Prasugrel vs. clopidogrel in acute coronary syndrome patients treated with prasugrel.

WHAT IS KNOWN AND OBJECTIVE: Current guidelines recommend a combination of clopidogrel and aspirin for management of patients who have experienced an acute coronary syndrome (ACS). Additional antiplatelet agents have been recently approved. Few comparative effectiveness studies are available for these new agents. Accordingly, we evaluated effect on time to hospital admission and resource utilization (number of hospitalizations, ER visits and outpatient visits) of prasugrel vs. clopidogrel in prasugrel-treated patients as assessed in a matched cohort. METHODS: Based on the Truven Health Analytics MarketScan database from 01 January 2009 through 31 July 2012, a retrospective prasugrel-clopidogrel matched cohort was created. Inferences for average treatment effect over 1 and 12 months on time to hospitalization and resource utilization were performed by (i) frequentist Kaplan-Meier estimation with a Cox proportional hazard model and Lin's cost history method for censored resource utilization outcomes and (ii) Bayesian discrete-time hazard and negative binomial models. RESULTS AND DISCUSSION: The 10,963 matched pairs were well balanced on baseline characteristics. Frequentist analyses of time to hospital admission over 365 days and mean all-cause resource utilization over 30 and 365 days showed no statistical differences between prasugrel and clopidogrel (P-values > 0·05). Based on Bayesian analysis of time to admission over 12 months, there was positive evidence of equivalence (0·987 probability of equivalence at a 10% equivalence margin and a Bayes factor of 0·611). Although the frequentist analyses for number of all-cause hospitalizations showed a lack of a significant difference at Months 1 and 12, the Bayesian data analysis showed positive evidence of superiority of clopidogrel at Month 1 (Bayes factor: 5·369); however, at Month 12, there was little evidence of superiority of one treatment over the other (Bayes factor: 0·422). WHAT IS NEW AND CONCLUSION: Using frequentist and Bayesian data analyses, in prasugrel-treated patients, clopidogrel was equivalent to prasugrel for time to hospital admission over 12 months and there was positive evidence that it was superior to prasugrel for number of hospitalizations over the first month of treatment.

Characterizing Deficit Accumulation Among Gulf War Era Veterans.

BACKGROUND: Veterans of the first Gulf War (1990-1991) are reaching middle and older adulthood in differing degrees of health and biological age. Many Gulf War veterans report myriad negative symptoms classified as Gulf War illness (GWI), a chronic multi-symptom illness. OBJECTIVES: To describe and analyze deficit accumulation, among veterans with Severe GWI (SGWI+) and those without Severe GWI (SGWI-), to assess the association between a medically unexplained illness and aging. DESIGN: This study uses a retrospective cohort design with quasi-longitudinal data. SETTING: The recruitment sample included 10,042 Gulf War era veterans across all four US Census regions. PARTICIPANTS: The analytic sample included 1,054 participants of the GWECB for whom SGWI case status could be determined and who had valid responses for at least 90% of the deficits included in the deficit accumulation index. MEASUREMENTS: Chronic health conditions were retroactively reported, including year of diagnosis, enabling us to create a longitudinal measure of deficit accumulation. This deficit accumulation index (DAI) ranged from 0-1 for each respondent in each year between 1991-2013. We compare veterans with SGWI+ to those with SGWI- using the CDC case definition. RESULTS: Most veterans in our sample could expect to spend more years with moderate or substantial deficits than without deficits. SGWI+ was associated with spending more years with substantial deficits than those with SGWI-. Veterans in middle age (age 35-65) experienced more years with substantial deficits than younger veterans. Individuals with SGWI+ had 13 times the hazard of accumulating substantial deficits than those without. CONCLUSIONS: This study demonstrated that veterans with SGWI+, even those in midlife, experienced aging as measured by accumulating deficits. Practitioners should consider patients with multi-symptom illnesses as at risk of accelerated aging, tailoring treatments to address patients' holistic needs.

An approach to the assessment of risk from chronic radiation to populations of European lobster, Homarus gammarus (L.).

