A patogenia na leishmaniose visceral (LV) não é totalmente conhecida. Em LV em hamsteres avaliamos a participação de imunoglobulinas nas lesões. IgG foi detectada no sinusóide hepático, nos septos pulmonares e nos capilares glomerulares, em maior intensidade aos 30 e 45 dias pós-infecção (PI); C3 estava ausente, exceto no rim. Os dados não sendo compatíveis com a deposição de imunocomplexo, estudamos ultraestruturalmente a internalização de imunoglobulinas. No fígado e no rim a quantidade de imunoglobulina em célula endotelial era maior aos 30 dias PI em relação ao controle não infectado e no pulmão, aos 30 dias PI em relação aos 60 dias PI. Imunoglobulina internalizada por célula endotelial observada neste estudo na LV em hamsteres, marcadamente aos 30 dias PI, pode ser um mecanismo alternativo de lesão na LV / Pathogenesis of visceral leishmaniasis (VL) is not fully known. In VL in hamsters we evaluated the participation of immunoglobulins in the lesions. IgG was detected in the hepatic sinusoid, in the lung alveolar walls and in the glomerular capillaries in higher intensity at 30 and 45 days post-infection (PI); there were no C3, except in the kidney. Since the data were not compatible with immune complex deposition, we studied ultraestructurally the internalization of immunoglobulins. In the liver and in kidney the amount of immunoglobulin within endothelial cells was greater at 30 days PI than in non infected control, and in the lung at 30 days PI in relation to 60 days PI. Immunoglobulin internalized by endothelial cells observed in VL in hamsters, remarkably at 30 days PI, may be an alternative mechanism of lesion in VL

Chiu Chi Pang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 121-134). / Abstracts in English and Chinese. / DECLARATION --- p.i / ACKNOWLEDGEMENTS --- p.ii / ABBREVIATIONS --- p.iii / ABSTRACT --- p.vi / 摘要 --- p.viii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- Cholesterol --- p.1 / Chapter 1.1.1 --- History of cholesterol --- p.1 / Chapter 1.1.2 --- Structure of cholesterol --- p.1 / Chapter 1.1.3 --- Biological function of cholesterol --- p.3 / Chapter 1.1.4 --- Sources of cholesterol in our body --- p.3 / Chapter 1.2 --- Lipid hypothesis --- p.4 / Chapter 1.2.1 --- Relationship between dietary cholesterol and plasma cholesterol --- p.4 / Chapter 1.2.2 --- "Hypercholesterolemia , atherosclerosis and coronary heart disease (CHD)" --- p.4 / Chapter 1.2.3 --- Individual variation --- p.5 / Chapter 1.3 --- Cholesterol homeostasis --- p.7 / Chapter 1.3.1 --- SREBPs up-regulates the expression of LDL-receptor and HMG-CoA reductase --- p.7 / Chapter 1.3.2 --- HMG-CoA reductase as the rate-limiting enzyme in cholesterol synthesis --- p.11 / Chapter 1.3.3 --- LDL-receptor as the major protein removing plasma cholesterol …… --- p.12 / Chapter 1.3.4 --- LXR-α as an activator of CYP7A1 --- p.14 / Chapter 1.3.5 --- CYP7A1 controls the classical pathway for the elimination of hepatic cholesterol --- p.16 / Chapter 1.3.6 --- Bile acids as the metabolites of CYP7A1 --- p.17 / Chapter 1.4 --- Previous works in our laboratory --- p.20 / Chapter 1.5 --- Objective of this project --- p.22 / Chapter CHAPTER 2: --- INCREASED EXPRESSION OF LDL-RECEPTOR IS RESPONSIBLE FOR THE HYPO-RESPONSIVENESS OF RATS TO DIETARY CHOLESTEROL --- p.23 / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Objective --- p.24 / Chapter 2.3 --- Methods and materials --- p.25 / Chapter 2.3.1 --- Animals --- p.25 / Chapter 2.3.2 --- Diets --- p.25 / Chapter 2.3.3 --- Determination of serum cholesterol --- p.26 / Chapter 2.3.4 --- Western blot --- p.26 / Chapter 2.3.5 --- Probe production