text: content Heavy Metal Toxicity ABSTRACTS Aaseth J., 1995. Treatment of mercury and lead poisonings with dimercaptosuccinic acid (DMSA) and sodium dimmercapto-propanesulfonate (DMPS). AHA., 2001. Chelation therapy. AHA recommendation.. Anderton RM., 2001. ADA statement on dental amalgam. Anon. 1993. Alzheimer's and aluminum: canning the myth. Anon., 2001. Management of the poisoned/overdosed patient. Anuradha B., 1999. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Bardin JA., 2000. Case-control studies of liver, gallbladder and pancreatic cancer and metalworking fluid exposure in the automobile industry. Beers MH., 1999. Poisoning. Brink W., 2000. Lactoferrin: the bioactive peptide that fights disease. Brown DJ., 1998. Characterizing risk at metal finishing facilities. Cai L., 2001. Roles of vitamin C in radiation-induced DNA damage in presence and absence of copper. Cha CW., 1987. A study on the effect of garlic to the heavy metal poisoning of rat. Chouchane S., 2001. In vitro effect of arsenical compounds on glutathione-related enzymes. Clarkson TW., 1990. Mercury: an element of mystery. Clayman CB., 2002. The American Medical Association Encyclopedia of Medicine. Cruz T., 1998. Oral administration of rutoside can ameliorate inflammatory bowel disease in rats. Daggett DA., 1998. Effects of lead on rat kidney and liver: GST expression and oxidative stress. De Flora S., 2001. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Deschner EE., 1993. The effect of dietary quercetin and rutin on AOM-induced acute colonic epithelial abnormalities in mice fed a high-fat diet. Dhir H., 1990. Modification of clastogenicity of lead and aluminium in mouse bone marrow cells by dietary ingestion of Phyllanthus emblica fruit extract. Dhir H., 1993. Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminium-induced sister-chromatid exchanges in mouse bone marrow. Dr. Joseph F. Smith Medical Library., 2001. Heavy metal poisoning. Dupler D., 2001. Heavy metal poisoning. Esteves AC., 2000. Study of the effect of the administration of Cd(II), cysteine, methionine, and Cd(II) together with cysteine or methionine on the conversion of xanthine dehydrogenase into xanthine oxidase. Ewan KB., 1996. Increased inorganic mercury in spinal motor neurons following chelating agents. FDA (no authors given)., 1999. DMPS. Ferner DJ., 2001. Toxicity, heavy metals. Fournier L., 1988. 2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans. Galvez J., 1997. Rutoside as mucosal protective in acetic acid-induced rat colitis. Gebel T., 1996. [Influence of chewing gum consumption and dental contact of amalgam fillings to different metal restorations on urine mercury content.] Ghio AJ., 1998. Depletion of iron and ascorbate in rodents diminishes lung injury after silica. Girodon F., 1999. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Glanze WD., 1996. Mosby Medical Encyclopedia, Revised Edition. Goering PL., 1999. The enigma of arsenic carcinogenesis: role of metabolism. Gonzalez-Correa JA., 2002. Effects of silymarin MZ-80 on hepatic oxidative stress in rats with biliary obstruction. Goyer RA., 1996. Toxic effects of metals: mercury. Gubrelay U., 2001. Role of S-adenosyl-L-methionine in potentiating cadmium mobilization by diethylenetriamine penta acetic acid in mice. Gurer H., 1999. Antioxidant role of alpha-lipoic acid in lead toxicity. Horikoshi T., 1979. Uptake of uranium by various cell fractions of Chlorella regularis. Huang K-C., 1993. The Pharmacology of Chinese Herbs. Ichimura S., 1973. Report (general meeting of the Pharmaceutical Society of Japan, Hokuriku Branch). International Occupational Safety and Health Information Centre., 1999. Metals. Isacsson G., 1997. Impact of nocturnal bruxism on mercury uptake from dental amalgams. James D., 2001. General methods for treating poisoning. Klein-Schwartz W., 2000. Clinical toxicology. Kostyuk VA., 1996. Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers. Kostyuk VA., 1998. Antiradical and chelating effects in flavonoid protection against silica-induced cell injury. Leung FY., 1998. Trace elements that act as antioxidants in parenteral micronutrition. Lide D., 1992. CRC Handbook of Chemistry and Physics, 73rd Edition. Lorico A., 2002. Role of the Multidrug Resistance Protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice. Lupton GP., 1985. Cutaneous mercury granuloma. A clinicopathologic study and review of the literature. Maiti S., 2001. Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. Marcus S., 2001. Toxicity, lead. Medical Management Guidelines (MMGs). 2001. Micromedex (no authors given). 1999.B.A.L.™ Milchak LM., 2002. The effects of glutathione and vitamin E on iron toxicity in isolated rat hepatocytes. Muller L., 1989. Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes. Muller L., 1990. Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium 2+ toxicity in isolated hepatocytes. Muller U., 1995. Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. National Medical Library., 2001. Poisoning first aid. O'Brien J., 2001. Mercury amalgam toxicity. Omura Y., 1995. Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and delivering effective antibiotics using various drug uptake enhancement methods. Treatment of mercury and lead poisonings with dimercaptosuccinic acid (DMSA) and sodium dimmercapto-propanesulfonate (DMPS). Aaseth J, Jacobsen D, Andersen O, Wickstron E. Analyst 1995 Mar;120:853ff SUMMARY: The organic mercury species with greatest toxicity are methylmercury compounds, which have a high affinity for the brain and nervous system. DMSA is shown to cross the blood brain barrier and remove mercury from that organ. DMPS is much less effective. DMPS is also 3 times more toxic than DMSA, based on LD-50. Animal studies show DMSA to be almost 3 times more effective than DMPS in removing brain mercury, as tabulated below. DMSA has the added advantage that it is taken by mouth in capsule form. DMPS is usually given by injection. STUDY OF MERCURY TOXIC MICE: Brain mercury before treatment averaged 2.3 nmol/g; brain mercury after DMPS treatment = 1.6 nmol.g; brain mercury after DMSA treatment = 0.6 nmol/g. CONCLUSION: DMSA may now be considered as the treatment of first choice in cases of acute or subacute lead poisoning and in methylmercury poisoning. All experimental and clinical experiences show a low toxicity for this drug. Chelation therapy. AHA recommendation. AHA (American Heart Association, no authors given). December 3, 2001 American Heart Association, Dallas, TX, U.S.A. No abstract available. ADA statement on dental amalgam. Anderton, R.M. May 2001 American Dental Association, Chicago, IL, U.S.A. No abstract available. Alzheimer's and aluminum: canning the myth. Anon. (no authors given). International Food Information Council Foundation, Washington, D.C., U.S.A. Food Insight 1993 Sep-Oct. No abstract available. Management of the poisoned/overdosed patient. Anon. (no authors given). Continuing Education No. 430-000-99-026-H01. U.S. Pharmacist 2001 Jobson, New York, NY, U.S.A. No abstract available. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Anuradha B, Varalakshmi P. Department of Medical Biochemistry, Dr. AL Mudaliar Post Graduate Institute of Basic Medical Sciences, Madras University, Taramani, Madras, 600 113, India. Pharmacol Res 1999 Jan;39(1):67-80 Experimental neurotoxicity in rat models was induced by an intramuscular injection of mercuric chloride. dl-alpha-lipoic acid was administered as an antidote in three protocols of experimental design. Two protocols of short-term exposure of mercury was designed, one with prophylactic therapy and the other with curative therapy of lipoic acid. The third protocol was with prophylactic therapy of lipoic acid on long-term exposure of mercury. Enhanced lipid peroxidation, depleted non-enzymic and perturbed enzymic antioxidant status were observed in cerebral cortex, cerebellum and sciatic nerves of the toxic groups. The ameliorating effect of lipoic acid and its therapeutic efficacy during various modes of therapy, on the antioxidant status was established in the nervous tissues. Copyright 1999 The Italian Pharmacological Society. Case-control studies of liver, gallbladder and pancreatic cancer and metalworking fluid exposure in the automobile industry. Bardin JA, Eisen EE, Wegman DH, Kriebel D, Woskie SR, Gore RJ. Paper presented to the 128th Annual Meeting of the American Public Health Association, November 14, 2000 American Public Health Association, Washington, D.C., U.S.A. No abstract available. Poisoning. Beers MH, Berkow MD. 1999 The Merck Manual of Diagnosis and Therapy. Section 23. Chapter 307. Merck & Co., Whitehouse Station, NJ, U.S.A. No abstract available. Lactoferrin: the bioactive peptide that fights disease. Brink W. Life Extension Magazine 2000 Oct; 6(10): 20-6 (http://www.lef.org/magazine/mag2000/oct2000_report_lactoferrin.html) Life Extension Foundation, Ft. Lauderdale, FL, U.S.A. No abstract available. Characterizing risk at metal finishing facilities. Brown DJ. May 1998 Report EPA/600/R-97/111. U.S. Environmental Protection Agency, Washington, D.C., U.S.A. Facility-based risk characterization for workers and surrounding communities is a high priority issue for stakeholders in the Environmental Protection Agency's Common Sense Initiative Metal Finishing Sector. Platers, environmental groups, community groups, labor, and regulators all need and want to know what emissions are coming out and in what amounts from metal finishing operations. They also want to know what health risks those emissions create for workers and the surrounding communities. A process is described herein that includes a problem formulation phase to identify the types and forms of information that are wanted by the different stakeholders and a risk assessment phase to quantify the health risks associated with facility emissions. A screening level risk assessment is performed in which toxicity information and exposure data are used to show how a facility-based risk assessment could be performed for a typical electroplating operation. Information needs for a more refined assessment are presented. A single iteration of the problem formulation and risk assessment processes may lead directly to a risk management decision or the steps may be modified and repeated, taking into account input from stakeholders obtained during the risk communication process. Uncertainties associated with toxicity information and exposure scenarios will present challenges for providing simple (but not simplistic) methods of risk assessment that can be applied by facility operators, community groups, and other stakeholders. This type of risk characterization is not only desired but possible to carry out for a variety of exposure scenarios. Roles of vitamin C in radiation-induced DNA damage in presence and absence of copper. Cai L, Koropatnick J, Cherian MG. Department of Pathology, University of Western Ontario, London, Ontario, Canada N6A 5C1. Chem Biol Interact 2001 Jul 31;137(1):75-88 