Comparison of dosimetry with magnetic resonance and computed tomography imaging delineation of surgical bed volume in breast cancer irradiation.

Background: Postoperative radiotherapy after conservative surgery for patients with breast cancer usually includes focal over-irradiation (boost) to the surgical bed (SB). Irradiation planning using computed tomography (CT) is difficult in many cases because of insufficient intrinsic soft tissue contrast. To ensure appropriate radiation to the tumor, large boost volumes are delineated, resulting in a higher dose to the normal tissue. Magnetic resonance imaging (MRI) provides superior soft tissue contrast than CT and can better differentiate between normal tissue and the SB. However, for SB delineation CT images alone remain the pathway followed in patients undergoing breast irradiation. This study aimed to evaluate the potential advantages in boost dosimetry by using MRI and CT as pre-treatment imaging. Methods: Eighteen boost volumes were drawn on CT and MRI and elastically co-registered using commercial image registration software. The radiotherapy treatment plan was optimized using the CT volumes as the baseline. The dose distributions of the target volumes on CT and MRI were compared using dose-volume histogram cutoff points. Results: The radiation volumes to the SB varied considerably between CT and MRI (conformity index between 0.24 and 0.67). The differences between the MRI and CT boost doses in terms of the volume receiving 98% of the prescribed dose (V98%) varied between 10% and 30%. Smaller differences in the V98% were observed when the boost volumes were delineated using MRI. Conclusion: Using MRI to delineate the volume of the SB may increase the accuracy of boost dosimetry.

Tylosin depletion in edible tissues of turkeys.

The depletion of tylosin residues in edible turkey tissues was followed after 3 days of administration of tylosin tartrate at 500 mg l-1 in drinking water, to 30 turkeys. Immediately after the end of the treatment (day 0) and at day 1, 3, 5 and 10 of withdrawal, six turkeys (three males and three females) per time were sacrificed and samples of edible tissues were collected. Tissue homogenates were extracted, purified and analysed by HPLC according to a method previously published for the analysis of tylosin residues in pig tissues. In all tissues, tylosin residues were already below the detection limits of 50 micrograms kg-1 at time zero. However, in several samples of tissues (skin + fat, liver, kidney, muscle), from the six turkeys sacrificed at that time, one peak corresponding to an unknown tylosin equivalent was detected at measurable concentrations. The identification of this unknown compound was performed by LC-MS/MS analysis of the extracts from incurred samples. The mass fragmentation of the compound was consistent with the structure of tylosin D (the alcoholic derivative of tylosin A), the major metabolite of tylosin previously recovered and identified in tissues and/or excreta from treated chickens, cattle and pigs.

Determination of tylosin residues in pig tissues using high-performance liquid chromatography.

In accordance with the maximum residue limit of 100 micrograms kg-1 established by EU legislation, a simple and sensitive high-performance liquid chromatographic (HPLC) method was developed for the measurement of tylosin residues in pig tissues (fat, kidney, liver and muscle). Tylosin, a macrolide antibiotic, is extracted with water-methanol and cleaned-up by solid-phase extraction (SPE) on cation-exchange cartridges using methanol elution. Tylosin was determined by reversed-phase HPLC with UV detection at 280 nm and the mean recovery from pig tissues fortified in the range 50-200 micrograms kg-1 was 70-85%, with intra- and inter-day RSDs in the ranges 3.4-9.1 and 3.9-10.1% respectively.

Distribution of the anthelmintic drug albendazole and its major metabolites in ovine milk and milk products after a single oral dose.

The distribution of albendazole (ABZ) and its main metabolites albendazole sulphoxide (ABZSO), albendazole sulphone (ABZSO2) and albendazole 2-aminosulphone (NH2ABZSO2) were investigated in bulk milk and milk products after administration of a single oral dose of the drug (12.5 mg/kg) to 80 Laticauda sheep. An analytical method was developed for this investigation from an existing procedure used for the determination of these compounds in plasma and digesta samples. No traces of the parent compound or NH2ABZSO2 were found in milk or milk products, with the exception of the milk collected 36 h after treatment in which 89 micrograms NH2ABZSO2/kg was detected. Results indicated that ABZ was rapidly oxidized to ABZSO and then to ABZSO2. These metabolites were found at high levels (1-4 mg/kg) in milk collected within 24 h after treatment. Products derived from such milk also contained high concentrations of the two oxidized metabolites, including up to 5 mg ABZSO/kg in Pecorino cheese. Only small quantities of these two metabolites were found in milk collected during the second day after treatment (range 50-500 micrograms/kg). They were no longer detectable in milk collected during the third day after dosing, nor were they found in products made from such milk. These findings confirm that the two polar metabolites ABZSO and ABZSO2 were efficiently excreted from the body. Considering that the established maximum residue limit for ovine milk is 100 micrograms/kg for ABZ plus its metabolites, our results confirmed the appropriateness of the currently prescribed withdrawal time (3 d) after the use of ABZ in lactating sheep. However, considerable levels of ABZSO were detected in milk collected within 24 h after treatment as well as in products and by-products derived from such milk. Owing to the known toxicity of the ABZSO, we stress the need for careful control to ensure adherence to the prescribed withdrawal time.

Distribution of cytosolic oestrogen and progesterone receptors in the genital tract of the mare.

The distribution of oestrogen and progesterone receptors in the equine genital tract was investigated by means of a modified dextran-coated charcoal method on samples collected from the vagina, the cervix and the uterus of 30 healthy adult Polish mares, divided into two groups on the basis of their serum progesterone levels. The concentrations of oestrogen and progesterone receptors were significantly (P < 0.05) lower in the vagina and the cervix than in the uterus, in agreement with data from human beings, cattle and pigs, which showed that the highest concentrations of oestrogen and progesterone receptors were localised respectively in the body and in the horns of the uterus.

In vitro comparison of aldicarb oxidation in various food-producing animal species.

Aldicarb (ALD) metabolism was studied in vitro using hepatic microsomes from chickens, rabbits, sheep and pigs. The microsomal activities of mono-ooxygenase enzymes (flavin-containing and cytochrome P-450-dependent mixed function oxygenases) were compared by measuring the quantity of the 2 oxidized metabolites, ALD sulfoxide and ALD sulfone, produced during 60 min of incubation. Pig microsomes produced the greatest quantity of ALD sulfoxide and the lowest quantity of ALD sulfone; the latter being produced in greater quantities in sheep than in chickens and rabbits. Aldicarb and its metabolites were degraded fastest in rabbits, probably by hydrolytic reactions. These in vitro results, which are consistent both with the levels of cytochrome P450 found in hepatic microsomes and previous in vivo data on ALD kinetics in pigs, rabbits and chickens, indicate that preliminary in vitro studies can limit the necessary use of animals for drug metabolism experiments.

The oxidative metabolism of aldicarb in pigs: in vivo-in vitro comparison.

Aldicarb was administered (1 mg/kg b.w.) to four female pigs and the kinetics of its major oxidized metabolites (sulfoxide and sulfone) was followed for 6 hours. The in vitro transformations of the carbamate pesticide into these two still active metabolites were also investigated in hepatocytes and in microsomes from pig livers. In all cases, aldicarb was quickly oxidized to the sulfoxide (major metabolite) and only a minor quantity of sulfone was produced. The in vivo toxic symptomatology was related to the peak serum concentration of sulfoxide, suggesting that this metabolite is principally responsible for the aldicarb toxicity. Selective in vitro inhibition of flavin-containing and cytochrome P-450 monooxygenases confirmed that the former enzymes catalyze mainly sulfoxide production whereas the latter that of sulfone.