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Estimation of CHD risk in a French working population using a modified Framingham model. The PCV-METRA Group.

We adapt a recent model from the Framingham study (Circulation 1991; 83: 356-362) to predict CHD in France for both sexes over a large age range. Calculations were based on data from the French PCV-METRA study. In France, the Paris Prospective Study model could predict CHD but only for men aged 43-53 years. Applied to men 43-53 years from the PCV-METRA, the Framingham model estimated a 5-year CHD risk (4%) lower than the risk reported in the Framingham sample, but significantly higher than the risk estimated by the French model (2%). Differences in estimated CHD risk between the Framingham and the PCV-METRA samples were explained for only 30% by adjustment on major CHD risk factors (mainly HDL-cholesterol and tobacco). Modifying the intercept in the Framingham model, agreement with estimated risk by the French model was improved from 29 to 80%. By an appropriate change of the intercept, the Framingham model might be used to estimate CHD risk in other populations.

Adult↗

Kinetic evidence for separate 3 beta-hydroxysteroid dehydrogenase-isomerases in androgen and 16-androstene biosynthetic pathways in the pig testis.

The microsomal fraction from the testes of immature pigs (less than 1 week old) contains 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-isomerase) activities that convert dehydroepiandrosterone (DHA) to 4-androstenedione and 5,16-androstadien-3 beta-ol (andien-beta) to 4,16-androstadien-3-one (dienone). These reactions are necessary for the biosynthesis of hormonally and pheromonally active steroids. Kinetic analyses of these activities were done to determine whether they are catalysed by a single enzyme or if there is any interaction between the substrates and products of one reaction on the activity of the other enzyme. Kinetic parameters were determined and the affinities for steroid substrate were similar (7-9 mumol/l) but the Vmaxapp value for the conversion of andien-beta to dienone was 10-fold that of the DHA to 4-androstenedione reaction. In analyses of the conversion of DHA to 4-androstenedione, neither andien-beta nor dienone inhibited the reaction and especially, no effect on the Kmapp for DHA was observed which would have indicated competition between DHA and andien-beta for the same active site (Kiapp from slope and intercept replots were between 3 and 80 times the values of the kinetic constants). Similarly, DHA and 4-androstenedione had minor or negligible effects on the conversion of andien-beta to dienone (Kiapp from slope replots were the same as the Kmapp but the Kiapp from the intercept replot was 12 to 25% of the Vmaxapp). It is concluded that substrate specific 3 beta-HSD-isomerases for andien-beta and DHA exist in the immature pig testis and there is little, if any interaction between these enzymes.

Androgens↗

Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis.

3 beta-Hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) activity in the pig testis is responsible for the conversion of dehydroepiandrosterone (DHA) to 4-androstenedione and also for the conversion of 5,16-androstadien-3 beta-ol (andien-beta) to 4, 16-androstadien-3-one (dienone). Therefore, 3 beta-HSD-I plays an essential role in the biosynthesis of hormonally and pheromonally active steroids. Previous studies from this laboratory have suggested that the 3 beta-HSD-I reactions in the androgen and 16-androstene biosynthetic pathways may be catalysed by different enzymes with selective substrate specificities [3, 4]. The aim of the present studies was to investigate the reactions further by examining the effects of two classical steroidal inhibitors of 3 beta-HSD-I, trilostane (WIN 24540) and cyanoketone (WIN 19578), on the kinetic parameters of the 3 beta-HSD-I reactions in immature (< 3 weeks) pig testis microsomes. In kinetic analyses of the conversion of DHA to 4-androstenedione, both trilostane and cyanoketone caused increases in the Km(app) for DHA which at the highest concentration used, were 15-fold the control Km(app) of 1.4 mumol/l. No effect on the Vmax(app) (6.55 +/- 0.74 nmol/h/mg protein) was observed, demonstrating that competitive inhibition was evident. Slope and intercept replots confirmed the competitive nature of the inhibition and Ki(app) values of 0.16 mumol/l for trilostane and 0.20 mumol/l for cyanoketone were respectively 9 and 7-fold lower than the Km(app) value. In contrast, trilostane and cyanoketone had no effect on the Km(app) for andien-beta (0.26 mumol/l). The Vmax(app) (1.12 nmol/h/mg protein) was decreased by 40-50% only by trilostane at the highest concentration used, demonstrating a very low affinity for the andien-beta active site. Ki(app) values for trilostane and cyanoketone, obtained from slope and intercept replots were, respectively 1.1 and 1.6 mumol/l, which were 4 and 6-fold greater than the Km(app) for andien-beta. Therefore, trilostane and cyanoketone were powerful competitive inhibitors of the conversion of DHA to 4-androstenedione but were weak non-competitive inhibitors of the conversion of andien-beta to dienone. The selective effects of trilostane and cyanoketone on the 3 beta-HSD-Is involved in the androgen and 16-androstene biosynthetic pathways strongly suggest that the reactions are catalysed by separate enzymes, or at least separate, non-interacting active sites on a single enzyme.