for LDL-receptor --- p.27 / Chapter 2.3.5.1 --- Extraction of total RNA --- p.27 / Chapter 2.3.5.2 --- Reverse-transcription reaction of total RNA --- p.28 / Chapter 2.3.5.3 --- Polymerase chain reaction (PCR) of LDL- receptor fragment from cDNA template --- p.28 / Chapter 2.3.5.4 --- Separation and purification of PCR products --- p.29 / Chapter 2.3.5.5 --- Polishing of purified PCR products --- p.29 / Chapter 2.3.5.6 --- Ligation of PCR products and pPCR-script Amp SK(+) cloning vector --- p.30 / Chapter 2.3.5.7 --- Transformation --- p.30 / Chapter 2.3.5.8 --- Preparing glycerol stocks containing the bacterial clones --- p.31 / Chapter 2.3.5.9 --- Plasmid DNA preparation --- p.31 / Chapter 2.3.5.10 --- Clones confirmation by restriction enzyme digestion --- p.32 / Chapter 2.3.5.11 --- Clones confirmation by automatic sequencing --- p.32 / Chapter 2.3.5.12 --- Linearization of the plasmid DNA --- p.33 / Chapter 2.3.5.13 --- DIG-labeling of RNA probe --- p.35 / Chapter 2.3.5.14 --- Testing of DIG-labeled probe --- p.35 / Chapter 2.3.6 --- Probe production for HMG-CoA reductase --- p.36 / Chapter 2.3.7 --- Probe production for GAPDH --- p.37 / Chapter 2.3.8 --- Northern blot --- p.38 / Chapter 2.3.9 --- Determination of hepatic cholesterol --- p.39 / Chapter 2.3.10 --- Statistics --- p.40 / Chapter 2.4 --- Results --- p.42 / Chapter 2.4.1 --- Growth and food intake --- p.42 / Chapter 2.4.2 --- Effect of cholesterol supplements on serum cholesterol --- p.42 / Chapter 2.4.3 --- Effect of cholesterol supplements on liver cholesterol content --- p.45 / Chapter 2.4.4 --- "Stimulatory effect of high cholesterol diet on nSREBP-2, LDL-receptor and HMG-CoA reductase in rats" --- p.45 / Chapter 2.4.5 --- "Effect of high cholesterol diet on nSREBP-2, LDL-receptor and HMG-CoA reductase in hamsters" --- p.49 / Chapter 2.4.6 --- The regulation of LDL-receptor and HMG-CoA reductase existed at transcriptional level --- p.54 / Chapter 2.5 --- Discussion --- p.59 / Chapter CHAPTER 3: --- RATS ARE HYPO-RESPONSIVE TO DIETARY CHOLESTEROL DUE TO EFFICIENT ELIMINATION OF CHOLESTEROL --- p.67 / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.2 --- Objective --- p.69 / Chapter 3.3 --- Methods and materials --- p.70 / Chapter 3.3.1 --- Animals and diets --- p.70 / Chapter 3.3.2 --- Western blot --- p.70 / Chapter 3.3.3 --- Probe production for CYP7A1 and LXR-α --- p.71 / Chapter 3.3.4 --- Northern blot --- p.71 / Chapter 3.3.5 --- Determination of fecal neutral and acidic sterols --- p.71 / Chapter 3.3.5.1 --- Separation of neutral and acidic sterols --- p.71 / Chapter 3.3.5.2 --- Neutral sterols analysis --- p.72 / Chapter 3.3.5.3 --- Acidic sterols analysis --- p.72 / Chapter 3.3.5.4 --- GLC analysis of neutral and acidic sterols --- p.73 / Chapter 3.3.6 --- Statistics --- p.73 / Chapter 3.4 --- Results --- p.76 / Chapter 3.4.1 --- Effect of cholesterol supplements on fecal total neutral sterols --- p.76 / Chapter 3.4.2 --- Effect of cholesterol supplements on fecal total bile acids --- p.76 / Chapter 3.4.3 --- CYP7A1 protein on rats showed a concentration-dependent increase with response to dietary cholesterol while hamsters did not --- p.79 / Chapter 3.4.4 --- The regulation of CYP7A1 was at transcriptional level --- p.79 / Chapter 3.4.5 --- LXR-α demonstrated a parallel changes in its expression at both translational and transcriptional level --- p.84 / Chapter 3.5 --- Discussion --- p.88 / Chapter CHAPTER 4: --- MECHANISM FOR INDIVIDUAL VARIATION OF SERUM CHOLESTEROL LEVEL IN RATS AND HAMSTERS FED A HIGH CHOLESTEROL DIET --- p.94 / Chapter 4.1 --- Introduction --- p.94 / Chapter 4.2 --- Objective --- p.96 / Chapter 4.3 --- Methods and materials --- p.97 / Chapter 4.3.1 --- Diet and animals --- p.97 / Chapter 4.3.2 --- Western blot --- p.97 / Chapter 4.3.3 --- Statistics --- p.97 / Chapter 4.4 --- Results --- p.99 / Chapter 4.4.1 --- Growth and food intake --- p.99 / Chapter 4.4.2 --- Change of serum cholesterol --- p.99 / Chapter 4.4.3 --- Correlation between various protein expression and serum cholesterol --- p.99 / Chapter 4.4.3.1 --- Correlation between LDL-receptor and serum total cholesterol in rats --- p.99 / Chapter 4.4.3.2 --- Correlation between CYP7A1 and serum total cholesterolin rats --- p.99 / Chapter 4.4.3.3 --- Correlation between nSREBP-2 and serum total cholesterolin rats --- p.105 / Chapter 4.4.3.4 --- Correlation between LXR-a and serum total cholesterol in rats --- p.105 / Chapter 4.4.3.5 --- Correlation between HMG-CoA reductase and serum total cholesterol in rats --- p.105 / Chapter 4.4.3.6 --- Correlation between LDL-receptor and serum total cholesterol in hamsters --- p.105 / Chapter 4.4.3.7 --- Correlation between CYP7A1 and serum total cholesterolin hamsters --- p.109 / Chapter 4.4.3.8 --- Correlation between nSREBP-2 and serum total cholesterolin hamsters --- p.109 / Chapter 4.4.3.9 --- Correlation between HMG-CoA reductase and serum total cholesterol in hamsters --- p.109 / Chapter 4.5 --- Discussion --- p.114 / Chapter CHAPTER 5: --- CONCLUSION --- p.117 / REFERENCES --- p.121

Grape seed proanthocyanidins (GSP) as a cholesterol-lowering nutraceutical has been investigated in both humans and animals, however, little is known of how it interacts with the genes and proteins involved in lipoprotein metabolism in vivo. So the first objective of the present study was to investigate the effect of GSP supplementation on blood cholesterol level and gene expression of cholesterol-regulating enzymes in Golden Syrian hamsters maintained on a 0.1% cholesterol diet. / Hypercholesterolemia is one of the major proven risk factors for atherosclerosis. Decreasing blood total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels with cholesterol-lowering nutraceuticals and dietary intake modification could slow or reverse the progression of cardiovascular disease. / In conclusion, the present study confirmed that hypocholesterolemic activity of GSP was most likely mediated by enhancement of bile acid excretion and up-regulation of CYP7A1. The present study also demonstrated that frequent cholesterol and myristic acid intake is associated with elevation of plasma TC level, while beta-sitosterol intake frequency had no effect on plasma cholesterol for a given amount. / In the beta-sitosterol consumption frequency study, hamsters fed the basal diet with a gavage-administration of 3 mg cholesterol 3 times (control), or a gavage-administration of 3 mg beta-sitosterol with 3 mg cholesterol 3 times per day (high beta-sitosterol intake frequency), or a gavage-administration of 9 mg beta-sitosterol with 3 mg cholesterol for one time and 3 mg cholesterol for the other two times (low beta-sitosterol intake frequency). The results demonstrated that for a given dose of beta-sitosterol, the administration frequency had no or little effect on plasma lipoprotein profiles. The present study also found that cholesterol-lowering activity of beta-sitosterol was mediated by its inhibition on the intestinal cholesterol absorption with up-regulation of NPC1L1, ATP binding cassette transporters G5 and G8 (ABCG5/8) and MTP. / In the cholesterol consumption frequency study, hamsters were given daily 9 mg of cholesterol either in diet (high cholesterol intake frequency) or a gavage-administration