Developmental neurotoxicology of in utero exposure to industrial solvents in experimental animals

In summary, relatively few solvents have been examined for developmental neurotoxicology. Although most of the studies have not been replicated, the majority of the solvents tested have produced significant differences from controls. Many used inhalation, which is often the most likely route of occupational or environmental exposure. The majority have extended the exposure for much of gestation of rats. The extensive usage of solvents and the proportion of those tested which have produced positive effects (although admittedly some not at environmentally-relevant exposure concentrations), make a strong case for additional testing of industrial solvents for developmental neurotoxicology.     

Correlation of perinatal brain growth with age, body size, sex, and race

This study compares the weight of the human brain to gestational age and body dimensions. A new formula for calculating the rate of growth is proposed. It consists of a second order polynomial function: Y = A0 + A1X + A2X2, in which Y is brain weight, body weight, height, or body surface area; X is gestational age in weeks and A0, A1, and A2 are statistically estimated coefficients. In utero, the growth rate is most rapid for body weight, followed in decreasing order by brain weight, body surface area, and height. Brain growth is the same for both sexes in black and white races; it accelerates between the 20th and 45th weeks of gestation. The size of the newborn infant brain is directly related to gestational age and body size and is not determined by sex or race.     

Inhibition by oral N-acetylcysteine of cigarette smoke-induced "bronchitis" in the rat

Specific pathogen-free rats were exposed to the cigarette smoke (CS) of 25 cigarettes daily for 14 days and concurrently given N-acetylcysteine (Nac) as 1% of their drinking water (average daily dose 973 mg/kg). The thickness of the epithelium was measured at four airway levels and the numbers of mucus-containing secretory cells, stained for neutral or acidic glycoprotein (NGP or AGP respectively), were counted in surface epithelium at eight airway levels. Cigarette smoke increased the thickness of the epithelium at three of the airway levels studied by between 37 and 72%. The number of secretory cells was increased at all airway levels distal to the upper trachea by between 102 and 421%. Secretory cells containing NGP were reduced in number but this was more than offset by a large increase in the number of secretory cells containing AGP at all airway levels. N-acetylcysteine inhibited CS-induced epithelial thickening. Nac also inhibited the CS-induced increase in the number of secretory cells with AGP, but had little effect on the CS-induced reduction in the number of cells with NGP. Thus, prophylactic oral N-acetylcysteine led to an overall inhibition of CS-induced mucous cell hyperplasia and epithelial hypertrophy. The results suggest a novel anti-inflammatory action for a drug with known mucolytic effects.     

Exercise intensity, training, diet, and lactate concentration in muscle and blood

With some, but not all, types and intensities of exercise, lactate accumulates in the blood and in the muscles engaged in the exercise. A great deal of attention has been directed towards attempting to understand the dynamics of lactate production and removal at the onset of exercise, during exercise, and during the recovery process following exercise. It has been hoped that an unravelling of these events would provide a key to understanding cellular metabolism and its regulation during exercise. The purpose of this introductory paper to a symposium on lactate is to present a brief overview of some of the conditions that influence the rate and magnitude of lactate accumulation during exercise. It is pointed out that many conditions influence the rate and magnitude of the accumulation of lactate in blood and muscles. Included are diet, state of physical fitness, and the type and duration of the exercise. We have cautioned against trying to evaluate the state of oxygen delivery to muscle and the state of tissue oxygenation from the appearance of lactate in blood. We have pointed out the positive aspects of lactate production based on how it augments the cellular supply of ATP, thereby allowing for high intensity exercise, and also the negative aspects that develop as a result the reduction in pH which adversely influences many cellular processes essential for muscular activity.     

Exposure to electromagnetic fields and the risk of leukemia

Evidence from animal experiments and human studies suggests that electromagnetic fields may be human leukemogens. Epidemiological studies of leukemia in occupational groups and in the general populations are reviewed. The results are inconsistent. In the few studies showing an association between exposure to electromagnetic fields and the risk of leukemia, the temporal relationship between exposure and effect was not established, the observed associations were weak, the dose-response relationships were based on qualitative levels of exposure without regard to the duration of exposure or secondary sources of exposure, and the risk ratios were probably biased due to the population selection procedures used and misclassification of exposure. The proportionate mortality or cancer incidence ratios are unreliable estimates of relative risk. Further epidemiological research is needed to establish an association between exposure to electromagnetic fields and the risk of leukemia.     

Antigen presentation by a B-cell line transfected with cloned immunoglobulin heavy- and light-chain genes specific for a defined hapten.

The rearranged genes encoding immunoglobulin heavy (mu) and light (kappa) chains specific for the hapten 2,4,6-trinitrophenyl (Tnp) were introduced into a B-lymphoma line that bears surface IgG with an unknown specificity and expresses surface Ia molecules. A transformant expressing surface IgM specific for Tnp was obtained. The transformant was found to present Tnp-proteins to antigen (protein)-specific T cells far more efficiently than the parenteral B-lymphoma line. This artificial system, utilizing recombinant DNA technology and gene transfer, provides several approaches for the study of T-cell-B-cell interactions.     

Xylose disposition in humans as a function of age

D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.     

Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett's esophagus

Sex and racial predilection, social history, and histology were analyzed in a biopsy-proven adenocarcinoma of the lower esophagus/esophagogastric junction collected over a 5-year period in two teaching institutions with different patient populations. Adenocarcinoma occurred in 11% of patients with biopsy-proven esophageal cancer. The disease occurred only in males at one center, and in a 7:1 ratio of males to females at the other center. Clear racial predilection was seen, since 12 of 13 patients with adenocarcinoma of the esophagus were white, whereas less than 20% of patients with squamous carcinoma of the esophagus were white. The finding of Barrett's epithelium in eight of the 13 cases strongly supports the theory that in white males, Barrett's epithelium is a precursor lesion of adenocarcinoma of the esophagus/esophagogastric junction.