Androstadienes↗

Left ventricular ejection fraction: single-plane and multiplanar transesophageal echocardiography versus equilibrium gated-pool scintigraphy.

The relative accuracy and precision of estimating left ventricular ejection fraction (EF) in dogs were assessed by two-dimensional transesophageal echocardiography (2D-TEE) and by three-dimensional transesophageal echocardiographic (3D-TEE) imaging and reconstruction. This assessment was accomplished by comparing each echocardiographic method to a gated equilibrium blood pool radionuclide (RN) standard. By using both correlation and regression analysis, 2D-TEE performed reasonably well in estimating RNEF (correlation coefficient [r] = 0.80, slope = 1.01, intercept = 6.37, standard error of the estimate [SEE], 8.98), but not as well as 3D-TEE (r = 0.86, slope = 0.83, intercept = 3.38, SEE, 5.74). Using Altman and Bland's methods of comparison analysis, it was found that 2D-TEE overestimated RNEF by 7% (standard deviation [SD], 8.8). This degree of overestimation was not consistent across the range of measurement. In contrast, 3D-TEE slightly underestimated RNEF by less than 3% and showed less variability (SD, 6.0). The accuracy of the 3D-TEE determinations was not dependent on the magnitude of EF. Additionally, a significantly higher proportion of the 2D-TEE measurements (0.30) compared with the 3D-TEE measurements (0.10) differed from RN values by more than 10% (P = 0.009, McNemar's test). At the clinically important low end of the EF range (RNEF less than or equal to 35%), 2D-TEE may be expected (with 95% confidence) to be within -15% to +28% EF of reference values, whereas 3D-TEE can be expected to be within -8% to +5% EF relative to RN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cross-cultural validity of the food-related lifestyles instrument (FRL) within Western Europe.

The food-related lifestyle instrument (FRL) was tested for its validity across food cultures in Western Europe. First, responses from samples of 1000 or more consumers from each of Denmark, France, Germany, Spain and the UK were compared using multi-sample confirmatory factor analysis with structured means. The loadings, covariances and variances of the factors were invariant across countries, although item intercepts and error variances were not. In the second part of the analysis, replication samples (also Ns of 1000 or more) from France, Germany and the UK were examined for intra-cultural stability using the same statistical models. The factorial structure was completely invariant over time in three of five FRL domains, and subject to only minor variations in the other two domains. In the third part of the analysis, a revised version of the FRL was tested for cross-cultural validity, using consumer samples of 1000 each from France and the UK. This version of the FRL was also cross-culturally valid in factor loadings, covariances and variances, but still subject to variation between countries in item intercepts and error variances.

Adult↗

Effect of inhibition of multiple steps of angiogenesis in syngeneic murine pleural mesothelioma.

