Synchrotron X-ray investigations into the lamellar gel phase formed in pharmaceutical creams prepared with cetrimide and fatty alcohols.

Semisolid liquid paraffin-in-water emulsions (aqueous creams) prepared from cetrimide/fatty alcohol mixed emulsifiers, and ternary systems formed by dispersing the mixed emulsifier in controlled percentages of water were examined as they aged using a combination of low and high angle X-ray diffraction measurements (Daresbury Laboratory Synchrotron Radiation Source). The results were correlated with the rheological properties measured in earlier studies. The cationic emulsifying wax showed phenomenal swelling in water. The reflection that incorporates interlamellar water increased continuously from 74 A at 28% water to over 500 A at 93% water. The trend was not influenced by the method of incorporation of the components and swollen lamellar phase was also identified in the corresponding emulsion. The swelling, which was due to electrostatic repulsion, was suppressed by salt and was reduced when the surfactant counterion was changed from Br(-) to Cl(-). Changes in rheological properties on storage and in the presence of salt were correlated with changes in water layer thickness. High angle diffraction confirmed that the hydrocarbon bilayers were in the hexagonal alpha-crystalline mode of packing. Ternary systems and creams prepared from pure alcohols, although initially semisolid, were rheologically unstable and broke down. Low angle X-ray study into the kinetics of structure breakdown showed that the swollen lamellar gel phase formed initially swells even further on storage before separating.

A strategy for statistical Master Person Index linking.

A linking program used by Connecticut Healthcare Information Management and Exchange to maintain the Master Person Index for its large, state-wide patient data repository is being stretched beyond its limits by the growing size and complexity of the database. This paper presents the early work into developing a second-generation linking program. Like the original program, the new linker will use a unique multi-step process to allow effective linking of data from a large number of dissimilar data sources. The new linker will use parallel multi-processing to allow improved performance and scalability. These changes will also make possible more sophisticated statistical methods of defining link confidence. The system is implemented using a scalable collection of inexpensive, PC based systems running the Linux operating system, a freely available database engine, and the Java programming language.

eXpTools: a C++ class library for animation, tachistoscopic presentation, and response timing.

The eXpTools Library is a general-purpose tool for developing psychological experiments that combine animation with tachistoscopic presentation. The library's C++ classes and assembly language functions are specialized for the creation of visual response time experiments. Its use is limited to variants of standard, 16-color, VGA high-graphics modes. However, it extends the capabilities of these modes through bit-plane animation techniques and a new, nonstandard, high-resolution graphics mode that will work with standard VGA cards and register-compatible cards. These techniques make possible a powerful animation class for managing complex animation or tachistoscopic presentations consisting of hundreds or thousands of frames. The library also combines such features as page flipping, screen blanking, video-refresh synchronization, interrupt-driven millisecond timing, interrupt-driven keyboard response collection, graphics primitives, bitmaps, and screen fonts. Utilities allow for the conversion of PCX graphics files and the creation of new screen fonts from monochrome bitmap files. The technologies and techniques underlying the library are presented along with an example program.

A near perfect temperature adaptation of bilayer order in vertebrate brain membranes.

The bilayer order of a brain synaptic membrane fraction from a number of fish, mammalian and avian species have been compared in relation to their respective body temperatures using steady-state and time-resolved fluorescence anisotropy techniques. Fluorescence anisotropy for both 1,6-diphenyl-1,3,5-hexatriene and trans-parinaric acid increased in the order: antarctic Notothenia, trout, perch, cichlid, rat and starling, this also being the order of increasing body temperature. This suggests that cold-adapted fish species possess more disordered brain membranes than warm-adapted fish species, and mammals and birds membranes were more ordered than fish membranes. Comparison of temperature profiles for both fluorescence probes showed that fish species display similar anisotropies, and by inference bilayer order, to mammals and birds when measured at their respective body temperatures. Time-resolved analysis showed that the interspecific differences in (P2) order parameter was consistently related to body temperature whilst the rotational diffusion coefficient was not. These results suggest that brain membrane order is highly conserved within the vertebrates despite large differences in thermal habits and phylogenetic position. Polar fish species have by far the lowest bilayer order indicating that invasion of extreme cold habitats involved an adaptive decrease in bilayer order and conversely adoption of a high body temperature by mammals involved an adaptive increase in bilayer order. The conservation of membrane static order for these species at their respective body temperatures indicates a regulatory control of this aspect of membrane hydrocarbon structure and the functional importance of this structure.

