Lipoprotein (a) metabolism estimated by nonsteady-state kinetics

Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL) particle with an additional apolipoprotein named apo(a). The concentration of Lp(a) in plasma is determined to a large extent by the size of the apo(a) isoform. Because elevated Lp(a) concentrations in plasma are associated with risk for premature coronary heart disease it is important to determine whether variations in production or catabolism mediate differences in Lp(a) concentration. We determined metabolic parameters of Lp(a) in 17 patients with heterozygous familial hypercholesterolemia or severe mixed hyperlipidemia by fitting a monoexponential function to the rebound of Lp(a) plasma concentration following LDL-apheresis. In 8 of those 17 patients this was done twice following two different aphereses. Although this approach allows one to estimate metabolic parameters without the use of a tracer, it requires several major assumptions such as that apheresis itself does not change production or catabolism of Lp(a) and that Lp(a) metabolism can be described by a single compartment. One apheresis decreased Lp(a) concentration by 59.1±8.3%. The fractional catabolic rate (FCR) was 0.16±0.12 d⁻¹ and production rate 6.27±5.26 mg·kg⁻¹·d⁻¹. However, observed (concentration before first apheresis) and predicted steady-state concentrations differed considerably (more than 20%) in 9 of 17 patients, indicating that not all assumptions were fulfille in all patients. Production rate but not FCR was correlated with Lp(a) plasma concentration (r ²=0.43. P=0.004) and molecular weight of apo(a) (r ²=0.48, P=0.011), which confirms radiotracer experiments showing that variations in Lp(a) plasma concentrations are due to differences in production not catabolism. When parameters were estimated tiwce in a subgroup of eight patients, satisfactory reproducibility was observed in six patients. Although parameters determined on two occasions correlated well, only FCR was concordant (intraclass correiation coefficient). Thus, despite the limitations arising from the assumptions implicit to this method, metabolic parameters of Lp(a) can be estimated from the rebound of plasma concentration following apheresis. Parts of this study were presented at the meeting of the International Atherosclerosis Society, Paris, October 5–9, 1997.     

Oxidized Lipoprotein(a) Increases Endothelial Cell Monolayer Permeability via ROS Generation

Oxidized lipoprotein(a) (oxLp(a)) is a more potent marker of atherogenesis than native Lp(a). However, the molecular mechanisms of oxLp(a) activity are not clear. Reactive oxygen species (ROS) have recently been suggested as acting as intracellular second messengers. In this study, the effects of oxLp(a) on endothelial cell monolayer permeability and the role of reactive oxygen species (ROS) generation in these effects were investigated. Our results showed that oxLp(a) inhibited desmoglein-1 (DSG1) and desmocollin-2 (DSC2) expression at both mRNA and protein levels in a dose- and time-dependent manner, and increased the generation of cellular ROS. Down-regulation of DSG1 and DSC2 was strengthened by pretreatment with H₂O₂ and attenuated by superoxide dismutase (SOD) treatment. Furthermore, oxLp(a) increased endothelial cell monolayer permeability, and this effect was enhanced by H₂O₂ and blunted by SOD. Taken together, these results demonstrate that oxLp(a) increases endothelial cell monolayer permeability, which is mediated at least in part via ROS generation.     

Serum Lipoprotein(a) Levels are Greater in Female than Male Patients with Type-2 Diabetes

Women with diabetes are faced with a higher risk of dyslipidemia and cardiovascular disorders than men with diabetes. We aimed to study the role of gender and menopausal status in serum Lp(a) levels in patients with type 2 diabetes. We quantified serum Lp(a) levels in a group of 477 patients with type 2 diabetes (men, premenopausal and postmenopausal women with diabetes), as well as in 105 controls. We stratified the patients into two groups of low Lp(a) levels (Lp(a) <35 mg/dl) and elevated Lp(a) levels (Lp(a) >35 mg/dl). Patients with diabetes had higher serum Lp(a) levels than the controls. Serum Lp(a) levels was significantly higher in women with diabetes than men with diabetes. Lp(a) levels did not differ between male and females in the control group. Premenopausal and postmenopausal women with diabetes did not differ significantly in serum Lp(a) levels. The odds ratio of having a serum Lp(a) level higher than 35 was 5.85 in premenopausal women with diabetes, 5.08 in postmenopausal women with diabetes, 2.41 in men with diabetes and 1.9 in the women in the control group compared to the men in the control group, after adjustment for age and BMI. This observational study clearly indicated that serum Lp(a) levels were significantly higher in women and men with diabetes. The increase in women was independent of menopause. The level of serum Lp(a) had no correlation with lipid parameters in men or women.     

