Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

Surveillance around hazardous waste sites: geographic information systems and reproductive outcomes.

The purpose of this paper is to discuss the potential for integrating surveillance techniques in reproductive epidemiology with geographic information system technology in order to identify populations at risk around hazardous waste sites. Environmental epidemiologic studies have had problems with estimating or measuring exposures to individuals, and of detecting effects when the exposure is low, but continuous. In addition, exposures around hazardous waste sites are complex and frequently involve chemical mixtures. The birth weight of human babies has been reported to be sensitive to many environmental influences. Birth weight can be analyzed as a continuous variable or as a dichotomous one using the standard cutpoint of 2500 g or less to indicate low birth weight. It has the potential to be a powerful surveillance tool since exposures to the fetus reflect maternal and paternal exposures. The advent of recent environmental regulations pertaining to hazardous waste sites has greatly increased the availability of environmental data for many sites. The major problem with incorporating these data into epidemiologic studies has been with the logistics of data management and analysis. Computer-assisted geographic information systems hold promise in providing capabilities needed to address the data management and analysis requirements for effective epidemiologic studies around to hazardous waste sites.     

Postnatal white matter necrosis in preterm infants.

One hundred twenty-seven infants less than 36 weeks of gestation (mean +/- SE = 31 +/- 3.2 weeks) were studied with echoencephalography to determine the incidence and complications associated with white matter necrosis. Ten infants (8%) developed cysts ten or more days after birth, indicating postnatal onset of white matter necrosis. Univariate analysis showed that postnatal white matter necrosis was significantly associated with maternal infection (other than urinary infection), respiratory distress syndrome, and longer requirement of an oxygen concentration greater than 40%. Forward logistic regression analysis showed postnatal white matter necrosis to be associated with maternal infection, chronic placental infarction, congenital pneumonia, and longer requirement of an oxygen concentration greater than 40%. Neurodevelopmental outcome was abnormal during infancy in 4 of the 6 survivors with postnatal white matter necrosis. Severe respiratory disease and maternal and/or fetal infection appear to increase the risk of the immature brain to white matter necrosis, predisposing the infants to subsequent neurodevelopmental delay.     

In vitro determination of lung airway compliance in small animals

An in vitro method for obtaining pressure/volume curves from the lungs of small animals is described. The excised lungs were inflated and deflated with saline or air by a motor-driven syringe controlled by a microcomputer. The computer was programmed to display the curves in real time, correcting when necessary for the compressibility of air in the system. Volume compliance (K=dV/dP×1/V) was calculated by differentiating a polynomial fitted to the measured pressure/volume points. Repeatable curves were obtained from mice aged 24h (body weight 1·3±0·14g (SD), residual lung volume 8·43±1·5 μl (SD). A nonlinear decrease in differential compliance (K=dV/dP×1/V) with increasing strain was observed while the ratio K_saline/K_air increased from 2·5 to 10 over the range of strains investigated (ε=1–5). The relative surface tension (calculated from the difference between the pressures required to inflate the air and saline-filled organs to a given volume) increased exponentially with increasing volume. We conclude that it is now possible to obtain reproducible pressure/volume curves for lungs with a residual volume of less than 10 μl, from animals weighing approximately 1·5 g and, from these curves, estimate airway compliance and surface tension.     

High energy phosphate metabolism in experimental permanent focal cerebral ischemia: an in vivo 31P magnetic resonance spectroscopy study

Relative levels of phosphate metabolites in the brain were examined in vivo by 31P magnetic resonance spectroscopy (MRS) in 50 Sprague-Dawley rats before, during, and after induction of focal permanent cerebral ischemia. After acquisition of baseline spectra, rats were subjected to injury within the core of the MR spectrometer, and 31P spectra were collected for 60 min after injury: in 7 rats, permanent, acute focal cerebral ischemia was induced (ischemia group); in 6 rats, mild hypoxia (FiO2 14%) was induced at the time of the ischemic insult and was maintained for 20 min (ischemia-hypoxia group); in 6 rats, mild hypoxia (FiO2 14%) only was induced for 20 min (hypoxia group). Control studies were performed in 25 rats. Cerebral intracellular pH, calculated from the chemical shift of inorganic phosphate (Pi), decreased immediately after injury in the ischemia and ischemia-hypoxia groups. The first 31P spectrum obtained after injury was characterized by an increase in Pi and a decrease in phosphocreatine (PCr) in the ischemia and ischemia-hypoxia groups; these changes in spectra were significantly greater in the ischemia-hypoxia group. No significant changes in adenosine triphosphate (ATP) were found in either group. Within 60 min of occlusion, 31P spectra returned toward baseline spectra in both ischemia-hypoxia and ischemia groups. No significant changes were seen in spectra of rats subjected to hypoxia alone. These results confirm that 31P MRS is a sensitive measure of early changes of high energy metabolites in focal cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular responses of pregnant women during aerobic exercise in water: a longitudinal study

To determine the effects of pregnancy on the cardiovascular responses to immersion and exercise in water, 12 women completed 20 min of immersion and 20 min of bicycle ergometry at 60% predicted VO2max in 30 degrees C water during their 15th, 25th, and 35th week of pregnancy as well as 8-10 weeks post partum. Immersion lowered the resting heart rate approximately 8 bts/min (P less than 0.05). Exercise in water also resulted in a lower heart rate as compared with the same level of exercise on land (132 +/- 4 vs 149 +/- 6 bts/min; P less than 0.05). Both the rest and exercise heart rate responses were independent of duration of pregnancy or pregnancy status. Post partum exercise cardiac output averaged 9.9 +/- 0.4 l/min, significantly lower (P less than 0.05) than the 15th (12.7 +/- 0.5), 25th (14.7 +/- 0.5), or 35th week (15.1 +/- 0.7 l/min). Total peripheral resistance was greatest (P less than 0.05) post partum (657 +/- 29 dyn.s/cm5) compared with either the 15th (515 +/- 27), 25th (407 +/- 18), or 35th week (450 +/- 23). The results indicate that exercise in water lowers the heart rate compared with land exercise at the same metabolic rate. The combined effect of exercise, water, and pregnancy may elevate the cardiac output more than expected on land, but the same general pattern of exercise response will be evident throughout the duration of pregnancy. The results further suggest that water alters the heart rate and blood pressure responses such that land-derived exercise target heart rates should not be used to prescribe exercise intensity in water.