Occupational hazards to fertility and pregnancy outcome.

Occupational reproductive hazards to women have been studied frequently despite the fact that many female reproductive endpoints are not readily observable or routinely recorded in occupational medical records (subfertility, delayed conception, early pregnancy loss, menstrual cycle dysfunction). However, a number of outcomes are fairly readily observable (low birthweight, clinically observed SAB, preterm labor) and medically recorded although they are not generally recorded in the occupational setting. In addition, techniques for observing reproductive outcomes in women are generally less invasive than those in men, particularly with recent developments in urinary monitoring for ovarian function and early pregnancy loss. Although studies of some exposures and outcomes (risk of SAB, low birthweight, or preterm birth with exposure to VDTs or EMFs or exposure to metals and menstrual dysfunction, infertility, or SAB) have shown inconsistent results, a number of findings regarding other associations have been fairly consistent and are very suggestive of causal relationships. Occupational exposure to solvents does appear to increase the risk of dysmenorrhea and SAB, particularly with exposure to organic solvents. Increased risk of adverse reproductive outcomes has also been observed among women working in agricultural settings, but no link has been made to specific exposures. In addition, physical stressors such as shift work, long hours standing, and lifting have been fairly consistently associated with increased risk of SAB or preterm birth. Finally, while complete agreement among studies is lacking, many have observed an increased risk of subfertility or SAB associated with work in medical occupations and with some specific medical exposures, such as nitrous oxide, anesthetic gases and antineoplastic drugs. Much remains to be explored, particularly clarification of the relationship for exposures and outcomes that have shown inconsistent results. These require specific efforts to validate exposures and outcomes, to investigate and control for confounding variables, to consider the effects of multiple comparisons, to study populations of adequate size to provide meaningful statistical analyses, and to make possible the evaluation of dose-response and timing of exposure effects.

Human glial cell production of lipoxygenase-generated eicosanoids: a potential role in the pathophysiology of vascular changes following traumatic brain injury.

Acute cerebrovascular changes which occur following traumatic brain injury represent a highly complex, multifactorial pathophysiologic process which is poorly understood. It is now recognized that, under normal conditions, the brain is a source of a variety of arachidonic acid metabolites which are synthesized by both cyclooxygenase and lipoxygenase. The specific cellular source of these highly vasoactive substances remains controversial. Recent work has demonstrated that lipoxygenase products were detected by immunosensitive assay in whole brain samples from a gerbil concussive injury model, yet the production of leukotrienes could not be accounted for by cerebral vessels and their contents alone. It has been theorized that the probable source for these metabolites is the cortical neuron. We sought to elucidate whether cultured human glial cells, obtained from specimens removed at the time of surgery, are a significant source of lipoxygenase products as measured by high performance liquid chromatography (HPLC). We observed that these cells consistently produced 5, 12, and 15-HETE class eicosanoids despite failure to produce significant cyclooxygenase products. These preliminary findings are of considerable interest because these lipoxygenase products are known to be highly vasoactive as well as potent mediators of increased vascular permeability. Since it is known that mechanical perturbation of cell membranes stimulates the release of arachidonic acid from membrane phospholipids, it is conceivable that the production of these eicosanoids following traumatic brain injury could account for local cerebrovascular changes including both vasospasm and interstitial edema formation.

Effects of 6-[p-(4-phenylacetylpiperazin-1-yl)phenyl]-4,5-dihydro-3(2H)pyridazinone (CCI 17810) and aspirin on platelet aggregation and adhesiveness.

1. The effects of 6-[p-(4-phenylacetylpiperazin-1-yl)]-4,5-dihydro-3(2H)pyridazinon (CCI 17810) on platelet aggregation and adhesiveness have been investigated and compared with those of aspirin. 2. In vitro, CCI 17810 was a potent inhibitor of the aggregation of human platelets induced by collagen, adenosine 5'-diphosphate (ADP) (primary response), thrombin and arachidonic acid, with EC50 values in the range 0.5 to 10 micrograms/ml. The second phase of the response to adrenaline was blocked by concentrations in the range 15 to 25 micrograms/mg. Platelets from rats, rabbits and dogs were as sensitive as human platelets to the effects of CCI 17810. Aspirin was nearly as effective as CCI 17810 against collagen, and adrenaline but about 10 times less active against arachidonic acid; it did not inhibit the primary response to ADP and was only a weak inhibitor of thrombin-induced aggregation. 3. In mice, single oral doses of CCI 17810 in the range 12.5 to 100 mg/kg inhibited collagen-induced thrombocytopenia. Arachidonic acid-induced mortality was markedly reduced by 10 mg/kg and possibly slightly reduced by 1 mg/kg. Aspirin was considerably less active than CCI 17810 in inhibiting collagen-induced thrombocytopenia but was almost as active as CCI 17810 in reducing arachidonic acid-induced mortality. 4. In vitro, CCI 17810 reduced the adhesiveness of human platelets to glass beads (retention of platelets in glass bead columns). Single oral doses of CCI 17810 in the range 25 to 200 mg/kg reduced mouse platelet adhesiveness; rat platelet adhesiveness was reduced by doses in the range 12.5 to 100 mg/kg. Aspirin (20 or 200 mg/kg) slightly increased mouse platelet adhesiveness.