The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice.

This study was performed to evaluate the beneficial effect of Undaria pinnatifida ethanol extract (UEFx) on insulin resistance in diet-induced obese mice. A high-fat diet was supplemented with the UEFx at 0.69% (wt/wt) dose, which contains an equivalent amount of 0.02% fucoxanthin (wt/wt), or with Fx at 0.02% (wt/wt) dose in diet. After 9 weeks, both UEFx supplement significantly lowered the amount of visceral fat, the size of adipocyte, the fasting blood glucose concentration, the plasma insulin and the insulin resistance index similar to pure as shown by Fx supplement, compared to the high-fat (HF) control group. Blood glucose level was negatively correlated with hepatic glucokinase activity (r = -0.533, p < 0.05), whereas positively correlated with hepatic gluconeogenic enzyme activities (r = 0.463, p < 0.05 for glucose-6-phosphatase; r = 0.457, p < 0.05 for phosphoenolpyruvate carboxykinase). Ratio of hepatic glucokinase/glucose-6-phosphatase and glycogen content were significantly elevated by the UEFx and Fx supplements. Supplementation of the UEFx as well as Fx seemed to stimulate the ß-oxidation activity and inhibit the phosphatidate phosphohydrolase activity resulting in a decrease in the hepatic lipid droplet accumulation. The results indicate that the UEFx can prevent insulin resistance and hepatic fat accumulation that is partly mediated by modulating the hepatic glucose and lipid homeostasis in the high fat-induced obese mice.

Anti-atherogenic property of ferulic acid in apolipoprotein E-deficient mice fed Western diet: comparison with clofibrate.

Anti-atherogenic effect of ferulic acid (0.02%, w/w) was investigated in comparison with the clofibrate (0.02%, w/w) in apolipoprotein E-deficient (apo E(-/-)) mice fed Western diet. Concentrations of total cholesterol (total-C), apolipoprotein B (apo B) in the plasma and epididymal adipose tissue weight were significantly lower in the ferulic acid and clofibrate supplemented groups compared to the control group. The ratio of apo B to apo A-I was also significantly lower in those groups than in the control group. Activities of hepatic ACAT and HMG-CoA reductase were only significantly lower in the ferulic acid and clofibrate groups, respectively than in the control group. The numbers of mice that exhibited aortic fatty plaque were 8/10 in control groups vs. 0/10 in the ferulic acid or clofibrate group. The activities of anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and paraoxonase) in the hepatocyte and erythrocyte were significantly higher in the ferulic acid group than in the control group. In contrast, hepatic TBARS level was only markedly lower in the ferulic acid group. These results provide a new insight into the anti-atherogenic property of ferulic acid in the apo E(-/-) mice fed a Western diet.

Compositional study on rice bran oil after lipase-catalyzed glycerolysis and solvent fractionations.

Rice bran oil (RBO) was modified through lipase-catalyzed glycerolysis. After 48 h reaction, the reactant (RBO-G, solved in hexane) containing 0.14 mg/mL of MAG, 0.19 mg/mL of DAG, and 0.93 mg/mL of TAG was obtained. Extending the reaction to 72 h resulted in 0.37 mg/mL of DAG with concomitant reduction in TAG (0.68 mg/mL). Two solvent fractionation methods, independent and sequential fractionation, were performed with acetone and hexane at 0, -8, -14, or -35 degrees C. The fraction with most unsaturated fatty acids (Sigma UFA) was liquid fraction from independent fractionation at -35 degrees C (-35 In) from hexane, showing 88.3%Sigma UFA content. Nevertheless, when yield (wt%) was considered, the highest amount of UFA was obtained from 0 In (liquid fraction from independent fractionation at 0 degrees C) with hexane, resulting in 82.3%Sigma UFA with 97.9 wt% recovery. Normal-phase HPLC was conducted for the compositional study of RBO-G. Overall, solid fractions from sequential fractionation at 0 degrees C (0 SeSo) and independent fractionation at -35 degrees C (-35 InSo) with hexane contained the high concentration of total MAG and DAG, ranging from 0.94 to 1.35 (mg/mL).

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet.

