Phosphate Metabolites Research Articles

Reproducibility of absolute quantification of adenosine triphosphate and inorganic phosphate in the liver with localized 31 P-magnetic resonance spectroscopy at 3-T using different coils.

Concentrations of the key metabolites of hepatic energy metabolism, adenosine triphosphate (ATP) and inorganic phosphate (Pi ), can be altered in metabolic disorders such as diabetes mellitus. 31 Phosphorus (31 P)-magnetic resonance spectroscopy (MRS) is used to noninvasively measure hepatic metabolites, but measuring their absolute molar concentrations remains challenging. This study employed a 31 P-MRS method based on the phantom replacement technique for quantifying hepatic 31 P-metabolites on a 3-T clinical scanner. Two surface coils with different size and geometry were used to check for consistency in terms of repeatability and reproducibility and absolute concentrations of metabolites. Day-to-day (n = 8) and intra-day (n = 6) reproducibility was tested in healthy volunteers. In the day-to-day study, mean absolute concentrations of γ-ATP and Pi were 2.32 ± 0.24 and 1.73 ± 0.26 mM (coefficient of variation [CV]: 7.3% and 8.8%) for the single loop, and 2.32 ± 0.42 and 1.73 ± 0.27 mM (CVs 6.7% and 10.6%) for the quadrature coil, respectively. The intra-day study reproducibility using the quadrature coil yielded CVs of 4.7% and 6.8% for γ-ATP and Pi without repositioning, and 6.3% and 7.1% with full repositioning of the volunteer. The results of the day-to-day data did not differ between coils and visits. Both coils robustly yielded similar results for absolute concentrations of hepatic 31 P-metabolites. The current method, applied with two different surface coils, can be readily utilized in long-term and interventional studies. In comparison with the single loop coil, the quadrature coil also allows measurements at a greater distance between the coil and liver, which is relevant for studying people with obesity.

Pesticide residue exposure effect on health, growth, and development among children from agricultural area

Nowadays, the exposure to pesticides has become a matter of public health concern. The primary and secondary take-home exposure of pesticides may influence the health of communities. Farmworkers’ families generally live close to agricultural areas, which may increase the risk of residential pesticide exposure. Pesticide exposure affects children more than adults. Environmental quality drives the shifting patterns of children’s major health problems, from infectious to chronic diseases. Children’s developing organs may be exposed to low-dose concentrations of environmentally disruptive pesticides such as organophosphates, organochlorines, carbamates, and pyrethroids. Several groups of pesticide metabolites induce and inhibit growth and development in children. Potential health problems such as chronic respiratory disease, asthma, and wheezing in children were more often reported from agricultural communities than children from rural areas. Children who were in contact with pesticides during both their prenatal development and childhood reported diminished cognitive scores. This can be attributable to the elevated levels of pesticides found in their urine, which have been extensively documented. Diammonium phosphate (DAP) metabolites as one of the organophosphate pesticides (OPPs) residues correlate with high KIM-1 levels in urine, significantly leading to chronic kidney disease. DNA damage may be A potential reported effect in children from agricultural communities. Thus, to ensure children’s health and development, it is necessary to strengthen the impact of pesticide studies on children.

Residual Dialkyl Phosphate Metabolite Concentrations of Organophosphate Pesticides Among Indian Farmworkers: Implication of Exposure and Hazard Assessment.

Biomonitoring of urinary dialkyl phosphate (DAP) metabolites, a sensitive biomarker to assess pesticides exposure and also to study the impact of the use of personal protective equipment (PPE). A preintervention-postintervention study to biomonitor dimethylphosphate, diethylphosphate, diethylthiophosphate, and diethyl-dithiophosphate using liquid chromatography with tandem mass spectrometry among Indian farmworkers (n = 120). Dimethylphosphate was detected in all samples at a mean concentration of 74.91 μg · L -1 (17.616 μg · g -1 creatinine), whereas diethylthiophosphate and diethyl-dithiophosphate were detected in 88% and 82% of samples, respectively, among farmworkers who adopted unsafe pesticide-handling practices. Intervention studies showed a significant reduction in the urinary DAP metabolites detected among the farmworkers using PPE provided to them ( P < 0.01). Study confirms the exposure to pesticides among farmworkers and highlights the importance of the use of PPE to minimize exposure.

