Biomedical subjects
C Colton
Publications and source records attributed to C Colton.
Mechanisms of the antioxidant effects of nitric oxide.
The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components under high local concentrations of NO. However, NO can also abate the oxidation chemistry mediated by reactive oxygen species such as H2O2 and O2- that occurs at physiological levels of NO. In addition to the antioxidant chemistry, NO protects against cell death mediated by H2O2, alkylhydroperoxides, and xanthine oxidase. The attenuation of metal/peroxide oxidative chemistry, as well as lipid peroxidation, appears to be the major chemical mechanisms by which NO may limit oxidative injury to mammalian cells. In addition to these chemical and biochemical properties, NO can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. This review will address these aspects of the chemical biology of this multifaceted free radical and explore the beneficial effect of NO against oxidative stress.
Workplace performance studies of half-mask respirators.
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Reconstruction after malunion and nonunion of intra-articular fractures of the distal humerus. Methods and results in 13 adults.
We reviewed the results of 13 adults of secondary reconstruction of malunited and ununited intraarticular distal humeral fractures. Their average age was 39.7 years, and preoperatively all had pain, loss of motion and functional disability; the average arc of motion was only 43 degrees and the average flexion contracture was 45 degrees. Nine patients had ulnar neuropathy. Elbow reconstruction, at an average of 13.4 months after the original injury, included osteotomy for malunion or debridement for nonunion, realignment with stable fixation and autogenous bone grafts, anterior and posterior capsulectomy and ulnar neurolysis. The elbows were mobilised 24 hours postoperatively. There were no early complications and all nonunions and intra-articular osteotomies healed. After a mean follow-up of 25 months, the average arc of motion was 97 degrees with no progressive radiographic degeneration. Ulnar nerve function improved in all cases and clinical assessment using the Morrey score showed two excellent, eight good and three fair results. Reconstruction of intra-articular malunion and nonunion of the distal humerus in young active adults is technically challenging, but can improve function by restoring the intrinsic anatomy of the elbow.
The effect of xanthine/xanthine oxidase generated reactive oxygen species on synaptic transmission.
The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xanthine oxidase produced a significant depression in evoked release, with no change in either resting membrane properties or in the action potential. Addition of catalase to the xanthine/xanthine oxidase-containing media partially blocked the synaptic depression, indicating that H2O2 contributes to the synaptic changes induced by exposure to xanthine/xanthine oxidase. H2O2 applied directly to the perfusing media also produced a decrease in synaptic efficacy. The results demonstrate that reactive oxygen species, in general, depress evoked synaptic transmission.
Perturbations of the endothelium.
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Blood cleansing by diafiltration in uremic dog and man.
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Species differences in the generation of reactive oxygen species by microglia.
Although a variety of potential sources for reactive oxygen species (ROS) exist in the CNS, brain macrophages, i.e., the microglia, generate large quantities of these reactive species, particularly in response to injury or inflammatory signals. In order to understand how microglia contribute to changes in oxidative status of the CNS and how this might related to disease states, such as Alzheimer disease (AD), we have examined the regulation of superoxide anion and nitric oxide production from rodent and human microglia. Our results indicate that microglia from all species we have studied release superoxide anion, but produce significantly different amounts in response to the same activating agents. Species differences are also found in the ability to generate nitric oxide (NO). In particular, mouse microglia generate large quantities of NO when stimulated, but human and hamster microglia do not produce measurable amounts under the same stimulation conditions. These species differences are important to consider when modeling human disease processes from rodent studies.
Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.
Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava. Incubation with NPY (50-1000 nM) for 48 h increased by up to twofold cell number and [3H]-thymidine incorporation in both cell types (aortic more sensitive to NPY than venous). Following incubation with NPY, the disappearance of NPY immunoreactivity (-IR) from media was markedly delayed in the presence of SMC, and cell content of NPY-IR increased in a dose-dependent manner, indicating that SMC either diminish degradation of the peptide (possibly by internalization) or secrete endogenous NPY (or both). Structure-activity relationship studies with NPY(18-36) indicated involvement of Y1 receptors in mitogenesis. Thus, NPY has a mitogenic effect (probably mediated by Y1 receptors) and, therefore, may be a sympathetic trophic factor involved in vascular hypertrophy.
Biological activity of interleukin-10 in the central nervous system.
Cytokines play a crucial role as mediators of inflammation. Astrocytes and microglia are the two major glial cells involved in the central nervous system immune responses. In this study we examined the effects of interleukin-10 (IL-10), one of the naturally occurring inhibitory cytokines, on different types of glial cells in culture such as rat astrocytes, hamster microglia and C6-2B glioma cells. Phosphorylation of signal transducers and activators of transcription (STAT) proteins was used as a marker for IL-10 activity. Within minutes, IL-10 elicited a strong and weak increase in STAT3 and STAT1 phosphorylation, respectively, in human T lymphocytes, suggesting that STAT3 is a main IL-10 signaling event in these cells. In contrast, IL-10 failed to induce STAT3 in glial cells, but elicited a weak increase in STAT1 phosphorylation in microglia and C6-2B glioma cells only, suggesting that in some glial cell population(s) IL-10 may produce cellular responses via activation of the STAT1 pathway. Moreover, in C6-2B cells, IL-10 elicited a decrease in the level of basic fibroblast growth factor mRNA. A similar decrease was observed in adult rat hypothalamus, indicating that this cytokine may regulate glial production of trophic factors. Our data suggest that IL-10 may play a role in glial cell differentiation and proliferation.
Transcellular urea gradients cause minimal depletion of extracellular volume during hemodialysis.
Concern exists that increasingly high-efficiency dialysis will result in large urea gradients between intracellular and extracellular compartments (VI, VE) leading to large amounts of extracellular volume depletion (delta VE) and hemodynamic instability induced by rapid water flow from VE to VI. The authors investigated this question with a two-compartment model that provided estimates of VI, VE, and osmotically active intracellular and extracellular urea and nonurea concentrations during hemodialysis. The authors found that the urea gradient-induced transcellular water shift is only a very small fraction of VE, even with high urea clearance and short hemodialysis time. The net water shift was small because the urea and nonurea transcellular osmolar gradients were of similar magnitudes but in offsetting directions.
Severely displaced supracondylar fractures of the humerus in children: a simple method of treatment.
A simple form of overhead olecranon traction has been used to treat 27 children with severely displaced supracondylar fractures, in whom a satisfactory reduction could not be obtained by closed means. All the children were assessed clinically and radiologically at an average of 54 weeks after injury. Twenty-two children (81%) had an excellent result, with preservation of the normal carrying angle and no significant loss of movement; the other five children had a good result. Only two children (7%) were left with a minimal cubitus varus deformity. The method is technically easy to perform and has not been associated with significant complications.