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Dietary non-digestible carbohydrates and the resistance to intestinal infections
Get PDFKeywords: Non-digestible carbohydrates, prebiotics, inulin, FOS, calcium, microflora, short-chain fatty acids, mucin, intestinal permeability, salmonella, infection, rat, humanDietary non-digestible carbohydrates and the resistance to intestinal infectionsNon-digestible carbohydrates (NDC) stimulate the protective gut microflora resulting in increased production of organic acids. This may result in increased luminal killing of acid-sensitive pathogens and hence reduce intestinal colonisation and translocation of a pathogen. However, host defence against invasive pathogens like salmonella also depends on the barrier function of the intestinal mucosa. High concentrations of organic acids may induce injury to the intestinal mucosa and impair the barrier function. The aim of this thesis was to determine the effects of NDC's on the intestinal barrier in rats and humans.In rats, well fermentable NDC (resistant starch, inulin, fructo-oligosaccharides and lactulose) stimulated the protective endogenous gut microflora and subsequently increased faecal lactate concentrations and lowered intestinal pH. However, in contrast to cellulose, wheat fiber and resistant starch, the rapid fermentable NDC inulin, fructo-oligosaccharides (FOS) and lactulose drastically stimulated mucosal translocation of invasive salmonella and the subsequent mucosal inflammation. Before infection, they increased luminal cytotoxicity and mucus secretion. This likely indicates that the fermentation-induced irritating luminal components can impair the intestinal barrier. Indeed, fermentable NDC increased intestinal permeability. Dietary calcium phosphate counteracted most adverse effects of well fermentable NDC. In humans, FOS also stimulated the endogenous gut microflora and increased faecal lactate concentrations. Moreover, FOS increased mucus secretion, indicating mucosal irritation. However, FOS consumption did not significantly affect luminal cytotoxicity and intestinal permeability.Stimulating the endogenous microflora by intestinal NDC fermentation is often assumed to be beneficial for intestinal health and resistance to infections. However, the work presented in this thesis does not support this concept
Mechanistic studies on the lipid-raising coffee diterpenes cafestol and kahweol in monkeys, mice and man
No full textCafestol and kahweol are lipid-raising diterpenes present in unfiltered coffee. The objective of this thesis was to study their lipid-raising action in man. Unravelling this action might lead to new insights into the regulation of serum cholesterol levels.We first studied the absorption and urinary excretion of cafestol and kahweol in eight ileostomy volunteers. About 70% of the consumed cafestol and kahweol was absorbed and thus available for raising serum lipids in humans. Only 1.2% of the diterpenes was subsequently excreted as a conjugate of glucuronic acid or sulphate in urine, suggestive for an extensive metabolism of coffee diterpenes.We then searched for an animal model to study the mechanism of action of cafestol and kahweol. In African green monkeys, both diterpenes raised total cholesterol less pronounced than in man. Unlike humans, the rise in cholesterol was predominantly due to a rise in HDL cholesterol rather than LDL cholesterol. In apolipoprotein E*3-Leiden mice, cafestol and kahweol increased total cholesterol with 61% after eight weeks of treatment. The increase in total cholesterol was mainly due to a rise in VLDL and IDL cholesterol. After three weeks of treatment, total cholesterol was increased due to suppression of bile acid synthesis, which caused a decreased expression of the LDL receptor. In addition, VLDL became enriched in cholesteryl esters.Two mechanistic studies were performed in healthy human subjects. Consumption of cafetiere (French-press) coffee increased CETP activity by 15% after 12 weeks of intervention. The increase in CETP activity clearly preceded the increase in LDL cholesterol. Cafestol increased serum triglycerides by an 80% increase in the production rate of VLDL 1 apolipoprotein B after two weeks of intervention. This resulted in an increased amount of VLDL 1 particles in the circulation. Cafestol did not change the composition of VLDL 1 . VLDL 2 became enriched with cholesteryl esters.In conclusion, cafestol first increases plasma triglycerides by increasing the production rate of VLDL 1 apolipoprotein B. The subsequent rise in LDL cholesterol might be due to suppression of bile acid synthesis, which probably leads to down-regulation of the LDL receptor and/or to an enrichment of VLDL 2 with cholesteryl esters. The mechanisms of action that raise plasma cholesterol and plasma triglycerides in humans might be regulated independently in the liver.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Influence of human diets containing casein, soy protein isolate, and soy protein concentrate on serum cholesterol and lipoproteins in humans, rabbits and rats
No full textIt is well known that feeding animals such as rabbits with semipurified diets containing animal proteins, as for example casein, results in hypercholesterolemia and atherosclerosis. On the other hand, diets containing vegetable proteins such as soybean protein maintain low levels of serum cholesterol. Little is known about the effects of the type of protein in the diet in humans.This thesis deals with the effects of casein and soy protein on serum cholesterol and lipoproteins, as observed in two experiments with human subjects and four experiments using animals. Three principle sources of protein were compared: caseinate; soy protein isolate, which is the purest soy protein preparation available commercially; and soy protein concentrate, a less refined soy protein preparation.In the first human experiment (Chapter 2), 69 young healthy students aged between 18 and 28 years were given