Increase In Blood Cholesterol Research Articles

Prediction of Blood Pressure and Cholesterol By Machine Learning Technique

Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Cholesterol is any of a class of certain organic particles called lipids [1]. High blood pressure along with high cholesterol are two of the main causes of heart disease. Heart disease, stroke, and other cardiovascular (blood vessel) diseases are among the primary cause of death. Approximately 10 million people every year die having high blood pressure and it was found that 6 in 10 Indians have abnormal levels of blood cholesterol [2]. An increase in blood cholesterol signifies an increase in a man's blood pressure, which can easily lead to abnormal blood pressure,e.g. high blood pressure. Generally, Prediction refers to the output of an algorithm after it has been trained on a dataset. Here Authors tried to predict whether a sample can have blood pressure and cholesterol or both present or not by analyzing some datasets. Generally, for making these types of predictions, machine learning algorithms are a very appropriate and most-used technique. A Multiple Linear Regression was applied in this study. Data has been analyzed through Multiple Linear Regression Analysis (MRA). The proposed model is tested on a Primary Data Set, prepared by Techno Engineering College Banipur’s students, and the relevant data of this Dataset has been collected from some districts in West Bengal, India. Through this research, approximately 76 percent of the data was predicted correctly.

Comparative effects of garlic (Allium sativum) powder and atorvastatin in female reproductive system of hypercholesterolemic rats: A histological and biochemical evaluation

Background and aims: The abnormal increase in blood cholesterol can cause many problems. Statins have a cholesterol-lowering effect, but they also have adverse effects. Garlic prevents the formation of cholesterol due to its antibiotic properties. This study aimed to investigate the comparative effect of garlic powder and atorvastatin on hypercholesterolemia-induced reproductive failure in female rats. Methods: In the present experimental study, 48 adult female Wistar rats were divided into eight groups (n=6), including control, atorvastatin (10 mg/kg/d; orally), atorvastatin (20 mg/kg/d; orally), garlic powder (100 mg/kg/d; orally), hypercholesterolemia (1.5 mg/kg/d of cholesterol; orally), hypercholesterolemia + atorvastatin (10 mg/kg/d), hypercholesterolemia + atorvastatin (20 mg/kg/d), and hypercholesterolemia + garlic powder. After 30 days, rats were euthanized and blood samples were obtained from their heart for serological assessments. The right ovary was transferred to 10% formalin for histological analyses, and the left ovary was transferred to a −80°C freezer for evaluation of oxidative stress markers. Data were statistically analyzed by ANOVA and Tukey’s test using SPSS version 24.0 (P<0.05). Results: The number of healthy primordial, primary, secondary, and antral follicles, catalase activity, total antioxidant capacity (TAOC) as well as estrogen and progesterone levels were lower in hypercholesterolemic rats compared to controls (P<0.001). Additionally, the number of the atretic primary, secondary, and antral follicles and malondialdehyde (MDA) levels were higher in hypercholesterolemic rats (P<0.001). However, garlic powder and atorvastatin 10 improved alterations in the mentioned parameters (P=0.99). Conclusion: The results showed that hypercholesterolemia could have adverse effects on rat ovaries. However, the garlic powder improves ovarian toxicity in hypercholesterolemia rats better than atorvastatin.

Efficacy and Safety of Front-Line Nilotinib Treatment and Discontinuation in Older Patients (≥65 years) with Chronic Myeloid Leukemia in Chronic Phase Who Have Achieved MR4.5: Results from ENESTfreedom

Efficacy and Safety of Front-Line Nilotinib Treatment and Discontinuation in Older Patients (≥65 years) with Chronic Myeloid Leukemia in Chronic Phase Who Have Achieved MR4.5: Results from ENESTfreedom

Hepatic and circulating levels of PCSK9 in morbidly obese patients: Relation with severity of liver steatosis