BACKGROUND: Angiogenesis is a multistep process in which the endothelial cell plays a pivotal role. We hypothesized that the combination of two antiangiogenic agents with distinct mechanisms of action would more effectively inhibit tumor growth than either agent alone in a murine mesothelioma model. METHODS: A syngeneic murine mesothelioma flank tumor model (AB-12) was established in BALB/c mice. Separate adenovirus vectors expressing the cDNAs for human pigment epithelium-derived factor (AdPEDF) and a soluble form of the human vascular endothelial growth factor receptor-1 (Adsflt-1) were administered intratumorally. End points measured included tumor size, animal survival, and microvessel density using CD31 immunohistochemistry. An orthotopic model of mesothelioma was established by implanting AB-12 cells into the murine pleural cavity. Simultaneously, AdPEDF and Adsflt-1 were instilled intrapleurally and tumor burden and survival were recorded. The development of pulmonary emphysema was also assessed by calculating the mean linear intercept (a measure of interalveolar septal distance) in histologic lung sections from tumor-free mice after vector administration. RESULTS: In the flank tumor model, the combination of AdPEDF and Adsflt-1 inhibited tumor growth, prolonged survival, and decreased microvessel density more profoundly compared with either AdPEDF or Adsflt-1 alone. In the orthotopic model, the combination was also more effective in prolonging survival. Intrapleural AdPEDF or Adsflt-1 did not increase the mean linear intercept compared with controls in tumor-free mice. CONCLUSIONS: In this murine model, inhibiting multiple mechanisms of angiogenesis using two agents is a more effective antineoplastic strategy than using either agent alone. In addition, instillation of antiangiogenic gene transfer vectors into the pleural space does not result in histologic evidence of pulmonary emphysema.

Angiogenesis Inhibitors↗

Frequency response characteristic of sympathetic mediated low-frequency blood pressure fluctuations in conscious rats.

A quantitative relationship between power densities of blood pressure (PBP) and sympathetic nerve activity (PSNA) in a low-frequency range (LF, 0.016-0.85 Hz), expressed as PSNA=PBPxax10bx(frequency) was proposed in pentobarbital-anesthetized rats. For evaluating the general applicability of this equation, the quantitative relationship of power density ratio Hf=PBP/PSNA across frequency was tested in a conscious state. Wistar rats were chronically instrumented with a femoral artery catheter and recording electrode around the renal sympathetic nerve. The blood pressure and renal sympathetic nerve activity were monitored both under pentobarbital anesthesia and in a conscious state. Linear regression analysis of the relationship between the frequency and logarithmic magnitude of the power density ratio in the LF range revealed excellent fit in both conditions (r=-0.96+/-0.01 and -0.93+/-0.01 for anesthetized and conscious rats, respectively). Comparing the regression lines, rats under pentobarbital anesthesia had significantly larger values for the y-intercept and slope compared to rats in a conscious state (y-intercepts: 0.80+/-0.09>0.53+/-0.08; slopes: -2.86+/-0.26>-1.62+/-0.21). Our results demonstrate that it is also feasible to use the weighted PBP in LF as a quantitative index of sympathetic variability in conscious rats, but the evaluation of possible complications controlling the regression parameters is called for.

Action Potentials↗

Merocyanine 540-sensitized photokilling of leukemia cells: role of post-irradiation chain peroxidation of plasma membrane lipids as revealed by nitric oxide protection.

The lipophilic dye merocyanine 540 (MC540) localizes primarily in the plasma membrane (PM) of tumor cells, where it can sensitize lethal photoperoxidative damage of potential therapeutic importance. We postulated (i) that chain peroxidation triggered by iron-catalyzed turnover of nascent hydroperoxides (LOOHs) generated by singlet oxygen ((1)O(2)) attack on PM lipids contributes significantly to overall cytolethality, and (ii) that nitric oxide (NO), a known scavenger of organic free radicals, would suppress this and, thus, act cytoprotectively. In accordance, irradiation of MC540-sensitized L1210 cells produced 5alpha-OOH, a definitive (1)O(2) adduct of PM cholesterol, which decayed during subsequent dark incubation with appearance of other signature peroxides, viz. free-radical-derived 7alpha/beta-OOH. Whereas chemical donor (SPNO or SNAP)-derived NO had little or no effect on post-irradiation 5alpha-OOH disappearance, it dose-dependently inhibited 7alpha/beta-OOH accumulation, consistent with interception of chain-carrying radicals arising from one-electron reduction of primary LOOHs. Using [(14)C]cholesterol as an L1210 PM probe, we detected additional after-light products of chain peroxidation, including diols (7alpha-OH, 7beta-OH) and 5,6-epoxides, the yields of which were enhanced by iron supplementation, but strongly suppressed by NO. Correspondingly, photoinitiated cell killing was significantly inhibited by NO introduced either immediately before or after light exposure. These findings indicate that prooxidant LOOH turnover plays an important role in photokilling and that NO, by intercepting propagating radicals, can significantly enhance cellular resistance.

