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Applied and Environmental Microbiology Aug 2021Rice is an important source of food for more than half of the world's population. Bacterial panicle blight (BPB) is a disease of rice characterized by grain...
Rice is an important source of food for more than half of the world's population. Bacterial panicle blight (BPB) is a disease of rice characterized by grain discoloration or sheath rot caused mainly by Burkholderia glumae. B. glumae synthesizes toxoflavin, an essential virulence factor that is required for symptoms of the disease. The products of the operons, ToxABCDE and ToxFGHI, are responsible for the synthesis and the proton motive force (PMF)-dependent secretion of toxoflavin, respectively. The DedA family is a highly conserved membrane protein family found in most bacterial genomes that likely function as membrane transporters. Our previous work has demonstrated that absence of certain DedA family members results in pleiotropic effects, impacting multiple pathways that are energized by PMF. We have demonstrated that a member of the DedA family from Burkholderia thailandensis, named DbcA, is required for the extreme polymyxin resistance observed in this organism. B. glumae encodes a homolog of DbcA with 73% amino acid identity to Burkholderia thailandensis DbcA. Here, we created and characterized a B. glumae Δ strain. In addition to polymyxin sensitivity, the B. glumae Δ strain is compromised for virulence in several BPB infection models and secretes only low amounts of toxoflavin (∼15% of wild-type levels). Changes in membrane potential in the B. glumae Δ strain were reproduced in the wild-type strain by the addition of subinhibitory concentrations of sodium bicarbonate, previously demonstrated to cause disruption of PMF. Sodium bicarbonate inhibited B. glumae virulence in rice, suggesting a possible non-toxic chemical intervention for bacterial panicle blight. Bacterial panicle blight (BPB) is a disease of rice characterized by grain discoloration or sheath rot caused mainly by Burkholderia glumae. The DedA family is a highly conserved membrane protein family found in most bacterial genomes that likely function as membrane transporters. Here, we constructed a B. glumae mutant with a deletion in a DedA family member named and report a loss of virulence in models of BPB. Physiological analysis of the mutant shows that the proton motive force is disrupted, leading to reduction of secretion of the essential virulence factor toxoflavin. The mutant phenotypes are reproduced in the virulent wild-type strain without an effect on growth using sodium bicarbonate, a nontoxic buffer that has been reported to disrupt the PMF. The results presented here suggest that bicarbonate may be an effective antivirulence agent capable of controlling BPB without imposing an undue burden on the environment.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Burkholderia; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Onions; Oryza; Plant Diseases; Proton-Motive Force; Pyrimidinones; Sodium Bicarbonate; Triazines; Virulence; Virulence Factors
PubMed: 34260305
DOI: 10.1128/AEM.00915-21 -
Archives of Razi Institute Jul 2021The present study aimed to assess the effect of tissue hypoxia induced by sodium cyanide (NaCN) on male mice fertility and the protective role of ethyl pyruvate (EP). A...
The present study aimed to assess the effect of tissue hypoxia induced by sodium cyanide (NaCN) on male mice fertility and the protective role of ethyl pyruvate (EP). A number of 30 adult mice were assigned to three groups: 1) a control group, 2) a treatment group treated with 2 mg/kg of NaCN, and 3) a treatment group treated with 2 mg/kg of NaCN, along with 40 mg/kg EP (NaCN+EP). After 35 days, animals were anesthetized and serum, sperm, and tissue samples were taken. The results demonstrated a significant decrease in sperm quality, reproduction potency, and anti-oxidant potential, as well as an increase in lipid peroxidation in the NaCN group (p <0.05). Moreover, the use of EP effectively restrained the disastrous effects of tissue hypoxia. It can be concluded that EP can moderate the complications resulting from tissue-hypoxia that is related to testes parameters.
Topics: Animals; Male; Mice; Hypoxia; Pyruvates; Reproduction; Sodium Cyanide
PubMed: 34223731
DOI: 10.22092/ari.2020.126806.1362 -
Toxins Jun 2021Cultures of the mussel are frequently affected by accumulation of the amnesic shellfish poisoning toxin domoic acid (DA). This species is characterized by a fast uptake...
Cultures of the mussel are frequently affected by accumulation of the amnesic shellfish poisoning toxin domoic acid (DA). This species is characterized by a fast uptake and release of the toxin. In this work, the main characteristics of the uptake mechanism have been studied by incubation of digestive gland thin slices in media with different composition and DA concentration. DA uptake seems to follow Michaelis-Menten kinetics, with a very high estimated K (1722 µg DA mL) and a V of 71.9 µg DA g h, which is similar to those found for other amino acids in invertebrates. Replacement of NaCl from the incubation media by Cl-choline (Na-free medium) did not significantly reduce the uptake, but replacement by sorbitol (Na-free and Cl-depleted medium) did. A new experiment replacing all chlorides with their equivalent gluconates (Na- and Cl-free medium) showed an important reduction in the uptake that should be attributed to the absence of chloride, pointing to a Na-independent, Cl (or anion-) dependent transporter. In media with Na and Cl, neither decreasing the pH nor adding cyanide (a metabolic inhibitor) had significant effect on DA uptake, suggesting that the transport mechanism is not H- or ATP-dependent. In a chloride depleted medium, lowering pH or adding CN increased the uptake, suggesting that other anions could, at least partially, substitute chloride.
