñón , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
This study investigated effect of extract containing quercetin-3-O-ß-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.
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PURPOSE: Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children. The present paper investigated the pattern of current practice in intravenous fluid prescription among Korean pediatric residents, to underscore the need for updated education. METHODS: A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question proposed a unique scenario in which the respondents had to prescribe either a hypotonic or an isotonic fluid for the patient. RESULTS: Ninety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy. CONCLUSION: In the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required.
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BACKGROUND: Recently, urinary exosomal WT1 has been proposed as a novel biomarker for simple podocyte injury. We investigated urinary exosomal WT1 to confirm its role as a non-invasive biomarker for predicting steroid responsiveness or renal pathological conditions in patients with idiopathic nephrotic syndrome (NS). CASE DIAGNOSIS: Forty children with active NS were recruited. Twenty-eight (70%) were steroid-sensitive, including 3 with minimal change NS (MCNS) and 1 with focal segmental glomerulosclerosis (FSGS). The remaining 12 (30%) were steroid-resistant, including 8 with FSGS and 4 with MCNS. Urinary exosomes were isolated by a differential centrifugation method, and WT1 was measured by Western blot analysis. RESULTS: WT1 was detected in 25 patients (62.5%). There was no significant difference in the proportion of the patients with a detectable amount of WT1 according to steroid responsiveness or renal pathological condition, the amount of WT1 showed no significant difference according to steroid responsiveness or renal pathological condition, and there was no significant difference in the amount of proteinuria between patients with or without detectable WT1. CONCLUSIONS: Urinary exosomal WT1 was detected in some patients with NS. However, its role as an appropriate biomarker in childhood NS was not verified in this study.
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Exosomas/química , Síndrome Nefrótico/orina , Proteínas WT1/orina , Corticoesteroides/uso terapéutico , Biomarcadores , Niño , Preescolar , Femenino , Humanos , Riñón/patología , Masculino , Síndrome Nefrótico/tratamiento farmacológico , Proteínas WT1/fisiologíaRESUMEN
Pseudohypoaldosteronism type 1 (PHA1) is a rare form of mineralocorticoid resistance characterized in newborns by salt wasting with dehydration, hyperkalemia and failure to thrive. This disease is heterogeneous in etiology and includes autosomal dominant PHA1 owing to mutations of the NR3C2 gene encoding the mineralocorticoid receptor, autosomal recessive PHA1 due to mutations of the epithelial sodium channel (ENaC) gene, and secondary PHA1 associated with urinary tract diseases. Amongst these diseases, autosomal dominant PHA1 shows has manifestations restricted to renal tubules including a mild salt loss during infancy and that shows a gradual improvement with advancing age. Here, we report a neonatal case of PHA1 with a NR3C2 gene mutation (a heterozygous c.2146_2147insG in exon 5), in which the patient showed failure to thrive, hyponatremia, hyperkalemia, and elevated plasma renin and aldosterone levels. This is the first case of pseudohypoaldosteronism type 1 confirmed by genetic analysis in Korea.
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Bartter syndrome (BS) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism. There have been several case reports of BS complicated by focal segmental glomerulosclerosis (FSGS). Here, we have reported the case of a BS patient who developed FSGS and subsequent end-stage renal disease (ESRD) and provided a brief literature review. The patient presented with classic BS at 3 months of age and developed proteinuria at 7 years. Renal biopsy performed at 11 years of age revealed a FSGS perihilar variant. Hemodialysis was initiated at 11 years of age, and kidney transplantation was performed at 16 years of age. The post-transplantation course has been uneventful for more than 3 years with complete disappearance of BS without the recurrence of FSGS. Genetic study revealed a homozygous p.Trp(TGG)610Stop(TGA) mutation in the CLCNKB gene. In summary, BS may be complicated by secondary FSGS due to the adaptive response to chronic salt-losing nephropathy, and FSGS may progress to ESRD in some patients. Renal transplantation in patients with BS and ESRD results in complete remission of BS.