Non-alcoholic fatty liver disease (NAFLD) is becoming the main cause of liver disease in Western countries, especially in morbidly obese patients (MOPs). The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently studied because of its possible involvement in the pathogenesis of NAFLD, but its role, at least in MOPs, is still controversial. The aim of this study was to clarify the correlation between the circulating levels of the PCSK9 protein (cPCSK9) and its hepatic expression with the severity of liver damage in a population of MOPs with NAFLD undergoing bariatric surgery. PCSK9 mRNA was positively correlated with FASN, PPARγ and PPARα mRNAs, while no significant differences were found in PCSK9 mRNA expression in relation to the severity of liver steatosis, lobular inflammation and hepatocellular ballooning. In addition, hepatic PCSK9 protein expression levels were not related to histological parameters of lobular inflammation and hepatocyte ballooning, decreased significantly only in relation to the severity of hepatic steatosis, and were inversely correlated with ALT and AST serum levels. cPCSK9 levels in the whole population were associated with the severity of hepatic steatosis and were positively correlated to total cholesterol levels. In multivariate analysis, cPCSK9 levels were associated with age, total cholesterol and HbA1c. In conclusion, in MOPs our findings support a role for PCSK9 in liver fat accumulation, but not in liver damage progression, and confirm its role in the increase of blood cholesterol, which ultimately may contribute to increased cardiovascular risk in this population.

EFEKTIFITAS PEMBERIAN JUS TOMAT DAN JAMBU BIJI MERAH TERHADAP PENURUNAN KOLESTEROL TOTAL PADA WANITA OVERWEIGHT

Background : Women are two times have hypercholesterolemia 14.5% after menopause due to blood cholesterol levels increase because of the hormone estrogen is not formed. Drugs can be used to reduce cholesterol levels, but using drugs to reduce cholesterol levels have side effects. An alternative way that can be used in preventing a long-term increase in blood cholesterol levels and to reduce the dosage of drugs use is by using natural ingredients such as red guava fruit and tomatoes.Objective : This research aim to know the effectiveness of tomato juice and red guava juice on total cholesterol in overweight women.Method : This research was a clinical nutrition research. Type of research was true experiment research and study design was randomized pre-and post-test control group design. The tomato and red guava juice consist of 300 grams of tomatoes and red guavas, was given for 21 days to 22 respondents (11 treatments and 11 controls).In the treatment group there was lowering in total blood cholesterol and the control group with an increase in blood cholesterol levels.Result : Total Blood Cholesterol influenced by the lycopene intake and a decrease in total blood cholesterol levels in the treatment and control groups (p 0.05).Conclusion : 250 ml of tomato juice and red guava juice was given everyday within 3 weeks could reduce total cholesterol 3,01 mg/dl clinically, but not significant statistically.

P4633The frequency of mutations in patients with familial hypercholesterolemia who underwent acute coronary syndrome and patients with stable ischemic heart disease

Abstract Introduction Familial hypercholesterolemia (FH) is the most common genetically inherited disease in the world, which leads to a significant increase in blood cholesterol and an increased risk of early atherosclerosis and, consequently, an increase in mortality from ischemic heart disease (IHD). The actual prevalence of genetic variants causing FH in every population remains unknown. Purpose To compare the frequency of mutations in patients with FH who underwent acute coronary syndrome (ACS) and patients with stable IHD. Material and methods We included 120 patients (male-79, female-41) who had a clinical diagnosis of FH based on the Dutch Lipid Clinic Network (DLCN) score and Simon Broome criteria. The men and women included in the study were ≤55 and ≤60 years of age, respectively. 40 of them were patients with ACS; the remaining 80 were patients with stable IHD. Genetic studies were performed using a multiple approach based on targeted Next Generation Sequencing (NGS) in the Health in code and the ReadSense laboratories. Results Variants of the three “classic” genes implicated in FH were detected in 46 patients (38,3%). The frequency of mutations was detected in 32.5% of cases, and in patients with stable IHD in 41.25% of cases (p=0.35). In the group of participants with stable IHD, a mutation in the LDLR gene was obtained in 85% of cases; mutations in the APOB, PCSK9 genes were detected in 15% of cases. The same rate of mutations in the APOB and LDLR genes (38.5% each) was detected in patients with ACS. One patient had a mutation in the PCSK9 gene. In two patients there were mutations at once in two genes responsible for the development of FH: in one case, mutations were determined in the APOB and LDLR genes, in the other - LDLR and PCSK9. All patients who carried variants of the studied genes were heterozygous. Patients with clinically established FH had mutations in other genes involved in lipid metabolism, such as APOE, which turned to be mutant in 20 participants (16,6%). This variant defines the apoE4 isoform (also called ε4 allele), which is one of the three common genetic isoforms (apoE2, apoE3, and apoE4) of the APOE gene. It has been shown that the choice of apoE4 isoform have TC and LDL levels and increased risk of cardiovascular events related to atherosclerosis. Two patients had LPA mutations. This variant is a genetic polymorphism that has been previously published in association with elevated lipoprotein (a) (Lp(a)) levels and increased risk of IHD. Three patients were found to have ABCG8 mutations thought to be associated with sitosterolemia: two were pathogenic and another one of uncertain significance. Conclusion Thus, the frequency of mutations in patients with FH does not depend on the presence or absence of ACS. Both groups of patients are patients of a very high risk of developing both primary and repeated cardiovascular events.

Evaluation of laboratory research data in patients with multiple sclerosis in the aspect of comboridity

The objective of the work – to study laboratory data in patients with multiple sclerosis in order to clarify the nature of the influence of comorbid pathology on the level of dysfunction of biochemical processes of the body. We examined 216 patients with multiple sclerosis with various forms of course. Patients of the general sample were divided into two groups: І (n = 109) – without concomitant diseases and ІІ (n = 107) – with the presence of concomitant diseases. The results of general clinical tests of blood and urine, a biochemical blood test, a study of cerebrospinal fluid, the immune status of the blood, and the level of autoantibodies to brain antigens were evaluated. General clinical blood and urine tests, a biochemical blood test were performed on all 216 patients with multiple sclerosis from the study group. The study of cerebrospinal fluid (macroscopic, microscopic, polymerase chain reaction) and immunological blood tests (study of indicators of cellular and humoral immunity, the level of autoantibodies to brain antigens) were performed in 42 patients with multiple sclerosis of both groups. As a result, it was found that significant differences between groups І and ІІ exist due to an increase in platelet counts in patients of group ІІ (P < 0.05) and AsAT concentration (P < 0.05), an increase in creatinine concentration (P < 0.05), an increase in blood cholesterol (P < 0.05). Such differences in the indicators of general clinical and biochemical blood tests are, in our opinion, due to the presence of cardiovascular and gastroenterological comorbidity in patients with multiple sclerosis and correlate with a decrease in their overall well-being. As a result of studying the general analysis of urine in 84.7 % of patients of the general sample, there were general inflammatory signs, which were more pronounced in several indicators in the ІІ group of patients, clinically correlated with the severity of pelvic disorders. Systemic and deeper changes in the level of NK cells, the main protein of myelin, the total human brain antigen, as well as the immunoregulatory cycle in patients with multiple sclerosis with comorbid pathology were also established.

Abstract 438: Cholesterol biosynthesis is a critical metabolic dependency in pancreatic cancer

