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PubMed1977

Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator.

Perchlorate treatment of mice increased by 1.5-2-fold the thyroid secretory response to TSH, hCG and LATS, in the McKenzie bioassay. Perchlorate alone did not increase basal plasma radioactivity. Perchlorate augmentation of the secretory response index was roughly proportional to the level of stimulation; it was similar for all three stimulators despite their different time courses of action which were unaltered by perchlorate; it was the same whether perchlorate administration preceded, coincided with or shortly followed injection of the stimulator, a finding in keeping with the slow clearance of this ion. The perchlorate effect was dose-related, although within a narrow range (6.25-12.5 microng/mouse). Near-maximal per chlorate effect was obtained with a dose (12.5 microng) which, when tested in different experimental conditions (MMI-blocked thyroid), discharged 80% of intrathyroidal radioiodide. Perchlorate exerted its augmenting effect by enhancing thyroid secretion: it increased plasma radioiodothyronines and radioiodide concentrations without decreaseing the blood disappearance rates of iodide and iodothyronines. The potentiating effect of perchlorate probably takes place at a step prior to cyclic AMP action since it did not affect dbcAMP-stimulated secretion. The perchlorate effect may be indirect, through mobilization of minute amounts of intrathyroidal iodide.

Animals↗

PubMed1999

1,25-Dihydroxyvitamin D3 increases the growth-promoting activity of autocrine epidermal growth factor receptor ligands in keratinocytes.

Topical treatment of normal skin with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or its synthetic analogs results in enhanced keratinocyte proliferation. Autocrine growth factors belonging to the epidermal growth factor (EGF) family play a major role in controlling keratinocyte proliferation. 1,25-(OH)2D3 enhanced the autonomous proliferation of HaCaT human keratinocytes in the absence of exogenous growth factors. Autonomous and 1,25-(OH)2D3-stimulated proliferations were inhibited by a specific inhibitor of EGF receptor (EGFR) tyrosine kinase, an EGFR-neutralizing antibody, heparin, the heparin antagonist hexadimethrine, and the proteoglycan sulfation inhibitor chlorate. These results indicate the involvement of proteoglycan-dependent EGFR ligands. The initial events in EGFR (i.e. ErbB1) mitogenic signal transduction are dimer formation with another ErbB protein and tyrosine cross-phosphorylation. By immunoprecipitation followed by Western blotting we showed that ErbB1/ErbB3 heterodimers are the major mitogenic signaling entity in 1,25-(OH)2D3-stimulated cells. 1,25-(OH)2D3 did not affect the levels of the proteoglycan-dependent EGFR ligands amphiregulin and heparin-binding EGF nor the synthesis of proteoglycans, as assessed by 35S labeling and ion exchange chromatography. 1,25-(OH)2D3 caused a marked increase in the cellular contents of ErbB1, ErbB2, and ErbB3 proteins. The increase in ErbB proteins that mediates signal transduction by EGFR ligands can account for the stimulatory effect of 1,25-(OH)2D3 on autonomous keratinocyte proliferation.

Autocrine Communication↗

PubMed1998

Regulation of BMP7 expression during kidney development.

Members of the Bone Morphogenetic Protein (BMP) family exhibit overlapping and dynamic expression patterns throughout embryogenesis. However, little is known about the upstream regulators of these important signaling molecules. There is some evidence that BMP signaling may be autoregulative as demonstrated for BMP4 during tooth development. Analysis of BMP7 expression during kidney development, in conjunction with studies analyzing the effect of recombinant BMP7 on isolated kidney mesenchyme, suggest that a similar mechanism may operate for BMP7. We have generated a beta-gal-expressing reporter allele at the BMP7 locus to closely monitor expression of BMP7 during embryonic kidney development. In contrast to other studies, our analysis of BMP7/lacZ homozygous mutant embryos, shows that BMP7 expression is not subject to autoregulation in any tissue. In addition, we have used this reporter allele to analyze the expression of BMP7 in response to several known survival factors (EGF, bFGF) and inducers of metanephric mesenchyme, including the ureteric bud, spinal cord and LiCl. These studies show that treatment of isolated mesenchyme with EGF or bFGF allows survival of the mesenchyme but neither factor is sufficient to maintain BMP7 expression in this population of cells. Rather, BMP7 expression in the mesenchyme is contingent on an inductive signal. Thus, the reporter allele provides a convenient marker for the induced mesenchyme. Interestingly LiCl has been shown to activate the Wnt signaling pathway, suggesting that BMP7 expression in the mesenchyme is regulated by a Wnt signal. Treatment of whole kidneys with sodium chlorate to disrupt proteoglycan synthesis results in the loss of BMP7 expression in the mesenchyme whereas expression in the epithelial components of the kidney are unaffected. Heterologous recombinations of ureteric bud with either limb or lung mesenchyme demonstrate that expression of BMP7 is maintained in this epithelial structure. Taken together, these data indicate that BMP7 expression in the epithelial components of the kidney is not dependent on cell-cell or cell-ECM interactions with the metanephric mesenchyme. By contrast, BMP7 expression in the metanephric mesenchyme is dependent on proteoglycans and possibly Wnt signaling.

