Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy.

Importance: Hyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice. Objective: To evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer. Design, Setting, and Participants: This prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria. Exposures: Neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points. Results: This study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001). Conclusions and Relevance: This study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

A Severe Cervical Spondylotic Myelopathy Patient Treated with Integrative Korean Medicine Including Acupuncture, Bee Venom Pharmacopuncture and Herbal Medicine: a case report.

Cervical spondylotic myelopathy (CSM) is common in elderly people and severe CSM patients are recommended to receive surgery. However, in some cases, surgery may fail to improve the patients' symptoms. An 80-year-old man diagnosed with CSM complained of right hemiplegia and right arm and leg pain with the presence of a Foley catheter, despite treatment with laminectomy and laminoplasty. Acupuncture, bee venom pharmacopuncture, and herbal medicine were administered for 129 days. As a result, manual muscle testing (MMT) and the Modified Barthel Index (MBI) improved, the pain in his right arm and leg decreased, and he was able to urinate by himself. This case report implies that integrative Korean medicine (IKM) can be an option for patients suffering from muscular weakness resulting from myelopathy.

Pregnancy loss and Income in the Republic of Korea using National Health Insurance Service Data, 2008-2014.

BACKGROUND: Although unintentional pregnancy loss is common, national representative statistics are lacking in high-income East Asian countries undergoing rapid demographic changes. It is necessary to confirm the income inequality of pregnancy loss even in universal national health insurance. METHOD: Using National Health Insurance Service data between 2008 and 2014, the annual prevalence of pregnancy loss was enumerated, and differences in pregnancy loss according to age and income levels were assessed by multivariable Poisson regression. Joint-point regression was used to examine the trend of pregnancy loss. RESULT: On average, there was a 15.0% annual pregnancy loss among 3,941,020 pregnancy cases from 2008 to 2014. Pregnancy loss inequality increased stepwise with income levels except for the highest income group. After adjusting for income levels, the annual percent change of age-standardized prevalence significantly increased by 2.6% every year since 2011. CONCLUSION: Even in high-income countries with universal national health insurance, income inequality in pregnancy loss is observed. Further appraisal is needed to explain the increasing trend of pregnancy loss between 2011 and 2014 even after adjusting income.

Meta-analysis of randomized controlled trials on calcium supplements and dairy products for changes in body weight and obesity indices.

This meta-analysis was performed to investigate whether calcium supplements and dairy products change obesity indices including fat mass. Original articles published in English between July 2009 and August 2019 were identified. Ten and 14 randomised controlled trials (RCTs) with ≥ 12 weeks interventions of calcium supplements and dairy products among overweight or obese adults aged ≥18 were critically reviewed. Mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) were obtained using a random effect meta-analysis. Dairy products significantly changed fat mass (SMD, 95% CI; -0.40 [-0.77, -0.02]) and BMI (MD, 95% CI: -0.46 kg/m2 [-0.67, -0.26]), and calcium supplements also showed changes in fat mass (SMD, 95% CI; -0.15[-0.28, -0.02]). However, in the analysis of RCTs with low risk of bias scores, the significant changes remained only in the dairy-products intervention. Our findings suggest that dairy products without distinction of fat percentage may help reduce fat mass and BMI, but calcium supplements may not.

Integrative cancer treatment may have a survival benefit in patients with lung cancer: A retrospective cohort study from an integrative cancer center in Korea.

