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Toxins Jun 2016Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and...
Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N',N'-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin.
Topics: Aflatoxins; Arachis; Aspergillus; Chelating Agents; Ethylenediamines; Seeds; Transcription Factors; Unithiol; Zinc
PubMed: 27271668
DOI: 10.3390/toxins8060171 -
Scientific Reports May 2016Local changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces...
Local changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. membranes) would therefore constitute an important pillar towards a physical mechanism of biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physicochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification and propagate - in analogy to sound - at velocities controlled by the interface's compressibility. With transient local pH changes of 0.6 directly observed at the interface and velocities up to 1.4 m/s this represents hitherto the fastest protonic communication observed. Furthermore simultaneously propagating mechanical and electrical changes in the lipid interface are detected, exposing the thermodynamic nature of these pulses. Finally, these pulses are excitable only beyond a threshold for protonation, determined by the pKa of the lipid head groups. This protonation-transition plus the existence of an enzymatic pH-optimum offer a physical basis for intra- and intercellular signaling via sound waves at interfaces, where not molecular structure and mechano-enyzmatic couplings, but interface thermodynamics and thermodynamic transitions are the origin of the observations.
Topics: Acoustics; Hydrogen-Ion Concentration; Lipids; Protons; Signal Transduction; Static Electricity; Thermodynamics; Unilamellar Liposomes; Unithiol
PubMed: 27216038
DOI: 10.1038/srep22874 -
Middle East Journal of Digestive... Jan 2016A 19-year-old woman was referred to the Emergency Surgery Department with severe abdominal pain, icterus, and anemia. The patient's clinical and paraclinical findings in...
A 19-year-old woman was referred to the Emergency Surgery Department with severe abdominal pain, icterus, and anemia. The patient's clinical and paraclinical findings in addition to her occupational and social history, convinced us to assay blood lead level (BLL), which was 41/5 μg/dL. Therefore toxicology consult was performed to treat lead toxicity. Recheck of the BLL showed the level as 53/7 μg/dL. So oral chelator with succimer was started. Despite consumption of oral chelator, there was no response and the pain continued. Because our repeated evaluations were negative, we decided to re-treat lead poisoning by intravenous and intramuscular chelators. Dimercaprol (BAL) + calcium EDTA was started, and after 5 days, the pain relieved dramatically and the patient was discharged. We recommend more liberal lead poisoning therapy in symptomatic patients, and also suggest parenteral chelator therapy, which is more potent, instead of oral chelators in patients with severe symptoms.
PubMed: 26933485
DOI: 10.15171/mejdd.2016.10 -
Indian Journal of Nuclear Medicine :... 2015Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal chelating moiety in variety of conditions. In nuclear medicine itself two types of Tc-99m DMSA... (Review)
Review
Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal chelating moiety in variety of conditions. In nuclear medicine itself two types of Tc-99m DMSA complexes are used, trivalent and pentavalent forms. In this review, we have discussed the mechanism of uptake of both complexes as well as diagnostic and therapeutic application in a clinical scenario.
PubMed: 26430311
DOI: 10.4103/0972-3919.164015 -
Scientific Reports Sep 2015Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse...
Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy, and offer a new alternative way to modulate autophagy.
Topics: Adenine; Autophagy; Carboxylic Acids; Cell Line, Tumor; Citrates; Gold; HeLa Cells; Humans; Lysosomal Membrane Proteins; Metal Nanoparticles; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Silver; Sodium Citrate; Succimer; Surface Properties; Suspensions; Unithiol; Up-Regulation
PubMed: 26394839
DOI: 10.1038/srep14361 -
Journal of Pediatric Intensive Care Sep 2015Inhalation of mercury vapor is an uncommon cause of acute respiratory distress syndrome. It may go unnoticed if appropriate environmental/occupational history is not...
Inhalation of mercury vapor is an uncommon cause of acute respiratory distress syndrome. It may go unnoticed if appropriate environmental/occupational history is not taken. A 2-year-old child presented with severe respiratory distress and progressed to develop acute respiratory distress syndrome, necessitating high-pressure mechanical ventilation. On detailed enquiry, history of exposure to mercury fumes was obtained (at home), during gold extraction by the father. Diagnosis of mercury poisoning was confirmed by blood levels, and despite treatment with dimercaprol (mercury chelator) and high-frequency ventilation, the child subsequently succumbed within 26 hours. This case reiterates the need for awareness regarding unusual environmental toxic exposures and need for stricter regulations for sale or use of toxic products.
PubMed: 31110868
DOI: 10.1055/s-0035-1559826 -
Journal of Medical Toxicology :... Dec 2015Lead encephalopathy is a severe manifestation of lead poisoning that can present with altered mental status and seizures and has been associated with illicit moonshine...
BACKGROUND
Lead encephalopathy is a severe manifestation of lead poisoning that can present with altered mental status and seizures and has been associated with illicit moonshine consumption. Lead encephalopathy has traditionally been treated using dimercaprol (British anti-Lewisite, BAL) and calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA).