Animals↗

Relationship between compressive properties of human os calcis cancellous bone and microarchitecture assessed from 2D and 3D synchrotron microtomography.

The aim of this study was to determine the contribution of 2D and 3D microarchitectural characteristics in the assessment of the mechanical strength of os calcis cancellous bone. A sample of cancellous bone was removed in a medio-lateral direction from the posterior body of calcaneus, taken at autopsy in 17 subjects aged 61-91 years. The sample was first used for the assessment of morphological parameters from 2D morphometry and 3D synchrotron microtomography (microCT) (spatial resolution=10 microm). The 2D morphometry was obtained from three slices extracted from the 3D microCT images. Very good concordance was shown between 3D microCT slices and the corresponding physical histologic slices. In 2D, the standard histomorphometric parameters, fractal dimension, mean intercept length, and connectivity were computed. In 3D, histomorphometric parameters were computed using both the 3D mean intercept length method and model-independent techniques. The 3D fractal dimension and the 3D connectivity, assessed by Euler density, were also evaluated. The cubic samples were subjected to elastic compressive tests in three orthogonal directions (X, Y, Z) close to the main natural trabecular network directions. A test was performed until collapse of trabecular network in the main direction (Z). The mechanical properties were significantly correlated to most morphological parameters resulting from 2D and 3D analysis. In 2D, the correlation between the mechanical strength and bone volume/tissue volume was not significantly improved by adding structural parameters or connectivity parameter (nodes number/tissue volume). In 3D, one architectural parameter (the trabecular thickness, Tb.Th) permitted to improve the estimation of the compressive strength from the bone volume/tissue volume alone. However, this improvement was minor since the correlation with the BV/TV alone was high (r=0.96). In conclusion, which is in agreement with the statistic's rules, we found, in this study, that the determination of the os calcis bone compressive strength using the 3D bone volume fraction cannot be improved by adding 3D architectural parameters.

Aged↗

Quantitative analysis of delta9-tetrahydrocannabinol in preserved oral fluid by liquid chromatography-tandem mass spectrometry.

A rapid and sensitive method for the analysis of delta9-tetrahydrocannabinol (THC) in preserved oral fluid was developed and fully validated. Oral fluid was collected with the Intercept, a Food and Drug Administration (FDA) approved sampling device that is used on a large scale in the U.S. for workplace drug testing. The method comprised a simple liquid-liquid extraction with hexane, followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Chromatographic separation was achieved using a XTerra MS C18 column, eluted isocratically with 1 mM ammonium formate-methanol (10:90, v/v). Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions. The use of the liquid-liquid extraction was demonstrated to be highly effective and led to significant decreases in the interferences present in the matrix. Validation of the method was performed using both 100 and 500 MicroL of oral fluid. The method was linear over the range investigated (0.5-100 ng/mL and 0. 1-10 ng/mL when 100 and 500 microL, respectively, of oral fluid were used) with an excellent intra-assay and inter-assay precision (relative standard deviations, RSD <6%) for quality control samples spiked at a concentration of 2.5 and 25 ng/mL and 0.5 and 2.5 ng/mL, respectively. Limits of quantification were 0.5 and 0.1 ng/mL when using 100 and 500 microL, respectively. In contrast to existing GC-MS methods, no extensive sample clean-up and time-consuming derivatisation steps were needed. The method was subsequently applied to Intercept samples collected at the roadside and collected during a controlled study with cannabis.

