Milk secretion of nitrofurantoin,as a specific BCRP/ABCG2 substrate,in assaf sheep: modulation by isoflavones1

Studies on residues in milk used for human consumption have increased due to health concerns and priority interest in the control of potentially risky drugs. The protein BCRP/ABCG2, present in the mammary epithelia, actively extrudes drugs into milk and can be modulated by isoflavones. Nitrofurantoin is a specific BCRP substrate which is actively excreted into milk by this transporter. In this research, we studied nitrofurantoin transport into milk in four experimental groups: G1‐calves fed forage with isoflavones; G2‐calves fed forage with isoflavones and administered exogenous genistein and daidzein; G3‐calves fed forage without isoflavones; G4‐calves fed forage without isoflavones and administered exogenous genistein and daidzein. Results show increased levels of nitrofurantoin in milk from calves without isoflavones (G3) and decreased nitrofurantoin residues in milk when isoflavones were present, either by forage (G1 and G2) or by exogenous administration (G4). The values of C_max in milk were significantly lower in those groups with isoflavones in forage (G1, G2). Plasma levels were low and unmodified among the groups. Inter‐individual variation was high. All these results seem to point to a feasible control of drug secretion into milk through isoflavones in the diet when the drug is a good BCRP/ABCG2 substrate.     

USE OF TRANSSPLENIC INJECTION OF AGITATED SALINE AND HEPARINIZED BLOOD FOR THE ULTRASONOGRAPHIC DIAGNOSIS OF MACROSCOPIC PORTOSYSTEMIC SHUNTS IN DOGS

We describe the use of ultrasonography‐guided percutaneous splenic injection of agitated saline and heparinized blood for the diagnosis of portosystemic shunts (PSS) in 34 dogs. Agitated saline mixed with 1 ml of heparinized autologous blood was injected into the spleen of 34 sedated dogs under sonographic guidance. The transducer was then sequentially repositioned to visualize the portal vein, the caudal vena cava, and the right atrium through different acoustic windows. It was possible to differentiate between intrahepatic and extrahepatic shunts depending on the entry point of the microbubbles into the caudal vena cava. Portoazygos shunts and portocaval shunts could be differentiated based on the presence of microbubbles in the caudal vena cava and/or the right atrium. In one dog, collateral circulation due to portal hypertension was identified. In dogs with a single extrahepatic shunt, the microbubbles helped identify the shunting vessel. The technique was also used postoperatively to assess the efficacy of shunt closure. All abnormal vessels were confirmed by exploratory laparotomy or with ultrasonographic identification of the shunting vessel. Ultrasound‐guided transsplenic injection of agitated saline with heparinized blood should be considered as a valuable technique for the diagnosis of PSS; it is easy to perform, safe, and the results are easily reproducible.     

PATHOLOGIC CORRELATION OF RESISTIVE AND PULSATILITY INDICES IN CANINE ABDOMINAL LYMPH NODES

We assessed the ability of the resistive index (RI) and pulsatility index (PI) to allow differentiation between normal, reactive, and neoplastic lymph nodes. Forty-seven medial iliac and 54 mesenteric lymph nodes from 83 dogs were evaluated sonographically. A cytologic sample was obtained in each dog that allowed categorization into one of the categories defined above. We found a significant difference in the RI and PI in nonneoplastic vs. neoplastic medial iliac and mesenteric lymph nodes. Values higher than 0.67 for the RI and 1.02 for the PI in medial iliac lymph nodes and higher than 0.76 for the RI and 1.23 for the PI in mesenteric lymph nodes had a high sensitivity and specificity for differentiating benign from neoplastic lymph nodes.     

