Decrease In Serum Cholesterol Concentration Research Articles

Renoprotective Effect of Plantago major Against Proteinuria and Apoptosis Induced by Adriamycin in Rat

ObjectiveAdriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of Plantago major (P. major), the aim of this study was to determine the effects of hydroalcoholic extract of P. major on ADR- induced nephropathy in rats.MethodsFifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + P. major (600 and 1200 mg/kg) and P. major (1200 mg/kg). The animals were treated with P. major extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment.ResultsAdministration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group (P < 0.001) while had no effect on glomerular filtration rate (P > 0.05). Treatment with P. major, in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group (P < 0.001).ConclusionOur results showed that the P. major extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.

Rosemary and lemongrass herbs as phytogenic feed additives to improve efficient feed utilization, manipulate rumen fermentation and elevate milk production of Damascus goats

This study was conducted to determine the effect of rosemary or lemongrass herbs at 10g daily on feed utilization, milk production, milk composition, and fatty acid profile in lactating Damascus goats. Fifteen goats were divided into 3 treatments (5 goats each) and fed a basal diet of berseem clover and concentrates (1:1 on dry matter (DM) basis; Control treatment) or the control diet supplemented with either 10g daily of rosemary (Rosemary treatment), or 10g daily of lemongrass (Lemongrass treatment) for 12 weeks. Inclusion of lemongrass and rosemary did not affect (P > 0.05) nutrient intake. However, inclusion of lemongrass or rosemary increased (P < 0.05) organic matter and fiber digestion. Ruminal pH was not influenced (P > 0.05) by dietary treatment. Feeding lemongrass or rosemary treatment increased (P < 0.05) ruminal concentration of short chain fatty acids, propionate, and serum glucose concentration and decreased serum cholesterol concentration. Feeding lemongrass or rosemary treatment increased (P < 0.05) milk production (actual and energy corrected milk), and milk fat and lactose concentration. Feeding rosemary or lemongrass containing diet increased (P < 0.05) total unsaturated fatty acids and total conjugated linoleic acid and decreased total saturated fatty acids (P < 0.05). In conclusion, supplementation of lemongrass and rosemary in the diet of lactating Damascus goats at 10g/goat daily enhanced nutrient digestibility and milk yield, with positive ruminal fermentation.

The Effects of Dietary Flavonoid Supplementation on the Antioxidant Status of Laying Hens

ABSTRACT Ninety-six 28-week-old Lohmann White laying hens were utilized to test the antioxidant effects of flavonoids (hesperidin, naringin, and quercetin at 0.5 g/kg diet) during an 8-wk experimental period. At the end of the experiment blood samples were collected to determine total protein, cholesterol, and malondialdehyde (MDA) serum levels as well as activities of glutathione reductase (GR), glutathione peroxidase (GSH-Px), glutathione- S -transferase (GST), and superoxide dismutase (SOD) and level of glutathione (GSH) in erythrocyte lysates. Data were analyzed using one-way ANOVA. Naringin supplementation did not alter serum cholesterol concentration, whereas hesperidin and quercetin supplementations decreased serum cholesterol concentration. Naringin and quercetin supplementations did not affect serum protein concentration. All flavonoids decreased MDA concentration as well as increased GSH-Px, GR, GST, and SOD activities and GSH level, being quercetion superior to hesperidin and naringin. In conclusion, flavonoids, especially quercetin, exert antioxidant activity, which may help improve wellbeing when laying hens are exposed to stressors.

Medication Adherence Improvement By Using Administration Timing Simplification Protocol (ATSP) in Cardiovascular Disease Patients.

