Exposure of the population to volatile organic compounds inside an automobile and a subway train

Air quality, in particular in urban regions, is affected by the emissions of the traffic and meanwhile for some substances motor vehicles became the dominating source. For valid quantitative risk assessment of the general population it is necessary to have informations about the main routes of exposure. Therefore in a pilot study 1994 and two times in summer 1995 and winter 1996 aromatic hydrocarbons, carbon monoxide (CO) and carbon dioxide (CO2) were determined under different meteorologic conditions inside of a car (a two year old VW-Golf with a three-way catalyst) and in a subway-train. The car route followed the subway (31 km underground) and crossed the central parts of Berlin in streets with high traffic density. The mean values for benzene obtained during the three measurement periods inside the car were 21.1/21.5 and 21.6 micrograms/m3 (daily maximum: 31.9/26.3 and 35.0 micrograms/m3) and inside the subway 8.4/5.4 and 7.4 micrograms/m3 (daily maximum: 16.0/7.4 and 10.3 micrograms/m3). The mean levels of CO in the car were 6 ppm (summer) and 5 ppm (winter) respectively, with peak concentrations of 33 and 70 ppm (10-minutes maximum). In the subway the values were 2 ppm (summer and winter); (10-minutes maximum: 5 and 12 ppm). A comparison between the two types of traffic shows three times higher concentrations of benzene inside the car. Our results demonstrate that the exposure of car occupants to benzene has to be taken into account for risk assessment. The concentration of CO inside the car is three to four times higher than in the subway train. Compared with other studies we found only low concentrations of CO inside the car.     

Exposure to phenol: analysis of environmental and urinary concentrations of phenol in a group of exposed subjects

The underlying metabolism and daily energy losses were studied in 22 patients with malignant tumours of the stomach and in 51 patients with pyloric stenosis and duodenal ulcer, preoperatively and over the first 9 days postoperatively. The preoperative studies revealed a rise in the underlying metabolism rate by 43.7 and 28.2%, respectively in the patients of both groups as compared to the metabolism in healthy individuals of the same sex, weight, height and age. Postoperatively, the underlying metabolism rate dropped in the oncological patients to the level seen in healthy people, whereas in duodenal ulcer patients the metabolic rates remained elevated. The patients' energy requirements are calculated respectively as 25-30 and 41-45 kcal per 1 kg body weight daily.     

Indoor air quality impacts of ventilation ducts: ozone removal and emissions of volatile organic compounds

The concentrations of contaminants in the supply air of mechanically ventilated buildings may be altered by pollutant emissions from and interactions with duct materials. We measured the emission rate of volatile organic compounds (VOCs) and aldehydes from materials typically found in ventilation ducts. The emission rate of VOCs per exposed surface area of materials was found to be low for some duct liners, but high for duct sealing caulk and a neoprene gasket. For a typical duct, the contribution to VOC concentrations is predicted to be only a few percent of common indoor levels. We exposed selected materials to approximately 100-ppb ozone and measured VOC emissions. Exposure to ozone increased the emission rates of aldehydes from a duct liner, duct sealing caulk, and neoprene gasket. The emission of aldehydes from these materials could increase indoor air concentrations by amounts that are as much as 20% of odor thresholds. We also measured the rate of ozone uptake on duct liners and galvanized sheet metal to predict how much ozone might be removed by a typical duct in ventilation systems. For exposure to a constant ozone mol fraction of 37 ppb, a lined duct would initially remove approximately 9% of the ozone, but over a period of 10 days of ozone removal efficiency would diminish to less than 4%. In an unlined duct, in which only galvanized sheet metal is exposed to the air-stream, the removal efficiency would be much lower, approximately 0.02%. Therefore, ducts in ventilation systems are unlikely to be a major sink for ozone.     

Application of a statistical model to simple discrimination learning in human subjects.

(This reprinted article originally appeared in Journal of Experimental Psychology, 1955, Vol 50, 81–88. The following abstract of the original article appeared in PA, Vol 30:4111.) Ss had to predict which of a pair of reinforcing lights would appear following a signal. Uniform reinforcement (conditioning phase) or nonreinforcement (extinction phase) was given in the presence of one stimulus set and 50% random reinforcement in the presence of the other. Correspondence of theory and data, although by no means perfect, tended to support the view that discrimination learning in this situation is a simple resultant of effects of reinforcement and nonreinforcement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Agonist-antagonist interactions at angiotensin receptors: application of a two-state receptor model

Interactions between agonists and antagonists at angiotensin receptors are characterized by a number of features: variation of antagonist dynamics between apparent simple competition, insurmountable antagonism and, occasionally, augmentation; the tendency for insurmountable antagonism to be saturable; slow recovery of agonist responses following agonist-induced tachyphylaxis; and the ability of competitive antagonists to accelerate recovery from the latter intervention. Some of these phenomena have also been observed in studies of 5-HT2 receptors where they were attributed to the operation of a two-state model with an allosteric site. In this article, Mark Robertson and colleagues propose that the properties of angiotensin AT1 receptors may be explained by a similar model, but without the need to evoke an allosteric site.     

