Lack of arterial PO2 downregulation in Atlantic salmon (Salmo salar L.) during long-term normoxia and hyperoxia.

Regulation of arterial partial pressure of O2 (PaO2) in Atlantic salmon (Salmo salar) was investigated during resting conditions in normoxic and hyperoxic water. Dorsal aorta cannulated adult Atlantic salmon (1.2-1.6 kg, n=8) were exposed to 2 week sequential periods of normoxia [16.7±1.1 kPa (mean±SD)] and hyperoxia (34.1±4.9 kPa) in individual tanks containing seawater (33.7±0.2 ppt) at stable temperature conditions (8.7±0.7°C) and a light regime of L:D=12:12. Tank design and sampling procedures were optimized to provide suitable shelter and current for the fish, and to allow repeated, undisturbed sampling of blood from free-swimming fish. Fish were sampled regularly through the experimental period. PwO2, PaO2, blood ion composition (Na+, K+, Cl-), acid-base status (pH, PCO2, HCO3-), haematocrit and glucose were measured. The most frequently observed PaO2 values were in the range of 60-80% of PwO2, both during normoxia and hyperoxia, and PaO2 values were significantly lower during normoxia than during hyperoxia. Blood pH, PCO2 and HCO3- were significantly elevated during hyperoxia, while, Na+, Cl- and Hct were significantly lower. K+ and glucose showed no significant differences. This study demonstrates a lack PaO2 regulation in Atlantic salmon to low partial pressures, in contrast to previous reports for many aquatic gill breathing animals. Both during normoxia and hyperoxia, PaO2 reflects PwO2, and alterations in external PO2 consequently result in proportional arterial PO2 changes. Physiological adaptation to hyperoxia, as illustrated by changes in several blood parameters, does not include down-regulation of PaO2 in Atlantic salmon. The lack of PaO2 regulation may make Atlantic salmon vulnerable to the oxidative stress caused by increased free radical formation in hyperoxic conditions.

Potentiation of radiation lethality in mouse melanoma cells by mild hyperthermia and chloroquine.

To test the hypothesis that radiosensitization by combined mild hyperthermia and chloroquine may be increased by the presence of melanin in treated cells, Cloudman melanotic mouse melanoma S91/6 cells, and the amelanotic S91/amel cells were incubated during a 3 h post-irradiation period with 0.03 mM chloroquine at 41 degrees C. A considerable increase in radiation lethality was observed (radiation potentiation factor > 1.6) in both cases. Addition of 0.1 mM isobutyl-methyl xanthine (IBMX), a promoter of melanin synthesis, to the growth medium of S91/6 cells 10 days before irradiation, did not further increase the lethality of radiation followed by combined heat and chloroquine treatment. Under these conditions, toxicity to unirradiated cells was slight. On the other hand, 10 microM chloroquine showed similar toxicity to unirradiated B-16 mouse melanoma cells, but did not increase radiation lethality. Factors other than melanin content therefore play a role in the potentiation of radiation lethality by mild hyperthermia and chloroquine.

The seven countries study: 2,289 deaths in 15 years.

Among 11,579 men ages 40-59 without evidence of cardiovascular disease, 2,289 died in 15 years, 618 from coronary heart disease. The 15 cohorts in seven countries (four regions) differed in all-causes death rate, mainly reflecting great differences in coronary mortality. Among characteristics of entry, only mean blood pressure helped to explain cohort differences in all-causes death rate. Three-quarters of the variance in coronary death rate was accounted for by differences in mean serum cholesterol and blood pressure of the cohorts. The mortality risk for individuals was examined in each of the regions. For coronary death, age, serum cholesterol, blood pressure, and smoking were highly significant in all regions except Japan, where coronary deaths were too few for evaluation. Relative weight was not significant anywhere. Physical activity was significant only in southern Europe, where differences are associated with socioeconomic status. For all-causes death, age and blood pressure were highly significant risk factors in all regions as was smoking habit, except in Japan. Relative body weight tended to be a negative risk factor everywhere, significantly so in southern Europe. Expectations for coronary death from the experience in the United States and northern Europe greatly exceeded observed deaths in southern Europe for men of their age, serum cholesterol, blood pressure, smoking habits, physical activity, and relative weight. The reverse, prediction of coronary deaths in America and in northern Europe from the southern European experience, greatly underestimated the deaths observed. Similar cross-predictions between the United States and northern Europe were good for all-causes deaths, excellent for coronary deaths. Analysis of time trends in relationships of mortality to entry characteristics showed continued importance of age, blood pressure, and smoking and a tendency for the importance of cholesterol to fall in the last 5 years of follow-up.