Elevated Serum Total Cholesterol Levels Research Articles

Serum total cholesterol levels associated with immediate memory performance in patients with chronic schizophrenia

Cognitive impairments are common in patients with schizophrenia. Changes in total cholesterol (TC) may be involved in the development of schizophrenia and associated with cognitive function. This study aimed to investigate differences in serum TC level and cognitive function between schizophrenia patients and healthy controls and explore the relationship between serum TC level and cognitive function in patients with schizophrenia. A total of 105 schizophrenia patients and 105 healthy controls were recruited. Results showed that patients with schizophrenia had significantly lower scores on the overall RBANS scale and subscales (i.e., immediate memory, language, attention, and delayed memory) than those of healthy controls. Pearson's correlation analyses showed that in patients with schizophrenia, serum TC levels were positively associated with RBANS subscale scores of immediate memory and language. Furthermore, multivariate regression analyses showed that serum TC level was positively associated with the immediate memory index in patients with schizophrenia. However, no significant association was found between serum TC level and RBANS score in the healthy control group. Our results suggest that elevated serum TC level may be related to improved cognitive function in patients with schizophrenia, especially that of immediate memory.

Serum apolipoprotein B/apolipoprotein A1 ratio in relation to intervertebral disk herniation: a cross-sectional frequency-matched case\u2013control study

Study designThis was a cross-sectional frequency-matched case–control study.Background and aimThe serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH.MethodThe study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules.ResultsPatients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R2LDL = 0.017; R2TC = 0.004; R2TG = 0.015; R2Apo B = 0.004; R2Lp(a) = 0.021) (P < 0.05).ConclusionThis study suggested that elevated levels of serum TC, TG, LDL, Apo B, Lp(a), and Apo B/Apo AI were associated with a higher risk of IDH. This study provided useful information to identify a population that might be at risk of developing IDH based on elevated lipid levels.

Study of lipid profile in cases of non-diabetic stroke

Background: To study serum lipid profile in non-diabetic patients with stroke and to determine whether there is any significant correlation between them and to compare the serum lipid profile between ischaemic and haemorrhagic group. Design: Case control study.Methods: The current study was done in the Department of Medicine VIMSAR, Burla, Odisha. Total 100 patients of completed stroke (Ischaemic63 and haemorrhagic37) and 30 controls were included in the study. All cases were adult (more than 14 years of age). Patients with suspected embolic stroke, diabetes (Type 1 and 2) and patients on lipid lowering drugs were excluded from the study. Routine investigations and fasting serum lipid profile was done.Results: 45 patients had elevated serum total cholesterol levels out of which 75.56% had Ischaemic stroke and 24.49% had haemorrhagic stroke. 24 cases had elevated serum Triglyceride levels of which 66.67% had Ischaemic stroke and 29.17% had haemorrhagic stroke. 76.47% of cases having elevated serum LDL cholesterol suffered from Ischaemic stroke where as 20.59% had haemorrhagic stroke.Conclusions: A statistically positive correlation was found between serum total cholesterol, Triglyceride, LDL levels and the risk of stroke.

Hypolipidemic effect of aqueous leaf extract of carmona microphylla G Don

Purpose: To investigate the hypolipidemic effects of the aqueous leaf extract of Carmona microphylla (Lam.) G. Don. (CAE) in vitro and in vivo.Methods: The lipid-lowering effect of CAE was investigated in oleic acid (OA)-induced steatosis in HepG2 liver cells, as well as in high-fat diet (HFD)- and triton WR-1339 (TRI)-induced hyperlipidemic mice. The levels of intracellular, serum and/or hepatic total cholesterol (TC); triglyceride (TG); low density lipoprotein-cholesterol (LDL-c); high density lipoprotein-cholesterol (HDL-c); hepatic superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by oil-red O staining and appropriate kits.Results: Treatment with CAE inhibited lipid accumulation in HepG2 cells and reduced the elevated levels of serum TC, TG and LDL-c as well as hepatic TC and TG in hyperlipidemic mice induced by HFD. CAE administration also significantly decreased arteriosclerosis index (AI) and LDL-c/HDL-c ratio, but improved oxidative status as revealed by increased hepatic SOD activity and decreased MDA level. The lipid ameliorating and antioxidative effects of CAE (600 mg/kg) were comparable to those of the standard lipid-lowering drug, sivastatin (5 mg/kg).Conclusion: These results suggest that C. microphylla aqueous extract (CAE) protects against hyperlipidemia induced by HFD in mice and may find therapeutic application in hyperlipidemic patients.Keywords: Carmona microphylla, Hyperlipidemia, Atherosclerosis, Oxidative stress, Sivastatin, Lipidlowering