Aims: In chronic diseases, keeping adherence to medication is very difficult. The objective of this study was to evaluate the impact of administration timing simplification protocol (ATSP) on medication adherence and clinical parameters of cardiovascular diseases.Methods: 210 out-patients with cardiovascular disease, who were taking two or more pills of any type of medication per day for more than one year, were enrolled and randomized. The intervention group followed the simplified administration schedule of ATSP with two main strategies: 1) moving medication from “pc” (30 minute after meal) to “stat. pc” (immediately after meal); and 2) moving medication time from “at evening” to “at morning.” In contrast, the control group maintained the same medication schedule. Both patient groups were equally educated about the names and effects of the medication.Results: The intervention group had more pills than the control group with marginal statistical significance (5.1 ± 2.3 vs 4.6 ± 1.8, p = 0.05). The total frequency of administration was significantly higher in the intervention group than that of the control group (2.9 ± 1.0 vs 2.6 ± 0.9, p = 0.03) at the baseline. In the intervention group, the frequency was significantly decreased to 1.5 ± 0.6 times per day after following ATSP application (p < 0.01). In both patient groups, knowledge about the medication was significantly improved by education. However, medication adherence was only improved in the intervention group. Interestingly, total cholesterol was significantly decreased in the intervention group (p < 0.01). The decrease in serum cholesterol concentration was significantly correlated with the improvement in medication adherence evaluated with Morisky Medication Adherence Scale (MMAS)-8 items (r = 0.507, p < 0.01).Conclusion: ATSP was shown to be an effective strategy to improve medication adherence in chronic cardiovascular disease patients.

The effect of grape seed extract and vitamin C feed supplementation on some blood parameters and HSP70 gene expression of broiler chickens suffering from chronic heat stress

In this experiment, the effect of hydroalcoholic grape seed extract (GSE) and vitamin C feed supplementation on some blood parameters and heat shock protein 70 (&lt;em&gt;HSP70&lt;/em&gt; gene) expression of broiler chickens suffering from chronic heat stress was investigated. Experimental diets included control diet (with no additive), 3 levels of GSE (150, 300, 450 mg/kg), and one level of vitamin C (300 mg/kg). Each diet was fed to 5 replicates of 12 male chicks each, from d 1 to 42. The birds suffered from chronic daily heat stress under 34±1°C temperature with 65 to 70% relative humidity for 5 h from 29 to 42 d of age. Results showed that 300 mg/kg GSE supplementation increased body weight of broilers both before and after heat stress condition (at 28 and 42 d, respectively). Also, birds fed 300 mg GSE/kg diet had higher European production efficiency factor during the whole period of the experiment. Supplementation of GSE decreased the concentration of serum glucose at 28 and 42 d; at 42 d (during heat stress condition) and at 450 mg/kg diet it decreased cholesterol, triglyceride, lowand very low density lipoprotein concentration of serum blood. Vitamin C supplementation decreased serum cholesterol concentration of broilers suffering from heat stress. &lt;em&gt;HSP70&lt;/em&gt; gene expression in heart and liver of broilers reduced by GSE and vitamin C supplementation pre- and during chronic heat stress condition.

Abstract 461: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice

Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, it is reported that voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Therefore, we hypothesized that cilnidipine, an N/L-type calcium channel blocker, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in mice. The purpose of this study was to evaluate whether cilnidipine influenced AngII-induced AAAs. Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) each by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. AngII infusion did not alter serum cholesterol concentrations. However, cilnidipine slightly decreased serumcholesterol concentrations in AngII-infused mice. Cilnidipine had no effect on body weights, heart rates, and urine total protein, but mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine did not affect ex vivo measurement of maximal diameter of abdominal aorta (1.04 ± 0.09 mm vs 1.11 ± 0.06 mm, n.s.) in saline infused mice. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas, but was attenuated by cilnidipine (1.79 ± 0.59 mm vs 1.26 ± 0.38 mm, P &lt; 0.05). In addition, cilnidipine significantly reduced the incidence of AngII-induced AAAs (Cilnidipine: 38 %, Vehicle: 88 %; P &lt; 0.05). Furthermore, gelatin zymography demonstrated that cilnidipine diminished AngII-induced increase in aortic MMP-9 protein abundance. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice.

The Effect of Grape Seed Extract and Vitamin C Feed Supplementation on Some Blood Parameters and HSP70 Gene Expression of Broiler Chickens Suffering from Chronic Heat Stress

In this experiment, the effect of hydroalcoholic grape seed extract (GSE) and vitamin C feed supplementation on some blood parameters and heat shock protein 70 (HSP70 gene) expression of broiler chickens suffering from chronic heat stress was investigated. Experimental diets included control diet (with no additive), 3 levels of GSE (150, 300, 450 mg/kg), and one level of vitamin C (300 mg/kg). Each diet was fed to 5 replicates of 12 male chicks each, from d 1 to 42. The birds suffered from chronic daily heat stress under 34±1°C temperature with 65 to 70% relative humidity for 5 h from 29 to 42 d of age. Results showed that 300 mg/kg GSE supplementation increased body weight of broilers both before and after heat stress condition (at 28 and 42 d, respectively). Also, birds fed 300 mg GSE/kg diet had higher European production efficiency factor during the whole period of the experiment. Supplementation of GSE decreased the concentration of serum glucose at 28 and 42 d; at 42 d (during heat stress condition) and at 450 mg/kg diet it decreased cholesterol, triglyceride, low- and very low density lipoprotein concentration of serum blood. Vitamin C supplementation decreased serum cholesterol concentration of broilers suffering from heat stress. HSP70 gene expression in heart and liver of broilers reduced by GSE and vitamin C supplementation pre- and during chronic heat stress condition.

