Ultrastructural myocardial preservation during coronary artery surgery: a controlled, prospective, randomized study in humans

Potassium cardioplegia was compared with normothermic, intermittent ischemic arrest in 30 patients undergoing multiple coronary artery bypass grafts. Group 1 comprised 15 patients in whom cold potassium cardioplegia with St. Thomas' Hospital solution was used. In Group 2 were 15 patients who underwent intermittent ischemic arrest during the construction of the distal anastomoses. Two myocardial transmural left ventricular biopsies were done in each patient. There was no operative mortality. Electron microscopical examination showed normal myocardial ultrastructure in both groups. In particular, mitochondria were well preserved in all samples. The postoperative electrocardiogram demonstrated a new Q wave in 1 patient in Group 2 whose level of the myocardial isoenzyme of creatine phosphokinase (CPK-MB) was within the normal range. The peak CPK-MB release in Group 1 was 23.2 +/- 20.1 IU and in Group 2, 19.9 +/- 15.1 IU. This difference was not statistically significant. The mean period of anoxic arrest in Group 1 was 49.5 +/- 15 minutes and in Group 2, 25.5 +/- 8 minutes (p less than 0.001). Total cardiopulmonary bypass time in Group 1 was 114.5 +/- 20 minutes and in Group 2, 90.2 +/- 16 minutes (p less than 0.01). It is concluded that both techniques can preserve myocardial subcellular architecture during multiple coronary artery bypass grafting in patients with normal left ventricular function.     

The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites

The displacement by glycine of 3H-strychnine binding to rat spinal cord membranes cannot be explained by a simple competitive interaction. Indeed, protein-modifying reagents can completely abolish the inhibition of 3H-strychnine binding by glycine and other agonists, whereas the interaction of strychnine itself and other related compounds with the binding site is unimpaired. Moreover, glycine cannot inhibit completely saturable 3H-strychnine binding, the extent of its maximum inhibitory effect depending on the ionic composition of the medium. Hill coefficients less than 1 (whose magnitude also depends on the assay medium) were obtained from glycine displacement curves. These properties are consistent with a mathematical model of two different, but mutually interacting, binding sites for strychnine and glycine on the glycine receptor. The effect of ions and protein-modifying reagents might be explained in this model as modifications of the mechanisms that mediate the allosteric interaction, and/or the affinity of glycine for the receptor. The agonists beta-alanine and taurine and the new antagonists, THAZ, iso-THAZ, and 4,5-TAZA, also seem to interact with a site different from the strychnine-binding site, probably the glycine-binding site.     

Cyclophosphamide affects the dynamics of granuloma formation in experimental visceral leishmaniasis

We observed histopathological and ultrastructural hepatic changes following the intracardiac inoculation ofLeishmania donovani amastigotes into inbred LHC hamsters (group I). Since granuloma formation is known to be T-cell-dependent, we also examined infected hamsters under cyclophosphamide immunosuppressive treatment (group ICy) and evaluated the production of interleukin-2 (IL-2) by their cells. Group I showed more intense hepatocyte and endothelial cell clasmatosis as well as hepatocyte degeneration and necrosis, deposits of connective tissue fibers, granulomas with multinucleated giant cells (MGCs) of foreign-body and Langhans' types and reduced production of IL-2 by spleen cells. In contrast, group ICy hamsters exhibited larger eosinophil and lymphocyte populations within sinusoids and peri-sinusoidal areas but showed no MGCs in granulomas. A striking decline in IL-2 production was noted. These results suggest that cyclophosphamide induces a delay in the natural evolution ofL. donovani-induced granulomatous hepatic inflammation.     

Synthesis of poly[isobutyl (2S,3R)-3-benzyloxyaspartate]

A chiral poly(3-substituted isobutyl D -aspartate) 12 was synthesized by polymerization of the chiral β-lactam 11 derived from D -glyceraldehyde. The new polyamide was characterized by elemental analyses, and infrared, ¹H- and ¹³C nuclear magnetic resonance spectroscopies. The molecular weight was estimated as 543 000 and 230 000 on the basis of viscosimetric measurements and gel-permeation chromatography, respectively. Polyamide 12 is soluble in a variety of organic solvents including chloroform.     