of 3 times 3 mg (regular cholesterol intake frequency) and 1 time 9 mg (low cholesterol intake frequency). The results demonstrated that there was an increasing trend in concentrations of plasma TC, Non-HDL-C, TC/HDL-C ratio and TG in association with the cholesterol intake frequency. It is the first time to demonstrate that the increasing cholesterol intake frequency increased the apparent cholesterol absorption. Elevation of plasma TC and cholesterol absorption is most likely mediated by up-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1), acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP) gene expression. / In the myristic acid consumption frequency study, hamsters were given daily 210 mg of myristic acid either in diet (high myristic acid intake frequency) or a gavage-administration of 3 times 70 mg (regular myristic acid intake frequency) and 1 time 210 mg (low myristic acid intake frequency). The results showed that the increasing consumption frequency elevated plasma TC, Non-HDL-C and HDL-C levels. Elevation of plasma TC and HDL-C is most likely mediated by up-regulation of NPC1L1 and down-regulation of scavenger receptor BI (SR-BI) gene expression via enhancement of dietary myristic acid absorption. / The results affirmed supplementation of 0.5% or 1.0% GSP could decrease plasma TC, non-high density lipoprotein cholesterol (Non-HDL-C) and triglyceride (TG) levels. In addition, dietary GSP was able to increase the excretion of bile acids by 3--4 folds, this was partially mediated by up-regulation of Cholesterol 7 alpha-hydroxylase (CYP7A1) in both transcriptional and translational levels. It was concluded that the hypocholesterolemic activity of GSP was most likely mediated by enhancement of bile acid excretion and up-regulation of CYP7A1. / The second objective of the present study was to investigate the effect of cholesterol, myristic acid and beta-sitosterol consumption frequency on plasma lipoprotein profiles in hamsters. Numerous studies reported that dietary cholesterol and saturated fatty acids elevated plasma TC level, whereas dietary phytosterols in moderate and high doses favorably reduced plasma TC and LDL levels. However, it is still unknown whether consumption frequency of sterols and fatty acids could affect plasma cholesterol level and lipid profiles. / Jiao, Rui. / Adviser: Chen Zhen Yu. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 123-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ma, Ka Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 113-129). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.VII / TABLE OF CONTENTS --- p.IX / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Calcium --- p.1 / Chapter 1.1.1 --- Recommendation of calcium intake --- p.1 / Chapter 1.1.2 --- Calcium toxicity --- p.2 / Chapter 1.1.3 --- Calcium homeostasis --- p.2 / Chapter 1.1.3.1 --- Role of parathyroid hormone in calcium homeostasis --- p.4 / Chapter 1.1.3.2 --- "Role of 1,25-dihydroxyvitamin D3 in calcium homeostasis" --- p.4 / Chapter 1.1.3.3 --- Role of calcitonin in calcium homeostasis --- p.6 / Chapter 1.2 --- Magnesium --- p.7 / Chapter 1.2.1 --- Recommendation of magnesium intake --- p.7 / Chapter 1.2.2 --- Absorption and secretion of magnesium --- p.8 / Chapter 1.3 --- Cholesterol --- p.9 / Chapter 1.3.1 --- Cholesterol homeostasis --- p.11 / Chapter 1.3.1.1 --- Role of LDLR --- p.14 / Chapter 1.3.1.2 --- Role of SREBP-2 --- p.17 / Chapter 1.3.1.3 --- HMGR as rate limiting step for cholesterol synthesis --- p.19 / Chapter 1.3.1.4 --- CYP7A1 as a key factor in production of bile acids --- p.21 / Chapter 1.3.1.5 --- Role of LXR in