[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Palmitic acid of Musa Paradisiaca induces apoptosis through caspase-3 in human oral squamous cell carcinoma.

OBJECTIVE: Despite apoptosis processes being conserved, cancer cells have developed mechanisms to inhibit apoptosis by altering anti-apoptotic molecules or inactivating pro-apoptotic. The aim of this study was to determine the palmitic acid of Musa paradisiaca var. sapientum (L) Kunz (MP) stem extracts against human oral squamous cell carcinoma (hOSCC) through caspase-3. MATERIALS AND METHODS: Ethanol and ethyl acetate extracts of MP stem were analyzed by gas chromatography-mass spectrometry (GC-MS). Computerized models of chemically active compounds were used to predict anticancer activity. Cytotoxicity was evaluated in Artemia salina Leach and hOSCC (OM-1) culture at concentrations 100, 90, 80, 70, 60, 50, 40, 30, 20, and 10 µg/mL respectively. The expression level of caspase-3 on hOSCC was measured by enzyme-linked immunoassay (ELISA). RESULTS: We found seven chemically active compounds in the ethanol extract and 15 compounds in the ethyl acetate extract of MP stem. The major component was hexadecanoic acid of palmitic acid derivates, and this was predicted to have anticancer activities as apoptosis through caspase-3 stimulants. However, cytotoxicity effects against hOSCC culture were assessed by values of the 50% inhibitory concentration (IC50) of 15.00 µg/mL for the ethanol extract, and an IC50 of 10.61 µg/mL for the ethyl acetate. There was a significant increase of caspase-3 level on treatment groups compared to control. CONCLUSIONS: Hexadecanoic acid of MP stem extracts has anticancer activity by inhibiting cell growth of hOSCC culture through caspase-3 stimulants.

Expression of lamin A/C protein in degenerated human intervertebral disc.

OBJECTIVE: This study aimed to evaluate the expression characteristics of lamin A/C proteins in intervertebral disc degeneration (IVD) specimens from patients with different degeneration grades. Lamin A/C proteins have been shown to result in age-related changes in the osteoarticular system. However, the expression characteristics of these nuclear proteins in degenerated human IVD tissues have not been explored previously. PATIENTS AND METHODS: Degenerated human IVD tissues were obtained during spinal surgery. Articular cartilage samples after total knee replacement surgery were used as controls. Sections of these tissues were stained with hematoxylin and eosin, Masson, safranin O, and immunostained using lamin A/C antibody. Western blot was performed to evaluate lamin A/C expression in IVD tissues. Lamin A/C expression was analyzed based on different degeneration grades. RESULTS: In patients with IVD degeneration, mild or moderate degenerative discs contained high amounts of lamin A/C proteins. Lamin A/C expression was primarily localized in the nuclear envelope of IVD cells, and associated with apoptosis in cell nuclei, as determined by immunostaining and TUNEL assay. CONCLUSIONS: This paper is the first to report that lamin A/C proteins are present in IVD tissues and its expression may be related to disc degeneration.

The Role of Uric Acid for Predicting Future Metabolic Syndrome and Type 2 Diabetes in Older People.

OBJECTIVE: Although it is known that high uric acid (UA) level is associated with type 2 diabetes (T2DM) and metabolic syndrome (MetS), most of the previous studies were focused on adults. Since aging becomes a major problem for many societies, in this longitudinal study, we investigated the role of UA in future T2DM and MetS in a large cohort of people who were older than 65 years. DESIGN: A cross-sectional and longitudinal study. SETTING/PARTICIPANTS: 18,907 elderly (9,732 men, 9,175 women) aged above 65 years, enrolled from health check-up centers, were classified into three subgroups by 10-year intervals (young old 65-74 years, YO; old old 75-84 years, OO; and oldest old 85-94 years, ODO), with the average follow-up period of 4.3 years. MEASUREMENTS: The optimal cut-off values (CoVs) of baseline UA to predict future MetS and T2DM were determined by receiving operating characteristic (ROC) curve analysis. Using these CoVs of UA, the participants were divided into normal- and high-level groups of UA. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of UA for the risk of future MetS and T2DM. In addition, Kaplan-Meier plots and log rank test were used to evaluate the time effect on the incidence of developing MetS and T2DM between the two groups. RESULTS: In ROC curve analysis, the optimal CoVs of baseline UA were 6.0, 6.3 and 6.7 mg/dl in YO, OO, and ODO men, respectively; 5.5 and 4.9 mg/dl in YO and OO women, respectively (all p < 0.05). However, the CoVs of UA in ODO women (6.1 mg/dl) failed to show its discriminant power (p = 0.13). The Cox regression analysis showed the YO subjects with a higher baseline level of UA had a higher risk of developing MetS (HRs 1.56 and 1.58 for men and women, respectively, both p < 0.001); as for T2DM the HRs were 1.39 and 1.57. In OO men, the HRs was 1.89 for developing future MetS. However, no significant findings could be noted in the ODO group. Kaplan-Meier plots and log rank test also showed the same findings. CONCLUSION: Our study showed that old subjects with high levels of UA will have a higher chance to have MetS and T2DM, particularly in the YO group (6.0 mg/dl for men and 5.5 mg/dl for women, respectively). Using UA as one of the metabolic biomarkers may help clinicians to early detect and prevent MetS and diabetes.