Integrative oncology is being increasingly adopted in mainstream cancer care to strengthen anticancer effects and to control cancer-related symptoms.The objective of this study is to identify the characteristics of patients with lung cancer treated at an integrative cancer center in Korea and to determine the effects of integrative cancer treatment (ICT) on survival outcome in traditional Korean medicine (TKM).We reviewed medical records for lung cancer patients who visited a single integrative clinical setting, East-West Cancer Center, between January 2014 and December 2015. We classified the patients into groups according to their ICT and whether or not they underwent anticancer traditional Korean Medicine treatment with a multiherbal formula containing Panax notoginseng Radix, Cordyceps militaris, P ginseng C.A.Mey., and Boswellia carterii BIRDWOOD (HangAmDan-B), with a herbal formula containing Rhus verniciflua Stoke, or with cultivated wild ginseng pharmacopuncture. A descriptive analysis of the characteristics and a survival analysis using the Kaplan-Meier curves with log rank test and a Cox proportional hazard model were performed.A total of 91 patients were included, and the majority had advanced-stage cancer. Of those patients, 45.1% were in the mono-TKM group and 39.6% were integrative group. Patients with advanced stage had significantly higher mortality than patients with early stage (crude hazard ratio [HR]: 4.41, 95% confidence interval [CI]: 1.56-12.5; adjusted HR: 6.31, 95% CI: 1.24-32.1). In the unadjusted model, for patients in the integrative group, the mortality rate was reduced by 50% compared to mono-TKM group with statistical significance. After adjusting confounders, the mortality rate of integrative group was reduced by 6% compared to mono-TKM group, suggesting positive effect on survival probability of integrative group.The results suggest that integration of TKM and conventional cancer treatment may have survival benefits in patients with lung cancer. Even though this study has limitations including heterogeneity between treatment groups, the study results suggest that ICT has positive effect on survival probability. To clarify the impacts of ICT for lung cancer and other cancers on survival outcome, further prospective study with a rigorous study design is required in multiclinical setting.

The effectiveness of anticancer traditional Korean medicine treatment on the survival in patients with lung, breast, gastric, colorectal, hepatic, uterine, or ovarian cancer: A prospective cohort study protocol.

Although anticancer traditional Korean medicine treatment (ACTKMT) is widely applied to patients with cancer together with, or in place of, conventional cancer treatment in Korea, the cohort evidence on its clinical effects is lacking. Therefore, this prospective cohort study is designed to evaluate the effect of ACTKMT on the survival and the clinical outcomes for patients being treated at an integrative oncology clinic.This is a single center, prospective cohort study of patients within 1 year after the diagnosis of primary lung, breast, gastric, colorectal, hepatic, uterine, or ovarian cancer. The event-free survival, disease-free survival/progression-free survival, the overall survival, the results of blood tests, and telomere-length information will be compared between patients receiving and patients not receiving a key ACTKMT (HangAmDan-B1, Geonchil-jung, and/or cultivated wild ginseng pharmacopuncture), and the correlation between the use of the key ACTKMT and the prognosis will be identified considering other risk factors.This study has received ethical approval from the Institutional Review Board, Dunsan Korean Medicine Hospital of Daejeon University (No. DJDSKH-16-BM-09). The results of this study will be published in a peer-reviewed journal.Clinical Research Information Service: KCT0002160.

Effects of Oral Stimulation Intervention in Newborn Babies with Cri du Chat Syndrome: Single-Subject Research Design.

The purpose of this study is to treat dysphagia in a newborn baby with cri du chat syndrome using an oral stimulation intervention and to examine its effects. The subject of this study was a baby born 2 weeks prematurely. Since birth, his oxygen saturation (SaO2) decreased while feeding, and he had difficulty with mouth feeding. Thus, an NG feeding tube was inserted, and dysphagia treatment was initiated on the sixth day after birth. A baseline phase and an intervention phase were performed using an AB design. The oral stimulation intervention was not performed in the baseline phase, as only nonnutritive sucking training using a rubber pacifier was used during the baseline phase. During the intervention phase, nonnutritive sucking training and oral stimulation intervention were simultaneously conducted. After the intervention period, daily oral milk intake and intake per feeding of the subject noticeably increased. The oxygen saturation while feeding rose over 90% on average, and the baby did not present with hypoxia. The oral stimulation intervention provided prior to feeding resulted in highly positive effects, including induced normal development of the baby, stimulation of his transition from the NG feeding tube to bottle feeding, increased oxygen saturation, and a shortened hospital stay.

