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Aim: The study aimed at evaluating the concentration levels of organochlorine pollutants in donkey milk and their modulation on the intestinal strongyle infection. Risk evaluation for consumer health was also investigated., Methods: We analyzed milk of grazing donkeys living in areas of Southern of Italy affected by organochlorine compounds environmental pollution and parasite infection. The presence of pollutants was assessed through summary statistics; regression analysis of intestinal strongyle on pollutant concentration was performed to investigate the relationship between the two variables., Results: PCB concentrations (mainly non-dioxin-like (ndl)-PCBs) were higher than OCP ones. Mean values of ndl-PCBs across areas ranged from 93.13 to 263.64 ng g -1 . In all sample units we detected the six indicator PCBs with the prevalence of the PCB 153, followed by the PCB 28 and the PCB 101. Among the dioxin-like (dl)-PCBs, non-ortho PCB 169, 77 and 126 were assessed in some milk samples; in all areas we detected the mono-ortho PCB 118 and PCB 105. Positive correlation between infection level and six indicator PCBs as well as between the former and HCB, on WW and LW, were observed (at least statistically significant at 5 percent). In some cases, Dl-PCB concentrations emerged as dangerous given the EU maximum residue limit for PCDD/Fs and dl-PCBs., Conclusion: Evidence supports the hypothesis of an immunosuppressive role of organochlorine pollutants; risk evaluation reveals the potential health impact of dl-PCB intake, particularly for major donkey milk consumers such as infants, children with cow milk and multiple food intolerance, and elders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: The cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development., Main Methods: Mice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults)., Key Findings: Plasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides., Significance: The additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The immunostimulating and therapeutic properties of Ginkgo biloba (GB) have always been the focus of traditional medicine over thousands of years. During last decade, special attentions were paid to use of GB in aquaculture to enhance fish health and survival. In the present study, we investigated for the first time the immunogenic effects of dietary GB against oxidative and toxicity induced by organophosphate pesticide, diazinon. In non-diazinon-exposed fish, the plasma total immunoglobulin, lysozyme activity, and peroxidase activity significantly elevated after 60-day experiment in fish supplemented with 1 and 2 g GB/kg diet (p < 0.05). The respiratory burst activity and complement activity significantly increased only in groups supplemented with 0.5 g GB/kg diet (p < 0.05). Furthermore, the peroxidase activity, total immunoglobulin, and lysozyme activity significantly declined in groups supplemented with 4 g GB/kg diet during feeding trial (p < 0.05). There were no significant differences in expression of interleukin 1 beta (IL-1β) and transforming growth factor beta 1 (TGF-β1) genes in kidney between control group (non-GB-supplemented fish) and GB-supplemented fish (p > 0.05). In diazinon-exposed fish, all immunity components significantly decreased during exposure in control and those fed 0.5 and 4 g GB/kg diet (p < 0.05). In fish fed 1 and 2 g GB/kg diet, no alternations were found in immunity components during exposure period (p > 0.05). In addition, diazinon induced the expression of IL-1β and TGF-β1 genes in control and fish fed 0.5 and 4 g GB/kg diet (p < 0.05). No significant changes were observed in expression of IL-1β and TGF-β1 genes in fish supplemented with 1 and 2 g GB/kg (p > 0.05). In conclusion, the results of the present study suggest an immunogenic role for dietary GB at optimum dietary levels (1-2 g GB/kg diet) against toxicity induced by diazinon. Nevertheless, GB at high dietary levels (4 g GB/kg diet) showed immunosuppressive effects, which makes it necessary to optimize its levels in diet.

People are exposed to a number of environmental, occupational, and therapeutic toxic agents which may be natural or man made. These hazardous substances may manifest as direct side effects on the function of organs or indirectly induced alteration of gene expression, cancer-associated metabolic pathways, and/or alter homeostasis. Lycopene, as a one of the most potent antioxidant, is found in fruits and vegetables. High-intake of lycopene has been shown to be effective in decreasing the risk of both natural toxins including mycotoxins, bacterial toxins, and chemical toxins including heavy metals, pesticides as well as herbicides. Recently, there is growing attention in understanding the mechanisms of the phytochemicals and carotenoids as antioxidative, antiapoptotic, radical scavenging, and chelating agents and their roles in the modulation of inflammatory pathways. This review summarizes available data from several recent studies about lycopene and its role against chemical and natural toxicants. © 2018 BioFactors, 45(1):5-23, 2019., (© 2018 International Union of Biochemistry and Molecular Biology.)

