Kinetics of lithium as a lithium chloride dose suitable for conditioned taste aversion in lactating goats and dry sheep.

Lithium chloride (LiCl) is widely used for inducing conditioned taste aversion (CTA) so that livestock will reduce or avoid ingestion of toxic plants and graze groundcover mingled with valuable crops. However, pharmacokinetic studies of LiCl at effective CTA doses are lacking. With this aim, 6 Murciano-Grandina dairy does during late lactation and 6 dry Manchega dairy ewes were orally dosed with 200 and 225 mg LiCl/kg BW, respectively. Does were placed in metabolism cages whereas ewes were group fed in pens. Lithium was measured over 168 (does) and 192 h (ewes) at predefined intervals in plasma, urine, feces, and milk using flame atomic absorption spectroscopy. Plasma Li concentrations reached a maximum at 4 h in does (13.4 ± 1.35 mg Li/L) and 12 h in ewes (17.7 ± 0.8 mg Li/L). The calculated plasma half-lives were 40.3 ± 3.8 and 30.9 ± 2.1 h for does and ewes, respectively. In goats, all Li administered was recovered at 96 h (92 ± 4% in urine, 6.5 ± 1.3% in feces, and 2.8 ± 0.4% in milk); however, the estimated clearance time in feces was 11 and 9 d for does and ewes, respectively. Additionally, maximum Li excretion in doe milk was 15.6 ± 0.5 mg/L, which was approximately half of the calculated effective dose for a 5-kg BW sucking kid. In conclusion, Li kinetics in goats and sheep were similar to cattle and elimination took longer than in monogastric species. The low concentration of Li in feces, urine, and milk, as well as the complete elimination of Li from the body after 1.5 wk allows us to conclude that LiCl is safe and suitable for inducing CTA in ruminants.

Hypoxic pulmonary vasoconstriction and gas exchange during exercise in chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD) studied at rest, nifedipine releases hypoxic pulmonary vasoconstriction (HPV) and worsens gas exchange. During exercise, this drug lowers pulmonary hypertension, but the effects of this lower pulmonary vascular tone on ventilation-perfusion (VA/Q) relationships are still poorly understood. To analyze them, we determined the VA/Q distributions in eight patients with stable COPD (FEV1, 36 percent of predicted) at rest and during exercise (60 percent VO2 max), before and after nifedipine (20 mg sublingually). Nifedipine shifted to the right the pulmonary pressure-flow relationship (p less than 0.01) and increased the dispersion of the blood flow distribution at rest and during exercise (p less than 0.005). These observations strongly suggest that nifedipine released HPV under both conditions. However, even after releasing HPV by nifedipine, exercise distributed blood flow more homogeneously than at rest (p less than 0.05). Besides, exercise greatly decreased the overall degree of VA/Q mismatching (p less than 0.001) not only before but also after nifedipine. Thus, we postulate that most of the VA/Q improvement that exercise may induce in patients with COPD, as it is shown here, is due to improvement in the ventilation distribution. Interestingly, this VA/Q improvement was not paralleled by a significant decrease of P(A-a)O2. This apparent paradox could be explained by 20 percent of the actual P(A-a)O2 during exercise due to diffusion limitation, as assessed through the inert gas approach. Taken all together, these results help to better understand the mechanisms that govern pulmonary gas exchange during exercise in COPD.

Species scaling of propafenone disposition and concentration--time relationships among eight mammalian species.

Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additionally, volume of distribution (Vdss = 6.5 B0.94) and clearance (CL = 0.17 B0.86) were correlated to body weight (B). Different units of pharmacokinetic time were evaluated with an Akaike Information Criterion test, and the Syndesichron was the unit that provided the best superimposition for the concentration-time plot for all animal species. It can be inferred that all mammalian species eliminated half of the dose from their bodies in 4759 Syndesichrons.

Prediction of the disposition of propafenone in humans and dogs from pharmacokinetic parameters in other animal species.

Most allometric studies performed until now have considered results obtained by different authors. The parameters mentioned in these studies reflect experiments made under very different conditions and have been calculated by assembling these heterogeneous data reported in the literature. In this paper, we present an allometric study of propafenone carried out in eight animal species, all treated and handled under the same conditions, and taking into account their weight to calculate different pharmacokinetic parameters. Propafenone plasma concentration-time data were analyzed by a model-independent method, and the pharmacokinetic parameters (Y) were correlated with body weight (B) using linear regression analysis by the equation Y = aBx. In addition, human and dog pharmacokinetic parameters were predicted from the results obtained in the other seven species and compared with the experimentally observed values. We demonstrated that these predictions are subject to great error when drugs with extensive metabolism, such as propafenone, are considered.

Comparative study on the fatty acid composition of two marine vertebrates: striped dolphins and loggerhead turtles.

