Ranking ecological risks of multiple chemical stressors on amphibians.

Populations of amphibians have been declining worldwide since the late 1960s. Despite global concern, no studies have quantitatively assessed the major causes of this decline. In the present study, species sensitivity distributions (SSDs) were developed to analyze the sensitivity of anurans for ammonium, nitrate, heavy metals (cadmium, copper), pesticides (18 compounds), and acidification (pH) based on laboratory toxicity data. Ecological risk (ER) was calculated as the probability that a measured environmental concentration of a particular stressor in habitats where anurans were observed would exceed the toxic effect concentrations derived from the species sensitivity distributions. The assessment of ER was used to rank the stressors according to their potential risk to anurans based on a case study of Dutch freshwater bodies. The derived ERs revealed that threats to populations of anurans decreased in the sequence of pH, copper, diazinon, ammonium, and endosulfan. Other stressors studied were of minor importance. The method of deriving ER by combining field observation data and laboratory data provides insight into potential threats to species in their habitats and can be used to prioritize stressors, which is necessary to achieve effective management in amphibian conservation.

Use of mechanistic data in IARC evaluations.

Consideration of mechanistic data has the potential to improve the analysis of both epidemiologic studies and cancer bioassays. IARC has a classification system in which mechanistic data can play a pivotal role. Since 1991, IARC has allowed an agent to be classified as carcinogenic to humans (Group 1) when there is less than sufficient evidence in humans but there is sufficient evidence in experimental animals and "strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity." Mechanistic evidence can also substitute for conventional cancer bioassays when there is less than sufficient evidence in experimental animals, just as mechanistic evidence can substitute for conventional epidemiologic studies when there is less than sufficient evidence in humans. The IARC Monographs have used mechanistic data to raise or lower a classification that would be otherwise based on epidemiologic studies and cancer bioassays only. Recently, the IARC Monographs have evaluated several agents where mechanistic data were pivotal to the overall evaluation: benzo[a]pyrene, carbon black and other poorly soluble particles, ingested nitrates and nitrites, and microcystin-LR. In evaluating mechanistic data, it is important to consider alternative mechanistic hypotheses, because an agent may induce tumors through multiple mechanisms.

[Use of nitrates in hospitalised elderly patients aged 65 and over]. / Utilisation des dérivés nitrés chez les patients âgés de 65 ans et plus hospitalisés en médecine interne.

BACKGROUND: Nitrates are frequently prescribed drugs, although their indications are limited. We studied nitrates' prescription in elderly patients hospitalised in the internal medicine ward of a French teaching hospital. METHODS: Hospitalised patients aged 65 years and more and receiving nitrates in their usual treatment were identified prospectively. A standardised questionnaire was used during a structured medical interview conducted by the same physician for all patients. Informations regarding nitrates' prescription were studied according to the actual recommendations for their use: angina in patients with contraindication to betablockers, acute myocardial infarction and acute pulmonary oedema. RESULTS: Among 256 hospitalised elderly patients, 49 (19% [IC95%: 15-25]) were under nitrates therapy, because of either angina pectoris, heart failure or unknown reason. Cardiologists prescribed nitrates in accordance with guidelines significantly more frequently than non-cardiologists. Transdermal treatment was used in 69% of patients. DISCUSSION: In hospitalised patients aged 65 years and more who are prescribed nitrates in their usual treatment, at least one quarter have no recommended indication for its use. As almost one fifth of patients are receiving nitrates in their usual treatment, the medicoeconomic impact of these useless prescriptions could be significant. Nitrates prescribing can be optimized by following guidelines for their use, and restraining from prescribing the transdermal treatment which is more costly and without evidence-based clinical benefit compared to the oral route.

Application of classification-tree methods to identify nitrate sources in ground water.

A study was conducted to determine if nitrate sources in ground water (fertilizer on crops, fertilizer on golf courses, irrigation spray from hog (Sus scrofa) wastes, and leachate from poultry litter and septic systems) could be classified with 80% or greater success. Two statistical classification-tree models were devised from 48 water samples containing nitrate from five source categories. Model 1 was constructed by evaluating 32 variables and selecting four primary predictor variables (delta 15N, nitrate to ammonia ratio, sodium to potassium ratio, and zinc) to identify nitrate sources. A delta 15N value of nitrate plus potassium > 18.2 indicated animal sources; a value < 18.2 indicated inorganic or soil organic N. A nitrate to ammonia ratio > 575 indicated inorganic fertilizer on agricultural crops; a ratio < 575 indicated nitrate from golf courses. A sodium to potassium ratio > 3.2 indicated septic-system wastes; a ratio < 3.2 indicated spray or poultry wastes. A value for zinc > 2.8 indicated spray wastes from hog lagoons; a value < 2.8 indicated poultry wastes. Model 2 was devised by using all variables except delta 15N. This model also included four variables (sodium plus potassium, nitrate to ammonia ratio, calcium to magnesium ratio, and sodium to potassium ratio) to distinguish categories. Both models were able to distinguish all five source categories with better than 80% overall success and with 71 to 100% success in individual categories using the learning samples. Seventeen water samples that were not used in model development were tested using Model 2 for three categories, and all were correctly classified. Classification-tree models show great potential in identifying sources of contamination and variables important in the source-identification process.

[Nitric oxide-dependent endogenous and exogenous vasodilators. The mechanism of action of nitrates]. / Vasodilatadores endógenos e exógenos dependentes do óxido nítrico. Mecanismo de acção dos nitratos.

The concept of endothelium-dependent vasodilation was developed after the discovery in 1980 of the endothelium-derived relaxing factor (EDRF) by Furchtgott and Zawadzki. In 1987 Furchgott and Ignarro identified the EDRF with nitric oxide. In the same year Moncada and coworkers demonstrated that the liberation of nitric oxide by endothelial cells was responsible by the biologic activity of EDRF. Nitric oxide is the endogenous mediator responsible by the endothelium-dependent vasodilation and can be considered the endogenous nitrovasodilator. But nitric oxide has a more complex spectrum of action, because it participates in the regulation of platelet activity and preservation of the normal structure of the vessel wall. Nitric oxide is also the terminal product of the biotransformation of therapeutic nitrates responsible by guanylate cyclase activation. Nitrates can be classified as endothelium non dependent vasodilators because some of them release spontaneously nitric oxide from their metabolites, and others are biotransformed to nitric oxide in vascular smooth muscle cells.

Do nitrates differ?

1. The organic nitrates all share a common biochemical and physiological mechanism of action. 2. The organic nitrates differ substantially in their pharmacologic potency and pharmacokinetics. In vitro potency differences appear larger than the corresponding in vivo activities. 3. The duration of action of organic nitrates, after a single immediate-release dose, is governed by the pharmacokinetics of the drug. However, the duration of action of available sustained-release preparations, whatever the nitrate or formulation, is limited to about 12 h, due to the development of pharmacologic tolerance. 4. Nitrates do not appear to differ in their production of undesirable effects.