Abstract Pancreatic cancer is rapidly rising to become the 2nd leading cause of cancer deaths by 2020 in the USA. The rise in pancreatic cancer incidence is paralleled by the epidemic of obesity, type 2 diabetes, and associated increase in blood cholesterol, although mechanistic explanations for this are currently unknown. We and others have demonstrated that cancers with activated EGFR and KRAS signaling have increased demands for cholesterol and are vulnerable to interference with cholesterol uptake or endogenous cholesterol biosynthesis. We recently identified a metabolic step in the distal cholesterol pathway, mediated by SC4MOL and NSDHL enzymes, as a critical regulator of cell growth in the keratinocyte model of KRAS-induced carcinogenesis via the LXR agonistic effect of accumulating C4-methylsterols. Based on these preliminary data, we set out to test if pancreatic cancer initiation and progression depend on accelerated cholesterol biosynthesis in a genetic mouse model containing a conditional cholesterol pathway enzyme deficiency (conditional knockout of Nsdhlf/f) in the context of pancreatic cancer development in KPC mice (LSL-KrasG12D;Tp53f/f;Pdx1-Cre). Results: Conditional inactivation of NSDHL alone in pancreatic tissue during normal development produced no apparent phenotype. As expected, the NSDHL-sufficient KPC mice as well as heterozygous Nsdhlf/+ littermates did not survive beyond 8 weeks of age due to rapid development of progressive pancreatic tumors showing complete displacement of pancreatic tissue with adenocarcinoma and high-grade PanIN lesions. Contrastingly, the survival of pancreatic conditional NSDHL-null mice was significantly extended beyond the median survival of 50 days in NSDHL-sufficient age-matched controls. Furthermore, the progression of pancreatic lesions from ADM to PanIN3 was remarkably delayed on NSDHL-null background, with only a proportion of animals developing adenocarcinoma. Evaluation of pancreatic tissues revealed a dramatic reduction of tumor-induced desmoplasia at all stages of pancreatic cancer development. Our ongoing studies will address the role of cholesterol metabolism in pancreatic cancer progression via regulation of tumor-specific production of stroma-recruiting growth factors. Conclusions: Our studies demonstrated for the first time essential genetic evidence for metabolic dependency of pancreatic cancer on cholesterol metabolism. We identified NSDHL as a critical target in the endogenous pathway of cholesterol biosynthesis, and determined that blockade of NSDHL has dramatic consequences on the reciprocal signaling between the KRAS-transformed pancreatic cancer cells and the stroma. Citation Format: Linara Gabitova, Alena Klochkova, Diana Restifo, Aleksandra Mazitova, Edna Cukierman, Tiffiney Hartman, Igor Astsaturov. Cholesterol biosynthesis is a critical metabolic dependency in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 438. doi:10.1158/1538-7445.AM2017-438

Efek Diet Tinggi Kolesterol Terhadap Peningkatan Kolesterol Darah, Gambaran Histopatologi Hati, dan Bobot Badan Kelinci New Zealand White Jantan

This study was conducted to analyze the high cholesterol diet effect of egg yolk powder toward the increase of blood cholesterol and body weight in male New Zealand White rabbit and learned their liver histophatology figure. The experimental studies with Completely Randomized Design (CRD) used 13 male New Zealand White rabbit aged 6 – 7 months and weight 2,9 – 4,0 kg. Rabbit were divided into 3 groups: group 0 (n=4) given the standard feed, group 1 (n=4) given high cholesterol diet from egg yolk powder, and group 2 (n=5) given high cholesterol diet from egg yolk powder and red palm oil mix. The intervention was implemented for 8 weeks after 4 weeks adaptation period. The results showed that intervention of high cholesterol diet from egg yolk powder significantly increased levels of serum cholesterol and fatty liver, but did not significantly affect body weight of male New Zealand White rabbit.

Evaluation of long-term side effects after shock-wave lithotripsy for renal calculi using a third generation electromagnetic lithotripter.

To assess the incidence of long-term side effects after shock-wave lithotripsy treatment performed with an electromagnetic Dornier Lithotripter S device. A specific follow-up was undertaken on a cohort of 100 selected patients that underwent SWL for a single renal stone in our center from 2002 to 2004. Previous and current data were compared using the Student t test. Factors associated with the incidence of hypertension and diabetes mellitus were determined. Ten years after treatment, mean serum creatinine level and glomerular filtration rate remained similar to previous values (serum creatinine level: 0.96±0.22 vs. 0.92±0.19mg/dL; glomerular filtration rate: 92.8±17.8 vs. 88.1±21.7mL/min). There were marked increases in blood cholesterol, blood pressure, and blood glucose levels, while smoking decreased. Age, glomerular filtration rate, body mass index, blood glucose and blood pressure at the time of treatment were significantly associated with the presence of hypertension and diabetes mellitus at follow-up; blood cholesterol was associated with diabetes mellitus development. After 10years, overall renal function appeared to have been unaffected by shock-wave lithotripsy treatment. The increased rate of hypertension and diabetes mellitus were consistent with the incidence in the global population. This is the first report on the long-term safety of a third generation electromagnetic lithotripter, and indicates that there are no long-term sequelae.