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20mg/kg/day), or HCD plus atorvastatin (10mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that flavocoxid would be useful in preventing oxidative stress, inflammation, and vascular dysfunction induced by HCD.

Serum total cholesterol: A mortality predictor in elderly hospitalized patients

Elevated serum total cholesterol levels are associated with increased risk of cardiovascular mortality among middle aged adults, but not the elderly. We therefore examined whether increased serum total cholesterol reduces mortality risk in the hospitalized elderly. Of 1852 patients consecutively admitted to an acute geriatric department from 1/1/99-12/31/00, only 298 (49.6% males, mean age 81.36 ± 6.3 years) who had measured serum total cholesterol and albumin levels were included in the study and followed until August 31, 2004. Mortality data were extracted from their death certificates. During follow-up of 3.47 ± 1.87 years, 248 patients died. These patients had significantly lower levels of baseline serum total cholesterol (183.3 ± 45.4 vs. 200.2 ± 37.9, p = 0.01) and albumin (3.6 ± 0.5 vs. 3.8 ± 0.3 g/l, p = 0.002) than the survivors. In the Cox regression analysis, serum total cholesterol emerged as a significant, independent predictor of mortality in this cohort. Specifically, each 1 mg/dl increase in serum total cholesterol reduced risk of death by 0.4%. This association persisted even after controlling for serum creatinine, age, body mass index, dementia and congestive heart failure. These factors were also significantly, independently associated with mortality. In very elderly hospitalized subjects, increased levels of serum total cholesterol and albumin may be associated with reduced mortality risk.

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

Augmented Atherogenesis in LDL Receptor Deficient Mice Lacking Both Macrophage ABCA1 and ApoE

AimABCA1 protects against atherosclerosis by facilitating cholesterol efflux from macrophage foam cells in the arterial wall to extracellular apolipoprotein (apo) A-I. In contrast to apoA-I, apoE is secreted by macrophages and can, like apoA-I, induce ABCA1-mediated cholesterol efflux. Yet, the combined effect of macrophage ABCA1 and apoE on lesion development is unexplored.Methods and ResultsLDL receptor knockout (KO) mice were transplanted with bone marrow from ABCA1/apoE double KO (dKO) mice, their respective single KO's, and wild-type (WT) controls and were challenged with a high-fat/high-cholesterol diet for 9 weeks. In vitro cholesterol efflux experiments showed no differences between ABCA1 KO and dKO macrophages. The serum non-HDL/HDL ratio in dKO transplanted mice was 1.7-fold and 2.4-fold (p<0.01) increased compared to WT and ABCA1 KO transplanted mice, respectively. The atherosclerotic lesion area in dKO transplanted animals (650±94×103 µm2), however, was 1.9-fold (p<0.01) and 1.6-fold (p<0.01) increased compared to single knockouts (ABCA1 KO: 341±20×103 µm2; apoE KO: 402±78×103 µm2, respectively) and 3.1-fold increased (p<0.001) compared to WT (211±20×103 µm2). When normalized for serum cholesterol exposure, macrophage ABCA1 and apoE independently protected against atherosclerotic lesion development (p<0.001). Moreover, hepatic expression levels of TNFα and IL-6 were highly induced in dKO transplanted animals (3.0-fold; p<0.05, and 4.3-fold; p<0.001, respectively). In agreement, serum IL-6 levels were also enhanced in ABCA1 KO transplanted mice (p<0.05) and even further enhanced in dKO transplanted animals (3.1-fold as compared to ABCA1 KO transplanted animals; p<0.05).ConclusionsCombined deletion of macrophage ABCA1 and apoE results in a defect in cholesterol efflux and, compared to ABCA1 KO transplanted mice, elevated serum total cholesterol levels. Importantly, these mice also suffer from enhanced systemic and hepatic inflammation, together resulting in the observed augmented atherosclerotic lesion development.

