Waterborne outbreak of tularemia associated with crayfish fishing.

In 1997, an outbreak of human tularemia associated with hare-hunting in central Spain affected 585 patients. We describe the identification of Francisella tularensis biovar palaearctica in a second outbreak of ulceroglandular tularemia associated with crayfish (Procambarus clarkii) fishing in a contaminated freshwater stream distant from the hare-associated outbreak. The second outbreak occurred 1 year after the first.

[An outbreak of trichinosis in Huerta del Marquesado (the Cañete-Cuenca basic health area). December 1992 to January 1993]. / Brote de triquinelosis en Huerta del Marquesado (ZBS Cañete-Cuenca). Diciembre-92 a enero-93.

BACKGROUND: A trichinellosis outbreak was investigated (December 1992-January 1993). It occurred in the village of Huerta del Marquesado among people who consumed sausages made with pork, meat. The aim of this study is to show the consequences of consuming meat without a sanitary control on human health. METHODS: A case-control study was carried out. Information was obtained using a standardized questionnaire for Foodbornes. A descriptive study was done and the relationship between the intake of sausages and disease was also investigated. RESULTS: 19 cases were reported, median frequency: 11 of January. The outbreak lasted 21 days. The mean incubation period was 26.47 days (SD 4.45 days). Most frequent symptoms were fever, myalgia, eyelid's edema. The age of the patients varied from 5 to 65 years old, being the mean 33 years old. Proportionally more women than men were diseased (58%). No cases died or were hospitalized. A significant statistic association was show between trichinellosis and intake of sausages (OR = 54; 95% Confidence interval 3.1- 2622.43; p < 0.0006). Trichinella spiralis larvae have been shown in samples of the pork meat which had been eaten. CONCLUSIONS: The disease did not last excessively and was not too severe, which suggest a low parasite density. After the laboratory confirmation the meat was confiscated and destroyed. The outbreak was controlled with the active collaboration of the public health veterinarians.

Stability of some phenolic antioxidants in fatty preparations.

Stability of butylated hydroxyanisole (BHA), propyl gallate (PG), trihydroxy butyrophenone (THBP), tert-butyl hydroquinone (TBHQ) and a mixture of PG and BHA (1:1) in fatty preparations stored under three different conditions was studied. Each antioxidant was added to a fatty model to determine its degradation kinetics and its evolution during the oxidation of the fatty product. Their degradation was adequately described by a first-order kinetic process. An opposite relationship between the stability of antioxidants and their rate protection against oxidation of the fatty product was obtained. At 25 degrees C, t90 values ranged between 10 days for TBHQ and 61 days for BHA. On the other hand, compared when they were formulated alone, the increase of PG and the diminution of BHA degradation kinetics were observed. A degradation product arising from TBHQ was found in samples and stock solutions; an HPLC method for its identification is proposed with detection at 254 nm.

Residence time distribution of diazepam in the isolated perfused rat liver. Analysis with the axial dispersion model.

The application of the axial dispersion model to diazepam hepatic elimination was evaluated using data obtained for impulse-response experiments with diazepam in the single-pass isolated perfused rat liver preparation. The transient form of the two-compartment dispersion model was applied to the output concentration versus time profile of diazepam after bolus input of a radiolabelled tracer into the hepatic portal vein (n = 4), providing DN and CLint estimates of 0.251 +/- 0.093 and 135 +/- 59 ml min-1, respectively. In contrast, the one-compartment form of the axial dispersion model, which assumes instantaneous transversal distribution of substance to the accessible spaces within the liver, could not adequately describe the residence time distribution (RTD) of diazepam. Furthermore, the magnitude of DN, a stochastic parameter which characterizes the axial spreading of solutes during transit through the liver, is similar to that determined for non-eliminated substances such as erythrocytes, albumin, sucrose and water. These findings suggest that the dispersion of diazepam in the perfused rat liver is determined primarily by the architecture of the hepatic microvasculature.