Assessment of four experimental models of hyperlipidemia.

Various animal models of hyperlipidemia are used in research. Four rodent hyperlipidemia experimental models are examined in this study: three chronic hyperlipidemia models based on dietary supplementation with lipid or sucrose for 3 months and one acute hyperlipidemia model based on administration of the nonionic surfactant poloxamer. Neither lipid supplementation nor sucrose supplementation in Wistar rats was effective for establishing hyperlipidemia. Combining both lipid and sucrose supplementation in BALB/c mice induced hypercholesterolemia, as reflected in a considerable increase in blood cholesterol concentration, but did not produce an increase in blood triglyceride concentration. Poloxamer administration in C57BL/J6 mice produced increases in blood cholesterol and triglyceride concentrations. The authors conclude that supplementation of both lipid and sucrose in BALB/c mice was the most effective method for developing chronic hypercholesterolemia.

The impact of cholesterol and its metabolites on drug metabolism

Introduction: Global prevalence of Western-type diet has increased in the last decades resulting in occurrence of certain chronic diseases. This type of diet is also linked to high-cholesterol intake and increase in blood cholesterol. Many of the molecular mechanisms of dealing with increased levels of cholesterol and its metabolites have been elucidated in animal models and humans. It is also evident that cholesterol metabolism is closely connected to drug metabolism. Cholesterol/bile acids and drugs share many transporters, enzymes and regulatory proteins which are key points in the crosstalk.Areas covered: This review presents an overview of the effect of cholesterol and its metabolites on drug metabolism with special emphasis on species-specific differences. The article focuses on the role of nuclear receptors farnesoid X receptor, vitamin D receptor and liver X receptor in the regulation of drug metabolism genes and the role of cholesterol biosynthesis intermediates, oxysterols and bile acids in the induction of drug metabolism through pregnane X receptor.Expert opinion: Studies show that the regulation of drug metabolism by sterols is multileveled. Many species-dependent differences were observed which hinder the transfer of findings from model animals to humans. As of now, there is little evidence available for cholesterol impact on drug metabolism in vivo in humans. There is also the need to confirm the results obtained in animal models and in vitro analyses in human cells but this is very difficult given the current lack of tools.

HYPERCHOLESTEROLEMIA DECREASE NO LEVELS IN RED BLOOD CELLS VIA OXIDATIVE STRESS: PP.11.429

Hypercholesterolemia is correlated with decreased nitric oxide (NO) bioavailability and increased oxidative stress in the vascular endothelium. An increase in blood cholesterol or a decrease in NO bioavailability affects rheological parameters, e.g. red blood cell (RBC) deformability. Evidence of an active NO synthesis in RBC has been presented in recent studies. We hypothesized that hypercholesterolemia-mediated decrease in RBC deformability might be mediated by a decrease in NO bioavailability in RBC. We compared the effect of diet-induced hyperlipidemia and genetic determined hyperlipidemia on NO levels, redox status and deformability of RBC. ApoE knock out (KO) and wild type (WT)-mice (C57/Bl6, n = 6–9) have been set on a high fat diet for 12 weeks. Blood samples were obtained at 0, 6 and 12 weeks. Intracellular NO levels were measured by staining RBC with 4-amino-5-methylamino-2,7-difluorofluorescein diacetate and analyzing the fluorescence signal in flow cytometry. ApoE KO-mice showed a 30% decrease in NO levels in RBC compared to WT-mice. High fat diet further decreased NO-bioavailability in both groups after 6 and even further after 12 weeks. To analyze the effects of hyperlipidemia on the redox status of RBC, reactive oxygen species (ROS) and intracellular glutathione levels were measured by staining RBC with dichlorofluorescein and ThiolTracker, respectively, with or without pre-incubation of H2O2 as a positive control. Hypercholesterolemia increased intracellular ROS and decreased GSH levels in wild type mice. In apoE KO mice GSH levels decreased after 12 weeks but ROS levels remained unchanged. Measuring RBC deformability by using a laser assisted optical rotational cell analyser revealed that hypercholesterolemia reduced deformability of RBC after 6 weeks in apoE KO and WT mice but was restored in both groups after 12 weeks. Hypercholesterolemia decreases NO bioavailability and deformability in RBC mainly by affecting the oxidative status. Thus, decreased NO bioavailability in RBC due to hyperlipidemia might impair blood rheology in the microcirculation which could predispose to endothelial dysfunction, tissue hypoxia and atherosclerosis.