Analysis of chemical signals in a primate species (Saguinus fuscicollis): Use of behavioral,chemical, and pattern recognition methods

Scent marking with specialized skin glands is a common behavior in the tamarin,Saguinus fuscicollis. The scent marks identify species, subspecies, gender, and individual, and they also contain information on the social position and hormonal condition of an animal. The marks are chemically complex, containing a large number of compounds. Analysis by means of gas chromatography-mass spectrometry has identified 16 major components (squalene and 15 esters of butyric acid). These compounds are present in the marks of males and females of two subspecies,Saguinus f. fuscicollis andSaguinus f. illigeri. Application of computerized pattern recognition techniques has shown that concentration patterns of some of the butyrates are diagnostic of the two subspecies while concentration patterns of other butyrates are diagnostic of males and females regardless of subspecies. Behavioral studies have shown that the concentration patterns of butyrates and squalene alone do not encode information on subspecies and gender. It is, however, likely that this information is partially encoded by these specific butyrate-squalene concentration patterns but that yet unidentified compounds in the scent marks serve as necessary synergists.     

Taste thresholds and suprathreshold responses to tannin-rich plant extracts and quinine in a primate species (Microcebus murinus)

Theories of plant chemical defenses discriminate between quantitative digestibility reducers (e.g., tannins) and qualitative toxins (e.g., alkaloids). Since the differential effect on taste of these compounds is poorly known, we recorded ingestive responses of a primate species, Microcebus murinus, to four tannin-rich plant extracts and to quinine, by using the behavioral method of the two-bottle test. The efficiency of tannic extracts at precipitating protein was measured with the blue BSA method. Inhibition taste thresholds for tannins added to a moderately sweet solution varied between 0.25 and 2 g/l. The threshold for quinine hydrochloride was 0.32 g/l. The profiles of the response/concentration curves established for these astringent and bitter substances were similar, with maximal inhibition of consumption occurring for near-threshold concentrations. The large amounts of quinine required to deter this small-bodied species from feeding were unexpected, given its unspecialized frugivorous/insectivorous diet. We propose that the taste responses of Microcebus to tannins have been shaped in relation to the widespread occurrence of efficient polyphenols in food plants, while low responsiveness to quinine reflects a low risk of ingesting toxic alkaloids when feeding on ripe fruits and insects.     

Analysis of unsteady solid-propellant combustion models (review)

Recent studies of solid-propellant combustion models are briefly analyzed. The models are divided into purely one-dimensional (classical and phenomenological models with various generalizations of the Zel’dovich approach) and non-one-dimensional. The latter include models with local non-one-dimensionality, which is always accompanied by local unsteadiness. This all can be eliminated by averaging. The main disadvantage of unsteady solid-propellant combustion models, which is no fault of their authors, is the same as in the case of steady-state models: the lack of detailed information on chemical and physical processes in the condensed phase. Impropriety of extending the purely one-dimensional approach to the instability region is noted. Possible directions for further development of unsteady (and quasi-steady-state) solid-propellant combustion models for homogeneous compositions may involve accounting for local non-one-dimensionality and the unsteadiness due to instability of the subsurface reactions zone and verification of the possibility of the existence of chemical instability capable of causing similar non-one-dimensionality and unsteadiness. __________ Translated from Fizika Goreniya i Vzryva, Vol. 44, No. 1, pp. 35–48, January–February, 2008.     