production of bile acids --- p.22 / Chapter 1.3.1.6 --- AC AT regulates cholesterol uptake in intestine --- p.22 / Chapter Chapter 2 --- Effect of Calcium Deficiency and Inadequacy on Blood Cholesterol Level in Intact Male and Castrated Hamsters --- p.25 / Chapter 2.1 --- Introduction --- p.25 / Chapter 2.2 --- Objective --- p.28 / Chapter 2.3 --- Materials and methods --- p.29 / Chapter 2.3.1 --- Hamsters --- p.29 / Chapter 2.3.1.1 --- Intact male hamster --- p.29 / Chapter 2.3.1.2 --- Castrated hamster --- p.30 / Chapter 2.3.2 --- Diets --- p.31 / Chapter 2.3.3 --- Determination of calcium content in animal diet --- p.33 / Chapter 2.3.4 --- "Determination of serum lipid, lipoproteins and calcium concentration" --- p.33 / Chapter 2.3.5 --- Determination of cholesterol concentration in organs --- p.34 / Chapter 2.3.6 --- Determination of fecal neutral and acidic sterols --- p.37 / Chapter 2.3.7 --- Determination of fecal neutral sterols --- p.37 / Chapter 2.3.8 --- Determination of fecal acidic sterols --- p.40 / Chapter 2.3.9 --- Statistics --- p.42 / Chapter 2.4 --- Results on intact male hamsters --- p.43 / Chapter 2.4.1 --- Diet composition --- p.43 / Chapter 2.4.2 --- Growth and food intake --- p.43 / Chapter 2.4.3 --- Organ weights --- p.43 / Chapter 2.4.4 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.43 / Chapter 2.4.5 --- Effect of calcium deficiency diet on hepatic cholesterol of hamsters --- p.44 / Chapter 2.4.6 --- Effect of calcium on fecal neutral sterol output --- p.48 / Chapter 2.4.7 --- Effect of calcium on fecal acidic sterol output --- p.48 / Chapter 2.5 --- Results on castrated hamsters --- p.50 / Chapter 2.5.1 --- Growth and food intake --- p.50 / Chapter 2.5.2 --- Organ weights --- p.50 / Chapter 2.5.3 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.50 / Chapter 2.5.4 --- Hepatic cholesterol --- p.50 / Chapter 2.5.5 --- Effect of calcium on fecal neutral sterol output --- p.53 / Chapter 2.5.6 --- Effect of calcium on fecal acidic sterol output --- p.53 / Chapter 2.6 --- Discussion --- p.55 / Chapter Chapter 3 --- Effect of Calcium Deficiency and Inadequacy on Blood Cholesterol Level in Intact Female and Ovariectomized Hamsters --- p.57 / Chapter 3.1 --- Introduction --- p.57 / Chapter 3.2 --- Objective --- p.58 / Chapter 3.3 --- Materials and methods --- p.59 / Chapter 3.3.1 --- Hamsters --- p.59 / Chapter 3.3.1.1 --- Intact female hamster --- p.59 / Chapter 3.3.1.2 --- Ovariectomized hamster --- p.60 / Chapter 3.3.2 --- Diets --- p.60 / Chapter 3.3.3 --- "Determination of serum lipid, lipoproteins and calcium concentration" --- p.60 / Chapter 3.3.4 --- "Determination of cholesterol concentration in organs, fecal neutral and acidic sterols" --- p.60 / Chapter 3.3.5 --- "Western blottting of liver SREBP-2, LDLR, HMGR, LXR and CYP7A1 proteins" --- p.61 / Chapter 3.3.6 --- Preparation of intestinal microsome --- p.62 / Chapter 3.3.7 --- Intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity measurement --- p.63 / Chapter 3.3.8 --- Statistics --- p.64 / Chapter 3.4 --- Results on intact female hamsters --- p.65 / Chapter 3.4.1 --- Growth and food intake --- p.65 / Chapter 3.4.2 --- Organ weights --- p.65 / Chapter 3.4.3 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.65 / Chapter 3.4.4 --- Effect of calcium deficiency diet on hepatic cholesterol of hamsters --- p.65 / Chapter 3.4.5 --- Effect of dietary calcium on fecal neutral sterol output --- p.66 / Chapter 3.4.6 --- Effect of dietary calcium on fecal acidic sterol output --- p.66 / Chapter 3.4.7 --- Effect of dietary calcium on liver LDLR immunoreactive mass --- p.71 / Chapter 3.4.8 --- Effect of dietary calcium on liver CYP7A1 immunoreactive mass --- p.71 / Chapter 3.4.9 --- Effect of dietary calcium on liver LXR immunoreactive mass --- p.71 / Chapter 3.4.10 --- Effect of dietary calcium on liver SREBP-2 immunoreactive mass --- p.71 / Chapter 3.4.11 --- Effect of dietary calcium on liver HMGR immunoreactive mass --- p.71 / Chapter 3.4.12 --- Effect of dietary calcium deficiency on intestinal ACAT activity --- p.77 / Chapter 3.5 --- Results on ovariectomized hamsters --- p.79 / Chapter 3.5.1 --- Growth and food intake --- p.79 / Chapter 3.5.2 --- Organ weights --- p.79 / Chapter 3.5.3 --- Effect of calcium deficiency diet on plasma lipid profile and calcium concentration of hamsters --- p.79 / Chapter 3.5.4 --- Hepatic cholesterol --- p.79 / Chapter 3.5.5 --- Effect of dietary calcium on fecal neutral sterol output --- p.80 / Chapter 3.5.6 --- Effect of dietary calcium on fecal acidic sterol output --- p.80 / Chapter 3.5.7 --- Effect of dietary calcium on liver LDLR immunoreactive mass --- p.85 / Chapter 3.5.8 --- Effect of dietary calcium on liver CYP7A1 immunoreactive mass --- p.85 / Chapter 3.5.9 --- Effect of dietary calcium on liver LXR immunoreactive mass --- p.85 / Chapter 3.5.10 --- Effect of dietary calcium on liver SREBP-2 immunoreactive mass --- p.85 / Chapter 3.5.11 --- Effect of dietary calcium on liver HMGR immunoreactive mass … --- p.85 / Chapter 3.6 --- Discussion --- p.91 / Chapter Chapter 4 --- Effect of Dietary Magnesium Supplementation on Blood Cholesterol Level in Intact Male Hamsters --- p.94 / Chapter 4.1 --- Introduction --- p.94 / Chapter 4.2 --- Objective --- p.96 / Chapter 4.3 --- Materials and methods --- p.97 / Chapter 4.3.1 --- Hamsters --- p.97 / Chapter 4.3.2 --- Diets --- p.98 / Chapter 4.3.3 --- "Determination of serum lipid, lipoproteins and magnesium concentration" --- p.100 / Chapter 4.3.4 --- "Determination of cholesterol concentration in organ, fecal neutral and acidic sterols" --- p.100 / Chapter 4.3.5 --- Statistics --- p.100 / Chapter 4.4 --- Results on male hamster --- p.101 / Chapter 4.4.1 --- Growth and food intake --- p.101 / Chapter 4.4.2 --- Organ weights --- p.101 / Chapter 4.4.3 --- Effect of dietary magnesium on plasma lipid profile and magnesium concentration in hamsters --- p.101 / Chapter 4.4.4 --- Effect of dietary magnesium on hepatic cholesterol of hamsters..… --- p.102 / Chapter 4.4.5 --- Effect of dietary magnesium on fecal neutral sterol output --- p.105 / Chapter 4.4.6 --- Effect of dietary magnesium on fecal acidic sterol output --- p.105 / Chapter 4.6 --- Discussion --- p.107 / Chapter Chapter 5 --- Conclusion --- p.110 / References --- p.113

Au Miocène (-25 à -5Ma) en Europe des changements climatiques entraînent des bouleversements dans les communautés de rongeurs (Mammalia), en particulier les Cricetinae. Une révision systématique des Democricetodon, utilisant une population actuelle d'Oryzomys comme modèle de variabilité morphologique, permet de proposer une phylogénie. L'étude du contour, en analyse de Fourrier, des molaires de trois lignées du genre Megacricetodon dans trois régions d'Europe montre des accélérations évolutives qui ne sont pas synchrones. L'étude de ces deux genres met en évidence l'importance des contextes géographique et climatique sur le dynamique des faunes de rongeurs. La distribution des espèces de rongeurs montre une différenciation biogéographique selon un gradient environnemental nord-sud succédant à un gradient géographique est-ouest. Cette étude démontre également que les changements intervenant à l'échelle des régions régulent la diversité à l'échelle du continental européen.