Fluvastatin Alters Both The Calcium Homeostasis And Cell Proliferation In Cultured Myotubes And The Calcium Release Events In Adult Muscle Fibers Of The Rat

Skeletal muscle cells of newborn rats were cultured in the absence and presence of fluvastatin (0.1 μM). Resting levels of intracellular calcium concentration ([Ca2+]i) were determined from Fura-2 fluorescence while proliferation was assessed by counting the number of nuclei in myogenic cells. The presence of the drug did not alter [Ca2+]i (130±11 vs 121±7 nM; n=12 vs 10 rats; mean±SE; control and treated, respectively) but reduced the number of myogenic nuclei by 50% after 24 hours of treatment. To assess the chronic effects of fluvastatin on skeletal muscles of adult animals, female rats were kept on diets that either contained 62.5 mg/kg (daily intake 6 mg/kg body weight) fluvastatin or not. Animals were either fed with an otherwise normal chow or with a chow that induced an increase in blood cholesterol. Similarly to cultured cells, [Ca2+]i of adult fibers was unaltered by the drug, however, a clear reduction of muscle mass was observed. Single fibers were enzymatically isolated from the m. extensor digitorum communis, permeabilized with Saponin and loaded with Fluo-4. Calcium release events (CRE) were captured using laser scanning confocal microscopy and analyzed with an automated computer program. Fluvastatin increased the frequency of CRE on both normo- and hypercholesterolaemic animals from 0.028 to 0.042 and 0.034 to 0.047 sarc-1s-1 (normo- and hypercholesterolaemic, respectively; n=14 vs 14 and 7 vs 15). While leaving the full width at half maximum unchanged the drug significantly increased the amplitude of sparks in both groups (0.405±0.005 vs 0.436±0.004 and 0.354±0.004 vs 0.422±0.005; n=605 vs 1429 and 741 vs 1052). This gave rise to an increased amount of released calcium in statin treated animals as reflected in the elevated signal mass.

Risk factors for cardiovascular disease in Sardinia from 1978 to 2001: A comparative study with Italian mainland

