Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets.

Anoxic stress attenuates NMDA-induced pial arteriolar dilation via a mechanism involving actions of cyclooxygenase (COX)-derived reactive oxygen species (ROS). We examined whether the selective COX-2 inhibitor NS398 would protect neuronal function after global hypoxia/ischemia (H/I) in piglets. Pial arteriolar responses to NMDA (10-100 micromol/l) were determined using intravital microscopy in anesthetized piglets before and 1 h after H/I. Study groups received vehicle, 0.3, 1, or 5 mg/kg NS398, or 0.3 mg/kg indomethacin (n = 7, 6, 6, 5 and 8, respectively) i.v. 20 min prior to H/I. H/I reduced NMDA- induced dilation to 44 +/- 6% (100 micromol/l NMDA, mean +/- s.e.m.) of the pre-ischemic response in vehicle animals (p < 0.05). However, NS398 dose-dependently protected arteriolar dilation to NMDA (77 +/- 8, 81 +/- 16, and 102 +/- 10% preservation at 0.3, 1 and 5 mg/kg, respectively). Indomethacin caused similar preservation. However, indomethacin but not NS398 reduced serum thromboxane B(2) levels to undetectable values. In conclusion, COX-2 appears to be a major source of ROS in the piglet cerebral cortex after H/I.

Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia.

Nitric oxide is a potent modulator of mitochondrial respiration, ATP synthesis, and K(ATP) channel activity. Recent studies show the presence of a potentionally new isoform of the nitric oxide synthase (NOS) enzyme in mitochondria, although doubts have emerged regarding the physiological relevance of mitochondrial NOS (mtNOS). The aim of the present study were to: (i) examine the existence and distribution of mtNOS in mouse tissues using three independent methods, (ii) characterize the cross-reaction of mtNOS with antibodies against the known isoforms of NOS, and (iii) investigate the effect of hypoxia on mtNOS activity. Nitric oxide synthase activity was measured in isolated brain and liver mitochondria using the arginine to citrulline conversion assay. Mitochondrial NOS activity in the brain was significantly higher than in the liver. The calmodulin inhibitor calmidazolium completely inhibited mtNOS activity. In animals previously subjected to hypoxia, mtNOS activity was significantly higher than in the normoxic controls. Antibodies against the endothelial (eNOS), but not the neuronal or inducible isoform of NOS, showed positive immunoblotting. Immunogold labeling of eNOS located the enzyme in the matrix and the inner membrane using electron microscopy. We conclude that mtNOS is a constitutively active eNOS-like isoform and is involved in altered mitochondrial regulation during hypoxia.

Stability of methylene chloride spiked passive samplers: an international shipping and transportation study.

A stability study was carried out by dynamically spiking Assay Technology Model 541 passive samplers with known amounts of methylene chloride (MeCl2) and shipping them to facilities around the world. Once arrived, these samples remained on site briefly and then were returned to the laboratory in North Chicago, III. A total of 22 sets of samples was prepared. Each sample set contained four passive samplers: blank, low (2.5 ppm), medium (25 ppm), and high (125 ppm) concentrations. Twelve of the 22 sets were separated into 4 groups of 3 sets, with each group defined as a cluster. One cluster was shipped to a pharmaceutical production facility in each country--South Africa, Pakistan, and Indonesia--and then shipped back to the lab, under normal shipping conditions. The fourth cluster was carried by one of the authors, who traveled through all three countries. The remaining 10 sets of samples were kept in the lab as controls. Each returning cluster was analyzed with two lab sets on arrival in the lab. Results obtained were evaluated using a t-test at a 95% confidence level. No significant differences were found in MeCl2 spiked passive samplers between traveled and lab controls, samples stored at room temperature and in the freezer, or analyzed right after being spiked and stored up to 7 weeks. It was concluded that MeCl2 spiked passive samplers were stable for at least 4 weeks at room temperature. There was no impact observed from international shipping and transportation on MeCl2 spiked passive samplers without temperature control.

Field validation of passive monitors for the determination of employee exposures to methylene chloride in pharmaceutical production facilities.

A series of field evaluations was performed to estimate the overall uncertainty of three manufacturers' passive monitors (Assay Technology Model 541 and 546, 3M Model 3520, and SKC Model 575-001) to determine methylene chloride (MeCl2) concentrations. Area samples were exposed in a pharmaceutical production facility at five MeCl2 air concentrations for both permissible exposure limit (PEL) and short-term exposure limit (STEL) periods. A specially designed evaluation chamber was used to concurrently expose six of each type of passive monitor while concurrently collecting six active samples from locations surrounding the dosimeter array. The active samples were used to estimate the actual concentration during the evaluation period. The precision, bias, and overall uncertainty were estimated for each monitor type at concentrations bracketing the Occupational Safety and Health Administration proposed exposure limits. The actual MeCl2 concentrations for the PEL sampling periods ranged from 0.9 to 63 ppm. The pooled overall uncertainty results for all the passive monitors evaluated under PEL sampling conditions met the NIOSH accuracy recommendations. Pooled overall uncertainty for PEL evaluations for the monitors were: Assay Technology Model 546 +/- 17%; 3M +/- 13%; and SKC +/- 17%. Actual MeCl2 concentrations for the STEL sampling periods ranged from 14 to 357 ppm. Pooled overall uncertainty results for Assay Technology and 3M monitors evaluated under STEL sampling conditions met the NIOSH accuracy recommendations; however, the SKC passive monitor was slightly greater than the NIOSH recommendation. Pooled overall uncertainty for STEL evaluations for the monitors were: Assay Technology Model 541 +/- 18%; 3M +/- 16%; and SKC +/- 27%.