Comparative plasma concentrations of quinidine following administration of one intramuscular and three oral formulations to 13 human subjects

A GLC method, based on flame-ionization detection, was developed for the assay of methotrimeprazine and its sulfoxide in plasma. For a 6-ml aliquot, the sensitivity was 2-3 ng/ml for the unchanged drug and 4-5 ng/ml for the sulfoxide. The coefficient of variation, calculated from duplicate analyses of plasma samples, was 8-15% for concentrations between 10 and 100 ng/ml. Patients treated with orally administered methotrimeprazine had higher plasma levels of the sulfoxide than of unmetabolized drug. The method also was applied to the analysis of promazine and chlorpromazine in patient plasma.     

Application of a first-pass effect model to characterize the pharmacokinetic disposition of venlafaxine after oral administration to human subjects

Venlafaxine (VEN), a drug used in the treatment of depression, undergoes significant first-pass metabolism after oral dosing to O-desmethylvenlafaxine (ODV), a metabolite with comparable therapeutic activity to that of parent drug. The pharmacokinetic disposition of VEN was characterized using a "first-pass" model that incorporates a presystemic compartment (liver) to account for the first-pass metabolism of VEN to ODV. A series of differential equations were simultaneously fitted to plasma concentrations of parent and metabolite. A good fit of the model to observed data was demonstrated, generating estimates for the following parameters: ka (1.31 +/- 0.009 hr-1), VVEN (252 +/- 87.6 liters), CLint (65.8 +/- 39.7 liters/hr), RL (liver:plasma partition coefficient, 29.6 +/- 18. 3), VODV (181 +/- 84.1 liters), and CLODV (23.5 +/- 12.5 liters/hr). Parameter estimates correlated closely with those obtained through noncompartmental methods. These results indicate that the time-course disposition of a compound undergoing first-pass hepatic metabolism after oral dosing can be successfully modeled.     

Stereoselective HPLC bioanalysis of atenolol enantiomers in plasma: application to a comparative human pharmacokinetic study

An enantioselective HPLC bioassay has been developed relying on extraction of (R)- and (S)-atenolol from alkalinized plasma or serum (pH > 12) into dichloromethane containing 5% (v/v) 1-butanol followed by an achiral derivatization of the drug with phosgene leading to (R)- and (S)-oxazolidine-2-one derivatives. Under these conditions there was quantitative conversion of the acetamido group to the corresponding nitrile. These stable derivatives were separated on a (R,R)-diaminocyclohexane-dinitrobenzoyl chiral stationary phase [(R,R)-DACH-DNB] using dichloromethane/methanol 98/2 as mobile phase. Determination limits of 0.5 ng for (R)- and 0.6 ng for (S)-atenolol could be achieved using fluorimetric detection. The assay was applied to a human pharmacokinetic study which was performed in a randomized cross-over, double-blind fashion in 12 healthy volunteers, administering single oral doses of 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol. AUC0-24 and Cmax values of (R)-atenolol were slightly but significant higher than those of (S)-atenolol. The R/S ratios were 1.09 for AUC(R)/AUC(S) and 1.03 for Cmax (R)/Cmax(S) (P < 0.01) respectively after administration of the racemic drug. However, there were no difference between AUC, Cmax, and t1/2 values of each enantiomer, whether they were administered as single enantiomers or in the form of its racemic mixture.     

The Swedish Centenarian Study: a multidisciplinary study of five consecutive cohorts at the age of 100

Centenarians born 1887-91, who lived in southern Sweden were asked to participate in this multidisciplinary study (N = 164). Of the survivors (N = 143), 70 percent agreed (N = 100). The purpose was to describe the population from physical, social, and psychological points of view; to characterize centenarians with various health conditions and diverse degrees of autonomy and life satisfaction; and to identify factors at 100 years that predict future survival. Results: Eighty-two percent were women, 25 percent lived in their own home, 37 percent in old age homes, and 38 percent in nursing homes. Socioeconomic status showed a similar distribution compared to nationally representative data. Fifty-two percent managed activities of daily living with or without minor assistance. The incidence of severe diseases was low. In 39 percent a disorder of the circulatory system was found. Thirty-nine percent (women) and 11 percent (men) had had at least one hip fracture. Twenty percent had good hearing and good vision. Twenty-seven percent were demented according to DSM III-R criteria. Means on cognitive tests (word-list, digit-span, learning, and memory) were lower compared to seventy to eighty year old groups. The variation in performance was extremely widespread. Personality profiles (MMPI) indicated that the centenarians were more responsible, capable, easygoing and less prone to anxiety than the population in general. Extensive neuropathological investigation revealed no major diseases or large lesions but mild through multiple changes. Results suggest that centenarians are a special group genetically. A causal structure model emphasized body constitution, marital status, cognition and blood pressure as particularly important determinants for survival after 100 years.     

