An Autopsy-Proven Case of Limbic-Predominant Age-Related TDP-43 Encephalopathy.

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently established neurodegenerative disease entity. LATE neuropathological change (LATE-NC) is characterized by a TDP-43 proteinopathy that mainly involves the amygdala and medial temporal structures, with or without hippocampal sclerosis. LATE-NC is typically observed in individuals aged 80 years or older and manifests clinically as amnestic memory decline. Herein, we report a case of LATE diagnosed by brain autopsy in an 82-year-old male who had an 11-year history of memory impairment. Pathological examination revealed high Alzheimer disease neuropathological changes, as well as amygdala-predominant Lewy body pathology. In addition, immunohistochemistry for TDP-43 revealed neuronal and glial cytoplasmic inclusions in the dentate gyrus of the hippocampus, amygdala, and inferior temporal cortex. Increasing awareness of the newly defined entity LATE will enhance our understanding of the neurodegenerative processes that occur in the oldest individuals.

Comparison of risk and protective factors associated with smartphone addiction and Internet addiction.

BACKGROUND AND AIMS: Smartphone addiction is a recent concern that has resulted from the dramatic increase in worldwide smartphone use. This study assessed the risk and protective factors associated with smartphone addiction in college students and compared these factors to those linked to Internet addiction. METHODS: College students (N = 448) in South Korea completed the Smartphone Addiction Scale, the Young's Internet Addiction Test, the Alcohol Use Disorders Identification Test, the Beck Depression Inventory I, the State-Trait Anxiety Inventory (Trait Version), the Character Strengths Test, and the Connor-Davidson Resilience Scale. The data were analyzed using multiple linear regression analyses. RESULTS: The risk factors for smartphone addiction were female gender, Internet use, alcohol use, and anxiety, while the protective factors were depression and temperance. In contrast, the risk factors for Internet addiction were male gender, smartphone use, anxiety, and wisdom/knowledge, while the protective factor was courage. Discussion These differences may result from unique features of smartphones, such as high availability and primary use as a tool for interpersonal relationships. CONCLUSIONS: Our findings will aid clinicians in distinguishing between predictive factors for smartphone and Internet addiction and can consequently be utilized in the prevention and treatment of smartphone addiction.

(-)-Epigallocatechin-3-gallate induces secretion of anorexigenic gut hormones.

The anorexigenic gut hormones, cholecystokinin (CCK), glucagon-like peptide (GLP)-1 and peptide tyrosine-tyrosine (PYY), are released in response to food intake from the intestines. Dietary nutrients have been shown to stimulate these hormones. Some non-nutrients such as polyphenols show anorexigenic effects on humans. In the present study, we examined whether dietary polyphenols can stimulate secretion of these gut hormones. Caco-2 cells expressed mRNA of the gut hormones, CCK, PC1 (prohormone convertase 1), GCG (glucagon) and PYY. CCK, GLP-1 and PYY were secreted from Caco-2 cells after adding sugars, amino acids or fatty acids. Using Caco-2 cells, epigallocatechin-3-gallate (EGCG), chlorogenic acid and ferulic acid induced secretion of anorexigenic gut hormones. Particularly, EGCG induced secretion of all three hormones. In an ex vivo assay using murine intestines, EGCG also released CCK from the duodenum, and GLP-1 from the ileum. These results suggest that EGCG may affect appetite via gut hormones.

Latent class analysis on internet and smartphone addiction in college students.

PURPOSE: This study aimed to classify distinct subgroups of people who use both smartphone and the internet based on addiction severity levels. Additionally, how the classified groups differed in terms of sex and psychosocial traits was examined. METHODS: A total of 448 university students (178 males and 270 females) in Korea participated. The participants were given a set of questionnaires examining the severity of their internet and smartphone addictions, their mood, their anxiety, and their personality. Latent class analysis and ANOVA (analysis of variance) were the statistical methods used. RESULTS: Significant differences between males and females were found for most of the variables (all <0.05). Specifically, in terms of internet usage, males were more addicted than females (P<0.05); however, regarding smartphone, this pattern was reversed (P<0.001). Due to these observed differences, classifications of the subjects into subgroups based on internet and smartphone addiction were performed separately for each sex. Each sex showed clear patterns with the three-class model based on likelihood level of internet and smartphone addiction (P<0.001). A common trend for psychosocial trait factors was found for both sexes: anxiety levels and neurotic personality traits increased with addiction severity levels (all P<0.001). However, Lie dimension was inversely related to the addiction severity levels (all P<0.01). CONCLUSION: Through the latent classification process, this study identified three distinct internet and smartphone user groups in each sex. Moreover, psychosocial traits that differed in terms of addiction severity levels were also examined. It is expected that these results should aid the understanding of traits of internet and smartphone addiction and facilitate further study in this field.