Phytochemicals and nutritional health benefits of soy plant

Health properties and uses of soybean, as well as the different chemical and botanical characteristics of this legume, are shown in this review. Soybean represents an excellent source of high quality protein; it has a low content in saturated fat, it contains a great amount of dietary fiber and its isoflavone content makes it singular among other legumes. Characterization and positive health effects of soybeans have been recently studied. Most of the studies have been focused on soybean protein as a possible source of prevention against cardiovascular disease. This positive effect may be due to a decrease in serum cholesterol concentrations. In addition, there are many studies on isoflavones, non-nutritive substances, associated with prevention and treatment of different chronic diseases. Moreover, some studies have shown the health properties of soy dietary fiber. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fibers, vitamins, and minerals and low content of saturated fat. Therefore, it would be interesting to consider the replacement of animal based foods for soybean foods in order to obtain some nutritional benefits.

Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU‐Induced Hepatopathy in Tumor‐Bearing Dogs

Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases. Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU. Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment. Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU. Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity. Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.

Proinflammatory gene expression and renal lipogenesis are modulated by dietary protein content in obese Zuckerfa/farats

Obesity is a risk factor for the development of chronic kidney disease (CKD) and end-stage renal disease. It is not clear whether the adoption of a high-protein diet in obese patients affects renal lipid metabolism or kidney function. Thus the aims of this study were to assess in obese Zuckerfa/fa rats the effects of different types and amounts of dietary protein on the expression of lipogenic and inflammatory genes, as well as renal lipid concentration and biochemical parameters of kidney function. Rats were fed different concentrations of soy protein or casein (20, 30, 45%) for 2 mo. Independent of the type of protein ingested, higher dietary protein intake led to higher serum triglycerides (TG) than rats fed adequate concentrations of protein. Additionally, the soy protein diet significantly increased serum TG compared with the casein diet. However, rats fed soy protein had significantly decreased serum cholesterol concentrations compared with those fed a casein diet. No significant differences in renal TG and cholesterol concentrations were observed between rats fed with either protein diets. Renal expression of sterol-regulatory element binding protein 2 (SREBP-2) and its target gene HMG-CoA reductase was significantly increased as the concentration of dietary protein increased. The highest protein diets were associated with greater expression of proinflammatory cytokines in the kidney, independent of the type of dietary protein. These results indicate that high soy or casein protein diets upregulate the expression of lipogenic and proinflammatory genes in the kidney.

Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice

Objective T and B lymphocytes are associated with atherosclerosis and aneurysms. Angiotensin II (AngII) infusion into hypercholesterolemic mice results in augmentation of atherosclerosis and abdominal aortic aneurysm (AAA) formation. In this study, we determined whether total lymphocyte deficiency reduced AngII-induced vascular diseases. Methods and Results ApoE deficient (apoE −/−) mice were cross-bred with recombination activating gene-1 (Rag-1) deficient mice that lack mature T and B lymphocytes. Heterozygous littermates (Rag-1 +/−) have normal lymphocytic function and served as controls. Male and female apoE −/− mice that were either Rag-1 +/− or −/− were fed a normal laboratory diet and infused with either saline or AngII (1000 ng/kg/min) subcutaneously via osmotic mini pump for 28 days. Total lymphocyte deficiency had no significant effect on body weight and systolic blood pressure prior to and during AngII infusion. However, it was associated with decreased serum cholesterol concentrations. AngII infusion increased atherosclerotic lesion area in Rag-1 +/− mice compared to saline ( P = 0.017 in males and P = 0.004 in females). This effect was significantly blunted in Rag-1 −/− male ( P = 0.044), but not female mice. AngII-infusion promoted increased width of the abdominal aorta, with a greater effect in males. Despite the reduction in atherosclerosis in males, Rag-1 deficiency had no significant effect on AngII-induced aortic dilation in either gender. Conclusion T and B lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not AAA formation in apoE −/− mice.