Serum concentrations of retinol, d-alpha-tocopherol and beta-carotene: effects of storage at -70 degrees C for five years

To investigate the effects of prolonged storage of serum samples at -70 degrees C on concentrations of micronutrients, we measured concentrations of retinol, d-alpha-tocopherol, and beta-carotene in serum samples drawn in 1986. We compared values we measured in 1991 to values we obtained in 1986, using the same analytical methods. The relative concentrations obtained in 1991 (mean +/- S.D.) were: retinol 99.7 +/- 12.6% (n = 23), d-alpha-tocopherol 100.7 +/- 6.4% (n = 19), and beta-carotene 103.4 +/- 13.7% (n = 28). Using these techniques of sample preparation and high-performance liquid chromatographic analysis, we found that the effects of storage of serum at -70 degrees C for five years appear insignificant in a small population of patients. However, we did identify clinically important changes in concentration (> 20% difference) in several individual subjects.     

Expression of progesterone receptor isoforms in corpora lutea of human subjects: correlation with serum oestrogen and progesterone concentrations

To understand the biological significance of progesterone receptor forms A (PR-A) and B (PR-B) in human corpus luteum, the expression of mRNA and serum steroid hormone concentrations were determined simultaneously in the luteal stages. The expression of PR-A mRNA predominated over PR-B mRNA in all samples analysed. Total PR (PR-AB) and PR-B mRNA concentrations at the late secretory phase were significantly (P < 0.01) lower than those at the early and mid secretory phases of the menstrual cycle. The ratio of PR-B to PR-AB mRNA concentration showed no significant change during the secretory phase. In the early and mid secretory phases, there was a negative correlation between PR-B mRNA concentration and serum progesterone concentration, and between the ratio of PR-B to PR-AB mRNA concentrations and serum progesterone concentration (P < 0.01). These findings suggest that human corpus luteum might intracellularly synthesize PR-A and PR-B, and thus be involved in the steroid functional regulation of the corpus luteum, especially at the early and mid secretory phases, and that progesterone might regulate the synthesis of PR-A and PR-B.     

Brachymesophalangia-V in five samples of children: a descriptive and methodological study

The occurrence of brachmesophalangia-V (BMP-V) in 2,012 individuals from five samples of children of different ethnic backgrounds was determined using two indices. Frequencies of BMP-V were analyzed for three variants: BMP-V alone, BMP-V with clinodactyly, and BMP-V with a cone-shaped epiphysis. The two indices used to identify BMP-V indicated highest relative frequencies among Mexican children, moderate frequencies among children of European ancestry (Pennsylvania White, Canadian, West German), and lower frequencies in Pennsylvania Black children. Index 1, based on the ratio of the width to the length of the fifth mid-phalanx, consistently produced higher frequencies than Index 2, based on the ratio of the length of the fifth to the length of the fourth mid-phalanges. Index 1 was also more selective of BMP-alone, while Index 2 selected primarily BMP-V with clinodactyly and/or cone-shaped epiphyses. The differences between indices were largely due to the fact that Index 1, which basically defines shape, selected both the shortest and/or widest mid-phalanges, while Index 2 related actual length differences. It is suggested that Index 2 provided a more suitable criterion of BMP-V in comparative studies, due to possible population differences in phalangeal shape.     

Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.     

In vitro activities of co-amoxiclav at concentrations achieved in human serum against the resistant subpopulation of heteroresistant Staphylococcus aureus: a controlled study with vancomycin

The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and beta-lactamase activity of two isogenic (beta-lactamase and non-beta-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model. A reduction of > or = 97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation. The same pattern was observed with amoxicillin and the beta-lactamase-negative strain. beta-Lactamase activity in the beta-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups. Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the beta-lactamase-producing methicillin-resistant S. aureus to a similar extent as vancomycin.     

PET study of competition between intravenous cocaine and [11C]raclopride at dopamine receptors in human subjects

OBJECTIVE: Animal data suggest that the strong euphoriant effects of cocaine are related to the drug's enhancement of available dopamine at the synaptic cleft. The authors' goal was to determine whether this mechanism is the same in humans because the development of putative pharmacological agents for treatment of cocaine dependence depends on this knowledge. METHOD: Positron emission tomography with [11C]raclopride was used to examine the effects of the intravenous administration of 48 mg of cocaine (a typical "street" dose) on the occupancy of dopamine 2 receptors in the putamen of 11 self-identified intravenous drug abusers. RESULTS: All 11 subjects reported subjective stimulation and euphoria in response to cocaine administration. Radioligand occupancy at dopamine receptors was decreased significantly after cocaine administration, suggesting that higher dopamine concentrations were competing at the receptor site. CONCLUSIONS: These results support the concept of dopamine system involvement in human cocaine abuse.     