Background This study is a survey of cardiovascular risk factors in Sardinia in the years 1999–2001 and allows us to update previously observed trends of such factors and to compare them with those in the Italian mainland. Methods Random samples of free living population of the Mediterranean island of Sardinia, Italy, were collected. Overall, 6818 subjects, 50% of each sex, and aged 20–80+ years constituted the sample. Personal and family data were collected using a semiquantitative questionnaire of frequencies. Blood biochemical variables related to risk for atherosclerosis were measured. In particular, serum total cholesterol, HDL-cholesterol, triglycerides, Apo A-1, Apo B, Lp(a), uric acid, blood glucose and plasma homocysteine were analyzed in each subject enrolled. Results In the age classes 20–59 years, during a 30 year period, prevalence of smoking among males continued to decrease from 58 to 24% ( p for trend < 0.001), and, for the first time, prevalence of smoking among females decreased as well: from 31% in 1995 to 20% in 2001 ( p for trend < 0.001). In contrast, a steady increase in TC (mg/dl) (189, 206, 215, 216, p for trend < 0.05 in males and 184 197, 212, 217, p for trend < 0.05 in females), and LDL-C (136, 143, 138, 144, p for tend < 0.05 in males and 127, 139, 136, 135, p for trend < 0.05 in females) was observed. HDL-C showed a steady increase ( p for trend < 0.01 in males and females). Lp(a) values were high in both sexes, a finding linked to the ethnic influence on them. Systolic and diastolic blood pressure values (mm Hg) increased with age. In the present survey (population aged 20–80+ years, current smokers were 17.5% among males and 13.8% among females. Total and HDL-cholesterol were higher than in other parts of Italy (209 vs 205 in males, and 211 vs 204 in females), while systolic and diastolic blood pressure were lower. Conclusion Overall, total- and LDL-cholesterol showed an increasing trend, while blood pressure and smoking habits had a decreasing tendency. The increase in blood cholesterol follows the trend in other areas of the world, mainly due to changing dietary habits. Therefore, a campaign of eating information and education (population strategy) could favourably modify cardiovascular risk, as occurred in Sardinia during the past decade with the Regional ATS-Sardegna Campaign.

Extract of black tea (pu‐ehr) inhibits postprandial rise in serum cholesterol in mice, and with long term use reduces serum cholesterol and low density lipoprotein levels and renal fat weight in rats

A water-soluble extract of a traditional Chinese fermented black tea, pu-ehr, decomposes bile acid cholesterol micelles. This black tea extract (BTE) was studied to see if it could decrease the postprandial elevation of blood cholesterol levels after a single administration in ddY mice. It was found that BTE (0.3 g/kg) significantly decreased the postprandial rise in blood cholesterol levels after oral administration of cholesterol (130 mg/kg). A non-fermented tea (i.e. green tea) extract did not prevent the postprandial increase in blood cholesterol. In a subsequent study, 5-week-old Sprague-Dawley (SD) rats were fed BTE for 3 weeks, following which a dose-dependent and significant decrease in serum total cholesterol levels (1.36 mmol/L, 0.1% BTE, p < 0.05) was found and also in renal fat weight (0.3% BTE, p < 0.05). LDL cholesterol levels (0.51 mmol/L, 0.1% BTE, p < 0.05) were also significantly decreased. There were no significant changes in the weights of other organs or in the serum levels of other clinical markers. Thus, BTE has a specific antihypercholesterol effect in rodents, which might potentially aid in the management of hyperlipidaemia in man.

Experimental studies of the hypolipidemic properties of pollen

Experiments on white rats with a model of “chronic” (two months) hyperlipidemia demonstrated the ability of pollen to produce significant delays in increases in blood cholesterol, triglycerides, and beta-lipoproteins and in liver cholesterol; pollen increased blood alpha-lipoprotein cholesterol. The effects of pollen approached those of Lipanor. The hypolipidemic action of pollen was linked with a reduction in cholesterol uptake and an increase in its metabolism into bile acids, along with reductions in peroxidation, membrane stabilization, and activation of adaptive anabolic reactions in tissues.

Activation of the unfolded protein response by cholesterol enrichment in human endothelium

Elevated blood cholesterol is a major risk factor for atherosclerosis, but how cholesterol affects the endothelium has not been well studied. The object of the present study was to determine whether hypercholesterolemia alters endothelial cell (EC) membrane cholesterol content in vivo, and whether excess membrane cholesterol might activate the unfolded protein response (UPR), also know as the ER stress response. In rabbits fed cholesterol for up to 12 days, EC membrane cholesterol content increased 2.3-fold, paralleling the increase in blood cholesterol, demonstrating that hypercholesterolemia leads to EC accumulation of excess cholesterol in-vivo. We mimicked this response in human umbilical vein EC by enriching cells in culture with cholesterol using a mixture of β-cyclodextrins and cholesterol-rich liposomes. This resulted in comparable enrichment with cholesterol and resulted in a 1.5-fold increase in the ER chaperon protein BiP, a hallmark of activation of the UPR, along with an increase in BiP mRNA determined using real-time PCR. We then measured the levels of the three known downstream UPR signaling proteins ATF4, ATF6 and XBP-1. While ATF4 and AFT6 protein and mRNA levels were decreased, spliced XBP-1 (active form of XBP-1) protein levels were elevated 13.8-fold. Thus, mobilization of the ER chaperone BiP and subsequent modulation of downstream UPR signaling proteins demonstrates activation of the UPR in EC by accumulation of cholesterol in EC membranes. These findings implicate a direct role for cholesterol in inducing ER stress in endothelium during the development of hypercholesterolemia and may contribute to EC participation in atherogenesis.