The objective of this study was to investigate the hypolipidemic effects of powdered whole persimmon leaf supplement in rats fed high-fat diet. Three groups of male Sprague-Dawley rats during 6 weeks were fed different diet: normal control (NC), high-fat (HF), and high-fat supplemented with powdered whole persimmon leaf (PL; 5%, wt/wt) groups. Body weight and relative weight of interscapular brown adipose tissue were significantly lower in the PL group than in the HF group, while plasma leptin concentration was higher. The supplementation of persimmon leaf significantly lowered the plasma total cholesterol and triglyceride concentrations, whereas elevated the ratio of HDL-C/total-C and improved the atherogenic index. Persimmon leaf supplementation led the hepatic cholesterol and triglyceride values to similar levels to the NC group. Accumulation of hepatic lipid droplets and the epididymal white adipocyte size of PL group were diminished comparing to the HF group. Hepatic HMG-CoA and ACAT activities were significantly higher in the PL group than in other groups. Contents of fecal triglyceride, cholesterol and acidic sterol were significantly higher in the PL group than in the HF group. Accordingly, we suggest that supplementation of the powdered whole persimmon leaf improves plasma and hepatic lipid levels profile partly via the increased fecal lipids in high-fat fed rats. These beneficial effects may be due to the properties of its phenolic compounds (1.15 g/100g) and high fiber (63.48 g/100g) content in the powdered persimmon leaf.

Inhibitory effects of Rumex japonicus Houtt. on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an antioxidative effect in human skin disease. OBJECTIVES: To examine whether RJH extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga mice, which are induced by the repeated application of picryl chloride (PC). METHODS: The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-gamma. RESULTS: Oral administration of RJH-E to NC/Nga mice treated with PC inhibited the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and infiltration of inflammatory cells in the skin. The scratching behaviour and numbers of S. aureus, which are known to be exacerbated in AD, were also significantly reduced by RJH-E. No significant change was observed in the serum levels of IFN-gamma, whereas IgE and IL-4 levels were significantly reduced by RJH-E. CONCLUSIONS: These results suggest that RJH-E inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. Our results indicate that RJH treatment could provide an effective alternative therapy for the management of AD.

Rapid in vitro adventitious shoot propagation of Scopolia parviflora through rhizome cultures for enhanced production of tropane alkaloids.

A rapid micropropagation system for Scopolia parviflora Nakai (Solanaceae), a rare medicinal plant native to Korea, was established using rhizome cultures. Shoots that originated from adventitious shoots of the rhizome were multiplied when the rhizomes were cultured on half-strength B5 liquid medium supplemented with various growth regulators. Optimum shoot multiplication was observed in half-strength B5 medium containing 3% (w/v) sucrose and 5.77 microM gibberellic acid (GA(3)). Each rhizome gave rise to an average of 12 shoots. Shoot elongation and root induction from multiple shoots occurred on growth regulator-free half-strength B5 solid medium. Healthy plantlets were transferred to a peat moss:vermiculite mixture for acclimatization, which was successful. The concentrations of tropane alkaloids, hyoscyamine and scopolamine were determined in different tissues of native growing plants, in vitro-propagated plants and acclimatized plants by high-performance liquid chromatography. The analysis revealed that the levels of hyoscyamine and scopolamine were higher in in vitro-propagated plants than in the native growing plants. When the rhizome was cut into segments and transferred to optimal culture conditions for multiple shoot propagation, only 12 weeks were required to produce a mature plant. We conclude that in vitro propagation techniques through rhizome cultures provide an efficient and rapid method for shoot propagation of S. parviflora.

Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects.

BACKGROUND AND AIMS: Preliminary studies have shown that naringin has a potent lipid-lowering effect and antioxidant capacity in high-cholesterol diet fed animals. Accordingly, the present study was conducted to investigate the effect of naringin on hypercholesterolemic subjects. METHODS: A hypercholesterolemic group (n=30) and healthy control group (n=30) were established based on the plasma cholesterol levels in the subjects, then all subjects received naringin (400mg/capsule/day) with regular meals for a period of 8 weeks. RESULTS: In the hypercholesterolemic subjects, naringin supplementation was found to lower the plasma total cholesterol by 14% and low-density lipoprotein cholesterol concentrations by 17%, while the plasma triglyceride and high-density lipoprotein cholesterol concentrations remained unaffected. The apolipoprotein B levels in the hypercholesterolemic subjects were significantly lowered after naringin treatment, yet no change was observed in the apolipoprotein A-1 levels. The erythrocyte superoxide dismutase and catalase activities in the hypercholesterolemic group were significantly increased, whereas the glutathione peroxidase activity and plasma TBARS levels were not different from the baseline measurements. Meanwhile, naringin supplementation had no affect on plasma lipids, apolipoproteins, and TBARS levels or antioxidant enzyme activities in the control group. CONCLUSIONS: Therefore, these data suggest that naringin may play an important role in lowering plasma cholesterol and regulating the antioxidant capacity in hypercholesterolemic subjects.