Dietary fiber does not displace energy but is associated with decreased serum cholesterol concentrations in healthy children

Dietary fiber has health benefits, but fiber recommendations for children are controversial because fiber may displace energy. The objective was to longitudinally evaluate dietary fiber intake in children and to study associations between growth variables, serum cholesterol concentrations, and intakes of fiber, energy, and nutrients. Altogether, 543 children from a prospective randomized atherosclerosis prevention trial (the Special Turku Coronary Risk factor Intervention Project; STRIP) participated in this study between the ages of 8 mo and 9 y. The intervention children (n = 264) were counseled to replace part of saturated fat with unsaturated fat. Nutrient intakes, weight, height, and serum total, HDL-, and LDL-cholesterol and triglyceride concentrations were analyzed. Children were divided into 3 groups according to mean dietary fiber intake in foods: low (lowest 10%), high (highest 10%), and average (middle 80%) fiber intakes. Fiber intake associated positively with energy intake and inversely with fat intake. Children with a high fiber intake received more vitamins and minerals than did children in other groups. In longitudinal growth analyses, weights and heights were similar in all 3 fiber intake groups, and fiber intake (g/d) associated positively with weight gain between 8 mo and 2 y. Serum cholesterol concentrations decreased with increasing fiber intakes. Children in the intervention group had a higher fiber intake than did the control children during the entire follow-up period. Fiber intake did not displace energy or disturb growth between 13 mo and 9 y of age. Serum cholesterol values correlated inversely with fiber intake, which indicated that part of the cholesterol-lowering intervention effect in the STRIP project may have been explained by dietary fiber.

Impact of Dietary Fat Type and Amount on Growth Performance and Serum Cholesterol in Rabbits

Problem statement: Literature data on the effect of dietary fat on growth performance in rabbits are inconclusive. For commercial rabbit production it is relevant to know to what extent dietary fat level and type can be manipulated. In the present study serum cholesterol was also analyzed because its relation to the amount and type of dietary fat was not known for rabbits. Approach: Young growing rabbits were fed diets containing one of four different levels (5.2-41.8 energy %) of either coconut fat or corn oil. Fat was added to the diets at the expense of an isoenergetic amount of corn starch and dextrose in a 1:1 ratio. The diets were in pelleted form and supplied ad libitum. Results: Increasing fat intakes in the form of either coconut fat or corn oil enhanced weight gain and improved feed efficiency. The effect of coconut fat was maximal at 20.9 energy % (9.9%, w/w) and the greatest effect of corn oil was seen at an inclusion level of 41.8 energy % (20.2%, w/w). As would be expected, replacement of dietary corn oil by coconut fat significantly decreased serum cholesterol concentrations. The cholesterol-lowering effect of corn oil versus coconut fat increased markedly with higher dietary inclusion levels of fat. Conclusion: The addition of fat to the diet improved growth performance. It is suggested to find out whether the present observations can be applied in the formulation of diets for fryer rabbits. The new observation for rabbits is that the hypocholesterolemic response to corn oil increased with higher intake levels.

Effects of dietary medium-chain triglyceride on weight loss and insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjects

Prior studies of medium-chain triglyceride (MCT) suggest that MCT might be a useful tool for body fat mass management in obese nondiabetic humans. We now report a pilot study that tests if MCT is beneficial for moderately overweight subjects with type 2 diabetes mellitus. The study was conducted in a group of 40 free-living subjects in an urban area of China. The subjects were randomized into 2 test groups, with one given MCT and the other corn oil as control for long-chain triglycerides (LCTs). The test oil (18 g/d) was administered as part of daily food intake for 90 days. All subjects completed the study with self-reported full compliance. Body weight, waist circumference (WC), and serum samples were analyzed on days 0, 45, and 90. The MCT group showed an across-time reduction in body weight and WC, an increase in serum C-peptide concentration, a reduction in homeostasis model assessment of insulin resistance, and a decrease in serum cholesterol concentration ( P < .05, repeated measures). No significant across-time difference for the above parameters was detected for the LCT group. These changes were associated with an involuntary reduction in energy intake in the MCT group ( P < .05, repeated measures). A between-group comparison also shows reduced body weight, WC, and homeostasis model assessment of insulin resistance in the MCT group compared with the LCT group at the end of the study. Collectively, our results suggest a link between moderate consumption of MCT and improved risk factors in moderately overweight humans in a low-cost, free-living setting.

