The Association between Serum Lipid Levels and Tinnitus Prevalence and Severity in Korean Elderly: A Nationwide Population-Based Cross-Sectional Study.

PURPOSE: We aimed to investigate the association between serum lipid level and tinnitus risk in Korean older adults. MATERIALS AND METHODS: This study used data from the 2016-2018 Korea National Health and Nutrition Examination Survey. Overall, 6021 subjects aged ≥60 years were included. Hypertriglyceridemia was defined as a serum triglyceride level of ≥200 mg/dL. The high-risk threshold of the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio was defined as above 5.0. The presence of tinnitus was assessed via health interviews. Tinnitus severity was classified as "not annoying," "irritating," and "severely annoying and causing sleep problems." Multivariate logistic regression analysis was performed to examine the association between serum lipid level and tinnitus risk. RESULTS: The odds ratio (OR) of tinnitus was 1.27-times higher in the group with hypertriglyceridemia than in the group without hypertriglyceridemia after adjusting for age, sex, hypertension, diabetes, dyslipidemia, anemia, current smoking, obesity, noise exposure, stress cognition, and depressive mood or anxiety [95% confidence interval (CI) 1.04-1.56, p=0.022]. The OR of tinnitus was 1.21-times higher in the group with a high TC/HDL-C ratio than in the group without a high TC/HDL-C ratio after adjusting for the same variables as above (95% CI 1.02-1.44, p=0.025). CONCLUSION: This study revealed that hypertriglyceridemia and high TC/HDL-C ratio were significantly associated with an increased OR of tinnitus in Korean older adults.

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro.

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.

Association between Daily Sunlight Exposure and Fractures in Older Korean Adults with Osteoporosis: A Nationwide Population-Based Cross-Sectional Study.

PURPOSE: We aimed to investigate the association between daily sunlight exposure duration and fractures in older Korean adults with osteoporosis. MATERIALS AND METHODS: We utilized data from the 2008-2011 Korea National Health and Nutrition Examination Survey. Osteoporosis was diagnosed based on a T-score of ≤-2.5 using dual energy X-ray absorptiometry. The duration of daily sunlight exposure and fracture were assessed via intensive health interviews by trained staff using standardized health questionnaires. Fracture was defined as one or more fractures of the femur, wrist, and spine. RESULTS: A total of 638 patients with osteoporosis aged ≥65 years were included. The odds ratio (OR) of total fractures was 0.55 times lower in the group with ≥5 h of daily sunlight exposure than in the group with <5 h of exposure after adjusting for age, sex, family history of osteoporosis or fracture, body mass index, bone mineral density of the femoral neck, serum 25-hydroxyvitamin D, current smoking, alcohol intake, daily calcium intake, and physical activity [95% confidence interval (CI) 0.31-0.97, p=0.040]. In patients with vitamin D insufficiency, the OR of total fracture was 0.52 times lower in the group with ≥5 h of daily sunlight exposure than in the group with less exposure after adjusting the above variables (95% CI 0.28-0.97, p=0.041). CONCLUSION: Sunlight exposure for ≥5 h a day was significantly associated with a decreased OR of fracture in older Korean adults with osteoporosis. This association was also significant in patients with vitamin D insufficiency.

Coagulant Effect and Tolerability of Yeast-Produced Recombinant Batroxobin in Healthy Adult Subjects.

BACKGROUND AND OBJECTIVE: Batroxobin, a snake venom thrombin-like enzyme, converts fibrinogen into fibrin by cleaving fibrinopeptide A. It is used for hemostasis; however, the supply of native batroxobin is limited. Therefore, we developed a recombinant batroxobin (r-batroxobin) from Pichia pastoris and evaluated its pharmacodynamics and safety in humans. METHODS: A randomized, double-blind, placebo-controlled, single ascending-dose study was performed. Eight healthy subjects were enrolled in each r-batroxobin dose group (2.5, 5.0, or 10.0 BU/2.0 mL administered intravenously), and randomized to receive r-batroxobin (n = 6) or matching placebo (n = 2). Safety was evaluated during the study, and pharmacodynamics was assessed using prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen level. RESULTS: All subjects in each cohort completed the study. No significant changes in PT or aPTT occurred after intravenous r-batroxobin administration. Compared with the placebo group, the fibrinogen level in all r-batroxobin dose groups decreased significantly to 8.68-33.57% from the baseline within 12 h (p ≤ 0.05). The TT in the 5.0 and 10.0 BU/2.0 mL groups significantly increased to 7.53-18.48% from baseline within 12 h compared with that of the placebo group (p ≤ 0.05), whereas that of the 2.5 BU/2.0 mL group exhibited non-significant changes compared with the placebo group. No serious adverse events occurred. CONCLUSIONS: A single intravenous injection of r-batroxobin within a dose range of 2.5-10.0 BU/2.0 mL was well tolerated and resulted in a significant decrease in fibrinogen and prolongation of TT. REGISTRATION: This study is registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ), number KCT0002518.