Evaluation of real-time techniques to measure hydrogen peroxide in air at the permissible exposure limit.

The major occupational concern from bio-decontamination of equipment using vapor phase hydrogen peroxide (VHP) generation systems is potential operator exposure outside the protective barrier from possible VHP leaks or accidental releases from the sealed piece of equipment during decontamination. For this reason, different real time monitoring techniques were evaluated to determine their ability to accurately measure VHP at concentrations ranging from 0.5 ppm to 5 ppm. The results of this laboratory evaluation suggest that two of the four methods evaluated (the ion mobility spectrometer [IMS] and Polytron) will approximate the National Institute for Occupational Safety and Health +/- 25% accuracy requirements for measuring the concentration of VHP at and near the Occupational Safety and Health Administration permissible exposure limit of 1.0 ppm. Over the range of 0.5 ppm to 5.1 ppm VHP, the IMS had an approximate pooled method accuracy of +/- 21%, while the Polytron had a pooled method accuracy of +/- 22%. However, both instruments had false readings when exposed to nominal concentrations of methanol, bleach, and sulfur dioxide. The two additional VHP monitoring techniques evaluated (the single point monitor [SPM] and Draeger tube) were unable to accurately measure the concentration of VHP when the relative humidity was below 20%.

Smoking cessation in women: findings from qualitative research.

The purpose of this descriptive exploratory study is to describe the experience of successful smoking cessation in adult women. The convenience sample included 10 women, ages 25 to 42, who had abstained from smoking for at least 6 months but not longer than 3 years. A semistructured interview format was used to elicit descriptions of the experience of successful smoking cessation from these subjects. The interview format explored the experience, including initial contemplation, the process of quitting, and maintenance of smoking abstinence. Interviews were audiotaped, transcribed, and then analyzed using methods outlined by Miles and Huberman [1]. Four themes emerged from the data: evolving commitment to health and personal growth, being stigmatized, changing conceptualization of smoking, and smoking cessation as a relational phenomenon. These findings were consistent with Pender's Health Promotion Model and have implications for nurse practitioners who counsel women on smoking cessation.

Analysis of organic vapors in the workplace by remote sensing Fourier transform infrared spectroscopy.

A Remote Sensing-Fourier Transform Infrared (RS-FTIR) system was applied to identify and quantify air contaminants along the beam, ranging from single compounds to mixtures, in various workplaces. Gas chromatography (GC) was used to provide information of point concentration variation by means of analyzing charcoal tube samples placed along the beam path. The results indicated a correlation between the charcoal tube-GC and the RS-FTIR for the analysis of most compounds. Discrepancies were found for some compounds, such as acetone, due to inhomogeneous concentration distributions along the IR beam, and due to the overlap of the acetone signal with off-scale water peaks. The study also demonstrated that there was little effect on quantitative analysis from partial or complete IR beam blockages during measurement. Qualitative analysis of unexpected compounds using RS-FTIR was also evaluated. In addition, the ability of the RS-FTIR to detect a sudden release of chemicals was demonstrated in the study.

Internal wall losses of pharmaceutical dusts during closed-face, 37-mm polystyrene cassette sampling.

A current practice for the determination of personal exposures to dusts involves the aspiration of known quantities of air through membrane filters held in 37-mm plastic cassettes. Samples are collected with the cassettes in the closed-face configuration. A major negative bias error has been identified with this sampling procedure for low-level pharmaceutical dusts. For the pharmaceuticals studied, on average, 62% of the active dust collected in each sample was found on the inside surface of the cassette top. Only 22% of the total active ingredient of the dust was found on the filters. The remaining 16% was found on the inside of the cassette bottoms; electrostatic attraction appears to be the reason that pharmaceutical dusts adhere to the inside surface of the cassette. Adherence to the inside surfaces of the polystyrene cassette occurs without regard to the type of material used to seal the two-piece cassette together. The use of shrink wrap versus plastic tape versus using no sealing material had no effect on where or how much of the active ingredient was found on the inside cassette surfaces. Because very little active ingredient was identified in backup cassettes, it is hypothesized that the active ingredient found on the inside of the bottom portion of the cassettes (past the filter and support pad) got there by falling off the filter during filter removal from the cassette prior to analysis. To eliminate both of these errors, an internal cassette extraction procedure was developed that (1) negates the error caused by static charging and (2) eliminates the need for opening the cassettes prior to analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and validation of a protocol for field validation of passive dosimeters for ethylene oxide excursion limit monitoring.

