Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model

OBJECTIVE: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. METHODS: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion. Tissue samples were collected for immunologic and immunopathologic evaluation. RESULTS: Pig cardiac xenografts survived more than 18 and 19 days without evidence of hyperacute rejection. Immunologic analysis of serum samples demonstrated that circulating xenoreactive natural antibody levels did not return to pretransplantation levels. The production of xenoreactive natural antibodies from the recipient's splenocytes was inhibited completely. Histologic examination of xenografts showed the feature of acute vascular rejection. Immunohistochemical studies demonstrated infiltration of cardiac xenografts by large numbers of macrophages, small numbers of natural killer cells, and a few T cells. The infiltrating macrophages also showed expression of interleukin-1 and tumor necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on xenograft vasculature was observed. Interleukin-2 expression was not found in rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of activation (expression of cytokines interleukin-1 and tumor necrosis factor). CONCLUSIONS: This study demonstrates prolonged discordant cardiac xenograft survival and delayed xenograft rejection in a pig-to-baboon model. The delayed xenograft rejection is mediated by both humoral and cellular mechanisms. Pretransplantation total lymphoid irradiation combined with cyclosporine A and methotrexate can inhibit xenoreactive natural antibody production but not elicited antipig antibody production and the xenoreactivity of macrophages.     

Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain

AIM: To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate. METHODS: The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains. RESULTS: Neonatal brains had the least [3H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 microM) and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. CONCLUSION: Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.     

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.     

An early stage in sodium channel clustering at developing rat neuromuscular junctions

Voltage-gated sodium channels (VGSCs) are concentrated in the postsynaptic membrane at the adult rat neuromuscular junction (NMJ). We have used immunolabelling to determine the pattern of initial VGSC accumulation during development. At birth, but not 3 days before, VGSC labelling is detectable at the NMJ and in the perijunctional (periJ) membrane but not elsewhere. A much higher density cluster of VGSCs forms at the NMJ itself 1-2 weeks later. If the nerve is cut 2 days after birth, VGSC labelling persists in the periJ region for at least 4 weeks but the clustering of VGSCs at the NMJ fails to develop. Thus an early, stable accumulation of VGSCs develops near the NMJ at least a week before high density postsynaptic VGSC clusters form.     

Transition to chronic pain in men with low back pain: Predictive relationships among pain intensity, disability, and depressive symptoms.

Pain intensity, disability, and depressive symptoms are hallmarks of chronic pain conditions, but little is known about the relationships among these symptoms in the transition from acute to chronic pain. In this study, an inception cohort of men with low back pain (N?=?78) was assessed at 2, 6, and 12 months after pain onset. At 6 months, pain intensity, disability, and depressive symptoms were predicted only by their respective levels at 2 months after pain onset. At 12 months, pain intensity and depressive symptoms were predicted by heightened disability at 6 months after pain onset; 12-month depressive symptoms also were predicted by 2-month disability. Pain intensity was not predictive of changes in disability or depressive symptoms. These findings suggest that functional disability plays a more prominent role than pain intensity in the transition from acute to chronic pain. A "failure to adapt" conceptual model is presented to account for these results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

3D Interaction with the Desktop Bat

Many applications now demand interaction with visualizations of 3D scenes and data sets. Current flat 2D displays are limited in their capacity to provide this not only by the display technology but the interaction metaphors and devices used. The Desktop Bat is a device that has 5 degrees of freedom whilst retaining the simplicity of use o fa mouse. To use it for general 3D interaction several metaphors were created for the tasks of navigation and cursor manipulation and a set of experiments were conducted to determine which metaphors were the most efficient in use. Of these metaphors, a velocity control metaphor was the best for navigation and a metaphor that applied rotations and translations relative to the eyepoint coordinate system was best for object control.     

Analysis of oxyanion (BO33?, CO32?, SO42?, PO43?, SeO44-) substitution in Y123 compounds studied by X-ray photoelectron spectroscopy

XPS core level spectra of Y123 compounds doped by C, B, S, P, and Se elements are presented. It is found that the C1s, E1s, S2p, P2p, and Se3d binding energies of doped compounds are close to those of CaCO₃, FeBO₃, CuSO₄, NaH₂,PO₄, and SeO₂, reference compounds. It is concluded that these impurity elements form oxyanion groups in Y123 compounds.