Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.     

Cell surface hydrophobicity, adherence to HeLa cell cultures and haemagglutination pattern of pyelonephritogenic Escherichia coli strains

Cell surface hydrophobicity, haemagglutination pattern and adherence to HeLa cells were examined in 230 strains of Escherichia coli collected from women (n = 61 strains) and children (n = 65 strains) with non-obstructive acute pyelonephritis and in 104 faecal control strains of E. coli from healthy adults (n = 71 strains) and children (n = 33 strains). Pyelonephritogenic E. coli strains showed a significantly increased incidence of hydrophobic properties (90%) and mannose resistant haemagglutination (MRHA) of human erythrocytes (83%) than faecal control strains (64 and 23% respectively, P less than 0.001 in both cases). Mannose sensitive haemagglutination (MSHA) was observed in 48% of the pyelonephritogenic E. coli strains and in 50% of the faecal control strains (NS). The incidence of adherence to HeLa cells was low both in pyelonephritogenic and faecal control strains, 6 and 7% respectively (NS). The bacterial phenotypes MRHA + MSHA + and MRHA + MSHA- appeared significantly more often in pyelonephritogenic E. coli strains (35 and 48% respectively) than in faecal control strains (5 and 17% respectively, P less than 0.001 in both cases). The phenotype MRHA- MSHA + occurred significantly more often in control strains (45%) than in pyelonephritogenic strains (13%, P less than 0.001). Eighty-three per cent of the pyelonephritogenic E. coli strains expressing hydrophobic properties showed MRHA and 50% of the hydrophobic strains showed MSHA. There were no significant correlations between cell surface hydrophobic properties and haemagglutination pattern or adherence to HeLa cells in pyelonephritogenic E. coli strains nor in faecal control strains.     

High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.     

Paramecium calcium channels are blocked by a family of calmodulin antagonists.

Although the voltage-sensitive Ca channel present in Paramecium has been subjected to detailed physiological and genetic analysis, no organic ligands have been described that block this channel with high affinity and that ultimately can be used to identify channel components. Based on a previous observation that the naphthalene sulfonamide calmodulin antagonist W-7 can block Paramecium Ca channels at high concentration, we have synthesized analogs of W-7 that block these channels at concentrations of less than 1 microM. The effectiveness of these compounds was tested both by a sensitive behavioral assay and on Ca channels that had been incorporated into planar lipid bilayers. Despite the fact that these compounds are effective Paramecium calmodulin antagonists, two independent lines of evidence suggest that W-7 and its analogs block the Ca channel by a mechanism that is independent of their action on calmodulin. In addition, the sensitivity to W-7 or dihydropyridines of Ca channels present in a number of eukaryotic phyla has been used to identify similarities in Ca channels from widely diverse organisms. It appears that the pharmacological specificity provides a means to group Ca channels.     

Use of somatosensory evoked potentials to detect peripheral ischemia and potential injury resulting from positioning of the surgical patient: case reports and discussion.

BACKGROUND: Somatosensory evoked potentials (SSEPs) have long been recognized as an excellent tool for detecting neural and vascular compromise during vascular, neurosurgical and orthopedic procedures. SSEPs have the ability to localize, central versus peripheral, the area of compromise. Many surgeons use only lower-limb SSEP monitoring when performing lumbar spinal surgery. The upper extremities are usually not monitored during such procedures, and monitoring oxygen saturation does not detect neural compromise. PURPOSE: To report that the expanded use of SSEP monitoring during surgery can be beneficial in detecting peripheral ischemia or neural compromise resulting from positioning. STUDY DESIGN: Three case reviews of orthopedic spine surgeries where SSEP monitoring provided early warnings of vascular and neural compression. METHODS: The cases review three different lumbar procedures in which evidence of peripheral ischemia and nerve compression were detected by SSEP monitoring. RESULTS: By the use of upper- and lower-extremity monitoring during lumbar procedures, early detection of ischemia and nerve compression were noted intraoperatively. These changes prompted examination of the patient and repositioning to correct the ischemia or compression. The repositioning in these cases corrected the problem, and no lasting effects were found. CONCLUSIONS: Including SSEP monitoring of the bilateral upper extremities should be considered during lumbar spinal procedures. Such monitoring can be offered for a slightly increased expense and only minimal time delay to place the additional required electrodes by the technician. As a direct result of the early warning of the SSEP monitoring, we were able to avoid potential ischemic injuries and improve patient outcomes.