Association between serum total cholesterol level and renal outcome in systemic lupus erythematosus

To determine whether an elevated serum total cholesterol level in a first-available sample obtained at a systemic lupus erythematosus (SLE) clinic is associated with worse renal outcome in patients with SLE. Survival analysis methods were used on prospectively gathered data on 1,060 patients with SLE who were registered in the University of Toronto Lupus Databank. The effect of total cholesterol and 15 additional variables on the outcomes of renal deterioration, end-stage renal disease (ESRD), and death was assessed using Cox proportional hazards methods. In 474 (45%) of the 1,060 patients, the total cholesterol level exceeded 5.2 mmoles/liter. In the entire study group, the median total cholesterol level was 5.1 mmoles/liter (range 1.6-17.1). During a mean followup period of 8.8 years, 93 patients (9%) experienced renal deterioration, 42 patients (4%) had ESRD, and 161 deaths occurred, 48 (30%) of which were associated with renal dysfunction (renal death), and 113 (70%) of which were not associated with renal dysfunction (nonrenal death). Kaplan-Meier survival estimates for each outcome were statistically significantly different between patients with normal versus those with elevated total cholesterol levels (cutoff 5.2 mmoles/ liter), with a worse outcome observed among those with an elevated total cholesterol concentration. In multivariate analyses, total cholesterol level (hazard ratio [HR] 1.17, 95 confidence interval [95% CI] 1.01-1.36), serum creatinine level (HR 1.06, 95% CI 1.04-1.07), proteinuria (HR 2.44, 95% CI 1.25-4.76), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (HR 1.44, 95% CI 1.16-1.80), and corticosteroid dose (HR 1.01, 95% CI 1.00-1.02) were associated with renal deterioration. Significant predictors of ESRD were baseline proteinuria (HR 6.24, 95% CI 1.96-19.88) and serum creatinine level (HR 1.15, 95% CI 1.08-1.22). The total cholesterol level was correlated with death (HR 1.20, 95% CI 1.11-1.29), retaining statistical significance for renal death (HR 1.33, 95% CI 1.20-1.47) but not for nonrenal death (HR 1.12, 95% CI 0.99-1.25). Those results indicate that an elevated serum total cholesterol level in a first-available sample obtained at an SLE clinic is associated with adverse renal outcomes and mortality.

Long term efficacy of simvastatin in renal transplant recipients treated with cyclosporine or tacrolimus

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In this study, 14 patients who had hypercholesterolemia [total cholesterol (TC) >200 mg/dL] and hypertriglyceridemia [triglyceride (TG) >150 mg/dL] 1 month after renal transplantation (post-transplantation), seven patients each under the treatment with immunosuppressant, either cyclosporine or tacrolimus started simvastatin treatment of 5-10 mg/d and continued the treatment for 4 yr. The effect of simvastatin treatment was assessed by comparison in serum lipid levels (TC, TG, cholesterol in lipoprotein fractions, and apolipoproteins) and the lipid metabolism related enzyme activities for post-transplantation, after 6-month and 4-yr simvastatin treatment. Simvastatin treatment of 4 yr significantly decreased the elevated levels of serum TC from 234.5 +/- 30.8 to 186.3 +/- 20.5 mg/dL (p < 0.001), low density lipoprotein cholesterol (LDL-C) from 116.7 +/- 22.5 to 82.7 +/- 16.6 mg/dL (p < 0.05) and TG from 200.3 +/- 109.2 to 97.0 +/- 45.2 mg/dL (p < 0.001). In addition, there were significant decreases in elevated serum very-low-density lipoprotein cholesterol (VLDL-C) from 47.8 +/- 18.4 to 28.6 +/- 9.5 mg/dL (p < 0.001) and LDL2 cholesterol (LDL2-C) from 20.8 +/- 8.2 to 5.7 +/- 1.8 mg/dL (p < 0.001). The results indicate that 4-yr treatment of simvastatin improves profiles of the atherogenic lipids in renal transplant patients with immunosuppressant caused hypercholesterolemia and hypertriglyceridemia treated either cyclosporine or tacrolimus in similar manner.