Pharmacokinetic interactions between glimepiride and rosuvastatin in healthy Korean subjects: does the SLCO1B1 or CYP2C9 genetic polymorphism affect these drug interactions?

To improve cardiovascular outcomes, dyslipidemia in patients with diabetes needs to be treated. Thus, these patients are likely to take glimepiride and rosuvastatin concomitantly. Therefore, this study aimed to evaluate the pharmacokinetic (PK) interactions between these two drugs in healthy males and to explore the effect of SLCO1B1 and CYP2C9 polymorphisms on their interactions in two randomized, open-label crossover studies. Glimepiride was studied in part 1 and rosuvastatin in part 2. Twenty-four participants were randomly assigned to each part. All subjects (n=24) completed part 1, and 22 subjects completed part 2. A total of 38 subjects among the participants of the PK interaction studies were enrolled in the genotype study to analyze their SLCO1B1 and CYP2C9 polymorphisms retrospectively (n=22 in part 1, n=16 in part 2). Comparison of the PK and safety of each drug alone with those of the drugs in combination showed that both glimepiride and rosuvastatin did not interact with each other and had tolerable safety profiles in all subjects. However, with regard to glimepiride PK, the SLCO1B1 521TC group had a significantly higher maximum plasma concentration (Cmax,ss) and area under the plasma concentration-time curve during the dose interval at steady state (AUCτ,ss) for glimepiride in combination with rosuvastatin than those for glimepiride alone. However, other significant effects of the SLCO1B1 or CYP2C9 polymorphism on the interaction between the two drugs were not observed. In conclusion, there were no significant PK interactions between the two drugs; however, the exposure to glimepiride could be affected by rosuvastatin in the presence of the SLCO1B1 polymorphism.

Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms on the pharmacokinetics of pitavastatin in humans.

Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP) transporter alleles on its disposition, the pharmacokinetic (PK) parameters were compared among the following groups: SLCO1B1 (*15 carrier and non-carrier), ABCC2 (G1249A, C3972T, C-24T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUC(last) was higher in individuals carrying the SLCO1B1*15 allele than those not carrying it (144.1 ± 55.3 vs. 84.7 ± 25.7 h·ng/mL [mean ± SD], p = 0.002). The AUC(last) varied significantly according to the ABCC2 C-24T allele (103.4 ± 42.2, 80.2 ± 23.8, and 39.0 h·ng/mL in CC, CT and TT, respectively; p = 0.027). Other SNPs of ABCC2 and ABCG2 were not significant. The effect of these transporters and body weight on the AUC(last) and C(max) were tested, and only SLCO1B1 and ABCC2 C-24T genotypes were significant factors by analysis of covariance. These variants accounted for almost 50% of the variation in AUC(last) and C(max) of pitavastatin. Therefore, ABCC2 C-24T was significantly associated with pitavastatin human PK when the known effect of SLCO1B1*15 was also considered.

Relationship Between Earlobe Crease and Brachial-ankle Pulse Wave Velocity in Non-hypertensive, Non-diabetic Adults in Korea.

OBJECTIVES: Several studies have found a significant association between the presence of earlobe crease (ELC) and cardiovascular disease (CVD). Brachial-ankle Pulse Wave Velocity (baPWV) is a non-invasive and useful measure of arterial stiffness predicting cardiovascular events and mortality. However, few studies have reported the relationship between ELC and baPWV as a new measure of arterial stiffness. The purpose of this study was to determine whether ELC is related to baPWV in non-diabetic, non-hypertensive, and apparently healthy Korean adults. METHODS: A cross-sectional study was conducted on 573 non-hypertensive, non-diabetic Korean adults aged 20-80 yr. Subjects were stratified into three groups according to gender and menopausal status. baPWV was measured by an automatic waveform analyser. The association between ELC and baPWV was assessed by multiple linear regression analysis after adjusting for conventional cardiovascular disease risk factors including age, gender, blood pressure, lipid profile, and smoking status etc. RESULTS: The overall frequency of ELC was 19.02% and the subjects with ELC showed significantly higher mean baPWV (p<0.0001). Multiple linear regression of subjects revealed that the presence of ELC was independently associated with baPWV (male, p<0.0001; premenopausal female p=0.0162; postmenopausal female p=0.0208). CONCLUSION: ELC had a significant correlation with baPWV, independently controlling for other classical cardiovascular risk factors in adults aged 20 yr or older. ELC is an important surrogate marker of increased arterial stiffness as measured by baPWV in Korean adults.