This study examined the degradation of organophosphate (OP) and carbamate pesticides using RSDL ® (Reactive Skin Decontamination Lotion Kit) lotion. Degradation occurs from a nucleophilic substitution (SN) reaction between an ingredient in the RSDL lotion, potassium 2,3-butanedione monoximate (KBDO), with susceptible sites in the pesticides. Evaluation at several molar ratios of KBDO:test articles using liquid chromatography-mass spectrometry (LC-MS) techniques was performed. The OP test articles, parathion, paraoxon, parathion-methyl, paraoxon-methyl and chlorpyrifos were effectively degraded at molar ratios of four and above in less than 6min contact time. Malathion and malaoxon were similarly converted to inactive by-products at molar ratios as low as two in less than 4min. A minimum molar ratio of nine was found to be effective against the carbamate pesticide carbofuran. In the case of aldicarb, complete destruction was achieved at a molar ratio of fifteen and a reaction time of one hour. It is important to note that these studies are based on a direct liquid phase RSDL lotion reaction with the toxic chemicals without the added physical removal decontamination efficacy component provided by the sponge component of the RSDL kit. The RSDL kit is intended to be used to remove or neutralize chemical warfare agents (CWA) and T-2 toxin from the skin. In actual use, the majority of the CWA decontamination occurs through the combined action of the sponge in both removing the chemical from the skin, and in rapidly mixing the chemicals at a high molar ratio of KBDO:CWA within the pores of the sponge to enhance rapid neutralization of the chemical., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Exposure to pesticides has been associated with neurodevelopmental toxicity. Usually people are exposed to mixtures of pesticides. However, most studies analyze the effects of individual pesticides. Developmental exposure to mixtures of pesticides may result in additive effects or in antagonistic or synergistic effects. The aim of this work was to compare the effects of developmental exposure of rats to cypermethrin or endosulfan with the effects of its mixture on cognitive and motor function and on some underlying mechanisms. Exposure to individual pesticides or the mixture was from gestational day 7 to postnatal day 21. We analyzed the effects, in males and females, on spatial learning and memory, associative learning, anxiety, motor coordination, and spontaneous motor activity. We also analyzed neuroinflammation and NMDA receptor subunits in hippocampus and extracellular GABA in cerebellum. Exposure to the mixture, but not to individual pesticides, impaired spatial memory in males, associative learning in females, and increased motor activity in males and females. This indicates a synergistic effect of cypermethrin and endolsufan exposure on these end points. In contrast, motor coordination was impaired by individual exposure to endosulfan or cypermethrin, associated with increased extracellular GABA in cerebellum, but these effects were prevented in rats exposed to the mixture, indicating an antagonistic effect of cypermethrin and endolsufan exposure on these end points. The results show different interaction modes (synergism or antagonism) of the pesticides, depending on the end point analyzed and the sex of the rats.

Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds. Basic treatments for these intoxications are based on immediate administration of atropine and acetylcholinesterase reactivators which are currently represented by mono- or bis-pyridinium aldoximes. However, these antidotes are not sufficient to ensure 100 % treatment efficacy even they are administered immediately after intoxication, and in general, they possess several drawbacks. Herein, we have reviewed new efforts leading to the development of novel reactivators and proposition of new promising strategies to design novel and effective antidotes. Structure-activity relationships and biological activities of recently proposed acetylcholinesterase reactivators are discussed and summarized. Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. We have also discussed new chemical entities as potential replacement of oxime functional group.

