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Blood Purification 2013Organizations such as the National Kidney Foundation, the American Kidney Fund, the National Institute of Diabetes and Digestive and Kidney Diseases, and the US... (Review)
Review
Organizations such as the National Kidney Foundation, the American Kidney Fund, the National Institute of Diabetes and Digestive and Kidney Diseases, and the US Department of Health and Human Services recommend not including whole grains as part of the renal diet. The rationale for this recommendation is the high phosphorus content in these foods. While the phosphorus content in whole grains may be indeed high, it is covalently bound to organic molecules (primarily phytate) and requires the enzyme phytase to be released and become available for absorption. While some phytase is contained in some whole grains (corn, oats, and millet have little to no phytase activity), the enzyme is decreased in milling, food preparation and over time. Since the human intestine does not express phytase, the enzyme required for the release of phosphorus from phytate is not present in the intestinal lumen when ingesting cooked food. Consequently, the bioavailability of phosphorus from whole grains is low. For the reasons presented here we believe that the 'grain ban' in the diet for kidney patients should be reconsidered. By doing this, the kidney diet would be enriched and it would provide needed fiber along with its health benefits, diversify the diet with low sodium choices, and possibly provide adequate protein without increasing phosphorous levels.
Topics: Diet; Edible Grain; Food; Humans; Organophosphates; Renal Insufficiency, Chronic
PubMed: 24496192
DOI: 10.1159/000356683 -
Environment International Jan 2021Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer and industrial products. Human exposure to OPEs raises concerns due to...
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer and industrial products. Human exposure to OPEs raises concerns due to their endocrine disruptive potentials. Till now, the effects of OPEs on thyroid hormones (THs) and the mediating role of oxidative stress in pregnant women have not been studied. In this study, prenatal urinary concentrations of OPE metabolites (mOPEs), levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and oxidative stress levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and malondialdehyde (MDA) were measured in pregnant women (n = 360) from a coastal urbanized region and moderate socioeconomic status. Neonatal TSH in heel blood was also measured in newborns (n = 309). Dibutyl phosphate (DBP) and diphenyl phosphate (DPHP) were extensively detected with a median creatinine-adjusted level of 0.19 μg/g and 0.66 μg/g, respectively, and the median of ∑mOPEs was 1.82 μg/g. DBP and DPHP were included in the analysis. The concentrations of DBP and DPHP were positively associated with either maternal or neonatal TSH levels, while not for maternal FT3 and FT4 levels. Positive associations for maternal and neonatal TSH were particularly observed in girls as stratified by newborn sex suggesting a sex-selective difference. Furthermore, 8-OHdG, the biomarker of DNA damage, was found to be a major mediator (>60%) for the association between neonatal TSH and DPHP, suggesting that DNA damage is involved in fetal thyroid function disruption. On the other hand, MDA showed a partially suppressing effect (<40%) for the associations between mOPEs and neonatal TSH, which needs further clarification. For maternal TSH, both 8-OHdG and MDA showed moderate mediating effects while the direct effects of mOPEs on maternal TSH also contributed. These results suggest thyroid disrupting effects of OPE exposure on mothers and fetuses during pregnancy and the potential influence mediated by the oxidative stresses of DNA damage and lipid peroxidation.
Topics: Esters; Female; Flame Retardants; Humans; Infant, Newborn; Organophosphates; Oxidative Stress; Plasticizers; Pregnancy; Thyroid Gland
PubMed: 33113466
DOI: 10.1016/j.envint.2020.106215 -
Ecotoxicology and Environmental Safety Mar 2024The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are...
The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007-2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (β = -0.209 (95% CI: -0.310, -0.114)), and caused an increased Tg concentration (β = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and β =-0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and β =-0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.
Topics: Adult; Humans; Male; Female; United States; Insecticides; Nutrition Surveys; Thyroid Hormones; Organophosphates; Organophosphorus Compounds
PubMed: 38428240
DOI: 10.1016/j.ecoenv.2024.116139 -
Rural and Remote Health Jan 2020Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well... (Review)
Review
INTRODUCTION
Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well known, while there has been limited research on their long-term effects. The objective of this review was to discuss the health effects of chronic organophosphate exposure in farmers.