Animals↗

PubMed2002

Specific heparan sulfate structures involved in retinal axon targeting.

Heparan sulfate (HS), a structurally diverse molecule comprising distinct sequences of sulfated disaccharide units, is abundant in the developing brain and binds to axon guidance molecules. Addition of HS to the developing Xenopus optic pathway causes severe targeting errors yet it is not known how the structural diversity of this molecule relates to its role in axon guidance. We have used an in vivo brain assay to identify the structural characteristics of HS that induce aberrant axon targeting. Inhibiting sulfation of endogenous HS with chlorate causes axons to bypass their target, the tectum, and treatment with chemically modified heparins reveals that 2-O- and 6-O-sulfate groups have potent bypass-inducing activity. Experiments with purified heparin saccharides show that bypass-inducing activity correlates with distinct structures, particularly those containing a combination of 2-O- and 6-O-sulfate groups. Taken together the results indicate that specific sequences, rather than gross structural composition, are critical for activity. In situ hybridisation revealed that HS 6-O-sulfotransferase is regionally expressed along the border of the dorsal optic tract whereas 2-O-sulfotransferase is expressed broadly. Our results demonstrate that specific HS sequences are essential for regulating retinotectal axon targeting and suggest that regionalised biosynthesis of specific HS structures is important for guiding axons into the tectum.

Animals↗

PubMed2003

Endothelial inflammation: the role of differential expression of N-deacetylase/N-sulphotransferase enzymes in alteration of the immunological properties of heparan sulphate.

Heparan sulphate N-deacetylase/N-sulphotransferase (NDST) enzymes catalyse the reaction that initiates sulphation and subsequent modification of the oligosaccharide, heparan sulphate (HS). The extent and distribution of sulphate substitution on HS plays a vital role in regulation of the binding of a range of proteins, including IFN-gamma, several interleukins and most chemokines. In this study, the expression of NDST transcripts was found to be non-uniform between a range of cell types, suggesting that different cells produce characteristic HS species. It was found that stimulation of the HMEC-1 microvascular endothelial cell line with the pro-inflammatory cytokines IFN-gamma and TNF-alpha caused a transient decrease in the level of NDST-1 and -2 transcripts after 4 hours (P < 0.05 and P < 0.01 respectively), but the expression of NDST-1 increased above control levels after 16 hours (P < 0.01). The change in NDST expression was concurrent with an increase in the abundance of sulphated HS epitopes on the cell surface; this was not caused by variation in the expression of proteoglycans or by changes in the rate of GAG turnover. Cytokine-stimulated endothelial cells also showed an increase in their potential to bind RANTES (CCL5); this was abrogated by chlorate blockade of sulphotransferase activity or by heparitinase cleavage of cell surface HS. Monolayers of cytokine-stimulated HMEC-1 also supported an enhanced leukocyte chemotactic response towards RANTES. This study demonstrated that pro-inflammatory cytokines can increase NDST expression leading to increased sulphation of HS and a corresponding increase in sequestration of functional RANTES at the apical surface of endothelial cells. This may enhance leukocyte extravasation at sites of inflammation.

Amidohydrolases↗

PubMed1998

Analysis of CD44 interactions with hyaluronan in murine L cell fibroblasts deficient in glycosaminoglycan synthesis: a role for chondroitin sulfate.