The fatty acid composition of total lipids extracted from seven different tissues (fat, liver, cerebrum, cerebellum, lung, kidney and muscle) of 10 striped dolphins (Stenella coeruleoalba) (weight 75.7 +/- 16.2 kg) found dead or moribund during a morbillivirus epizootic, and from two tissues (fat and liver) of 54 loggerhead turtles (Caretta caretta) (18.5 +/- 10.5 kg) seized dead after illegal capture, both from the Mediterranean Sea, have been determined by high resolution chromatography techniques. When comparing both species, fatty acid composition is surprisingly similar, with a predominance of the monoenoic followed by the saturated group of fatty acids, and a very close ratio of polyunsaturates n-3/n-6. The relatively high arachidonic acid content in the liver of the two marine species is remarkable. The similar diet can play an important role in these findings, but it is suggested that probably metabolic pathways and essential fatty acid requirements between both marine vertebrates are similar, more than is expected from their earlier filogenetic evolutionary divergence.

The effects of grit supplementation and feed type on steel-shot ingestion in mallards.

Lead poisoning by shot-pellet ingestion is an important cause of death in waterfowl from wetlands that have high densities of lead-shot pellets and low availabilities of grit in their sediments. To evaluate grit supplementation when mixed with baited grain as a method of reducing shot ingestion in waterfowl, 24 mallards (Anas platyrhynchos) were kept in captivity to study the relationship between steel-shot, grit and grain ingestion in four experiments. Steel-shot ingestion was more related to seeking grit than to feeding on grain, and it did not differ between two types of grain offered (rice or sorghum). Grit ingestion increased with grit supplementation and shot ingestion was only slightly reduced. Calcareous grit used in the experiments had a shorter half-life (1.4 days) in the gizzard than values reported for siliceous grit (3.1 days).

Lead shot pellets in the Ebro delta, Spain: densities in sediments and prevalence of exposure in waterfowl.

Lead (Pb) poisoning has been found to be a serious problem for waterfowl in some southern European countries, but few studies have been conducted in Spain. In order to obtain these data, studies were made in the Ebro delta, a Spanish Ramsar site, during 1992 and 1993. Lead shot densities in the first 20 cm of sediment ranged from < 8 900 to 2 661 000 shot ha(-1). A similar proportion of birds had lead shot in the gizzard and elevated liver lead (> 5 microg g(-1) DW) concentrations. Northern pintail and common pochard (both with declining populations in Europe) showed the highest levels of shot ingestion, with 70.8 and 69.2%, respectively. Body condition index in the northern pintail was negatively correlated with the number of pellets in the gizzard and liver Pb concentration. Levels of exposure were higher than in other northern countries of the western Palearctic flyway, where lead shot have been banned recently.

Analysis of polychlorinated dioxins and furans in samples of the toxic oil syndrome.

1 Polychlorinated dioxins (PCDDs) and furans (PCDFs) are known to produce a wide range of toxic effects. 2 PCDDs and PCDFs are typical contaminants of chlorinated phenols, and pentachlorophenol and related compounds have been shown to be widely distributed among selected oil samples taken from the 1981 Spanish toxic oil epidemic. 3 Six control and eight case oil samples were analysed using GC/MS for PCDDs and PCDFs. Only small concentrations, normally below 1 ng g-1, of the higher chlorinated PCDDs and PCDFs were detected. There were no statistical differences between the case and control oils. 4 These levels seem to be too low to elicit toxic effects, although they could be enough to potentiate the toxicity of other xenobiotics present in the oils. However, it is uncertain whether the levels of these compounds measured in 1990 reflect the levels present when the oils were consumed in 1981, or whether or not the levels measured in crude oils are representative of fried oils.

High Prevalences of Lead Poisoning in Wintering Waterfowl in Spain

Some Mediterranean wetlands are found between the areas with the highest prevalence of lead pellet exposure for waterfowl in the world. To assess the situation in Spain, availability of pellets in sediments and rates of ingestion by waterfowl were determined in four important wetlands: Albufera de València, El Fondo, Tablas de Daimiel, and Doñana (Guadalquivir Marshes). Lead pellet density in sediment was maximum in the Albufera, with 2.8 million pellets/ha. In Tablas de Daimiel, where hunting was banned in 1965, about 1.0 million pellets/ha were found. Percentages of shot waterfowl with ingested pellets were maximum in the wetlands on the Mediterranean coast (El Fondo and Albufera de València): 87.5% of common pochard (Aythya ferina) and approximately 33% of mallard (Anas platyrhynchos) and shoveler (Anas clypeata) contained ingested pellets. It was found that mallards with > 5 µg/g dry weight of lead in the liver had 8.5% lower body condition and 7.7% less body weight than birds with lower lead concentrations. Moreover, lead poisoning was diagnosed as the cause of death in 16 out of 75 birds, mainly greylag geese (Anser anser), found dead in some of these zones.