METHODS
Medline, Scopus and Web of Science were searched to find the relevant articles. Articles published only in English and until December 2018 were reviewed. The selected articles were then categorised as neurological (neurobehaviour, neurodevelopmental, neurological signs and symptoms) or non-neurological subheadings.
RESULTS
A total of 53 articles for neurological effects and 17 articles for non-neurological effects were identified. Chronic organophosphates exposure was associated with deficits in the neurobehaviour subsets of attention and short-term memory, increased incidence of neurodegenerative diseases and effects on peripheral nerves and neurodevelopment. However, research to support non-neurological effects such as respiratory symptoms, increased cancer risk, endocrine disruption, cardiac issues, chronic fatigue and infertility was limited.
CONCLUSION
Chronic organophosphate exposure was found to affect four of the five areas of described neurological effects in the literature. A large proportion of the research in this area was not methodologically strong, therefore few recommendations can be conclusively made. Future research is warranted to investigate the non-neurological effects of chronic exposure to ensure the occupational risks of low-level chronic exposure are clearly communicated to farmers and farm workers.
Topics: Agricultural Workers' Diseases; Farmers; Humans; Insecticides; Occupational Exposure; Organophosphates
PubMed: 31902214
DOI: 10.22605/RRH4508 -
Environmental Research Jun 2023Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of...
Sex-specific effects of prenatal organophosphate ester (OPE) metabolite mixtures and adverse infant birth outcomes in the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy cohort.
BACKGROUND
Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort.
METHODS
Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA = 31.5 ± 2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex.
RESULTS
We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p = 0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and GA at birth among female infants (p = 0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. No associations were observed between OPE mixtures and BW for GA z-scores.
CONCLUSION
Higher BDCIPP and DNBP + DIBP concentrations were associated with earlier GA at birth among male and female infants, respectively. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants. However, we saw no associations between prenatal OPEs and BW for GA. Our results suggest sex-specific impacts of prenatal OPE exposures on GA at birth.
Topics: Pregnancy; Infant, Newborn; Humans; Male; Infant; Female; Bayes Theorem; Organophosphates; Phosphates; Flame Retardants; Esters
PubMed: 36934865
DOI: 10.1016/j.envres.2023.115703 -
Frontiers in Endocrinology 2024Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate...
Association between urinary organophosphate ester metabolite exposure and thyroid disease risk among US adults: National Health and Nutrition Examination Survey 2011-2014.
BACKGROUND
Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate the relationship between OPEs exposure and thyroid disease risk in the general population in the United States.
METHOD
Data were obtained from the 2011-2014 National Health and Nutrition Examination Survey cycle. All participants were tested for seven OPE metabolites in their urine and answered questions about whether they had thyroid disease through questionnaires. Logistic regression was employed to analyze the association between exposure to individual OPE metabolites and thyroid disease. Weighted Quantile Sum (WQS) regression modeling was utilized to assess exposure to mixed OPE metabolites and risk of thyroid disease. Bayesian kernel machine regression(BKMR) models to analyze the overall mixed effect of OPE metabolites.
RESULT
A total of 2,449 participants were included in the study, 228 of whom had a history of thyroid disease. Bis(1,3-dichloro-2-propyl) phos (BDCPP), Diphenyl phosphate (DPHP) and Bis(2-chloroethyl) phosphate (BCEP) were the top three metabolites with the highest detection rates of 91.75%, 90.77% and 86.57%, respectively. In multivariate logistic regression models, after adjustment for confounding variables, individuals with the highest tertile level of BCEP were significantly and positively associated with increased risk of thyroid disease (OR=1.57, 95% CI=1.04-2.36), using the lowest tertile level as reference. In the positive WQS regression model, after correcting for confounding variables, mixed exposure to OPE metabolites was significantly positively associated with increased risk of thyroid disease (OR=1.03, 95% CI=1.01-1.06), with BCEP and DPHP having high weights. In the BKMR model, the overall effect of mixed exposure to OPE metabolites was not statistically significant, but univariate exposure response trends showed that the risk of thyroid disease decreased and then increased as BCEP exposure levels increased.
