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Biomedical subjects

David W Wright

Publications and source records attributed to David W Wright.

At least 19 recordsLinked to original sources

beta-Hematin (hemozoin) mediated decompostion of polyunsaturated fatty acids to 4-hydroxy-2-nonenal.

beta-Hematin is an important heme metabolite of malarial infection. Its role as an agent mediating the formation of the reactive electrophile 4-hydroxynonenal (HNE) from polyunsaturated fatty acids was investigated. In vitro formation of HNE was found to be facilitated by the presence of hemozoin in a concentration-dependent fashion. The reactivity of HNE derived from reaction with beta-hematin was confirmed through its ability to form protein adducts on myoglobin.

Aldehydes↗

Size control of dendrimer-templated silica.

One of the most significant challenges facing the biomimetic synthesis of materials is achieving the requisite level of dimensional and spatial control. Typical reaction conditions for biomimetic silica synthesis allow for continued growth and ripening leading to the formation of larger nanospheres on the order of 200-600 nm in diameter. Herein, we have used polyamidoamine and polypropylenimine dendrimers as templates to expand the reaction conditions of biogenic silica production to produce a more robust synthesis leading to size-selective precipitation of silica nanospheres. Through the use of defined concentrations of phosphate buffer and main group metal chloride salts, we have shown that the biomimetic silica growth process is controlled by cationic neutralization of the anionic silica nanosphere surface. Neutralization minimizes electrostatic repulsions, allowing for agglomerization and continued growth of nanospheres. By controlling these concentrations, we can selectively produce silica nanospheres of desired dimensions between 30 and 300 nm without adversely affecting the template's activity.

Chemical Precipitation↗

Quartz crystal microbalance detection of glutathione-protected nanoclusters using antibody recognition.

A quartz crystal microbalance (QCM) immunosensor was developed for the quantitative detection of glutathione-protected nanoclusters. Advantages intrinsic to QCM were employed to make it an attractive alternative to other immunosensing techniques. We have addressed challenges in the area of QCM mass sensing through experimental correlation between damping resistance and frequency change for a reliable mass measurement. Electrode functionalization was optimized with the use of protein A to immobilize and present polyclonal IgG for antigen binding. This method was developed for the detection of glutathione (antigen)-protected clusters of nanometer size with high surface area and thiolate valency. Quantitation of glutathione-nanocluster binding to immobilized polyclonal antibody provides equilibrium constants (K(a) = (3.6 +/- 0.2) x 10(5) M(-1)) and kinetic rate constants (k(f) = (5.4 +/- 0.7) x 10(1) M(-1) s(-1) and k(r) = (1.5 +/- 0.4) x10(-4) s(-1)) comparable to literature reports. These observations further imply that immunoreactive nanoparticles have potential in medical diagnostics and materials assembly.

Antibodies↗

National practice guidelines for mental health care: a comparative policy analysis of the United kingdom and the United States.

Mental disorders are the leading cause of disability worldwide, according to the World Health Organization (WHO, 1996). In a report on health indicators of premature death and disability, the World Bank concluded that mental health problems account for 8.1% of the global burden of disease (GBD). Industrialized nations have taken different approaches in applying innovations to mental health care and mental health care policy. This paper uses the K. McInnis-Dittrich model of policy analysis (Ginsberg, 1994) to analyze the approaches of the United Kingdom (U.K.) and the United States (U.S.) to mental health treatment, specifically examining the effects of the U.K.'s national practice guidelines and the U.S.'s lack of similar guidelines. Recommendations for changes in current U.S. mental health policy are presented.

Health Planning Guidelines↗

Proxy identification: a time-dependent analysis.

