Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers.

The model reaction of photoinduced donor-acceptor interaction in linked systems (dyads) has been used to study the comparative reactivity of a well-known anti-inflammatory drug, (S)-naproxen (NPX) and its (R)-isomer. (R)- or (S)-NPX in these dyads is linked to (S)-N-methylpyrrolidine (Pyr) using a linear or cyclic amino acid bridge (AA or CyAA), to give (R)-/(S)-NPX-AA-(S)-Pyr flexible and (R)-/(S)-NPX-CyAA-(S)-Pyr rigid dyads. The donor-acceptor interaction is reminiscent of the binding (partial charge transfer, CT) and electron transfer (ET) processes involved in the extensively studied inhibition of the cyclooxygenase enzymes (COXs) by the NPX enantiomers. Besides that, both optical isomers undergo oxidative metabolism by enzymes from the P450 family, which also includes ET. The scheme proposed for the excitation quenching of the (R)- and (S)-NPX excited state in these dyads is based on the joint analysis of the chemically induced dynamic nuclear polarization (CIDNP) and fluorescence data. The (1)H CIDNP effects in this system appear in the back electron transfer in the biradical-zwitterion (BZ), which is formed via dyad photoirradiation. The rate constants of individual steps in the proposed scheme and the fluorescence quantum yields of the local excited (LE) states and exciplexes show stereoselectivity. It depends on the bridge's length, structure and solvent polarity. The CIDNP effects (experimental and calculated) also demonstrate stereodifferentiation. The exciplex quantum yields and the rates of formation are larger for the dyads containing (R)-NPX, which let us suggest a higher contribution from the CT processes with the (R)-optical isomer.

Latex sensitization in health care workers and in the US general population.

Sensitization to natural rubber latex is a prerequisite to type I immediate hypersensitivity reactions (urticaria, angioedema, anaphylaxis, and allergic rhinitis) that result from subsequent latex exposure. This study examines occupations in which latex glove use is common to determine whether it is associated with increased prevalence odds of latex sensitization (measured by latex-specific immunoglobulin E antibodies) by using data from 5,512 adults aged 17--60 years from the Third National Health and Nutrition Examination Survey (1988--1991). After other factors associated with latex sensitization were controlled for, there was a nonsignificant association between longest-held jobs in health care and latex sensitization (odds ratio (OR) = 1.49, 95 percent confidence interval (CI): 0.92, 2.40). For current occupations, latex sensitization was not associated with health care work in which gloves were used (OR = 1.17, 95 percent CI: 0.51, 2.65) or with other occupations in which latex glove use is common (OR = 1.01, 95 percent CI: 0.49, 2.07) compared with other occupations. Current health care workers who reported not using gloves were at increased risk of latex sensitization, both among those without a history of childhood atopy (OR = 2.30, 95 percent CI: 1.04, 5.13) and those with such a history (OR = 28.04, 95 percent CI: 3.64, 215.97). This odds ratio heterogeneity suggests that subjects with childhood atopy may be at high risk of latex sensitization.

Assessment of recent ozone short-term epidemiologic studies.

The U.S. Environmental Protection Agency (EPA) revised the National Ambient Air Quality Standards (NAAQS) for ozone in 1997 based largely on short-term ozone studies published up to 1995. The U.S. EPA's conclusions must now be updated because (1) the agency did not consider many new studies published since 1995 and (2) the agency did not critically review the studies published before 1995 (i.e., it accepted the stated conclusions). In this article, we examine many recently published short-term ozone studies including 17 hospital admissions studies, 10 mortality studies, and 6 summer-camp studies. Almost all of these studies reported a significant association between ambient levels of ozone and adverse health effects. However, on close examination, it is apparent that there are mixed findings from one study to another and even within the results of a single study. Moreover, questionable statistical analyses and failure to consider confounders make a number of the reported findings doubtful and even negative.

Prevalence of IgE to natural rubber latex in unselected blood donors and performance characteristics of AlaSTAT testing.