Marine debris ingestion in loggerhead sea turtles, Caretta caretta, from the Western Mediterranean.

Marine debris represents an important threat for sea turtles, but information on this topic is scarce in some areas, such as the Mediterranean sea. This paper quantifies marine debris ingestion in 54 juvenile loggerhead sea turtles (Caretta caretta) illegally captured by fishermen in Spanish Mediterranean waters. Curved carapace length was measured, necropsies were performed and debris abundance and type was recorded. Different types of debris appeared in the gastrointestinal tract of 43 turtles (79.6%), being plastics the most frequent (75.9%). Tar, paper, Styrofoam, wood, reed, feathers, hooks, lines, and net fragments were also present. A regression analysis showed that the volume of debris increased proportionally to the size of the turtles. The high variety of debris found and the large differences in ingestion among turtles indicated low feeding discrimination of this species that makes it specially prone to debris ingestion. Our data suggest that more severe control of litter spills and greater promotion of environmental educational programmes are needed in the Western Mediterranean.

Blood sampled in rats from right ventricle may not always be truly representative of a mixed venous sample.

Blood samples from the right ventricle (RV) in rats are usually assumed to be representative of mixed venous blood. However, results presented here suggest that this assumption may not be true in all experimental circumstances. Nineteen male Wistar rats were anaesthetized with urethane and mechanically ventilated. The six gases used in the multiple inert gas elimination technique (MIGET) were administered continuously and samples of mixed expired air and blood from the left carotid artery and RV were simultaneously withdrawn. While inert gas concentrations in arterial blood and mixed expired air were almost homogeneous, those obtained from RV blood showed a high variability, specially evident for the less soluble gases in blood. As inert gases are cleared in the lungs according to their solubility in blood and they are only replaced through the lower systemic circulation, higher or lower concentrations found in RV samples than those expected suggests a preferential collection of blood from the lower or upper systemic circulation, respectively.

An epizootic of lead poisoning in greater flamingos (Phoenicopterus ruber roseus) in Spain.

During November 1992 to March 1993, and November 1993 to February 1994, 106 greater flamingos (Phoenicopterus ruber) were collected dead or moribund in the wetlands of El Fondo and Salinas de Santa Pola, eastern Spain. Birds still alive were emaciated and had a bile-stained diarrhea. On necropsy, they had liquid in the upper digestive tract and the walls of their gizzards were stained dark green. Fifty-three (93%) of 57 gizzards examined contained lead shot (range one to 277 shot), and fifty-five (96%) of 57 livers contained levels of lead greater than 5 micrograms/g dry weight (DW) (median = 192.3 micrograms/g DW, range < 2.5 to 992.2 micrograms/g DW).

Tissue distribution of propafenone in the rat after intravenous administration.

Tissue distribution of propafenone has been studied in the rat. Measurement of propafenone was made in several tissues: plasma, heart, kidney, lung, liver, muscle, fat and brain, after i.v. administration of 2 mg/kg of the drug. The plasma propafenone kinetics profile can be described by a two-compartmental model. The pharmacokinetic parameters, derived from plasma levels, showed a t1/2 beta of 55.4 min, the central Vd/kg of 2.4 ml/kg, the Cl of 62.8 ml/min.kg and the AUC0-oo of 31.6 micrograms.min/ml. The analysis of the propafenone tissue distribution showed the highest concentration of drug in the lung, followed by the heart and kidneys. A significant concentration was found in brain, muscle and adipose tissue, with concentration ratios (tissue/plasma) above 1. The half-life values obtained for individual organs and tissues are similar to those obtained in plasma, around 1 h. In the post-distributive phase, plasma and tissue concentrations decline in parallel.

Persistent organochlorine residues in livers of six species of Ciconiiformes (aves) from Spain.

Liver samples of 42 birds belonging to 6 species of Ciconiiformes (grey heron (n = 17), little egret (n = 12), cattle egret (n = 1), glossy ibis (n = 1), little bittern (n = 1), and white stork (n = 10)), collected from two different zones of Spain (Ebro Delta and Madrid) in 1992-1997, were analyzed for organochlorine pesticides and PCBs. SigmaPCBs (sum of concentrations of individual congeners), p,p'-DDE, HCB, gamma-HCH, and heptachlor epoxide were the most prevalent residues detected in all samples (occurrence > 95%). There were no statistically significant differences in organochlorine levels between grey herons and little egrets, while levels of SigmaPCBs, p,p'-DDE, HCB, gamma-HCH, and heptachlor were significantly lower for white storks. These results could be explained by the different habitat of these species, aquatic in the Ebro Delta (grey herons, little egrets) and dry in Madrid (white stork), and their diverse feeding habits.

[Solubility of 6 gases in blood and various liquid media]. / Solubilidad de seis gases en sangre y en diversos medios líquidos.