Pharmacokinetics of diazepam in the rat: influence of a carbon tetrachloride-induced hepatic injury.

The pharmacokinetics of diazepam in normal rats and in rats pretreated with carbon tetrachloride to induce hepatic cirrhosis (cirrhotic rats) was studied after intravenous and oral administration of the drug (4 mg/kg). Animals pretreated with this hepatotoxic agent showed a significant prolongation in the half-life of diazepam in plasma that is due more to an increase in volume of distribution rather than to a decrease in clearance. This study confirmed that diazepam was highly extracted by the rat liver and was not affected by the hepatotoxic agent, although there probably was a saturation of the activity of the cytochrome P450 enzyme when the drug was administered orally. Diazepam binds to plasma proteins to a high degree in both normal and cirrhotic rats; however, in the latter, a significant increase in the fraction of unbound drug in plasma was observed. Pretreatment of rats with carbon tetrachloride did not produce any change either in the distribution of diazepam into erythrocytes or in the disposition of the metabolite desmethyldiazepam.

Application of the axial dispersion model of hepatic drug elimination to the kinetics of diazepam in the isolated perfused rat liver.

The application of the axial dispersion model to diazepam hepatic elimination was evaluated using data obtained for several conditions using the single-pass isolated perfused rat liver preparation. The influence of alterations in the fraction unbound in perfusate (fu) and perfusate flow (Q) on the availability (F) of diazepam was studied under steady conditions (n = 4 in each case). Changes in fu were produced by altering the concentration of human serum albumin (HSA) in the perfusion medium while maintaining diazepam concentration at 1 mg L-1. In the absence of protein (fu = 1), diazepam availability was 0.011 +/- 0.005 (mean +/- SD). As fu decreased, availability progressively increased and at a HSA concentration of 2% (g/100 ml), when fu was 0.023, diazepam availability was 0.851 +/- 0.011. Application of the axial dispersion model to the relationship between fu and F provided estimates for the dispersion number (DN) of 0.337 +/- 0.197, and intrinsic clearance (CL(int)) of 132 +/- 34 ml min-1. The availability of diazepam during perfusion with protein-free media was also studied at three different flow rates (15, 22.5, and 30 ml min-1). Diazepam availability always progressively increased as perfusate flow increased, with the axial dispersion model yielding estimates for DN of 0.393 +/- 0.128 and CL(int) of 144 +/- 38 ml min-1. The transient form of the two-compartment dispersion model was also applied to the output concentration versus time profile of diazepam after bolus input of a radiolabeled tracer into the hepatic portal vein (n = 4), providing DN and CL(int) estimates of 0.251 +/- 0.093 and 135 +/- 59 ml min-1, respectively. Hence, all methods provided similar estimates for DN and CL(int). Furthermore, the magnitude of DN is similar to that determined for noneliminated substances such as erythrocytes, albumin, sucrose, and water. These findings suggest that the dispersion of diazepam in the perfused rat liver is determined primarily by the architecture of the hepatic microvasculature.

Pharmacokinetics of diazepam in the rat: influence of an experimentally induced hepatic injury.

The aim of this study was to compare the pharmacokinetics of diazepam in normal rats and rats with a carbon tetrachloride-induced hepatic cirrhosis after intravenous and oral administration of the drug (4 mg/Kg). When animals are pretreated with this hepatotoxic agent, a significant prolongation in plasma half-life of diazepam is observed, due more to an increase in volume of distribution rather than to a decrease in clearance. Our findings confirm that diazepam is highly extracted by the liver of the rat. This parameter is not affected by the hepatotoxic agent, but probably there is a saturation of the hepatic enzyme activity when the drug is orally administered at the dose of 4 mg/Kg. Diazepam binds to a high degree to plasma proteins in normal and damaged rats, though in the last case a significant increase in the unbound fraction of drug in plasma is observed. Pretreatment of rats with Cl4C does not produce any change in distribution of diazepam into erythrocytes.