Lactobacillus gasseri BNR17 Supplementation Reduces the Visceral Fat Accumulation and Waist Circumference in Obese Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

Lactobacillus gasseri BNR17 is a probiotic strain isolated from human breast milk. Animal studies reported that BNR17 inhibited increases in body weight and adipose tissue weights. The purpose of this study was to evaluate the antiobesity effects of BNR17 in humans. In a randomized, double-blind, placebo-controlled trial, 90 volunteers aged 20-75 years with body mass index (BMI) from 25 to 35 kg/m2 were randomized to receive a placebo, low-dose BNR (BNR-L, 109 CFU/day), or high-dose BNR (BNR-H, 1010 CFU/day) for 12 weeks. Body weight, BMI, waist and hip circumferences, waist-to-hip ratio, abdominal adipose tissue areas, body fat mass, lean body mass, and biochemical parameters were assessed at the beginning and end of the trial. Visceral adipose tissue (VAT) was significantly decreased in the BNR-H group compared with the placebo group (P = .038). Difference of VAT areas of the BNR-H group compared with the placebo group after 12-week consumption of BNR17 was significant (-21.6 cm2, P = .012). Waist circumferences were significantly decreased in both the BNR-L and BNL-H groups (P = .045 and .012, respectively) compared with the baseline values, but not in the placebo group. Biochemical parameters were not significantly different among the groups. These findings suggest that daily consumption of BNR17 may contribute to reduced visceral fat mass in obese adults.

Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized, Double Blind, Placebo-Controlled Trial.

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. METHODS/DESIGN: In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. DISCUSSION: The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. TRIAL REGISTRATION: Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

The cross-sectional relationships of dietary and serum vitamin D with cardiometabolic risk factors: Metabolic components, subclinical atherosclerosis, and arterial stiffness.

OBJECTIVE: There has been increasing interest in non-skeletal interactions between vitamin D insufficiency, which is common, and cardiovascular event and cardiovascular disease (CVD) risk factors. METHODS: To evaluate cross-sectional associations between dietary and serum vitamin D status and metabolic abnormalities and arterial changes among 1054 adults aged ≥40 y (404 men and 650 women) in a rural area of South Korea. Study subjects were divided into three groups according to dietary vitamin D intake (tertiles) measured by food frequency questionnaire and serum 25(OH)D levels (≤20, 21-29, and ≥30 ng/mL). Metabolic components (blood pressure, lipid profiles, and glycemic index) and arterial changes (brachial ankle pulse wave velocity [baPWV] and carotid artery intima-media wall thickness [cIMT]) were measured. RESULTS: Dietary vitamin D was inversely associated with diastolic blood pressure (DBP) and baPWV among men, but the association disappeared after multinutrient supplement users were excluded. Among women, there was an inverse association between dietary vitamin D and triacylglycerol (TG) levels. However, serum 25(OH)D showed a significant positive relationship with HDL cholesterol in both men and women, while a positive linear trend or nonlinear trend with serum 25(OH)D levels was shown in TG levels among men and in systolic blood pressure (SBP), DBP, total cholesterol, and baPWV among women. The positive relationship between serum 25(OH)D with baPWV disappeared after adjustment for blood pressure. CONCLUSIONS: Serum 25(OH)D may be favorably related to HDL cholesterol. However, serum 25(OH)D may not favorably related to subclinical atherosclerosis and arterial stiffness measured by cIMT and baPWV. The positive relationship between 25(OH)D and baPWV is likely to be mediated by blood pressure.

Habitual dietary intake of ß-carotene, vitamin C, folate, or vitamin E may interact with single nucleotide polymorphisms on brachial-ankle pulse wave velocity in healthy adults.

PURPOSE: The interaction between genetics and diet may explain the present disagreement in the protective role of vitamin intake on cardiovascular disease. We cross-sectionally assessed the interaction of habitual dietary intake of ß-carotene, vitamin C, folate, and vitamin E with single nucleotide polymorphisms (SNPs) on brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness. METHODS: Dietary intakes of ß-carotene, vitamin C, folate, and vitamin E were quantified by a food frequency questionnaire in 3198 healthy men and women (≥ 40 years) from the Korea Multi-Rural communities Cohort study. baPWV was measured, and 19 SNPs were genotyped. The associations and interactions between dietary vitamin intake, SNP genotype, and baPWV were assessed using general linear models. RESULTS: In both men and women, dietary intake of ß-carotene, vitamin C, folate, or vitamin E and baPWV were not directly associated. Vitamin C, folate, and vitamin E intake had an interaction with rs4961 (ADD1) genotype on baPWV in men. rs4961 also interacted with folate intake on baPWV in women. In women, rs10817542 (ZNF618) and rs719856 (CD2AP) had an interaction with ß-carotene and folate intake and rs5443 (GNB3) had an interaction with vitamin E intake on baPWV. In general, minor allele homozygotes with low vitamin intake had higher baPWV than other subgroups. Results were similar when supplement users were excluded. CONCLUSIONS: Higher intake of dietary vitamin C, folate, and vitamin E may be related to high baPWV in healthy Korean men who are minor allele homozygotes of rs4961. In healthy Korean women, dietary folate, ß-carotene, and vitamin E intake may affect baPWV differently according to rs4961, rs10817542, rs719856, or rs5443 genotype. Greater dietary intake of these nutrients may protect those that are genetically vulnerable to stiffening of the arteries.

Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the ß-catenin pathway in colorectal cancer.

AIM OF THE STUDY: In this study, we examined the effect of different fractions and components of Chaga mushroom (Inonotus Obliquus) on viability and apoptosis of colon cancer cells. Among them, one component showed the most effective growth inhibition and was identified as ergosterol peroxide by NMR analysis. We investigated the anti-proliferative and apoptosis mechanisms of ergosterol peroxide associated with its anti-cancer activities in human colorectal cancer (CRC) cell lines and tested its anti-tumor effect on colitis-induced CRC developed by Azoxymethane (AOM)/Dextran sulfate sodium (DSS) in a mouse model. MATERIALS AND METHODS: We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, Western blot analysis, colony formation assays, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and AOM/DSS mouse models to study the molecular mechanism of metastatic activities in CRC cells. RESULTS: Ergosterol peroxide inhibited cell proliferation and also suppressed clonogenic colony formation in HCT116, HT-29, SW620 and DLD-1 CRC cell lines. The growth inhibition observed in these CRC cell lines was the result of apoptosis, which was confirmed by FACS analysis and Western blotting. Ergosterol peroxide inhibited the nuclear levels of ß-catenin, which ultimately resulted in reduced transcription of c-Myc, cyclin D1, and CDK-8. Ergosterol peroxide administration showed a tendency to suppress tumor growth in the colon of AOM/DSS-treated mice, and quantification of the IHC staining showed a dramatic decrease in the Ki67-positive staining and an increase in the TUNEL staining of colonic epithelial cells in AOM/DSS-treated mice by ergosterol peroxide for both prevention and therapy. CONCLUSION: Our data suggest that ergosterol peroxide suppresses the proliferation of CRC cell lines and effectively inhibits colitis-associated colon cancer in AOM/DSS-treated mice. Ergosterol peroxide down-regulated ß-catenin signaling, which exerted anti-proliferative and pro-apoptotic activities in CRC cells. These properties of ergosterol peroxide advocate its use as a supplement in colon cancer chemoprevention.

The cross-sectional relationship between dietary calcium intake and metabolic syndrome among men and women aged 40 or older in rural areas of Korea.

BACKGROUND/OBJECTIVES: Studies conducted in Western populations have suggested that dietary calcium may protect against metabolic abnormalities, but there is little evidence of this effect in Asians, who have relatively low calcium intake. We evaluated the cross-sectional relationship between dietary calcium and metabolic syndrome among Korean men and women aged 40 years and over. SUBJECTS/METHODS: A total of 6,375 subjects aged 40 years and over and were recruited between January 2005 and February 2010 from the baseline study of the Multi-Rural Communities Cohort Study in Rural Communities (MRCohort). A food frequency questionnaire was used to collect dietary information. Metabolic syndrome was defined using the modified criteria published in the Third Report of the National Cholesterol Education Program Adult Treatment Panel. RESULTS: Calcium intake was related inversely to metabolic syndrome in women (P-value = 0.0091), but not in men (P = 0.1842). Among metabolic components, high waist circumference (WC) (P = 0.0426) and high blood glucose (P = 0.0027) in women and hypertriglyceridemia (P = 0.0017) in men were inversely correlated with calcium intake. Excluding those who used calcium or multinutrient supplements did not attenuate the relationship between dietary calcium and metabolic abnormalities. CONCLUSION: Dietary calcium intake from foods may be inversely related to metabolic syndrome, WC, and blood glucose among women in rural areas of Korea.