CD44 is a widely expressed cell adhesion molecule that binds the extracellular matrix component, hyaluronan, in a tightly regulated manner. Previous studies have shown that the CD44-hyaluronan interaction is affected by changes in the glycosylation state of CD44. In this study, we take advantage of several well-characterized murine L cell mutants defective in heparan sulfate synthesis (gro2C cells), heparan sulfate and chondroitin sulfate synthesis (sog9 cells), and glycosaminoglycan and oligosaccharide processing (sog8 cells) to assess the effects of these defects on the hyaluronan binding ability of CD44. In parental L cells and gro2C cells, CD44 was induced to bind hyaluronan after addition of the activating, anti-CD44 monoclonal antibody, IRAWB 14. By contrast, no inducible binding was observed in sog9 cells. Treatment of L cells with sodium chlorate, an inhibitor of sulfation, also abolished inducible hyaluronan binding. However, inducible and some constitutive hyaluronan binding was observed in sog8 cells. This indicates that sulfation and, in particular, the addition of chondroitin sulfate are required for inducible hyaluronan binding by CD44 in L cells. However, in the absence of fully processed oligosaccharides, chondroitin sulfate is not essential for hyaluronan binding, indicating that the effect of chondroitin sulfate is dependent upon the glycosylation state of the cell. Thus, in addition to glycosylation, chondroitin sulfate biosynthesis is an important post-translational modification that can affect the hyaluronan binding ability of CD44.

3T3 Cells↗

PubMed2001

Chondroitin sulfate is involved in lysosomal transport of lysozyme in U937 cells.

Human promonocytes U937 synthesize lysozyme and retain approximately one third of it within lysosomes. Lysozyme is not glycosylated; thus, it cannot be subject to mannose-6-phosphate-dependent targeting to lysosomes. It is a basic protein with a pI of 10.5 and is known to interact with negatively charged macromolecules like proteoglycans. Therefore, we examined whether the latter are involved in the lysosomal targeting of lysozyme in U937 cells. We partially diminished the electronegative charge of newly synthesized proteoglycans by inhibiting their sulfation with chlorate. This increased the rate of secretion of lysozyme. Upon treatment of U937 cells with phorbol esters, the rate of secretion of lysozyme was increased to more than 90%. This coincided with an almost complete redistribution of a [(35)S]sulfate bearing proteoglycan to the secretory pathway. After a brief pulse with [(35)S]sulfate in the control, 80% of the [(35)S]sulfate-bearing proteoglycan was retained within the cells, whereas in the treated cells this proportion was decreased to 13%. The secreted proteoglycan was sensitive to chondroitinase ABC and bound to immobilized lysozyme. This interaction was disrupted by 50-300 mM NaCl. The intracellularly retained proteoglycan was degraded with a half-life of 50-60 minutes and seemed to be directed to lysosomes because in the presence of NH(4)Cl the degradation was strongly inhibited. Our results suggest that the proteoglycan is involved in lysosomal targeting of lysozyme in U937 cells.

Ammonium Chloride↗

PubMed1982

Health effects among newborns after prenatal exposure to ClO2-disinfected drinking water.

Because chlorination of potable surface waters may be associated with increased risk of carcinogenicity, substitute methods for the routine disinfection of public water supplies are being explored. As part of this search, it is especially important that the potential health effects of each alternative method should be considered. Chemical treatment of drinking water by chlorine dioxide (ClO2) is a likely alternative mode of disinfection. Two common by-products of the ClO2 disinfection of surface water are chlorate and chlorite. These oxidants may have negative health effects on certain high risk groups. Newborns, in particular, would seem to be at increased risk to red cell damage from oxidant stress. The historical record study being reported here compares the morbidity and mortality experience of newborns in two similar communities, one of which used chlorination and the other which used high levels of chlorine dioxide for potable water disinfection. A statistically significant positive association was found between exposure of the mother to ClO2-treated water during pregnancy and prematurity of the newborn as assessed by the attending physician and by a greater weight loss after birth. The rates of jaundice, birth defects and fetal and neonatal mortality did not differ significantly between communities. Because of the limitations of the study design, the findings reported here should be considered suggestive rather than definitive.

Adolescent↗

PubMed1982

Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate.

Subchronic toxicities of ClO2, NaClO2, NaClO3 and NH2Cl were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by ClO2; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaClO2 and NaClO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaClO4 or NH2Cl did not cause T-4 suppression in doses of 10 mg/kg/day. The selective thyroid effect of ClO2 was unexplained and it appeared to be paradoxical since ClO2 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested approximately 1 mg/l. of ClO2 in drinking water as a result of routine use in the community water treatment process. Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaClO2 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals.

Animals↗

PubMed2005

Standoff detection of high explosive materials at 50 meters in ambient light conditions using a small Raman instrument.

