Cholesterol lowering and the vessel wall: new insights and future perspectives.

The basis for most acute coronary events is either rupture or fissuring of unstable atherosclerotic plaques with subsequent thrombosis leading to coronary artery occlusion. The development of atherosclerotic plaques takes several decades, but the mechanical features determining its stability and the risk of rupture can change very rapidly depending on a number of internal factors. Unstable plaques have a large lipid core, a thin overlying fibrous cap and an abundance of inflammatory cells. The most important factor determining the plaque stability is the plasma level of atherogenic LDL particles. Increased levels of these particles cause endothelial dysfunction with impaired vasodilatation capacity and prevalence of vasoconstriction, maintain inflammatory infiltration of the plaque, impair the strength of the fibrous cap and facilitate aggregation and coagulation. Effective lowering of plasma cholesterol by pharmacological and non-pharmacological means can revert most of these processes and increase the plaque's mechanical stability within several hours to days. Lipid lowering therapy can therefore decrease the risk of acute coronary events within a very short space of time. Thus a radical decrease in lipid levels, along with modification of other risk factors, may become the cornerstone for treatment of acute coronary syndromes, in addition to being an effective treatment in primary and secondary prevention of coronary heart disease (CHD).     

Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome.

OBJECTIVE--To see if the claim that lowering cholesterol values prevents coronary heart disease is true or if it is based on citation of supportive trials only. DESIGN--Comparison of frequency of citation with outcome of all controlled cholesterol lowering trials using coronary heart disease or death, or both, as end point. SUBJECTS--22 controlled cholesterol lowering trials. RESULTS--Trials considered by their directors as supportive of the contention were cited almost six times more often than others, according to Science Citation Index. Apart from trials discontinued because of alleged side effects of treatment, unsupportive trials were not cited after 1970, although their number almost equalled the number considered supportive. In three supportive reviews the outcome of the selected trials was more favourable than the outcome of the excluded and ignored trials. In the 22 controlled cholesterol lowering trials studied total and coronary heart disease mortality was not changed significantly either overall or in any subgroup. A statistically significant 0.32% reduction in non-fatal coronary heart disease seemed to be due to bias as event frequencies were unrelated to trial length and to mean net reduction in cholesterol value; individual changes in cholesterol values were unsystematically or not related to outcome; and after correction for a small but significant increase in non-medical deaths in the intervention groups total mortality remained unchanged (odds ratio 1.02). CONCLUSIONS--Lowering serum cholesterol concentrations does not reduce mortality and is unlikely to prevent coronary heart disease. Claims of the opposite are based on preferential citation of supportive trials.     

Cholesterol and mortality in New Zealand Maoris.

The relation between serum cholesterol concentration and mortality was studied prospectively over 11 years in 630 New Zealand Maoris aged 25-74. Serum cholesterol concentration was measured at initial examination in 1962-3 in 94% of the subjects and whether each was dead or alive was determined in 1974. The causes of death were divided into three categories: cancer, cardiovascular disease, and "other." The Mantel-Haenszel method of analysis of survivorship data showed a significant inverse relation between serum cholesterol concentration and overall mortality in men (x 2/2 = 11.6; p = 0.003) and women (x 2/2 = 7.6; p = 0.02) with odds ratios of 2.3 and 1.9 respectively. Similar significant inverse relations were found for cancer and "other" causes of death. These relations remained significant when baseline age, systolic blood pressure, and the Quetelt index were controlled in Cox''s proportional hazards regression model. The results of this study provide evidence for a potentially deleterious effect of low serum cholesterol concentration. Hence, further research is needed before indiscriminate efforts are made to lower serum cholesterol concentrations in New Zealand Maoris.     

牛樟芝固态发酵产物的降胆固醇作用

本实验主要探究牛樟芝(S-29)固态发酵产物对高脂饮食小鼠胆固醇调节的影响。小鼠随机分为正常组、高脂模型组、护肝片阳性对照组、固态发酵组及液态发酵组;小鼠经高脂饲料喂养6周,相应物质灌胃4周。检测小鼠血清及肝脏相关指标; q-PCR检测胆固醇代谢相关基因的mRNA表达量。结果表明,与模型组比较,固态发酵组小鼠血清游离脂肪酸(NEFA)及谷丙转氨酶(ALT)浓度显著降低,分别降低了38. 5%和40. 7%;肝脏总胆固醇(TC)浓度显著降低,降低了23. 5%;低密度脂蛋白受体(LDL-R)的mRNA表达量显著增加,增加了3. 6倍。结果证明,牛樟芝固态发酵产物具有较好的降胆固醇作用,其主要机制可能是通过上调LDL-R基因的表达,以促进胆固醇的分解代谢,进而降低小鼠体内胆固醇浓度。     

Nicotinic acid reverses fasting ketosis by lowering the level of cyclic AMP.