for a period of 38 days diets containing 13% of energy as protein of which 65% consisted of protein from caseinate, or soy protein isolate, or a 2:1 mixture of caseinate and soy protein isolate. After a control period of 10 days during which all the subjects received the casein-soy diet, the subjects were divided into three groups, each group receiving one of the test diets for a test period of 28 days. In the second human experiment (Chapter 3), 57 healthy subjects aged between 29 and 60 years were given for a period of 45 days diets containing 16% of energy as protein of which 60% consisted of protein from caseinate, or soy protein isolate, or soy protein concentrate. After a control period of 17 days during which they received the casein diet, the subjects were divided into three groups, each group receiving one of the test diets for a test period of 28 days. Subjects in both studies were under strict dietary control. Apart from 0.5 MJ (120 kcal) per day in the first study and 1.0 MJ (240 kcal) per day in the second, all of the food eaten was supplied daily to the subjects in amounts appropriate to individual energy requirements. Food records and chemical analysis of the diets indicated that within each study, there were essentially no differences between the experimental diets except for the type of protein and/or the amount of non-protein material derived from the protein preparations. Blood samples were taken at the end of the control and test periods.During the experiments with human volunteers, two extra portions of each diet were collected. These were later homogenised and fed to animals in two experiments with rabbits and one with rats. A further experiment with rabbits was carried out using semipurified diets, the total protein content of which was test protein. The designs of the animal experiments were similar to those of the human experiments (Chapter 4).In the two human studies, there was no clear difference in response with respect to total serum cholesterol between the casein and the soy diets. A decrease in low-density-lipoprotein (LDL)- cholesterol and an increase in high-density-lipoprotein (HDL)- cholesterol were observed in those on the soy isolate diet when compared with those on the casein diet. The results on apolipoprotein-B and -A, suggest that the changes in cholesterol concentrations in the lipoprotein fractions resulted mainly from changes in the number of lipoprotein particles. However, these effects were only observed in those on the diets containing soy isolate and not in those on diets containing soy concentrate. With regard to the risk of coronary heart disease, the soy isolate diet can be considered to be beneficial, but the effects are small when compared with the effects of the fat composition and cholesterol content of the diet.The results of the animal studies using human diets confirm the results reported for semipurified diets. In rabbits, casein was found to be highly hypercholesterolemic when compared with the soy preparations, while in rats the effects were much smaller. The results stress the danger of extrapolating too readily from data from animal experiments on the effect of protein on serum cholesterol directly to man.Large decreases in level of serum cholesterol have been reported in hypercholesterolemic patients on diets containing soybean protein. Therefore, with regard to prevention of coronary heart disease, it has been suggested that animal protein in the diet should be replaced by vegetable protein. However, the results of the present studies with healthy subjects suggest that the normocholesterolemic human is probably relatively insensitive to the type of protein in his diet. It should be noted, however, that these experiments were of short duration and that the subjects were adults. Effects of a long-term intake of various proteins commencing at an early age have still to be determined.Although the effects of the type of protein are probably small in normocholesterolemic subjects, the replacement of foods containing animal protein with foods containing vegetable protein in the normal diet may still lead to changes in the concentration of serum lipids, because the main sources of animal protein are often also rich in saturated fat and cholesterol.In modifying the diet in order to influence certain physiological parameters, it should be realised that other parameters may also be affected (see Chapter 5). Caseinates are practically free of purines, while soy protein preparations like other protein sources such as meat. contain considerable amounts of purines. Uric acid is the end product of human purine metabolism and the subjects on the soy diets showed significantly higher levels of serum urate than the subjects on the casein diets. It is well known that the prevalence of gout is directly related to serum urate concentration
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
comparison of various cholesterol lowering diets in young healthy volunteers : effects on serum lipoproteins and on other risk indicators for cardiovascular diseases
No full textThis thesis deals with the effect of type and amount of dietary fat on the concentration and composition of serum lipoproteins, colonic function, plasma glucose and serum insulin levels and blood pressure in healthy human volunteers.Two experiments were carried out. In the first experiment with 60 volunteers a moderate fat diet with a high proportion of polyunsaturated fatty acids (as recommended by several advisory bodies), was compared with three other diets during a test period of 5 weeks. One diet was low in total fat with a low proportion of polyunsaturated fatty acids, one diet was high in total fat with a high proportion of polyunsaturated fatty acids and one was high in total fat with a low proportion of polyunsaturated fatty acids. In the second experiment with 35 volunteers the moderate fat diet rich in polyunsaturated fatty acids and the low fat, low polyunsaturated fatty acid diet were compared again, but this time the test period lasted 13 weeks. The diets were composed of regular foodstuffs and differed in carbohydrate and fat content or fatty acid composition only. There were only minor differences in intake of dietary fiber and other nutrients known to affect cholesterol metabolism. Subjects in both studies were under strict dietary control. All foodstuffs, except for 100 kcal (0,4 MJ) per day were supplied individually according to each person's energy need. Actual food intake was measured by food records and analysis of double portions. The fatty acid composition of cholesterol esters in serum was analysed in the second experiment in order to check adherence to the diets.The serum lipoprotein composition and concentration observed during the experiments are given in Chapters 2 and 3. In serum, total cholesterol , triglycerides, apolipoprotein-A I and -B were measured; in high-density-lipoprotein (HDL), cholesterol was measured; in low-density-lipoprotein (LDL), cholesterol and triglycerides were measured and in very-low-density-lipoprotein (VLDL), triglycerides, apolipoprotein-B and the apolipoprotein-C II /C III ratio were measured. From these experiments two conclusions can be drawn. Firstly, that both a low fat diet, low in polyunsaturated fatty acids and a moderate fat diet, high in polyunsaturated fatty acids lower total serum cholesterol levels when compared with the habitual diet of affluent communities. Secondly, that a low fat diet causes lower HDL-cholesterol and higher fasting VLDL-triglyceride levels than a moderate-fat diet, high in polyunsaturated fat.It is by no means certain that changes in the concentration of HDL and VLDL really result in changes in the risk of death from cardiovascular diseases. In long-term intervention trials, such a hypothesis has not been tested; only the effect of changes in serum total cholesterol has been studied in intervention trials.Chapter 4 deals with effects on colonic function. No changes in mean transit time through the gut, fecal wet and dry weight, frequency of stools and concentration of fecal steroids were found. This shows that the intake of dietary fiber had been roughly equal in all diet groups within each experiment. Because there were no consistent short- or long-term changes in fecal bile acid or neutral steroid excretion, it is concluded that changes at the intestinal level do not explain the changes in total serum cholesterol concentration.Chapter 5 gives the results of measurements of fasting and postprandial serum insulin and glucose concentrations. The results show, that neither the amount nor the type of dietary fat had a strong influence on these variables in healthy subjects.Chapter 6 describes the effect of type and amount of dietary fat on blood pressure as well as the effect of dietary fiber from various sources and type of protein. None of these dietary components had a demonstrable effect on blood pressure in young normotensive subjects.The results of these experiments do not call for changes in the dietary recommendations of the Netherlands Nutrition Council, as far as the risk of death from cardiovascular diseases is concerned.<p/
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Bioavailability of flavonoids and cinnamic acids and their effect on plasma homosysteine in humans
No full textDietary antioxidants might prevent oxidative damage to tissues and therefore protect against cardiovascular disease and cancer. Dietary phenols are strong antioxidants in vitro but their role in vivo is uncertain. Furthermore, there are only limited data on their bioavailability in humans. The aim of this thesis was to investigate whether bioavailability data on flavonoids and cinnamic acids support the hypothesis that they can affect health in humans . Because the group of phenols in foods is huge, we focussed our research on major phenols in foods; the flavonol quercetin, black tea phenols and chlorogenic acid (5-caffeoylquinic acid). We studied their bioavailability and effect on plasma homocysteine in humans, a potential risk factor for cardiovascular disease.The bioavailability of quercetin and chlorogenic acid depends upon their conjugated moieties. Hollman et al. found that the bioavailability of quercetin-3-rutinoside, a major flavonol in tea, was only 20% of that of quercetin-4'-glucoside. We found that transformation of quercetin-3-rutinoside into quercetin-3-glucoside will improve its bioavailability because the 3-glucoside had the same high bioavailability as the 4'-glucoside. Caffeic acid is a major phenol in coffee, but it is present as a conjugate with quinic acid, called chlorogenic acid. We found that the conjugation of caffeic acid with quinic acid hinders absorption in humans: absorption of chlorogenic acid was only 30% of that of its caffeic acid moiety.Furthermore, we found that chlorogenic acid, black tea solids and quercetin-3-rutinoside are extensively metabolized in the human body, mainly before they reach the circulation. Their metabolites have no, or less, antioxidant activity in vitro than their parent phenols. Therefore the role of dietary phenols as antioxidants in vivo might be less important than suggested by their in vitro antioxidant activity.Coffee consumption increases plasma homocysteine, a potential risk factor for cardiovascular disease. Chlorogenic acid from coffee is partly responsible for the homocysteine-raising effect of coffee, because we found that it increased plasma homocysteine. Black tea solids also raised plasma homocysteine, whereas quercetin-3-rutinoside did not. Furthermore, we found that glycination of metabolites of phenols in the body is not involved in the homocysteine-raising effect of phenols.In conclusion, chlorogenic acid, tea phenols and quercetin are available in the human body, but their effects on health are uncertain. Further research on bioavailability and health effects of dietary phenols is needed.</p
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