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The World Health Organization (WHO) has supported several pilot studies to assess the feasibility of improved pesticide storage to prevent pesticide self-poisoning [[6]]. Effectiveness of household lockable pesticide storage to reduce pesticide self-poisoning in rural Asia: a community-based, cluster-randomised controlled trial. [Extracted from the article]

Background: Although Pichia pastoris has been successfully used to produce various recombinant heterologous proteins, the efficiency varies. In this study, we used methyl parathion hydrolase (MPH) from Ochrobactrum sp. M231 as an example to study the effect of protein amino acid sequence on secretion from P. pastoris. Results: The results indicated that the protein N-terminal sequence, the endoplasmic reticulum (ER) retention signal (KKXX) at the protein C-terminus, and the acidic stability of the protein could affect its secretion from P. pastoris. Mutations designed based on these sequence features markedly improved secretion from P. pastoris. In addition, we found that the secretion properties of a protein can be cumulative when all of the above strategies are combined. The final mutant (CHBD-DQR) designed by combining all of the strategies greatly improved secretion and the secreted MPH activity of CHBD-DQR was enhanced up to 195-fold compared with wild-type MPH without loss of catalytic efficiency. Conclusions: These results demonstrate that the secretion of heterologous proteins from P. pastoris could be improved by combining changes in multiple protein sequence features. [ABSTRACT FROM AUTHOR]

The article presents a study focusing on identification of the para-nitrophenol (PNP) catabolic pathway, and enzymes involved in the hydroquinone pathway, in pseudomonas sp. 1-7. The study showed that pseudomonas was isolated from methyl parathion (MP)-polluted activated sludge and resulted in degradation of PNP.

Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (∼80%) and down-regulation of M1 and M2 muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat’s locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed. [ABSTRACT FROM AUTHOR]

Assessment of the risks posed by the residential use of methyl parathion requires an understanding of its pharmacokinetics after different routes of exposure. Thus, studies were performed using adult female rats to define the pharmacokinetic parameters for methyl parathion after intravenous injection and to apply the described model to an examination of its pharmacokinetics after single oral or dermal exposure. The pharmacokinetics of methyl parathion after intravenous administration (1.5 mg/kg) were best described by a three-compartment model; the apparent volume of the central compartment was 1.45 liters/kg, clearance was 1.85 liters/h/kg and the terminal half-life was 6.6 h with an elimination constant of 0.50 h[sup –1] . The apparent oral absorption coefficient for methyl parathion (1.5 mg/kg) was 1.24 h[sup –1] , and its oral bioavailability was approximately 20%. The latter likely includes a significant first pass effect. Concentrations of methyl parathion increased during the initial 10–60 min and then declined during the next 15–36 h. After dermal administration (6.25–25 mg/kg), methyl parathion concentrations peaked within 12–26 h and then declined dose dependently. The apparent dermal absorption coefficient was approximately 0.41 h[sup –1] , and only two pharmacokinetic compartments could be distinguished. In conclusion, the pharmacokinetics of methyl parathion are complex and route dependent. Also, dermal exposure, because of sustained methyl parathion concentrations, may pose the greatest risk.Copyright © 2002 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30–48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37°C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (≥6 h) and was prolonged (≥48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects.Copyright © 2002 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD[sub 50] ) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1–3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory.Copyright © 2001 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Bacillus subtilis is developed to be an attractive expression host to produce both secreted and cytoplasmic proteins owing to its prominent biological characteristics. Chromosomal integration is a stable expression strategy while the expression level is not ideal compared with plasmid expression. Thus, to meet the requirement of protein overexpression, promoter, as one of the key elements, is important. It is necessary to obtain an ideal promoter for overproduction of foreign proteins from a single copy expression cassette. Results: The activity of promoter Pylb was further enhanced by optimizing the − 35, − 10 core region and upstream sequence (UP) by substituting both sequences with consensus sequences. The final engineered promoter exhibited almost 26-fold in β-galactosidase (BgaB) activity and 195-fold in super-folded green fluorescent protein (sfGFP) intensity than that of WT. The two proteins account for 43% and 30% of intracellular proteins, respectively. The promoter was eventually tested by successful extracellular overproduction of Methyl Parathion Hydrolase (MPH) and Chlorothalonil hydrolytic dehalogenase (Chd) to a level of 0.3 g/L (144 U/mL) and 0.27 g/L (4.4 U/mL) on shake-flask culture condition. Conclusions: A strong promoter was engineered for efficient chromosomally integrated expression of heterologous proteins. [ABSTRACT FROM AUTHOR]