Numerous pesticides are used in agriculture, gardening, and wildlife-control. Despite their intended toxicity to pests, these compounds can also cause harm to wildlife and humans due to their ability to potentially bioaccumulate, leach into soils, and persist in the environment. Humans and animals are commonly exposed to these compounds through agricultural practices and consumption of contaminated foods and water. Pesticides can cause a range of adverse effects in humans ranging from minor irritation, to endocrine or nervous system disruption, cancer, or even death. A convenient and cost-effective method to reduce unavoidable pesticide absorption in humans and wildlife could be the use of probiotic lactobacilli. Lactobacillus is a genus of Gram-positive gut commensal bacteria used in the production of functional foods, such as yoghurt, cheese, sauerkraut and pickles, as well as silage for animal feed. Preliminary in vitro experiments suggested that lactobacilli are able to degrade some pesticides. Probiotic Lactobacillus rhamnosus GR-1-supplemented yoghurt reduced the bioaccumulation of mercury and arsenic in pregnant women and children. A similar study is warranted to test if this approach can reduce pesticide absorption in vivo, given that the lactobacilli can also attenuate reactive oxygen production, enhance gastrointestinal barrier function, reduce inflammation, and modulate host xenobiotic metabolism.

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl₂, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Aluminum phosphide is used as a fumigant. It produces phosphine gas (PH₃). PH₃ is a mitochondrial poison which inhibits cytochrome c oxidase, it leads to generation of reactive oxygen species; so one of the most important suggested mechanisms for its toxicity is induction of oxidative stress. In this regard, it could be proposed that a drug like N-acetylcysteine (NAC) as an antioxidant would improve the tolerance of aluminum phosphide-intoxicated cases. The objective of this study was to evaluate the protective effects of NAC on acute aluminum phosphide poisoning., Methods: This was a prospective, randomized, controlled open-label trial. All patients received the same supportive treatments. NAC treatment group also received NAC. The blood thiobarbituric acid reactive substances as a marker of lipid peroxidation and total antioxidant capacity of plasma were analyzed., Results: Mean ingested dose of aluminum phosphide in NAC treatment and control groups was 4.8 ± 0.9 g vs. 5.4 ± 3.3 g, respectively (p = 0.41). Significant increase in plasma malonyldialdehyde level in control group was observed (139 ± 28.2 vs. 149.6 ± 35.2 μmol/L, p = 0.02). NAC infusion in NAC treatment group significantly decreased malondialdehyde level (195.7 ± 67.4 vs. 174.6 ± 48.9 μmol/L, p = 0.03), duration of hospitalization (2.7 ± 1.8 days vs. 8.5 ± 8.2 days, p = 0.02), rate of intubation and ventilation (45.4% vs. 73.3%, p = 0.04). Mortality rate in NAC treatment and control groups were 36% and 60%, respectively with odds ratio 2.6 (0.7-10.1, 95% CI)., Conclusion: NAC may have a therapeutic effect in acute aluminum phosphide poisoning.

Rotenone causes cytotoxicity in astrocytic cell culture by glial activation, which is linked to free radical generation. The present study is an investigation to explore whether rotenone could also cause cellular toxicity in mouse neuroblastoma cells (Neuro-2a) under treatment similar to astroglial cells. The effect of rotenone (0.1, 1, and 10 μM) on mitochondrial dehydrogenase enzyme activity by MTT reduction assay, PI uptake, total reactive oxygen species (ROS)/superoxide levels, nitrite levels, extent of DNA damage (by comet assay), and nuclear morphological alteration by Hoechst staining was studied. Caspase-3 and Ca⁺²/calmodulin-dependent protein kinase II (CaMKIIα) gene expression was determined to evaluate the apoptotic cell death and calcium kinase, respectively. Calcium level was estimated fluorometrically using fura-2A stain. Rotenone decreased mitochondrial dehydrogenase enzyme activity and generated ROS, superoxide, and nitrite. Rotenone treatment impaired cell intactness and nuclear morphology as depicted by PI uptake and chromosomal condensation of Neuro-2a cells, respectively. In addition, rotenone resulted in increased intracellular Ca⁺² level, caspase-3, and CaMKIIα expression. Furthermore, co-exposure of melatonin (300 μM), an antioxidant to cell culture, significantly suppressed the rotenone-induced decreased mitochondrial dehydrogenase enzyme activity, elevated ROS and RNS. However, melatonin was found ineffective to counteract rotenone-induced increased PI uptake, altered morphological changes, DNA damage, elevated Ca⁺², and increased expression of caspase-3 and CaMKIIα. The study indicates that intracellular calcium rather than oxidative stress is a major factor for rotenone-induced apoptosis in neuronal cells.