CONCLUSION
The study revealed a significant association between exposure to OPE metabolites and an increased risk of thyroid disease, with BCEP emerging as the primary contributor. The risk of thyroid disease exhibits a J-shaped pattern, whereby the risk initially decreases and subsequently increases with rising levels of BCEP exposure. Additional studies are required to validate the association between OPEs and thyroid diseases.
Topics: Adult; Humans; United States; Nutrition Surveys; Bayes Theorem; Flame Retardants; Organophosphates; Thyroid Diseases; Phosphates; Esters
PubMed: 38405137
DOI: 10.3389/fendo.2024.1329247 -
Viruses May 2021Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the... (Review)
Review
Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the interaction between Env and the host receptor CD4. This interaction, referred to as the attachment step, has long been considered an attractive target for inhibitor discovery and development. Fostemsavir, recently approved by the FDA, represents the first-in-class drug in the attachment inhibitor class. This review focuses on the discovery of temsavir (the active compound of fostemsavir) and analogs, mechanistic studies that elucidated the mode of action, and structural studies that revealed atomic details of the interaction between HIV-1 Env and attachment inhibitors. Challenges associated with emerging resistance mutations to the attachment inhibitors and the development of next-generation attachment inhibitors are also highlighted.
Topics: Animals; Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Virus Internalization
PubMed: 34066522
DOI: 10.3390/v13050843 -
Ecotoxicology and Environmental Safety Oct 2021In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used...
In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used in building materials, textiles, and electric equipment. Elucidating the relationship between OPFRs and tumors holds great significance for the treatment and prevention of diseases. In this work, we found a new method for predicting the correlation between the interactive genes of OPFRs and tumors. Transcriptome profiles and OPFR information were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression, Comparative Toxicogenomics, and PharmMapper databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer, steroid metabolic process, and steroid hormone regulation. Furthermore, protein-protein interaction network analysis revealed 33 biological hub genes. The operating characteristic curves and survival analysis showed the role of key genes in predicting the prognosis of prostate cancer. Gene target prediction and gene set variation analysis proved that OPFRs and their metabolites exert potential effects on prostate cancer. Colony formation assay showed that the cells with AR, mTOR and DDIT3 knockdown could remarkably mitigate the cell proliferation ability in both PC-3 and LNCap cells. Transwell assay demonstrated that the silencing of AR, mTOR and DDIT3 could significantly inhibit the cell invasion capacity of prostate cells. Triphenyl phosphate (TPP) significantly increase the cell proliferation ability and promote cell invasion capacity. AR, mTOR and DDIT3 in the PC-3 and LNCap cells were significantly upregulated with 10-6 M TPP treated.
Topics: Comprehension; Flame Retardants; Humans; Male; Organophosphates; Organophosphorus Compounds; Prostatic Neoplasms
PubMed: 34358932
DOI: 10.1016/j.ecoenv.2021.112589 -
Environmental Science and Pollution... May 2016Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of... (Review)
Review
Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties.
Topics: Catalysis; Decontamination; Environmental Pollutants; Organophosphates; Organophosphorus Compounds; Pesticides
PubMed: 26832878
DOI: 10.1007/s11356-016-6143-1 -
Biochemistry. Biokhimiia Oct 2012Development of new ways of creating catalytic antibodies possessing defined substrate specificity towards artificial substrates has important fundamental and practical... (Review)
Review
Development of new ways of creating catalytic antibodies possessing defined substrate specificity towards artificial substrates has important fundamental and practical aspects. Low immunogenicity combined with high stability of immunoglobulins in the blood stream makes abzymes potent remedies. A good example is the cocaine-hydrolyzing antibody that has successfully passed clinical trials. Creation of an effective antidote against organophosphate compounds, which are very toxic substances, is a very realistic goal. The most promising antidotes are based on cholinesterases. These antidotes are now expensive, and their production methods are inefficient. Recombinant antibodies are widely applied in clinics and have some advantage compared to enzymatic drugs. A new potential abzyme antidote will combine effective catalysis comparable to enzymes with high stability and the ability to switch on effector mechanisms specific for antibodies. Examples of abzymes metabolizing organophosphate substrates are discussed in this review.
Topics: Animals; Antibodies, Catalytic; Organophosphate Poisoning; Organophosphates; Substrate Specificity
PubMed: 23157294
DOI: 10.1134/S0006297912100069