We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed 18F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed 18F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

Purpose: The purpose of this pilot study is to evaluate the reliability and validity of the Korean version of the oral health impact profile (OHIP-EDENT K) for edentulous patients. Materials and Methods: The study was conducted on 12 patients who fabricated overdenture in the Department of Prosthodontics, Korea University, Guro Hospital. All subjects completed the Korean version of Oral Health Impact Profile (OHIP K) questionnaire. Shorten version of the OHIP called OHIP-14 K and OHIP-EDENT K were derived from the datasets. Cronbach's alpha was used to measure internal consistency of the summary scores for OHIP-EDENT K. The Spearman's correlation coefficient between the summary scores for OHIP-EDENT K and OHIP K was calculated to evaluate concurrent validity. Results: The reliability of the summary scores for OHIP-EDENT K was acceptable (α=.736). The Spearman's correlation coefficient of the summary scores for OHIP-EDENT K and OHIP K was 0.966, which was statistically significant (P<.001). OHIP-EDENT K exhibited less susceptibility to floor effects than OHIP-14 K and appeared to measure change as effectively as OHIP K. In order to prove the reliability, responsiveness and validity of OHIP-EDENT K, further studies with more samples are needed. Conclusion The OHIP-EDENT K, a questionnaire on oral health-related QOL comprising 19 items, has measurement properties comparable with the full 49-item version. This modified shortened version can be an alternative questionnaire to full version of OHIP K and OHIP-14 K in edentulous patients.

Purpose: The purpose of this pilot study is to evaluate the reliability and validity of the Korean version of the oral health impact profile (OHIP-EDENT K) for edentulous patients. Materials and Methods: The study was conducted on 12 patients who fabricated overdenture in the Department of Prosthodontics, Korea University, Guro Hospital. All subjects completed the Korean version of Oral Health Impact Profile (OHIP K) questionnaire. Shorten version of the OHIP called OHIP-14 K and OHIP-EDENT K were derived from the datasets. Cronbach's alpha was used to measure internal consistency of the summary scores for OHIP-EDENT K. The Spearman's correlation coefficient between the summary scores for OHIP-EDENT K and OHIP K was calculated to evaluate concurrent validity. Results: The reliability of the summary scores for OHIP-EDENT K was acceptable (α=.736). The Spearman's correlation coefficient of the summary scores for OHIP-EDENT K and OHIP K was 0.966, which was statistically significant (P<.001). OHIP-EDENT K exhibited less susceptibility to floor effects than OHIP-14 K and appeared to measure change as effectively as OHIP K. In order to prove the reliability, responsiveness and validity of OHIP-EDENT K, further studies with more samples are needed. Conclusion The OHIP-EDENT K, a questionnaire on oral health-related QOL comprising 19 items, has measurement properties comparable with the full 49-item version. This modified shortened version can be an alternative questionnaire to full version of OHIP K and OHIP-14 K in edentulous patients.

OBJECTIVETo examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines.

METHODSA549 cells were treated with varying concentrations (50-200 μg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively.

RESULTSThe exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK).

CONCLUSIONSBXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

A549 Cells ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase Inhibitors ; pharmacology ; Cisplatin ; pharmacology ; DNA Fragmentation ; drug effects ; Humans ; Plant Extracts ; pharmacology

BACKGROUND: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to NAD+ by various quinones and thereby elevates the intracellular NAD⁺ levels. In this study, we examined the effect of increase in cellular NAD⁺ levels on bleomycin-induced lung fibrosis in mice. METHODS: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with β-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor β1 (TGF-β1) and β-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). RESULTS: β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1–induced ECM expression and EMT in A549 cells. CONCLUSION: Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1–induced EMT in vitro, by elevating the NAD+/NADH ratio through NQO1 activation.
Actins ; Animals ; Bleomycin ; Bronchoalveolar Lavage Fluid ; Cytokines ; Epithelial-Mesenchymal Transition ; Extracellular Matrix ; Fibrosis* ; Idiopathic Pulmonary Fibrosis ; In Vitro Techniques ; Inflammation ; Lung Diseases ; Lung Diseases, Interstitial ; Lung* ; Mice* ; NAD ; Pneumonia ; Pulmonary Fibrosis ; Quinones ; Transforming Growth Factor beta1 ; Transforming Growth Factors

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.
Animals ; Antioxidants/*metabolism/*pharmacology ; Apoptosis/drug effects ; Caspase 3/metabolism ; Caspase 8/metabolism ; Cell Line ; Cisplatin/*toxicity ; Cysteine/*analogs & derivatives/pharmacology ; Gene Expression Regulation/*drug effects ; Gene Knockdown Techniques ; Glutathione/*metabolism ; Heme Oxygenase-1/genetics ; Intracellular Space/metabolism ; Male ; Metabolic Detoxication, Phase II/genetics ; Mice ; NF-E2-Related Factor 2/genetics ; Nitric Oxide/biosynthesis ; Organ of Corti/*drug effects/*metabolism ; RNA Interference ; Rats ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/genetics

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.
Cisplatin ; Diuretics ; DNA Damage ; Drug Therapy ; Humans ; Kidney* ; Oxidative Stress ; Prevalence

BACKGROUND/AIMS: The hepatitis B virus (HBV) genome contains binding sites for hepatocyte nuclear factors (HNF) 3 and 4 in the core domain of enhancer 1 (Enh1), and mutations in this domain have a strong impact on virus replication. We aimed to identify frequent base-mutation sites in the core domain of Enh1 and to examine the impact of these mutations on viral replication. METHODS: We studied virological characteristics and genetic sequences in 387 patients with chronic hepatitis B. We evaluated functional differences associated with specific mutations within the core domain of Enh1. RESULTS: Mutations in the core domain were found with significant frequency in C1126 (122/387 [31.5%], the binding site for HNF3) and in C1134 (106/387 [27.4%], the binding site for HNF4). A single mutation at nt 1126 (C1126) was identified in 17/123 (13.8%), and 105/123 (85.4%) had double mutations (C1126/1134). The level of HBV DNA (log10 copies/mL) was lower in single mutants (C1126, 5.81+/-1.25) than in wild (6.80+/-1.65) and double mutants (C1126/1134, 6.81+/-1.54). Similarly, the relative luciferase activity of C1126 and C1126/C1134 was 0.18 and 1.12 times that of the wild-type virus, respectively. CONCLUSIONS: Mutations in the HNF3 binding site inhibit viral replication, whereas mutations at the HNF4 binding site restore viral replication.
Binding Sites ; DNA ; Genome ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Hepatocyte Nuclear Factors ; Humans ; Luciferases ; Virus Replication ; Viruses

Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibitors, including gadolinium and ruthenium red, which resulted in markedly inhibited GTTR uptake and gentamicin-induced hair cell damage in rodent and zebrafish ototoxic model systems. These results indicate that the cytotoxic vulnerability of cochlear hair cells in the basal turn to gentamicin may depend on effective uptake of the drug, which was, in part, mediated by the TRPV1 and TRPV4 proteins.
Animals ; Cell Death/drug effects ; Cell Polarity/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Gadolinium/metabolism ; Gentamicins/*metabolism/pharmacology ; Hair Cells, Auditory/drug effects/*metabolism ; Hair Cells, Auditory, Inner/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Ruthenium Red/metabolism ; TRPV Cation Channels/*metabolism ; Time Factors ; Xanthenes/metabolism ; Zebrafish