Dual strategy for 13C-Metabolic flux analysis of central carbon and energy metabolism in Mammalian cells based on LC-isoMRM-MS

Central carbon and energy metabolism are the most concerned metabolic pathways in 13C-Metabolic flux analysis (13C-MFA). However, some α-keto acids, ribonucleoside triphosphate (NTPs) and deoxyribonucleoside triphosphate (dNTPs) involved in central carbon and energy metabolism pathways were unstable or reactive, leading to inaccurate metabolic flux analysis. To achieve accurate 13C-MFA of central carbon and energy metabolism, we proposed a dual strategy for the detection of 101 metabolites in glucose metabolism pathways. N-Methylphenylethylamine (MPEA) was utilized for derivatization of 4 carboxyl (α-keto acids) and 8 phosphate metabolites (NTPs and dNTPs). After derivatization, the MPEA derivatives were investigated to be stable for 4 weeks under 4 °C and detected with high intensity in ∼104 cells. On the other hand, we analyzed an additional 89 metabolites in central carbon and energy metabolic pathways were directly analyzed by liquid chromatography tandem mass spectrometry (LC-MRM-MS). The limit of detection (LODs) of our method were as low as 0.05 ng/mL and the linear range was at least two orders of magnitude with determination coefficient (R2) > 0.9701. The relative standard divisions (RSDs) of intra- and inter-day of 95% metabolites were below 20%. In addition, the isotope list of 82 detected metabolites in central carbon and energy metabolism were generated according to isotopologues and isotopomers for each metabolite resulting from 13C incorporation. Accurate assessment of mass isotopomer distributions (MIDs) of intracellular 13C-labeled metabolites was achieved in [U–13C]-glucose cultured HepG2 cells by our dual strategy. Finally, we performed MID analysis of 101 metabolites in central carbon and energy metabolism. Overall, this dual method is reproducible and robust for application on 13C-MFA and has a great potential for studying clinical isotope labeled samples.

The Association Between Urinary Concentrations of Organophosphate Metabolites and Asthma-Related Outcomes Among Schoolchildren From Informal Settlements.

Objectives: There is inconsistent evidence on the relationship between pesticide exposure and childhood respiratory outcomes in non-agricultural settings. This study investigated the association between organophosphate (OP) pesticide exposure and asthma-related outcomes in children residing in four informal settlements. Methods: The study was a longitudinal study of 590 schoolchildren, with a 12months follow-up period. A standardised questionnaire adopted from the International Study of Asthma and Allergies in Childhood was administered to caregivers for child's respiratory symptoms and household characteristics. Spirometry and fractional-exhaled nitric oxide, including a phadiatop test (atopy status) and urinary dialkyl phosphate (DAP) metabolites were measured at baseline and follow-up. DAP metabolites included diethylphosphate (DEP) and dimethyl phosphate (DMP) measured at baseline and follow-up and dimethylthiophosphate (DMTP) measured only at baseline. Results: The mean ages of schoolchildren were 9.9 ± 0.91years and the overal incidence proportions of new doctor diagnosed asthma was 2.2%. No consistent patterns of increased risk of asthma outcomes with increasing DAP concentrations was found in multivariate analysis. Conclusion: Future studies with longer follow-up periods and repeated OP biomonitoring are recommended.

Ferric Ions Modulated Carbon Dots as a Fluorescent Probe for the Detection of Neopterin: An Inflammatory Prognostic Marker for Risk Prediction and Severity of Covid‐19

AbstractNeopterin (NPT) is a Guanosine Tri Phosphate (GTP) metabolite produced by activated macrophages and is considered a pro‐inflammatory and atherosclerotic agent. Beyond this NPT is a multi‐utility biomarker for assessing the status of various diseases including cardiovascular disease, depression, and malignant tumors as well as infections including viral and bacterial origin. Recent clinical investigations suggest the use NPT as a prognostic marker for the early prediction of the severity of Covid‐19, which is the prime concern of global public health. One of the main immunopathological characteristics of Covid‐19 is an excessive inflammatory response, and the severity of the infection is linked with macrophage activation syndrome (MAS). Hence the assessment of neopterin serves as an effective diagnostic tool for the risk prediction of Covid‐19. We present a fluorescence turn‐on sensor for neopterin using ferric ion‐modulated sulfur and nitrogen co‐doped carbon quantum dots. The linear detection of NPT was achieved with a limit of detection of 3.11 nM.