Lipid-lowering and antioxidative activities of 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate in cholesterol-fed rats.

BACKGROUND: Polyphenols appear to have antioxidant activities and may mediate lipid lowering. METHODS: Four groups of rats, a high-cholesterol control (HC), HC+lovastatin, HC+3,4-di(OH)-cinnamate, and HC+3,4-di(OH)-hydrocinnamate, were given a semi-synthetic diet. The cinnamate derivative or lovastatin (0.1 g/100 g) supplements were given for 6 weeks. RESULTS: The plasma total cholesterol concentration was significantly lowered by the 3,4-di(OH)-cinnamate supplement compared to the control or lovastatin group. The 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements significantly lowered both the hepatic cholesterol and triglyceride levels, while lovastatin only lowered the hepatic cholesterol. The hepatic HMG-CoA reductase activities were significantly lower in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups than in the control or lovastatin group. The ACAT activity was only significantly lower in the lovastatin group compared to the other groups. With regards the hepatic antioxidant enzyme system, the CAT activity was significantly higher in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups compared to the control or lovastatin group. The two cinnamate derivatives resulted in an increased hepatic GSH-Px activity. Meanwhile, all the supplements significantly lowered the hepatic thiobarbituric acid reactive substances (TBARS) content. However, the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements did not alter the neutral sterol and total fecal sterol. CONCLUSIONS: Both cinnamate derivatives were potent in lipid-lowering and altering the antioxidative enzyme. Furthermore, these results also suggest that 3,4-di(OH)-cinnamate is more effective than 3,4-di(OH)-hydrocinnamate in its lipid-lowering action.

Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits.

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.

Effect of naringin supplementation on cholesterol metabolism and antioxidant status in rats fed high cholesterol with different levels of vitamin E.

Some bioflavonoids are potent antioxidants and have pharmacological effects similar to those of vitamin E. The interactive effect of naringin and vitamin E was studied with respect to cholesterol metabolism and antioxidant status. Naringin supplementation (0.1%, wt/wt) with comparable levels of vitamin E was given to rats with a high-cholesterol (1%, wt/wt) diet for 5 weeks. The amount of vitamin E included in naringin-free and naringin diets was a low (low-E) and a normal (normal-E) level. The naringin supplementation significantly lowered the concentrations of plasma cholesterol and triglyceride compared to the naringin-free group in low vitamin E-fed rats. HMG-CoA reductase activity was significantly lowered by naringin supplementation within both the low-vitamin E group (794.64 +/- 9.87 vs. 432.18 +/- 12.33 pmol/min/mg protein, mean +/- SE; p < 0.05) and normal-vitamin E group (358.82 +/- 11.4 vs. 218.22 +/- 9.47 pmol/min/mg protein, mean +/- SE; p < 0.05) compared to each of the naringin-free group. The HMG-CoA reductase activity was also significantly lowered by increased dietary vitamin E when compared within the naringin and naringin-free group, respectively. Neither dietary naringin nor vitamin E did significantly change the activities of hepatic antioxidant enzymes and plasma thiobarbituric acid-reactive substance level. These data indicate that naringin lowers the plasma lipid concentrations when the dietary vitamin E level is low. The HMG-CoA reductase-inhibitory effect of naringin was more potent when dietary vitamin E was at a normal level. These data may contribute to understanding the interactive effect of naringin and vitamin E on cholesterol biosynthesis in high-cholesterol-fed rats.

Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

Effects of gamma-irradiated fats on plasma lipid concentrations and hepatic cholesterol metabolism in rats.

Currently, there is a growing need for food irradiation that is effective in food preservation and quality improvement. Accordingly, this study was designed to observe the effects of gamma-irradiated dietary fat on plasma lipid concentrations and hepatic cholesterol metabolism in rats. Male rats were fed 5-kGy-gamma-irradiated beef tallow (gammaBT), corn oil (gammaCO), perilla oil (gammaPO), and nonirradiated fats (BT, CO, and PO) for 6 weeks. The gamma-irradiated fat feeding did not affect the plasma lipid concentrations. However, the hepatic cholesterol content was significantly higher in the rats fed gamma-CO as compared with the rats fed nonirradiated CO (40.0 vs. 28.2 mg/g liver). The hepatic HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activities were not significantly different between the controls and the gamma-irradiated fat fed groups. However, the hepatic ACAT (acyl-CoA:cholesterol acyltransferase) activity was significantly lower in the gammaPO group as compared with its control group (138.2 vs. 404.5 pmol min(-1) mg(-1)). Among the nonirradiated groups, the ACAT activities of the CO and PO groups were higher than that of the BT group. The amounts of coprostanone, cholesterol, and total fecal neutral sterol were significantly higher in the gammaPO group as compared with the other groups. These results indicate that although slight changes in the lipid metabolism were observed as a result of 5-kGy-gamma-irradiated fat feeding, they were relative to the fat type and had no harmful consequences.