The basic principles underlying a four-discrete age group, logistic, growth model for the European lobster Homarus gammarus are presented and discussed at proof-of-concept level. The model considers reproduction, removal by predation, natural death, fishing, radiation and migration. Non-stochastic effects of chronic low linear energy transfer (LET) radiation are modelled with emphasis on (99)Tc, using three endpoints: repairable radiation damage, impairment of reproductive ability and, at higher dose rates, mortality. An allometric approach for the calculation of LD(50/30) as a function of the mass of each life stage is used in model calibration. The model predicts that at a dose rate of 1 Gy day(-1), lobster population reproduction and survival become severely compromised, leading eventually to population extinction. At 0.01 Gy day(-1), the survival rate of an isolated population is reduced by 10%, mainly through loss of fecundity, comparable to natural migration losses. Fishing is the main ecological stress and only dose rates in the range 0.03-0.1 Gy day(-1) can achieve discernible effects above it. On the balance of radiation and other ecological stresses, a benchmark value of 0.01 Gy day(-1) is proposed for the protection of lobster populations. This value appears consistent with available information on radiation effects in wildlife.

Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro.

F2-isoprostanes are prostaglandin F2-like compounds that are known to be formed in vivo by free radical oxidation of arachidonyl-containing lipids, and their plasma levels have been suggested as indicators of in vivo oxidative stress. As oxidation of LDL, a likely causal factor in atherosclerosis, involves lipid peroxidation, we investigated whether F2-isoprostanes are formed in plasma and LDL exposed to oxidative stress, and how F2-isoprostane formation is related to endogenous antioxidant status. In plasma exposed to aqueous peroxyl radicals, lipid hydroperoxides and esterified F2-isoprostanes were formed simultaneously after endogenous ascorbate and ubiquinol-10 had been exhausted, despite the continued presence of urate, alpha-tocopherol, beta-carotene, and lycopene. In isolated LDL exposed to aqueous peroxyl radicals or Cu2+, consumption of endogenous ubiquinol-10 and alpha-tocopherol was followed by rapid formation and subsequent breakdown of lipid hydroperoxides and esterified F2-isoprostanes, and a continuous increase in LDL's electronegativity, indicative of atherogenic modification. In Cu(2+)-exposed LDL, the decrease in esterified F2-isoprostane levels was paralleled by the appearance of free F2-isoprostanes, suggesting that hydrolysis by an LDL-associated activity had occurred. Our data suggest that F2-isoprostanes are useful markers of LDL oxidation in vivo. As F2-isoprostanes are potent vasoconstrictors and can modulate platelet aggregation, their formation in LDL demonstrated here may also have important implications for the etiology of cardiovascular disease.

Evaluation of a web-based weight loss intervention in overweight cancer survivors aged 50 years and younger.

PURPOSE: Half of adult cancer survivors under age 50 years are obese. Excess body weight is associated with cancer recurrence, and effective weight loss interventions for younger cancer survivors are needed. Commercially available, online weight loss programmes are readily accessible, but few have been studied in this population. This study employed a single-arm, pre-post intervention (baseline-6 month/baseline-12 month comparisons) to preliminarily explore feasibility, efficacy and safety of an online, commercially available weight loss programme in breast (n = 30) and testicular (n = 16) cancer survivors under age 50 years. METHODS: The intervention included three daily components: exercise, nutritional/behavioural modification strategies and health lessons. Intention-to-treat and completers analyses were conducted. Feasibility was measured by participation (number of participants enrolled/number screened), retention (number of participants attending 6/12 month study visit/number of enrolled) and self-reported adherence rates (average of mean percent adherence to each of the three intervention components). Efficacy was assessed by changes in initial weight (percent weight loss). Safety was assessed by adverse events. RESULTS: The mean participation rate was 42%. The retention rate was 59% at 6 and 49% at 12 months. The adherence rate for all participants (completers/dropouts/lost-to-follow-up) was 50.1% at 6 and 44% at 12 months. Completers reported adherence rates of 68% at 12 months. Study participants lost 5.3% body weight at 12 months; completers lost 9%. Only three unexpected adverse events (unrelated to the intervention) were reported. CONCLUSION: Clinically significant weight loss was observed, although retention rates were low. Findings generally support preliminary feasibility, efficacy and safety of this online weight loss programme, and future randomized control trials should be explored.

