Apolipoprotein E—associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.     

Exchangeable magnesium pool masses in healthy women: effects of magnesium supplementation.

BACKGROUND: Studying magnesium pools in the body with use of stable isotopes may be helpful for evaluating magnesium status. Data on the evaluation of magnesium pools in humans are scarce. OBJECTIVE: We undertook this study to evaluate the effects of a magnesium supplementation program on the size of the exchangeable body pools of magnesium and on classic indexes of magnesium status in healthy women with normal magnesium status. DESIGN: Ten healthy women participated in a kinetic study with magnesium stable isotopes before and after 8 wk of magnesium supplementation. Each woman received 3 supplements containing 5.08 mmol (122 mg) elemental Mg/d (366 mg/d). Before and at the end of the supplementation period, each woman received an intravenous injection of 1.67 mmol (40 mg) (25)Mg, and the plasma magnesium disappearance curve was followed for the next 7 d. Two methods were used to analyze the exchangeable pools of magnesium: 1) formal multicompartmental modeling and 2) a simplified estimation of the total mass of the rapidly exchangeable magnesium pool (EMgP). RESULTS: In these healthy women, exchangeable magnesium pools represented 11-12% of total body magnesium on the basis of multicompartmental analysis. The simplified estimation of EMgP overestimated the size of the exchangeable magnesium pools by approximately 45-50%. Eight weeks of magnesium supplementation did not significantly modify the size of the exchangeable magnesium pools, whereas urinary magnesium excretion was significantly higher after 8 wk of supplementation. CONCLUSION: Women with no clinical evidence of magnesium deficiency may not respond to short-term supplementation with increases in the mass of the exchangeable magnesium body pool or in magnesium turnover rates.     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Transitional properties of the mechanically evoked perioral reflex from infancy through adulthood

The organization of motor responses in the orbicularis oris muscle following the delivery of punctate mechanical inputs to vermilion skin of the lips was studied in a group of young infants, school-age children, and adults during periods of voluntary lip muscle activation. A specially designed multi-point array skin contactor, coupled to a position-servo controlled linear motor, was highly effective in driving the early component of the perioral reflex (R1). Overall, the evoked R1 response obtained from the infant was of variable amplitude relative to the children and adults, lacked response specificity, and occurred it a longer latency. This brainstem mediated sensorimotor action appears to take on several characteristics of the adult form by the age of 12. The emergence and maturation of mechanically evoked perioral reflexes is discussed in relation to the acquisition of motor skills, including speech and smiling.     

Comparison of Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid in Patients With Chronic Renal Failure: Effects of Differential Pharmacokinetics on Serum Bactericidal Activity

Study Objectives . To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design . Randomized, crossover, controlled study. Setting . National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients . Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions . On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results . The mean observed apparent β-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-β-lactamase-producing (Nβ-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against β-lactamase-producing (β-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against β-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion . Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from β-lactamase degradation.     

Flip side of synaptic plasticity: Long-term depression mechanisms in the hippocampus

There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca²⁺ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc.     

High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.