The effects of smoking on bone mass and the rates of bone loss among elderly Japanese-American men

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.     

Effect of pregnancy on maternal oxygen saturation values: use of reflectance pulse oximetry during pregnancy

Our objective was to evaluate the usefulness of pulse oximetry monitoring in a large population of pregnant patients. We designed our study to measure pulse oximetry saturation in a cross section of 952 obstetric inpatients and outpatients. A group of 366 patients identified as normal were compared with abnormal subgroups. A subgroup of 64 patients with saturation measurements less than 96% were further evaluated. Our results indicated that oxygen saturation values did not change appreciably during the course of pregnancy in normal patients. Hypoxemia (saturation measurement less than 96%) was associated with smoking, and hypoxemia with preterm labor occurred more frequently in patients who smoked. Obesity and magnesium sulfate use appeared to be synergistic in the presence of hypoxemia. We concluded that the routine use of pulse oximetry during pregnancy may not be justified. Smoking, obesity, and magnesium sulfate use have some effect on oximetry in pregnant patients.     

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.     

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.