Brain tissue reaction following intracerebral injection of free or liposomally encapsulated BSH

Boron neutron capture therapy (BNCT) is a potentially valuable treatment of malignant brain gliomas. A primary requirement for successful BNCT is achieving high local concentration of boron drugs in tumors. Intratumoral injection of liposomes containing boron drug has potential to meet this requirement and could prove to be of significance for BNCT. The brain tissue reaction following the intracerebral injection of a boron drug, BSH, either in solution form or in liposomally encapsulated form, was studied in rats. On histological examination, no evidence of tissue reaction was found after injecting BSH solution, suggesting that high local concentration of BSH was well tolerated. Injection of liposomal BSH was characterized by phagocytic activity at the site of injection, which was regressing by 24 h. Neither group of animals exhibited any signs of abnormal behavior or neurologic deficit. Direct intracerebral injection of BSH liposomes as per-formed in this report could be regarded as tolerable.     

Hypothermia and the Approximate Entropy of the Electroencephalogram

Background: The electroencephalogram is commonly used to monitor the brain during hypothermic cardiopulmonary bypass and circulatory arrest. No quantitative relationship between the electroencephalogram and temperature has been elucidated, even though the qualitative changes are well known. This study was undertaken to define a dose-response relationship for hypothermia and the approximate entropy of the electroencephalogram.

Methods: The electroencephalogram was recorded during cooling and rewarming in 14 patients undergoing hypothermic cardiopulmonary bypass and circulatory arrest. Data were digitized at 128 Hz, and approximate entropy was calculated from 8-s intervals. The dose-response relationship was derived using sigmoidal curve-fitting techniques, and statistical analysis was performed using analysis of variance techniques.

Results: The approximate entropy of the electroencephalogram changed in a sigmoidal fashion during cooling and rewarming. The midpoint of the curve averaged 24.7[degrees]C during cooling and 28[degrees]C (not significant) during rewarming. The temperature corresponding to 5% entropy (T0.05) was 18.7[degrees]C. The temperature corresponding to 95% entropy (T0.95) was 31.3[degrees]C during cooling and 38.2[degrees]C during rewarming (P < 0.02).     

Chronic ethanol treatment alters the behavioral effects of Ro 15-4513, a partially negative ligand for benzodiazepine binding sites

Pentylenetetrazol (PTZ)-induced convulsion were studied in control, chronic ethanol-maintained, and ethanol-withdrawal rats. The convulsive doses of PTZ varied among the different groups of rats. Ethanol-maintained rats required higher doses of PTZ to produce convulsions, compared to control and ethanol-withdrawal rats. The partially negative ligands for benzodiazepine binding sites, Ro 15-4513 (2 mg/kg, i.p.) and FG 7142 (20 mg/kg, i.p.) produced proconvulsant effect in saline (control) and ethanol-withdrawal rats as they potentiated the effect of subconvulsive dose of PTZ. A higher dose of Ro 15-4513 (4 mg/kg, i.p.), but not FG 7142 (up to 80 mg/kg, i.p.), also produced proconvulsant effect in ethanol-maintained rats. Furthermore, Ro 15-4513 (5, 10 mg/kg, i.p.), but not FG 7142 (up to 80 mg/kg, i.p.), produced clonic-tonic seizures of short duration in ethanol-withdrawal rats. These effects of Ro 15-4513 and FG 7142 were reversed by diazepam (2 mg/kg, i.p.), as well as by the GABA-neutral Ro 15-1788 (10 mg/kg, i.p.), thereby, indicating the involvement of central benzodiazepine receptors in the action of Ro 15-4513 and FG 7142. These observations suggest that chronic ethanol treatment selectively alters the receptor sensitivity to Ro 15-4513, an ethanol antagonist and partially negative ligand for BZ sites, and this observation supports the notion that ethanol effects are more susceptible to reversal by the imidazobenzodiazepine as compared to other negative ligand for BZ binding sites.     

Biopsy excision through a fiberoptic bronchoscope in the palliative management of airway obstruction

Simple biopsy resection through the rigid bronchoscope has been described in the past. We successfully performed such resection through a flexible bronchoscope in six patients with symptomatic and relatively less vascular lesions without complications. In selected patients simple biopsy resection of endobronchial lesion can be safely performed through flexible bronchoscope.     

Common pancreaticobiliary channels and their relationship to gallstone size in gallstone pancreatitis.

Bile reflux into the pancreatic duct after impaction of a stone in a common pancreaticobiliary channel has been suggested to be the initiating factor in gallstone pancreatitis. Such reflux would require that the impacted stone be smaller than the length of the common channel. The incidence of common channels was studied and gallstone size was compared with common channel length in patients with gallstone pancreatitis and those with cholelithiasis or choledocholithiasis without pancreatitis. Sixty-seven per cent of patients with gallstone pancreatitis had a common channel present on intraoperative cholangiography versus 32% of patients with cholelithiasis or choledocholithiasis without pancreatitis (p less than 0.005). Common channel length was greater than the diameter of the smallest stone in nine of 27 patients with gallstone pancreatitis and in 13 of 109 patients with cholelithiasis or choledocholithiasis without pancreatitis (p less than 0.025). In conclusion, common channels are more frequent in patients with gallstone pancreatitis than in patients with other biliary tract disease. Furthermore, gallstone pancreatitis is associated with stones that are smaller than the common channel, which favors obstruction of both pancreatic and bile ducts while allowing reflux of contents between them.     

Characterization of a CD38-like 78-kilodalton soluble protein released from B cell lines derived from patients with X-linked agammaglobulinemia.

Studies on murine B lymphocytes showed that Bruton's tyrosine kinase mediates signal transduction induced via CD38, a nonlineage-restricted 45-kD ectoenzyme. This signaling is defective in B cells from X-linked immunodeficient mice affected with the analogue of human X-linked agammaglobulinemia (XLA). We performed a structural and functional analysis of CD38 in XLA and other immunodeficiencies, using EBV-immortalized B cells derived from such patients. Membrane CD38 was not significantly different from controls in structure, epitope density, enzymatic activity, and internalization upon binding of agonistic mAbs. Meanwhile, an increased release of soluble CD38 from XLA cells was observed: immunoprecipitation from XLA culture media yielded a protein of approximately 78 kD (p78), reacting also in Western blot and displaying both enzymatic activities and a peptide map similar to membrane CD38. Soluble forms and homotypic aggregations of CD38 were documented in different cell models and by crystallographic analysis of the Aplysia ADP-ribosyl cyclase, the ancestor of human CD38. p78 might represent the product of an altered turn-over of membrane CD38, a starting point for studying its association with Bruton's tyrosine kinase and its role in XLA and other B cell immunodeficiencies.     

Adsorption of Salmon Calcitonin to PLGA Microspheres

Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-co-glycolide) was detected during preparation and evaluation of microspheres. The purpose of this study was to quantitate the extent and nature of the interaction. Methods. Blank microspheres were prepared by an aqueous emulsification solvent extraction technique. Adsorption studies were carried out at six concentrations of sCT and three concentrations of microspheres. Adsorption isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 µg/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 µg/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 µg/ml, indicating formation of a monolayer. Multilayer interaction, described by the Freundlich isotherm, occurred at higher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation was 0.09 and the plateau surface concentration was 5.1 µg/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 µg/mg) than the monolayer peptide-polymer adsorption. Conclusions. The results show that poly (d,l-lactide-co-glycolide) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this peptide.