Body Fluids↗

Determination of lanthanides in international geochemical reference materials by reversed-phase high-performance liquid chromatography using error propagation theory to estimate total analysis uncertainties.

The weighted least-squares (WLS) regression method was successfully applied to establish calibration curves with variable amounts of lanthanides ranging from 0.002 to 0.430 microg. These curves were employed for the analysis of 13 lanthanides (La-Nd, Sm-Tb, and Ho-Lu) in 12 international geochemical reference materials (IGRM). The separation of the lanthanide group was achieved in approximately 15 min. Dysprosium could not be determined in IGRM because of its co-elution with Yttrium. A linear gradient program of alpha-HIBA eluent with a concentration ranging from 0.05 to 0.5 M (0.1 M OS, pH 3.8 with NH(4)OH, and a flow-rate of 1.0 ml/min) was employed. The detection was performed with a UV-vis system at 658 nm using a post-column reagent of Arsenazo III (0.5 ml/min). With this set of RP-HPLC conditions together with the use of both the ordinary least-squares (OLS) and the WLS regressions, we report the results of the measurements along with the total propagated uncertainties in individual concentration values. The uncertainties were obtained by combining standard errors in both regression parameters (slope and intercept) with those related to the chromatographic peak areas. The straight-line slopes and intercepts calculated by the WLS method provided not only considerably smaller errors than the conventional OLS method but also a much better estimation of the limits of detection. The concentrations calculated were compared with the "most probable" concentration values of these reference materials reported in the literature. Statistically significant agreement was consistently observed between the HPLC data and the literature values. The total uncertainties in estimated concentration values for the WLS were consistently smaller than the respective errors for the OLS.

Algorithms↗

Hansen solubility parameters for polyethylene glycols by inverse gas chromatography.

Inverse gas chromatography (IGC) has been applied to determine solubility parameter and its components for nonionic surfactants--polyethylene glycols (PEG) of different molecular weight. Flory-Huggins interaction parameter (chi) and solubility parameter (delta(2)) were calculated according to DiPaola-Baranyi and Guillet method from experimentally collected retention data for the series of carefully selected test solutes. The Hansen's three-dimensional solubility parameters concept was applied to determine components (delta(d), delta(p), delta(h)) of corrected solubility parameter (delta(T)). The molecular weight and temperature of measurement influence the solubility parameter data, estimated from the slope, intercept and total solubility parameter. The solubility parameters calculated from the intercept are lower than those calculated from the slope. Temperature and structural dependences of the entopic factor (chi(S)) are presented and discussed.

Chromatography, Gas↗

Isometric shoulder muscle activation patterns for 3-D planar forces: a methodology for musculo-skeletal model validation.

OBJECTIVE: To present an isometric method for validation of a shoulder model simulation by means of experimentally obtained electromyography and addressing all muscles active around the shoulder joints. BACKGROUND: Analysis of muscle force distribution in the shoulder by means of electromyography during motion tasks is hampered by artificial and non-linear amplitude modulation and is often limited to downward directed external forces. This application of EMG is therefore inadequate and insufficient for the validation of shoulder model simulations. We suggest an isometric method including multi-directional forces to overcome these problems. METHODS: A force with constant magnitude is actively rotated stepwise in 20 directions perpendicular around the arm while kept in one position. The isometric muscle activation (EMG) is a function of the clockwise-rotated force angle, characterized by baseline activation, and a section of increased muscle activation characterized by baseline interception and direction and magnitude of maximum muscle activation. Comparison of the parameterized muscle activation with predicted muscle forces from model simulation illustrates the applicability for musculo-skeletal model validation. RESULTS: All recorded shoulder muscles were active over a section of force angles of at least 180 degrees. Some muscles demonstrated two activation sections. The estimated model sensitivity for the baseline interception was SD=5 degrees -10 degrees. The Principal Action was the most reliable parameter (SD=4 degrees ). A correlation of 0.778 was observed between model simulations and EMG recordings. CONCLUSIONS: The methodology addresses all shoulder muscles over a substantial section of planar force directions. This enables the comparison of experimentally determined direction of activation on- and offset and direction of maximum activation with equivalent muscle forces, predicted from model simulation.

Algorithms↗

Development of a population pharmacokinetic model for carbamazepine based on sparse therapeutic monitoring data from pediatric patients with epilepsy.

BACKGROUND: Population models can be important extensions of therapeutic drug monitoring (TDM), as they allow estimation of individual pharmacokinetic parameters based on a small number of measured drug concentrations. OBJECTIVE: This study used a Bayesian approach to explore the utility of routinely collected and sparse TDM data (1 sample per patient) for carbamazepine (CBZ) monotherapy in developing a population pharmacokinetic (PPK) model for CBZ in pediatric patients that would allow prediction of CBZ concentrations for both immediate- and controlled-release formulations. METHODS: Patient and TDM data were obtained from a pediatric neurology outpatient database. Data were analyzed using an iterative 2-stage Bayesian algorithm and a nonparametric adaptive grid algorithm. Models were compared by final log likelihood, mean error (ME) as a measure of bias, and root mean squared error (RMSE) as a measure of precision. RESULTS: Fifty-seven entries with data on CBZ monotherapy were identified from the database and used in the analysis (36 from males, 21 from females; mean [SD] age, 9.1 [4.4] years [range, 2-21 years]). Preliminary models estimating clearance (Cl) or the elimination rate constant (K(el)) gave good prediction of serum concentrations compared with measured serum concentrations, but estimates of Cl and K(el) were highly correlated with estimates of volume of distribution (V(d)). Different covariate models were then tested. The selected model had zero-order input and had age and body weight as covariates. Cl (L/h) was calculated as K(el) . V(d), where K(el) = [K(i) - (K(s) . age)] and V(d) = [V(i) + (V(s) . body weight)]. Median parameter estimates were V(i) (intercept) = 11.5 L (fixed); V(s) (slope) = 0.3957 L/kg (range, 0.01200-1.5730); K(i) (intercept) = 0.173 h(-1) (fixed); and K(s) (slope) = 0.004487 h(-1) . y(-1) (range, 0.0001800-0.02969). The fit was good for estimates of steady-state serum concentrations based on prior values (population median estimates) (R = 0.468; R(2) = 0.219) but was even better for predictions based on individual Bayesian posterior values (R(2) = 0.991), with little bias (ME = -0.079) and good precision (RMSE = 0.055). CONCLUSIONS: Based on the findings of this study, sparse TDM data can be used for PPK modeling of CBZ clearance in children with epilepsy, and these models can be used to predict Cl at steady state in pediatric patients. However, to estimate additional pharmacokinetic model parameters (eg, the absorption rate constant and V(d)), it would be necessary to combine sparse TDM data with additional well-timed samples. This would allow development of more informative PPK models that could be used as part of Bayesian dose-individualization strategies.

Adolescent↗

Judgments of associative memory.

Judgments of associative memory (JAM) were indexed by ratings given to pairs of cue and response words. The normed probabilities, p(response|cue), were obtained from free association norms. The ratings were linearly related to the probabilities. The JAM functions were characterized by high intercepts ( approximately 50 on a 100 point scale) and shallow slopes (<0.5). The JAM function generalized across materials and method of rating. The function was not affected by expectancies or semantic similarity. Attempts to alter the function by making alternative responses more available were unsuccessful. A computer simulation model (MINERVA 2) exhibited the linear JAM function and successfully accounted for more complex phenomena (like the joint influence of forward and backward associative strengths on ratings). The shallow JAM slope appears to result from a fundamental lack of discrimination among associative strengths. The high intercept appears to result partly from an independent post-mnemonic source of bias producing over-estimation of association.