Exposure to either ionizing radiation or certain transition metals results in generation of reactive oxygen species that induce DNA damage, mutation, and cancer. Vitamin C (a reactive oxygen scavenger) is considered to be a dietary radioprotective agent. However, it has been reported to be genotoxic in the presence of certain transition metals, including copper. In order to explore the capacity of vitamin C to protect DNA from radiation-induced damage, and the influence of the presence of copper on this protection, we investigated vitamin C-mediated protection against radiation-induced damage to calf thymus DNA in vitro in the presence or absence of copper(II). Vitamin C (0.08-8.00 mM, pH 7.0) significantly reduced DNA damage induced by gamma-irradiation (30-150 Gy) by 30-50%, similar to the protective effect of glutathione. However, vitamin C plus copper (50 microM) significantly enhanced gamma-radiation-induced DNA damage. Low levels of added copper (5 microM), or chelation of copper with 1-N-benzyltriethylenetetraine tetrahydrochloride (BzTrien) and bathocuprinedisulfonic acid (BCSA), abolished the enhanced damage without diminishing the protective effect of vitamin C. These results indicate that vitamin C can act as: (1) an antioxidant to protect DNA damage from ionizing radiation; and (2) a reducing agent in the presence of copper to induce DNA damage. These effects are important in assessing the role of vitamin C, in the presence of mineral supplements or radioprotective therapeutic agents, particularly in patients with abnormally high tissue copper levels. A study on the effect of garlic to the heavy metal poisoning of rat. Cha CW. Department of Preventive Medicine, College of Medicine, Korea University, Seoul. J Korean Med Sci 1987 Dec;2(4):213-24 When garlic (Allium sativum) was administered to rat per os simultaneously with cadmium, methylmercury and phenylmercury to detect the protective effect against the heavy metal poisoning, accumulation of heavy metals in liver, kidneys, bone and testes were decreased, and histopathological damages and the inhibition of serum alkaline phosphatase activities by heavy metals were reduced. Such effect of garlic was not shown in the 1.7% garlic treated group and most remarkable in the 6.7% garlic treated group. The protective effect of garlic was superior to those of 2,3 dimercapto-1-propanol (BAL) and D-penicillamine (PEN), and nearly similar to those of 2,3-dimercaptosuccinic acid (DMSA) and N-acetyl-DL-penicillamine (APEN), the current remedies, while garlic was not effective as a curative agent for heavy metal poisoning. The excretion of cadmium was enhanced, more through feces than urine by garlic but the effect to the urinary excretion of cadmium was not significant comparing with DMSA or APEN when cadmium was ip injected in the first 3 days during the 12 days of oral administration of DMSA, APEN or garlic. In vitro effect of arsenical compounds on glutathione-related enzymes. Chouchane S, Snow ET. Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, U.S.A. Chem Res Toxicol 2001 May;14(5):517-22 The mechanism of arsenic toxicity is believed to be due to the ability of arsenite (As(III)) to bind protein thiols. Glutathione (GSH) is the most abundant cellular thiol, and both GSH and GSH-related enzymes are important antioxidants that play an important role in the detoxification of arsenic and other carcinogens. The effect of arsenic on the activity of a variety of enzymes that use GSH has been determined using purified preparations of glutathione reductase (GR) from yeast and bovine glutathione peroxidase (GPx) and equine glutathione S-transferase (GST). The effect on enzyme activity of increasing concentrations (from 1 microM to 100 mM) of commercial sodium arsenite (As(III)) and sodium arsenate (As(V)) and a prepared arsenic(III)-glutathione complex [As(III)(GS)(3)] and methylarsenous diiodide (CH(3)As(III)) has been examined. GR, GPx, and GST are not sensitive to As(V) (IC(50) > 50 mM), and none of the enzymes are inhibited or activated by physiologically relevant concentrations of As(III), As(III)(GS)(3), or CH(3)As(III), although CH(3)As(III) is the most potent inhibitor (0.3 mM < IC(50) < 1.5 mM). GPx is the most sensitive to arsenic treatment and GST the least. Our results do not implicate a direct interaction of As with the glutathione-related enzymes, GR, GPx, and GST, in the mechanism of arsenic toxicity. CH(3)As(III) is the most effective inhibitor, but it is unclear whether this product of arsenic metabolism is produced at a sufficiently high concentration in critical target tissues to play a major role in either arsenic toxicity or carcinogenesis. Mercury: an element of mystery. Clarkson TW. N Engl J Med 1990;323:1137-9 No abstract available. The American Medical Association Encyclopedia of Medicine. Clayman CB. 1989 Random House, New York, NY, U.S.A. No abstract available. Oral administration of rutoside can ameliorate inflammatory bowel disease in rats. Cruz T, Galvez J, Ocete MA, Crespo ME, Sanchez de Medina L-H F, Zarzuelo A. Department of Pharmacology, School of Pharmacy, University of Granada, Spain. Life Sci 1998;62(7):687-95 Rutoside, a flavonoid with antioxidant properties, was tested for acute and chronic antiinflammatory activity in trinitrobenzenesulfonic acid-induced rat colitis. Pretreatment with 10 or 25 mg/kg of rutoside by the oral route reduced colonic damage at 2 days. Several mechanisms can be involved in this activity, and one of these may be related to its ability in preventing glutathione depletion of colitic animals, and this could result in mucosal protection against oxidative insult. When rutoside was tested for 1 and 2 weeks after colitis induction, it was able to promote colonic healing. The chronic effect of the flavonoid was also related with its ability to increase colonic glutathione levels and thus reduce the tissue damage derived from intestinal oxidative stress which characterizes inflammatory colitis. Effects of lead on rat kidney and liver: GST expression and oxidative stress. Daggett DA, Oberley TD, Nelson SA, Wright LS, Kornguth SE, Siegel FL. The Environmental Toxicology Center, University of Wisconsin, Madison, WI 53705, U.S.A. Toxicology 1998 Jul 17;128(3):191-206 The effect of acute exposure to lead acetate on the expression of glutathione S-transferase (GST) subunits and the levels of reduced and oxidized glutathione (GSH) and malondialdehyde (MDA) in rat kidney and liver was determined. The purpose of this study was to determine if GSH depletion and/or oxidative stress were responsible for changes in the expression of some or all GSTs that followed lead exposure. In kidney, all GST subunits increased following injection of lead. The level of kidney GSH was not changed at either 0.5 or 1 h after lead exposure, but increased 3, 6, 12 and 24 h after a single injection of lead. MDA levels (a marker of lipid peroxidation) did not change in kidney following lead injection. Immunohistochemical markers of oxidative stress and nitric oxide production were also unchanged by lead administration. Therefore, we conclude that the increases in GST levels in kidney following lead exposure were not dependent on oxidative stress. In liver, lead injection caused GSH depletion (61% of control 12 h after lead treatment) and increased MDA production (2.5-fold increase 6 h after lead exposure), while GSTA1, GSTA2, GSTM1 and GSTM2 did not increase. Analysis of the effects of lead on GST mRNA and GST cellular localization were performed by Northern blot and immunohistochemical techniques. Immunoperoxidase light microscopy and immunogold electron microscopy revealed that the increase in kidney GSTM1 and GSTP1 occurred in nuclei, cytoplasm and microvilli of proximal tubules. Northern blot analysis of GSTA2 and GSTP1 mRNAs showed that their increase following lead exposure was inhibited by actinomycin D, suggesting transcriptional induction. This study demonstrates that acute lead exposure causes dramatic changes in the subcellular distribution and expression of rat kidney GSTs, and that these changes are not a result of oxidative stress. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. De Flora S, Izzotti A, D'Agostini F, Balansky RM. Department of Health Sciences, Section of Hygiene and Preventive Medicine, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy. firstname.lastname@example.com Carcinogenesis 2001 Jul;22(7):999-1013 Although smoking cessation is the primary goal for the control of cancer and other smoking-related diseases, chemoprevention provides a complementary approach applicable to high risk individuals such as current smokers and ex-smokers. The thiol N-acetylcysteine (NAC) works per se in the extracellular environment, and is a precursor of intracellular cysteine and glutathione (GSH). Almost 40 years of experience in the prophylaxis and therapy of a variety of clinical conditions, mostly involving GSH depletion and alterations of the redox status, have established the safety of this drug, even at very high doses and for long-term treatments. A number of studies performed since 1984 have indicated that NAC has the potential to prevent cancer and other mutation-related diseases. N-Acetylcysteine has an impressive array of mechanisms and protective effects towards DNA damage and carcinogenesis, which are related to its nucleophilicity, antioxidant activity, modulation of metabolism, effects in mitochondria, decrease of the biologically effective dose of carcinogens, modulation of DNA repair, inhibition of genotoxicity and cell transformation, modulation of gene expression and signal transduction pathways, regulation of cell survival and apoptosis, anti-inflammatory activity, anti-angiogenetic activity, immunological effects, inhibition of progression to malignancy, influence on cell cycle progression, inhibition of pre-neoplastic and neoplastic lesions, inhibition of invasion and metastasis, and protection towards adverse effects of other chemopreventive agents or chemotherapeutical agents. These mechanisms are herein reviewed and commented on with special reference to smoking-related end-points, as evaluated in in vitro test systems, experimental animals and clinical trials. It is important that all protective effects of NAC were observed under a range of conditions produced by a variety of treatments or imbalances of homeostasis. However, our recent data show that, at least in mouse lung, under physiological conditions NAC does not alter per se the expression of multiple genes detected by cDNA array technology. On the whole, there is overwhelming evidence that NAC has the ability to modulate a variety of DNA damage- and cancer-related end-points. The effect of dietary quercetin and rutin on AOM-induced acute colonic epithelial abnormalities in mice fed a high-fat diet. Deschner EE, Ruperto JF, Wong GY, Newmark HL. Laboratory of Digestive Tract Carcinogenesis, Sloan-Kettering Institute, New York, NY, U.S.A. Nutr Cancer 1993;20(3):199-204 Dietary