Effects of policosanol on borderline to mildly elevated serum total cholesterol levels: a prospective, double-blind, placebo-controlled, parallel-group, comparative study

BackgroundHypercholesterolemia is a major risk factor for coronary heart disease. Clinical studies have shown that lowering elevated serum cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is beneficial for patients with borderline to mildly elevated serum total cholesterol (TC) levels (5.0–6.0 mmol/L). Policosanol is a cholesterol-lowering drug made from purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d. ObjectiveThis study investigated the efficacy and tolerability of policosanol 5 mg/d in patients with borderline to mildly elevated serum TC levels. MethodsThis 14-week, single-center, prospective, double-blind, placebo-controlled, parallel-group, comparative study was conducted in men and women aged 25 to 75 years with a serum TC level ≥4.8 to <6.0 mmol/L. After a 6-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, patients were randomly assigned to receive policosanol 5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and the diet was continued throughout the study. Lipid profile variables, safety indicators, adverse events (AEs), and compliance with study medications were assessed. ResultsOne hundred patients (71 women, 29 men; mean [SD] age, 52 [10] years) entered the study after the dietary run-in period. After 8 weeks of treatment, the mean (SD) serum LDL-C level decreased significantly in the policosanol group (P<0.001 vs baseline and placebo) from 3.57 (0.30) mmol/L to 2.86 (0.41) mmol/L (change, −19.9%). Significantly more patients in the policosanol group (42 patients [84%]) achieved a ≥15% decrease in serum LDL-C than in the placebo group (2 patients [4%]) (P<0.001). Also in the policosanol group, the mean (SD) serum TC level decreased significantly, from 5.20 (0.22) mmol/L to 4.56 (0.44) mmol/L (P<0.001 vs baseline and placebo) (change, −12.3%); the mean (SD) triglyceride (TG) level decreased significantly, from 1.59 (0.57) mmol/L to 1.48 (0.57) mmol/L (P<0.01 vs baseline; P<0.05 vs placebo) (change, −6.9%); and the mean (SD) high-density lipoprotein cholesterol (HDL-C) level increased significantly from 1.05 (0.18) mmol/L to 1.16 (0.21) mmol/L (P<0.001 vs baseline and placebo) (change, +10.5%). The percentage changes were significantly different between the policosanol and placebo groups for serum LDL-C, TC, and HDL-C levels (P<0.001, P<0.001, and P<0.05, respectively), but not for TG. In the placebo group, changes in lipid profile variables from baseline were not significant. Policosanol did not significantly impair any safety indicator and was well tolerated. Three patients (3%) (1 patient [2%] in the policosanol group; 2 patients [4%] in the placebo group) withdrew from the trial, none because of AEs. Two patients (1 patient [2%] each in the policosanol and placebo groups) withdrew from the study because of an unwillingness to return for follow-up; 1 patient (2%) in the placebo group had a change of address and could not be followed up. Overall, 4 patients (4%) (1 patient [2%] in the policosanol group; 3 [6%], placebo) reported AEs; all were mild. Of the patients who received placebo and reported AEs, all 3 (6%) experienced heartburn, and 1 (2%) also experienced dry skin, while the policosanol-treated patient (2%) who reported an AE experienced headache. ConclusionsIn this study of patients with borderline to mildly elevated serum TC levels, based on the criterion that ≥70% of policosanol-treated patients reached the LDL-C goal of a decrease ≥15% from baseline whenever this proportion was different with respect to placebo, 8 weeks of treatment with policosanol 5 mg/d was effective. The decreased LDL-C, TC, and TG levels, increased HDL-C level, and good tolerability found with this treatment support its use in such patients.

Characterization and geographic distribution of the low density lipoprotein receptor (LDLR) gene mutations in northwestern Greece.

