BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

Adverse drug reactions: physicians' opinions versus a causality assessment method

Since spontaneous reporting of adverse drug reactions depends on the physician's opinion of the relationship between the drug and the adverse event, we compared physicians' opinions with the scores obtained by the causality assessment method used in France. During a 2 month period, all physicians who reported adverse drug reactions (ADRs) to our pharmacovigilance centre expressed their opinions on the causal link by means of visual analogue scales. ADR reports were then assessed with the French causality assessment method by a clinical pharmacologist who was blind to physicians' opinions.The assessment by both physicians and the standardized method was performed for 75 ADR cases involving 120 drugs. Physicians used a wide range of assessments, with a preponderance of extreme scores, resulting in a U-shaped distribution, while the standardized method gave generally low scores. Scores given by physicians were very high (causality considered very likely or likely) in 60% of cases and very low (causality considered unlikely or dubious/possible) in 32% of cases. Scores obtained using the causality assessment method were low (causality dubious/possible) in 89% of cases and causality considered likely in only 11 cases, essentially in cases with positive rechallenge. Complete agreement occurred in only 6% of cases. Adding complete agreement and minor discrepancies raised the percentage to 49%.     

On the effects of Fusarium toxin contaminated wheat and wheat chaff on nutrient utilisation and turnover of deoxynivalenol and zearalenone in vitro (Rusitec).

The objective of the present study was to investigate the effects of Fusarium toxin contaminated wheat and wheat chaff (mycotoxin diet) on nutrient degradability and the metabolism of the mycotoxins deoxynivalenol (DON) and zearalenone (ZON) using the rumen simulations technique (Rusitec). A 6 day application period with control wheat and wheat chaff (control diet) was followed by an 8 day sampling phase. During this time three fermenters received the mycotoxin diet (64.9 mg DON/kg dry matter (DM) and 500 microg ZON/kg DM) and the remaining fermenters served as the controls (1.0mg DON/kg DM and 6 microg ZON/kg DM). Feed residues of the bags and samples of the effluent liquids were pooled per fermenter during the last 8 days of the experiment. Additionally, effluents of the mycotoxin fermenters were taken 6, 12 and 24h after the morning feeding on the first day of the sampling phase. The degradation of organic matter (OM; P<0.05), neutral detergent fibre (NDF; P<0.01) and protein (P<0.001) were increased by administration the Fusarium contaminated diet which was accompanied by an increased ammonia concentration (P<0.01) and increased butyrate (P<0.01), isobutyrate (P<0.01) and isovalerate (P<0.05) values of the mycotoxin effluents in relation to the controls. High proportions of ingested DON of 90% (85-93%) and ingested ZON of 93% (80-104%) were recovered at the pooled feed residues and effluents in form of DON and de-epoxy DON, and ZON and alpha-ZOL after administering the Fusarium toxin contaminated feed. While adsorption of DON as DON and de-epoxy DON in the feed particles was only minor (5%), a higher amount of 38% of ingested ZON was recovered as ZON and alpha-ZOL at the feed residues. The total recovery of DON plus de-epoxy DON in effluents as a percentage of DON intake reached 8%, 9% and 22% of ingested DON at 6, 12 and 24h after application of the contaminated diet the first time, whereby the recovery of de-epoxy DON as percentage of DON intake was only 5% at 24h. Concentrations of ZON and metabolites were lower than detection limits in the time dependent effluent samples.     

Schwannoma of the lateral ventricle: eight-year follow-up and literature review.

Intracerebral and intramedullary schwannomas are uncommon; but, in general, spinal intramedullary schwannomas are more frequent than intracerebral schwanomas. We present a case of right lateral ventricle schwannoma in a 21-year-old man and review the associated literature. The 21-year-old right-handed man presented with loss of the left-eye vision approximately 8 months before referral to an ophthalmologist. The patient was immediately subjected to computed tomography (CT) scan, which showed an enhanced lesion with cystic component in the right occipital horn of the lateral ventricle. And consecutively, he was admitted to our department. The tumor was evacuated via craniotomy with marked improvement in his clinical state. The postoperative course was uneventful and postoperative CT control showed no residue. On MRI control no recurrence was noted after a follow-up period of 8 years. Intracerebral schwannoma is a rare, benign neoplasm. It is usually located superficially or adjacent to a ventricle. Characteristic imaging features include cyst formation, calcification, and evidence of peritumoral edema or gliosis. The recognition of this benign and potentially curable neoplasm and its differentiation from other neoplasms, some of which have less favourable outcomes, is of obvious importance.     

Positive autoradiographic findings in brains of four MS patients

Autoradiography of brain slices from 4 multiple sclerosis (MS) and 9 control patients was performed. After 6 weeks of exposure the exact picture of the white matter appeared on the X-ray films in all cases with MS, but only in one of the controls. The high level of autoradiographic signal from MS white matter suggests that an abnormal accumulation of radioactive trace elements takes place within the brains of MS victims.     

The cholinergic innervation of the rat fascia dentata: identification of target structures on granule cells by combining choline acetyltransferase immunocytochemistry and Golgi impregnation

A monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, was used to study cholinergic synapses on identified (Golgi stained) granule cells in the rat fascia dentata. Choline acetyltransferase immunocytochemistry was applied to 40-microns Vibratome sections cut perpendicular to the longitudinal axis of the hippocampus. Light microscopy revealed fine varicose ChAT-immunoreactive axons in all layers of the fascia dentata, i.e., in the stratum moleculare, the stratum granulosum, and the subgranular polymorph zone. Most fibers were observed in the vicinity of granule cell bodies where they ran mainly parallel to the granular layer. Next, the immunostained Vibratome sections were sandwiched between small pieces of Parafilm and piled to form a block that was covered with agar and Golgi stained. After that, the sections were separated by cutting away the agar and removing the Parafilm. Sections containing well-impregnated granule cells were gold-toned (Fairén et al., '77), embedded in Araldite, and subjected to ultrathin sectioning for electron microscopy. A total of 14 gold-toned granule cells were examined in the electron microscope for synaptic contacts with cholinergic afferents. Choline acetyltransferase-immunoreactive axon terminals were observed that established symmetric synaptic contacts with the cell bodies and dendritic shafts of the gold-toned identified granule cells. Two types of contact were observed on spines arising from gold-toned granule cell dendrites. Immunoreactive terminals established asymmetric synaptic contacts with the head of small spines and symmetric contacts with the stalk of large, complex spines. The boutons forming asymmetric synaptic contacts with the cup-shaped spine head of the complex spines were not found to be immunoreactive. Our results demonstrate that cholinergic fibers to the rat fascia dentata establish characteristic types of synaptic contact with different postsynaptic elements of granule cells, suggesting a complex function of this afferent system.