quercetin (QU) and rutin (RU), phenolic flavonoids found in many fruits and vegetables, when fed to mice on a low-fat diet successfully modified the response to azoxymethanol (AOM) by initially inhibiting hyperproliferation and the formation of foci of dysplasia (FADs) and ultimately reducing tumor incidence (Carcinogenesis 12, 1193-1196, 1991). In this study, we tested the efficacy of QU and RU when a high-fat diet was presented. An AIN 76A diet made with 20% corn oil (CO) was supplemented with QU (0.5%, 2.0%, or 5.0%) and RU (2.0% or 4.0%). These five diets, as well as a 5.0% and a 20.0% CO diet, were fed to a group of CF1 female mice for nine weeks. Both QU and RU showed nonsignificant dose-related trends toward normalization of the AOM-induced upward extension of S phase cells. Examination of 500 microns of serially sectioned distal colon revealed that 29% of mice fed the 20% CO control diet were free of FADs. Among the mice fed QU, regardless of dose, > 80% were free of FADs. When the three groups fed QU were pooled and compared with the control 20% CO-fed mice, the degree of protection was significant (p < 0.01). Mice fed RU expressed a level of protection that bordered on the significant (p < 0.08). These data suggest that, regardless of the fat content of the diet, QU and RU are capable of modifying or inhibiting events in the development of chemically induced colonic neoplasia. Modification of clastogenicity of lead and aluminium in mouse bone marrow cells by dietary ingestion of Phyllanthus emblica fruit extract. Dhir H, Roy AK, Sharma A, Talukder G. Department of Botany, University of Calcutta, India. Mutat Res 1990 Jul;241(3):305-12 Extract of Phyllanthus emblica fruit and ascorbic acid were evaluated separately for protection against clastogenicity induced by lead (Pb) and aluminium (Al) salts on mouse bone marrow chromosomes. Oral administration of Phyllanthus fruit extract (PFE) for 7 days before exposure to both metals by intraperitoneal injection increased the frequency of cell division and reduced the frequency of chromosome breaks significantly. Comparable doses of synthetic ascorbic acid (AA) were less effective and could protect against the effects of Al and only a low dose of Pb (10 mg/kg body weight). AA administered before treatment in mice given higher doses of Pb (40 mg/kg body weight) enhanced the frequency of chromosome breaks, giving a synergistic effect. The higher protection afforded by PFE may be due to the combined action of all ingredients, rather than to AA alone. Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminium-induced sister-chromatid exchanges in mouse bone marrow. Dhir H, Roy AK, Sharma A. Department of Botany, University of Calcutta, India. Environ Mol Mutagen 1993;21(3):229-36 The identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)-induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract. Heavy metal poisoning. Dr. Joseph F. Smith Medical Library (no authors given). November 2001 Dr. Joseph F. Smith Medical Library, Wassau, WI, U.S.A. No abstract available. Heavy metal poisoning. Dupler D. 2001 Gale Encyclopedia of Alternative Medicine, Gale Group, Farmington Hills, MI, U.S.A. No abstract available. Study of the effect of the administration of Cd(II), cysteine, methionine, and Cd(II) together with cysteine or methionine on the conversion of xanthine dehydrogenase into xanthine oxidase. Esteves AC, Felcman J. Department of Chemistry, Pontificia Universidade Catolica de Rio de Janeiro, Rio de Janeiro, Brazil. Biol Trace Elem Res 2000 Jul;76(1):19-30 Cadmium is known as to be a potent pulmonary carcinogen to human beings and to induce prostate tumor. The sequestration of cadmium, an extremely toxic element to living cells, which is performed by biological ligands such as amino acids, peptides, proteins or enzymes is important to minimize its participation in such deleterious processes. The synthesis of metallothionein is induced by a wide range of metals, in which cadmium is a particularly potent inducer. This protein is usually associated with cadmium exposure in man. Because metallothioneins may act as a detoxification agent for cadmium and chelation involves sulfur donor atoms, we administered only cadmium, cysteine, or methionine to rats and also each of these S-amino acids together with cadmium and measured the production of superoxide radicals derived from the conversion of xanthine dehydrogenase to xanthine oxidase. It could be seen in this work that the presence of cadmium enhances this conversion. However, its inoculation with cysteine or methionine almost completely diminishes this effect and this can be the result of the fact that these amino acids complex Cd(II). Thus, these compounds can be a model of the action of metallothionein, removing cadmium from circulation and preventing its deleterious effect. Increased inorganic mercury in spinal motor neurons following chelating agents. Ewan KB, Pamphlett R. Department of Pathology (Neuropathology Division), University of Sydney, Australia. Neurotoxicology 1996 Summer;17(2):343-9 Heavy metal toxicity has been implicated in the pathogenesis of motor neuron diseases. In an attempt to assess the efficacy of chelating agents to remove mercury from motor neurons, we quantitated the effect of the chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3- dimercaptopropane -1-sulphonate (DMPS) on the burden of inorganic mercury in mouse spinal motor neurons. Mice were injected intraperitoneally with 1.0 mg HgCl2/kg body weight and one week later with either 4,400 mg/kg DMPS, 3,600 mg/kg DMSA or 5% NaHCO3 (control) over 4 weeks. Mercury deposits in motor neurons of 50 micron frozen sections of lumbar spinal cord were visualised with an autometallographic technique. Optical sections of silver-enhanced deposits were acquired using a confocal microscope in reflective mode and the volume of the deposits within the perikaryon was estimated. Mercury deposits occupied significantly more volume in motor neurons after both DMPS (7.4%, SD +/- 0.7%) and DMSA (8.0% +/- SD 0.7%) treatment than in controls (4.3%, SD +/- 1.7%). The higher levels of neuronal inorganic mercury may be due to increased entry of mercury into motor axons across the neuromuscular junction as a result of chelator-induced elevated circulating mercury. DMPS. FDA (no authors given). 1999 (http://www.fda.gov/cder/fdama/pclist.txt). Food and Drug Administration, Washington, D.C., U.S.A. Toxicity, heavy metals. Ferner DJ. eMed.J 2001 May 25;2(5):1 No abstract available. 2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans. Fournier L, Thomas G, Garnier R, Buisine A, Houze P, Pradier F, Dally S. Department of Clinical Toxicology, Fernand Widal Hospital, Paris, France. Med Toxicol Adverse Drug Exp 1988 Nov-Dec;3(6):499-504 14 patients with heavy metal poisoning received 2,3-dimercaptosuccinic acid (DMSA). 12 subjects were given 30 mg/kg/day for 5 days; 1 subject was started on a lower dose because of a history of atopy; another subject was treated for 15 days because of very high initial blood lead concentrations. In the 9 subjects who had lead poisoning, DMSA decreased blood lead concentrations by 35 to 81%, and induced a 4.5- to 16.9-fold increase in mean daily urinary excretion of the metal. In the acutely arsenic-poisoned case, the plasma arsenic concentration on day 7 was half the pretreatment value, while no clear decrease was observed in a chronically exposed subject. In 3 mercury cases, DMSA increased daily mercury urinary excretion 1.5-, 2.8- and 8.4-fold, respectively, while blood mercury concentrations remained below detection limits. No serious side effects were observed and 3 weeks after administration of the drug the clinical condition of all subjects was either stable or improved. These results indicate the efficacy of DMSA for lead poisoning in humans and provide a rationale for further investigating its usefulness in mercury and arsenic poisoning cases. Rutoside as mucosal protective in acetic acid-induced rat colitis. Galvez J, Cruz T, Crespo E, Ocete MA, Lorente MD, Sanchez de Medina F, Zarzuelo A. Department of Pharmacology, School of Pharmacy, University of Granada, Spain. Planta Med 1997 Oct;63(5):409-14 The effect of the flavonoid rutoside on acetic acid-induced rat colitis was studied. Rats were pretreated orally with different doses of the flavonoid (10, 25, and 100 mg/kg) 48, 24, and 1 hour prior to colitis induction and examined for colonic damage 24 hours later. Colonic inflammation was characterized by gross and microscopical injury, bowel wall thickening, abolition of fluid absorption, glutathione depletion, enhanced leukotriene B4 synthesis, and increased levels of myeloperoxidase and alkaline phosphatase activities. Rutoside treatment (25 and 100 mg/kg) reduced histologic injury and prevented the increase in alkaline phosphatase activity, but it had no effect on myeloperoxidase levels or leukotriene B4 synthesis. In addition, glutathione depletion was effectively counteracted at the dose of 25 mg/kg, whereas fluid absorption was achieved at the highest dose assayed. It is concluded that rutoside has an acute anti-inflammatory activity in this model which may be related to a putative direct protective effect on intestinal cells, mainly enterocytes, in which the antioxidative properties of the flavonoid may play a role. [Influence of chewing gum consumption and dental contact of amalgam fillings to different metal restorations on urine mercury content.][Article in German] Gebel T, Dunkelberg H. Abteilung fur Allgemeine Hygiene und Umweltmedizin, Zentrum Umwelt- und Arbeitsmedizin, Universitat Gottingen. Zentralbl Hyg Umweltmed 1996 Nov;199(1):69-75 It had been shown previously by various authors that contact of amalgam fillings to metal fillings of different type can increase the electrochemically caused amalgam corrosion in vitro thus leading to an elevated release of mercury. So it was recommended to renounce of a dental contact of amalgam to metal fillings of other type. One aim of the present study was to evaluate possible influences of this contact in vivo on the urinary mercury contents in human volunteers. Neither proximal nor occlusal contacts had any influence on the urinary mercury excretion in comparison to a reference group with similar amalgam status. Furthermore, the influence of gum chewing on urinary mercury levels was taken into account. It could be shown that the consumption of chewing gum resulted in a significantly higher mean urinary mercury content in probands with amalgam fillings in comparison to people with similar amalgam status (gum chewers: 1.36 Hg/24 h vs. non-chewers 0.70 microgram Hg/24 h). Thus, gum chewing has to be considered as important parameter of influence on the urinary mercury levels of people with amalgam fillings. Depletion of iron and ascorbate in rodents diminishes lung injury after silica. Ghio AJ, Kennedy TP, Crissman KM, Richards JH, Hatch GE. National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711, U.S.A. Exp Lung Res 1998 Mar-Apr;24(2):219-32 Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We tested the study hypothesis that lung injury after silica is associated with the availability of both iron and ascorbate in the host by depleting this metal and reductant in the lungs of rats and guinea pigs, respectively. Rats were fed either a normal diet or a diet deficient of iron. After 30 days, animals were instilled with either saline or 1.0 mg Minusil-5 silica. Relative to saline, silica significantly increased neutrophils and lavage protein. Iron depletion significantly diminished both the cellular influx and injury but only at 1 week after silica exposure. Guinea pigs were provided either a normal diet supplemented with 1,000 ppm vitamin C or a diet deficient in ascorbate. After 14 days, the guinea pigs were instilled with either saline or 1.0 mg silica. Silica exposure significantly increased neutrophils and lavage protein. Ascorbate depletion significantly diminished the influx of inflammatory cells and injury at both 1 day and 1 week after silica exposure. We conclude that host concentrations of both iron and ascorbate can affect lung injury after silica exposure. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Herchberg S. Scientific and Technical Institute for Foods and Nutrition, Conservatiore National des Arts et Mettiers, Paris, France. Arch Intern Med 1999 Apr 12;159(7):748-54 BACKGROUND: Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables. OBJECTIVE: To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people. METHODS: This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2 x 2 factorial design for 2 years. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality. RESULTS: Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P = .06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups. CONCLUSIONS: Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections. Mosby Medical Encyclopedia, Revised Edition. Glanze WD. 1996 C.V. Mosby, St. Louis, MO, U.S.A. No abstract available. The enigma of arsenic carcinogenesis: role of metabolism. Goering PL, Aposhian HV, Mass MJ, Cebrian M, Beck BD, Waalkes MP. Division of Life Sciences, Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20852, U.S.A. firstname.lastname@example.com Toxicol Sci 1999 May;49(1):5-14 Inorganic arsenic is considered a high-priority hazard, particularly because of its potential to be a human carcinogen. In exposed human populations, arsenic is associated with tumors of the lung, skin, bladder, and liver. While it is known to be a human carcinogen, carcinogenesis in laboratory animals by this metalloid has never been convincingly demonstrated. Therefore, no animal models exist for studying molecular mechanisms of arsenic carcinogenesis. The apparent human sensitivity, combined with our incomplete understanding about mechanisms of carcinogenic action, create important public health concerns and challenges in risk assessment, which could be met by understanding the role of metabolism in arsenic toxicity and carcinogenesis. This symposium summary covers three critical major areas involving arsenic metabolism: its biodiversity, the role of arsenic metabolism in molecular mechanisms of carcinogenesis, and the impact of arsenic metabolism on human risk assessment. In mammals, arsenic is metabolized to mono- and dimethylated species by methyltransferase enzymes in reactions that require S-adenosyl-methionine (SAM) as the methyl donating cofactor. A remarkable species diversity in arsenic methyltransferase activity may account for the wide variability in sensitivity of humans and animals to arsenic toxicity. Arsenic interferes with DNA methyltransferases, resulting in inactivation of tumor suppressor genes through DNA hypermethylation. Other studies suggest that arsenic-induced malignant transformation is linked to DNA hypomethylation subsequent to depletion of SAM, which results in aberrant gene activation, including oncogenes. Urinary profiles of arsenic metabolites may be a valuable tool for assessing human susceptibility to arsenic carcinogenesis. While controversial, the idea is that unique arsenic metabolic properties may explain the apparent non-linear threshold response for arsenic carcinogenesis in humans. In order to address these outstanding issues, further efforts are required to identify an appropriate animal model to elucidate carcinogenic mechanisms of action, and to define dose-response relationships. Effects of silymarin MZ-80 on hepatic oxidative stress in rats with biliary obstruction. Gonzalez-Correa JA, de la Cruz JP, Gordillo J, Urena I, Redondo L, Sanchez de la Cuesta F. Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga, Spain. Pharmacology 2002 Jan;64(1):18-27 This study was designed to evaluate the effects of three pharmaceutical forms of silymarin (silymarin MZ-80, silybinin-beta-cyclodextrin, and silybinin) on the liver oxidative status in vitro and after oral administration to rats with extrahepatic biliary obstruction (EBO) and sham-operated animals. We evaluated thiobarbituric acid-reactive substances (TBARS), glutathione (GSH + GSSG) and their related enzyme activities (GSH peroxidase, GSSG reductase and GSH transferase). All three compounds inhibited the in vitro production of TBARS (IC(50) 56-533 micromol/l). These compounds, mainly silymarin MZ-80, also increased GSH peroxidase and GSH transferase activities. In EBO rats we found increases in TBARS production which was inhibited by 50-70% after treatment. Glutathione was reduced by 55% and elevated by silymarin MZ-80. GSH transferase increased in the group given silymarin MZ-80. We conclude that all three derivatives of silymarin show a clear ability to reduce lipid peroxidation in the liver. Silymarin MZ-80 was the only compound that enhanced the glutathione antioxidant system. Copyright 2002 S. Karger AG, Basel. Toxic effects of metals: mercury. Goyer RA. 1996 Casarett and Doull's Toxicology: The Basic Science of Poisons, Fifth Edition. McGraw-Hill, New York, NY, U.S.A. No abstract available. Role of S-adenosyl-L-methionine in potentiating cadmium mobilization by diethylenetriamine penta acetic acid in mice. Gubrelay U, Mathur R, Kannan GM, Flora SJ. School of Studies in Zoology, Jiwaji University, Gwalior, India. Cytobios 2001;104(406):99-105 The beneficial effects of S-adenosyl-L-methionine (SAM) in potentiating the obilization of cadmium by cadmium trisodium diethylenetriamine penta acetic acid (DTPA) from the major target organs and restoration of depleted tissue glutathione (GSH), zinc and copper concentration, were determined in cadmium-exposed mice. The results indicated a significant depletion of cadmium concentration from the blood in DTPA plus SAM treated animals compared with DTPA or SAM alone treated groups. The treatment with SAM alone was also effective in correcting the zinc and GSH concentrations. The results indicated few beneficial effects of concomitant SAM administration during chelation of cadmium with DTPA. Antioxidant role of alpha-lipoic acid in lead toxicity. Gurer H, Ozgunes H, Oztezcan S, Ercal N. Department of Chemistry, University of Missouri-Rolla, Rolla, MO 65409-0010, U.S.A. Free Radic Biol Med 1999 Jul;27(1-2):75-81 The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival that was inhibited by lead treatment in a concentration-dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator (succimer) that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent. Uptake of uranium by various cell fractions of Chlorella regularis. Horikoshi T, Nakajima A, Sakaguchi T. Radioisotopes 1979 Aug;28(8):485-8 To know what kinds of the cell components of Chlorella regularis are concerned with uranium binding, uptake of uranium by various cell fractions was examined. The uptake value (microgramU/mg starting dry cells) of the hot water-treated cells was almost the same as that of the starting dry Chlorella cells, showing that the cell components extracted with hot water were not so concerned with uranium binding. The cell components extracted with dilute alkali seemed to play an important role in uranium binding, and those extracted with chloroform-methanol seemed to be partly concerned with uranium binding. The cellulose fraction of the cells was scarcely concerned with uranium binding. In the dry cells, 34% of uranium taken up existed in the cell walls. However, in the living cells, 85% existed in the cell walls. The above results showed that the dry or the hot water-treated cells are the most convenient for uranium recovery from the aqueous systems. The Pharmacology of Chinese Herbs. Huang K-C. 1993 CRC Press, Boca Raton, FL, U.S.A. No abstract available. Report (general meeting of the Pharmaceutical Society of Japan, Hokuriku Branch). Ichimura, S. October 27, 1973 Toyoma City, Japan. No abstract available. Metals. International Occupational Safety and Health Information Centre. September 1999 Basics of Chemical Safety, Chapter 7. International Labour Organization, Geneva, Switzerland. No abstract available. Impact of nocturnal bruxism on mercury uptake from dental amalgams. Isacsson G, Barregard L, Selden A, Bodin L. Orofacial Pain Clinic, Postgraduate Dental Education Centre, Orebro County Council, Sweden. email@example.com Eur J Oral Sci 1997 Jun;105(3):251-7 The mercury (Hg) release from dental amalgam fillings increases by mechanical stimulation. The aim of this study was to investigate the possible impact of nocturnal bruxism on Hg exposure from dental amalgams and to evaluate the effect of an occlusal appliance. 88 female patients from an orofacial pain clinic with a complete maxillary and mandibular dentition, a normal frontal vertical overbite with cuspid guidance, and at least 4 occlusal amalgam fillings in contact with antagonists in intercuspidal position, were examined with the Bruxcore bruxism monitoring device to measure the level of on-going nocturnal bruxism. Based on the degree of abrasion recorded, the subjects were divided into a group defined as bruxists, (n = 29), another group defined as non-bruxists, (n = 32), serving as controls, the intermediate group being discarded. The Hg exposure was assessed from the Hg concentration in plasma and urine, corrected for the creatinine content. In a regression model with bruxism as the only explanatory variable, no significant effect of bruxism was found, but when the number of amalgam fillings, chewing gum use, and other background variables were taken into account, there was a limited impact of bruxism on Hg in plasma. The nocturnal use of an occlusal appliance did not, however, significantly change the Hg levels. This study indicates that mechanical wear on amalgams from nocturnal bruxism may increase the Hg uptake, but the magnitude of this effect seems to be less than from the use of chewing gum. General methods for treating poisoning. James D. 2001 University of Alberta, Alberta, Canada. No abstract available. Clinical toxicology. Klein-Schwartz W, Oderda GM. 2000 Textbook of Therapeutics: Drug and Disease Management, Seventh Edition, p. 51. Williams & Wilkins, Baltimore, MD, U.S.A. No abstract available. Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers. Kostyuk VA, Potapovich AI, Speransky SD, Maslova GT. Laboratory of Bioenergetics, Byelorussian State University, Minsk, Belarus. Free Radic Biol Med 1996;21(4):487-93 Exposure of macrophages to asbestos fibers resulted in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation, and reducing peritoneal macrophages injury caused by asbestos. The concentrations pre-treatment of antioxidants that were required to prevent the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90 microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.-. These findings indicate that flavonoids are able to prevent the respiratory burst in rat peritoneal macrophages exposed to asbestos at the stage of activated oxygen species generation, mainly as superoxide scavengers. On the basis of this study it was concluded that natural flavonoids quercetin and rutin would be promising drug candidates for a prophylactic asbestos-induced disease. Antiradical and chelating effects in flavonoid protection against silica-induced cell injury. Kostyuk VA, Potapovich AI. Laboratory of Bioenergetics, Byelorussian State University, Scorina St. 4, Minsk, 220050, Belarus. firstname.lastname@example.com Arch Biochem Biophys 1998 Jul 1;355(1):43-8 Quercetin, dihydroquercetin, and rutin are capable of scavenging superoxide anion (rate constants of the reaction with superoxide at pH 10 were 1.7 x 10(5), 1.5 x 10(5), and 0.5 x 10(5) M-1 s-1, respectively). At the same time rutin and quercetin but not dihydroquercetin are iron ion chelators. These substances were used to elucidate the role of radical scavenging and iron chelating in flavonoid protection against asbestos-induced oxidative cellular injury. Exposure of rat peritoneal macrophages to chrysotile asbestos fibers resulted in "frustrated" phagocytosis, cell injury, and a LDH release. Quercetin, dihydroquercetin, and rutin were effective in protecting the phagocytic cells against injury caused by asbestos. Moreover, these flavonoids exhibited cellular protection in the same order of effectiveness as that observed for the quenching of superoxide: quercetin > dihydroquercetin > rutin. Exposure of human red blood cells to asbestos fibers also caused progressive cell injury and lysis. Quercetin and rutin protected the red cells (quercetin > rutin), whereas dihydroquercetin was ineffective in preventing asbestos-induced hemolysis. The protective ability of quercetin and rutin may be related to their iron-chelating activity. Due to this these flavonoids can be located on asbestos surface in sites of initiation of free radical reactions and their antiradical moieties can scavenge reactive oxygen species immediately after the appearance. Thus, both antiradical and chelating effects appear to be involved in the flavonoid protection against silica-induced cell injury. Copyright 1998 Academic Press. Trace elements that act as antioxidants in parenteral micronutrition. Leung FY. Can J Nutr Biochem 1998;9(6):304-7 No abstract available. CRC Handbook of Chemistry and Physics, 73rd Edition. Lide D. 1992 Boca Raton, FL: CRC Press. No abstract available. Role of the Multidrug Resistance Protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice. Lorico A, Bertola A, Baum C, Fodstad O, Rappa G. Department of Tumor Biology, Norwegian Radium Hospital, Montebello, 0310, Norway. email@example.com Biochem Biophys Res Commun 2002 Mar 1;291(3):617-22 The Multidrug Resistance Protein 1 (MRP1) is a membrane pump that mediates the efflux of a wide variety of xenobiotics, including arsenical and antimonial compounds, as demonstrated by the study of MRP1-transfected cell lines. We have previously shown that mrp1(-/-) cells are hypersensitive to sodium arsenite, sodium arsenate, and antimony potassium tartrate. We now report that the retroviral vector-mediated overexpression of MRP1 and of the two subunits of gamma-GCS (heavy and light) resulted in higher intracellular glutathione levels and in a greater level of resistance to sodium arsenite and antimony potassium tartrate, compared to the overexpression of MRP1 and gamma-GCS heavy alone. These observations further demonstrate that glutathione is an important component of MRP1-mediated cellular resistance to arsenite and antimony. However, the constitutive expression of MRP1 did not protect mice from the lethality of sodium arsenite and antimony potassium tartrate nor reduced the tissue accumulation of arsenic in mice injected i.p. with sodium arsenite. It is conceivable that, in vivo, other pump(s) effectively vicariate for MRP1-mediated transport of heavy metal oxyanions. Cutaneous mercury granuloma. A clinicopathologic study and review of the literature. Lupton GP, Kao GF, Johnson FB, Graham JH, Helwig EB. J Am Acad Dermatol 1985 Feb;12(2 Pt 1):296-303 Cutaneous mercury granulomas are rarely encountered. Clinically they pose difficulty in diagnosis when there is no clear history of penetrating injury by objects containing metallic mercury. Histologic, chemical, and scanning electron microscopic studies of such cutaneous lesions were performed on four cases from the Armed Forces Institute of Pathology files. Reported cases from the literature were reviewed. Metallic mercury in tissue sections appears as dark, opaque globules, usually spherical in shape and of varying sizes and numbers. A zone of collagen necrosis often surrounds the mercury globules. A granulomatous foreign body-giant cell reaction and a mixed inflammatory cellular infiltrate composed of neutrophils, lymphocytes, histiocytes, plasma cells, and occasional eosinophils are usually present. Epidermal and dermal necrosis, with or without ulceration or pseudoepitheliomatous hyperplasia, is also a common finding. The gold lysis test and energy-dispersive x-ray analysis confirmed the presence of metallic mercury in the tissue. Following cutaneous injury from mercury, systemic toxicity may develop and death may even occur. An approach to clinical management is discussed. Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. Maiti S, Chatterjee AK. University Grants Commission, New Delhi 110002, India. firstname.lastname@example.com Arch Toxicol 2001 Nov;75(9):531-7 Arsenic is a potent toxin, carcinogen and modulator of antioxidant defense system. In this study, male rats of Wistar strain, maintained on either 18% or 6% protein (casein) diet, received an acute i.p. exposure to sodium arsenite (As3+) at its LD50 dose (15.86 mg/kg body weight). One hour after the arsenic exposure, glutathione (GSH) concentration was significantly depleted and lipid peroxidation was increased. A relationship between any two of tissue arsenic concentrations, GSH levels and lipid peroxidation values was observed only for liver when the proportional changes of respective parameters in either of the dietary groups of animals were compared. This suggests that, in liver, arsenic metabolism appears dependant upon the GSH concentration. Acute arsenic exposure significantly increased the glutathione peroxidase (GPx) activity in liver of both dietary groups and in kidney of only the 18% protein-fed group of animals. The glutathione-S-transferase (GST) activity significantly decreased in liver of the 18% protein-fed animals while GST increased in kidney of both the 18% and the 6% protein-fed groups. No significant change in glutathione reductase (GR) or glucose-6-phosphate dehydrogenase (G6PDH) activity was observed. In the present investigation, liver as a whole seems to be more affected in terms of GSH level and GST activity. The mode of responses of GPx and GR activities as well as the unaltered G6PDH activity might result in arsenic-induced GSH depletion and increase in lipid peroxidation. The animals of the 6% protein-fed group, appeared to be affected less in terms of tissue arsenic concentration, lipid peroxidation, GSH level and GST activity. Toxicity, lead. Marcus S. eMed. J. 2001 Jun 4; 2(6):7 No abstract available. Medical Management Guidelines (MMGs). Medical Management Guidelines (MMGs) (no authors given). Managing Hazardous Material Incidents, Volume III (http://www.atsdr.cdc.gov). 2001 Agency for Toxic Substances and Disease Registry Centers for Disease Control, Atlanta, GA, U.S.A. No abstract available. B.A.L.™ Micromedex (no authors given). 1999 Thompson/Micromedex, Greenwood Village, CO, U.S.A. No abstract available. The effects of glutathione and vitamin E on iron toxicity in isolated rat hepatocytes. Milchak LM, Douglas Bricker J. Department of Pharmacology-Toxicology, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, U.S.A. Toxicol Lett 2002 Feb 7;126(3):169-77 This study examined the acute toxicity of ferrous sulfate on rat hepatocyte suspensions, the correlation between lipid peroxidation and cell death, and the roles of glutathione and vitamin E in protecting against iron toxicity. Incubation with ferrous sulfate for 2 h produced lipid peroxidation, but did not decrease cell viability in the hepatocytes. When diethyl maleate (DEM) was added to deplete cellular glutathione concentrations, ferrous sulfate treatment (2.0-5.0 mM) did cause cell death and lipid peroxidation developed more extensively, suggesting that iron-mediated hepatotoxicity is influenced by glutathione content. Reduced glutathione (GSH), N-acetylcysteine (NAC) and alpha-tocopherol (vitamin E), alone and in combination, were added to hepatocyte suspensions in an attempt to protect cells against iron-induced damage. In iron-DEM-treated cells, GSH and NAC treatment increased viability by 43 and 36%, respectively, but only the combination of the two agents reduced lipid peroxidation (53% decrease). Vitamin E treatment reduced lipid peroxidation by 39% and also increased cell viability by 12%. The greatest protection against iron-induced lipid peroxidation occurred with the combination of GSH, NAC and vitamin E, which reduced lipid peroxidation by 94% in iron-treated cells, and by 98% in iron-DEM-treated cells. However, this combination did not prevent iron-induced cell death, although it did increase viability by 18%. These esults suggest that iron-induced cell death may not be dependent upon lipid peroxidation, at least in short-term exposures. The results also suggest an interaction between GSH and vitamin E in protecting against lipid peroxidation. Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes. Muller L. Institute of Toxicology, University of Dusseldorf, F.R.G. Toxicology 1989 Oct 2;58(2):175-85 The suitability of DL-alpha-lipoic acid (LA) to serve as an antidote in cadmium (Cd) toxicity in rat hepatocytes was investigated. Isolated hepatocytes were exposed to 200 and 450 microM Cd in the presence of 0.2, 1.0 and 5.0 mM LA, respectively. After 30 min of incubation various criteria of cell viability were monitored. Lipoic acid markedly diminished Cd uptake. Concomitantly, Cd-induced membrane injury, as reflected by the leakage of aspartate aminotransferase and sorbitol dehydrogenase (SDH) was decreased. Moreover, LA protected against intracellular toxic responses to Cd, such as a decrease in cellular SDH activity, a decrease in cellular acid soluble thiols, especially in total glutathione, a decrease in cellular urea and an increase in thiobarbituric acid (TBA) reactants, as a measure of lipid peroxidation. Most protective effects were seen in hepatocytes challenged with the lower Cd concentration and coincubated with 5 mM LA. In contrast, at 450 microM Cd even the highest LA concentration applied either did only reverse Cd-effects incompletely (SDH-response, TBA-reactants) or did not protect at all (Cd uptake, enzyme leakage, loss of glutathione). The data indicate that DL-alpha-lipoic acid serves as a protective tool against Cd-induced membrane damage and cell dysfunction in hepatocytes. This stands as long as Cd exposure is low enough to permit interaction with LA prior to interaction with cell structures. Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium 2+ toxicity in isolated hepatocytes. Muller L, Menzel H. Institute of Toxicology, University of Dusseldorf, F.R.G. Biochim Biophys Acta 1990 May 22;1052(3):386-91 Lipoate (thioctic acid) is presently used in therapy of a variety of diseases such as liver and neurological disorders. However, nothing is known about the efficacy of lipoate and its reduced form dihydrolipoate in acute cadmium (Cd2+) toxicity which involves severe liver disturbances. Therefore, we investigated the effects of these redox compounds on Cd2(+)-induced injuries in isolated rat hepatocytes. The cells were coincubated with 150 microM Cd2+ and either 1.5-6.0 mM lipoate or 17-89 microM dihydrolipoate for up to 90 min and Cd2+ uptake as well as viability criteria were monitored. Both exposure regimens diminished Cd2+ uptake in correspondence to time and concentration. They also ameliorated Cd2(+)-induced cell deterioration as reflected by the decrease in Cd2(+)-induced membrane damage (leakage of aspartate aminotransferase), by the lessening of the Cd2(+)-stimulated lipid peroxidation (TBA-reactants) and by the increase in Cd2(+)-depleted cellular glutathione (GSH + 2 GSSG). Half-maximal protection was achieved at molar ratios of 9.9 to 19 (lipoate vs. Cd2+) and 0.25 to 0.74 (dihydrolipoate vs. Cd2+), indicating a 19.5 to 50.6 lower protective efficacy of lipoate as compared to dihydrolipoate. Lipoate induced an increase in extracellular acid-soluble thiols different from glutathione. It is suggested that dihydrolipoate primarily protects cells by extracellular chelation of Cd2+, whereas intracellular reduction of lipoate to the dihydro-compound followed by complexation of both intra- and extracellular Cd2+ contributes to the amelioration provided by lipoate. Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. Muller U, Krieglstein J. Institut fur Pharmakologie und Toxikologie, Philipps-Universitat, Marburg, Germany. J Cereb Blood Flow Metab 1995 Jul;15(4):624-30 The antioxidant dihydrolipoic acid has been shown to reduce hypoxic and excitotoxic neuronal damage in vitro. In the present study, we tested whether pretreatment with alpha-lipoic acid, which presumably allows endogenous formation of dihydrolipoic acid, can protect cultured neurons against injury caused by cyanide, glutamate, or iron ions, using the trypan blue exclusion method to determine neuronal damage. One hour of preincubation with dihydrolipoic acid (1 microM), but not with alpha-lipoic acid, reduced damage of neurons from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions. alpha-lipoic acid (1 microM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pretreatment with alpha-lipoic acid for > 24 h enhanced this neuroprotective effect. Both the R- and the S-enantiomer of alpha-lipoic acid exerted a similar neuroprotective effect. Pretreatment with alpha-lipoic acid (1 microM) from the day of plating onward prevented the degeneration of chick embryo telencephalic neurons that had been exposed to Fe2+/Fe3+. alpha-lipoic acid (1 microM) added to the culture medium the day of plating also reduced neuronal injury induced by 1 mM L-glutamate in rat hippocampal cultures, whereas 30 min of preincubation with alpha-lipoic acid failed to attenuate glutamate-induced neuronal damage. Our results indicate that neuroprotection by prolonged pretreatment with alpha-lipoic acid is probably due to the radical scavenger properties of endogenously formed dihydrolipoic acid. Poisoning first aid. National Medical Library (no authors given). 2001 Medical Encyclopedia (http://www.nlm.nih.gov/medlineplus/ency/article/000003.htm) National Institutes of Health, Bethesda, MD, U.S.A. No abstract available. Mercury amalgam toxicity. O'Brien J. Life Extension Magazine 2001 May. 7(5):43-51 (http://www.lef.org/magazine/mag2001/may2001_report_mercury_1.html) Life Extension Foundation, Ft. Lauderdale, FL, U.S.A. No abstract available. Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and delivering effective antibiotics using various drug uptake enhancement methods. Omura Y, Beckman SL. Heart Disease Research Foundation, New York, NY U.S.A. Acupunct Electrother Res 1995 Aug-Dec;20(3-4):195-229 The authors found that antibiotics used to treat various infections often were ineffective in the presence of abnormal localized deposits of heavy metals like Hg and Pb, which were often observed to co-exist with Chlamydia trachomatis, Herpes Simplex Types I & II, Cytomegalovirus(CMV), and other micro-organisms. Our earlier research revealed that despite rigorous treatment with antibiotics together with various drug uptake enhancement techniques, subjects who had been treated for Chlamydia trachomatis infections, seemingly successfully with disappearance of their symptoms, were often experiencing recurrences within several months after completion of their treatment despite taking precautions against reinfection. Careful examination of the entire body of these symptom-free patients with the Bi-Digital O-Ring Test revealed that the Chlamydia trachomatis had retreated to 3 approximately 5 hiding places with localized increase in uric acid levels: 1) sublingual caruncle, 2) a small round area in the right and/or left axillae, 3) the genitals (Corona Glandis area of the Glans Penis at the Fossa Navicularis of the urethra in the male, and near the orifice of the urethra in the female), 4) Insulin-like Growth Factor positive horizontal lines, particularly above and below the knees, 5) the maxillary, ethmoid and frontal sinuses and the horizontal lines at the base of the nostrils (particularly small areas where Insulin-like Growth Factors exist). We found that all these areas contain Insulin-like Growth Factors I & II which are reduced in the presence of infection. Even when drug uptake of antibiotics was selectively increased in these 3 approximately 5 areas by various drug uptake enhancement methods developed by the 1st author, still the infection persisted. In the spring of 1995, use of Chinese parsley for successful elimination of Hg deposits existing in various organs of the first author as the result of the decay of radioactive Thallium 201 injected for cardiac SPECT, was accidentally discovered after eating Vietnamese soup, which happened to contain Chinese parsley, also called cilantro. We also found Chinese parsley accelerates the excretion of Hg, Pb, and A1 from the body though the urine. Our subjects were given a course of antibiotics (Doxycycline for Chlamydia trachomatis infection) or anti-viral agents (EPA with DHA for Herpes Family Viruses) together with Chinese parsley. Since these vegetable/herbs were eaten, the amount of effective substance absorbed varied and some people did not like the taste of these relatively large amounts of either cooked or raw parsley or its juice, but together with effective antibiotics delivered by drug uptake enhancement methods to the infected areas, the substances worked synergistically, rapidly reducing the generalized symptoms and infection. The micro-organisms retreated to the 3 approximately 5 areas listed above where, with continued treatment, they were significantly reduced, but not completely eliminated. Because of these problems, a pharmaceutical company was asked to produce a Chinese parsley table containing a controlled amount in a highly absorbable form. When 11 subjects were treated with Doxycycline for Chlamydia trachomatis infection, or anti-viral agents (EPA with DHA) for Herpes Family Viruses, drug uptake enhancement methods to selectively increase delivery of the drugs to the affected areas, and Chinese parsley tablets to remove the heavy metal deposits, the last traces of the infections and clinical symptoms disappeared completely. Therefore we hypothesized that the infectious micro-organisms mentioned above, somehow utilize the Hg or Pb to protect themselves from what would otherwise be effective antibiotics, and/or that heavy metal deposits in some way make antibiotics ineffective. Since the micro-organisms retreat to areas in which Insulin-like Growth Factors I & II normally exist, they may be utilizing them for their own growth and multiplication. Page12


text:
AN EMPTY HOUSE (Poem by Dan Collins)
Regret is one thing, but
when the lock turned
behind me and the
line of the door jamb
crack disappeared,
the lights went black
and nothing moved
on the other side
of the laced up
windows. Board
by board, tile by tile,
your little house
is dismantled.
If I had known we would
be sorting your things,
nothing could stop
this poem burning down.
Copyright 2013 by Dan Collins. (aka Atticus)
Image: Andrew Ferez

subset: commoncrawl


text:
Rapid Review Histology and Cell Biology, 2nd Edition
With STUDENT CONSULT Online Access
Please note that due to a system merger our fulfillment system will be down beginning September 22nd with an anticipated date to begin shipping orders October 10th. We would like to apologize for any inconvenience by offering you a special 20% discount on select products. Please use Promotional Code 12760. Click here for promotion details.
Get the most from your study time...and experience a realistic USMLE simulation! These new additions to the Rapid Review Serieshighly rated in the First Aid rankingsmake it easy for you to master all of the basic science material covered on the USMLEâ"¢ Step 1 Exam.
Key Features
- Each title focuses on a particular basic science subject, providing an at-a-glance, outline-format review of all the information you need to know.
- A user-friendly 2-color layout, Hi-Yield Margin Notes, and Key Points make studying easy.
- 100 high-quality USMLE-style review questions inside each book allow you to practice for the USMLE, and include a full rationale that lets you know why every possible answer is right or wrong.
- Another 250 USMLE-style questions for each title are available at www.studentconsult.com—mirroring the look and feel of the actual exam, and providing detailed feedback on which areas you may need to study more.