Differential Stimulation of Noradrenaline Release by Reversal of the Na+/Ca2+ Exchanger and Depolarization in Chromaffin Cells

We compared the effectiveness of Ca²⁺ entering by Na⁺/Ca²⁺ exchange with that of Ca²⁺ entering by channels produced by membrane depolarization with K⁺ in inducing catecholamine release from bovine adrenal chromaffin cells. The Ca²⁺ influx through the Na⁺/Ca²⁺ exchanger was promoted by reversing the normal inward gradient of Na⁺ by preincubating the cells with ouabain to increase the intracellular Na⁺ and then removing Na⁺ from the external medium. In this way we were able to increase the cytosolic free Ca²⁺ concentration ([Ca²⁺]_c) by Na⁺/Ca²⁺ exchange to 325 ± 14 nM, which was similar to the rise in [Ca²⁺]_c observed upon depolarization with 35 mM K⁺ of cells not treated with ouabain. After incubating the cells with ouabain, K⁺ depolarization raised the [Ca²⁺]_c to 398 ± 31 nM, and the recovery of [Ca²⁺]_c to resting levels was significantly slower. Reversal of the Na⁺ gradient caused an −6-fold increase in the release of noradrenaline or adrenaline, whereas K⁺ depolarization induced a 12-fold increase in noradrenaline release but only a 9-fold increase in adrenaline release. The ratio of noradrenaline to adrenaline release was 1.24 ± 0.23 upon reversal of the Na⁺/Ca²⁺ exchange, whereas it was 1.83 ± 0.19 for K⁺ depolarization. Reversal of the Na⁺/Ca²⁺ exchange appeared to be as efficient as membrane depolarization in inducing adrenaline release, in that the relation of [Ca²⁺]_c to adrenaline release was the same in both cases. In contrast, we found that for the same average [Ca²⁺]_c, the Ca²⁺ influx through voltage-gated channels was much more efficient than the Ca²⁺ entering through the Na⁺/Ca²⁺ exchanger in inducing noradrenaline release from chromaffin ceils. This greater effectiveness of membrane depolarization in stimulating noradrenaline release suggests that there is a pool of noradrenaline vesicles which is more accessible to Ca²⁺ entering through voltage-gated Ca²⁺ channels than to Ca²⁺ entering through the Na⁺/Ca²⁺ exchanger, whereas the adrenaline vesicles do not distinguish between the source of Ca²⁺.     

Development of an open case-based decision-support system for diagnosis in oral pathology

BACKGROUND: Making diagnoses in oral pathology are often difficult and confusing in dental practice, especially for the less-experienced dental student. One of the most promising areas in bioinformatics is computer-aided diagnosis, where a computer system is capable of imitating human reasoning ability and provides diagnoses with an accuracy approaching that of expert professionals. This type of system could be an alternative tool for assisting dental students to overcome the difficulties of the oral pathology learning process. This could allow students to define variables and information, important to improving the decision-making performance. However, no current open data management system has been integrated with an artificial intelligence system in a user-friendly environment. Such a system could also be used as an education tool to help students perform diagnoses. The aim of the present study was to develop and test an open case-based decision-support system. METHODS: An open decision-support system based on Bayes' theorem connected to a relational database was developed using the C++ programming language. The software was tested in the computerisation of a surgical pathology service and in simulating the diagnosis of 43 known cases of oral bone disease. The simulation was performed after the system was initially filled with data from 401 cases of oral bone disease. RESULTS: The system allowed the authors to construct and to manage a pathology database, and to simulate diagnoses using the variables from the database. CONCLUSION: Combining a relational database and an open decision-support system in the same user-friendly environment proved effective in simulating diagnoses based on information from an updated database.