Topics: Animals; Chlorides; Cyanides; Gastrointestinal Tract; Gluconates; Hydrogen-Ion Concentration; Kainic Acid; Mytilus; Seawater
PubMed: 34208992
DOI: 10.3390/toxins13070458 -
International Journal of Molecular... Jun 2021Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the... (Review)
Review
Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from HS, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.
Topics: Animals; Gastrointestinal Hormones; Humans; Hydrogen Sulfide; Metabolic Networks and Pathways; Oxidation-Reduction; Reperfusion Injury; Thiosulfates
PubMed: 34208631
DOI: 10.3390/ijms22126452 -
Drugs in Context 2021Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration... (Review)
Review
BACKGROUND
Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration of an antidote specific for the poison is essential for the management of children with suspected poisoning. This is a narrative review on antidotes for toxidromes in paediatric practice.
METHODS
A literature search was conducted on PubMed with the keywords "antidote", "poisoning", "intoxication", "children" and "pediatric". The search was customized by applying the appropriate filters (species: humans; age: birth to 18 years) to obtain the most relevant articles for this review article.
RESULTS
Toxidrome recognition may offer a rapid guide to possible toxicology diagnosis such that the specific antidote can be administered in a timely manner. This article summarizes toxidromes and their respective antidotes in paediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are discussed. Antidotes are only available for a limited number of poisons responsible for intoxication. Antidotes for common poisonings include N-acetyl cysteine for paracetamol and sodium thiosulphate for poisoning by cyanide.
CONCLUSION
Poisoning is a common cause of paediatric injury. Physicians should be familiar with the recognition of common toxidromes and promptly use specific antidotes for the management of childhood toxidromes.
PubMed: 34122588
DOI: 10.7573/dic.2020-11-4 -
Journal of Environmental & Analytical... Feb 2021In 2006, the Agency for Toxic Substances and Disease Registry received a request to determine whether a cluster of polycythemia vera patients existed in a northeast...
In 2006, the Agency for Toxic Substances and Disease Registry received a request to determine whether a cluster of polycythemia vera patients existed in a northeast Pennsylvania community. A significant cluster of PV cases was identified at the nexus of three counties near several hazardous waste sites. The current study evaluated the potential for a select number of environmental contaminants previously detected in the cluster area to induce DNA damage using assays with hematopoietic stem-cell derived progenitor cells. CD34+ cells were isolated from normal cord blood samples and were cultured for 48-72 hours to generate erythroid progenitor cells. Eighteen compounds were chosen for the assay; arsenic trioxide, benzo(a)pyrene, benzene, methylene chloride, 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), trichloroethylene, potassium chloride, ethylbenzene, benzo[k]fluoranthene, styrene, cadmium chloride, hydroquinone, 1,1,1-trichloroethane, sodium cyanide, manganese chloride, chromium oxide, lead oxide, and sodium arsenite. Genotoxicity of the compounds was determined using the comet assay, and toxicity determined via the cell viability assay. Using the comet assay, 16 compounds at 10 nM concentration, induced a significant amount of DNA damage compared to the control. When evaluating whether a dose-dependent relationship was present, seventeen of the eighteen compounds led to greater DNA damage with increasing exposure concentrations. 2,3,7,8-TCDD was particularly potent, inducing DNA damage in virtually all cells at 1 μM. In conclusion, most of the toxins evaluated using the comet assay showed potential to induce DNA damage in hematopoietic cells, and the genotoxic effects were dose-dependent.
PubMed: 34094707
DOI: 10.4172/2161-0525.1000551 -
PeerJ 2021Rubber () is a perennial plant crop grown in many parts of Africa, South East Asia, and South America, especially within the hot and humid climatic regions. Rubber seed,...