Normal fasting plasma glucose predicts type 2 diabetes and cardiovascular disease in elderly population in Taiwan.

BACKGROUND: Hyperglycemia increases prevalence of metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular disease (CVD). But the role of normoglycemia on the development of T2D and CVD in elderly population remains unclear. AIM: To determine an optimal cut-off for fasting plasma glucose (FPG) to predict MetS and subsequent risk of T2D and CVD in an elderly Taiwanese population with normal FPG levels. DESIGN: Two stages included cross-sectional (Stage 1) and prospective (Stage 2) cohort study. METHODS: In Stage 1 18 287 subjects aged ≥60 years were enrolled; of these, 5039 without T2D and CVD advanced to Stage 2 and a mean follow-up of 3.8 years. MetS components were analysed, and in Stage 1, FPG cut-offs for MetS risk were calculated using receiver operating characteristic (ROC) curve analyses. In Stage 2, subjects without T2D and CVD in Stage 1 were classified into high-FPG and low-FPG groups based on cut-offs, and sex specific differences in incidence for T2D and CVD were calculated. RESULTS: ROC curve analysis gave an optimal FPG cut-off for MetS of 93 mg/dl and 92 mg/dl for males and females, respectively. The high-FPG group had a 1.599- and 1.353-fold higher chance of developing T2D compared with the low-FPG group for males and females, respectively (95% CI: 1.606-2.721 and 1.000-1.831, P = 0.015 and 0.05). The high-FPG group had a 1.24-fold higher chance of developing CVD for females (95% CI: 1.015-1.515, P = 0.035); however, there was no difference for males. CONCLUSIONS: Our results suggest that FPG within the normal range was associated with MetS, and elderly subjects with high normal levels have a higher incidence of developing T2D for both sexes, and CVD for females, over the short-term.

Partial Protection from Metabolic Syndrome in Chronic Hepatitis C Elderly Subjects Due to Lower Triglyceride Level.

BACKGROUND: In Taiwan, persons over 65 years old have higher prevalence of hepatitis C. Among these patients, around 50% have non-alcoholic fatty liver disease (NAFLD). Since cardiovascular diseases and diabetes are main causes of death in this age group, in this cross-sectional study, we tried to evaluate the effects of NAFLD and hepatitis C on the risk of metabolic syndrome (MetS). METHODS: In total, 25 116 subjects over 65 years old who presented for routine health check-ups were enrolled. From the results of seropositivity for hepatitis C and abnormal echogenicity, they were classified into four groups: normal (N), subjects with only hepatitis C (C), subjects with only abnormal echogenicity (E) and subjects with both hepatitis C and abnormal echogenicity (CE). RESULTS: Subjects in both groups E and CE had higher abnormal MetS components than group C. Among all five components, triglyceride (TG) was the one having the highest odds ratio (OR) in determining the incidence of MetS in groups C and E. Finally, compared to group N, both groups E and CE had significantly higher OR for having MetS. However, after adjusting for confounding factors, only the significance between groups E and N remained. In other words, higher MetS was noted in group E compared to group N and there was no difference in incidence of MetS between group CE and group N. CONCLUSIONS: Chronic hepatitis C is a protective factor against having MetS and this effect might be due to lower TG level in the elderly. Further studies are warranted for the underlying mechanisms.

