SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Kinetic aspects of cholesterol dynamics are described, with flux from the gut, to the liver, to the tissues, and back to the liver and gut, with a discussion of modifying mechanisms, synthesis, and transport. Overproduction of cholesterol, and bile acid and cholesterol malabsorption, are related to clinical problems.
Explore the source record for details and available documents.
M. leprae in the host multiplies abundantly in macrophages rich in cholesterol. Host-grown leprosy bacilli have an extremely high cholesterol content and in this respect they occupy a unique place among procariotic cells. M. leprae takes up cholesterol from the environment and it is not clear whether it can synthesize cholesterol and if so from which precursors. Mycobacteria can be grown from leprous tissues in primary cultures only in the presence of cholesterol. These strains quickly adapt to in vitro substrates and are able to synthesize cholesterol from still-unknown chemical entities, which are also sources of carbon and energy. These still unknown substrates will probably have to be discovered before cultivation of these elusive microorganisms is achieved and we approach a better understanding of the chemical mediators in the cellular defence and/or pathology of leprosy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and sterol and fatty acid synthesis from [1-14C]acetate and [2-14C]mevalonate were examined in the liver from fasted-refed rats. Rats fasted for 2 days were refed a fat-free diet or diets containing various fats (tricaprylin, trilaurin, trimyristin, tristearin, camellia oil, or safflower oil) at the 10% level for 1, 3, or 7 days. The activity of HMG-CoA reductase was restored to about one-half of the pre-fasting levels in all groups after refeeding for 1 day and increased to above the pre-fasting levels after 3 days, with the exception of safflower oil, the rise was especially noticeable when fat-free, tricaprylin, and tristearin diets were fed. After 7 days, the activity of HMG-CoA reductase, except for rats refed tristearin, was decreased to levels that were far below those observed after 1 day-refeeding. This was particularly marked with tricaprylin, trilaurin, and camellia oil. The response of sterogenesis resembled that of the reductase. Dietary fat-dependent modification of fatty acid synthesis from [1-14C]acetate was first demonstrated after 7 days. Hepatic esterified cholesterol tended to accumulate and the deposition was marked after 3 days of refeeding. However, fat-dependent alterations of this parameter were remarkable on day 7. The concentration of plasma cholesterol also showed dietary fat-dependent changes after refeeding. Dietary fats appear to play an important role not only in the regulation of hepatic HMG-CoA reductase and sterol synthesis, but also in the overall processes of cholesterol dynamics.
Explore the source record for details and available documents.
Functional dynamic studies of the adrenal in vivo employing 131I-19-cholesterol were carried out as a further screening test, according to the method previously described (Pavonia and Magrini, 1977), on seven patients in whom hyperadrenocorticism was suspected on the basis of clinical symptoms. The data obtained in basal conditions, under ACTH stimulation, and under dexamethasone suppression, compared with each other and supported by the results of conventional examinations, demonstrate that the quantitative information provided by this radioisotope test is correlated with the functional state of each adrenal, thus confirming the potential value of the method for diagnostic purposes. The functional dynamic test proposed does not require a higher dose of tracer than morphologic studies and the radiation risk (approximately 2.5 rad to the ovaries or gonads) seems acceptable in adult subjects.
In vivo grown M. lepraemurium suspensions were inoculated into a basal medium containing cholesterol and lecithin. Slow growing strains of mycobacteria were cultured regularly in these media. The presence of free cholesterol or cholesterol in serum or cholesterol in trypsin-digested egg yolk was essential for growth. The primary cultures were difficult to obtain, but the strains were easily subcultured. A heavy inoculum was necessary to obtain primary cultures in the liquid media, no growth occurred on semisolid agar slants. Similarly slow-growing primary cultures were obtained on Ogawa egg yolk media. Growth developed in a considerably shorter time if Ogawa's medium was enriched with 0.4% yeast extract (Difco). The cultures obtained on Ogawa egg yolk media were successfully subcultered in liquid cholesterol-lecithin media. The relation of the cultured strains of mycobacteria to the pathology of murine leprosy is not yet clear. The dynamics of cholesterol metabolism in the macrophages related to murine leprosy is discussed.