We have designed and demonstrated a standoff Raman system for detecting high explosive materials at distances up to 50 meters in ambient light conditions. In the system, light is collected using an 8-in. Schmidt-Cassegrain telescope fiber-coupled to an f/1.8 spectrograph with a gated intensified charge-coupled device (ICCD) detector. A frequency-doubled Nd : YAG (532 nm) pulsed (10 Hz) laser is used as the excitation source for measuring remote spectra of samples containing up to 8% explosive materials. The explosives RDX, TNT, and PETN as well as nitrate- and chlorate-containing materials were used to evaluate the performance of the system with samples placed at distances of 27 and 50 meters. Laser power studies were performed to determine the effects of laser heating and photodegradation on the samples. Raman signal levels were found to increase linearly with increasing laser energy up to approximately 3 x 10(6) W/cm2 for all samples except TNT, which showed some evidence of photo- or thermal degradation at higher laser power densities. Detector gate width studies showed that Raman spectra could be acquired in high levels of ambient light using a 10 microsecond gate width.

Environmental Monitoring↗

PubMed2025

Repair of oxidized methionine residues in the chaperone Spy maintains periplasmic proteostasis under chlorite stress in Escherichia coli.

The bacterial cell envelope is exposed to various stresses, including oxidative stress caused by different types of oxidants, such as reactive oxygen species (ROS) and reactive chlorine species (RCS). In Escherichia coli, the reduction of chlorate into chlorite, a toxic RCS compound, induces the expression of the MsrPQ system, which repairs periplasmic proteins oxidized at methionine residues (methionine sulfoxide, Met-O). In this study, using a proteomic-based approach, we show that chlorite stress also triggers the overproduction of the periplasmic molecular chaperone Spheroplast Protein Y (Spy). This response is mediated by the activation of the BaeSR two-component system. Furthermore, both in vivo and in vitro evidence reveal that Spy's susceptibility to oxidation is critical for its chaperone activity. We demonstrate that the MsrPQ repair system ensures Spy's functionality by reducing its Met-O, thereby safeguarding its role in periplasmic protein homeostasis. Overall, this work reveals Spy as a key target of chlorite-induced oxidative damage and underscores the essential role of MsrPQ in preserving periplasmic protein quality control.

Methionine↗

PubMed1975

Reduced ferredoxin: CO2 oxidoreductase from Clostridium pasteurianum. Effect of ligands to transition metals on the activity and the stability of the enzyme.

Reduced ferredoxin: CO2 oxidoreductase (CO2-reductase) from Clostridium pasteurianum catalyzes the reduction of CO2 to formate at the expense of reduced ferredoxin, an isotopic exchange between CO2 and formate in the absence of ferredoxin, and the oxidation of formate to CO2 with oxidized ferredoxin. The three activities were found to be equally affected by monovalent anions known to be ligands to transition metals: The enzyme was reversibly inhibited by azide (Ki = 0.004mM), cyanate (Ki = 0.3 mM), thiocyanate (Ki = 1mM), nitrite (Ki = 0.4mM), nitrate (Ki = 6mM), chlorate (Ki = 3mM), fluoride (Ki = 5mM), and by chloride, bromide, iodide (Ki greater than 5mM). There was no observable effect of pH on the inhibition constants. The enzyme was not inhibited by carbon monoxide. The enzyme was irreversibly inactivated by low concentrations (10muM) of cyanide. The rate of inactivation increased with increasing pH with an inflection point near pH 9.5. Reduced ferredoxin and formate rather than oxidized ferredoxin or CO2 protected the enzyme from inactivation by cyanide. The enzyme was protected by azide and cyanate from inactivation. In the presence of high concentrations of the monovalent anions the rate of inactivation by heat (55 degrees C), by molecular oxygen, and by cyanide was decreased by a factor of more than 100. Half maximal protection was observed at the Ki concentrations of the two reversible inhibitors. The data are interpreted to indicate that a transition metal of weak "a class" character and a disulfide are catalytically significant groups of CO2-reductase from C. pasteurianum.

Anions↗

PubMedDate not supplied

Assimilatory nitrate reductase of Rhodopseudomonas capsulata AD2: a molybdo-hemeprotein.