Rubber () is a perennial plant crop grown in many parts of Africa, South East Asia, and South America, especially within the hot and humid climatic regions. Rubber seed, either as feed or food, is a useful raw material to produce edible oil and protein. Despite the huge quantity of rubber seeds produced in Nigeria and its potential as a protein source, rubber seeds still appear neglected and under-utilised as feed/food given its perception as inedible and toxic due to the high concentration of cyanogenic glycoside. Therefore, the quest for effective processing technique(s) that would enhance its food use application is very fitting. This current study was directed to determine the changes in anti-nutrient, phytochemical, and micronutrient contents of different processed rubber seed meals. Specifically, the rubber seeds underwent processing, which employed boiling and the combined action of boiling and fermentation methods that brought about three seed meal flour groups, i.e., raw (RRSM), boiled (BRSM), and fermented (FRSM) seed meals. These were subsequently analysed for anti-nutrient/phytochemical (oxalate, phytate, tannin, phenols, saponin, hydrogen cyanide (HCN), alkaloids, flavonoids, and trypsin inhibitors), and micronutrient (which involved minerals (magnesium, phosphorus, calcium, iron, zinc, potassium, sodium, manganese, lead, and selenium) and vitamin (vitamin B1, B2, B3, C, E, and beta carotene)) contents. The results showed that the processing methods used to achieve the RRSM, BRSM, and FRSM, reduced the anti-nutrients (phytate, tannin, and oxalate) below the acceptable limits, and the HCN below the toxic levels. Importantly, the processing methods herein have not yet succeeded in removing HCN in the (processed) rubber seed meals, but can be seen to be heading toward the right direction. The FRSM obtained significantly lower ( < 0.05) anti-nutrient/phytochemical, but significantly higher ( < 0.05) mineral contents, compared with the other groups (RRSM and BRSM), except for flavonoids that obtained a 30% increase over the BRSM. Some mineral and vitamin contents could be lost in the BRSM compared to the others (RRSM and FRSM) in this study. Additionally, the FRSM obtained higher vitamin contents, after those of RRSM. Overall, the combined action of boiling and fermentation should be recommended for the proper utilisation of rubber seed as food/feed.
PubMed: 34055479
DOI: 10.7717/peerj.11327 -
Frontiers in Pharmacology 2021Hypertension contributes to cardiac damage and remodeling. Despite the availability of renin-angiotensin system inhibitors and other antihypertensive therapies, some...
Hypertension contributes to cardiac damage and remodeling. Despite the availability of renin-angiotensin system inhibitors and other antihypertensive therapies, some patients still develop heart failure. Novel therapeutic approaches are required that are effective and without major adverse effects. Sodium Thiosulfate (STS), a reversible oxidation product of hydrogen sulfide (HS), is a promising pharmacological entity with vasodilator and anti-oxidant potential that is clinically approved for the treatment of calciphylaxis and cyanide poisoning. We hypothesized that Sodium Thiosulfate improves cardiac disease in an experimental hypertension model and sought to investigate its cardioprotective effects by direct comparison to the ACE-inhibitor lisinopril, alone and in combination, using a rat model of chronic nitric oxide (NO) deficiency. Systemic nitric oxide production was inhibited in Sprague Dawley rats by administering N-ω-nitro-l-arginine (L-NNA) with the food for three weeks, leading to progressive hypertension, cardiac dysfunction and remodeling. We observed that STS, orally administered the drinking water, ameliorated L-NNA-induced heart disease. Treatment with STS for two weeks ameliorated hypertension and improved systolic function, left ventricular hypertrophy, cardiac fibrosis and oxidative stress, without causing metabolic acidosis as is sometimes observed following parenteral administration of this drug. STS and lisinopril had similar protective effects that were not additive when combined. Our findings indicate that oral intervention with a HS donor such as STS has cardioprotective properties without noticeable side effects.
PubMed: 33935760
DOI: 10.3389/fphar.2021.650968 -
Journal of Dental Research, Dental... 2021This study evaluated the incorporation of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), calcium sodium phosphosilicate bioactive glass (BAG), chitosan...
This study evaluated the incorporation of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), calcium sodium phosphosilicate bioactive glass (BAG), chitosan (CH), and methacryloyloxydodecylpyridinium bromide (MDPB) on the compressive and flexural strength, fluoride (F ) release, and bacterial adhesion of conventional glass-ionomer cement (C-GIC). Modifications were implemented by adding CPP-ACP, BAG, and CH to the glass powder, while MDPB-GIC was prepared by incorporating MDPB to the liquid of C-GIC. Custom-made molds were used for specimen preparation. Compressive and flexural strengths were evaluated using a universal testing machine. F release was calculated with Erichrome cyanide reagent, using UV-spectrophotometry, at two time intervals of 24 hours and seven days. For bacterial adhesion, the test specimens were exposed to the bacterial suspension of and for 4 hours, and the adherent bacteria were quantified using colorimetry as the optical density (OD). The incorporation of MDPB increased the flexural strength of C-GIC, with no effect on its compressive strength. CH significantly improved the compressive and flexural strength; modifications with CPP-ACP, BAG, and MDPB significantly improved the flexural strength of C-GIC. While MDPB-GIC released significantly higher F at 24 hours, CPP-ACP- and BAG-modified GICs were comparable to C-GIC on day 7. C-GIC exhibited the highest bacterial adhesion, and MDPB-GIC showed the least. The data were analyzed with one-way (ANOVA), and pairwise comparisons were made with Tukey HSD tests. Hence, it can be concluded that the incorporation of CPP-ACP, BAG, and CH improved the mechanical properties of C-GIC, whereas MDPB improved the resistance of C-GIC to bacterial adhesion.
PubMed: 33927836
DOI: 10.34172/joddd.2021.004