CASE REPORT
We describe a patient with lead encephalopathy related to lead-contaminated moonshine consumption, who was treated using dimercaptosuccinic acid (DMSA) due to a national shortage of CaNa2EDTA. A 66-year-old woman presented to a hospital with headache, irritability, and altered mental status. On hospital day 16, she was found to have a whole blood lead concentration of 148.2 μg/dL and a 24-h urine lead concentration of 232 μg/day. Due to a national shortage of CaNa2EDTA, the patient was given one dose of BAL and then started on DMSA via nasogastric tube. She dramatically improved over 4 days and was subsequently transitioned to oral DMSA and outpatient treatment. One day prior to discharge, her whole blood lead concentration was 47.2 μg/dL and her mental status was normal. DMSA was used in lieu of CaNa2EDTA to treat the patient with lead encephalopathy. The patient subsequently experienced clinical improvement and declining whole blood level concentrations.
CONCLUSION
Further prospective studies are needed to compare the efficacy of DMSA versus CaNa2EDTA in patients with lead encephalopathy.
Topics: Aged; Brain Diseases; Female; Food Contamination; Humans; Lead Poisoning; Succimer
PubMed: 26245877
DOI: 10.1007/s13181-015-0493-9 -
Annals of Indian Academy of Neurology 2015Tremors are reported as the most frequent neurological manifestation of Wilson's disease (WD) in some series. Postural tremors, rest tremors, action tremors and...
Tremors are reported as the most frequent neurological manifestation of Wilson's disease (WD) in some series. Postural tremors, rest tremors, action tremors and wing-beating (rubral) tremors are the different types of tremors seen in WD. We report a patient of WD with unilateral rubral tremors refractory to 1-year therapy with Penicillamine and anti-tremor medications. The tremors decreased considerably after adding chelation therapy with dimercaprol. Combination of Penicillamine and dimercaprol is an effective decoppering measure in rubral tremors of WD.
PubMed: 25745328
DOI: 10.4103/0972-2327.144286 -
Journal of Advanced Pharmaceutical... 2015Acne vulgaris is a chronic inflammatory disease, and its treatment is challenging due to the multifactorial etiology and emergence of antibiotic-resistant...
Acne vulgaris is a chronic inflammatory disease, and its treatment is challenging due to the multifactorial etiology and emergence of antibiotic-resistant Propionibacterium acnes strains. This study was focused to reduce antibiotics usage and find an alternate therapeutic source for treating acne. Lipid extracts of six Chlorella species were tested for inhibition of lipase, reactive oxygen species (ROS) production, cytokine production using P. acnes (Microbial Type Culture Collection 1951). Lipase inhibitory assay was determined by dimercaprol Tributyrate - 5, 5'- dithiobis 2-nitrobenzoic acid method and ROS production assay was performed using nitro-blue tetrazolium test. The anti-inflammatory activity of algal lipid extracts was determined by in vitro screening method based on inhibition of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) produced by human peripheral blood mononuclear cells. Minimum inhibitory concentration (MIC) values of lipid extracts were determined by microdilution method, and the fatty acid methyl esters (FAME) were analyzed by gas chromatography-mass spectroscopy. Chlorella ellipsoidea has the highest lipase inhibitory activity with 61.73% inhibition, followed by Chlorella vulgaris (60.31%) and Chlorella protothecoides (58.9%). Lipid extracts from C. protothecoides and C. ellipsoidea has significantly reduced the ROS production by 61.27% and 58.34% respectively. Inhibition of pro-inflammatory cytokines TNF-α showed the inhibition ranging from 58.39% to 78.67%. C. vulgaris has exhibited the MICvalue of 10 μg/ml followed by C. ellipsoidea, C. protothecoides and Chlorella pyrenoidosa (20 μg/ml). FAME analysis detected 19 fatty acids of which 5 were saturated fatty acids, and 14 were unsaturated fatty acids ranging from C14 to C24. The results suggest that lipid extracts of Chlorella species has significant inhibitory activity on P. acnes by inhibiting lipase activity. Further, anti-inflammatory reaction caused by the pathogen could be reduced by the inhibiting the production of ROS and inflammatory mediators TNF-α and exposes new frontiers on the antiacne activities of Chlorella lipid extracts.
PubMed: 25709963
DOI: 10.4103/2231-4040.150364 -
Indian Journal of Critical Care... Nov 2014Hexavalent chromium compounds are most commonly used in printing, dyeing, plastics and rayon manufacturing. Poisoning in children by ammonium dichromate, an odorless and...
Hexavalent chromium compounds are most commonly used in printing, dyeing, plastics and rayon manufacturing. Poisoning in children by ammonium dichromate, an odorless and bright orange-red crystal, are rarely reported. Acute poisoning will result in death due to multi-organ failure. The target organs that are affected by this poison are the respiratory system, kidneys, liver, eyes and skin. On ingestion, initially there is a relative lack of severe symptoms and signs. Hence, the delay in seeking medical attention could lead to the increased rate of mortality. In this case study, we report the ingestion of ammonium dichromate by a child. Despite appropriate management, such as hepatic supportive measures and plasma transfusion, the toxicity progressed to multi-organ failure and death.
PubMed: 25425845
DOI: 10.4103/0972-5229.144024