The Relationship between Zinc Status and Inflammatory Marker Levels in Rural Korean Adults Aged 40 and Older.

BACKGROUND: Serum cytokines and C-reactive protein (CRP) are known as one of the major risk factors in atherosclerosis. The antioxidant and anti-inflammatory properties of zinc have been suggested, but few data are available on the relationship between zinc status and inflammatory markers in epidemiological studies. OBJECTIVE: The present study aims to investigate the cross-sectional relationships of serum cytokines and CRP with dietary zinc intake and serum zinc levels in healthy men and women aged 40 and older in rural areas of South Korea. MATERIALS AND METHODS: A group of 1,055 subjects (404 men, 651 women) was included in dietary zinc analysis while another group of 695 subjects (263 men, 432 women) was included in serum zinc analysis. Serum IL-6, TNF-α, and CRP were measured as inflammatory markers. RESULTS: There was no significant inverse relationship between dietary zinc intake and inflammatory markers. We found a significant inverse relationship between serum zinc levels and all three inflammatory markers in women (P for trend = 0.0236 for IL-6; P for trend = 0.0017 for TNF-α; P for trend = 0.0301 for CRP) and between serum zinc levels and a single inflammatory marker (IL-6) in men (P for trend = 0.0191), although all R2 values by regression were less than 10%. CONCLUSION: In conclusion, serum zinc levels may be inversely related to inflammatory markers (IL-6, TNF-α, and CRP), particularly in women.

Loquat (Eriobotrya japonica) extract prevents dexamethasone-induced muscle atrophy by inhibiting the muscle degradation pathway in Sprague Dawley rats.

In the Orient, loquat (Eriobotrya japonica) extract (LE) is widely used in teas, food and folk medicines. The leaves of the loquat tree have been used for generations to treat chronic bronchitis, coughs, phlegm production, high fever and gastroenteric disorders. One of the major active components of loquat leaves is ursolic acid, which was recently investigated in the context of preventing muscle atrophy. The present study investigated the therapeutic potential of LE on dexamethasone­induced muscle atrophy in rats. Daily intraperitoneal injections of dexamethasone caused muscle atrophy and evidence of muscle atrophy prevention by LE was demonstrated using various assays. In particular, dexamethasone­induced grip strength loss was alleviated by LE and the increase in serum creatine kinase activity, a surrogate marker of muscle damage, caused by dexamethasone injection was reduced by LE. Western blot analysis and immunoprecipitation demonstrated that dexamethasone markedly increased the protein expression levels of muscle ring finger 1 (MuRF1), which causes the ubiquitination and degradation of myosin heavy chain (MyHC), and decreased the protein expression levels of MyHC as well as increased the ubiquitinated MyHC to MyHC ratio. However, LE reduced the dexamethasone­induced protein expression levels of MuRF1 and ubiquitinated MyHC. Additional experiments revealed that LE supplementation inhibited the nuclear translocation of FoxO1 induced by dexamethasone. These findings suggested that LE prevented dexamethasone­induced muscle atrophy by regulating the FoxO1 transcription factor and subsequently the expression of MuRF1.

The effect of coffee, tea, and caffeine consumption on serum uric acid and the risk of hyperuricemia in Korean Multi-Rural Communities Cohort.