Convergent and discriminant validity of five classroom observation systems: Testing a model.

Evaluated the convergent and discriminant validity of selected behaviors measured by 5 classroom observation systems: the Observation Schedule and Record, the Spaulding Teacher Activity Rating Schedule, the Flanders Systems of Interaction Analysis, CERLI Verbal-Behavior Classification System, and the Classroom Communication Observational System. Five pairs of raters were trained in using each observation system, and data were obtained from the coding of 3 50-min videotapes of classroom interaction for each of 12 junior high school teachers. Comparisons of the 5 systems with one another yielded 23 categories that measured similar behaviors across 2 or more systems. Approximately half of the 23 categories passed all tests for both convergent and discriminant validity. Implications for future process–product studies and future use of the convergent and discriminant validity model are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Calmodulin binding to myosin light chain kinase begins at substoichiometric Ca2+ concentrations: a small-angle scattering study of binding and conformational transitions

We have used small-angle scattering to study the calcium dependence of the interactions between calmodulin (CaM) and skeletal muscle myosin light chain kinase (MLCK), as well as the conformations of the complexes that form. Scattering data were measured from equimolar mixtures of a functional MLCK and CaM or a mutated CaM (B12QCaM) incompetent to bind Ca2+ in its N-terminal domain, with increasing Ca2+ concentrations. To evaluate differences between CaM-enzyme versus CaM-peptide interactions, similar Ca2+ titration experiments were performed using synthetic peptides based on the CaM-binding sequence from MLCK (MLCK-I). Our data show there are different determinants for CaM binding the isolated peptide sequence compared to CaM binding to the same sequences within the enzyme. For example, binding of either CaM or B12QCaM to the MLCK-I peptide is observed even in the presence of EGTA, whereas binding of CaM to the enzyme requires Ca2+. The peptide studies also show that the conformational collapse of CaM requires both the N and C domains of CaM to be competent for Ca2+ binding as well as interactions with each end of MLCK-I, and it occurs at approximately 2 mol of Ca2+/mol of CaM. We show that CaM binding to the MLCK enzyme begins at substoichiometric concentrations of Ca2+ (< or = 2 mol of Ca2+/mol of CaM), but that the final compact structure of CaM with the enzyme requires saturating Ca2+. In addition, MLCK enzyme does bind to 2Ca2+ x B12QCaM, although this complex is more extended than the complex with native CaM. Our results support the hypothesis that CaM regulation of MLCK involves an initial binding step at less than saturating Ca2+ concentrations and a subsequent activation step at higher Ca2+ concentrations.     

Biomonitoring of possible human exposure to environmental genotoxic chemicals: lessons from a study following the wreck of the oil tanker Braer

In January 1993 the oil tanker Braer ran aground in the Shetland Islands, Scotland. Approximately 80,000 tons of crude oil were released. Exceptionally high winds caused extensive pollution and exposure of the local population to crude oil. We describe the study which was immediately set in place to examine the exposed population for evidence of genotoxic exposure. Blood samples were taken and primary DNA damage was measured in the mononuclear cell fraction by the butanol modification of the 32P-postlabelling method. Mutation was measured at the hprt locus in T lymphocytes. No evidence of genotoxicity was obtained for either end point, but nevertheless, we believe that useful lessons were learnt, which should be incorporated into the design of future studies: (1) A rapid response is essential, and even if sufficient funds are not immediately available, it is still worth attempting to obtain samples quickly and use cryopreservation, also to attempt to estimate exposure. (2) Adequate numbers of volunteers must be sought, together with enough controls, not just to allow meaningful analysis but to overcome loss of samples and failure of things to go according to plan. (3) Points concerning laboratory practice include: (i) samples should be coded, (ii) clearly defined and proven protocols should be used, (iii) irreplaceable samples should not be used for method development, (iv) should a problem become apparent during the study, work on such samples should cease immediately until the problem is solved, (v) all critical experimental components should be pretested against a laboratory standard. (4) The study design should include replicate experiments to monitor experimental variability and reproducibility, as well as internal standards and cryopreserved "in house" samples. Care must be taken that samples from any one exposure group are spread between a number of independent experiments and that each experiment includes samples from a number of exposure groups. (5) A computerised data base should be maintained with full details of experimental variables, donor attributes, and raw data so that any contribution of experimental artefacts to "outlier" results can be monitored. (6) Because of the nature of the statistical variation for many environmental genotoxicity end points, only a large-scale study is likely to be capable of yielding useful information.