An exposure and analysis protocol is described for the field validation of passive dosimeters for ethylene oxide (EtO) excursion limit monitoring. The protocol calls for the use of a field exposure chamber with concurrent sampling using Tedlar air-sampling bags. The bags are analyzed immediately after sampling by gas chromatography with flame ionization detection (GC-FID). The chamber design allows all monitors to be exposed for the exact same time in the field. The sampling and analysis procedure not only determines the actual concentration of EtO present during the monitor's exposure but estimates if concentrations of EtO vary from point to point in the monitor array during the exposure. In chamber operation, the accuracy of the standard generator used to calibrate the GC-FID was independently verified in the field by the standard additions method. The sampling bias of the sampling train was determined to be -3.5% in the 2.4 ppm to 14.3 ppm concentration range. To estimate the stability of collected EtO samples in Tedlar bags, the rate of EtO loss in the bags was determined to be 0.011 ppm/hr at 2.57 ppm and 0.066 ppm/hr at 8.07 ppm. Sampling bias of the passive methods by additional EtO exposure of the monitors in the closed chamber after sampling and during purging was determined to be +1.5%. The Tedlar bag sampling method with subsequent GC-FID determination demonstrated a coefficient of variation of 1.8% at 2.43 ppm.

Field validation of three passive dosimeters for excursion limit monitoring of ethylene oxide.

The Occupational Safety and Health Administration (OSHA) set a 5-ppm excursion limit (EL) for ethylene oxide (EtO) in April 1988. Both active and passive sampling methods have been proposed for monitoring workers against this new standard. Passive dosimetry has considerable advantages over active sampling for monitoring short-term exposures to EtO, including reduced sampling and analysis complexity, increased chemical stability, and reduced cost. The major disadvantage of these passive methods is their questionable ability to meet the OSHA requirement for the test result to fall within +/- 35% of the "true" result with 95% confidence at the EL over a 15-min sampling period. A field validation study was performed to estimate the accuracy of three EtO EL passive dosimeters: 3M 3550/3551, Crystal Diagnostics AirScan, and Assay Technology EO CHEM CHIP. Area samples were taken at four unique concentration areas within a hospital products sterilization facility. A specially designed field exposure chamber was used to expose 12 dosimeters of each type concurrently at each sampling location while concurrently collecting six Tedlar bag samples from locations surrounding the dosimeter array. The Tedlar bag samples were analyzed on-site by gas chromatography with flame ionization detection (GC-FID). To enhance the strength of this validation study, manufacturers of the dosimeters were requested to take part in the investigation. Their input was used during the design of the exposure chamber and study protocol and in the interpretation of the results. Two of the three dosimeter types were analyzed by the investigators.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory and field validation of a JXC charcoal sampling and analytical method for monitoring short-term exposures to ethylene oxide.

A sampling and analytical method for the measurement of ethylene oxide (EtO) short-term exposure limits (STEL) was validated under both laboratory and field conditions. These studies were designed to examine the method against both the Occupational Safety and Health Administration (OSHA) EtO permissible exposure limit (PEL) method requirements and the National Institute for Occupational Safety and Health (NIOSH) industrial hygiene method validation criteria. The method's pooled accuracy was shown to be within both OSHA requirements and NIOSH guidelines. The EtO was collected on a JXC charcoal tube at a sample flow rate of 100 mL/min for 15 min. The samples were shipped on dry ice and were stored in a freezer until analyzed. The EtO was desorbed by carbon disulfide and the eluent was analyzed by gas chromatography with flame ionization detection (GC-FID). The desorption efficiency of EtO from JXC charcoal tubes was determined to be 84% over the 15-min time-weighted average concentrations: 2.5, 5.0 and 10 ppm EtO. The method limit of detection was determined to be 1.0 ppm. The coefficient of variation of the combined sampling and analytical method was 5.7%. A -7% method bias was calculated. Field validation of the method included data from a portable GC-FID for the determination of method bias. Results of the field validation study over the concentration range of 2.4 ppm to 19.9 ppm generated a field precision of 8.1% with an absolute bias of 3.9%. The method accuracy was determined to be +/- 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourier transform infra-red spectroscopy applied to hazardous waste: I--Preliminary test of material analysis for improvement of personal protection strategies.

Many chemicals, when mixed, can produce potentially hazardous effects which are harmful to human health and to the environment such as heat, pressure, fire, explosion, violent reaction, and toxic dusts, mists, fumes, and/or gases. Waste chemicals handled on a remedial action site are analyzed by simple chemical methods for compatibility. Because it is difficult to base worker and community protection programs on this limited knowledge of material content, extreme precautions must be taken to ensure safety to all working on or living near hazardous waste remedial action sites. The approach used in this study involved the application of Fourier transform infra-red spectroscopy (FTIR) to the analysis of samples taken from the Chem-Dyne remedial action hazardous waste site. The data generated are compared to the results obtained using compatibility and GC-MS analysis procedures. Illustrations are given of improved personal protection strategies, based on drum material composition obtainable by FTIR. The requirements for further testing are defined.