Chronic ethanol inhibits inositol metabolism in specific brain regions

Many neurotransmitters and hormones in the nervous system transmit signals through receptors coupled to the poly-phosphoinositide (PI) signaling pathway. In this study, an in vivo protocol with [3H]inositol was used to examine the effect of chronic ethanol administration on inositol metabolism and poly-PI turnover in the cerebral cortex, hippocampus, and cerebellum of mouse brain. C57BL/6 mice were given a nutritionally complete liquid diet containing either ethanol (5%, w/v) or isocaloric sucrose for 2 months. Mice were injected intracerebrally with [3H]inositol; after 16 or 24 hr, they were injected intraperitoneally with lithium (8 mEq/kg body weight) to inhibit the inositol monophosphatase (IP1) activity. All mice were decapitated 4 hr after lithium injection. Labeled inositol phospholipids accounted for 16 to 23% of total labeled inositol in different regions of control mouse brain, and the percentages in the hippocampus were consistently higher than the cerebral cortex and cerebellum. In control mice, the percentages of labeled IP1 after a 4-hr lithium treatment were 11.5%, 9.9%, and 3.7% for cerebral cortex, hippocampus, and cerebellum, respectively. Chronic ethanol feeding resulted in a significant (p < 0.05) decrease in the percent of labeled IP1 and inositol phospholipids, and this effect was observed in the cerebral cortex and, to a lesser extent, hippocampus but not cerebellum. When ratios of labeled IP1 were expressed against labeled inositol phospholipids as an index of the poly-PI turnover activity, significant decreases in IP/lipid ratios were observed in the cerebral cortex, but not the hippocampus or cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would have experienced an 8-hr period of ethanol withdrawal, compared with the 16 + 4-hr group, no differences in IP/lipid ratios were observed between the two time groups. These results illustrate regional differences in the effect of chronic ethanol on inositol metabolism in the brain, but no difference in poly-PI turnover in brain due to ethanol withdrawal.     

Effects of dietary manipulations and glucose infusion on glucagon response during exercise in rats

OBJECTIVE: To describe our initial experience with a computerized telecommunication system, termed the interactive voice-response system, to record resident performance of laparoscopic surgery. METHODS: After completing a laparoscopic procedure, the surgeon and resident telephone a toll-free number independently and respond to three prerecorded statements using a Likert scale of 1 to 5. The caller then is asked to describe the resident's response to critical incidents or elements of surprise that arose during the surgery. The ratings and verbal comments are compiled, transcribed, and forwarded to the respective resident. The resident (and program director) can hear the verbal comments by entering a four-digit code. RESULTS: Between May 1, 1995, and May 31, 1996, 430 cases were reported by 11 surgeons and 16 residents using the interactive voice-response system. One hundred ninety-five (45%) procedures were entered by both the resident and surgeon. A survey undertaken during the introductory phase of the project revealed that five of the seven residents exposed to the system found that it provided useful feedback and preferred the system to traditional in-service reporting methods. In addition, five residents thought that the system complemented the personal feedback they received in the operating room. CONCLUSION: The system has been accepted by both residents and surgeons and has addressed the important components of resident in-training evaluation, namely, evaluation on a case-by-case basis, timely feedback, and self-assessment of resident performance.     

Electrostatic and non-electrostatic contributions to the binding free energies of anthracycline antibiotics to DNA

The knowledge about molecular factors driving simple ligand-DNA interactions is still limited. The aim of the present study was to investigate the electrostatic and non-electrostatic contributions to the binding free energies of anthracycline compounds with DNA. Theoretical calculations based on continuum methods (Poisson-Boltzmann and solvent accessible surface area) were performed to estimate the binding free energies of five selected anthracycline ligands (daunomycin, adriamycin, 9-deoxyadriamycin, hydroxyrubicin, and adriamycinone) to DNA. The free energy calculations also took into account the conformational change that DNA undergoes upon ligand binding. This conformational change appeared to be very important for estimating absolute free energies of binding. Our studies revealed that the absolute values of all computed contributions to the binding free energy were quite large compared to the total free energy of binding. However, the sum of these large positive and negative values produced a small negative value of the free energy around -10 kcal/mol. This value is in good agreement with experimental data. Experimental values for relative binding free energies were also reproduced for charged ligands by our calculations. Together, it was found that the driving force for ligand-DNA complex formation is the non-polar interaction between the ligand and DNA even if the ligand is positively charged.     

alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors

Through a study of cloned nicotinic receptors expressed in Xenopus oocytes, we provide evidence that alpha-conotoxin ImI, a peptide marine snail toxin that induces seizures in rodents, selectively blocks subtypes of nicotinic acetylcholine receptors. alpha-Conotoxin ImI blocks homomeric alpha 7 nicotinic receptors with the highest apparent affinity and homomeric alpha 9 receptors with 8-fold lower affinity. This toxin has no effect on receptors composed of alpha 2 beta 2, alpha 3 beta 2, alpha 4 beta 2, alpha 2 beta 4, alpha 3 beta 4, or alpha 4 beta 4 subunit combinations. In contrast to alpha-bungarotoxin, which has high affinity for alpha 7, alpha 9, and alpha 1 beta 1 gamma delta receptors, alpha-conotoxin ImI has low affinity for the muscle nAChR. Related Conus peptides, alpha-conotoxins MI and GI, exhibit a distinct specificity, strictly targeting the muscle subtype receptor but not alpha 7 or alpha 9 receptors. alpha-Conotoxins thus represent selective tools for the study of neuronal nicotinic acetylcholine receptors.     

Myotonic dystrophy protein kinase gene expression in skeletal muscle from congenitally affected infants

Thiothrix spp., sulfide-oxidizing filamentous bacteria, were found to be a principal bacterial component of aquatic biofilms causing biofouling in selected municipal water storage tanks, private wells, and drip irrigation systems in Florida. Treatments of up to 200 ppm chlorine in the affected systems could not prevent return of the biofouling problem. The water originated from the upper Floridan aquifer and associated surficial aquifers in central and north Florida. Samples were examined where visible biofilms had a white, filamentous appearance, indicative of Thiothrix spp. The detection of Thiothrix spp. was confirmed by enzyme-liked immunosorbent assay (ELISA), indirect immunofluorescence (IIF), and microbiological procedures. It was estimated through immunocytochemical procedures that Thiothrix spp. comprised 18% of the biofilm in the municipal water storage tanks. These observations confirm that specific biological and chemical interactions may induce physical changes leading to significant biofouling.     

Ewing's sarcoma of the pelvis: changes over 25 years in treatment and results

The pelvic localisations of Ewing's sarcoma have the worst prognosis due to large size at diagnosis, frequent distant metastases, radiosensitive organs next to the tumour and difficult surgery. The purpose of the present study was to analyse treatment results over a period of 25 years and to investigate the impact of newer chemotherapy schedules, improved radiotherapy techniques and newer surgical methods on the prognosis. 35 children and young adults were identified from 1967 to 1994 for whom diagnosis, presentation, performed treatment and outcome were available. Tumour size, as measured from CT scans, response to chemotherapy and radiotherapy target volume, could be reviewed in the later years. Actuarial 5-year survival for the whole group was 31% and for the 24 non-metastatic patients 40%, with a disease-free interval of 19%. Tumour size could be measured in 27 patients and ranged from 36 to 1540 cm3. There were 12 local recurrences, 1 in the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients developed local failure. 3 patients had adequate fields and one a close field which did not cover completely the prechemotherapy extent and 3 of these recurred. All 4 patients with stable disease after neoadjuvant CT failed locally, not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended to be shorter in patients without local relapse. There was no significant difference in survival before and after 1983.