Abstract  Guinea-pig assays have been used extensively to detect contact sensitizers. In contrast, almost no reliable assays are available to detect the potential for low-molecular-weight drugs and chemicals to induce systemic allergic reactions in humans. Based on clinical data, and, to some extent, on recent immunological findings, it is proposed that guinea-pig assays can predict the hazard for systemic allergic reactions in man. Seventy drugs and chemicals were compared from published results in guinea-pig assays and in the clinic. A close correlation was found with 43 substances and a relatively good one with 16 substances. Conflicting results were found with 11 substances only. However, substances known to induce systemic allergic reactions in man were all detected as weak sensitizers, at least in guinea-pigs. Guinea-pig contact sensitization assays may therefore prove useful until more suitable and specific assays are available to predict the risk for systemic allergic rea

Abstract  The rapidly expanding field of medical geology deals with the relationships between natural geological factors and health, both human and animal. It also aims to improve our understanding of the ways in which the geological environment has an impact on the geographical distribution of health problems. This new book brings together the work of geoscientists and medical/public health researchers, and addresses the health problems caused, or exacerbated, by geological materials (rocks, minerals, atmospheric dust and water) and processes (including volcanic eruptions and earthquakes). Among the environmental health problems discussed in the volume are: human and animal exposure to toxic levels of trace essential and non-essential elements such as arsenic and mercury; trace element deficiencies; exposure to natural dusts and to radioactivity; naturally occurring organic compounds in drinking water; and the effects of volcanic emissions. Examining the positive side of the equation as well as the negative, the book also deals with the many health benefits of geologic materials and processes. This wide-ranging volume covers issues in medical geology all over the world with each author covering their respective region. It provides examples from different continents as well as a state-of-the-art review of the latest developments in the discipline. The authors are all recognized geoscientific and medical experts working in the field. The book is written for a wide variety of specialists from geologists, geochemists, pathologists and medical doctors to veterinarians and biologists.

Abstract  Mining and smelting at Kellogg-Smelterville, Idaho, resulted in high concentrations of lead in Coeur d'Alene (CDA) River sediments 15-65 km downstream, where ospreys (Pandion haliaetus) nested. Adult and nestling ospreys living along the CDA River had significantly higher lead concentrations than those at Lake Coeur d'Alene (intermediate area) or Pend Oreille and Flathead Lakes (reference areas). Lead concentrations in fish collected from the sandy areas paralleled those found in ospreys. Inhibition of blood .delta.-aminolevulinic acid dehydratase (ALAD) activity and elevation of protoporphyrin concentration provided evidence of lead exposure. In adult ospreys, ALAD activity was negatively correlated with lead in blood (r = -0.57), whereas protoporphyrin was positively correlated with lead in blood (r = +0.40). Neither hemoglobin nor hematocrit was adversely affected by the relatively modest lead concentrations found in the blood. Pronounced accumulation of lead by adults or young could ultimately result in behavioral abnormalities or death, both of which would reduce productivity of the nesting osprey population. We did not observe death related to lead, behavioral abnormalities, or reduced productivity during this 1986-87 study. Despite some lead-induced biochemical changes in blood parameters, ospreys produced young at nearly identical rates in the three study areas; these rates were among the highest ever reported in the western United States. Post-fledging survival of ospreys exposed to lead early in life remains an unknown. Lead does not biomagnify in the food chain as do organochlorine pesticides and mercury and several osprey behavior traits reduce the potential for the species to accumulate critical levels of lead. Swans, which feed at a lower trophic level, continue to die from environmental lead in the region.

Abstract  DNA double strand breaks (DSBs), induced by gamma-irradiation in Chinese hamster ovary cells, were used to examine whether antimony compounds affect the repair of DNA damage. The cells were first incubated with antimony trichloride or antimony potassium tartrate (both Sb(III)) for 2 h, and then irradiated with gamma-rays at a dose of 40 Gy. The DNA DSB was quantified with pulsed field gel electrophoresis immediately after irradiation (non-repair group) as well as at 30 min post-irradiation (repair group). The degree of repair inhibition was determined by the differences in the amount of DNA DSB between non-repair and repair groups. Both antimony compounds inhibited repair of DNA DSB in a dose dependent manner. In trichloride, 0.2 mM antimony significantly inhibited the rejoining of DSB, while 0.4 mM was necessary in potassium antimony tartrate. The mean lethal doses, D(0), for the treatment with antimony trichloride and antimony potassium tartrate, were approximately 0.21 and 0.12 mM, respectively. This indicates that the repair inhibition by antimony trichloride occurred in the dose range near D(0), but the antimony potassium tartrate inhibited the repair at doses where most cells lost their proliferating ability. This is the first report to indicate that antimony compounds may inhibit the repair of radiation-induced DNA DSB.