Vascular disease risk factors in multiple sclerosis: Effect on metabolism and brain volumes.

Vascular disease risk factors (VDRF) such as hypertension, hyperlipidemia, obesity, diabetes and heart disease likely play a role in disease progression in people with multiple sclerosis (PwMS) (Marrie, Rudick etal. 2010). Studies exploring the mechanistic connection between vascular disease and MS disease progression are scant. We hypothesized that phosphate energy metabolism impairment in PwMS with VDRFs (VDRF+) will be greater compared to PwMS without VDRFs (VDRF-) and is related to increased brain atrophy in VDRF+. To test this hypothesis, we planned to study the differences in the high energy phosphate (HEP) metabolites in cerebral gray matter as assessed by 31P magnetic resonance spectroscopic imaging (MRSI) and MRI brain volumetric in the VDRF+ and VDRF- PwMS at four different timepoints over a 3 yearlong period using a 7T MR system. We present here the results from the cross-sectional evaluation of HEP metabolites and brain volumes. We also evaluated the differences in clinical impairment, blood metabolic biomarkers and quality of life in VDRF+ and VDRF- PwMS in this cohort. Group differences in high energy phosphate metabolites were assessed from a volume of interest in the occipital region using linear mixed models. Brain parenchymal and white matter lesion volumes were determined from MR anatomic images. We present here the cross-sectional analysis of the baseline data collected as part of a longitudinal 3 yearlong study where we obtained baseline and subsequent 6-monthly clinical and laboratory data and annual 7T MRI volumetric and 31P MR spectroscopic imaging (MRSI) data on 52 PwMS with and without VDRF. Key clinical and laboratory outcomes included: body mass index (BMI), waist and thigh circumferences and disability [Expanded Disability Status Scale (EDSS)], safety (complete blood count with differential, complete metabolic), lipid panel including total cholesterol and HbA1C. We analyzed clinical and laboratory data for the group differences using student's t or χ2 test. We investigated relationship between phosphate metabolites and VDRF using mixed effect linear regression. Complete MRI data were available for 29 VDRF+, age 56.3 (6.8) years [mean (SD)] (83% female), and 23 VDRF-, age 52.5 (7.5) years (57% female) individuals with MS. The mean value of normalized adenosine triphosphate (ATP) (calculated as the ratio of ATP to total phosphate signal in a voxel) was decreased by 4.5% (p < .05) in VDRF+ compared to VDRF- MS group. White matter lesion (WML) volume fraction in VDRF+ individuals {0.007 (0.007)} was more than doubled compared to VDRF- participants {0.003 (0.006), p= .02}. We found significantly lower brain ATP and higher inorganic phosphate (Pi) in those PwMS with VDRFs compared to those without. ATP depletion may reflect mitochondrial dysfunction. Ongoing longitudinal data analysis from this study, not presented here, will evaluate the relationship of phosphate metabolites, brain atrophy and disease progression in PwMS with and without vascular disease.

Increased GH/IGF-I Axis Activity Relates to Lower Hepatic Lipids and Phosphor Metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1H/31P magnetic resonance spectroscopy. In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = -0.31; P = .02), GH during oral glucose tolerance test (R = -0.51; P < .01), and IGF-I (R = -0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism.

Myo-Inositol and D-Chiro-Inositol as Modulators of Ovary Steroidogenesis: A Narrative Review.