Organophosphate pesticides (OPPs; e.g. chlorpyrifos, diazinon, paraoxon) are a wide and heterogeneous group of organophosphorus compounds. Their biological activity of inhibiting acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) ranks them as life endangering agents. The necessary treatment after OPP exposure involves the use of parasympatolytics (e.g. atropine), oxime reactivators (e.g. obidoxime), and anticonvulsive drugs (e.g. diazepam). Therefore, the reactivators of AChE are essential compounds in the treatment of OPP intoxications. Commercial AChE reactivators (e.g. pralidoxime, HI-6, obidoxime, trimedoxime, methoxime) were originally developed for other members of the organophosphate family, such as nerve agents (e.g. sarin, soman, tabun, VX). Pralidoxime, HI-6, and methoxime were found to be weak reactivators of OPP-inhibited AChE. Obidoxime and trimedoxime showed satisfactory reactivation against various OPPs with minor toxicity issues. During the last two decades, the treatment of OPP exposure has become more widely discussed because of growing agricultural production, industrialization, and harmful social issues (e.g. suicides). In this review is the summarized design, evaluation, and structure-activity relationship studies of recently produced AChE reactivators. Since pralidoxime, over 300 oximes have been produced or tested against OPP poisoning, and several novel compounds show very promising abilities as comparable (or higher) to commercial oximes. Some of these are highlighted for their further testing of OPP exposure and, additionally, the main structure-activity relationship of AChE reactivators against OPP is discussed., (© 2009 Wiley Periodicals, Inc.)

Montmorillonite K-10 functionalized with α-nucleophilic 2-pralidoxime (PAM) and its zwitterionic oximate form (PAMNa) is introduced as a versatile material for chemical protection against organophosphorous (OP) compounds such as pesticides and chemical warfare agents (CWA). Upon inclusion into the montmorillonite interlayer structure, the pyridinium group of PAMNa is strongly physisorbed onto acidic sites of the clay, leading to shrinking of the interplanar distance. Degradation of diethyl parathion by PAMNa-functionalized montmorillonite in aqueous-acetonitrile solutions occurred primarily via hydrolytic conversion of parathion into diethylthio phosphoric acid, with the initial stages of hydrolysis observed to be pseudo-first-order reactions. Hydrolysis catalyzed by the clay intercalated by PAMNa was 10- and 17-fold more rapid than corresponding spontaneous processes measured at 25 and 70 °C, respectively. Hydrolytic degradation of diisopropyl fluorophosphate (DFP), a CWA simulant, was studied on montmorillonite clay functionalized by PAMNa and equilibrated with water vapor at 100% relative humidity by ³¹P high-resolution magic angle spinning NMR and was observed to be rather facile compared with the untreated montmorillonite, which did not show any DFP hydrolysis within 24 h. The incorporation of the functionalized clay particles into elastomeric film of polyisobutylene was shown to be a means to impart DFP-degrading capability to the film, with clay particle content exceeding 18 wt %.

Dopamine is cytotoxic and may play a role in the development of Parkinson's disease. However, its interaction with environmental risk factors such as pesticides remains poorly understood. The vesicular monoamine transporter (VMAT) regulates intracellular dopamine content, and we have tested the neuroprotective effects of VMAT in vivo using the model organism Drosophila melanogaster. We find that Drosophila VMAT (dVMAT) mutants contain fewer dopaminergic neurons than wild type, consistent with a developmental effect, and that dopaminergic cell loss in the mutant is exacerbated by the pesticides rotenone and paraquat. Overexpression of DVMAT protein does not increase the survival of animals exposed to rotenone, but blocks the loss of dopaminergic neurons caused by this pesticide. These results are the first to demonstrate an interaction between a VMAT and pesticides in vivo, and provide an important model to investigate the mechanisms by which pesticides and cellular DA may interact to kill dopaminergic cells., ((c) 2010 Elsevier Inc. All rights reserved.)