Physiological thiol compounds exert pro- and anti-oxidant effects, respectively, on iron- and copper-dependent oxidation of human low-density lipoprotein.

The effects of thiol compounds on oxidation of human low-density lipoprotein (LDL, 0.2 mg of protein/ml) by Cu2+ or Fe3+ (10 microM, each) were investigated in an in vitro system. L-Cysteine (CYS, 25 microM-1 mM) inhibited Cu2+-dependent, but facilitated Fe3+-dependent, oxidation of LDL in a dose-dependent manner. D,L-Homocysteine (HCY, 1 mM) and glutathione (GSH, 1 mM) similarly inhibited Cu2+-dependent, while facilitating Fe3+-dependent, oxidation of LDL. However, the effectiveness of these thiols (CYS, HCY, and GSH; 1 mM each) at mediating either Cu(2+)- or Fe3+-dependent LDL oxidation was not equivalent. Thus, Cu2+-dependent oxidation of LDL was most effectively inhibited by GSH, an intermediate effect was observed with HCY, and CYS was least effective. In contrast, a reversal of this pattern was observed for facilitation of Fe3+-dependent oxidation of LDL, with CYS being most effective and GSH being least effective. Interestingly, although the disulfides cystine and homocystine (0.5 mM, each) were without effect on either Cu(2+)- or Fe3+-dependent LDL oxidation, both glutathione disulfide (GSSG, 0.5 mM) and methionine (1 mM), an S-methylated derivative of HCY, inhibited Cu2+-dependent oxidation of LDL. However, neither GSSG nor methionine had any effect on Fe3+-dependent oxidation of LDL. Thus, while a free (reduced) thiol group is important for stimulation of Fe3+-dependent oxidation of LDL by CYS, HCY, and GSH, inhibition of Cu2+-dependent oxidation of LDL by these compounds seems to be thiol-independent. Our results show that thiol compounds differentially mediate Cu(2+)- and Fe3+-dependent LDL oxidation, an important early event in atherogenesis. Mediation of metal ion-dependent LDL oxidation by thiol compounds may have important implications for the etiology of atherosclerosis and may help explain the recent epidemiologic observation that plasma HCY concentration is an independent risk factor for cardiovascular disease.

Plasma thiols inhibit hemin-dependent oxidation of human low-density lipoprotein.

Oxidative modification of human low-density lipoprotein (LDL) renders it atherogenic. Previous studies demonstrated that plasma thiols promote oxidation of LDL by free ferric iron (Fe3+). The current study investigated effects of plasma thiols on oxidation of LDL by hemin, a physiological Fe3+-protoporphyrin IX complex thought to be capable of initiating LDL oxidation in vivo. In contrast to free Fe3+ which is incapable of oxidizing LDL in the absence of an exogenous reductant, hemin readily promoted LDL oxidation. During incubation of LDL (0.2 mg of protein/ml) with hemin (10 microM) at 37 degrees C for 6 h, thiobarbituric acid-reactive substances (TBARS), a marker of lipid oxidation, increased from 0.3 (+/-0.1) nmol/mg of LDL protein to a maximal concentration of 45.8 (+/-5.2) nmol/mg of LDL protein. Under the same experimental conditions, lipid-conjugated dienes, another marker of lipid oxidation, increased from non-detectable to near-maximal levels of 78-187 nmol/mg of LDL protein, and lipoprotein polyunsaturated fatty acyl-containing cholesteryl ester content decreased to 15-36% of that present in native (i.e. unoxidized) LDL. Continued incubation of LDL with hemin for up to 24 h resulted in no further significant alterations in lipoprotein levels of TBARS, lipid-conjugated dienes, and cholesteryl esters. In addition to these chemical modifications indicative of lipoprotein oxidation, agarose gel electrophoretic analysis indicated that exposure of LDL to hemin resulted in conversion of the lipoprotein to an atherogenic form as evidenced by its increased anodic electrophoretic mobility. Addition of physiological concentrations of plasma thiols (either cysteine, homocysteine or reduced glutathione; 1-100 microM, each) inhibited hemin-mediated oxidation of LDL. Thus, whereas the maximal TBARS concentration was achieved following 6 h of incubation of LDL with hemin alone, addition of thiol extended the time required to attain maximal TBARS concentration to > or = 12 h. Similar antioxidant effects of thiols on formation of lipid-conjugated dienes, loss of cholesteryl esters, and lipoprotein anodic electrophoretic mobility were also observed. However, all thiols were not equally effective at inhibiting hemin-dependent LDL oxidation. Thus, whereas reduced glutathione was most effective at inhibiting hemin-dependent LDL oxidation, an intermediate effect was observed for homocysteine, and cysteine was least effective. The inhibition of hemin-mediated LDL oxidation by plasma thiols reported here confirms a previous observation that, under certain conditions, thiols can function as antioxidants, but contrasts with the previously documented pro-oxidant effect of the same thiols on oxidation of LDL by free Fe3+. These contrasting effects of plasma thiols on hemin- and free Fe3+-mediated LDL oxidation indicate that, in vivo, the ability of thiols to function as either anti- or pro-oxidants during LDL oxidation may, at least in part, be determined by the type of oxidant stress to which the lipoprotein is exposed.

