Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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On the basis of the contradiction between data on experimental head trauma showing oxidative stress-mediated cerebral tissue damage and failure of the majority of clinical trials using free radical scavenger drugs, we monitored the time-course changes of malondialdehyde (MDA, an index of cell lipid peroxidation), ascorbate, and dephosphorylated ATP catabolites in cerebrospinal fluid (CSF) of traumatic brain-injured patients. ⋯ On the whole, these data demonstrate the early onset of oxygen radical-mediated oxidative stress, proposing a valid explanation for the failure of clinical trials based on the administration of oxygen free radical scavenger drugs and suggesting a possible rationale for testing the efficacy of lipid peroxidation "chain breakers" in future clinical trials.
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Diabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in the United States. We reviewed our experience with DN as a cause of ESRD in a predominantly poor, African American (AA) population. ⋯ We conclude that AA females in Mississippi are significantly more predisposed to DN as a cause of ESRD than are AA males. Patients with DN in our population had poor BP control, presented to nephrologists with advanced disease, and often were not on an ACE inhibitor. The optimal level of BP control and which BP agents are best for this population need to be determined.
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Cigarette smoke augments asbestos-induced bronchogenic carcinoma in a synergistic manner by mechanisms that are not established. One important mechanism may involve alveolar epithelial cell (AEC) injury resulting from oxidant-induced DNA damage that subsequently activates poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair that can deplete cellular energy stores. We previously showed that whole aqueous cigarette smoke extracts (CSE) augment amosite asbestos-induced DNA damage and cytotoxicity to cultured AEC in part by generating iron-induced free radicals. We hypothesized that CSE increase asbestos-induced AEC injury by triggering PARP activation resulting from DNA damage caused by iron-induced free radicals. ⋯ CSE and asbestos induced PARP activation in cultured AEC in a nonsynergistic manner. These data provide further support that asbestos and cigarette smoke are genotoxic to relevant lung target cells and that iron-induced free radicals in part cause these effects.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function.
A nasal spray form of nicotine replacement therapy (Nicotrol NS, McNeil Consumer Products Co, Fort Washington, Pa) has been approved and, because of its rapid absorption across the nasal mucosa, may be more effective than nicotine gum or transdermal patches. We tested the hypothesis that the nicotine absorbed into the nasal mucosa would produce significant changes in hemodynamics and pulmonary function in 20 healthy, nonsmoking men and women. ⋯ In this population of nonsmokers, hemodynamic effects of the nicotine nasal spray were observed shortly after administration and before the peak serum nicotine concentration.
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To protect against the extracellular activity of serine proteinases, the lung is equipped with serine proteinase inhibitors including secretory leukocyte proteinase inhibitor (SLPI) and elafin. Both SLPI and elafin are locally produced by airway epithelial cells, but the mechanisms that regulate the expression of these proteinase inhibitors are relatively unknown. Previous studies using airway epithelial cell lines indicated that neutrophil elastase (NE) increases SLPI mRNA transcripts while decreasing SLPI protein release. Similar results were observed for elafin. The aim of the present study was to investigate the effect of NE on SLPI and elafin synthesis in cultures of human primary bronchial epithelial cells (PBEC). ⋯ The results from the present study indicate that NE may play a role in the regulation of the antiproteinase screen in the lung and the formation of a protective surface at the epithelial site.