Abstract  Bovine alveolar macrophages were exposed in vitro to quartz dusts, metal-containing dusts or silica particles coated with a single metal oxide. The release of reactive oxygen intermediates (ROI) was measured in short-term incubations (90 min). The secretion of both ROI was markedly enhanced by silica particles coated with vanadium oxide and lowered by copper oxide-coated particles. The particle-induced ROI release was significantly decreased by the inhibition of protein kinase C (PKC) as well as phospholipase A2, suggesting the involvement of both enzymes in the NADPH oxidase activation. Quartz dusts induced a transient increase of free cytosolic calcium ion concentration, slight intracellular acidification, and depolarization of the plasma membrane. In the presence of EGTA or verapamil the rise of [Ca2+]i was diminished, suggesting an influx of extracellular calcium ions. The PKC inhibitor GF 109203X did not inhibit the quartz-induced calcium rise, while both the cytosolic acidification and depolarization were prevented. BSA-coating of the quartz particles abolished the calcium influx as well as the decrease of pHi, and possibly hyperpolarized the plasma membrane.

Abstract  A number of metal compounds have been shown to be human carcinogens. Others, while not proven human carcinogens, are able to cause tumors in laboratory animals. Short-term bacterial assays for genotoxic effects have not been successful in predicting the carcinogenicity of metal compounds. We report here the ability of some metal compounds to cause the induction of lamda prophage in E coli WP2S(lamda). By far the strongest inducing ability was observed with K2CrO4, followed by Pb(N03)2 > MnCl2 > Ni(OOCCH3)2 > CrCl2 > NaWO4 > Na2MoO4 > KMnO4. With the exception of chromate, long-term exposures in a narrow, subtoxic dose range were required in order to demonstrate phage induction. A new microtiter assay for lamda prophage induction, which incorporates these features, is described. This system also was able to detect very small amounts of organic carcinogens.

Abstract  The purpose of this study was to examine relations between metal concentrations in periphyton and the abundance of algal species, heterotrophic use of 95 carbon sources, and phospholipid fatty acids (PLFA) of the periphyton in a small stream spanning a mine in Lemhi County, Idaho, USA. Two upstream, two mine, and two downstream sites were examined. Elevated concentrations of As and Cu at the mine sites were associated with communities that were depleted of diatoms and filamentous blue-green algae and characterized by a low- diversity community dominated by a single blue-green alga. and patchy populations of the diatom Achnanthidium minutissimum and a filamentous green alga. Carbon source use and PLFA profiles provided a rapid assessment of stream conditions that were consistent with algal taxonomy and with our hypotheses constructed from previous reports on periphyton responses to metal stress.