In vitro metabolism of jaceosidin and characterization of cytochrome P450 and UDP-glucuronosyltransferase enzymes in human liver microsomes.

Jaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. Jaceosidin was metabolized to jaceosidin glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This study characterized the human liver cytochrome P450 (CYP) and UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of jaceosidin. CYP1A2 was identified as the major enzyme responsible for the formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the basis of a combination of correlation analysis and experiments including immuno-inhibition, chemical inhibition in human liver microsomes, and metabolism by human cDNA-expressed CYP enzymes. Jaceosidin glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic CYP1A2, UGT1A1, and UGT1A7 responsible for the metabolism of jaceosidin or by the coadministration of relevant CYP1A2 or UGT inhibitors or inducers.

Pharmacokinetics of magnolin in rats.

This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the V ( ss ) after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3-76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3-80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were dose-independent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed.

Effect of ethanol extracts from red pepper seeds on antioxidative defense system and oxidative stress in rats fed high-fat . high-cholesterol diet.

The purpose of the present study was to investigate the effect of ethanol extracts from red pepper seeds on the antioxidative defense system and oxidative stress in rats fed a high fat . high cholesterol diet. Rats were divided into four experimental groups which were composed of high fat . high cholesterol diet group (HF), high fat . high cholesterol diet with 0.1% ethanol extracts from red pepper seeds supplemented group (HEA), high fat . high cholesterol diet with 0.2% ethanol extracts from red pepper seeds supplemented group (HEB) and high fat.high cholesterol diet with 0.5% ethanol extracts from red pepper seeds supplemented group (HEC). Supplementation of ethanol extracts from red pepper seeds groups (HEA, HEB and HEC) resulted in significantly increased activities of hepatic glutathione peroxidase and catalase. Hepatic superoxide radical contents in microsome and mitochondria were significantly reduced in the groups supplemented with red pepper seeds ethanol extracts. Hepatic hydrogen peroxide content in the mitochondria was reduced in ethanol extracts from red pepper seeds supplemented groups. TBARS values in the liver were reduced in red pepper seeds ethanol extracts supplemented groups. Especially, HEB and HEC groups were significantly decreased compared to the HF group. Hepatic carbonyl values were significantly reduced in mitochondria in these supplemented groups. These results suggest that red pepper seeds ethanol extracts may reduce oxidative damage, by activation of antioxidative defense system in rats fed high fat . high cholesterol diets.

Liquid chromatography-tandem mass spectrometry for the determination of jaceosidin in rat plasma.

Jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone), isolated from Artemisia species as well as Eupatorium species, has antiallergic, anticancer, anti-inflammatory and antioxidant activity. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the quantification of jaceosidin in rat plasma was developed to characterize the pharmacokinetics of jaceosidin. Jaceosidin and the internal standard, linezolid, were extracted from rat plasma with ethyl acetate at acidic pH and analyzed on a Luna phenyl-hexyl column using the mixture of acetonitrile and 0.1% formic acid (45:55, v/v) as a mobile phase. The analytes were determined using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The calibration curve was linear (r(2)=0.9973) over the concentration range of 2.00-500ng/ml. The lower limit of quantification for jaceosidin was 2.0ng/ml using 50 microl of plasma sample. The coefficients of variation of intra- and inter-assay at four QC levels were 2.4-9.6% and the relative errors were -9.1 to 10.0%. The matrix effects for jaceosidin and linezolid were practically absent. The recoveries of jaceosidin and linezolid were 87.0 and 87.7%, respectively. This method was successfully applied to the pharmacokinetic study of jaceosidin in rats.

Simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study of a standardized fraction of Salvia miltiorrhiza, PF2401-SF.

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone, the active components of Salvia miltiorrhiza in rat plasma, was developed. After liquid-liquid extraction with tariquidar as an internal standard, tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone were eluted from an Atlantis dC18 column within 5 min with a mixture of methanol and ammonium formate (10 mm, pH 6.5; 85:15, v/v). The analytes were detected by an electrospray ionization tandem mass spectrometry in the selected reaction monitoring (SRM) mode. The standard curves were linear (r=0.999) over the concentration range of 0.25-80 ng/mL for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma. The coefficients of variation and the relative errors of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone for intra- and inter-assay at four quality control (QC) concentrations were 1.1-5.1% and -4.0-6.0%, respectively. The lower limit of quantification for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone was 0.25 ng/mL from 100 microL of plasma. This method was successfully applied to the pharmacokinetic study of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone after oral administration of PF2401-SF, the standardized fraction of Salvia miltiorrhiza enriched with tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone to male Sprague-Dawley rats.