Theoretical calculation of relative binding affinity in host-guest systems.

The relative free energy of binding the anions Cl- and Br- to the macrotricyclic receptor SC24 in water has been computed by a computer simulation technique. This result and an incidental result for the relative free energy of hydration of the anions are in excellent agreement with experimental data. The simulation approach to ligand-receptor interactions that is described here has significant potential as a predictive tool in chemistry, biochemistry, and pharmacology.     

A worldwide survey of the use of simulation in anesthesia

PURPOSE: To gather information regarding the global use of simulation technology in education, evaluation and research in anesthesia. METHODS: The WorldWide Web was searched and located sites with simulation centres (n = 158) were mailed a 67-item questionnaire requesting information regarding demographics, personnel, education use and research involvement. Comments were solicited. Medical school data only are reported in this article. RESULTS: Two web sites were used to generate the list of simulation centres. Sixty responses were received (38%), with 41 emanating from medical schools. Seventy-seven percent of centres were involved in undergraduate education and 85% in postgraduate education. Few centres were involved in evaluation and/or competency assessments. Sixty-one percent of centres indicated ongoing research with a further 25% interested in international collaboration. University or university departmental-based funding largely supported simulation technology used in medical schools. The lack of financial and human resources was the single most common problem identified by respondents. CONCLUSIONS: From the survey responses received, opportunities for the simulator to be used for the assessment of performance appear to be under-utilized. This may be due to the lack of research in this area, lack of standardized, valid and reliable tests and the fact that most centres have only recently acquired this technology. Further research supporting the use of the simulator in education and evaluation is required.     

Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)