Hormonal effects on mitochondrial respiration: potential role of endogenous lipolytic activities.

Hormonal effects on heart mitochondrial metabolism are investigated by comparing respiratory rates, Ca2+ uptake capacity, and lipolytic activities of mitochondria isolated from control rats to those of mitochondria isolated from thyroparathyroidectomized animals. Two biochemically and morphologically distinct populations of heart mitochondria are prepared--one derived from the region of the cell directly beneath the sarcolemma (subsarcolemmal mitochondria), the other originally between the myofibrils (interfibrillar mitochondria). Subsarcolemmal mitochondria isolated from normal rat cardiac tissue have both lower respiratory rates and Ca2+ uptake capacity than do interfibrillar mitochondria. However, when these mitochondrial populations are isolated from hearts from thyroparathyroidectomized rats, there is a selective increase in the maximal ability of the subsarcolemmal mitochondria to accumulate Ca2+, which is accompanied by a proportionate increase in their maximal respiratory rates. Neither Ca2+ uptake capacity nor respiratory rates are similarly increased in the interfibrillar mitochondria. Cytochrome contents and mitochondrial protein recoveries are not significantly changed in either of these mitochondrial preparations. The relationship between these selective increases in respiratory properties of the subsarcolemmal mitochondria to endogenous lipolytic activities is also investigated. It was previously demonstrated that, in the absence of Ca2+, both the rate and extent of formation of free fatty acids from endogenous phospholipids is greater in subsarcolemmal than interfibrillar mitochondria (J. W. Palmer et al. (1981) Arch. Biochem. Biophys. 211, 674-682). In this study it is shown that lipolysis is also more sustained in the subsarcolemmal mitochondria when Ca2+ is added. In the subsarcolemmal mitochondria isolated from thyroparathyroidectomized rats, however, the rates of release of stearic acid and oleic acid are reduced in both the presence and absence of Ca2+. In the presence of added Ca2+, the rate of release of arachidonic acid is also decreased compared to control subsarcolemmal mitochondria, suggesting that the expressed activity of Ca2+-activated phospholipase A2 is lower in those mitochondria isolated from the thyroparathyroidectomized animals, in which respiratory rates and Ca2+ uptake capacity are increased.

The effects of anti-inflammatory and other agents on the rat dermal arthus reaction.

The inhibitory effects of selected drugs on the Arthus reaction, a model of immune-complex-induced tissue injury, were studied. The reverse passive Arthus reaction (RPAR) was elicited in the dorsal skin of rats, using bovine serum albumin and the gamma-globulin fraction of rabbit anti-BSA. The optimal amounts of antigen and antibody required to elicit the reaction, as well as the reaction kinetics, were examined. Chlorpheniramine, cyproheptadine, d-penicillamine, chloroquine, indomethacin, phenylbutazone, naproxen, and mefenamic acid were found to be inactive despite high doses; aspirin and ibuprofen were only weakly active. Hydrocortisone and colchicine were strong inhibitors of the RPAR: the calculated ED50 values were 13 mg/kg p.o. and 0.3 mg/kg i.v., respectively. The RPAR exhibits a different sensitivity to drug inhibition than conventional models of inflammation (e.g., carrageenin paw edema) end may be useful to detect new types of anti-inflammatory agents.

Chemotherapy of neuroblastoma in mice with anticancer agents.

Neuroblastoma-inoculated A/J mice were treated with various anticancer chemotherapeutic agents, including cyclophosphamide, daunorubicin, vincristine, alpha-bungarotoxin, dihydroxytryptamine, and diaminopropane. Cyclophosphamide and diaminopropane inhibited neuroblastoma as effectively as bromoacetylcholine and bromacetate. The effectiveness of these drugs could be related to the inhibition of ornithine decarboxylase, a rate-limiting enzyme for the synthesis of polyamines.