Parallel activation of Ca(2+)-induced survival and death pathways in cardiomyocytes by sorbitol-induced hyperosmotic stress.

Hyperosmotic stress promotes rapid and pronounced apoptosis in cultured cardiomyocytes. Here, we investigated if Ca(2+) signals contribute to this response. Exposure of cardiomyocytes to sorbitol [600 mosmol (kg water)(-1)] elicited large and oscillatory intracellular Ca(2+) concentration increases. These Ca(2+) signals were inhibited by nifedipine, Cd(2+), U73122, xestospongin C and ryanodine, suggesting contributions from both Ca(2+) influx through voltage dependent L-type Ca(2+) channels plus Ca(2+) release from intracellular stores mediated by IP(3) receptors and ryanodine receptors. Hyperosmotic stress also increased mitochondrial Ca(2+) levels, promoted mitochondrial depolarization, reduced intracellular ATP content, and activated the transcriptional factor cyclic AMP responsive element binding protein (CREB), determined by increased CREB phosphorylation and electrophoretic mobility shift assays. Incubation with 1 mM EGTA to decrease extracellular [Ca(2+)] prevented cardiomyocyte apoptosis induced by hyperosmotic stress, while overexpression of an adenoviral dominant negative form of CREB abolished the cardioprotection provided by 1 mM EGTA. These results suggest that hyperosmotic stress induced by sorbitol, by increasing Ca(2+) influx and raising intracellular Ca(2+) concentration, activates Ca(2+) release from stores and causes cell death through mitochondrial function collapse. In addition, the present results suggest that the Ca(2+) increase induced by hyperosmotic stress promotes cell survival by recruiting CREB-mediated signaling. Thus, the fate of cardiomyocytes under hyperosmotic stress will depend on the balance between Ca(2+)-induced survival and death pathways.

The risk of low birthweight.

Descriptive analyses of birthweight for single live births in the United States during 1974, using birth certificate information, show that several factors are associated with a high incidence of low birthweight babies. Multivariate analyses were performed to determine correlates of low birthweight. When other factors are held constant, race not white, previous reproductive loss, short interpregnancy interval, out-of-wedlock birth, no prenatal care, and maternal age under 18 years or over 35 years each increase the risk of having an infant of low birthweight. High birth order and maternal education under 12 years of schooling were not consistent risk factors for low birthweight. Odds ratios are presented and the method for combining these, to estimate the risk for an individual mother having a low-birthweight infant, is illustrated.

Improvement in infant and perinatal mortality in the United States, 1965--1973: I. Priorities for intervention.

Changes in United States infant and perinatal mortality in the period 1965--1973 were examined by race, age at death or length of gestation, and degree of urbanization. The decline of postneonatal mortality rates was greater than the declines of fetal and neonatal mortality rates. Other-than white infant and fetal mortality rates improved more than the white rates, except in the first day of life. Postneonatal mortality rates improved more in rural than in urban areas, while neonatal and perinatal mortality rates improved more in urban areas than in rural. These improvements in mortality rates have occurred at the same time as changes in medical techniques and the organization and availability of health services, improvements in economic conditions and standards of living, and changes in the demographic characteristics of the child-bearing population of the United States. Each of these changes was in a direction expected to have a favorable effect on infant and perinatal mortality. Nevertheless, the improvement of infant mortality rates has not changed the relative position of the United States in comparison with other countries. Programs to improve infant and perinatal mortality can use the data in this study to define high priority target groups using a method based on the size of the problem in the target group, the severity of the problem, and the amount and direction of change.

The results of a 13-year training program in maternal and child health for physicians.

This paper describes the 13-year experience of one school of public health in preparing physicians for the field of maternal and child health. Some 256 (87.7 percent) of the 292 graduates have remained in community health work. Of the 292 graduates, 106 (36.3 percent) are engaged in some teaching responsibilities.

Patterns of infant and early childhood mortality in the California Project of a collaborative Inter-American Study.

The California Project of the Inter-American Investigation of Mortality in Childhood was carried out in San Francisco and three surrounding counties in 1969 and 1970. The study found infant death rates of 18.5 per 1,000 live births in San Francisco and 17.2 per 1,000 live births in the three counties. Mortality in the neonatal period (the first 28 days of life) accounted for two-thirds of these deaths. Low birth-weitht played a key role in neonatal mortality, one that was particularly marked during the first day of life. Overall, the study found that 77.7 per cent of the neonatal fatalities and 85.6 percent of those dying in the first day of life weighed 2,500 grams or less at birth. Mortality was also very high among infants of mothers under 20 and over 34 years of age., the risks being especially great in the case of young mothers. Moreover, the vast majority of babies that were born to young mothers and died the first day had very low birth-weights. It is therefore concluded that young mothers ran a relatively high risk of having low birth weight babies prone to dying in the first day of life. This demonstrates a clear need for special measures capable of reducing the health risk faced by both young mothers and their children. Besides providing a more detailed explanation of these points, the authors recommend various specific measures that should be taken and present data obtained by the California Project on other aspects of mortality among infants and preschool children 1-4 years of age