The assimilatory nitrate reductase of the phototrophic bacterium Rhodopseudomonas capsulata strain AD2 was purified to homogeneity by a combination of ammonium sulfate fractionation, chromatography on DEAE-cellulose and isoelectric focusing (isoelectric point of 4.8). The purified enzyme was active only with reduced viologen dyes or reduced flavin as electron donors. Contrary to other bacterial assimilatory nitrate reductases, the enzyme was not inhibited by chlorate, but rather accepted this substance as an alternate substrate. The molecular weight of the enzyme was 185,000 dalton as determined by gelfiltration. Subunit analysis by sodium dodecyl sulfate (SDS) gel electrophoresis yielded a single protein band with a molecular weight of 85,000 dalton,, suggesting that the enzyme was composed of two identical subunits. The nitrate reductase contained 0.8 g-atoms molybdenum per 1.85 x 10(5) g protein and exhibited absorption maxima at 418, 523 and 552 nm in the reduced state (dithionite as reductant). The nitrate reductase of Rps. capsulata AD2 is the first prokaryotic enzyme of the assimilatory type that has been shown to contain heme.

Hemeproteins↗

PubMed2005

Molecular analysis of microbial community in a groundwater sample polluted by landfill leachate and seawater.

Seashore landfill aquifers are environments of special physicochemical conditions (high organic load and high salinity), and microbes in leachate-polluted aquifers play a significant role for intrinsic bioremediation. In order to characterize microbial diversity and look for clues on the relationship between microbial community structure and hydrochemistry, a culture-independent examination of a typical groundwater sample obtained from a seashore landfill was conducted by sequence analysis of 16S rDNA clone library. Two sets of universal 16S rDNA primers were used to amplify DNA extracted from the groundwater so that problems arising from primer efficiency and specificity could be reduced. Of 74 clones randomly selected from the libraries, 30 contained unique sequences whose analysis showed that the majority of them belonged to bacteria (95.9%), with Proteobacteria (63.5%) being the dominant division. One archaeal sequence and one eukaryotic sequence were found as well. Bacterial sequences belonging to the following phylogenic groups were identified: Bacteroidetes (20.3%), beta, gamma, delta and epsilon-subdivisions of Proteobacteria (47.3%, 9.5%, 5.4% and 1.3%, respectively), Firmicutes (1.4%), Actinobacteria (2.7%), Cyanobacteria (2.7%). The percentages of Proteobacteria and Bacteroides in seawater were greater than those in the groundwater from a non-seashore landfill, indicating a possible influence of seawater. Quite a few sequences had close relatives in marine or hypersaline environments. Many sequences showed affiliations with microbes involved in anaerobic fermentation. The remarkable abundance of sequences related to (per)chlorate-reducing bacteria (ClRB) in the groundwater was significant and worthy of further study.

Bacteria↗

PubMed2003

Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue.

Methaemoglobin is formed by oxidation of ferrous (FeII) haem to the ferric (FeIII) state and the mechanisms by which this occurs are complex. Most cases are due to one of three processes. Firstly, direct oxidation of ferrohaemoglobin, which involves the transfer of electrons from ferrous haem to the oxidising compound. This mechanism proceeds most readily in the absence of oxygen. Secondly, indirect oxidation, a process of co-oxidation which requires haemoglobin-bound oxygen and is involved, for example, in nitrite-induced methaemoglobinaemia. Thirdly, biotransformation of a chemical to an active intermediate that initiates methaemoglobin formation by a variety of mechanisms. This is the means by which most aromatic compounds, such as amino- and nitro-derivatives of benzene, produce methaemoglobin. Methaemoglobinaemia is an uncommon occupational occurrence. Aromatic compounds are responsible for most cases, their lipophilic nature and volatility facilitating absorption during dermal and inhalational exposure, the principal routes implicated in the workplace. Methaemoglobinaemia presents clinically with symptoms and signs of tissue hypoxia. Concentrations around 80% are life-threatening. Features of toxicity may develop over hours or even days when exposure, whether by inhalation or repeated skin contact, is to relatively low concentrations of inducing chemical(s). Not all features observed in patients with methaemoglobinaemia are due to methaemoglobin formation. For example, the intravascular haemolysis caused by oxidising chemicals such as chlorates poses more risk to life than the methaemoglobinaemia that such chemicals induce. If an occupational history is taken, the diagnosis of methaemoglobinaemia should be relatively straightforward. In addition, two clinical observations may help: firstly, the victim is often less unwell than one would expect from the severity of 'cyanosis' and, secondly, the 'cyanosis' is unresponsive to oxygen therapy. Pulse oximetry is unreliable in the presence of methaemoglobinaemia. Arterial blood gas analysis is mandatory in severe poisoning and reveals normal partial pressures of oxygen (pO2) and carbon dioxide (pCO2,), a normal 'calculated' haemoglobin oxygen saturation, an increased methaemoglobin concentration and possibly a metabolic acidosis. Following decontamination, high-flow oxygen should be given to maximise oxygen carriage by remaining ferrous haem. No controlled trial of the efficacy of methylene blue has been performed but clinical experience suggests that methylene blue can increase the rate of methaemoglobin conversion to haemoglobin some 6-fold. Patients with features and/or methaemoglobin concentrations of 30-50%, should be administered methylene blue 1-2 mg/kg/bodyweight intravenously (the dose depending on the severity of the features), whereas those with methaemoglobin concentrations exceeding 50% should be given methylene blue 2 mg/kg intravenously. Symptomatic improvement usually occurs within 30 minutes and a second dose of methylene blue will be required in only very severe cases or if there is evidence of ongoing methaemoglobin formation. Methylene blue is less effective or ineffective in the presence of glucose-6-phosphate dehydrogenase deficiency since its antidotal action is dependent on nicotinamide-adenine dinucleotide phosphate (NADP+). In addition, methylene blue is most effective in intact erythrocytes; efficacy is reduced in the presence of haemolysis. Moreover, in the presence of haemolysis, high dose methylene blue (20-30 mg/kg) can itself initiate methaemoglobin formation. Supplemental antioxidants such as ascorbic acid (vitamin C), N-acetylcysteine and tocopherol (vitamin E) have been used as adjuvants or alternatives to methylene blue with no confirmed benefit. Exchange transfusion may have a role in the management of severe haemolysis or in G-6-P-D deficiency associated with life-threatening methaemoglobinaemia where methylene blue is relatively contraindicated.