Familial Hypercholesterolaemia (FH) is a clinical syndrome characterised by elevated serum total cholesterol levels due to an increase in low density lipoprotein (LDL) cholesterol, by tendon xanthomata and clinical manifestations of ischaemic heart disease in early life. Typically, it results from mutations in the low-density lipoprotein receptor (LDLR) gene. So far, over 600 mutations have been reported for the LDLR gene and account for FH. The nature of LDLR gene mutations is different in various ethnicities and has also regional distribution within each ethnicity. Eleven mutations have already been described in the Greek population. This report describes seven LDLR gene mutations accounting for FH in Northwestern Greece (81T>G, 517T>C, 858C>A, 1285G>A, 1352T>C, 1646G>A and 1775G>A) and their geographic distribution. We have recently described one of these mutations (1352T>C) as a novel point mutation in a Greek family originating from Northwestern Greece. Furthermore, two previously identified mutations (81T>C, 1775G>A) were also detected in the Greek FH patients for the first time. The 1775G>A mutation was responsible for all the homozygous patients in our area, indicating a founder effect. These data will favor the development of tailed information and screening programs in Northwestern Greece for the primary prevention of cardiovascular disease in FH patients.

Elevated Serum Triglyceride Levels and Long-Term Mortality in Patients With Coronary Heart Disease

The association between elevated blood triglyceride levels and subsequent mortality risk in patients with established coronary heart disease (CHD) has been investigated rarely. The aim of the present study was to investigate this association. We evaluated mortality over a mean follow-up time of 5. 1 years among 9033 male and 2499 female CHD patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) Study. A stepwise increase in mortality with increasing serum triglyceride levels was observed in patients with desirable or elevated serum total cholesterol levels and in patients with either desirable or abnormally low HDL cholesterol levels. Multivariate adjustment for factors other than HDL cholesterol yielded a slightly increased adjusted mortality risk with a 1-natural-log-unit elevation of triglyceride levels in men (hazard ratio [HR] 1.14, 95% CI 1.00 to 1.30) and women (HR 1.37, 95% CI 1.04 to 1.88). Excess covariate-adjusted risk was noted among patients with elevated total and LDL cholesterol and in women with HDL cholesterol levels >45 mg/dL. After additional adjustment for HDL cholesterol, the risk of mortality with a 1-natural-log-unit elevation of triglycerides declined in men (HR 1.09, 95% CI 0.94 to 1.26) and in women (HR 1.10, 95% CI 0.80 to 1.50). A trend for increased mortality risk remained in patients with elevated total and LDL cholesterol and in women with HDL cholesterol >45 mg/dL. Elevated triglyceride levels were associated with a small, independent increased mortality risk in CHD patients. This risk may be increased among subgroups of patients with elevated total cholesterol and LDL cholesterol levels.

Inhibitors of acyl-CoA:cholesterol acyltransferase. 1. Synthesis and hypocholesterolemic activity of dibenz[b,e]oxepin-11-carboxanilides.

A series of N-phenyl-6,11-dihydrodibenz[b,e]oxepin-11-carboxamides and related derivatives were prepared on the basis of structures of the reported inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). These compounds were tested for their ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters in vivo. The structure-activity relationships in vitro were as follows. Substitution at positions 2 and 6 in the anilide resulted in potent inhibitory activity, and the potency increased with increasing size of the substituents, with maximum potency being obtained with a 2,6-diisopropyl substitution. The position of the substituent on the dibenz[b,e]oxepin ring system influenced the activity, and substitution at position 2 was critical for potent activity. The electronic effect of the substituent at position 2 does not influence activity, but bulkiness seems to be a significant factor. The lipophilicity of the compounds also plays an important role in determining ACAT inhibitory activity. Among the compounds tested, 2-bromo-N-(2,6-diisopropylphenyl)-6,11-dihydrodibenz-[b,e]++ +oxepin-11- carboxamide (33, KF17828) showed significant in vitro activity (rabbit liver microsomes IC50 = 23 nM) and the most potent in vivo activity (complete reduction in elevated serum total cholesterol levels at a dose of 10 mg/kg in hamsters).