Caffeine, a commonly consumed food constituent, is known to exert beneficial physiological effects in humans. There is a lack of comprehensive population data for the effects of caffeine intake on urate metabolism. Therefore, the aim of this study was to determine whether coffee, tea, and caffeine intake influences serum uric acid and the risk of hyperuricemia in the Korean Multi-Rural Communities Cohort. We enrolled 9,400 participants in this study. An assessment of various dietary intake amounts of substances such as coffee and tea was performed using a food frequency questionnaire. The content of caffeine was calculated from coffee (74 mg/cup) and tea (15 mg/cup) intake information from the past year. Multivariate logistic regression models, multiple linear regression models, and analysis of covariance were applied to identify any association of dietary intake with serum uric acid levels or the risk of hyperuricemia. No trends for coffee, tea, or caffeine intake were found according to each quintile with serum uric acid in males, although there were weak, marginally significant trends between the content of coffee and caffeine intake and serum uric acid level in females (p = 0.07 for both). Tea intake in males and caffeine intake in females were significantly different between non-hyperuricemia and hyperuricemia (p = 0.04 and p = 0.04, respectively). In addition, a significant association of serum uric acid level with tea intake in males (ß = 0.0006, p = 0.02) and with tea intake and caffeine intake in females (ß = 0.0003, p = 0.04 and ß = 0.0006, p = 0.02, respectively) was observed. There was no effect of coffee, tea, or caffeine intake on the risk of hyperuricemia in either males or females. This study suggests that caffeine consumption might have an effect on serum uric acid in females. However, coffee, tea, and caffeine intake amounts were not associated with the risk of hyperuricemia.

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO3) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO3 is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO3 in comparison with that of bulk- or reagent grade nano CaCO3 in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO3 particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO3 nanoparticles were different from bulk CaCO3 or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO3 nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO3 particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.

Toxicologic assessment of Paecilomyces tenuipes in rats: renal toxicity and mutagenic potential.

Paecilomyces tenuipes is entomogenous fungus that is called snow-flake Dongchunghacho in Korea. Although it is widely used in traditional medicines, its safety has not yet been comprehensively investigated. Therefore, the aim of this study was to evaluate the genotoxicity, acute and subchronic toxicity of P. tenuipes. The acute oral LD50 of P. tenuipes extract in rats was estimated to be greater than 2000mg/kg of body weight. In the subchronic study, the oral treatment of rats with 500, 1000 or 2000mg/kg P. tenuipes extract daily for 13weeks did not induce any dose-related changes (body weight, food consumption, clinical observation, urinalysis, hematology, clinical chemistry and organ weight). In contrast, histopathological observation revealed that P. tenuipes extract induced karyomegaly in outer medulla of kidney in all treated rats. Importantly, P. tenuipes extract exerted the mutagenic potential in Ames assay. Since karyomegalic alterations have been known to be associated with carcinogenicity, our finding on the mutagenicity of P. tenuipes extract supports the possibility on the potential involvement of P. tenuipes in carcinogenicity at least partially. In conclusion, the subchronic oral exposure of P. tenuipes may induce kidney abnormality at the concentration higher than 500mg/kg body weight, although further studies using other animal models are needed to identify the toxicity of P. tenuipes.

Chinese prescription Kangen-karyu and Salviae Miltiorrhizae Radix improve age-related oxidative stress and inflammatory response through the PI3K/Akt or MAPK pathways.

This study examined whether Kangen-karyu and its crude drug, Salviae Miltiorrhizae Radix, have a reno-protective effect on the age-related oxidative stress and inflammatory response through the phosphoinositide 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK) pathways in aged rats. Kangen-karyu or Salviae Miltiorrhizae Radix (20 mg/kg body weight/day) was administered orally to old groups of rats for 16 days, and their effects were compared with the vehicle-treated old and young rats. The administration of Kangen-karyu caused a slight decrease in the serum glucose level and a significant decrease in the serum insulin level in the old rats. The increased levels of serum renal functional parameter (urea-nitrogen) and oxidative parameter were significantly reduced by both Kangen-karyu and Salviae Miltiorrhizae Radix. The old rats exhibited a dysregulation of the protein expression related to insulin resistance, oxidative stress, and inflammation in the kidneys, but Kangen-karyu administration significantly reduced the expression of the inflammatory proteins through the PI3K/Akt pathway. On the other hand, the Salviae Miltiorrhizae Radix-treated old rats showed a decrease in the inflammatory cytokines through the MAPK pathway. These results provide important evidence that Kangen-karyu and Salviae Miltiorrhizae Radix have a pleiotropic effect on the PI3K/Akt and MAPK pathways, showing renoprotective effects against the development of inflammation in old rats. This study provides scientific evidence that Kangen-karyu and Salviae Miltiorrhizae Radix improve the inflammatory responses via the PI3K/Akt or MAPK pathways in the kidney of old rats.