Enzyme Inhibitors↗

PubMed2006

Preharvest control of Escherichia coli O157 in cattle.

Bovine manure is an important source of Escherichia coli O157 contamination of the environment and foods; therefore, effective interventions targeted at reducing the prevalence and magnitude of fecal E. coli O157 excretion by live cattle (preharvest) are desirable. Preharvest intervention methods can be grouped into 3 categories: 1) exposure reduction strategies, 2) exclusion strategies, and 3) direct antipathogen strategies. Exposure reduction involves environmental management targeted at reducing bovine exposure to E. coli O157 through biosecurity and environmental niche management such as feed and drinking water hygiene, reduced exposure to insects or wildlife, and improved cleanliness of the bedding or pen floor. In the category of exclusion, we group vaccination and dietary modifications such as selection of specific feed components; feeding of prebiotics, probiotics, or both; and supplementation with competitive exclusion cultures to limit proliferation of E. coli O157 in or on exposed animals. Direct antipathogen strategies include treatment with sodium chlorate, antibiotics, bacteriophages, in addition to washing of animals before slaughter. Presently, only 1 preharvest control for E. coli O157 in cattle has been effective and has gained widespread adoption-the feeding probiotic Lactobacillus acidophilus. More research into the effectiveness of parallel and simultaneous application of 1 or more preharvest control strategies, as well as the identification of new pre-harvest control methods, may provide practical means to substantially reduce the incidence of human E. coli O157-related illness by intervening at the farm level.

Animal Feed↗

PubMed1978

A comparison of iron histochemical methods for use on glycol methacrylate embedded tissues.

Four histochemical tests for iron and four procedures for its removal were investigated in regard to their suitability for glycol methacrylate embedded tissues. The HCl-ferrocyanide and chlorate hematoxylin methods were easily modified for plastic sections. The latter does not use iron-containing reagents. Desiderization was complete both after a fifteen minute exposure in 1% Na2S2O4 in 0.1 M acetate-HCl buffer (pH 4.5) and, if an acid method is preferred, after twelve hours in 5% oxalic acid. A six hour treatment in 3.7 N H2SO4 also removed all histochemical iron but was accompanied by a relatively greater loss of tissue basophilia.

Animals↗

PubMed1996

Suicidal chloral hydrate poisoning.

BACKGROUND: The cumulative reports of chlorate hydrate toxicity suggest an unacceptable risk for this commonly used sleep aid. CASE REPORT: A 29-year-old male was admitted after ingestion of 70 g of chloral hydrate. He was hypotensive and hypothermic. Spontaneous respiration was insufficient. Fluid resuscitation did not restore adequate blood pressure levels. Low dose catecholamine infusion resulted in ventricular arrhythmias. The patient was treated with combined hemoperfusion and hemodialysis during an eight hour period. During this time, serum concentrations of trichlorethanol fell. Blood pressure and heart rate increased and consciousness was regained without signs of neurological deficits. CONCLUSIONS: Although outcome was favorable, this case report illustrates the potentially high acute toxicity of chloral hydrate and supports its removal from the market.

Adult↗