Photophysical models of aromatic polyesters: excited state interactions in bis(phenalkyl)terephthalate

Summary The nature of the excited state interactions in poly(ethylene terephthalate) is still subject to debate. We study a new series of model compounds composed of a central terephthaloyl group condensed with -hydroxy--phenyl-n-alkanes. Although the molecular architecture prevents these molecules from achieving symmetric ring-ring overlap, the steady-state fluorescence spectra are remarkably similar to those of other models studied earlier, where such overlap was expected. The solvent polarity dependence suggests that the excited state complex is an exciplex and not an excimer.     

The Effect of an Energy Restricted Low Glycemic Index Diet on Blood Lipids, Apolipoproteins and Lipoprotein (a) Among Adolescent Girls with Excess Weight: a Randomized Clinical Trial

Some studies focused on the effect of the dietary glycemic index on lipoproteins and apolipoproteins in adults; however, little evidence exists among adolescents regarding the effect of a low glycemic index (LGI) diet on apolipoproteins and lipoprotein (a) (Lpa). This study was conducted to evaluate the effect of an LGI diet on the lipid profile, apolipoproteins and Lpa among overweight and obese adolescent girls. For this parallel designed randomized clinical trial, 50 healthy overweight/obese girls at pubertal ages were randomly allocated to an LGI or a healthy nutritional recommendations (HNR) based diet. Equal macronutrient distributed diets were prescribed to both groups. Biochemical measurements included lipid profile, apolipoprotein A, apolipoprotein B and Lpa were conducted before and after 10 weeks of intervention. Forty one adolescent girls completed the study. The dietary glycemic index in the LGI group was 42.67 ± 0.067. There were no differences in the mean of blood lipid indices baseline and after intervention between two groups. There were no significant differences between the two groups regarding lipid profiles, apolipoproteins and Lpa. There were no significant differences in lipid profiles, apolipoproteins and Lpa between the LGI diet and the HNR-based diet and the impact of these two diets on lipid profile was equal in this trial. Trial registry code: IRCT201109272839N4.     

High Density Lipoprotein Level is Negatively Associated With the Increase of Oxidized Low Density Lipoprotein Lipids After a Fatty Meal

Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL‐specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) consumed a test meal (a standard hamburger meal) rich in lipid peroxides, and blood samples were taken before, 120, 240, and 360 min after the meal. The study subjects were divided into four subgroups according to the pre‐meal HDL cholesterol value (HDL subgroup 1, 0.66–0.91; subgroup 2, 0.93–1.13; subgroup 3, 1.16–1.35; subgroup 4, 1.40–2.65 mmol/L). The test meal induced a marked postprandial increase in the concentration of oxidized LDL lipids in all four subgroups. The pre‐meal HDL level was associated with the extent of the postprandial rise in oxidized LDL lipids. From baseline to 6 h after the meal, the concentration of ox‐LDL increased by 48, 31, 24, and 16 % in the HDL subgroup 1, 2, 3, and 4, respectively, and the increase was higher in subgroup 1 compared to subgroup 3 (p = 0.028) and subgroup 4 (p = 0.0081), respectively. The pre‐meal HDL correlated with both the amount and the rate of increase of oxidized LDL lipids. Results of the present study show that HDL is associated with the postprandial appearance of lipid peroxides in LDL. It is therefore likely that the sequestration and transport of atherogenic lipid peroxides is another significant mechanism contributing to cardioprotection by HDL.     

Lipoprotein lipase as a new tool in steryl ester analysis

A new method for the quantitative hydrolysis of steryl esters is described. Using lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 3.1.1.34), steryl esters are cleaved to yield free sterols and fatty acids. In comparison to alkaline hydrolysis, the method is more gentle, more accurate and less laborious. Quantification of the hydrolysis products was done with capillary gas chromatography. The practicability of the method is demonstrated for authentic steryl esters and steryl esters as they occur in needles of Scots pine (Pinus sylvestris L.).     

