In vivo effects of triorganotins on calmodulin activity in rat brain.

We have recently reported that the triorganotins are effective inhibitors of calmodulin (CaM) activity in vitro. The present experiments were designed to investigate the in vivo effects of triorganotins, that is, tributyltin (TBT), triethyltin (TET), and trimethyltin (TMT) on rat brain CaM activity. Male Sprague-Dawley rats were treated orally with TET (0.5, 1.0, and 1.5 mg/kg/d), TMT (0.75, 1.50, and 2.50 mg/kg/d), and TBT (0.75, 1.50, and 2.50 mg/kg/d) for 6 d and they were sacrificed 24 h after the last dose. There was significant loss of body weight in the high-dose group of the organotin treated rats. Ca(2+)-ATPase activity was determined in rat brain synaptic membranes. TET and TMT inhibited Ca(2+)-ATPase in a dose-dependent manner but TBT exhibited its inhibitory effect only at the highest dose (2.5 mg/kg/d). The inhibition of Ca(2+)-ATPase by these triorganotin compounds was reversed to control levels by the addition of CaM (5-10 micrograms) exogenously. The CaM levels of the synaptic membranes of the organotin-treated rats were not significantly changed. The data presented in this paper demonstrate that triorganotins impair the Ca(2+)-pump activity by interacting with CaM, which is a regulatory protein of Ca(2+)-ATPase. The present in vivo data and our previously reported in vitro data together indicate that triorganotins associated neurotoxicity may be due to an altered CaM activity in brain.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Glial S100B Positive Vacuoles In Purkinje Cells: Earliest Morphological Abnormality In SCA1 Transgenic Mice

Spinocerebellar ataxia-1 (SCA1) is caused by the expansion of a polyglutamine repeat within the disease protein, ataxin-1. The overexpression of mutant ataxin-1 in SCA1 transgenic mice results in the formation of cytoplasmic vacuoles in Purkinje neurons (PKN) of the cerebellum. PKN are closely associated with neighboring Bergmann glia. To elucidate the role of Bergmann glia in SCA1 pathogenesis, cerebellar tissue from 7 days to 6 wks old SCA1 transgenic and wildtype mice were used. We observed that Bergmann glial S100B protein is localized to the cytoplasmic vacuoles in SCA1 PKN. These S100B positive cytoplasmic vacuoles began appearing much before the onset of behavioral abnormalities, and were negative for other glial and PKN marker proteins. Electron micrographs revealed that vacuoles have a double membrane. In the vacuoles, S100B colocalized with receptors of advanced glycation end-products (RAGE), and S100B co-immunoprecipated with cerebellar RAGE. In SCA1 PKN cultures, exogenous S100B protein interacted with the PKN membranes and was internalized. These data suggest that glial S100B though extrinsic to PKN is sequestered into cytoplasmic vacuoles in SCA1 mice at early postnatal ages. Further, S100B may be binding to RAGE on Purkinje cell membranes before these membranes are internalized.     

Stable Anticonvulsant Action of Benzodiazepines During Development in Rats

Abstract— The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg^?1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0·1 and 0·02 mg kg^?1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.