Myo-inositol is a natural polyol, the most abundant among the nine possible structural isomers available in living organisms. Inositol confers some distinctive traits that allow for a striking distinction between prokaryotes and eukaryotes, the basic clusters into which organisms are partitioned. Inositol cooperates in numerous biological functions where the polyol participates or by furnishing the fundamental backbone of several related derived metabolites, mostly obtained through the sequential addition of phosphate groups (inositol phosphates, phosphoinositides, and pyrophosphates). Overall myo-inositol and its phosphate metabolites display an entangled network, which is involved in the core of the biochemical processes governing critical transitions inside cells. Noticeably, experimental data have shown that myo-inositol and its most relevant epimer D-chiro-inositol are both necessary to permit a faithful transduction of insulin and of other molecular factors. This improves the complete breakdown of glucose through the citric acid cycle, especially in glucose-greedy tissues, such as the ovary. In particular, while D-chiro-inositol promotes androgen synthesis in the theca layer and down-regulates aromatase and estrogen expression in granulosa cells, myo-inositol strengthens aromatase and FSH receptor expression. Inositol effects on glucose metabolism and steroid hormone synthesis represent an intriguing area of investigation, as recent results have demonstrated that inositol-related metabolites dramatically modulate the expression of several genes. Conversely, treatments including myo-inositol and its isomers have proven to be effective in the management and symptomatic relief of a number of diseases associated with the endocrine function of the ovary, namely polycystic ovarian syndrome.

Impaired Physical Performance in X-linked Hypophosphatemia Is not Caused by Depleted Muscular Phosphate Stores.

X-linked hypophosphatemia (XLH) is a rare genetic disease, characterized by renal phosphate wasting and complex musculoskeletal manifestations including decreased physical performance. To characterize muscular deficits in patients with XLH and investigate phosphate stores in muscles. Case-control study (Muscle fatigability in X-linked Hypophosphatemia [MuXLiH]) with a 1-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019, including patients with XLH cared for at the Osteology Department, University of Wuerzburg. Thirteen patients with XLH and 13 age/sex/body weight-matched controls aged 18-65 years were included. The main outcome measure was 31P-magnetic resonance spectroscopy (31P-MRS)-based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included magnetic resonance imaging-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing, and jumping mechanography. By means of 31P-MRS, no significant differences were observed between XLH and controls regarding phosphate metabolites except for a slightly increased phosphocreatine to inorganic phosphate (PCr/Pi) ratio (XLH: 13.44 ± 3.22, control: 11.01 ± 2.62, P = .023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 ± 309.0 mL, control: 1391.1 ± 306.2 mv, P < .001). No significant differences were observed regarding isokinetic maximum torque (MVC) adjusted to quadriceps muscle volume. Jumping peak power and jump height were significantly reduced in XLH vs controls (both P < .001). The content of phosphoric compounds within the musculature of patients with XLH was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different either. Reduced physical performance in patients with XLH may result from long-term adaptation to reduced physical activity due to skeletal impairment.

Factors affecting urinary organophosphate pesticide metabolite levels among Californian agricultural community members

Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP exposure.

Descriptive analysis of organophosphate ester metabolites in a pan-Canadian pregnancy cohort

Organophosphate esters (OPEs) are widely used in numerous consumer products for their flame retardant and plasticizing properties. Despite potential widespread exposure, biomonitoring data during critical windows of development are scarce and limited to the most widely studied metabolites. We quantified urinary concentrations of multiple OPE metabolites in a vulnerable Canadian population. Using data and biobanked specimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008–2011), we measured first trimester urinary concentrations of 15 OPE metabolites as well as one flame retardant metabolite and quantified associations with sociodemographic and sample collection characteristics in 1865 pregnant participants. We applied 2 different analytical methods to quantify OPEs, one using UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and the other using Atmospheric Pressure Gas Chromatography coupled to mass spectrometry (APGC-MS/MS) with sensitive limits of detection (0.008–0.1 μg/L). We modelled associations between sociodemographic and sample collection characteristics and specific gravity-standardized chemical concentrations. Six OPE metabolites were detected in the majority (68.1–97.4 %) of participants. Bis-(2-chloroethyl) hydrogen phosphate had the highest detection rate (97.4 %). Diphenyl phosphate had the highest geometric mean concentration (0.657 μg/L). Metabolites of tricresyl phosphate were detected in few participants. Associations between sociodemographic characteristics varied according to each OPE metabolite. Pre-pregnancy body mass index tended to be positively associated with OPE metabolite concentrations whereas age tended to be inversely associated with OPE concentrations. OPE concentrations were, on average, higher in urine samples collected in the summer than other seasons the winter. We present the largest biomonitoring study of OPE metabolites in pregnant people to date. These findings demonstrate widespread exposure to OPEs and their metabolites and identify subpopulations who may experience heightened exposure.

Evaluation of Silybum marianum seed extract and vitamin B6 derivatives on methylglyoxal and sugar-induced oxidative DNA damage

AbstractReducing sugars are known to generate reactive oxygen species (ROS), mainly by means of the glycation reaction. The hydroxyl radical, a prominent entity of ROS, is known to alter cellular DNA and induces damage to DNA, and plays a role in diseases such as diabetes mellitus. In this study, the oxidative damage of DNA induced by the lysine/Fe3+/MG reaction was investigated. Silybum marianum seeds extract (SlyE), standard silymarin (Sly), and vitamin B6 derivatives, pyridoxal-5-phosphate (PLP), pyridoxamine (PM), and pyridoxine (P) in reversing glycation-induced damage in DNA were evaluated. In addition, different sugars and sugar phosphates were incubated with plasmid pBR 322 DNA to control and compare their harmful effects. Our results revealed that SlyE protected lysine/Fe3+/MG induced oxidative DNA damage more effectively than Sly. Vitamins, on the other hand, prevented this DNA damage in the order of PLP&gt;P&gt;PM. The DNA altering and damaging intensity of sugars and sugar phosphates tested increased considerably in the following order: Ribose-5-phosphate &gt; fructose-6-phosphate &gt; ribose &gt; fructose &gt; fructose-1,6 biphosphate &gt; glucose-6 phosphate &gt; glucose. The results show that the lysine/Fe3+/MG glycation reaction can cause oxidative damage of DNA through a mechanism involving hydroxyl radicals. It also provides evidence that ribose-5-phosphate and fructose and its phosphate metabolites can alter DNA more rapidly in vitro than glucose and its phosphate metabolites.

Facile synthesis of amino-functionalized magnetic materials for efficient enrichment of anionic metabolites from biological samples

The analysis of biological samples is often affected by the background matrix. Proper sample preparation is a critical step in the analytical procedure for complex samples. In this study, a simple and efficient enrichment strategy based on Amino-functionalized Polymer-Magnetic MicroParticles (NH2-PMMPs) with coral-like porous structures was developed to enable the detection of 320 anionic metabolites, providing detailed coverage of phosphorylation metabolism. Among them, 102 polar phosphate metabolites including nucleotides, cyclic nucleotides, sugar nucleotides, phosphate sugars, and phosphates, were enriched and identified from serum, tissues, and cells. Furthermore, the detection of 34 previously unknown polar phosphate metabolites in serum samples demonstrates the advantages of this efficient enrichment method for mass spectrometric analysis. The limit of detections (LODs) were between 0.02 and 4 nmol/L for most anionic metabolites and its high sensitivity enabled the detection of 36 polar anion metabolites from 10 cell equivalent samples. This study has provided a promising tool for the efficient enrichment and analysis of anionic metabolites in biological samples with high sensitivity and broad coverage, facilitating the knowledge of the phosphorylation processes of life.

Apparent diffusion coefficients of 31P metabolites in the human calf muscle at 7 T

PurposeIn this study, we aimed to measure the apparent diffusion coefficients (ADCs) of major phosphorous metabolites in the human calf muscle at 7 T with a diffusion-weighted (DW)-STEAM sequence.MethodsA DW-STEAM sequence with bipolar gradients was implemented at 7 T, and DW MR spectra were acquired in three orthogonal directions in the human calf muscle of six healthy volunteers (TE/TM/TR = 15 ms/750 ms/5 s) at three b-values (0, 800, and 1200 s/mm2). Frequency and phase alignments were applied prior to spectral averaging. Averaged DW MR spectra were analyzed with LCModel, and ADCs of 31P metabolites were estimated.ResultsFour metabolites (phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and glycerol phosphorylcholine (GPC)) were quantified at all b-values with mean CRLBs below 10%. The ADC values of PCr, ATP, Pi, and GPC were (0.24 ± 0.02, 0.15 ± 0.04, 0.43 ± 0.14, 0.40 ± 0.09) × 10–3 mm2/s, respectively.ConclusionThe ADCs of four 31P metabolites were successfully measured in the human calf muscle at 7 T, among which those of ATP, Pi and GPC were reported for the first time in humans. This study paves the way to investigate 31P metabolite diffusion properties in health and disease on the clinical MR scanner.