The safety of New Zealand bovine colostrum: Nutritional and physiological evaluation in rats

The potential detrimental effects of two different oral doses of bovine colostrum were assessed in young rats according to OECD guidelines. Colostrum was supplemented at 3% and 10% into a normal rat chow. A control group received the rat chow with no supplementation. After 90 days there was no difference between colostrum-fed animals and the control group in body weight, food consumption, clinical signs, haematology and most parameters of blood chemistry including carbohydrate metabolism, liver function and kidney function. The only effects of statistical significance were a decrease in serum cholesterol concentration in the rats receiving 10% colostrum ( p < 0.025), and a 33% increase in serum triglyceride concentration in the rats receiving 3% colostrum ( p < 0.005) although this was not apparent in the 10% colostrum group. Further, histological examination of most organs and tissues confirmed that there were no apparent differences between the animals receiving colostrum compared to controls. Based on these results, it can be concluded that the young growing rats had no observed toxicological and histopathological abnormalities caused by colostrum at the levels of supplementation used.

The Effects of Vitamin D Supplementation to Peak-producing Hens Fed Diets Differing in Fat Source and Level on Laying Performance, Metabolic Profile, and Egg Quality

This experiment was designed to examine the effects of supplemental vitamin D on laying performance, metabolic profile and egg quality of hens fed diets containing different fat sources and levels. Lohman strains (n = 480) were assigned to one of 10 diets: basal diet (BD), BD plus 2.5 and 5.0% sunflower oil (SO) or tallow (T) at vitamin D provided 1× and 3x of the current recommendation. The experiment lasted from week 30 to 44 of age. Each diet was tested in 12 replicate cages of 4 hens. Production, metabolism, and egg quality data were subjected to three-way ANOVA. Both fats decreased feed intake (FI) as compared to BD. Increasing SO and T levels linearly decreased and quadratically increased FI, respectively. The dietary factors did not affect egg production (EP) and egg weight. Vitamin D supplementation increased and decreased EP when diets contained SO and T, respectively. Feed conversion efficiency (FCE) for hens fed SO was lower than for hens fed T. However, increasing T level improved FCE, whereas increasing SO level worsened FCR. Vitamin D supplementation increased serum vitamin D and glucose concentrations. Vitamin D supplementation also caused a decrease and an increase in serum vitamin D concentration when diets contained SO and T, respectively. Serum glucose concentration for hens fed SO was lower than hens fed T. Increasing fat level linearly increased serum triglyceride and VLDL concentrations, regardless of the fat type. Increasing SO level linearly decreased serum cholesterol concentration. Vitamin D supplementation did not alter lipid metabolites. The dietary factors did not affect serum total protein, Ca, and P concentrations. As compared with BD, feeding SO decreased dry tibia and ash weights more than feeding T. Vitamin D supplementation tended to increase dry tibia weight and decrease tibia ash weight. Eggshell strength and thickness, yolk and albumen indexes, and Haugh unit were not responsive to the dietary factors. Eggshell strength quadratically increased with increasing T level. Yolk color for hens fed SO was lower than for hens fed T. The dietary factors did not affect most of yolk fatty acids. Increasing SO level quadratically decreased yolk C 18:2 concentration. Vitamin D supplementation increased and decreased yolk C 18:2 concentration when diets contained SO and T, respectively. In conclusion, increasing fat level improved laying performance without altering metabolic profile and egg quality. Vitamin D supplementation had minor alteration effects on laying performance, metabolic profile, and egg quality in response to fat feeding.

Hypocholesterolaemic effects of milk-kefir and soyamilk-kefir in cholesterol-fed hamsters

This study aimed to evaluate the hypocholesterolaemic property of milk-kefir and soyamilk-kefir. Male hamsters were fed on a cholesterol-free or cholesterol-enriched diet containing 10 % skimmed milk, milk-kefir, soyamilk or soyamilk-kefir for a period of 8 weeks. The soyamilk, milk-kefir and soyamilk-kefir diets all tended towards a lowering of serum triacylglycerol and total cholesterol concentrations, and a reduction of cholesterol accumulation in the liver, the decrease in serum cholesterol concentration being mainly in the non-HDL fraction. The soyamilk-kefir diet led to a significant increase in the faecal excretion of neutral sterols and bile acids compared with the other two diets. The soyamilk-kefir diet also elicited a significant decrease in the serum ratio of non-HDL-cholesterol to HDL-cholesterol, compared with the control, than was the case for the other diets. These findings demonstrate that soyamilk-kefir may be considered to be among the more promising food components in terms of preventing CVD through its hypocholesterolaemic action.

Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects

To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g/day) single-dose yoghurt drink. Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period. Subjects recruited from the general community. A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women) (age 57+/-2 years) completed the study. The study product was a 100-g single-dose yoghurt drink with or without added PS in the form of PS esters. The subjects were randomly assigned to one of five 4-week treatments: (i) drink A (0.1% dairy fat, 2.2% total fat) with a meal, (ii) drink A without a meal, (iii) drink B (1.5% dairy fat, 3.3% total fat) with a meal, (iv) drink B without a meal and (v) placebo drink with a meal. LDL-cholesterol (LDL-C) was significantly lowered when the single-dose drink was taken with a meal independent of its fat content (drink A: -9.5% (P<0.001, 95% CI: -13.8 to -5.2); drink B: -9.3% (P<0.001, 95% CI: -13.7 to -4.9)) as compared to placebo. When consumed without a meal, LDL-C was also significantly decreased (drink A: -5.1% (P<0.05, 95% CI: -9.4 to -0.8); drink B: -6.9% (P<0.01, 95% CI: -11.3 to -2.5) as compared to placebo, however the effect was significantly smaller as compared to the intake with a meal. These results indicate that a PS-ester-enriched single-dose yoghurt drink effectively reduces LDL-C irrespective of the fat content of the product. A substantially larger decrease in serum cholesterol concentration was achieved when the single-dose drink was consumed with a meal emphasizing the importance of the intake occasion for optimal cholesterol-lowering efficacy. Unilever Research and Development, Vlaardingen, The Netherlands.

Systemic toxicity of tacrolimus given by various routes and the response to dose reduction

To evaluate the long-term systemic toxicity of tacrolimus (FK-506) administered by various routes, and to assess the effect of dose reduction on toxicity. The study animals were 120 experimentally naive adult female Wistar rats weighing 200-250 g each. The rats were randomly divided into 10 equal groups (n=12 in each) and treated with tacrolimus administered topically (in drops, 0.3%, q.i.d.), intravitreally (0.5 mg/kg bodyweight/week), intramuscularly (1 mg/kg bodyweight/week), low-dose intravenously (1 mg/kg bodyweight/week) and in high-dose intravenously (2 mg/kg bodyweight/week) for 3 months. The rats in the control groups (one for each different route of administration) were treated with 0.9% NaCl. The blood concentration of tacrolimus, complete blood count and biochemistry parameters were measured each month for the 3-month study period. The rats in the control groups and experimental groups administered topical and intravitreal tacrolimus did not demonstrate any systemic toxic effects. The rats that developed certain toxic effects (hyperglycaemia, hyperkalaemia and nephrotoxicity) in the groups given low-dose or high-dose i.v. tacrolimus responded well to dose reduction. Following dose reduction, blood glucose concentrations decreased from 247.4 +/- 42.3 mg/dL to 189.6 +/- 37.9 mg/dL (P <0.05), and from 237.4 +/- 41.1 mg/dL to 182.3 +/- 22.7 mg/dL (P <0.05) in the low- and high-dose i.v. tacrolimus-treated rats, respectively. The rats that developed impaired hepatic function after high-dose tacrolimus did not respond to dose reduction. Baseline cholesterol concentrations for the intramuscular and low- and high-dose i.v. tacrolimus-treated groups, demonstrated decreases, respectively, from 87.4 +/- 14.0 mg/dL, 86.4 +/- 14.0 mg/dL and 90.4 +/- 14.3 mg/dL to 53.6 +/- 9.8 mg/dL, 52.1 +/- 12.5 mg/dL and 63.5 +/- 11.7 mg/dL by the end of the second month. The differences were found to be statistically significant (P <0.05 for each result). Topical or intravitreal administration of tacrolimus seems to be systemically safe whereas parenteral administration can cause some systemic haematological changes such as dose-dependent decreased serum cholesterol concentrations. Dose reduction may prevent such adverse effects.

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.