Occupational paraquat exposure of agricultural workers in large Costa Rican farms

Objective  Paraquat is an herbicide widely used worldwide. This study determined the extent of occupational exposure to paraquat among farm workers in Costa Rica and identified determinants of occupational exposure. Methods  Twenty-four hour urine samples were collected from 119 paraquat handlers and 54 non-handlers from banana, coffee and palm oil farms. Information about herbicide handling operations was also collected. The urinary paraquat levels were determined by an enzyme-linked immunosorbent assay (ELISA) with a limit of quantification (LOQ) of 2 ng/mL. Inhalable dust and airborne paraquat levels were simultaneously measured for a subset of the participants. Results  Urinary paraquat measurements were non-detectable or very low when workers did not handle paraquat. For handlers, 83.3, 47.1 and 63.9% of the samples were below the LOQ on before-, during- and after-paraquat spray days, respectively. The arithmetic mean (±SD) of urinary paraquat level on days when workers handled paraquat was 6.3 (±10.45) μg/24 h. Paraquat exposures among handlers on spray day were significantly associated with the type of crop. Conclusion  Non-handlers had negligible urinary paraquat, while detectable paraquat exposures were observed among handlers on spray day. Urinary paraquat levels were different by crop.     

Pityriasis alba: a study of pathogenic factors

BACKGROUND: The aetiology of pityriasis alba (PA), a common dermatosis in childhood, is still controversial. The objective of this study was to assess the possible aetiopathogenic factors of this disease in infants. METHODS: Forty-four patients with PA and 31 healthy children were examined and compared. Personal hygiene habits, sun exposure, presence of Staphylococcus aureus in nasal fossae and presence of major or minor signs of atopy were assessed during anamnesis and physical examination. Susceptibility to ultraviolet (UV) B radiation was measured by the onset of a contact hypersensitivity reaction to diphenylcyclopropenone in individuals sensitized in previously irradiated areas. RESULTS: The prevalence of PA was higher in individuals with darker skin, in high phototype categories, as well as in males. The number of daily baths and sun exposure between 10.00 h and 15.00 h were significantly higher in the PA group when compared with controls (P = 0.03 and P = 0.0015, respectively). The presence of atopy signs was more common in pityriasis patients (P = 0.002). Susceptibility to UVB radiation was 29.6% in the PA group vs. 29.0% in the control group; nevertheless, important differences were found after stratification in order to control possible confounding factors. The presence of S. aureus in the nostrils was equal in both groups. CONCLUSIONS: Our results confirm that PA, in our population, is more prevalent in males and in individuals in higher phototype categories. In those with inadequate personal hygiene and sun exposure habits the disease is more accentuated, demonstrating that the xerosis presenting in individuals with atopic diathesis is an important element in the development of the disease. S. aureus is not an important aetiopathogenic factor in PA. Susceptibility to UVB becomes important when related to the patient's phototype.     

Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell proliferation

Atherosclerosis, in its myriad incarnations the foremost killer disease in the industrialized world, is characterized by aberrant proliferation of vascular smooth muscle (VSM) cells in part as a result of the recruitment of inflammatory cells to the blood vessel wall. The epoxyeicosatrienoic acids are synthesized from arachidonic acid in a reaction catalyzed by the cytochrome P450 system and are vasoactive substances. Metabolism of these compounds by epoxide hydrolases results in the formation of compounds that affect the vasculature in a pleiotropic manner. As an outgrowth of our observations that urea inhibitors of the soluble epoxide hydrolase (sEH) reduce blood pressure in spontaneously hypertensive rats as well as the findings of other investigators that these compounds possess antiinflammatory actions, we have examined the effect of sEH inhibitors on VSM cell proliferation. We now show that the sEH inhibitor 1-cyclohexyl-3-dodecyl urea (CDU) inhibits human VSM cell proliferation in a dose-dependent manner and is associated with a decrease in the level of cyclin D1. In addition, cis-epoxyeicosatrienoic acid mimics the growth-suppressive activity of CDU; there is no evidence of cellular toxicity or apoptosis in CDU-treated cells when incubated with 20 microM CDU for up to 48 h. These results, in light of the antiinflammatory and antihypertensive properties of these compounds that have been demonstrated already, suggest that the urea class of sEH inhibitors may be useful for therapy for diseases such as hypertension and atherosclerosis characterized by exuberant VSM cell proliferation and vascular inflammation.     

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

During inflammation, a large amount of arachidonic acid (AA) is released into the cellular milieu and cyclooxygenase enzymes convert this AA to prostaglandins that in turn sensitize pain pathways. However, AA is also converted to natural epoxyeicosatrienoic acids (EETs) by cytochrome P450 enzymes. EET levels are typically regulated by soluble epoxide hydrolase (sEH), the major enzyme degrading EETs. Here we demonstrate that EETs or inhibition of sEH lead to antihyperalgesia by at least 2 spinal mechanisms, first by repressing the induction of the COX2 gene and second by rapidly up-regulating an acute neurosteroid-producing gene, StARD1, which requires the synchronized presence of elevated cAMP and EET levels. The analgesic activities of neurosteroids are well known; however, here we describe a clear course toward augmenting the levels of these molecules. Redirecting the flow of pronociceptive intracellular cAMP toward up-regulation of StARD1 mRNA by concomitantly elevating EETs is a novel path to accomplish pain relief in both inflammatory and neuropathic pain states.     

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.