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Biomedical subjects

L McCann

Publications and source records attributed to L McCann.

14 recordsLinked to original sources

Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin.

BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.

Acetylcholine↗

Effects of water salinity on acid-base balance in decapod crustaceans.

Extracellular acid-base balance in decapod crustaceans is influenced by water salinity, although the nature of this relationship is unclear. In euryhaline crabs, a decrease in salinity results in a metabolic alkalosis in the haemolymph and an increase in salinity results in a metabolic acidosis. Alterations in acid-base status by external changes in salinity are thought to be secondary to the adjustments required for ionic and osmotic regulation. In the present study, acid-base adjustments in the haemolymph of Eriocheir sinensis after transfer to 30 % sea water accompanied alterations in muscle pH and [HCO(3)(-)], as an initial acidosis coincided with an alkalosis in the leg muscle. By 48 h transfer, haemolymph pH increased as muscle pH and HCO(3)(-) declined. Haemolymph [Cl(-)] decreased significantly 3 h after transfer to a new steady state but haemolymph [Na(+)] and muscle [Na(+)] and [Cl(-)] remained unchanged. Muscle free amino acid concentration increased twofold 6 h after transfer, followed by a 2.5-fold increase in the haemolymph after 24 h. In contrast, 30 % sea water had no effect on haemolymph acid-base adjustments in the osmoconforming crab, Necora puber, which lacks ion and osmo-regulatory mechansims. Collectively these observations support the view that salinity-induced alterations in acid-base status are caused by adjustments consistent with cell volume regulation.

Acid-Base Equilibrium↗

Policy analysis of the use of hepatitis B, Haemophilus influenzae type b-, Streptococcus pneumoniae-conjugate and rotavirus vaccines in national immunization schedules.

After the development of national vaccine programmes to deliver six vaccines to infants, new vaccine adoption has been limited. Analysis of the health and economic implications of new vaccination options can help national policy-makers. Country specific quantitative policy analyses were conducted to estimate the impact of vaccination against hepatitis B (HB), Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (SP) and rotavirus. Disease burden, programme costs and the potential reduction of disease from vaccination was assessed for each vaccine. Without vaccination, these four vaccine preventable diseases contribute up to 4.1 million deaths in each successive birth cohort. Routine scheduled use of HB and Hib vaccines could prevent up to 1.7 million deaths; SP and rotavirus vaccines, an additional 1.4 million deaths, annually. The global cost per life-year saved ranged from $29 to $150 with great variation by income and economic groups. With a few exceptions for a few countries, these vaccines would cost a fraction of average per-capita gross domestic product to save a life-year. The addition of HB and Hib vaccines, should be considered for integration in all national immunization programmes. SP and rotavirus vaccines, with the given assumptions, would also be cost-effective. Proactive analysis of the economic and epidemiologic impact of these vaccines can hasten their introduction into national vaccination schedules.

Bacterial Vaccines↗

Effect of intradialytic parenteral nutrition on delivered Kt/V.

The purpose of the study is to determine the effect of intradialytic parenteral nutrition (IDPN) and its components on delivered Kt/V (Kt/Vd). Nineteen patients undergoing routine outpatient hemodialysis and receiving IDPN were enrolled onto this prospective, crossover study. To reduce the confounding of time, assigned treatment in the first week was random, with patient crossover in the fourth week. Patients served as their own controls. In the successive 6 weeks, patients received IDPN solutions differing in whether amino acids (AAs), dextrose, or lipids were included or excluded. The primary end point was Kt/Vd, measured with a single-pool, variable-volume urea kinetic model. Other factors with the potential to impact on Kt/Vd were controlled and/or monitored. The administration of IDPN with all three components resulted in a significantly reduced mean Kt/Vd. When patients received AA-containing solutions, mean Kt/Vd was significantly less than when IDPN was withheld. Administration of solutions without AA resulted in a mean Kt/Vd not significantly different from mean Kt/Vd when IDPN was withheld. The mean prescribed Kt/V did not differ from mean Kt/Vd when IDPN was withheld. Simulation analyses of increased urea generation (Gu) showed an increase in patient urea volume and decreased Kt/V similar to the study findings. AA-containing IDPN solutions resulted in a significant reduction in Kt/Vd, possibly mediated by increased Gu. Administration of IDPN solutions may have important clinical and economic consequences that warrant further investigation.

