The ability of anthraflavic acid to inhibit the mutagenicity of IQ was investigated using the Ames test and employing hepatic activation systems from Aroclor 1254-pretreated rats. Incorporation of anthraflavic acid into the S9 mix caused a concentration-dependent decrease in the mutagenicity of IQ. A similar effect was seen when microsomes only were employed as activation systems. Cytosol, as we have previously demonstrated, potentiated the microsome-mediated mutagenicity of IQ and this potentiation was also inhibited by anthraflavic acid. In contrast, anthraflavic acid had no effect on the mutagenicity of the direct-acting microsome-generated metabolites of IQ. It is concluded that anthraflavic acid is a potent inhibitor of IQ mutagenicity by virtue of its ability to inhibit both its microsomal and cytosolic activation pathways.

Animals↗

PubMedDate not supplied

Induction of rat hepatic cytochrome P-450 I proteins by the antimutagen anthraflavic acid.

Administration of the antimutagen anthraflavic acid to rats gave rise to significant increases in the hepatic microsomal O-deethylations of ethoxyresorufin and ethoxycoumarin, but not in the O-dealkylation of pentoxyresorufin nor in cytosolic glutathione S-transferase activity. Immunoblot studies of solubilized microsomes from anthraflavic acid-treated rats revealed that anthraflavic acid induced the apoproteins P-450 I A1 and A2 but not P-450 B1 and B2. Pretreatment with anthraflavic acid resulted in a marked increase in the in vitro bioactivation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-amino-3,2-amino-3-methylimidazomethylimidazo[4,5-f]-quinoline (IQ) to mutagenic intermediate(s); IQ is a carcinogen against which anthraflavic acid has displayed strong antimutagenic effect in the Ames test when incorporated into the metabolic activation system. The increase in mutagenicity of IQ was the result of enhancement of both the microsomal and cytosolic activation steps. It is concluded that anthraflavic acid is a specific inducer of P-450 I proteins in the rat and this compound is not only unlikely to exhibit any anticarcinogenic effect in vivo but may act as a co-carcinogen.

Animals↗

PubMedDate not supplied

Induction of the P-450 I family of proteins by polycyclic aromatic hydrocarbons: possible relationship to their carcinogenicity.

The hypothesis has been put forward that mutagenic polycyclic aromatic hydrocarbons which induce the P-450 I family of cytochromes, the major enzyme system responsible for their activation, are likely to be carcinogenic. In order to test this hypothesis, rats have been pretreated with a number of polycyclic aromatic hydrocarbons of different mutagenic and carcinogenic potency and hepatic P-450 I activity was monitored using chemical probes such as the O-deethylation of ethoxyresorufin and metabolic activation of Glu-P-1 to mutagens, and immunologically employing polyclonal antibodies against purified rat P-450 I A1. All compounds studied enhanced P-450 I activity and induced P-450 I apoproteins but the extent of induction was very markedly different. The results are discussed with reference to the mutagenicity of these chemicals in the Ames test and their carcinogenicity in the classical mouse skin model. A relationship appears to exist between carcinogenicity of polycyclic aromatic hydrocarbons and their ability to induce hepatic P-450 I activity.

Animals↗

PubMedDate not supplied

Landau-Kleffner syndrome: temporal lobe tumor resection results in good outcome.

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Aphasia↗

PubMedDate not supplied

Reduction in dissociation due to aging and cognitive deficit.

Our objective was to investigate whether dissociative experiences occur less frequently in older psychiatric patients than in younger adult patients, and to examine the role of cognitive deficits in the frequency of dissociative events. Fifty-two outpatients 60 years and older were administered the Dissociative Experiences Scale (DES) and the Mini-Mental State Exam (MMSE). Their scores were compared with those of 50 outpatients 35 to 55 years old. Each group included patients sampled from the Mental Health Center (MHC) and University Medical Center clinics. Older patients showed significantly lower DES and MMSE median scores than younger patients. Cognitive deficit reflected by reduced MMSE scores also was associated with reduced DES scores for younger and older patients. Older patients with little or no cognitive deficit continued to show reduced DES scores. Decreases in dissociativity continue well beyond the fourth decade and do not rely on age-related cognitive deficit. Factors related to the aging process seem to mediate reductions in dissociativity independent of reductions mediated by cognitive deficit. The use of the DES for screening without adjusting for age and cognitive status is questioned.

Adult↗

PubMedDate not supplied

Time-sensitive clinical management: a case study of acute asthma care.

This paper emerged from a study of change in a major teaching hospital subsequent to the introduction of casemix-based funding--a management tool designed to support the development of industrial practices in hospital management. A clinical unit had been advised to become more financially efficient. The unit staff redefined the task as becoming more clinically effective, as well as more efficient. One of the important themes to emerge was the importance of time. The resultant changes in the provision of care reflected a sophisticated approach to time.

Acute Disease↗

PubMedDate not supplied

Hazard characterisation of chemicals in food and diet. dose response, mechanisms and extrapolation issues.

Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling approaches may be applied. The default position is that rodents are good models for humans. However, some chemicals cause species-specific toxicity syndromes. Information on quantitative species differences is used to modify the default uncertainty factors applied to extrapolate from experimental animals to humans. A central theme for extrapolation is unravelling the mode of action for the critical effects observed. Food can be considered as an extremely complex and variable chemical mixture. Interactions among low molecular weight chemicals are expected to be rare given that the exposure levels generally are far below their NOAELs. Hazard characterisation of micronutrients must consider that adverse effects may arise from intakes that are too low (deficiency) as well as too high (toxicity). Interactions between different nutrients may complicate such hazard characterisations. The principle of substantial equivalence can be applied to guide the hazard identification and hazard characterisation of macronutrients and whole foods. Macronutrients and whole foods must be evaluated on a case-by-case basis and cannot follow a routine assessment protocol.