When nicotinic acid was administered intraperitoneally to fasted rats, it reversed ketosis, decreased concentrations of cyclic AMP in adipose tissue and liver, and partially suppressed lipolysis. Administration of dibutyryl cyclic AMP reinduced ketosis in fasted rats previously treated with nicotinic acid. The results that nicotinic acid reverses ketosis by lowering tissue levels of cyclic AMP with a consequent suppression of lipolysis and ketogenesis.     

Ecological biogeography of southern ocean islands: the importance of considering spatial issues

Understanding patterns of among-island variation in species richness has long been an important question in ecology and biogeography. However, despite the clear spatial nature of the data used for such investigations, the spatial distribution of the different sampled locations is rarely explicitly considered, which may be critical for statistical and biological reasons. In a recent study, Chown et al. (1998) investigated the relationships between species richness of different indigenous and introduced taxonomic groups and a variety of variables characterizing Southern Ocean islands, and here, we use these data to address spatial issues. As predicted, we found spatial autocorrelation in species richness for terrestrial taxa with high dispersal ability or for terrestrial taxa that had time to disperse locally (introduced land birds and indigenous taxa) but not for taxa that had low opportunity to disperse to nearby islands (introduced plants, insects, and mammals), which suggests that colonization from nearby islands has played an important role in shaping present-day patterns of among-island variation in species richness. Interestingly, in several cases, the estimated effect of variables changed when spatial covariance was incorporated. Moreover, the absence of autocorrelation of some variables allowed us to confirm some important results of Chown et al. (1998), notably those involving the potential impact of human presence on the biodiversity of these islands. Overall, our results illustrate the importance of considering spatial structures in ecological studies. This is notably the case when dispersal processes can be expected to explain some of the observed patterns.     

Satiation of predispersal seed predators: the importance of considering both plant and seed levels

Plants can reduce the fitness costs of granivory by satiating seed predators. The most common satiation mechanism is the production of large crops, which ensures that a proportion of the seeds survive predation. Nevertheless, satiation of small granivores at the seed level may also exist. Larger seeds would satiate more efficiently, enhancing the probability of seed survival after having been attacked. However, a larger seed size could compromise the efficiency of satiation by means of large crops if there were a negative relationship between seed size and the number of seeds produced by an individual plant. We analyze both types of satiation in the interaction between the holm oak Quercus ilex and the chestnut weevil Curculio elephas. Both crop size and acorn size differed strongly in a sample of 32 trees. Larger crop sizes satiated weevils, and higher proportions of the seeds were not attacked as crop size increased. Larger seeds also satiated weevil larvae, as a larger acorn size increased the likelihood of embryo survival. Seedling size was strongly related to acorn size and was reduced by weevil attack, but seedlings coming from large weeviled acorns were still larger. The number and the size of the acorns produced by individual trees were negatively related. Larger proportions of the crop were infested in oaks producing less numerous crops of larger acorns. However, contrary to expectations, these trees did not satiate more effectively at the seed level either. Effective satiation by larger acorns was precluded by larger multi-infestation rates associated to smaller seed crops, in such a way that the proportion of attacked seeds that survived did not vary among trees with different acorn sizes. These results highlight the need of considering satiation by means of large crops and large seeds in studies of predispersal seed predation. Long-term monitoring on individual oaks will help to assess whether there is a trade-off between the number and the size of the acorns and, if it existed, how it could condition the fitness consequences of both types of satiation.     

Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group.

OBJECTIVE--To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. DESIGN--Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. SUBJECTS--Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. MAIN OUTCOME MEASURES--The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. RESULTS--Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. CONCLUSION--These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance.     