Despite extensive research for more than six decades on medical countermeasures against poisoning by organophosphorus compounds (OP) the treatment options are meagre. The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Up to now, the therapeutic efficacy of oximes was mostly evaluated in animal models but substantial species differences prevent direct extrapolation of animal data to humans. Hence, it was considered essential to establish relevant experimental in vitro models for the investigation of oximes as antidotes and to develop computer models for the simulation of oxime efficacy in different scenarios of OP poisoning. Kinetic studies on the various interactions between erythrocyte AChE from various species, structurally different OP and different oximes provided a basis for the initial assessment of the ability of oximes to reactivate inhibited AChE. In the present study, in vitro enzyme-kinetic and pharmacokinetic data from a minipig model of dimethoate poisoning and oxime treatment were used to calculate dynamic changes of AChE activities. It could be shown that there is a close agreement between calculated and in vivo AChE activities. Moreover, computer simulations provided insight into the potential and limitations of oxime treatment. In the end, such data may be a versatile tool for the ongoing discussion of the pros and cons of oxime treatment in human OP pesticide poisoning., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

The objective of the study was to evaluate the potential risk of DNA damage due to exposure to a mixture of the most widely used pesticides, namely endosulfan, chlorpyriphos and thiram at an environmentally relevant concentration (5 microM each) and the DNA protective capacity of sulforaphane (SFN) (10-30 microg/mL). DNA damage in human lymphocytes was ascertained with Single Cell Gel Electrophoresis (SCGE), also called Comet Assay. For positive control, H(2)O(2) at 100 mM was used. The pesticide mixture produced DNA damage at the concentration used in the lymphocytes. SFN was able to offer a statistically significant (P < 0.01), concentration-dependant protection to DNA damage between 10-20 microg/mL in both the pre-incubation and co-incubation strategies. The results indicate that exposure to low levels of these pesticide mixtures can induce DNA damage, and the presence of SFN in diet may reduce the incidence of genetic damage, especially in farm workers. However, it is not clear whether SFN is involved in quenching of the free radicals generated by the pesticide mixture or it is involved in DNA repair mechanism.

The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

Background: Pesticide exposure is a recognized risk factor for neurodegenerative diseases. Recently, bifenthrin, a pyrethroid pesticide, was shown to inhibit the formation of neurites and cause neurite retraction, raising concern that these newer and less toxic pesticides may also contribute to neurodegenerative diseases. PolicosanolPlus and Neuroprevin are nutraceutical supplements which promote the survival of neurites in neuronal cell cultures. Here we determine if PolicosanolPlus and Neuroprevin can ameliorate the neurodegenerative effects of bifenthrin., Material/methods: PC12 cells were treated with NGF, bifenthrin, PolicosanolPlus and Neuroprevin in various combinations and the formation of neurites was assessed microscopically at times ranging from 12 to 72 hours post treatment. Bifenthrin was also withheld at the time of NGF, PolicosanolPlus and Neuroprevin treatment and added after neurite formed to assess neurite retraction., Results: Bifenthrin (1 x 10(-6) M) inhibits neurite outgrowth, in the absence of cell death, by more than 50% at 12 hours and by more than 80% at 72 hours. With addition of PolicosanolPlus and/or Neuroprevin at the time of cell seeding, bifenthrin does not inhibit neurite outgrowth. Addition of bifenthrin to differentiated cells results in a retraction of 90% of neurites, while those with PolicosanolPlus and Neuroprevin show no significant retraction of neurites., Conclusions: The pesticide, bifenthrin, inhibits neurite formation and causes neurite retraction. PolicosanolPlus and Neuroprevin are nutraceutical supplements which ameliorate the effects of bifenthrin on neurite outgrowth and retraction. Dietary supplementation with PolicosanolPlus and Neuroprevin may protect against developmental and long-term neurodegenerative events that result from exposure to pesticides.