Associations between genetic variants and the severity of metabolic syndrome in subjects with type 2 diabetes.

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted.

Higher normal range of fasting plasma glucose still has a higher risk for metabolic syndrome: a combined cross-sectional and longitudinal study in elderly.

INTRODUCTION: It is well known that higher fasting plasma glucose (FPG) is associated with metabolic syndrome (MetS). This relationship still exists even the FPG is within the normal range. However, most of these studies did not exclude subjects who were on medications which would affect the results of the studies. At the same time, there is no longitudinal study done to validate this correlation, especially in elderly. In this study, the relationships between normal FPG and MetS were evaluated. METHOD: We randomly selected 57,517 subjects who were ≥ 60-years old from health screening centre. In the first part of study, subjects were enrolled in the cross-sectional study to find out the optimal cut-off value of FPG with higher chances to have MetS. In the second part of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 5.3-year longitudinal study. RESULTS: There were 18,287 subjects enrolled in this study. In the first part of study, the cross-sectional study, optimal cut-off values of FPG were determined by the ROC curve and the sensitivity for these cut-off values were 56.6% in men and 60.9% in women, respectively. The result showed that lower FPG is healthier than the higher (log-rank test, p < 0.001). During the follow-up period, 5039 subjects showed hazard ratios of 2.09 for men and 1.884 for women developing future MetS. CONCLUSION: Our study is the first longitudinal design in elderly and showed that older subjects with higher FPG proved to have higher risk of Mets even the FPG is still within its normal range.

Metabolic syndrome in normoglycaemic elderly men.

OBJECTIVE: Type-2 diabetes is mainly the metabolic defect involving multiple organs. To conclude their intricate relationships, the term 'ominous octet' had been proposed to denote this phenomenon. In this study, we enrolled older men without any medications for MetS components to further elucidate the relationships between normoglycaemic state and MetS. METHODS: We enrolled male subjects with FPG less than 100 mg/dl and aged 65 and older undergoing routine health check-ups in Taiwan. After excluding subjects taking medications that might affect the components of MetS, a total of 6679 men were eligible for the analysis. Study subjects were further grouped into FPG tertiles (< 91 mg/dl, 92-95 mg/dl and > 95 mg/dl for tertil 1, tertil 2 and tertil 3, respectively). RESULTS: There was a significant trend between the FPG and percentages of subjects having MetS (p = 0.009). The relationships between the MetS components were higher in FPG 2 and FPG 3 than FPG 1. In simple correlation, all of the MetS and LDL-C were positively correlated with FPG level and multiple regression further confirmed the same result except for HDL-C that became non-significant. Subjects in FPG3 had significantly higher ORs (ORs = 1.19) for having MetS than those in FPG1. CONCLUSIONS: In conclusion, higher FPG still had higher risk of having MetS in normoglycaemic range in elderly male. More strict FPG level control may be valuable in CVD prevention and warrants further investigations.

Investigation of a fenofibrate-hydroxypropyl-beta-cyclodextrin system prepared by a co-grinding method.

Considering the poor water solubility and the low oral bioavailability in humans, the complex formation of fenofibrate (FNB) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solution was studied. The effect of temperature on the complexation was examined and thermodynamic parameters of the complexation process such as Gibbs free energy change (deltaG), enthalpy change (deltaH) and entropy (deltaS) change were also determined. Meanwhile, the solid dispersion of FNB with HP-beta-CD was prepared and characterized by X-ray diffractometry and Fourier IR spectroscopy. The experimental results indicated that a 1:1 molar ratio complex of FNB with HP-beta-CD could form in aqueous solution and the complexation was exothermic and enthalpy-driven process. The FNB-HP-beta-CD solid dispersion presented a remarkable improvement in the solubility and dissolution rate of the drug. This might be attributed to the amorphous state, the enhanced wettability and as well as the complex formation of the drug with HP-beta-CD in aqueous solution.

Ultraviolet ZnO nanorod photosensors.