Vitamin E improves microsomal phospholipase A2 activity and the arachidonic acid cascade in kidney of diabetic rats.

The purpose of the present study was to investigate the effects of vitamin E on microsomal phospholipase A2 activity and the arachidonic acid cascade in the kidneys of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100 +/- 10 g were randomly assigned to one normal and three STZ-induced diabetic groups. The diabetic groups were fed a vitamin E-free diet (the DM-0E group), 40 mg vitamin E/kg diet (the DM-40E group) or a 400 mg vitamin E/kg diet (the DM-400E group). The kidney vitamin E concentrations were 59 and 49% lower in the DM-0E and DM-40E groups, respectively, than in the normal group. The kidney thiobarbituric acid reactive substance concentrations in the DM-0E, DM-40E and DM-400E groups were 119, 84 and 33% greater, respectively, than that in the normal group. The concentration in the DM-400E group was 39% lower than that in the DM-0E group. The phospholipase A2 (PLA2) activity in the kidney microsomes of the DM-0E-40E and DM-400E groups were 88, 58 and 35% greater, respectively, than that in the normal group. The activity in the DM-400E group was 28% lower than that in the DM-0E group and 16% lower than that in the DM-40E group. The differences in the phospholipids in the kidney microsomes included reductions in the phosphatidylcholine and phosphatidylethanolamine compositions. Phosphatidylethanolamine hydrolysis in the kidney microsomes of the DM-0E and DM-40E groups were 84 and 64%, which did not differ from the DM-400E group. The formation of thromboxane A2 (TXA2) in the kidney microsomes was 137 and 70% greater in the DM-0E and DM-40E groups, respectively, than in the normal group. TXA2 formation did not differ between the DM-400E and normal groups. The formation of prostacyclin in the kidney microsomes was 60 and 44% lower in the DM-0E and DM-40E groups, respectively, than in the normal group, whereas the DM-400E group did not differ from that in the normal group. The ratio of prostacyclin to TXA2 was 82 and 65% lower than normal in the DM-0E and DM-40E groups, respectively. Kidney function appears to be improved by vitamin E supplementation due to its antithrombus action, which in turn controls the arachidonic acid cascade system.

Lipiodol accumulation in focal peliosis hepatis with sinusoidal dilatation.

Peliosis hepatis is a rare benign condition that is histologically characterized by multiple cystic blood-filled spaces in the liver. Although the cause is unknown, the condition occurs in association with several diseases or medications. We report a patient who was found to have a lesion with lipiodol accumulation in the liver 2 months after its intraarterial injection. The lesion was diagnosed and treated as a small hepatocellular carcinoma. However, subsequent right hepatic lobectomy and histologic examination confirmed the diagnosis of focal peliosis hepatis.

Interactive effect of hesperidin and vitamin E supplements on cholesterol metabolism in high cholesterol-fed rats.

Certain bioflavonoids are potent antioxidants and have pharmacologic effects similar to those of vitamin E. Accordingly, the interactive effect of hesperidin and vitamin E was studied with respect to cholesterol metabolism and the antioxidant status. Hesperidin supplement (0.1%, wt/wt) with comparable levels of vitamin E was provided with a high-cholesterol (1%, wt/wt) diet to rats for 5 weeks. The amount of vitamin E included in the hesperidin-free and hesperidin diets was either a low (low-E) or a normal (normal-E) level. The hesperidin supplement and different levels of dietary vitamin E did not significantly alter the concentrations of plasma triglycerides. However, the inclusion of hesperidin significantly lowered the concentration of plasma cholesterol in both the low-vitamin E group and the normal-vitamin E group compared to the hesperidin-free groups (p < 0.05). The hepatic triglyceride content was significantly lowered by the hesperidin supplement, as opposed to the plasma triglyceride content, regardless of the vitamin E level in the diet. The hepatic HMG-CoA reductase activity was significantly lowered by the hesperidin supplement with both the low-vitamin E and the normal-vitamin E compared to the hesperidin-free groups (p < 0.05). The hepatic HMG-CoA reductase activity was also significantly lowered with an increase in the dietary vitamin E within the hesperidin and hesperidin-free groups. The excretion of fecal neutral sterol and acidic sterols tended to be lower with the hesperidin supplement. Neither dietary hesperidin nor vitamin E significantly changed the hepatic antioxidant enzyme activity. This data indicates that hesperidin lowers the concentration of plasma cholesterol and the hepatic triglyceride content regardless of the dietary vitamin E level. However, the concentration of plasma cholesterol in the hesperidin-free groups was dependent on the dietary vitamin E level. This information may contribute to understanding the interactive effect of hesperidin and vitamin E on cholesterol biosynthesis in high cholesterol-fed rats.