The dynamics of cholesterol-system in the plasma is characterized by a parameter which is a linear function of the internal secretion of cholesterol. So, the level of plasma cholesterol from synthesis is a low as its flow is high. Moreover, the level of plasma cholesterol from diet is simultaneously proportional to the flow of cholesterol intestinal absorption and dependent on the dynamics controlled by the internal secretion. The laws of the cholesterolemia cumulate these partial laws. Similar relations concern the esterified cholesterol in the liver.
Explore the source record for details and available documents.
Oriented dipalmitoyllecithin-cholesterol multibilayers with 11% water have been studied with the cholestane spin label. From the ESR spectra the order parameters and the mobility of the spin label about its long axis have been calculated. The results on pure lecithin multibilayers indicate a transition from gel to liquid crystalline phase at 52 plus or minus 2 degrees C. In the gel phase the lecithin alkyl chains are highly ordered, but tilted with respect to the normal to the bilayers by about 25 degrees. Above 52 degrees C the tilt disappears and the mobility of the cholestane spin label increases, indicating an increase of mobility of the lecithin alkyl chains. When cholesterol is added, below about 52 degrees C a decrease of order is found. Furthermore, already small cholesterol contents (smaller than or equal to 10 mole %) remove the tilt. Above about 52 degrees C cholesterol improves the order by decreasing the amplitude of the librational motions. Cholesterol lowers the transition temperature of the system and reduces the mobility of the lecithin alkyl chains in the liquid crystalline phase. However an increase in mobility is found at cholesterol contents up to 10 mole %. A very broad phase transition is observed at 50 mole % cholesterol. In all systems an increase in temperature results in a reduction of order through an increase of the amplitude of the librational motions of the molecules. The librational motions are to some extent cooperative. The asymmetry of the order matrix is found to be a measure for the lateral ordering. Cholesterol increases the lateral ordering, indicating that the flat cholesterol molecules orient parallel to each other.
Explore the source record for details and available documents.
During the past century, a variety of explanations have been proposed to explain the pathogenesis of cholesterol gallstones. Early attempts to account for the phenomenon of cholelithiasis focused on events in the gallbladder and stressed mucosal inflammatory changes, gallbladder stasis, stratification of bile, and absorption of bile salts from a damaged mucosa. The advent of the concept of "lithogenic bile" redirected attention to the liver and led to the proposal that an enzyme-mediated genetic and/or metabolic defect is the initiator of cholesterol cholelithiasis. While recognizing that the pathogenesis of gallstones is probably multifactorial, alterations in gallbladder and biliary ductal motor function constitute a plausible, but as yet unexplored, mechanism for alterations in enterohepatic circulation dynamics and subsequent cholesterol cholelithiasis. Gallbladder motor function is a complex phenomenon influenced by dynamic compliance, autonomic pharmacology, hormonal responses, and sphincter dynamics. Attempts to describe these aspects of biliary physiology may characterize the next phase in our understanding of the pathogenesis of cholesterol cholelithiasis.
Effects of cholesterol on the dynamic structure of the hydrocarbon region of dipalmitoyllecithin vesicles were examined. Decays of the emission anisotropy and the fluorescence intensity of 1,6-diphenyl-1,3,5-hexatriene embedded in lecithin-cholesterol vesicles were measured over a temperature range of 10--60 degrees C. The emission anisotropy decreased rapidly with time and then leveled off. The rotational motion of the probe was analyzed by a model of wobbling diffusion confined in a cone. Cholesterol (10--50 mol%) decreased the cone angle in the liquid-crystalline phase and increased it in the gel phase. In the presence of 33 mol% cholesterol, the wobbling diffusion constant increased in the gel phase and changed little in the liquid-crystalline phase. The viscosity in the cone decreased in the gel phase and remained almost unchanged in the liquid-crystalline phase in the presence of 33 mol% cholesterol. The total fluorescence intensity followed a singel exponential decay independently of the cholesterol content 0--50 mol%.
