Comparison of abrasion model differences in heavy ion fragmentation: optical versus geometric models

Using an abrasion-ablation collision model, which includes contributions from frictional-spectator interactions and electromagnetic dissociation, analyses of the sensitivities of predicted fragmentation cross sections to the choice of a particular abrasion formalism are made using both geometric and optical potential abrasion models. Most cross section differences obtained using the two abrasion models are less than the present experimental uncertainties, suggesting that either abrasion model is suitable for estimating isotopic and elemental fragment distributions.     

Cerebral complications of murine monoclonal CD3 antibody (OKT3): CT and MR findings

Treatment of acute renal allograft rejection with mouse monoclonal antibody (OKT3) is associated with systemic and neurologic side effects. We describe cerebral abnormalities in a 13-year-old boy with steroid-resistant renal allograft rejection. After treatment with OKT3, an acute neurologic syndrome developed, including seizures, lethargy, and decreased mental function. CT and MR imaging revealed confluent cerebral lesions at the corticomedullary junction. Contrast-enhanced MR images showed patchy enhancement, indicating blood-brain barrier dysfunction. The diagnosis of OKT3-induced encephalopathy with cerebral edema and capillary leak syndrome was made. Although CT and MR findings are nonspecific, neuroradiologists should be aware of this condition in transplant patients treated with OKT3.     

In vitro metabolic N- and C-oxidation of phenanthridine

In order to compare an acceleromyograph (TOF-Guard) with a mechanomyograph (Grass FT03), the dose-response relationship of rocuronium was simultaneously determined in both arms of 15 children aged 3-11 years during anaesthesia with thiopentone, alfentanil and nitrous oxide. Three subgroups of five children received rocuronium 120, 180 or 240 micrograms.kg-1 randomly. The effective doses to produce 50% and 95% depression of the first twitch of the train-of-four determined by acceleromyography were 206 and 337 micrograms.kg-1, respectively, while these values determined by mechanomyography were 151 and 331 micrograms.kg-1, respectively. The dose-response curve obtained by acceleromyography was steeper and shifted to the right compared with that obtained by mechanomyography (p < 0.0001). The difference between the effective dose producing 50% twitch depression determined by the two devices was highly significant (p < 0.0001). In 13 out of 15 children, the acceleromyograph control train-of-four ratio was significantly greater than unity. Although there was a good correlation (r = 0.85) between simultaneous pairs of measurements of neuromuscular block, the acceleromyograph exhibited a bias of -25% relative to the mechanomyograph with wide limits of agreement (-62 to +12%). We conclude that acceleromyographic and mechanomyographic measurements should not be used interchangeably when determining the potency of muscle relaxants.     

3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima

Oxidation of LDL may be of pivotal importance in atherogenesis, but the mechanisms that promote oxidation in vivo remain poorly understood. We have explored the possibility that one pathway involves myeloperoxidase, a heme protein secreted by phagocytes. Myeloperoxidase is the only human enzyme known to generate hypochlorous acid (HOCl), a potent oxidizing agent, at physiological halide concentrations. LDL exposed to the complete myeloperoxidase-H2O2-Cl- system underwent chlorination of its protein tyrosyl residues. Treatment of LDL with reagent HOCl resulted in 3-chlorotyrosine formation, implicating HOCl as an intermediate in the enzymatic reaction pathway. In contrast, 3-chlorotyrosine was undetectable in LDL oxidized by hydroxyl radical, copper, iron, hemin, glucose, peroxynitrite, horseradish peroxidase, lactoperoxidase, or lipoxygenase. These results indicate that 3-chlorotyrosine is a specific marker for LDL oxidation by myeloperoxidase. To address the role of myeloperoxidase in promoting LDL oxidation in vivo, we used stable isotope dilution gas chromatography-mass spectrometry to quantify 3-chlorotyrosine in human aortic tissue and in LDL isolated from atherosclerotic lesions. The level of 3-chlorotyrosine in atherosclerotic tissue obtained during vascular surgery was sixfold higher than that of normal aortic intima. Moreover, the level of 3-chlorotyrosine was 30-fold higher in LDL isolated from atherosclerotic intima compared with circulating LDL. The detection of 3-chlorotyrosine in human atherosclerotic lesions indicates that halogenation reactions catalyzed by the myeloperoxidase system of phagocytes constitute one pathway for protein oxidation in vivo. These findings raise the possibility that the myeloperoxidase-H2O2-Cl- system plays a critical role in converting LDL into an atherogenic form.     

Novel qualitative structure-activity relationships for the antinociceptive actions of H2 antagonists, H3 antagonists and derivatives

Recent studies have shown that cimetidine, burimamide and improgan (also known as SKF92374, a cimetidine congener lacking H2 antagonist activity) induce antinociception after intracerebroventricular administration in rodents. Because these substances closely resemble the structure of histamine (a known mediator of some endogenous analgesic responses), yet no role for known histamine receptors has been found in the analgesic actions of these agents, the structure-activity relationships for the antinociceptive effects of 21 compounds chemically related to H2 and H3 antagonists were investigated in this study. Antinociceptive activity was assessed on the hot-plate and tail-flick tests after intracerebroventricular administration in rats. Eleven compounds induced time-dependent (10-min peak) and dose-dependent antinociceptive activity with no observable behavioral impairment. ED50 values, estimated by nonlinear regression, were highly correlated across nociceptive assays (r2 = 0.98, n = 11). Antinociceptive potencies varied more than 6-fold (80-464 nmol), but were not correlated with activity on H1, H2 or H3 receptors. Although highly potent H3 antagonists such as thioperamide lacked antinociceptive activity, homologs of burimamide and thioperamide containing N-aromatic substituents retained H3 antagonist activity and also showed potent, effective analgesia. A literature review of the pharmacology of these agents did not find a basis for their antinociceptive effects. Taken with previous findings, the present results suggest: 1) these compounds act on the brain to activate powerful analgesic responses that are independent of known histamine receptors, 2) the structure-activity profile of these agents is novel and 3) brain-penetrating derivatives of these compounds could be clinically useful analgesics.