BACKGROUND: The prevalence of IgE to natural rubber latex (NRL) proteins in the general population remains unsettled, both because of the difficulty of obtaining an unbiased population representative of the general population of the United States and because of concerns about the reproducibility of tests for anti-latex IgE antibodies. Establishing the prevalence in the population is important toward defining the potential risks of persons entering areas where latex exposure may occur. OBJECTIVE: The purposes of this study were to determine the prevalence of IgE to latex in a general population and to assess the performance characteristics of the AlaSTAT microtiter plate test for anti-latex IgE when performed independently by different laboratories. METHODS: One thousand nine hundred and ninety-seven consecutive blood samples obtained from the Oklahoma Blood Institute were assayed independently in three laboratories for IgE to NRL using the FDA-approved AlaSTAT ELISA for IgE to NRL. The group consisted of 56% men and 44% women. Ninety percent were Caucasian, 4% African American, and 6% were "other." RESULTS: The prevalence IgE to NRL between the 3 laboratories varied from 5.4% to 7.6% at the designated cut off of 0.35 kU/L. Examination of results for specific individuals demonstrated >90% agreement between the three sites with the most reproducible results at the Class II cutoff of > or =0.7 kU/L. There was no difference in the percent of positive values at the three laboratories. CONCLUSIONS: There is good agreement between laboratories as to NRL IgE reactive and non-reactive sera using the AlaSTAT test. This report of the largest sample of blood donors confirms earlier reports as to the prevalence of IgE NRL in blood donors.

Random-effects linear regression meta-analysis models with application to the nitrogen dioxide health effects studies.

As the field of epidemiology grows and multiple studies of the same topic are more frequently available, increased focus is placed on quantitative methods for synthesis of results to yield an overall conclusion. A major difficulty encountered in practice has been the lack of convenient methodology for addressing groups of studies which are similar, but not exactly alike, in features which may affect study results. The age group from which subjects were selected, the general health of subjects when selected, and the specific health endpoint examined are examples of such features. Some previous investigators have addressed the problem using iterative techniques, although most have opted for simpler models which assume that differences in the studies do not appreciably affect the outcome under investigation. That is, he studies are taken to be homogeneous in that the underlying effect being investigated is the same in each study. This paper presents a random-effects linear regression technique which allows differences in the individual study features. The proposed methodology does not require iterative or other complicated procedures, making it more readily accessible to the applied researcher. We demonstrate this technique on a set of studies of the health effects of indoor NO2 exposure in children. It is seen that odds ratios from these studies vary considerably according to subject age, the study location, and the health endpoint considered. A simple synthesis which does not account for these differences may be misleading.

Alcoholic beverages and breast cancer: some observations on published case-control studies.

We identified 38 case-control studies investigating possible associations between alcoholic beverage consumption and cancer of the female breast. Each study was characterized according to design features such as: control type (hospital or community based), risk factors controlled for, matching strategy, and statistical power. We examined the effect of these design variables on several outcome variables including identification of any significant elevation in odds ratio and characterization of any dose-response effect. The major finding of this study is that of a striking difference between hospital and community based controlled studies with respect to (1) the level of any estimated dose-response effect, and (2) the finding of statistically significant elevations in odds ratios at levels of consumption below 4 drinks per week. In summary, the generally weak associations reported in these case-control studies along with the measurement and/or selection biases implied by our findings would lead one to the conclusion that present evidence does not support a causal association. This conclusion seems to be in accord with results from cohort studies and with similar conclusions from several other reviews.

Health risks of short-term SO2 exposure to exercising asthmatics.

A method is described for quantifying health risks to asthmatics briefly exposed to elevated levels of SO2. By combining symptomological and physiological measurements, we have developed a dose-response surface that relates both severity and incidence of response to ambient air quality levels. The complete model to assess potentially avoidable risks includes power plant emission data; ambient SO2 background levels; demographic and activity patterns of asthmatics, the identified population at risk; and the dose-response surface. The estimated annual risk to persons experiencing an SO2-induced response due to a nearby power plant is quite small (response rates under 3 percent). Uncertainties due to modeling errors, variations in activity patterns, demographics and physiological response are discussed.

Photooxidation of chlorins by quinones studied by nuclear magnetic resonance techniques.

The reactions of photo-excited chlorophylls and pheophytins with quinones have been investigated by nuclear magnetic resonance techniques. In slightly alkaline solutions the quinone signals showed line broadening which is explained by degenerate electron transfer between semiquinone radical ions and their benzoquinone parents. In neutral solutions, chemically induced dynamic nuclear polarization was observed which is ascribed to the pair, chlorophyll cation-semiquinone anion. A kinetic analysis of the dependence of these effects upon the quinone concentration suggests that only the reactions of triplet-chlorophyll with the quinones give rise to chemically induced dynamic nuclear polarization effects.