Alginate-containing systems for oral delivery of superoxide dismutase. Comparison of various configurations and their properties

The regularities of release of therapeutic antioxidant enzyme superoxide dismutase (SOD) from various alginate-based delivery systems (DS) into simulated gastric and intestinal fluids were determined. The following systems were used: Ca-alginate granules (AG) prepared by various methods, porous carbonate cores with multilayer polyelectrolyte coating as well as the new two-level DS (Ca-AG containing carbonate cores loaded with proteins). The influence of the method of granule preparation, composition of gelation bath and ionic composition of the simulated fluids on release profiles of the protein from different DS was revealed. SEM images demonstrated changes in DS structures in various simulated fluids. The correlation between these changes and in vitro protein release was shown. The comparison of enzymatic activity of SOD encapsulated in DS of various configurations (including the systems containing different peptidase inhibitors) was made. The efficiency of protection of SOD activity in simulated intestinal fluid with trypsin was demonstrated.     

Symmetry requirements for effective blocking of pore-forming toxins: comparative study with alpha-, beta-, and gamma-cyclodextrin derivatives

We compared the abilities of structurally related cationic cyclodextrins to inhibit Bacillus anthracis lethal toxin and Staphylococcus aureus α-hemolysin. We found that both β- and γ-cyclodextrin derivatives effectively inhibited anthrax toxin action by blocking the transmembrane oligomeric pores formed by the protective antigen (PA) subunit of the toxin, whereas α-cyclodextrins were ineffective. In contrast, α-hemolysin was selectively blocked only by β-cyclodextrin derivatives, demonstrating that both symmetry and size of the inhibitor and the pore are important.     

Local diversity and fine-scale organization of receptive fields in mouse visual cortex

Many thousands of cortical neurons are activated by any single sensory stimulus, but the organization of these populations is poorly understood. For example, are neurons in mouse visual cortex--whose preferred orientations are arranged randomly--organized with respect to other response properties? Using high-speed in vivo two-photon calcium imaging, we characterized the receptive fields of up to 100 excitatory and inhibitory neurons in a 200 μm imaged plane. Inhibitory neurons had nonlinearly summating, complex-like receptive fields and were weakly tuned for orientation. Excitatory neurons had linear, simple receptive fields that can be studied with noise stimuli and system identification methods. We developed a wavelet stimulus that evoked rich population responses and yielded the detailed spatial receptive fields of most excitatory neurons in a plane. Receptive fields and visual responses were locally highly diverse, with nearby neurons having largely dissimilar receptive fields and response time courses. Receptive-field diversity was consistent with a nearly random sampling of orientation, spatial phase, and retinotopic position. Retinotopic positions varied locally on average by approximately half the receptive-field size. Nonetheless, the retinotopic progression across the cortex could be demonstrated at the scale of 100 μm, with a magnification of ≈ 10 μm/°. Receptive-field and response similarity were in register, decreasing by 50% over a distance of 200 μm. Together, the results indicate considerable randomness in local populations of mouse visual cortical neurons, with retinotopy as the principal source of organization at the scale of hundreds of micrometers.     

Treatment of Chronic Chest Wall Pain in a Patient With Loeys-Dietz Syndrome Using Spinal Cord Stimulation

Objective: Spinal cord stimulation (SCS) has been used with increased frequency for the treatment of intractable pain including chronic chest pain. Methods: The patient with a history of Loeys‐Dietz syndrome who underwent repair of pectus excavatum with subsequent chronic chest wall pain underwent an uneventful SCS trial with percutaneous epidural placement of two temporary eight‐electrode leads placed at the level of T3‐T4‐T5. Results: After experiencing excellent pain relief over the next two days, the patient was implanted with permanent leads and rechargeable generator four weeks later and reported sustained pain relief at 12‐month follow‐up visit. Conclusion: SCS provides an effective, alternative treatment option for select patients with Loeys‐Dietz syndrome who underwent repair of pectus excavatum with subsequent chronic chest wall pain who have failed conservative treatment. SCS may provide pain relief with advantages over conservative treatments and more invasive techniques.     

Influence of different supplementation on platelet aggregation in patients with rheumatoid arthritis

Clinical Rheumatology - Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim...