scholarly journals Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Stephen J. Genuis ◽  
Sanjay Beesoon ◽  
Rebecca A. Lobo ◽  
Detlef Birkholz
Keyword(s):  
High Performance ◽  
Effective Means ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
High Exposure ◽  
Estrogenic Effects ◽  
Toxicological Studies ◽  
Liquid Chromatography Tandem Mass ◽  
Ethylhexyl Phthalate

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion.Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry.Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels.Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body.

scholarly journals Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Di Nisio ◽  
Maria Santa Rocca ◽  
Luca De Toni ◽  
Iva Sabovic ◽  
Diego Guidolin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endocrine Disruption ◽  
Bone Development ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
Target Cells ◽  
Surface Plasmon Resonance Analysis ◽  
Cellular Targets ◽  
Toxicological Studies

Abstract Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.

Effect of carbon source on Phenobarbital metabolism by Rhizopus stolonifer

2010 ◽  
Vol 3 (2) ◽  
pp. 1022-1027
Author(s):  
Kavitha K ◽  
Asha S ◽  
Hima Bindu T.V.L ◽  
Vidyavathi M
Keyword(s):  
Carbon Source ◽  
High Performance ◽  
Carbon Sources ◽  
In Vitro Models ◽  
Rhizopus Stolonifer ◽  
Safety And Efficacy ◽  
Alternative Systems ◽  
Toxicological Studies ◽  
Microbial Model

The safety and efficacy of a drug is based on its metabolism or metabolite formed. The metabolism of drugs can be studied by different in vitro models, among which microbial model became popular. In the present study, eight microbes were screened for their ability to metabolize phenobarbital in a manner comparable to humans with a model to develop alternative systems to study human drug metabolism. Among the different microbes screened, a filamentous fungi Rhizopus stolonifer metabolized phenobarbital to its metabolite which is used for further pharmacological and toxicological studies. The transformation of phenobarbital was identified by high- performance liquid chromatography (HPLC). Interestingly, Rhizopus stolonifer sample showed an extra metabolite peak at 3.11min. compared to its controls. The influence of different carbon sources in media used for growth of fungus, on metabolite production was studied, to find its effect in production of metabolite as the carbon source may influence the growth of the cell.

Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 270-277 ◽  
Author(s):  
Vijay Kumar ◽  
Simranjeet Singh ◽  
Ragini Bhadouria ◽  
Ravindra Singh ◽  
Om Prakash
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Biologically Active ◽  
Toxicological Studies ◽  
Wide Range ◽  
Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

scholarly journals Exploring the Bile Stress Response of Lactobacillus mucosae LM1 through Exoproteome Analysis

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5695
Author(s):  
Bernadette B. Bagon ◽  
Ju Kyoung Oh ◽  
Valerie Diane V. Valeriano ◽  
Edward Alain B. Pajarillo ◽  
Dae-Kyung Kang
Keyword(s):  
Stress Response ◽  
Ribosomal Proteins ◽  
High Performance ◽  
Phosphoglycerate Kinase ◽  
Label Free ◽  
Beneficial Effects ◽  
Extracellular Proteome ◽  
Liquid Chromatography Tandem Mass ◽  
Lactobacillus Mucosae

Lactobacillus sp. have long been studied for their great potential in probiotic applications. Recently, proteomics analysis has become a useful tool for studies on potential lactobacilli probiotics. Specifically, proteomics has helped determine and describe the physiological changes that lactic acid bacteria undergo in specific conditions, especially in the host gut. In particular, the extracellular proteome, or exoproteome, of lactobacilli contains proteins specific to host– or environment–microbe interactions. Using gel-free, label-free ultra-high performance liquid chromatography tandem mass spectrometry, we explored the exoproteome of the probiotic candidate Lactobacillus mucosae LM1 subjected to bile treatment, to determine the proteins it may use against bile stress in the gut. Bile stress increased the size of the LM1 exoproteome, secreting ribosomal proteins (50S ribosomal protein L27 and L16) and metabolic proteins (lactate dehydrogenase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenases, among others) that might have moonlighting functions in the LM1 bile stress response. Interestingly, membrane-associated proteins (transporters, peptidase, ligase and cell division protein ftsH) were among the key proteins whose secretion were induced by the LM1 bile stress response. These specific proteins from LM1 exoproteome will be useful in observing the proposed bile response mechanisms via in vitro experiments. Our data also reveal the possible beneficial effects of LM1 to the host gut.

scholarly journals Critical Review of Synthesis, Toxicology and Detection of Acyclovir

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6566
Author(s):  
Yan-Ping Wei ◽  
Liang-Yuan Yao ◽  
Yi-Yong Wu ◽  
Xia Liu ◽  
Li-Hong Peng ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Electrochemical Sensors ◽  
Antiviral Drug ◽  
Preparation Methods ◽  
Detection Techniques ◽  
Toxicological Studies ◽  
Liquid Chromatography Tandem Mass ◽  
Past Life ◽  
Flow Injection Chemiluminescence

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV’s ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection–chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.

scholarly journals A Survey of Methylobacterium Species and Strains Reveals Widespread Production and Varying Profiles of Cytokinin Phytohormones

2021 ◽  
Author(s):  
Daniel Palberg ◽  
Anna Kisiała ◽  
Gabriel Lemes Jorge ◽  
R. J. Neil Emery
Keyword(s):  
High Performance ◽  
Active Form ◽  
Plant Growth Promoting Bacteria ◽  
Liquid Chromatography Tandem Mass ◽  
Plant Growth Promoting ◽  
Growth Promoting ◽  
Selection For ◽  
Indole 3 Acetic Acid

Abstract BackgroundSymbiotic Methylobacterium strains comprise a significant part of plant microbiomes. Their presence enhances plant productivity and stress resistance, prompting classification of these strains as plant growth-promoting bacteria (PGPB). Methylobacteria can synthesize unusually high levels of plant hormones, called cytokinins (CKs), including the most active form, trans-Zeatin (tZ). ResultsThis study provides a comprehensive inventory of 46 representatives of Methylobacterium genus with respect to phytohormone production in vitro, including 16 CK forms, abscisic acid (ABA) and indole-3-acetic acid (IAA). High performance-liquid chromatography - tandem mass spectrometry (HPLC-MS/MS) analyses revealed varying abilities of Methylobacterium strains to secrete phytohormones that ranged from 5.09 to 191.47 pmol mL-1 for total CKs, and 0.46 to 82.16 pmol mL-1 for tZ. Results indicate that reduced methanol availability, the sole carbon source for bacteria in the medium, stimulates CK secretion by Methylobacterium. Additionally, select strains were able to transform L-tryptophan into IAA while no ABA production was detected.ConclusionsTo better understand features of CKs in plants, this study uncovers CK profiles of Methylobacterium that are instrumental in microbe selection for effective biofertilizer formulations.

scholarly journals Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 180
Author(s):  
Jinfeng Chen ◽  
Xiaoyu Guo ◽  
Yingyuan Lu ◽  
Mengling Shi ◽  
Haidong Mu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Direct Injection ◽  
Carthamus Tinctorius ◽  
Tandem Mass ◽  
Comparative Pharmacokinetic ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

The combination of Carthamus tinctorius extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergistic mechanisms. A large volume direct injection ultra-high performance liquid chromatography–tandem mass spectrometry (LVDI-UHPLC-MS/MS) platform was developed for sensitively assaying the multi-component pharmacokinetic and in vitro cocktail assay of cytochrome p450 (CYP450) before and after compatibility of CTE and NGTS. The pharmacokinetic profiles of six predominantly efficacious components of CNP, including hydroxysafflor yellow A (HSYA); ginsenosides Rg1 (GRg1), Re (GRe), Rb1 (GRb1), and Rd (GRd); and notoginsenoside R1 (NGR1), were obtained, and the results disclosed that CNP could increase the exposure levels of HSYA, GRg1, GRe, GRb1, and NGR1 at varying degrees. The in vitro cocktail assay demonstrated that CNP exhibited more potent inhibition on CYP1A2 than CTE and NGTS, and GRg1, GRb1, GRd, quercetin, kaempferol, and 6-hydroxykaempferol were found to be the major inhibitory compounds. The developed pharmacokinetic interaction-based strategy provides a viable orientation for the compatibility investigation of herb medicines.