Abstract  The past decade has seen substantial developments in our understanding of the physiology, pathology, and pharmacology of heme oxygenases (HO), to the point that investigators in the field are beginning to contemplate therapies based on administration of HO agonists or HO inhibitors. A significant amount of our current knowledge is based on the judicious application of metalloporphyrin inhibitors of HO, despite their limitations of selectivity. Recently, imidazole-based compounds have been identified as potent and more selective HO inhibitors. This ‘next generation’ of HO inhibitors offers a number of desirable characteristics, including isozyme selectivity, negligible effects on HO protein expression, and physicochemical properties favourable for in vivo distribution. Some of the applications of HO inhibitors that have been suggested are treatment of hyperbilirubinemia, neurodegenerative disorders, certain types of cancer, and bacterial and fungal infections. In this review, we address various approaches to altering HO activity with a focus on the potential applications of second-generation inhibitors of HO. Au cours de la dernière décennie, de nombreuses études ont contribué à enrichir notre compréhension de la physiologie, de la pathologie et de la pharmacologie des hèmes oxygénases (HO) ; on envisage d’ailleurs des traitements basés sur l’administration d’agonistes de l’HO et d’inhibiteurs de l’HO. Notre connaissance actuelle est basée principalement sur l’application judicieuse des métalloporphyrines, inhibiteurs de l’HO car elles posent des problèmes de sélectivité. Récemment, on a identifié des composés à base d’imidazole dotés d’un pouvoir plus sélectif concernant les inhibiteurs de l’HO. La prochaine génération d’inhibiteurs de l’HO pré... [ABSTRACT FROM AUTHOR] Copyright of Canadian Journal of Physiology & Pharmacology is the property of NRC Research Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Abstract  The (1)H-NMR spectra of complexes involving the paramagnetic metal center [(NH(3))(5)Ru(III)] coordinated at ring nitrogens have been examined with pyridine, purine, nucleoside, and nucleotide ligands along with (31)P-NMR of the nucleotide complexes and EPR of representative complexes. Variations in the spectra have been investigated as a function of the coordination site and pH. Pseudocontact and contact shifts have been calculated for various protons, and an attempt has been made to correlate sugar conformations in coordinated 5'GMP, 5'IMP, Guo, and Ino with paramagnetically induced shifts. The compound [(7MeGuakappa(N9))(NH(3))(5)Ru]Cl(3).3H(2)O crystallizes in the orthorhombic space group Pna2(1) with cell parameters a = 25.375(4) Å, b = 11.803(4) Å, c = 6.958(2) Å, Z = 4, and R = 0.042. The autoxidation of [L(NH(3))(5)Ru(III)], where L = Guo, dGuo, and 1MeGuo, to the corresponding 8-oxo complexes under atmospheric oxygen is first order in the complex and [OH(-)]. For L = Guo, k = 6.6 x 10(-5) M(-1) s(-1), DeltaH = 58 kJ/mol, and DeltaS = -124 J/(mol K).

Abstract  Viral protein expression is postulated to play a critical role in the pathogenesis of human T-cell lymphotropic virus type 1 (HTLV-1)-associated diseases. Therefore, knowledge of the cellular events which initiate or enhance viral gene expression is important in understanding the mechanism of HTLV-1-induced disease. In this report, we examined the modulation of transcription of the HTLV-1 long terminal repeat (LTR) following induction of the cellular stress response. We demonstrate by both in vitro transcription assays and transient transfections that induction of the stress response increases basal transcription from the LTR. Transient cotransfection assays indicate that stress induction of viral transcription is Tax independent. In addition, we provide evidence that the sequences responsible for the enhanced transcription are -52 through +157 of the U3/R region of the HTLV-1 LTR. Finally, our data suggest that the increase in transcription is mediated through an intermediate polymerase II/polymerase III transcriptional complex, demonstrated by the inability to abolish the effect with low concentrations of alpha-amanitin.

Abstract  Lipid-laden foam cells were considered to be targets for therapeutic intervention in atherosclerosis. Several studies proposed new approaches to alter both lipid accumulation and inflammatory responses in macrophages. Finding anti-inflammatory signals during foam cell formation would provide new valid targets for anti-atherosclerotic treatment. The aim of the present study was to see whether oxidized low-density lipoprotein (ox-LDL) can active heme oxygenase (HO)-1 expression level in a human monocyte line, U937 cells, associated with the increase of cytokine secretion. We used hemin (HO-1 activator) and zinc protoporphyrin IX (ZnPP IX, HO-1 inhibitor) to determine the effect of HO-1 on the regulation of cytokine expressions. The results showed that hemin can significantly decrease pro-inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels, while enhancing IL-10 production in a dose-dependent manner in U937 foam cells. ZnPP IX did not significantly affect cytokine levels in foam cells. Our present results suggested that HO-1 is an important anti-inflammatory therapeutic target through inhibiting pro-inflammatory cytokines and enhancing anti-inflammatory cytokines for the management of atherogenesis.

Abstract  Synthetic peptides corresponding to microbial epitopes stimulate T cell immunity but their immunogenicity is poor and their half-lives are short. A viral epitope inserted into the complementarity-determining region 3 (CDR3) loop of the heavy chain of a self immunoglobulin (Ig) molecule was generated from the Ig context and was presented by I-Ed class II molecules to virus-specific, CD4+ T cells. Chimeric Ig-peptide was presented 100 to 1000 times more efficiently than free synthetic peptide and was able to prime virus-specific T cells in vivo. These features suggest that antigenized Ig can provide an improved and safe vaccine for the presentation of microbial and other peptides.