This study fabricates and characterizes ultraviolet (UV) photosensors with ZnO nanorods (NRs). The NR arrays were selectively grown in the gap between interdigitated (IDT) electrodes of devices using hydrothermal solution processes and a lithography-based technique. Compared with a conventional ZnO photosensor without NRs, the proposed UV NR photosensors have much higher photoresponse in the UV region. Additionally, the photoconductive gain of an NR photosensor increased as UV illumination time increased; it varied at 34.45-5.32 x 10(2) under illumination by 18.28 mW/cm(2) optical power. Consequently, the substantial photoconductive gain can be attributed to high surface-to-volume ratio of ZnO NRs. The high density of hole-trap states on NR surfaces lead to a persistent photoconductivity (PPC) state, promoting the transport of carriers through devices.

Effects of carbon nanotubes and metal catalysts on hydrogen storage in magnesium nanocomposites.

This paper reports a study on nanostructured magnesium composites with carbon nanotubes (CNTs) and catalytic transition metals with high H2 adsorption capacity and fast adsorption kinetics at reduced hydrogenation temperatures. Nanostructures in such a composite are shown to be responsible for improvements in both adsorption capacity and kinetics. It is found that the carbon nanotubes significantly increase the hydrogen storage capacity, and the catalytic transition metals (Fe and Ti) greatly improve the kinetics. This could be understood from the enhancement of diffusion by CNTs and decrease in energy barrier of hydrogen dissociation at the magnesium surface.

An experimental study on biomass air-steam gasification in a fluidized bed.

The characteristics of biomass air-steam gasification in a fluidized bed are studied in this paper. A series of experiments have been performed to investigate the effects of reactor temperature, steam to biomass ratio (S/B), equivalence ratio (ER) and biomass particle size on gas composition, gas yield, steam decomposition, low heating value (LHV) and carbon conversion efficiency. Over the ranges of the experimental conditions used, the fuel gas yield varied between 1.43 and 2.57 Nm3/kg biomass and the LHV of the fuel gas was between 6741 and 9143 kJ/Nm3. The results showed that higher temperature contributed to more hydrogen production, but too high a temperature lowered gas heating value. The LHV of fuel gas decreased with ER. Compared with biomass air gasification, the introduction of steam improved gas quality. However, excessive steam would lower gasification temperature and so degrade fuel gas quality. It was also shown that a smaller particle was more favorable for higher gas LHV and yield.

Characterization of gaseous and solid product from thermal plasma pyrolysis of waste rubber.

Pyrolysis of waste rubber in thermal plasma is studied for the purpose of producing gaseous fuel and recovering carbon black filler. The plasma reactor has a dc arc nitrogen plasma generator with a maximum electric power input of 62.5 kVA and a reaction chamber of 50 mm inner diameter and 1000 mm height. The results of a series of experiments have shown that the main components of the gaseous product are H2, CO, C2H2, CH4, and C2H4; the heat value of the gas is about 5-9 MJ/Nm3. The solid product contains more than 80 wt % elemental carbon, has a surface area of about 65 m2/g, and is referred to as pyrolytic carbon black (CBp). X-ray photoelectron spectroscopy (XPS) analysis has revealed that the CBp has mainly graphitic carbon structure similar to those of commercial carbon black. The CBp may be used as semireinforcing carbon black in nontire rubber applications, or, after upgrading, as carbon black filler for tire. Thus thermal plasma pyrolysis is potentially a useful way of treating waste rubber for resource recovery.

An economic analysis of biomass gasification and power generation in China.

With vast territory and abundant biomass resources China appears to have suitable conditions to develop biomass utilization technologies. As an important decentralized power technology, biomass gasification and power generation (BGPG) has a potential market in making use of biomass wastes. In spite of the relatively high cost for controlling secondary pollution by wastewater, BGPG is economically feasible and can give a financial return owing to the low price of biomass wastes and insufficient power supply at present in some regions of China. In this work, experimental data from 1 MW-scale circulating fluidized bed (CFB) BGPG plants constructed recently in China were analyzed; and it was found that the unit capital cost of BGPG is only 60-70% of coal power station and its operation cost is much lower than that of conventional power plants. However, due to the relatively low efficiency of small-scale plant, the current BGPG technology will lose its economic attraction when its capacity is smaller than 160 kW or the price of biomass is higher than 200 Yuan RMB/ton. The development of medium-scale BGPG plants, with capacity ranging from 1000 to 5000 kW, is recommended; as is the demonstration of BGPG technology in suitable enterprises (e.g. rice mill and timber mill) in developing countries where large amounts of biomass wastes are available so that biomass collection and transportation can be avoided and the operation cost can be lowered.