The importance of invertebrates when considering the impacts of anthropogenic noise

Anthropogenic noise is now recognized as a major global pollutant. Rapidly burgeoning research has identified impacts on individual behaviour and physiology through to community disruption. To date, however, there has been an almost exclusive focus on vertebrates. Not only does their central role in food webs and in fulfilling ecosystem services make imperative our understanding of how invertebrates are impacted by all aspects of environmental change, but also many of their inherent characteristics provide opportunities to overcome common issues with the current anthropogenic noise literature. Here, we begin by explaining why invertebrates are likely to be affected by anthropogenic noise, briefly reviewing their capacity for hearing and providing evidence that they are capable of evolutionary adaptation and behavioural plasticity in response to natural noise sources. We then discuss the importance of quantifying accurately and fully both auditory ability and noise content, emphasizing considerations of direct relevance to how invertebrates detect sounds. We showcase how studying invertebrates can help with the behavioural bias in the literature, the difficulties in drawing strong, ecologically valid conclusions and the need for studies on fitness impacts. Finally, we suggest avenues of future research using invertebrates that would advance our understanding of the impact of anthropogenic noise.     

Markov mortality models: implications of quasistationarity and varying initial distributions

This paper explains some implications of Markov-process theory for models of mortality. We show that an important qualitative feature common to empirical mortality data, and which has been found in certain models-the convergence to a "mortality plateau"-is, in fact, a generic consequence of the models' convergence to a "quasistationary distribution". This phenomenon has been explored extensively in the mathematical literature. Not only does this generalization free important results from specifics of the models, it also suggests a new explanation for the convergence to constant mortality. At the same time that we show that the late behavior of these models-convergence to a finite asymptote-is almost logically immutable, we also point out that the early behavior of the mortality rates can be more flexible than has been generally acknowledged. We show, in particular, that an appropriate choice of initial conditions enables one popular model to approximate any reasonable hazard-rate data. This illustrates how precarious it can be to read a model's vindication from its consilience with a favored hazard-rate function, such as the Gompertz exponential.     

Seeds in droppings of tropical fruit-eating birds: importance of considering seed composition

Summary The probability of interspecific seedling competition from bird droppings is high because fruit-eating birds, on average, deposit more than two species in a single dropping. Moreover, birds vary both in the number of plant species they deposit in a given dropping and in the seed composition of those droppings. In a preliminary experiment, I examined effects of interspecific seedling competition from seeds found in bird droppings. Certain plant species were competitively superior in pairwise growth experiments using six common second-growth species. The survival of certain shrubs depended on which species it was disseminated with in bird droppings. Rapid germination time may promote competitive superiority in some cases. Birds affect plant fitness not only because of their behavior following dispersal, but also because they deposit seeds in different densities and combinations.     

Cholesterol screening of children at high risk: behavioural and psychological effects

OBJECTIVE: To assess the behavioural and psychosocial effects of screening asymptomatic children at high risk for hyperlipidemia. DESIGN: Observational study involving prospective longitudinal and cross-sectional portions. SETTING: Two tertiary care pediatric lipid clinics in Montreal. SUBJECTS: Longitudinal portion: all children aged 4 to 17 years who presented for screening at the lipid clinics between April 1990 and June 1991. Of the 56 eligible children 52 (93%) (and their mothers) agreed to participate, 34 with hyperlipidemia (case subjects) and 18 without hyperlipidemia (control subjects). Thirty-five children (67%) completed 3 assessments over 12 months. Cross-sectional portion: all children aged 4 to 17 years in whom hyperlipidemia had been diagnosed 2 to 5 years earlier at one of the lipid clinics. Of the 58 eligible children 48 (83%) (and their mothers) participated. OUTCOME MEASURES: For children, mean scores on the Child Behavior Checklist (Behavior Problems subscale) (CBCL), the Children''s Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC); for mothers, mean scores on the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). RESULTS: In the longitudinal portion of the study, there was no significant difference between the case and control subjects in the mean CDI or STAIC scores at 1 or 12 months. At 1 month after diagnosis the case subjects in the longitudinal portion had a significantly higher mean CBCL score than the children in the cross-sectional component (p = 0.01). With the control group as the reference group, the adjusted odds ratios for a high CBCL score (greater than 62) for the case subjects were 15.5 (95% confidence interval [CI] 2.4 to 99.8) at 1 month and 15.8 (95% CI 1.1 to 223.4) at 12 months. The corresponding values for the children in the cross-sectional component were 1.3 (95% CI 0.3 to 6.2) and 5.0 (95% CI 0.5 to 50.9). CONCLUSIONS: The observed behavioural problems in children with a recent diagnosis of hyperlipidemia were independent of other risk factors, such as age and sex of child and mother''s age and BDI score. Our results suggest that identification of hyperlipidemia in children may have harmful psychological effects in the families involved. This evidence strengthens arguments for the exclusion of cholesterol measurement from the periodic health examination of children at moderately high risk.