Author Information
By E. Robert Burns, PhD, Course Director, Microscopic Anatomy, Professor of Anatomy, Department of Anatomy and Neurobiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR; and M. Donald Cave, PhD, Professor of Anatomy, Department of Anatomy and Neurobiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
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- 336 Pages
- Trim Size: 7 1/2 X 9 1/4 in
- Imprint: Mosby
- Copyright: 2007


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This disk, along with its companion Clarinet Methods, Studies & Ensembles (HL00220334) comprises the largest collection of clarinet music ever assembled. Includes solos with piano accompaniment as well as duos, trios, and other ensembles. The disk also includes composer biographies and related articles from the 1911 edition of Grove's Dictionary of Music and Musicians. Works on Mac and PC computers. Uses Adobe Reader® (available for free) and requires no special software or skill!
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Product Recall: We are voluntarily recalling fewer than 8,000 cases of regular Kraft American Singles Pasteurized Prepared Cheese Productlimited to 4 SKUs on two "Best When Used By" dates of February 20, 2015 and February 21, 2015. Click Here.
HEAT oven to 400°F.
TOSS tortilla strips with oil; spread into single layer on rimmed baking sheet. Bake 10 to 12 min. or until crisp, stirring occasionally.
MEANWHILE, mix cream cheese spread, 2 Tbsp. milk and taco seasoning until blended. Cook chicken in large saucepan sprayed with cooking spray on medium-high heat 8 to 10 min. or until done, stirring frequently. Stir in cream cheese mixture, remaining milk, beans, corn and tomatoes; simmer on medium-low heat 6 to 8 min. or until heated through, stirring frequently.
SERVE topped with tortilla strips and cilantro.


text:
Washington's newest sports stars are among the 300 under-fortysomethings on this year's Young and the Guest List, the annual who's who of the District's social scene produced by Washington Life. It was a first for Redskins quarterback Robert Griffin III and Nationals Rookie of the Year Bryce Harper to grace the list, which came out this week. Michelle Kwan, who traded in her figure skates for a State Department gig, also made it. Other newbies include congressional freshman Reps. Joaquin Castro, D-Texas, Kyrsten Sinema, D-Ariz., and Joseph P. Kennedy III, D-Mass. And there wasn't just American political royalty in the group of young professionals and socialites, but real royalty. American University student and Princess
Iman Bint Al Hussein of Jordan rounds out the list.


text:
22 U.S. Code § 1251 to 1255 - Omitted
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Section 1251, act Apr. 30, 1946, ch. 244, title II, § 201,60 Stat. 143, provided for entry of Philippine articles into the United States, between May 1, 1946 and July 3, 1954, free of ordinary customs duty.
Section 1252, act Apr. 30, 1946, ch. 244, title II, § 202,60 Stat. 143. Subsec. (a), related to ordinary customs duties on Philippine articles between July 4, 1954 and July 3, 1974. Subsec. (b), which related to ordinary customs duties on Philippine articles for the period after July 3, 1974, was omitted on authority of former section 1345 of this title which nullified subchapter I of this chapter upon the expiration of the revised agreement between the United States and the Republic of the Philippines which occurred on July 4, 1974.
Section 1253, act Apr. 30, 1946, ch. 244, title II, § 203,60 Stat. 144, related to customs duties on Philippines articles other than ordinary customs duties. See note above for section 1252 (b) of this title.
Section 1254, act Apr. 30, 1946, ch. 244, title II, § 204,60 Stat. 144, related to equality in special import duties. See note above for section 1252 (b) of this title.
Section 1255, act Apr. 30, 1946, ch. 244, title II, § 205,60 Stat. 144, related to equality in duties for products of the Philippines which did not come within the definition of Philippine articles. See note above for section 1252 (b) of this title.
Extension of Duty-Free Period Until December 31, 1955
Act July 5, 1954, ch. 459, 68 Stat. 448, provided that the duty-free treatment of this section was to be applied in lieu of section 1252 (a)(1), (2) of this title for Philippine articles entered or withdrawn from United States warehouses for consumption during periods between July 3, 1954 and December 31, 1955 provided the President declared by proclamation that such period was one in which United States articles were admitted into the Philippines free of ordinary customs duties.
Proc. No. 3060. Extension of the Period of Duty-Free Treatment
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Welcome to the Bob Bullard Photography website. Our goal is to provide you with award winning digital wedding photography that you will treasure for years to come.
From the "getting ready" shots, to the ceremony and reception, your wedding day is of utmost importance. We utilize a mix of photojournalism, artistic, fine art and portraiture styles with our digital photography in order to seamlessly blend your wedding photos into a variety of exquisite imagery.
We cover the New England states of New Hampshire, Massachusetts, Maine and Vermont as well as New York and California.
If your day involves a national or international destination wedding or civil commitment ceremony, from beginning to end, we will capture the beauty, architecture and subtle nuances of your special day.
I anticipate that you will find the information and imagery contained within this website, both pleasing and interesting. In this event, please let it prompt you to inquire as to how we may collaborate on this very special occasion.
Best Regards,
Bob Bullard, Wedding Photographer
NH Wedding Photography Style Wedding Photos Wedding Photography Packages Clients NH Wedding Photographer


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SUPERIOR, WI (WTAQ) - The new wave of crude oil from North Dakota will not be shipped from Superior any time soon.
The Superior Calumet Refinery has delayed plans to open a terminal to move crude by boat on the Great Lakes to the East Coast.
Refinery manager Kollin Schade tells Wisconsin Public Radio the project needs a refinery in the Eastern U.S. as a partner. He says there's been interest from various partners, but none have stepped forward to make a long-term commitment that's needed to make the Superior terminal feasible.
Calumet was planning to open it in two years. The firm is still seeking state permits just in case it can proceed down the line.
The terminal would ship crude oil from the Bakken fields in North Dakota. It's where production has risen so quickly, that normal transporting methods are having a hard time keeping up.
For now, at least, Adolph Ojard of the Duluth Seaway Port Authority says it's more efficient to move the North Dakota crude by pipelines and trains.


text:
Constrained Probabilistic Continuous Review Inventory System with Mixture Shortage and Stochastic Lead Time Demand
Full Text:pdf indexed/included/archived
[1] Posner, M., & Yansouni, B. (1972). A class of inventory models with customer impatience. Naval Research Logistics Quarterly, 19(3), 483–492.
[2] Montgomery, D. C., Bazaraa, M., & Keswani, A. K. (2006). Inventory models with a mixture of backorders and lost sales. Naval Research Logistics Quarterly, 20(2), 255–263.
[3] Rosenberg, D. (1979). A new analysis of a lotsize model with partial backlogging. Naval Research Logistics Quarterly, 26(2), 349–353.
[4] KYUNG, S. (1982). Inventory model with partial backorders. International Journal of Systems Science, 13(12), 1313–1317.
[5] Rabinowitz, G., Mehrez, A., Chu, C.-W., & Patuwo, B. E. (1995). A partial backorder control for continuous review (r, q) inventory system with poisson demand and constant lead time. Computers &
operations research, 22(7), 689–700.
[6] Zipkin, P. (2000). Foundations of Inventory Management McGraw-Hill.
[7] Fergany, H., & El-Wakeel, M. (2006). Constrained probabilistic lost sales inventory system with continuous distributions and varying order cost. Journal of Association for the Advancement of Modeling &Simulation Techniques in Enterprises, 27, 3–4.
[8] Fergany, A., & El-Wakeel, M. (2006). Constrained probabilistic lost sales inventory system with normal distribution and varying order cost. Journal of Mathematics and Statistics, 2(1), 363–366.
[9] El-Wakeel, M. F. (2012). Constrained backorders inventory system with varying order cost: Lead time demand uniformly distributed. Journal of King Saud University-Science, 24(3), 285–288.
[10] Hadley, G. (1963). Analysis of Inventory Systems: By G. Hadley and TM Whitin. Prentice-Hall.
[11] Fabrycky,W. J., & Banks, J. (1967). Procurement and inventory systems: theory and analysis. Reinhold.
[12] Hillier, F. S., & Lieberman, G. J. (1995). Introduction to operations research, volume 6. McGraw-Hill New York.
[13] Nahmias, S., & Cheng, Y. (1997). Production and operations analysis.
DOI: http://dx.doi.org/10.3968%2Fj.ans.1715787020130601.1646
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text:
I apologize for the long delay. I am in the midst of applying for two grants. The first is to the National Endowment for the Arats for the next Big Read grant– due Feb 1 for next October. We are going to read The Adventures of Tom Sawyer. The second grant is the Illinois Public Library Construction Grant — due on April 1. More on that one later. Wish us luck in the writing of detailed grants.
Long Time
16 Jan


text:
NewsApril 25 2012
Absentee Balloting begins for June Primary
PIERRE, S.D. -- South Dakota Secretary of State Jason Gant announced that voters can now cast absentee ballots for the 2012 primary election on June 5th.
"South Dakotans have widely embraced absentee voting as a matter of convenience," Gant said. "In the 2010 general election, we had 411 members of the military vote overseas. However, we had an additional 63,339 South Dakota voters cast their ballots through mailed and in-person absentee balloting. This comprised 19.71% of all ballots cast in the 2010 general election."
According to primary data from the 2010 primary election, 11,651 or 11.3% of voters cast absentee ballots during the last June primary. "From reports I am receiving from County Auditors across South Dakota, current absentee requests are light, but as we get closer to the election, experience shows us that the pace picks up greatly. Many people decide to cast their vote through absentee balloting as a matter of convenience to avoid lines at the polls," Gant said.
"If a person believes they may not be available to vote on election day, they can vote at their County Auditor's office or visit sdsos.gov to complete an application for an absentee ballot," Gant noted.
- Raider colors on parade
- Lutherans observe 100 years in Presho
- Rails to the Future Applauds Receipt of $13 Million TIGER Grant to Build Railroad to Presho
- Homecoming King and Queen Crowned
- Survey indicates pheasants numbers strong in central South Dakota
- Celebrate South Dakota's 125 years of Statehood at the museum Sunday
- Booster Club hosts kick off
- Market features sunflower blooms and more
- Kennebec to celebrate Lake Byre; DayTriathlon set for Saturday
- Pool season comes to an end
- Hoping for a favorable nod from the judge
- Reminiscing at school reunions


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The Lighthouse Blog
Tips for running on a rainy day
Published on Wed, Jan 23, 2013
Read More
When the weather takes a turn for the worse, it can be difficult to get motivated to even get off the couch much less go for a run. But if you're determined to stay fit no matter what the gray skies may bring, here are a few tips from Tracy Niemier at Forward Motion Coaching in Bellingham.