Alkaline pH in intracranial tuberculomas: A 31Phosphorus magnetic resonance spectroscopy study.

Intracranial tuberculomas are one of the common causes of space-occupying lesions of the brain in developing countries. Proton (1H) magnetic resonance spectroscopy (MRS) has shown lipid peak in intracranial tuberculomas as a characteristic feature. Phosphorus (31P) MRS has been used to evaluate intracranial lesions and to calculate tissue pH non-invasively. The aim of this study is to evaluate intracranial tuberculomas using 31PMRS. Intracranial tuberculomas proven by stereotactic or surgical biopsy were included in the study. After routine T1- and T2-weighted sequences, 31P MRS was performed using single-voxel intravoxel in vivo spectroscopy (ISIS) technique in the central core of the tuberculoma (voxel size 1-2 mm3). The pH was estimated using Petroff 's method using the chemical shift between phosphocreatine and Pi. 31P MRS was available for 26 patients, in which there was significant positive correlation between high-energy phosphate metabolites, (markers of bioenergetic status), and low-energy phosphate metabolites (membrane phospholipids and inorganic phosphate). The calculated pH was slightly alkaline and varied from 6.97 to 7.22. Intracranial tuberculomas showed alkaline pH in 31P MRS and this may be useful in the characterization of these lesions and possibly also in their treatment.

Organophosphate pesticide exposure as a risk factor for attempted suicide in Cape Town, South Africa: A case-control study

Pesticides are a commonly used agent for suicide in many Low- and Middle-Income countries (LMICs). However, accumulating evidence suggests that exposure to organophosphate (OP) pesticide may also increase the risk of suicide. We conducted a hospital-based case-control study to investigate whether prior household, garden or occupational OP exposure were associated with attempted suicide using conditional logistic regression modeling. Participants who attempted suicide with any means and were admitted to two Western Cape Province hospitals in South Africa were compared to a sample of controls matched by age, sex and time of admission with unrelated conditions, between August 2015 and August 2017. The means of attempted suicide was not recorded. OP exposure was determined by dialkyl phosphate (DAP) metabolites detected in hair and by environmental and occupational history. Approximately 85% of participants reported using pesticides in the home or garden and 15% of participants reported current or past occupational exposure while working on a farm. Attempted suicide was not associated with reported home or garden OP use (Odds ratio [OR] = 0.59, 95%CI 0.33–1.04), hair DAP metabolites (OR = 1.00, 95%CI 0.98–1.02) or current or past agricultural work (OR = 1.08, 95%CI 0.62–1.87), but was associated with hazardous drinking and unemployment with no household income. We found no evidence that attempted suicide was associated with environmental or occupational pesticide use in an urban South African population attending an emergency center.

The association between organophosphate insecticides, blood pressure dysregulation, and metabolic syndrome among U.S. Adults: NHANES 2015-2016

Organophosphate (OP) insecticides represent some of the most common environmental contaminants in the United States. Organophosphate insecticide use has been associated with numerous adverse health outcomes, including hypertension (HTN) and metabolic syndrome (MetS), but results from current studies are conflicting and inconclusive. In a study of 916 U.S. adults from the 2015–2016 NHANES cycle, we investigated the association between five dialkyl phosphate (DAP) metabolites of OP insecticides and blood pressure parameters (systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, HTN), as well the association between total body burden of DAPs with HTN and MetS. Weighted, multivariable linear regression revealed significant, inverse associations between diethylphosphate and systolic blood pressure (β= -0.16 p = 0.02), diethylthiophosphate and systolic blood pressure (β= -0.91 p = 0.01), total DAP exposure and systolic blood pressure (β= -0.13, p = 0.04), and between dimethylphosphate and diastolic blood pressure (β= -0.15, p = 0.0075). No significant associations were observed between total DAP exposure and odds of HTN. We additionally modeled the odds of abnormally high pulse pressure given specific quartile of total DAP exposure. Results showed a significant association between diethylphosphate and odds of abnormal pulse pressure (OR=1.29, 95% CI[1.01,1.65]), and between total DAP exposure and odds of abnormal pulse pressure (OR=1.05, 95% CI[1.03,1.10]). Lastly, we found that adults in the 3rd quartile of OP metabolite exposure had a 3.61 increased odds of having MetS when compared to individuals in the 1st quartile (OR=3.61, 95% CI[1.32,9.85]).Our preliminary findings support data from previous studies suggesting a role for OP insecticides in the pathogenesis of blood pressure dysregulation and MetS. Future studies are warranted to corroborate these findings, determine population-level clinical significance, and to elucidate potential mechanisms explaining these associations.