Risk assessment of dietary exposure to methylmercury in fish in the UK

2007 ◽  
Vol 26 (3) ◽  
pp. 185-190 ◽  
Author(s):  
B J Maycock ◽  
D J Benford
Keyword(s):  
Risk Assessment ◽  
Dietary Exposure ◽  
Epidemiological Studies ◽  
Consumer Products ◽  
Laboratory Animals ◽  
Human Data ◽  
Toxicological Studies ◽  
Assessment Approach ◽  
Nutritional Data ◽  
The Uk

Risk assessment of chemicals in food is generally based upon the results of toxicological studies in laboratory animals, allowing for uncertainties relating to interspecies differences, human variability, and gaps in the database. Use of quantitative human data is preferable if available, as in the example of methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which fish is the main source of dietary exposure. Human data from poisoning incidents and epidemiological studies have been used by expert committees to derive a guideline intake level for methylmercury, based on the susceptibility of the most sensitive lifestage, the developing fetus. In the UK, an expert group of nutritionists and toxicologists was formed to review the benefits and risks associated with fish consumption. A formal risk–benefit analysis was not possible because the nutritional data were not sufficiently quantitative. The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), therefore, modified the risk assessment approach to derive different guideline intake levels for different subgroups of the population. The COT opinion was used to provide targeted advice on how much fish can be consumed without undue risk from the contaminants. Consumption by adults of one weekly portion (140 g) of shark, swordfish or marlin, would lead to an exceedance of the guideline intake for methylmercury of 40–90%, set to protect the developing fetus, without considering intake from the rest of the diet. Pregnant women and women who may become pregnant within 1 year were, therefore, advised to avoid consumption of these species. Intakes in other adults would be within a higher guideline intake, set to protect groups of the population other than the developing fetus. However, consumption by children of one weekly portion of these species could lead to an exceedance of this guideline intake by up to 60%, without considering intake from the rest of the diet. It was, therefore, advised that consumption of these species by children should be avoided.

scholarly journals Desbutyl-Lumefantrine Is a Metabolite of Lumefantrine with PotentIn VitroAntimalarial Activity That May Influence Artemether-Lumefantrine Treatment Outcome

2011 ◽  
Vol 55 (3) ◽  
pp. 1194-1198 ◽  
Author(s):  
Rina P. M. Wong ◽  
Sam Salman ◽  
Kenneth F. Ilett ◽  
Peter M. Siba ◽  
Ivo Mueller ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Performance ◽  
Geometric Mean ◽  
Artemisinin Combination Therapy ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
The Relationship

ABSTRACTDesbutyl-lumefantrine (DBL) is a metabolite of lumefantrine. Preliminary data fromPlasmodium falciparumfield isolates show greater antimalarial potency than, and synergy with, the parent compound and synergy with artemisinin. In the present study, thein vitroactivity and interactions of DBL were assessed from tritium-labeled hypoxanthine uptake in cultures of the laboratory-adapted strains 3D7 (chloroquine sensitive) and W2mef (chloroquine resistant). The geometric mean 50% inhibitory concentrations (IC50s) for DBL against 3D7 and W2mef were 9.0 nM (95% confidence interval, 5.7 to 14.4 nM) and 9.5 nM (95% confidence interval, 7.5 to 11.9 nM), respectively, and those for lumefantrine were 65.2 nM (95% confidence interval, 42.3 to 100.8 nM) and 55.5 nM (95% confidence interval, 40.6 to 75.7 nM), respectively. An isobolographic analysis of DBL and lumefantrine combinations showed no interaction in either laboratory-adapted strain but mild synergy between DBL and dihydroartemisinin (sums of the fractional inhibitory concentrations of 0.92 [95% confidence interval, 0.87 to 0.98] and 0.94 [95% confidence interval, 0.90 to 0.99] for 3D7 and W2mef, respectively). Using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry assay and 94 day 7 samples from a previously reported intervention trial, the mean plasma DBL was 31.9 nM (range, 1.3 to 123.1 nM). Mean plasma DBL concentrations were lower in children who failed artemether-lumefantrine treatment than in those with an adequate clinical and parasitological response (ACPR) (P= 0.053 versusP> 0.22 for plasma lumefantrine and the plasma lumefantrine-to-DBL ratio, respectively). DBL is more potent than the parent compound and mildly synergistic with dihydroartemisinin. These properties and the relationship between day 7 plasma concentrations and the ACPR suggest that it could be a useful alternative to lumefantrine as a part of artemisinin combination therapy.

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