Sulfur hexafluoride, ethane, cyclopropane, enflurane, diethyl ether and acetone are six gases commonly used in the measurement of the distribution of ventilation-perfusion ratios. In order to obtain reference data, their liquid/gas partition coefficients (K) have been determined in water at three different temperatures and in several inorganic, organic and biologic media at 37 degrees C, by a headspace-gas chromatographic method. As expected, an increase in temperature and concentration of solutes in the liquid matrix reduces the solubility of the gases. All gases, except acetone, are more soluble in olive oil than in water. The solubility of SF6, ethane, cyclopropane and enflurane in human and rat blood is greater than in water, the solubility of ether remains practically unchanged, and that of acetone is lower in blood than in water.

Heavy metals in livers of waterbirds from Spain.

Wetlands tend to accumulate heavy metals from local sources, such as Pb shot used for waterfowl hunting, and from regional sources, such as atmospheric deposition and riverine or marine inputs. We determined concentrations of six heavy metals (Cr, Mn, Cu, Zn, Cd, and Pb) in livers of waterbirds shot by hunters in five Spanish wetlands to study the different factors that can contribute to the accumulation of these metals (sex, age, diet, grit, and Pb shot ingestion). Differences among wetlands were observed only for Cr, Cu, and Cd. Differences among species were observed for all the metals, and Cu was notably higher in pochards (Aythya and Netta genus) than in other waterfowl. Cu, Zn, and Cd concentrations increased with age, and only Pb showed differences related to sex, with males having higher concentrations than females. Most metals other than Pb were correlated with each other. Lead was dependent on Pb shot ingestion. Grit ingestion positively correlated with concentrations of Cr and to a lesser extent with Mn, Zn, and Cd. Ingestion of grit or shot may obscure relationships between metals and diet. Herbivorous species, which had more grit in the gizzard, had higher Cr, Zn, and Cd concentrations. Granivorous birds, which have the highest rates of Pb shot ingestion, had the highest concentrations of Pb. Grit and Pb shot ingestion are both important sources of heavy metals for waterbirds. Lead was the single metal studied whose concentrations exceeded toxicity thresholds.

Quantitative determination of aflatoxin B1 in chick liver.

A method for the rapid and quantitative determination of aflatoxin B1 from small quantities of liver, around 1-2 g, is described. The extraction procedure involves acidification to pH 2 of the aqueous liver homogenates, extraction with chloroform: acetone and HPLC-fluorimetric detection after derivatization with trifluoroacetic acid. Quantitative recovery of aflatoxin B1 from chick liver was achieved and detection at levels of 0.2-1 ppb was proved feasible. The aflatoxin B1 concentration in chick liver after oral administration is also shown.

Rapid headspace gas chromatographic method for the determination of liquid/gas partition coefficients.

A rapid, efficient and low-cost headspace technique useful for the determination of liquid/gas partition coefficients of gases and volatile substances of low and intermediate solubility is described. The equilibration step is carried out at constant pressure using glass syringes, with a ratio of liquid/gas phase volumes of ca. 1:3; after 30 min at the desired temperature, the headspace is recovered by transfer into another syringe and analyzed by gas chromatography. A study of the partition coefficients in water at 37 degrees C of 27 volatile compounds demonstrated that the method is fully applicable for all gases, with exception of those with a partition coefficient higher than 300.

A review of the effects of agricultural and industrial contamination on the Ebro delta biota and wildlife.

The Ebro delta (NE Spain) is a 320 km2 wetland area of international importance for conservation. The area is devoted to rice farming and receives large amounts of pesticides. Industrial pollutants are also carried to the delta by the river. The information accumulated during the last 25 year on the effect of such pollution on the biota is reviewed in order to identify the existing gaps and needs for management. Organochlorine pesticides were legally used until 1977, which has resulted in the widespread presence of these compounds in the Ebro delta biota. Lethal, sublethal or other detrimental effects of these pesticides on wildlife in the area were poorly investigated, but negative effects on the reproduction of ducks and herons were reported. Nowadays, polychlorinated biphenyls (PCBs) are the main responsible of organochlorine pollution in the area: concentrations in biota samples are higher than levels observed in nearby coastal areas, as a result of the significant PCB inputs by the river which, in 1990, were evaluated at 126 kg yr(-1). The massive use of herbicides is thought to have contributed to the elimation of macrophyte vegetation in the lagoons during the eighties, which had strong consequences on diving ducks and coot populations. Weed control is also related to the loss of biodiversity held by rice fields. The massive and inadequate use of organophosphorus and carbamate pesticides (involving more than 20,000 t yr(-1) has produced some waterbird mortality events, and may have direct and indirect effects on other non-target organisms. The accumulation in the soil of lead pellets used in waterfowl shooting is estimated to kill some 16,300 waterbirds in the Ebro delta every year.