Ascorbic acid and atherosclerotic cardiovascular disease.

In this chapter, we have briefly reviewed the current scientific knowledge of the role of vitamin C in the prevention of atherosclerosis and its associated clinical manifestations. There is good evidence from animal studies that vitamin C can slow the progression of experimental atherosclerosis. Most of these studies, however, were done either in guinea pigs, using ascorbic acid depletion, or in cholesterol-fed rabbits, using ascorbic acid supplementation. Both animal models have limitations, as guinea pigs are not a well-established (nor well-studied) model of atherosclerosis, and rabbits develop atherosclerosis at high serum beta-VLDL cholesterol levels, and in addition can synthesize ascorbic acid. In contrast, humans develop atherosclerosis spontaneously and readily at moderately elevated serum LDL cholesterol levels and have lost the ability to synthesize ascorbic acid. Thus, the animal studies discussed, although quite promising and suggestive of an anti-atherogenic effect of ascorbic acid, need to be expanded to primates before more definitive conclusions can be drawn. Similar to the animal data, the current evidence from epidemiological studies on the role of vitamin C in the prevention of CVD is inconclusive, with some studies showing a very strong correlation between increased vitamin C intake and incidence of CVD events and other studies showing no correlation at all. Studies on CVD risk factors indicate that vitamin C may moderately decrease total serum cholesterol levels, increase HDL levels, and exert a hypotensive effect. These findings are particularly intriguing and should be pursued vigorously in basic research studies to elucidate biological mechanisms. In addition, it appears that large placebo-controlled, double-blind, randomized trials of vitamin C supplementation (without simultaneous supplementation with vitamin E) in populations with a wide range of vitamin C body levels are needed in order to confirm or refute a role for vitamin C in the prevention of CVD. Unfortunately, no such trials are currently being conducted. The possible mechanisms by which ascorbic acid may affect the development of atherosclerosis and the onset of acute coronary events include effects on arterial wall integrity related to biosynthesis of collagen and GAGs, altered cholesterol metabolism mediated by vitamin C-dependent conversion of cholesterol to bile acids, and effects on triglyceride levels via modulation of lipoprotein lipase activity. A particularly intriguing possible mechanism for the anti-atherogenic effect of vitamin C is prevention of atherogenic, oxidative modification of LDL. Numerous in vitro studies have demonstrated that ascorbic acid strongly inhibits LDL oxidation by a variety of mechanisms. The potential effects of ascorbic acid on platelet function and EDRF metabolism are particularly intriguing, as they might have widespread consequences for the prevention of atherosclerotic lesion development as well as acute clinical events. Thus, both metabolic and antioxidant functions may contribute to the possible reduction of CVD risk by vitamin C.

Success and future of demography: the role of data and methods.

Demography typifies paradigmatic success; that is, cumulative scientific work that has provided useful perspectives on a set of important questions. This success can be traced partly to the core subject matter of demography, which is relatively conducive to quantitative, observational science. The development of demography was further aided by extrinsic factors, such as the import of its data for government administration, for business purposes, and the import of demographic questions for social problems and public policy. These observations make suspect any simple projection of demography's success into the future or the transport of its experience to other disciplines.

Use of levarterenol bitartrate in massive hemorrhage after retropubic prostatectomy.

A case of massive hemorrhage following retropubic prostatectomy is presented. There was a dramatic decrease in bleeding with the use of levarterenol bitartrate in the irrigation solution. The implications of this finding are discussed.

Caregiving networks of elderly persons: variation by marital status.

Using data from the 1982 National Long-Term Care Survey, this study examines the relationship between marital status and two dimensions of caregiving networks, size and composition. Results indicate that widowed and never married people have helping networks that are larger than those of married people. Diversity across marital statuses in sources of assistance is revealed in analyses of two measures of caregiving network composition: (a) having more kin than nonkin helpers and (b) presence of specific helpers (adult children, siblings, friends, and formal helpers). Moreover, gender interacts with marital status to influence the composition of caregiving networks.

Reliability of measurements obtained with a modified functional reach test in subjects with spinal cord injury.

BACKGROUND AND PURPOSE: The primary purpose of this study was to determine whether the Functional Reach Test (FRT) could be modified to provide reliable measurements of sitting balance. A secondary purpose was to determine whether the test could be used to measure differences among levels of spinal cord injury. SUBJECTS: Thirty male subjects with spinal cord injuries were divided into into three groups based on injury type. Group 1 consisted of subjects with C5-6 tetraplegia, group 2 consisted of subjects with T1-4 paraplegia, and group 3 consisted of subjects with T10-12 paraplegia. METHODS: Subjects sat on similar mat tables (tables varied based on what was available at a given clinic) against the same backboard, set at 80 degrees. During two sessions, forward reach was measured with a yardstick, with a 10-minute break between sessions. RESULTS: Intraclass correlation coefficients (3,2) were high and varied from .85 to .94. Post hoc testing revealed that differences occurred between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. CONCLUSION AND DISCUSSION: Test-retest reliability was high with modification of the FRT with a single rater. The measurements reflected differences among levels of lesion. Further study is needed to determine normal values for all levels of lesion, relationships to functional outcomes, and effects of equipment on sitting balance. The modified FRT appears to provide reliable measurements of sitting balance in nonstanding persons with spinal cord injuries.

Dietary saturated or polyunsaturated fat and copper deficiency in the rat.

Dietary fat-type and copper (Cu) deficiency have been independently identified as potentially important factors in the etiology of ischemic heart disease (IHD); a disease that has been linked to inflammation and oxygen free radical (OFR) mediated damage. Group (n = 6) of male, weanling, Wistar rats were provided ad libitum with deionized water and control or low Cu diets containing (200 g/kg) either saturated or polyunsaturated fatty acids (SFA or PUFA, respectively) for 56 d. Measurement of several indices of Cu status indicated that both groups fed the low Cu diets were Cu-deficient. SFA consumption resulted in significantly increased hepatic Cu (p less than 0.001) and iron (Fe) (p less than 0.001) concentrations and xanthine oxidase activity (p less than 0.05) and significantly decreased hepatic glucose-6-phosphate dehydrogenase activity (p less than 0.001). Although Cu deficiency resulted in significantly decreased hepatic copper-zinc superoxide dismutase (CuZnSOD) activity (p less than 0.01), no significant effect on the activities of the other hepatic antioxidant enzymes, manganese superoxide dismutase, catalase, and glutathione peroxidase, or glutathione reductase, were observed. Cu deficiency also resulted in significantly decreased hepatic Cu levels (p less than 0.001) and cytochrome c oxidase activity (p less than 0.01). No significant difference in hepatic thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation, was found between groups consuming SFA or PUFA, but both Cu-deficient groups exhibited significantly increased hepatic TBARS (p less than 0.001), compared to controls. This was probably owing to the significantly decreased hepatic CuZnSOD activity observed in the Cu-deficient, compared to control animals.

Incidence of MSDs and neck and back pain among logging machine operators in the southern U.S.

There are limited data about the incidence and prevalence of musculoskeletal disorders (MSDs) among loggers in the southern U.S. despite the risk factors associated with these occupations. Risk factors are both personal (age, body mass index, etc.) and job-related (awkward postures, repetitive hand and foot movements, vibration, etc.). A survey was conducted to estimate the incidence of self-reported pain and diagnosed MSDs and to study the relationship with known risk factors. Respondents were loggers attending training and continuing education classes. Respondents were asked to identify personal attributes, machine use, awkward postures, repetitive movements, and recent incidence of pain and medical diagnoses. All were male with an average age of 44 (range of 19-67) and an average body mass index of 31.3. Most were machine operators (97%) who have worked in the logging industry for an average of 22.9 years. Most machines identified were manufactured within the past ten years (average machine age 6.7 years). For machine operators, 10.5% (16) reported an MSD diagnosis, 74.3% (113) reported at least mild back pain, and 71.7% (109) reported at least mild neck pain over the past year. Further analysis attempted to identify an association between personal attributes, machine use, posture, and pain. Risk factors related to machine use may be biased since most survey respondents had considerable choice or control in working conditions, as they were firm owners and/or supervisors.

Reduction of copper, but not iron, by human low density lipoprotein (LDL). Implications for metal ion-dependent oxidative modification of LDL.

Cell-mediated oxidative modification of human low density lipoprotein (LDL), most likely an important early step in atherosclerosis, requires redox active metal ions such as copper or iron. We have previously shown that iron-dependent, in contrast to copper-dependent, oxidative modification of LDL requires superoxide, a physiological reductant. In the present study, we sought to explain these discrepant results. LDL was incubated at 37 degrees C with Cu2+ (10 microM) and bathocuproine (BC, 360 microM), an indicator molecule which specifically complexes Cu+, but not Cu2+. In a time- and concentration-dependent manner, LDL reduced Cu2+ to Cu+. An LDL concentration as low as 10 micrograms of protein/ml (about 20 nM) reduced about 7 microM Cu2+ within 1 h of incubation. Complexation of the Cu+ formed under these conditions with BC significantly inhibited oxidative modification of LDL, as assessed by agarose gel electrophoresis. Preincubation of LDL with N-ethylmaleimide had no effect on the rate and extent of Cu2+ reduction nor LDL oxidation, indicating that free sulfhydryl groups associated with apolipoprotein B are not involved. Addition of either superoxide dismutase or catalase or increasing the alpha-tocopherol content of LDL from 11.8 +/- 3.0 to 24.4 +/- 2.8 nmol/mg of protein also had no significant effect on the kinetics of Cu2+ reduction by LDL. In contrast, incubation of LDL with Fe(3+)-citrate (10 microM) and the indicator bathophenanthroline (BP, 360 microM) resulted in no significant Fe2+ formation, even at LDL concentrations as high as 200 micrograms of protein/ml. However, incubation of LDL with Fe(3+)-citrate and an enzymatic source of superoxide led to rapid formation of Fe2+ and consequent oxidative modification of LDL. Addition of BP inhibited iron-mediated LDL oxidation under these conditions. Our results indicate that reduced metal ions are important mediators of LDL oxidation, and that LDL specifically reduces Cu2+, but not Fe3+. These data, therefore, help explain why copper, in addition to being chemically more reactive, is more potent than iron at mediating LDL oxidation.

Contrasting effects of a dietary copper deficiency in male and female mice.

Female rats are protected from the lethal effects of a dietary copper (Cu) deficiency, but female mice fed a Cu-deficient diet develop atrial thromboses and die. To further investigate the effect of sex on Cu status in mice (n = 16), male and female adult Swiss-Webster mice were fed Cu-supplemented (8.4 mg Cu/kg) or Cu-deficient (0.3 mg Cu/kg) diets with deionized water for 43-49 days. Six female mice, but only one male mouse, fed the Cu-deficient diet died during the experiment. Both male and female mice fed the Cu-deficient diet exhibited typical features of deficiency. The severity of anemia and the values observed for several indicators of Cu status (plasma ceruloplasmin [EC 1.16.3.1.] and erythrocyte copper-zinc superoxide dismutase [EC 1.15.1.1.] activities, cardiac Cu) were similar in both male and female Cu-deficient mice. However, cardiac enlargement (0.97 vs 0.73 g/100 g body wt, P < 0.05), cardiac edema (79.9% vs 78.2% cardiac water, P < 0.05) and depletion of renal Cu (10.4 vs 12.5 micrograms/g dry weight, P < 0.05) were more severe in female compared with male, Cu-deficient mice. Furthermore, although hepatic Cu was significantly (P < 0.05) lower in female Cu-deficient compared with Cu-supplemented mice, it was not significantly decreased by deficiency in male mice. These data indicate that the female mice experienced a more extreme form of Cu deficiency than the males.

Reconsidering mortality compression and deceleration: an alterative model of mortality rates.

In this research we develop a model of mortality rates that parameterizes mortality deceleration and compression, permits hypothesis tests for change in these parameters over time, and allows for formal gender comparisons. Our model fits mortality data well across all adult ages 20-105 for 1968-1992 U.S. white data, and the results offer some confirmation of findings of mortality research using conventional methods. We find that the age at which mortality deceleration begins is increasing over time, that decompression of mortality is occurring, and that these trends vary substantially across genders, although male and female mortality patterns appear to be converging to some extent.

Mechanisms of metal ion-dependent oxidation of human low density lipoprotein.

Although either copper or iron is essential for oxidation of human low density lipoprotein (LDL) by vascular cells, the mechanism is unknown. In our experiments copper- and iron-mediated LDL oxidation was found to proceed by different mechanisms. Oxidation of LDL by iron requires superoxide and proceeds by a hydroxyl radical-independent mechanism involving reduction of iron from the ferric to the ferrous form. In contrast, copper-mediated LDL oxidation involves direct reduction of copper from the cupric to the cuprous form by LDL.

Effects of copper deficiency on hepatic and cardiac antioxidant enzyme activities in lactose- and sucrose-fed rats.

1. A number of dietary sugars are known to mediate the effects of copper deficiency. The effects of lactose (compared with sucrose) and a dietary Cu deficiency on hepatic and cardiac antioxidant enzyme activities and tissue mineral element status were investigated in the rat. 2. Groups (n 6) of male weanling Wistar rats were provided ad lib. with deionized water and diets containing sucrose (580 g/kg) or sucrose and lactose (387 g/kg and 193 g/kg respectively) with either control (12.0 mg/kg) or deficient (1.5 mg/kg) quantities of Cu for 77 d. 3. Animals consuming the low-Cu diets exhibited significantly decreased tissue Cu levels (P less than 0.01), hepatic and cardiac cytochrome c oxidase (EC 1.9.3.1, CCO) activities (P less than 0.01 and P less than 0.001 respectively) and hepatic Cu-zinc superoxide dismutase (EC 1.15.1.1, CuZnSOD) activity (P less than 0.05). The low-Cu diets also significantly decreased cardiac manganese superoxide dismutase (EC 1.15.1.1, MnSOD), catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9, GSH-Px) activities (P less than 0.01, P less than 0.05 and P less than 0.001 respectively). 4. Hepatic Mn was significantly increased in both lactose-fed (P less than 0.001) and Cu-deficient (P less than 0.01) animals. These increases were unrelated to hepatic MnSOD activity. Cardiac Zn was significantly (P less than 0.01) increased in Cu-deficient animals. 5. Lactose feeding resulted in significantly increased cardiac CCO activity (P less than 0.001) but significantly decreased hepatic CuZnSOD (P less than 0.05), catalase (P less than 0.01) and GSH-Px (P less than 0.001) activities. 6. The activities of lactose dehydrogenase (EC 1.1.1.27, LDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PDH) were found to be significantly (P less than 0.05 and P less than 0.01 respectively) increased in Cu-deficient animals and G6PDH activity was significantly (P less than 0.01) decreased as a result of lactose consumption. 7. The observed changes in antioxidant enzyme activities associated with both Cu deficieny and lactose consumption may have important implications for the development of free radical mediated cell damage. However, no significant differences in either hepatic or cardiac levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation, were found.