Aged↗

Prevention of Unwanted Pregnancy.

These two studies explored the cognitive decision-making process which differentiate effective contraceptors form the ineffective contraceptors (Study 1), and applied these findings to the development and testing of educational and cognitive interventions aimed at a group of sexually active young women at risk of becoming pregnant (Study 2). The results identified factors related to unnecessary contraceptive risk-taking. The interventions changed attitudes and knowledge about contraception in the college population in general and increased effective contraception in the at-risk population of women who were initially using either ineffective methods of birth control or no methods at all.

Contraception↗

Oxidative phosphorylation in Escherichia coli K12. An uncoupled mutant with altered membrane structure.

1. A new mutant strain (AN228) of Escherichia coli K12, unable to couple phosphorylation to electron transport, has been isolated. The mutant allele (unc-405), in strain AN228, was found to map near the uncA and uncB genes at about minute 74 on the E. coli genome. 2. A transductant strain (AN285) carrying the unc-405 allele is similar to the uncA and uncB mutants described previously in that it is unable to grow on succinate, gives a low aerobic yield on limiting concentrations of glucose, has a normal rate of electron transport, is unable to couple phosphorylation to electron transport, and lacks ATP-dependent transhydrogenase activity. 3. Strain AN285 (unc-405) is similar to an uncA mutant, but different from an uncB mutant, in that it is unable to grow anaerobically in a glucose-mineral-salts medium, and membrane preparations do not have Mg(2+)-stimulated adenosine triphosphatase activity. 4. Strain AN285 (unc-405) does not form an aggregate analogous to the membrane-bound Mg(2+)-stimulated adenosine triphosphatase aggregate found in normal cells. In this respect it differs from strain AN249 (uncA(-)), which forms an inactive membrane-bound Mg(2+)-stimulated adenosine triphosphatase aggregate.

Adenosine Triphosphatases↗

Reconstitution of oxidative phosphorylation and the adenosine triphosphate-dependent transhydrogenase activity by a combination of membrane fractions from unCA- and uncB- mutant strains of Escherichia coli K12.

1. Membrane preparations from both uncA(-) and uncB(-) mutant strains of Escherichia coli K12, in which electron transport is uncoupled from phosphorylation, were fractionated by washing with a low-ionic-strength buffer. The fractionation gave a ;5mm-Tris wash' and a ;membrane residue' from each strain. This technique, applied to membranes from normal cells, separates the Mg(2+),Ca(2+)-stimulated adenosine triphosphatase activity from the membrane-bound electron-transport chain and the non-energy-linked transhydrogenase activity. 2. Reconstitution of both oxidative phosphorylation and the ATP-dependent transhydrogenase activity was obtained by a combination of the ;membrane residue' from strain AN249 (uncA(-)) with the ;5mm-Tris wash' from strain AN283 (uncB(-)). 3. Valinomycin plus NH(4) (+) inhibited oxidative phosphorylation both in membranes from a normal strain of E. coli and in the reconstituted membrane system derived from the mutant strains. 4. The electron-transport-dependent transhydrogenase activity was located in the membrane residue and was de-repressed in both the mutant strains. 5. The spatial and functional relationships between the proteins specified by the uncA and uncB genes and the transhydrogenase protein are discussed.

Adenosine Triphosphatases↗

Grateful Med: getting started.

When a local medical library is not available, it is often necessary for physicians to discover alternate ways to receive medical information. Rural physicians, particularly, can make use of a computer program called Grateful Med that provides access to the same literature available to physicians in large cities. This program permits the user to perform database searches on the National Library of Medicine database (MEDLINE), corresponding to the primary index to medical literature, Index Medicus. In this article, we give the procedure for procuring a National Library of Medicine password and for making efficient use of the Grateful Med program.

Computer User Training↗

A primer for users of medical bibliographic databases.

A database is electronic information. Perhaps one of the most important information sources in medicine is that which is accessed electronically through a database named MEDLINE, the core medical literature published since 1966. MEDLINE is sold by three major vendors (BRS, Dialog, and the National Library of Medicine) to information experts and to medical experts. Information experts (librarians) and medical experts (physicians) can access MEDLINE by two different methods. This article discusses both and emphasizes use by the medical practitioner. An annotated guide to database vendors is provided, and guidelines are offered that will assist the physician in selecting equipment and assessing services.

MEDLARS↗