Association↗

Sugary food robbing in ants: a case of temporal cleptobiosis.

This study reports new information on interactions between Ectatomma tuberculatum (Ponerinae) and Crematogaster limata parabiotica (Myrmicinae). Workers of these sympatric arboreal ant species forage on the same pioneer trees. Diurnally, Ectatomma preyed on Crematogaster workers that avoided overt aggression by respecting a 'safe distance'. At night, Crematogaster initiated raids within the Ectatomma nests that they apparently left with their abdomen empty, then remained near the nest entrances where they successfully intercepted 75.2% of the returning Ectatomma foragers (N = 322). Certain intercepted workers rapidly resumed their return trip. Others (39.1%) were stopped, explored and licked during a long time by the Crematogaster. Most of them were carrying between their mandibles a droplet of liquid food that was stolen. This relationship, that appears to be a typical case of interspecific cleptobiosis, whose expression varies during the daytime, demonstrates for the first time sugary-food robbing, instead of prey robbing, in ants.

Aggression↗

Alcohol use from ages 9 to 16: A cohort-sequential latent growth model.

This study examined alcohol use from pre-adolescence to mid-adolescence and determined the influence of hypothesized covariates on changes in alcohol use rates during this developmental period. The sample comprised 405 randomly recruited youth from three age cohorts (9, 11, and 13 years), assessed annually for 4 years. Youth were 48.4% female, 50.4% African-American, and 49.6% White. A cohort-sequential latent growth model was employed which modeled alcohol use (use versus non-use) from ages 9 to 16 years, accounting for demographic variables of gender, race, parent marital status, and family economic status. Covariates of alcohol use included parent alcohol use, family alcohol problems, family cohesion, parent supervision, peer deviance, peer alcohol use, and peer encouragement of alcohol use. Results showed that proportions of alcohol users increased steadily from ages 9 to 16 years. Significant covariates were found on the intercept and slope. Being female and higher levels of parent alcohol use were associated with higher initial rates of alcohol use, whereas greater friends' encouragement of alcohol use was related to lower initial rates of alcohol use (intercept). Alternatively, more peer deviance and friends' encouragement of alcohol use was related to an increase in alcohol use rates from ages 9 to 16 years (slope), as was being White and from a single-parent family.

Adolescent↗

Lens lipids and maximum lifespan.

Unlike in most organs, the lipid composition of lenses varies dramatically among species and with age. The focus of this study is to assess how these changes relate to lifespan. Studies on cataract suggest that the lens may serve as a window into the processes leading to accelerated mortality. As a first step toward elucidating cellular processes in the lens that may serve as markers for accelerated mortality, we examined the correlation between species-dependent and age-related lens lipid compositional differences and maximum life span. We included data from camels, which, even in old age, rarely develop cataracts although they live under adverse conditions. Camel lens lipids were mainly composed of sphingolipids (77%) and phosphatidylcholines (23%). Bovine lens lipid composition was comparable to a previous study, and both bovine lens sphingolipids, phosphatidylcholines and camel lens phosphatidylcholines content fit well (within the 95% confidence limits) in the curve obtained by plotting maximum life spans of other species with sphingolipids and phosphatidylcholines. Lifespan was directly related to lens sphingolipid content and indirectly related to lens phosphatidylcholine content. The camel lens sphingolipid value was significantly above the curve for other species. Except for the camel lens nucleus, lipid order and sphingolipid content were linearly related, p < 0.005 with a slope of 0.85+/-0.07, and intercept of 6.9+/-3.8. Lipid phase transition temperature and sphingolipid content were also linearly related, p = 0.01 with a slope of 0.20+/-0.07, and intercept of 21.7+/-5.3. Our data support the hypothesis that humans have adapted so that their lens membranes have a high sphingolipid content that confers resistance to oxidation, allowing these membranes to stay clear for a relatively longer time than is the case in many other species. Age-related changes in human lens lipid composition may serve as a marker for oxidative stress and may reflect systemic oxidative insult, providing a window into the health of an individual.

Animals↗