Local Likelihood for non‐parametric ARCH(1) models

Abstract. We propose a non‐parametric local likelihood estimator for the log‐transformed autoregressive conditional heteroscedastic (ARCH) (1) model. Our non‐parametric estimator is constructed within the likelihood framework for non‐Gaussian observations: it is different from standard kernel regression smoothing, where the innovations are assumed to be normally distributed. We derive consistency and asymptotic normality for our estimators and show, by a simulation experiment and some real‐data examples, that the local likelihood estimator has better predictive potential than classical local regression. A possible extension of the estimation procedure to more general multiplicative ARCH(p) models with p > 1 predictor variables is also described.     

Local asymptotic normality and efficient estimation for INAR(p) models

Abstract. Integer‐valued autoregressive (INAR) processes have been introduced to model non‐negative integer‐valued phenomena that evolve in time. The distribution of an INAR(p) process is determined by two parameters: a vector of survival probabilities and a probability distribution on the non‐negative integers, called an immigration distribution. This paper provides an efficient estimator of the parameters, and in particular, shows that the INAR(p) model has the Local Asymptotic Normality property.     

活性污泥模型(ASMs)研究进展及其发展前景

简述了活性污泥模型(ASMs)的发展历程,并对ASMs在实际中的应用、活性污泥中微生物动力学参数研究、活性污泥模型进水组分研究三个方面进行了综述,总结了活性污泥模型在实际中应用的局限性,最后对活性污泥的应用前景进行了展望。     

Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction

Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure-activity relationships. Significant correlations were observed between the number of -OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.     

Evaluation of a new organic azide: Hexakis(azidomethyl)benzene (HAB)

HAB is a thermally- and hydrolytically-stable solid, easily prepared from available raw materials. It is not highly sensitive to shock, friction, or electrostatic charge, but is sensitive to some types of impact, although not to others. It shows preliminary promise for possible use as a substitute for normal lead styphnate in less-sensitive bridgewire detonators, and as a substitute for tetracene in percussion detonators, e.g. the M-42 primer. Easy ignition, and a high burning rate without detonation, suggest application as an igniter. HAB is not sufficiently powerful to dent an aluminum witness block; therefore, it would not be suitable as a replacement for lead azide as an intermediate detonator charge.     

Ag44(SR)30(4-): a silver-thiolate superatom complex

Intensely and broadly absorbing nanoparticles (IBANs) of silver protected by arylthiolates were recently synthesized and showed unique optical properties, yet question of their dispersity and their molecular formulas remained. Here IBANs are identified as a superatom complex with a molecular formula of Ag(44)(SR)(30)(4-) and an electron count of 18. This molecular character is shared by IBANs protected by 4-fluorothiophenol or 2-naphthalenethiol. The molecular formula and purity is determined by mass spectrometry and confirmed by sedimentation velocity-analytical ultracentrifugation. The data also give preliminary indications of a unique structure and environment for Ag(44)(SR)(30)(4-).     

Chemical mimicry in a parasitoid (Hymenoptera: Eucharitidae) of fire ants (Hymenoptera: Formicidae)

A wasp (Orasema sp.) parasitic on the fire ant,Solenopsis invicta Buren, develops to the adult stage within the ant colony, where wasp larvae are ectoparasitic on ant pupae. This phase of the parasite's life cycle requires a mechanism of integration into the host colony. Gas Chromatographic profiles of hexane soaks of various stages of the parasite and host suggest that during development within the ant colony the parasite acquires the colony odor of the host through a passive mechanism, based on simple contact and other social interactions. No parasite-specific components were observed. After leaving the host nest as adults, the parasite biosynthesizes a parasite-specific cuticular compound, while retaining residual amounts of the host acquired components. This complicated scenario is consistent with current knowledge of nestmate recognition and the preferential treatment of ant workers to their brood.     

<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. l ‐Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of l ‐carnitine/simvastatin co‐administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low‐density lipoprotein cholesterol (LDL‐C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive l ‐carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the l ‐carnitine/simvastatin group [?19.4%, from 52 (20–171) to 42 (15–102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [?6.7%, from 56 (26–108) to 52 (27–93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL‐C, apolipoprotein (apo) B and TAG were observed in both groups. Co‐administration of l ‐carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels.