Anaphylactic shock and its implication for nurses

We report the case of a voluminous melanotic neuroectodermic tumor, also termed melanotic progonoma, which developed in a 5 month old infant, recalling the main aspects of such uncommon non-odontogenic tumors with characteristic histological features. The large size of the tumor can hinder feeding in infants. Surgical cure is generally easy and outcome quite satisfactory without recurrence.     

Autoimmune diabetes induced by the beta-cell toxin STZ. Immunity to the 60-kDa heat shock protein and to insulin

Administered at a suitably low dose, the toxin streptozotocin (STZ) can trigger an autoimmune process leading to destruction of the beta-cells of the pancreatic islets. In this study, we examined specific immunological reactions in mice before and during the development of STZ-induced autoimmune diabetes. We now report that the development of spontaneous autoantibodies to insulin can serve as a marker of susceptibility to a low dose of STZ. Susceptible male mice of the C57BL/KsJ strain manifested such anti-insulin antibodies, and resistant female mice did not. Administration of a low dose of STZ (five daily doses each of 30 mg/kg) induced transient hyperglycemia approximately 20-30 days later, which temporarily remitted but was followed by intractable diabetes approximately 2.5 months later. The diabetogenic process triggered by the low dose of STZ was associated with an increase in the level of anti-insulin antibodies bearing the Dana and Micha (DM) idiotype, later followed by the appearance of anti-idiotypic antibodies that peaked before the onset of diabetes. Antibodies and T-cells reactive to hsp60 (heat shock protein) were triggered by the low-dose STZ administration and persisted throughout the period that preceded clinical diabetes. T-cells reactive to the p277 peptide of hsp60 were also observed. Finally, active immunization to hsp60 caused transient hyperglycemia by itself and also aggravated the hyperglycemia induced by low-dose STZ. Thus, autoantibodies to insulin can indicate susceptibility to a toxic trigger of diabetes, and a low dose of a toxin can activate the insulin and hsp60 autoimmunity that has been detected previously in the spontaneous autoimmune diabetes of NOD strain mice.     

Neuropathological findings after intracerebral implantation of microdialysis catheters

The neuropathological and immunocytochemical changes in the sheep forebrain following 7 days of microdialysis, using a catheter approved for human use, are described. There was no behavioural dysfunction and light microscopy revealed mild astrogliosis and patchy macrophage infiltration immediately adjacent to the catheter track. The surrounding neuropil was normal. There was one small subcortical haemorrhage (10 x 1.5 mm). These findings are similar to those following microdialysis in rodents and suggest that the risk of significant damage to the human brain is low, that neuropathological changes in the brain around the catheter should not interfere with local brain metabolism, and that the catheter should be affixed in such a way as to minimize movement-induced damage to the brain.     

Antibiotic pharmacodynamics in cerebrospinal fluid

The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum. In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent. However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness. With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.     

Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands

The 2-isopropyl thiazolyl group is a highly optimized P3 ligand for C2 symmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P3 ligand into a piperazine hydroxyethylamine series also yielded novel, highly potent inhibitors. In tissue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed.     

Elimination of dislocations in heteroepitaxial MBE and RTCVD Ge x Si1-x grown on patterned Si substrates

We have grown Ge _x Si_1-x (0 <x < 0.20,1000–3000Å thick) on small growth areas etched in the Si substrate. Layers were grown using both molecular beam epitaxy (MBE) at 550° C and rapid thermal chemical vapor deposition (RTCVD) at 900° C. Electron beam induced current images (EBIC) (as well as defect etches and transmission electron microscopy) show that 2800Å-thick, MBE Ge_0.19Si_0.81 on 70-μm-wide mesas have zerothreading and nearly zero misfit dislocations. The Ge_0.19Si{0.81} grown on unpatterned, large areas is heavily dislocated. It is also evident from the images that heterogeneous nucleation of misfit dislocations is dominant in this composition range. 1000Å-thick, RTCVD Ge_0.14Si_0.86 films deposited on 70 μm-wide mesas are also nearly dislocation-free as shown by EBIC, whereas unpatterned areas are more heavily dislocated. Thus, despite the high growth temperatures, only heterogeneous nucleation of misfit dislocations occurs and patterning is still effective. Photoluminescence spectra from arrays of GeSi on Si mesas show that even when the interface dislocation density on the mesas is high, growth on small areas results in a lower dislocation density than growth on large areas.     

Measurements and analysis of transmitted spectra from LOTUS fission-suppressed hybrid blanket driven by D-T neutrons

The neutron spectra transmitted across a fission-suppressed hybrid blanket and its components, driven by a low intensity 14 MeV Haefely neutron generator, were measured with a 2×2 NE213 detector at LOTUS facility. These experiments have been analyzed with 2D and 3D codes DOT3.5 and MCNP, respectively. The spectral integrals between 15 to 1 MeV show good agreement among the 2D, the 3D, and the NE213 for 15 cm lead, 18 cm beryllium, and 25 cm graphite slabs. However, there are large discrepancies for 6.2 cm stainless steel and 15 cm lithium carbonate slabs. The assemblies involving two or more of these slabs reflect these tendencies. We observe also considerable disagreement over pointwise spectra for a number of assemblies.Work done while on visiting assignment to Institut de Génie Atomique, E.P.F.L.     

Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases

Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.     

Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.     

Some aspects of the role of coal thermoplasticity and coke structure in coal gasification. 2. The effects of pressure and heating rate on dilatometric parameters and optical anisotropy development

An examination of the influence of pressure and heating rate on the thermoplastic properties of a weakly coking coal and of coal with various pitch-like additives was carried out using a high pressure dilatometer. Pressure up to 4 MPa markedly increased the swelling properties and increased the plastic range by decreasing the softening temperature, but the effects of pressure were strongly influenced by rate of heating with high heating rates enhancing the effects. Additions of tar or pitch also enhanced swelling at low pressure. The solid carbonization residues from the dilatometer were examined by polarized light microscopy to determine the content and composition of optically anisotropic species. The anisotropic content was increased by increases in pressure and heating rate and pitch additives enhanced the anisotropic content, especially at low pressure, without affecting the composition of the anisotropy. No direct correlations exist between the dilatometric parameters and the optical anisotropy but their dependence on the conditions emphasizes that when considering high pressure gasification of coal, it is necessary to obtain data under appropriate conditions.