1. Have good rain gear – find the jacket, hat, gloves and pants that work for you and pay attention to the temperature so you wear the right combination of clothes. Vents are nice so you can let some heat out without letting the rain in.
2. Choose your route – one of the reasons I don't like to get out the door is because I will be cold at first, or I may dress too warm and then I'm too hot. Choose a route where you can do a small circuit back to your house to drop off a layer when you warm up.
3. Learn to appreciate the types of rain – a soft mist is my favorite rain to run in. I love the feel of it on my cheeks. A really heavy rain removes any thoughts you might have of staying dry, so you are free to play in the puddles like a kid. You are going home wet no matter what. Warm rain makes me feel like part of the outdoors. Cold rain makes me feel tough.
4. Time your run – This works great if your schedule allows for it. Get your running clothes on and then watch out the window for a break in the downpour. When it stops raining, get out there. Sometimes you'll get lucky and it won't start again until you get home. Even if it does start raining while you are out there it doesn't seem as bad as standing at the window looking at the rain and stepping from your nice dry house into it.
5. Wear a hat – a ball cap with a brim is a must-have for those of us who wear glasses. It'll keep the rain from dripping into your eyes and help you feel a little less soaked.
6. Phone up a friend and tell them you are going – either they will think you are nuts (which is a pretty good motivator) or they will say, "What time? I'll meet you."
7. Think about saving on laundry – your clothes are getting a shower the whole time you are out there.
8. Run on a treadmill – the less said the better.
9. Become one with the rain – I have never gotten so wet that I never got dry again. We are waterproof creatures. I don't wear waterproof gear for running, I just get wet and dry off when I get home.
10. Use the 20 minute rule – I tell myself that I only have to run for 20 minutes. If I run for 20 minutes and I want to come back home, I give myself permission to come back home. I know I can do almost anything for 20 minutes and worst-case scenario, I get a 20-minute run in.


text:
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User Error Parts 1 and 2 are a two-part Single Player expansion mod for TRON 2.0 on the PC. This updated version now self-installs, and adds proper widescreen support when used with the Killer App Mod.
New Light Cycle type, and a new DataWraith type riding it.


text: SHEBOYGAN, WI (WHBL) - The Sheboygan City Council voted Monday night to approve the city's 2014 budget, but not before amending it to increase the tax levy by 293-thousand dollars. Alderman Jim Bohren was one of three aldermen to vote against the budget. He said it wouldn't have been necessary to increase the levy if the city got a handle on employee benefits - specifically health insurance. Citing a national study, Bohren said the city is paying nearly 2-million dollars more for health insurance than the private sector would. He said, "It's not sustainable and if we get a handle on that alone we can maintain all city services." Finance Chair Don Hammond agreed, but said the city also has to stay competitive. He said the city can look at that again as the city negotiates union contracts for 2014 and 15. He called it a good budget with a property tax levy that's less than 2012. Total city spending will increase by about 1 percent next year. The tax rate for city purposes will go up by about a dime per thousand or about 15 dollars on a 150-thousand dollar home - not including the school, county or state tax. The final figures won't be available for several weeks, but last year's total tax rate, with all components, in the city of Sheboygan was $23.78 per thousand.


text:
A new coffee-table book featuring images of many of the world's greatest rock musicians' guitars will be published on September 16. As its title suggests, 108 Rock Star Guitars features photos of instruments belonging to 108 rockers, including such legends as Jack White , Dave Navarro , Slash , Soundgarden 's Kim Thayil , Rage Against the Machine 's Tom Morello , Dave Mustaine , Jimmy Page and Ace Freely .
The 396-page book was compiled by photographer Lisa S. Johnson , who began the project 17 years ago when she snapped pics of Les Paul 's guitar during one of the late, great music innovator's famous shows at New York City's Iridium club. She also contributes recollections and commentary about her experiences photographing the various instruments and meeting their famous owners. In addition, the book includes a foreword penned by Paul shortly before his death in 2009.
108 Rock Star Guitars is priced at $108 and features a high-quality red leatherette binding. It also comes with a black guitar pick boasting one of three holographic designs and a 16-page booklet featuring Johnson explanation of what inspired the project. A limited-edition version, hand-signed and numbered by the author, also will be available. Costing $540, the deluxe volume will be packaged in a specially designed box, and will feature a hand-woven silk scarf as well as a guitar pick and booklet.
To check out the full complete list of artists whose guitars appear in the book, visit 108RockStarGuitars.com . Both versions of the book can be pre-ordered now at the website.
Copyright 2013 ABC News Radio


text:
Shred and destroy.
- Railkiller edges use double-thickness material to resist cracks, dings, and blowouts
- Tip-to-tail wood Powercore II is lightweight, durable, and pops like a flaming fireworks stand
- Reflex Profile thins out the core between your feet for easier ollies and more independent foot control
- Pop Band gives the board a snappy feel without any extra torsional stiffness
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Is this 2010-2011 snow season product?
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Is this 2010-2011 snow season product?
Tim Bohlken
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the top of the description will usually have the year if it is not the current model. "Nitro T1 Snowboard - 2011"
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Love the board! perfect size and feel. very responsive and just an all around amazing board. Wish the top graphic art was a bit cooler or had more of it
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T1 or T1 zero? Nitro has two versions of this board: zero and trad camber. The tech spec says zero but the description says standard...? And the picture looks like the zero version from the nitro website.
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Sorry for the confusion... we have the zero camber versions. We'll get the description updated as soon as possible.
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To anyone looking for a zero camber as shown here do not buy this product it is incorrectly listed still.
Dont get stuck having to ship a board internationally back to get a refund due to Dogfunks blunder like me.
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text:
July 4 – 9, 2011
Satish Kumar, Stephan Harding and Alastair McIntosh
This course is open for bookings.
Our popular Earth Pilgrim course returns to our summer programme. The course centres around the experiences and reflections of Satish Kumar, who has undertaken many pilgrimages throughout his life, beginning with an 8,000-mile peace pilgrimage from India to America. More recently, a BBC documentary Earth Pilgrim followed Satish through the landscapes of Dartmoor in different seasons as he reflected on the profound insights and spiritual experiences that come from spending time close to nature.
During this course, Satish will share his thoughts on the importance of bringing soul into the heart of everything we do, and how this can enhance our creativity and our work for sustainability and peace. On Dartmoor, participants will visit with Satish some of the landscapes pictured in the Earth Pilgrim documentary – woods, rivers, tors, stone circles, and the open moor – walking together, talking, sitting quietly and reflecting individually and as a group. The group will be joined on one of the walks by Stephan Harding who will introduce Gaia theory and deep ecology as a way of connecting more deeply with the natural world. The course will also include a guided visit to the beautiful Dartington Hall Gardens and a walk along a section of the South Devon coast.
Alastair McIntosh will join the group for an evening to discuss his "poacher's pilgrimage through the Outer Hebrides". In 2008, he felt moved to journey by foot through his home island of Lewis and Harris in the Scottish Hebridean islands. Disguised as a poacher, he spent 12 days camping out in some of the remotest parts of Britain and walking though coastal villages meeting people he knew and making new friends. Two years later the pilgrimage continues to deepen as he writes it up – a magical realist exploration of God, war trauma and the function of "faerie" in the indigenous Celtic psyche. During the course of this evening he will share with the course participants a preview of his work in progress.
The Earth Pilgrim course offers the opportunity to slow down. As we explore some of the beautiful Dartmoor and coastal landscapes, we will enjoy periods of quiet reflection through mindful walking and sitting, as well as sharing some of our thoughts and ideas. Journal writing, drawing, meditation, and experiential exercises will complement discussions with Satish about the place of spirituality in the modern world.
This week aims to help you engage with the natural world and to reconnect.
Satish Kumar: When he was only nine years old, Satish renounced the world and joined the wandering brotherhood of Jain monks. Dissuaded from his path by an inner voice at the age of 18, he left the monastic order and became a campaigner for land reform, and has been working to turn Gandhi's vision of a peaceful world into reality ever since. He undertook an 8,000 mile peace pilgrimage, walking from India to America without any money to deliver packets of peace tea to leaders of the four nuclear powers. In 1973, he settled in England, becoming editor of Resurgence magazine – a position he has held ever since. Satish is the guiding spirit behind a number of ecological, spiritual and educational ventures in Britain and was one of the founders of Schumacher College.
Stephan Harding is Programme Coordinator of the MSc in Holistic Science at Schumacher College teaching on the MSc core modules and as part of several of the short courses at the College. He is a close associate of James Lovelock and an expert in the study of Gaia theory and deep ecology. He is the author of Animate Earth.
Alastair McIntosh is an activist, scholar, broadcaster and writer of books including Soil and Soul, Hell and High Water: Climate Change, Hope and the Human Condition and a Schumacher Briefing, Rekindling Community. His books have been described as "world-changing" by George Monbiot, "life-changing" by the Bishop of Liverpool, "inspirational" by Starhawk and "truly mental" by Thom Yorke of Radiohead.
Facilitator: Rosalind J.Turner is a group facilitator and an open-air coach. As a group facilitator, Rosalind works with authenticity and integrity; she brings to the role her understanding of mindfulness techniques, combined with a flair for working creatively and spontaneously. As a coach, she specialises in giving people supported time and space in nature; away from the usual distractions, offering the opportunity for deeper reflection and a more embodied experience. For further information please visit her website www.walkingtomeetourselves.co.uk
All course fees include accommodation, food, field trips and all teaching sessions.
For further information about Schumacher College please see About the College
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We will hold the place for five working days for reservations – three weeks before a course or earlier. After five days we will automatically offer your place to someone else if we have not received your application.