Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP.

The osteoclast is unique in its ability to resorb bone, and excessive osteoclastic activity has been implicated in osteoporosis, Paget disease of bone, rheumatoid arthritis, and the growth of metastases in bone. The activity of this cell is controlled by the main circulating inhibitor, calcitonin, in association with locally produced modulators. We show that nitric oxide (NO) may be an important member of the latter group. NO is produced by the vascular endothelium and nervous system and is involved in both neurotransmission and the regulation of blood pressure. However, our results show that the autocoid is also a potent inhibitor of osteoclast function. NO (30 microM) produced a decrease to approximately 50% of the original osteoclast spread area. Similar effects were also produced by 3-morpholinosydnonimine or sodium nitroprusside, reagents that spontaneously release NO. These shape changes were associated with a reduction of bone resorption after a 24-hr incubation of isolated osteoclasts on devitalized bone slices. NO is thought to act by stimulating guanylate cyclase, with a consequent increase in cyclic GMP, but a different mode of action is likely in the osteoclast since dibutyryl or 8-bromo cyclic GMP have no effect. It should be noted that calcitonin can produce similar changes in shape and activity but is associated with an increase in osteoclast intracellular calcium and cessation of membrane movement; neither of these is produced by NO, suggesting that its mode of action is different. The abundance of NO-producing endothelial cells in bone marrow and their proximity to osteoclasts suggests that marrow endothelial cells may play a physiological role in the regulation of osteoclastic activity.     

O6-methylguanine-DNA methyltransferase in human fetal tissues: fetal and maternal factors

O6-Methylguanine methyltransferase (O6-MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race and of maternal smoking and drug usage. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin, and brain. Each fetal organ homogenate exhibited a 3- to 5-fold level of interindividual variation of O6-MT. There did not appear to be any significant differences of O6-MT as a function of fetal race and age and in the tissues obtained from mothers who smoked cigarettes during pregnancy. The fetal tissues obtained from an individual using phenobarbital exhibited 4-fold increases in O6-MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest a possible enhancement of human fetal O6-MT by certain xenobiotics, with little if any modulation by racial factors and maternal smoking habits.     

Increased mitral valve insufficiency during precordial "whoop"

A patient with rheumatic mitral valve stenosis and regurgitation presented with shortness of breath and a "noise" in her chest. Cardiac auscultation revealed an intermittent late systolic "whoop." An increase in severity of mitral valve insufficiency during the periods of "whoop" was observed by pulsed Doppler, hemodynamic tracings and left ventriculography.     

Wartime determinants of arteriographically confirmed coronary artery disease in Beirut

This study investigates the association of wartime stress variables and coronary artery disease as determined by coronary angiography in Lebanon in 1986, a country with an ongoing civil war for over a decade. A total of 127 patients who underwent coronary angiography at the American University of Beirut Medical Center were individually matched on age and sex with visitor controls free from any evidence of clinical coronary artery disease. Arteriographic cases (greater than or equal to 70% maximal stenosis) were compared with two control groups: arteriographic controls (entirely normal coronaries) and visitor controls. Findings suggest that there is a relation between exposure to both acute and chronic war events and coronary artery disease in this patient population. The reporting of exposure to acute war events was significantly higher in cases compared with both visitor controls (odds ratio (OR) = 2.4, 95% confidence interval (Cl) 1.17-4.90) and arteriographic controls (OR = 2.8, 95% Cl 0.93-8.47). Crossing the "green-lines" that separate two belligerent sides, considered as an attribute of war-related chronic stress, was more frequent in cases compared with visitor controls (OR = 3.25, 95% Cl 1.54-6.89) and arteriographic controls (OR = 5.38, 95% Cl 1.65-17.6). The relation observed between wartime stress and coronary artery disease could not be explained by possible overreporting of stressful events in patients with suspected coronary artery disease or by an increase in clinical awareness for the disease for those under continuous stress. Adjusting for the effect of the well-established coronary artery disease risk factors did not alter the above findings.