OBJECTIVES: To describe the availability of next-of-kin (NOK) for proxy consent over the 24-hour time period following presentation of major trauma patients to a Level I trauma center. METHODS: The study was conducted by using a prospective, observational study design. Consecutive patients meeting predefined major trauma criteria during a three-month study period were enrolled and followed until NOK were contacted, or up to 24 hours. Survival analysis was used to determine the probability of NOK contact during the 24-hour follow-up period. RESULTS: Three hundred fifty (92%) of 382 subjects had NOK contacted during the follow-up period. The probabilities (95% confidence intervals [CIs]) of NOK contact at the time of arrival (t = 0) and 2, 4, 6, and 24 hours postpresentation were 0.25 (95% CI = 0.21 to 0.30), 0.68 (95% CI = 0.63 to 0.72), 0.77 (95% CI = 0.73 to 0.82), 0.80 (95% CI = 0.76 to 0.84), and 0.87 (95% CI = 0.84 to 0.90), respectively. The median time to contact was 40 minutes (95% CI = 27 to 54 min). CONCLUSIONS: One third of the trauma patients in this study did not have NOK available two hours following arrival in the emergency department. For time-critical research protocols, the time to NOK contact can significantly impact the ability to ensure prompt enrollment and treatment in clinical trials. Further studies are needed to assess the generalizability and consistency of these data.

Adult↗

Shedding new light on the "safe" club drug: methylenedioxymethamphetamine (ecstasy)-related fatalities.

OBJECTIVES: To report the pathology, toxicology, cause, and manner of death in 3,4-methylenedioxymethamphetamine (MDMA)-associated fatalities in the United States. Although use trends are increasing, data regarding the hazards of MDMA are limited. METHODS: The authors obtained fatality reports from participating medical examiners in the United States. Cases were identified as "drug-unrelated" when MDMA did not directly cause death (e.g., motor vehicle collision); deaths from drug toxicity were judged "drug-related." RESULTS: Thirty-eight (8%) of the surveyed medical examiners reported 102 deaths associated with MDMA use from 1999 to 2001. Ten percent of fatalities occurred in 1999 and 90% thereafter, representing a 400% relative increase. Victims tended to be young (mean age = 25), white (n = 87 [85%]), male (n = 70 [69%]), and otherwise healthy. Seventy-one (70%) deaths were drug-related (DR) and 31 (30%) were drug-unrelated (DU). Twenty-four (35%) DR deaths had a mean delay of 6.7 hours (95% CI = 5.1 to 8.2) in activating emergency medical services. Fifty-five DR cases (81%) were found in asystole and pronounced dead at the scene. CONCLUSIONS: The MDMA-associated fatal events typically occur in young, otherwise healthy individuals. MDMA's impact on the public health and safety of young adults and teenagers needs further assessment.

Adolescent↗

Metalloporphyrin probes for antimalarial drug action.

Metal-substituted protoporphyrin IXs (Co(III)PPIX (1), Cr(III)PPIX (2), Mn(III)PPIX (3), Cu(II)PPIX (4), Mg(II)PPIX (5), Zn(II)PPIX (6) and Sn(IV)PPIX (7)), phthalocyanine tetrasulfonates (PcS (8) and Ni(II)PcS (9)), and anionic and cationic porphyrins (meso-tetra(4-sulfonatophenyl)porphine (TPPS4, 10), meso-tetra(4-carboxyphenyl)porphine (TPPC4, 11), tetrakis(4-N-trimethylaminophenyl)porphine (TMAP, 12) and meso-tetra(N-methyl-4-pyridyl)porphine (TMPyP4, 13)) have been used as probes to compare two different assays for the inhibition of beta-hematin formation. The results demonstrate that the efficacy of these probes in either the beta-hematin inhibition assay (9, 7, 6, 5>4>11, 3>10, 8>2, 1; 12 and 13 did not inhibit.) or the bionucleating template assay (8>1>11>9, 2>4>3>7>10>5>6; 12 and 13 did not inhibit.) differ significantly. These differences are examined in light of possible interactions between the inhibitor probes, heme, beta-hematin and the bionucleating template. This detailed analysis highlights the fact that while dominant modes of interactions may be occasionally identified, the precise mechanism of inhibition undoubtedly consists of the interplay between multiple interactions.

Antimalarials↗