Cardiovascular disease (CVD) is a major health problem in developed countries and, with increasing prevalence in developing countries and Eastern Europe. Due to the increased incidence with advancing age, there is a need to develop primary preventive interventions to prolong the period of healthy life. Diet has a substantial influence on health and aging. The composition of the human diet plays an important role in the management of lipid and lipoprotein. In this respect, we have focused on the effects of two kinds of functional foods, tea seed oil and dietary onion on their hypocholesterolemic activities and underlying mechanisms in the present study. / Clearly, there are many claims on health benefits of Alliums , however, most, with the exception of garlic, have not received any rigorous or even gentle scientific investigation. Thus, the present study was carried out to explore hypocholesterolemic effects of onion supplementation. After fed for 2 weeks of the high fat high cholesterol diet, thirty-six 8-week male hamsters were divided into four groups. Control group was continued fed with high fat high cholesterol diet, while the other two experimental groups were fed control diet plus 1% (1OP) and 5% (5OP) onion powder for 8 weeks. It was found that feeding high dose of onion powder diet significantly prevented the increase in serum TC, Non-HDL-C and the ratio of non-HDL-C/HDL respectively in hamsters fed a 0.1% cholesterol diet. In contrast, the ratio of HDL/TC in high dose group was significantly increased than that in the control. Low onion dose group tended to have the similar effects as high dose group but, statistically, no difference was observed between the control and low dose groups. Besides, both doses of onion powder diets could significantly countered the increase in serum TG levels. High dose of onion supplementation tended to increase output of fecal neutral and acidic sterols, resulting in reduction of cholesterol retained and absorption. High dose of onion powder diet could significantly up- regulate SREBP-2, LXRbeta, and CYP7A1 protein expressions. The hypocholesterolemic activities of onion might due to the richness in alkyl and alkenyl sulfoxide compounds, anthocyanin, quercetin and cycloalliin, all of which have therapeutic effects. / In conclusion, diet plays an important role in reducing the risk of CVD. This has led to the search for specific foods and food components that may help to improve the serum lipoprotein profile. In present study, tea seed oil and onion was proved to help favorably modify the plasma lipoprotein profile, serving as health supplementation. However, their potential mechanisms were not fully studied and need to be further explored. / Interest in tea seed oil (named tea oil) as a cooking oil is increasing. However, its effect on blood cholesterol is not known. This study was therefore conducted to compare the hypocholesterolemic activity of tea oil with grape seed, canola and corn oils. Fifty 8-week-old male hamsters were first fed a high fat diet (5% lard), and supplemented with 0.1% cholesterol for 2 weeks and then divided into five groups. Control group was continuously fed high fat high cholesterol diet, while the experimental groups were fed high fat, high cholesterol diet plus 10% tea oil, grape seed oil, canola oil and corn oil for 12 weeks. Results showed that plasma total cholesterol (TC), non-HDL-cholesterol (non-HDL-C) and triacylglycerols (TG) in hamsters fed a 0.1% cholesterol diet containing tea, grape, canola or corn oil was significantly reduced compared with those in lard-fed group. Tea oil decreased only non-HDL-C and had no or little effect on HDL-C concentration, while grape oil reduced both. Besides, tea oil-fed hamsters excreted less neutral but greater acidic sterols compared with other three oils. Unlike grape oil, tea oil up-regulated sterol regulatory element binding protein (SREBP-2) and LDL receptor. Differences between tea oil and the tested vegetable oils could be attributable partially to >80% oleic acid in tea oil. / Guan, Lei. / Adviser: Chung Hau Yin. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 98-125). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Hippocampal mineralocorticoid receptor mRNA expression was increased in male hamsters exposed to 18 days of short photoperiod relative to animals maintained under long day illumination (p < 0.05). Short day hamsters were also characterized by increased weight gain, and heavier adrenal glands (p < 0.05). The larger adrenals showed selective increases in the widths of the zonae reticularis and glomerulosa (p < 0.001). Incidences of torpor and reduced body temperature were observed in the short day animals. No changes were found in reproductive organ weights, systolic blood pressure, open-field behavior, or stress levels of plasma corticosteroids. We conclude that the hamster brain-adrenal axis responds rapidly to changes in photoperiod, raising the possibility that this axis is a primary mediator of shortened photoperiod responses.