大柴胡湯の動脈硬化症に対する効果に関する研究

Dai-Saiko-To (D-ext) has been noted to exhibit anti-atherogenesis. Following administration, New Zealand White (NZW) rabbit aortas were studied to determine the drug's effect against atherosclerosis induced by a rations high in cholesterol. A total of 101 NZW rabbits were divided into: Group A (experimental group): D-ext administration (1, 000mg/kg body weight/day, Tsumura, Tokyo) for 1 or 2 years after giving feed containing 1.5% cholesterol for 3 months; Group B (control): Received a normal diet (vehicle, CR-1, CLEA JAPAN, INC., Tokyo) for 1 or 2 years after the same atherogenic diet; Group C: Received a normal diet through experimental periods; Group D (hypercholesterol group) Received the same atherogenic diet for 3 months; Group E (simultaneous group): Received feed contaming 1.5% cholesterol and D-ext simultaneously for 3 months. Body weight, levels of serum total cholesterol (TC), triglyceride (TG), and cholesterol ester (CE) were periodically monitored until sacrifice. Serum lipids and aortic tissue lipids were analyzed, and aortas were processed for pathological analysis, including Surface Involvement (SI) and Atherosclerotic Index (AI).After 2-year administration of D-ext, the elevated levels of serum TC dropped back to the same level as at the start of the experiment. There was no significant difference in serum TC between groups A and B, but serum TG in group A at 3 and 6 months was significantly lower than in group B. The values of CE in group A aorta decreased relative to group B, though the difference was not significant. FC/PL ratios in the aortic intima-medial components of the group A tended to be lower than in the group B. AI in the group A at 6 months administration of D-ext was significantly lower than in the group B, and group E showed a significant lowering of AI compared to group D. There was no significant difference in SI among the groups. Histologically, lesions in group A had fewer foam cells, and the intimal thickness was thinner than in group B.Two-year administration of D-ext was less effecfive against advanced atherosclerosis induced by 1.5% cholesterol. But, D-ext exhibited a lowering of serum TG, aortic CE, and FC/PL ratios in the intima-medial cellular component. D-ext may have anti-atherogenesis in the progression of atherosclerosis in NZW rabbit aorta.

Nutritional status and food consumption in 10-11 year old Dutch boys (Dutch Nutrition Surveillance System).

As part of the Dutch Nutrition Surveillance System, cardiovascular risk factors and food consumption (24 h recall) as well as haematological, Fe and vitamin status (A, B6, C) were assessed in 126 Dutch boys aged 10-11 years (response 71%). Body mass index (BMI) and the sum of four skinfolds were strongly associated (r 0.85, P less than 0.01) and 8% of the boys were overweight (BMI greater than 20.1 kg/m2). Elevated serum total cholesterol levels (greater than 4.4 mmol/l) were observed in 38%; total cholesterol and low-density-lipoprotein-cholesterol levels were strongly associated (r 0.88, P less than 0.001). Intake of fat was high (38% of energy) and too much fat was saturated (polyunsaturated: saturated 0.44, guideline: 0.5-1.0), whereas intake of carbohydrate (49% of energy) and dietary fibre was low. About 12% of the boys had insufficient Fe stores (plasma ferritin less than 12.0 micrograms/l) and the mean Fe intake (9.0 mg/d) was below recommended daily allowance (10.0 mg/d). Plasma ferritin was, however, not associated with haematological indices and no frank anaemias were observed. No marginal values were observed for vitamins A, B6 and C status. In conclusion, the main nutritional risks in boys aged 10-11 years are cardiovascular risk factors and Fe nutrition.

The effects of zinc sulphate on hypercholesterolaemia induced by cholesterol-choleate in rats

The effects of zinc sulphate on cholesterol-choleate-induced hypercholesterolaemia were studied in rats. Zinc sulphate (20 or 40 mg/kg, p.o. once daily for 5 days) administration, which raised serum zinc levels, significantly increased bile acid secretion and lowered high-density lipoprotein-cholesterol (HDL-C) levels in the serum. Cholesterol-choleate, given by the same route and schedule, markedly elevated serum total cholesterol level, but decreased serum HDL-C concentration. Bile acid in serum and in bile was also increased, but these changes were inhibited by zinc sulphate pretreatment. Zinc sulphate also worsened the decrease in HDL-C and slightly prolonged the elevation in total cholesterol produced by cholesterol-choleate administration. It is concluded that the moderate increase in serum total cholesterol level by zinc sulphate could be due to inhibition of hepatic metabolism of cholesterol to bile acid. The specific action of zinc ions on HDL-C metabolism is discussed.