Release of hydrogen chloride from combustibles in municipal solid waste.

Study of the inorganic chlorides in municipal solid waste (MSW) shows that the main source of inorganic chlorides in MSW is food. The main organic source of HCl emission from MSW is plastic. But wood, textiles, and food also produce a large amount of HCl when they are combusted. Each combustible shows a different HCl releasing temperature range. At 973 K, there are 30-70% of the total chlorine left in the char of each combustibles in MSW.

Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals.

The effect of ginseng saponins isolated from red ginseng (a steamed and dried root of Panax ginseng) has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, chylomicrons and very low density lipoprotein (VLDL) accumulation was known to occur as a result of reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of ginseng saponins at a dose of 0.01 g/kg for 4 weeks was found to reverse the increase in serum triglycerides (TG) and concomitant increase in cholesterol produced by CPM treatment, especially in chylomicrons and VLDL. In addition, ginseng saponins treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity, which were markedly reduced by CPM treatment. In rats given 15% glycerol/15% fructose solution, postheparin plasma LPL activity declined to two third of normal rats, whereas ginseng saponins reversed it to normal levels. In the present study we first demonstrated that ginseng saponins sustained LPL activity at a normal level or protected LPL activity from being decreased by several factors, resulting in the decrease of serum TG and cholesterol.

Repression of acyl-CoA:cholesterol acyltransferase by a traditional herbal medicine (Kampo medicine), Ogi-Keishi-Gomotsu-To-Ka-Kojin.

Ogi-Keishi-Gomotsu-To-Ka-Kojin (OKGK) is a traditional herbal medicine (Kampo medicine) which has been found to ameliorate hypercholesterolemia and hypertriglyceridemia in rats and rabbits. In the present study, the effect of OKGK on acyl-CoA:cholesterol acyltransferase (ACAT) was studied in order to elucidate the mechanism of its antihypercholesterolemic action. Oral administration of OKGK to rats fed a cholesterol-enriched diet for 4 weeks markedly repressed the increase in ACAT activity in the small intestine. In contrast, OKGK did not influence hepatic ACAT activity. These results indicate that OKGK selectively inhibits ACAT activity in the small intestine relative to that in the liver, resulting in a reduction of cholesterol absorption, followed by a decrease in serum cholesterol.

Antihyperlipidemic action of Ogi-Keishi-Gomotsu-To-Ka-Kojin against cyclophosphamide-induced hyperlipidemia in rabbits.

The effect of Ogi-Keishi-Gomotsu-To-Ka-Kojin (OKGK), a Japanese traditional herbal medicine (Kampo medicine), has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, the accumulation of chylomicrons and very low density lipoprotein (VLDL) was known to occur as a result of a reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of OKGK for 4 weeks was found to reverse the increase in serum triglycerides and cholesterol produced by CPM treatment especially in chyromicrons and VLDL. In addition, OKGK treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity which were reduced markedly by CPM treatment. We previously reported that OKGK increased LPL activity in postheparin plasma in rats. In this study, we have also found that OKGK improved hyperlipidemia in the CPM-induced hyperlipidemia model in rabbits, mainly due to an increase in heparin-releasable heart LPL activity and postheparin plasma LPL activity.

Antihypercholesterolemic action of a traditional Chinese medicine (Kampo medicine), Ogi-Keishi-Gomotsu-To-Ka-Kojin.

The effect of Ogi-Keishi-Gomotsu-To-Ka-Kojin (OKGK), a traditional Chinese herbal medicine (Kampo medicine), on cholesterol metabolism was studied in male Sprague-Dawley rats. Intake of OKGK at doses of 1.38 g/kg for 4 weeks significantly reduced total cholesterol levels in the serum and liver of hypercholesterolemia rats fed a cholesterol-enriched diet. OKGK suppressed cholesterol absorption through the intestine and stimulated excretion of cholesterol into feces as bile acids. Biochemical study indicated that OKGK treatment enhanced cholesterol 7alpha-hydroxylase activity the rate limiting enzyme of cholic acid synthesis, in the liver without any effect on the rate limiting enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Further, cholesterol-enriched diet containing cholic acid suppressed cholesterol 7alpha-hydroxylase activity, whereas OKGK administration reversed the suppression. In conclusion, these results supported the idea that OKGK may be an effective agent for treatment of patients with hypercholesterolemia.