Animals↗

PubMedDate not supplied

Threshold of toxicological concern for chemical substances present in the diet: a practical tool for assessing the need for toxicity testing.

The de minimis concept acknowledges a human exposure threshold value for chemicals below which there is no significant risk to human health. It is the underlying principle for the US Food and Drug Administration (FDA) regulation on substances used in food-contact articles. Further to this, the principle of Threshold of Toxicological Concern (TTC) has been developed and is now used by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in their evaluations. Establishing an accepted TTC would benefit consumers, industry and regulators, since it would preclude extensive toxicity evaluations when human intakes are below such threshold, and direct considerable time and cost resources towards testing substances with the highest potential risk to human health. It was questioned, however, whether specific endpoints that may potentially give rise to low-dose effects would be covered by such threshold. In this review, the possibility of defining a TTC for chemical substances present in the diet was examined for general toxicity endpoints (including carcinogenicity), as well as for specific endpoints, namely neurotoxicity and developmental neurotoxicity, immunotoxicity and developmental toxicity. For each of these endpoints, a database of specific no-observed-effect levels (NOELs) was compiled by screening oral toxicity studies. The substances recorded in each specific database were selected on the basis of their demonstrated adverse effects. For the neurotoxicity and developmental neurotoxicity databases, it was intended to cover all classes of compounds reported to have either a demonstrated neurotoxic or developmentally neurotoxic effect, or at least, on a biochemical or pharmacological basis were considered to have a potential for displaying such effects. For the immunotoxicity endpoint, it was ensured that only immunotoxicants were included in the database by selecting most of the substances from the Luster et al. database, provided that they satisfied the criteria for immunotoxicity defined by Luster. For the developmental toxicity database, substances were selected from the Munro et al. database that contained the lowest NOELs retrieved from the literature for more than 600 compounds. After screening these, substances showing any effect which could point to developmental toxicity as broadly defined by the US were recorded in the database. Additionally, endocrine toxicity and allergenicity were addressed as two separate cases, using different approaches and methodology. The distributions of NOELs for the neurotoxicity, developmental neurotoxicity and developmental toxicity endpoints were compared with the distribution of NOELs for non-specific carcinogenic endpoints. As the immunotoxicity database was too limited to draw such a distribution of immune NOELs, the immunotoxicity endpoint was evaluated by comparing immune NOELs (or LOELs-lowest-observed-effect levels-when NOELs were not available) with non-immune NOELs (or LOELs), in order to compare the sensitivity of this endpoint with non-specific endpoints. A different methodology was adopted for the evaluation of the endocrine toxicity endpoint since data currently available do not permit the establishment of a clear causal link between endocrine active chemicals and adverse effects in humans. Therefore, this endpoint was analysed by estimating the human exposure to oestrogenic environmental chemicals and evaluating their potential impact on human health, based on their contribution to the overall exposure, and their estrogenic potency relative to endogenous hormones. The allergenicity endpoint was not analysed as such. It was addressed in a separate section because this issue is not relevant to the overall population but rather to subsets of susceptible individuals, and allergic risks are usually controlled by other means (i.e. labelling) than the Threshold of Toxicological Concern approach. (ABSTRACT TRUNCATED)

Animals↗

PubMedDate not supplied

Root cause analysis of laboratory delays to an emergency department.

The Q-Probes study has identified benchmark interinstitutional laboratory median turnaround times (TAT) of 25 min for hemoglobin and 36 min for potassium. Our objectives were to measure the emergency department (ED)/laboratory TAT and other relevant laboratory processing and reporting times, and to identify root causes of laboratory delay. A flow chart was developed for the ordering, collecting, analyzing, and reporting of laboratory results. Time intervals were prospectively recorded for complete blood count (CBC) and K+ in a cross-sectional study, using the flow chart, and defined as follows: TAT was the interval from blood draw (BD) to ED report; BD time was the interval from order processing to BD; and order processing time was the interval from physician ordering to the unit coordinator processing the orders. Median times with interquartile ranges are reported. CBC TAT was 38 min (29-51.5), and K+ TAT 58 min (45-76.5). Order processing time was 7 min (4-15). The laboratory assistant BD time was 17 min (8-30) for CBC and 15 min (7.75-32.25) for K+ as compared to 0 min for a nurse, yet the venipuncture method (laboratory assistant technique) had a recollection rate of 1% (1/93) due to hemolysis vs. 20% (19/95) via the i.v. catheter (nurse technique). Of stat ED blood work, 24% was for admitted patients held in the ED. Laboratory reporting times are delayed with these root causes: laboratory assistant availability; recollection rate; volume of tests for ED admitted patients; and order processing time.

Benchmarking↗

PubMedDate not supplied

The influence of intravenous Albunex injections on pulmonary arterial pressure, gas exchange, and left ventricular peak intensity.

Contrast ultrasonography may be used to assess regional tissue perfusion. The purpose of this study was to evaluate the safety and efficacy of a new, commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections were administered from peripheral intravenous (IV), right atrial (RA), and pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10, 20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately before and after each injection, pulmonary artery pressure (PAP) and oxygen tension (PO2) were determined. In addition, left ventricular cavity opacification was assessed visually and by videodensitometric off-line analysis. Visual assessment was performed by four blinded observers who graded on a scale of 0 to 3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement; and 3 = attenuation of the ultrasound signal following a contrast injection). Peak pixel intensity was also determined with videodensitometric analysis. Results showed that significant changes in PAP or PO2 were not noted after Albunex injections, regardless of injection site or dose range. The average change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS). The left ventricular cavity peak pixel intensity was dependent on both injection site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