Cholesterol 24-hydroxylase (CYP46A1) regulates brain cholesterol homeostasis and synaptic plasticity, playing a crucial role in ischemic stroke. Although previous studies have reported post-ischemic CYP46A1 upregulation, its spatiotemporal dynamics remain poorly defined. To elucidate these dynamics, we investigated the expression of CYP46A1 and other essential cholesterol homeostasis-related genes from 6 h to 3 days after permanent middle cerebral artery occlusion (pMCAO) in CB-17 mice. We utilized single-cell and single-nucleus transcriptomics, regional quantitative PCR, and high-resolution immunohistochemistry. CYP46A1 is predominantly expressed in neurons. Following ischemia, the cholesterol network exhibited a dynamic spatiotemporal divergence. Acutely (6 h post-ischemia), surviving regions transiently upregulated cell-autonomous cholesterol synthesis genes and CYP46A1. Subacutely (3 days), this response shifted toward a widespread upregulation of glia-dependent cholesterol transport genes and general CYP46A1 downregulation. At 24 h, CYP46A1 protein was substantially reduced in the necrotic core and superficial layer II/III of the peri-infarct cortex, but upregulated in deeper layer V, hippocampus, and lateral striatum. Notably, this localized upregulation spatially coincided with reactive microglial hypertrophy. These findings indicate that CYP46A1 is dynamically modulated in viable tissues following ischemic stress. This spatial divergence likely reflects a synergistic interaction between inflammatory propagation and neural circuit-mediated oxidative stress. Resolving these spatiotemporal profiles provides a rigorous foundation for evaluating CYP46A1 functionality and developing stage-specific therapeutic interventions.
The rapid induction of cholesterol cholelithiasis in a new experimental model, the prairie dog, has recently been reported by two groups. In this model they were able to induce gallstones in as brief a period as 2 weeks, using a 1.2 per cent cholesterol diet. This unprecedented time intensity or telescoping of the induction process provided a unique opportunity for observation of physicochemical changes occurring rapidly over a short period of time and to correlate these with degree of biliary cholesterol saturation. To make such observations, 97 adult male and female prairie dogs were used in the present study. Seventy-two were fed the high cholesterol diet and sacrificed at intervals over a 14-day period; the remaining 25 were used as controls. The primary objective of this work was to determine whether or not there was any relationship between the in vivo events induced in prairie dog bile and our recently reported detailed observations of cholesterol precipitation phenomena in synthetic bile analogs. In these studies, solutions of physiologically relevant composition were constructed, which, when plotted according to convention on a tri-linear graph, fell within the zone of metastable or suspended supersaturation. These solutions revealed a consistent and previously undescribed liquid crystal to solid crystal phase transition during their approach to equilibrium at 37 degrees C. The in vivo studies of prairie dog bile following rapid induction of supersaturation revealed identical changes. At first, the supersaturated biles were isotropic followed by a period of turbidity and invariable formation of mesophase. After a few days, the liquid crystals decreased and solid cholesterol crystallites appeared. The most striking aspect of these observations is that the in vitro work has now predicted not only static, but dynamic processes as well, with respect to cholesterol precipitation beginning with the metastably supersaturated state and eventuating in gallstone formation. Ancillary new findings, resulting from the high cholesterol diet, included the induction of human-like hyper-beta-lipoproteinemia and rapid hepatocyte degranulation shown by electron microscopy.
Cholesteryl-phosphoryl-choline (CPC), a hybrid between cholesterol and lecithin, is incorporated into sonicated liposomes and erythrocyte membranes similarly to cholesterol. The effect of CPC on lipid microviscosity and degree of order is smaller, but not significantly than that of cholesterol. It is proposed that CPC may be employed as an efficient modulator of lipid dynamics.