Drought associated poisoning of cattle in South Texas by the high quality forage legume Leucaena leucocephala.

Approximately 80 head of yearling cattle grazing on 680 acres exhibited signs of Leucaena leucocephala toxicosis, which was confirmed in 3 animals by detection of 3-hydroxy-4 (IH)-pyridone, the metabolite of the poisonous principle mimosine, in their urine. The animals had grazed leucaena almost exclusively due to lack of alternative forage resulting from drought conditions. Toxicosis from this otherwise high quality forage would likely not have occurred had animals consumed lower amounts of leucaena and could probably have been prevented, as it has been elsewhere, had the animals been colonized with Synergistes jonesii, a beneficial ruminal bacterium capable of degrading the toxic metabolites.

Population monitoring: experience with residents exposed to uranium mining/milling waste.

More emphasis should be placed upon using biomarkers to address potential health risk among populations exposed to high concentrations of environmental toxicants. Among these studies, those which integrate exposure measurements with analyses of validated biomarkers may provide more reliable information for risk assessment and disease prevention. We have used a multidisciplinary approach to elucidate potential health hazards in a population living around uranium mining/milling facilities. The study included 24 target and 24 control residents who were matched for age and gender and selected based on time of residence in the study areas and proximity to mining/milling sites. Environmental samples were analyzed for uranium-238 (238U) concentrations and lead isotope ratios using inductively coupled plasma-mass spectrometry (ICP-MS) procedures, and blood samples were collected for cytogenetic analysis. We found that the 238U concentrations in soil samples were significantly higher than those in the control areas. In addition, the concentrations in the surface soil were significantly higher than in the subsurface soil (p<0.05) from target areas indicating environmental contamination by the mining/milling activities. Lead isotope data from soil samples taken near a railroad transfer location was significantly different from those of other sites, indicating contamination by non-native ore transported from sources outside of the region to local milling facilities for processing. Therefore, local residents have been exposed to low levels of radioactive contamination from the mining/milling activities on a daily basis for many years. From our cytogenetic analysis, the target population had more chromosome aberrations than the controls, although the differences were not significant (p<0.05). However, using our challenge assay, cells from the target population had a significantly abnormal DNA repair response, compared to cells from the same control population. In conclusion, the observed environmental contamination by uranium is consistent with the observed genotoxic effects in the target residents. Therefore, the residents have increased health risk and some of the health problems will most likely be related to exposure to the radioactive contaminants. Since the chromosome aberration frequency revealed increased, but not significant differences between the exposed and the control populations, we conclude that the health risk among the exposed residents is similar to those among nuclear workers.

Biomarker monitoring of a population residing near uranium mining activities.

We investigated whether residents residing near uranium mining operations (target population), who are potentially exposed to toxicants from mining waste, have increased genotoxic effects compared with people residing elsewhere (reference population). Population surveys were conducted, and 24 target and 24 reference residents were selected. The selected subjects and controls were matched on age and gender and they were nonsmokers. Blood samples were collected for laboratory studies. The standard cytogenetic assay was used to determine chromosome aberration frequencies, and the challenge assay was used to investigate DNA repair responses. We found that individuals who resided near uranium mining operations had a higher mean frequency of cells with chromosome aberrations and higher deletion frequency but lower dicentric frequency than the reference group, although the difference was not statistically significant. After cells were challenged by exposure to gamma-rays, the target population had a significantly higher frequency of cells with chromosome aberrations and deletion frequency than the reference group. The latter observation is indicative of abnormal DNA repair response in the target population.

Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.

1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence.

Overcoming perioperative spasm of the internal mammary artery: which is the best vasodilator?

After mobilization, vasospasm often reduces flow through the internal mammary artery. An established method of relaxing the artery and increasing flow is to wrap it in a papaverine-soaked swab. To our knowledge the ability of other topical vasodilators to overcome spasm of the internal mammary artery has not been studied clinically. In 50 patients in whom the left mammary artery was used for myocardial revascularization, we have investigated the effect of five agents on internal mammary artery free flow. The agents investigated were normal saline, papaverine, nifedipine, glyceryl trinitrate, and sodium nitroprusside. Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 18.5 minutes after the pedicle had been sprayed with one of the five agents. Normal saline produced a small increase in flow from a median of 23 ml/min (range 17 to 88) to 38 ml/min (20 to 84) (not significant), whereas a significant increase occurred with papaverine, from 25 (16 to 78) to 43 ml/min (34 to 112) (p less than 0.01). Nifedipine and glyceryl trinitrate raised free flow by almost threefold, from 23 (14 to 66) to 71 ml/min (45 to 118) and from 23 (14 to 58) to 62 ml/min (46 to 126), respectively (both p less than 0.001). Sodium nitroprusside, however, with an increase in flow from 26 (10 to 58) to 108 ml/min (46 to 196), 250% over control, proved to be more effective than nifedipine and glyceryl trinitrate (p less than 0.05). We therefore recommend the topical use of sodium nitroprusside to relieve perioperative spasm of the internal mammary artery.

Gastric cancer in New Mexico counties with significant deposits of uranium.

Several counties in northern New Mexico display high rates of mortality from gastric cancer. Significant differences in sex-specific, age-adjusted, average annual stomach cancer mortality rates among whites from 1970-1979 were found between counties with significant deposits of uranium compared to those without significant deposits. These results remained unchanged when either socioeconomic status or Hispanic ethnicity were considered. Additional research needs to consider individual characteristics and competing risk factors for individuals with gastric cancer in these counties. A working hypothesis is that residents of counties with significant deposits of uranium are exposed to higher-than-average environmental levels of radionuclides such as radon and radon daughters, or to trace elements such as arsenic, cadmium, selenium, and lead which are commonly found in areas with uranium deposits.

Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination.

The plasma clearances of antipyrine (AP) and indocyanine green (ICG) have been measured after intravenous administration in each of 20 normal male subjects aged 22 to 72 yr. An additional 4 subjects aged 65 to 73 yr received only ICG. AP clearance fell with age in the group as a whole (r = 0.56; p less than 0.01), but when cigarette smoking habits were considered the relationship was apparent only in smokers (r = 0.68; p less than 0.02). In the under 40 yr group. AP clearance was higher in smokers than nonsmokers (p less than 0.02). There was no such difference in men over 40 yr of age. These observations suggest that the enzyme-inducing effect of smoking diminishes with advancing years. In contrast, and consistent with a reduction in liver blood flow, the clearance of the highly extracted ICG fell with age, irrespective of smoking habits (r = 0.57; p less than 0.004). These findings suggest that while hepatic drug clearance may be impaired in elderly people, the outcome depends not only on the effects of the aging process on the physiologic determinants of hepatic clearance (liver blood flow and the activity of the drug-metabolizing enzymes) but also on the effects of environmental factors, such as smoking.