A doubly resonant cavity was used to search for nonlinear radiofrequency (RF) energy conversion in a range of biological preparations, thereby testing the hypothesis that living tissue can demodulate RF carriers and generate baseband signals. The samples comprised high-density cell suspensions (human lymphocytes and mouse bone marrow cells); adherent cells (IMR-32 human neuroblastoma, G361 human melanoma, HF-19 human fibroblasts, N2a murine neuroblastoma (differentiated and non-differentiated) and Chinese hamster ovary (CHO) cells) and thin sections or slices of mouse tissues (brain, kidney, muscle, liver, spleen, testis, heart and diaphragm). Viable and non-viable (heat killed or metabolically impaired) samples were tested. Over 500 cell and tissue samples were placed within the cavity, exposed to continuous wave (CW) fields at the resonant frequency (f) of the loaded cavity (near 883 MHz) using input powers of 0.1 or 1 mW, and monitored for second harmonic generation by inspection of the output at 2f. Unwanted signals were minimised using low pass filters (</= 1 GHz) at the input to, and high pass filters (>/= 1 GHz) at the output from, the cavity. A tuned low noise amplifier allowed detection of second harmonic signals above a noise floor as low as -169 dBm. No consistent second harmonic of the incident CW signals was detected. Therefore, these results do not support the hypothesis that living cells can demodulate RF energy, since second harmonic generation is the necessary and sufficient condition for demodulation.

No / The identification of an agent that is selectively activated by a cytochrome P450 (CYP) has the potential for tissue specific dose intensification as a means of significantly improving its therapeutic value. Towards this goal, we disclose evidence for the pathway of activation of a duocarmycin analogue, ICT2700, which targets CYP1A1 for biological activity.

No / We identify cytochrome P450 1A1 (CYP1A1) as a target for tumor-selective drug development in bladder cancer and describe the characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1. Elevated CYP1A1 expression was shown in human bladder cancer relative to normal human tissues. RT112 bladder cancer cells, endogenously expressing CYP1A1, were selectively chemosensitive to ICT2700, whereas EJ138 bladder cells that do not express CYP1A1 were significantly less responsive. Introduction of CYP1A1 into EJ138 cells resulted in 75-fold increased chemosensitivity to ICT2700 relative to wild-type EJ138. Negligible chemosensitivity was observed in ICT2700 in EJ138 cells expressing CYP1A2 or with exposure of EJ138 cells to CYP1B1- or CYP3A4-generated metabolites of ICT2700. Chemosensitivity to ICT2700 was also negated in EJ138-CYP1A1 cells by the CYP1 inhibitor alpha-naphthoflavone. Furthermore, ICT2700 did not induce expression of the AhR-regulated CYP1 family, indicating that constitutive CYP1A1 expression is sufficient for activation of ICT2700. Consistent with the selective activity by CYP1A1 was a time and concentration-dependent increase in gamma-H2AX protein expression, indicative of DNA damage, associated with the activation of ICT2700 in RT112 but not EJ138 cells. In mice-bearing CYP1A1-positive and negative isogenic tumors, ICT2700 administration resulted in an antitumor response only in the CYP1A1-expressing tumor model. This antitumor response was associated with detection of the CYP1A1-activated metabolite in tumors but not in the liver. Our findings support the further development of ICT2700 as a tumor-selective treatment for human bladder cancers.