Characterization of Urinary Pesticide Metabolite Concentrations of Pregnant Women in Suriname.

Prenatal exposure to pesticides and the association with adverse health outcomes have been examined in several studies. However, the characterization of pesticide exposure among Surinamese women during pregnancy has not been assessed. As part of the Caribbean Consortium of Research in Environmental and Occupational Health research program, 214 urine samples were collected from pregnant women living in three regions in Suriname with different agricultural practices: capital Paramaribo, the rice producing district Nickerie, and the tropical rainforest, the Interior. We used isotope dilution tandem mass spectrometry to quantify urinary concentrations of biomarkers of three pesticide classes, including phenoxy acid herbicides and organophosphate and pyrethroid insecticides, all of which are commonly used in agricultural and residential settings in Suriname. We observed that participants residing in Nickerie had the highest urinary metabolite concentrations of 2,4-dichlorophenoxyacetic acid and pyrethroids compared to those from Paramaribo or the Interior. Paramaribo had the highest concentrations of organophosphate metabolites, specifically dialkyl phosphate metabolites. Para-nitrophenol was detected in samples from Paramaribo and the Interior. Samples from Nickerie had higher median urinary pesticide concentrations of 2,4-dichlorophenoxyacetic acid (1.06 μg/L), and the following metabolites, 3,5,6-trichloro-2-pyridinol (1.26 μg/L), 2-isopropyl-4-methyl-6-hydroxypyrimidine (0.60 μg/L), and 3-phenoxybenzoic acid (1.34 μg/L), possibly due to residential use and heavy rice production.

Assessment of Bioenergetic Deficits in Patients With Parkinson Disease and Progressive Supranuclear Palsy Using 31P-MRSI.

Bioenergetic disturbance, mainly caused by mitochondrial dysfunction, is an established pathophysiologic phenomenon in neurodegenerative movement disorders. The in vivo assessment of brain energy metabolism by 31phosphorus magnetic resonance spectroscopy imaging could provide pathophysiologic insights and serve in the differential diagnosis of parkinsonian disorders. In this study, we investigated such aspects of the underlying pathophysiology in patients with idiopathic Parkinson disease (PwPD) and progressive supranuclear palsy (PwPSP). In total, 30 PwPD, 16 PwPSP, and 25 healthy control subjects (HCs) underwent a clinical examination, structural magnetic resonance imaging, and 31phosphorus magnetic resonance spectroscopy imaging of the forebrain and basal ganglia in a cross-sectional study. High-energy phosphate metabolites were remarkably decreased in PwPD, particularly in the basal ganglia (-42% compared with HCs and -43% compared with PwPSP, p < 0.0001). This result was not confounded by morphometric brain differences. By contrast, PwPSP had normal levels of high-energy energy metabolites. Thus, the combination of morphometric and metabolic neuroimaging was able to discriminate PwPD from PwPSP with an accuracy of up to 0.93 [95%-CI: 0.91-0.94]. Our study shows that mitochondrial dysfunction and bioenergetic depletion contribute to idiopathic Parkinson disease pathophysiology but not to progressive supranuclear palsy. Combined morphometric and metabolic imaging could serve as an accompanying diagnostic biomarker in the neuroimaging-guided differential diagnosis of these parkinsonian disorders. This study provides Class III evidence that 31phosphorus magnetic resonance spectroscopy imaging combined with morphometric MRI can differentiate PwPD from PwPSP.