A squaric monoester monoamide motif was employed as an effective reactive immunogen for the discovery of monoclonal antibodies with reactive residue(s) in their combining sites. Two antibodies, 2D4 and 3C8, were uncovered that enhance paraoxon hydrolysis over background. Kinetic analysis of these antibodies was performed and interestingly both undergo a single turnover event due to covalent modification within the antibody combining site. Because antibodies 2D4 and 3C8 result in covalent attachment and thus inactivation of paraoxon, they could be useful probes for investigating paraoxon intoxication.

Background: This study investigates the role of black tea extract in protection against oxidative damage induced in mice by a subacute oral dose of a combination of pesticides., Methods: Liver damage markers like amino-acid transferases and alkaline phosphatase, oxidative damage markers indicating extent of lipid peroxidation, host antioxidant reserve indicators like reduced glutathione (GSH) and total thiol levels, GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) superoxide dismutase (SOD) and catalase (CAT) were measured by spectrophotometric techniques in four different groups namely (1) control, (2) black tea extract, (3) pesticide alone and (4) pretreatment with black tea extract followed by pesticide treatment., Results: Following exposure to pesticides lipid peroxidation was increased compared to that in the control [0.50+/-0.083 (mean+/-S.E.) vs. 0.21+/-0.02 micromol/mg protein, p<0.001]. Moreover, levels of antioxidants like GSH and total thiol were also significantly decreased in comparison to control, e.g., GSH [5.16+/-0.78 vs. 6.96+/-1.35 micromol/mg protein, p<0.001], total thiol [19.3+/-2.74 vs. 26.15+/-2.8 micromol/mg protein, p<0.001]. In addition, the activities of antioxidant enzymes like GPx, GST, GR, SOD and catalase were also likewise diminished by oxidant damage. Treatment with aqueous black tea extract significantly protects the liver tissue from the oxidative damage and shifts the trend towards amelioration and replenishment of the antioxidant status., Conclusions: The active components present in natural extracts like that of black tea can be very effective in perhaps reducing the extent of injury and in overcoming oxidant damage caused by exposure to environmental agents like pesticides.

Pseudomonas spp. that can colonise the roots of crop plants and produce antifungal metabolites represent a real alternative to the application of chemical fungicides. Presently, much research is aimed at understanding, at the molecular level, the mechanisms that enable Pseudomonas strains to act as efficient biological control agents. This approach is facilitating the development of novel strains with modified traits for enhanced biocontrol efficacy. However, without solving some inherent problems associated with the effective delivery of microbial inoculants to seeds and without knowledge on the biosafety aspects of novel biocontrol agents, the commercial potential of Pseudomonas spp. for plant disease control will not be realised.

Soil inoculation with liquid cultures of Bacillus megaterium 501 and Exophiala nigrum A-29 capable of degrading several organophosphorus pesticides accelerated growth and development of experimental plants, formation of their generative organs, and improved their productivity. This was particularly observed under stress plant growth conditions on phytotoxic peach substrates. The microorganisms inoculated can probably degrade phytotoxins present in soils, thereby favoring the plant development.

The effect of IV amitraz on the transit of barium sulfate through the stomach and duodenum as well as amitraz-induced bradycardia was studied in 4 dogs. Control transit time and heart rates were determined after IV injection of dimethyl sulfoxide (0.1 ml/kg), which was subsequently used as the vehicle for amitraz administration. The time for barium sulfate to move from the stomach to the duodenojejunal junction was 6.1 +/- 1.3 minutes (mean +/- SEM). An IV injection of amitraz (1 mg/kg) prolonged the transit time to 251.2 +/- 27.0 minutes, and induced marked bradycardia for at least 60 minutes. During the amitraz-induced prolongation of gastrointestinal transit, there were no vigorous gastric contractions for at least 180 minutes. Yohimbine, an alpha 2-adrenergic blocking agent, given IV 20 minutes after amitraz administration, at a dosage of 0.1 mg/kg, reversed both the gastrointestinal and bradycardic effects of amitraz. It was concluded that 1) amitraz causes decreased gastrointestinal motility and bradycardia, and 2) yohimbine may be useful in the control of the untoward reactions caused by amitraz administration.