Supplementation of Areca catechu L. extract alters triglyceride absorption and cholesterol metabolism in rats.

Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on triglyceride absorption in triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of triglyceride and the plasma lipid concentration. The absorbed triglyceride that appeared in the blood after an oral dose of [9,10(n)-(3)H] triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group. The hepatic and intestinal ACAT (acyl-CoA:cholesterol acyltransferase) activities were significantly decreased in the Areca group compared with the control group. Hence, further studies are needed to elucidate the structure and chemical properties of the active compound in the water-soluble Areca extract that lowers cholesterol absorption.

Lower absorption of cholesteryl oleate in rats supplemented with Areca catechu L. extract.

Areca catechu L. extracts I and II, prepared using two different solvent systems, exhibited strong inhibitory activities against pancreatic cholesterol esterase (pCEase) in vitro. To determine their cholesterol-lowering effects, these two extracts were investigated by analyzing plasma lipid levels, intestinal enzyme activities, and the absorption of cholesteryl oleate. For 6 days, male rats were fed a diet containing cholesteryl oleate (0.5 g/100 g of body weight) either with or without the Areca nut extract supplements. The supplementation of the two Areca nut extracts significantly lowered the concentrations of plasma cholesterol by 13. 4 and 11.7% and plasma triglycerides by 35.0 and 36.9%, respectively, compared with the pre-experimental values. However, when the cholesteryl oleate diet was fed without any Areca nut extract in high-cholesterol control, the plasma cholesterol and triglyceride concentrations significantly increased by 13.6 and 15.9%, respectively, compared with the pre-experimental values. After 6 days of treatment, the intestinal pCEase activities were significantly lower in the groups supplemented with the Areca nut extracts (37.8 and 26.5%) than in the group with no extract supplement (83.2%). The supplements also significantly elevated the excretion of [1,2(n)-(3)H]cholesteryl oleate administered orally, when determined by the large intestinal contents, 930.5 Bq/day (Areca I) and 1,766.3 Bq/day (Areca II) vs. 98.1 Bq/day (high-cholesteryl oleate (CO) control). The inhibition of pCEase activity with the supplementation of the Areca nut extracts could account for the decrease in [1,2(n)-(3)H]cholesteryl oleate absorption that resulted in decreased radioactivity in blood.

An increased rectal maximum tolerable volume and long anal canal are associated with poor short-term response to biofeedback therapy for patients with anismus with decreased bowel frequency and normal colonic transit time.

PURPOSE: Biofeedback is an effective therapy for a majority of patients with anismus. However, a significant proportion of patients still failed to respond to biofeedback, and little has been known about the factors that predict response to biofeedback. We evaluated the factors associated with poor response to biofeedback. METHODS: Biofeedback therapy was offered to 45 patients with anismus with decreased bowel frequency (less than three times per week) and normal colonic transit time. Any differences in demographics, symptoms, and parameters of anorectal physiologic tests were sought between responders (in whom bowel frequency increased up to three times or more per week after biofeedback) and nonresponders (in whom bowel frequency remained less than three times per week). RESULTS: Thirty-one patients (68.9 percent) responded to biofeedback and 14 patients (31.1 percent) did not. Anal canal length was longer in nonresponders than in responders (4.53 +/- 0.5 vs. 4.08 +/- 0.56 cm; P = 0.02), and rectal maximum tolerable volume was larger in nonresponders than in responders. (361 +/- 87 vs. 302 +/- 69 ml; P = 0.02). Anal canal length and rectal maximum tolerable volume showed significant differences between responders and nonresponders on multivariate analysis (P = 0.027 and P = 0.034, respectively). CONCLUSIONS: This study showed that a long anal canal and increased rectal maximum tolerable volume are associated with poor short-term response to biofeedback for patients with anismus with decreased bowel frequency and normal colonic transit time.