The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions.

Recent data indicate that the catechol estrogen, 2-hydroxyestrone (2-OHE(1)), has no effect on any target tissue including bone, whereas 16 alpha-hydroxyestrone (16 alpha-OHE(1)) exerts tissue-selective estrogen agonist activity. The effect of the catechol estrogen, 4-hydroxyestrone (4-OHE(1)), putatively associated with tumorigenesis, has not been studied in the skeleton. The purpose of this study was to assess the effect of 4-OHE(1) on tibia, uterine and mammary gland histology and blood cholesterol in ovariectomized (OVX'd) growing rats. Ten-week-old female Sprague-Dawley rats were injected subcutaneously with 200 microg/kg BW per day with 4-OHE(1), 17 beta-estradiol (E(2)) or vehicle for three weeks. OVX resulted in uterine atrophy, increased body weight, radial bone growth and cancellous bone turnover, and hypercholesterolemia. E(2) prevented these changes with the expected exception that the subcutaneous infusion of this high dose of estrogen did not prevent the hypercholesterolemia. 4-OHE(1) prevented the increase in blood cholesterol and the increase in body weight. 4-OHE(1) appeared to have partial estrogen activity in the uterus; uterine weight and epithelial cell height were significantly greater than the OVX rats but significantly less (twofold) than the E(2) animals. Analysis of variance indicated that 4-OHE(1) slightly decreased the periosteal mineral apposition rate (P<0.05) compared with vehicle-treated rats but had no effect on double-labeled perimeter or bone formation rate. Similarly, 4-OHE(1) was a partial estrogen agonist on cancellous bone turnover. The data suggest that the catechol estrogen, 4-OHE(1), unlike 2-OHE(1), has estrogen activity. Furthermore, the profile of activity differs from that of 16 alpha-OHE(1). Our results suggest that estrogen metabolites may selectively influence estrogen-target tissues and, concomitantly, modulate estrogen-associated disease risk.

Risk factors of cholelithiasis relapse after lithotripsy and during prophilactic treatment with bile acids: Preliminary results of two-years follow-up study

RISK FACTORS OF CHOLELITHIASIS RELAPSE AFTER LITHOTRIPSY AND DURING PROPHILACTIC TREATMENT WITH BILE ACIDS: PRELIMINARY RESULTS OF TWO-YEARS FOLLOW-UP STUDY V. Isakov l, T. Petukhova, M. Brekhova, A. Mironov, I. Ivanikov Central Hospital Medical Centre of RF President Adm. Dep., Department of Gastroenterology, Moscow Russia. 1MONIKI, Moscow, Russia. The aim: To establish risk factors of cholelithiasis relapse after lithotripsy and during long-term prophylactic therapy with bile acids. 205 patients (Male/Female=55/150; mean age 45,6 yrs) after successful gallbladder lithotripsy were enrolled for the prophylactic therapy with ursodeoxycholic acid (dosage 10mg/kg per day) for 24 months with ultrasound control every 3 months. During the follow-up period 128 (62,4%) patients relapsed. Multivariate analysis revealed that age (Table), 20% increase of body mass index, 10% increase of blood cholesterol indelmndently increase risk o f relapse of cholelithiasis. Age group Patients in remission after 2 years (%) p