ULTRASONOGRAPHIC APPEARANCE OF THE INTRAVASCULAR TRANSIT OF AGITATED SALINE IN NORMAL DOGS FOLLOWING ULTRASOUND GUIDED PERCUTANEOUS SPLENIC INJECTION

Portosystemic shunts (PSSs) allow portal blood to bypass the liver and enter the systemic circulation. Definitive diagnosis requires surgical identification, positive contrast portography, ultrasonography, or scintigraphy. This study was designed as a preliminary step to developing an alternative/adjuvant protocol to these imaging modalities. The main goals were to establish a technique for ultrasound‐guided percutaneous trans‐splenic injection of agitated saline, to evaluate the feasibility of performing the test to explore the postsplenic portal vasculature highlighted by the microbubbles, and to ascertain whether agitated saline microbubbles cross the sinusoidal barrier. Agitated saline was injected into the spleen of 20 healthy sedated dogs under sonographic guidance. The transducer was then repositioned to visualize the portal vein, the caudal vena cava, and the right atrium through different acoustic windows. Satisfactory results were achieved in all dogs. The microbubbles were visualized in all dogs as small intense echo signals within the portal vein at the level of the porta hepatis immediately after injection. In 18 out of 20 dogs, the echogenic signal of the microbubbles disappeared immediately once within the hepatic parenchyma, whereas in two dogs, the echoes from the microbubbles lasted for several seconds within the intrahepatic portal vasculature. The absence of microbubbles beyond the sinusoidal barrier in all of the healthy dogs included in this study makes trans‐splenic injection of agitated saline a candidate as an adjuvant technique for the diagnosis of PSS, being easy to perform and repeat, as well as safe and technically feasible.     

A Bayesian model for anchovy (Engraulis encrasicolus): the combined forcing of man and environment

Fishery collapses frequently result from combined pressures of the environment and man, which are difficult to discern because of the complexities involved and our limited knowledge. Models to resolve this complexity often become too sophisticated, with too many assumptions and, consequently, with little capacity to predict beyond calibration data. In this paper we implement a different procedure where the model is kept simple and uncertainty accounts for the equation imperfectness to reproduce ecological complexity. Human and environmental forcing on an anchovy ( Engraulis encrasicolus ) stock are simulated with only six parameters plus their error terms, and the uncertainty is computed with Bayesian methods. The simple structure is able to reproduce the major dynamical features of this species in the Gulf of Cádiz, including data on life stages and age structure that had no contact with the model. This is a distinct performance for a frugal approach working on a mid-trophic species and a positive instance where parsimony can simulate the interaction of man, fish and the environment, provided uncertainty is accounted for in the process.     

Bioavailability of albendazole sulphoxide after netobimin administration in sheep: effects of fenbendazole coadministration.

After oral co-administration of two dosages of netobimin (7.5 and 20 mg kg-1 with fenbendazole (1.1 mg kg-1) to Merino sheep, the AUC0-infinity of albendazole sulphoxide at the lower dosage of netobimin, was significantly increased (75.5 per cent) from control value (34.43 +/- 7.91 versus 60.33 +/- 11.93 microg h ml-1). The pharmacokinetic parameters MRT and T1/2 were also increased: 18.96 +/- 2.54 vs 26.44 +/- 4.69 h and 10.31 +/- 1.72 vs 22.28 +/- 6.75 h respectively. No data corresponding to the higher dosage of netobimin (20 mg kg-1) were statistically different from control values. It is concluded that fenbendazole increases the bioavailability of albendazole sulphoxide in sheep at the 7.5 mg kg-1 dosage, and this may produce a potentiated anthelmintic action.     

Detection of infectious pancreatic necrosis in a carrier population of rainbow trout, Oncorhynchus mykiss(Richardson), by flow cytometry

Abstract. A non-lethal study of the disease status of adult rainbow trout, Oncorhynchus mykiss (Walbaum), suspected of being carriers of infectious pancreatic necrosis virus (IPNV) was carried out using purified leucocytes from pooled blood samples. Leucocytes were stained by indirect immunofluorcscence to detect IPN viral antigen and analysed by flow cytometry. Leucocytes from an IPN free source were also used as controls. Three populations of leucocytes were analysed: (1) leucocytes examined immediately following purification from blood, which gave positive results with 30–58% of fluorescent cells: (2) purified leucocytes cultured for 7 days in medium at 15 °C. which gave a higher number of fluorescent cells, suggesting multiplication of IPNV; and (3) leucocytes co-cultured on CHSE-214 cell monolayers for 7 days at 15 °C, which amplified the number of infected leucocytes to more than 90% but delayed the result 7 days. Isolation and serological identification of the pathogen was carried out on CHSE-214 cells, which confirmed the positive results obtained by flow cytometry analysis. Further experiments are in progress to complete the applications of flow cytometry to salmonid virus studies.