24-h Concentrations Research Articles

Mortality assessment attributed to long-term exposure to fine particles in ambient air of the megacity of Tehran, Iran.

Few studies regarding the health effects of long-term exposure to particulate matter with an aerodynamic diameter of 2.5μm or less (PM2.5) have been carried out in Asia or the Middle East. The objective of our study was to assess total, lung cancer and chronic obstructive pulmonary disease (COPD) mortality attributed to long-term exposure to PM2.5 among adults aged over 30years in Tehran from March 2013 to March 2016 using AirQ+ software. AirQ+ modeling software was used to estimate the number of deaths attributed to PM2.5 concentrations higher than 10μgm-3. Air quality data were obtained from the Department of Environment (DOE) and Tehran Air Quality Control Company (TAQCC). Only valid stations with data completeness of 75% in all 3years were selected for entry into the model. The 3-year average of the 24-h concentrations was 39.17μgm-3. The results showed that the annual average concentration of PM2.5 in 2015-2016 was reduced by 13% compared to that in 2013-2014. The annual average number of all natural, COPD, and lung cancer deaths attributable to long-term exposure to PM2.5 in adults aged more than 30years was 5073, 158, and 142 cases, respectively. The results of all three health endpoints indicate that the mortality attributable to PM2.5 decreased yearly from 2013 to 2016 and that the reduced mortality was related to a corresponding reduction in the PM2.5 concentration. Considering these first positive results, the steps that have been currently taken for reducing air pollution in Tehran should be continued to further improve the already positive effects of these measures on reducing health outcomes.

Health risk assessment associated with volatile organic compounds in a parking garage

Most volatile organic compounds are considered potentially harmful air pollutants to the environment and most importantly human health. The present work investigated the concentrations of 72 volatile organic compounds commonly emitted from the vehicular exhausts at a hospital parking garage. The objective was set to assess the associated health risk due to inhalation of these compounds during weekdays versus weekends. Carcinogenic and non-carcinogenic health risks were assessed using the US Environmental Protection Agency conventional approach. A total of 112 air samples were collected inside the hospital parking garage using six-liter evacuated Silonite™-coated polished stainless steel canisters. Triplicate sampling was used for quality assurance/quality control purposes. The air samples were analyzed using the gas chromatography with flame ionization detection system, which followed the US Environmental Protection Agency TO-15 Method. The overall 24-h concentrations of benzene, toluene, ethylbenzene, and xylenes were 6.78, 31.14, 11.35, and 27.85 μg/m3, respectively. These values were comparable to values reported in Europe, North America, and Asia. The weekend concentrations were lower than the weekday ones. Halogenated compounds had the highest contribution of volatile organic compounds groups to total concentrations in both weekday and weekend. The weekday and weekend concentrations temporal cycles were characterized, and they were correlated with the traffic activity inside the parking garage. Two of the measured compounds (i.e., tetrachloromethane and 1,2-dibromoethane) were discovered to pose definite cancer risk. To our knowledge, this is the first study in the region which looks at volatile organic compound levels in a parking garage and the associated health risks.

A nanoparticle-based approach to improve the outcome of cancer active immunotherapy with lipopolysaccharides

This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like Receptor 4 (TLR4), for immunotherapy in cancer. Despite holding promise within this context, the strong pro-inflammatory properties of LPS also account for its low tolerability given localized and systemic side effects, which restrict the administrable dosage. Herein, we investigated the effect of LPS decoration as a surface-active molecule on a polymeric matrix upon its efficiency and tolerability. The LPS-decorated nanoparticles (LPS-NP) were about 150 nm in size, with slightly negative zeta potential (about −15 mV) and acceptable LPS incorporation (about 70%). In vitro, the particles accounted for a higher induction of apoptosis in tumor cells cultured with murine splenocytes compared to LPS solution. When used for the treatment of a murine syngeneic colorectal tumor model, higher intratumoral deposition of the particle-bound LPS was observed. Furthermore, unlike LPS solution, which accounted for localized necrosis at high concentrations, treatment of tumor-bearing animals with equivalent doses of LPS-NP was well tolerated. We propose that the observed localized necrosis can be Shwartzman phenomenon, which, due to modulated 24-h post-injection systemic TNF-α and LPS concentrations, have been avoided in case of LPS-NP. This has in turn enhanced the therapeutic efficiency and enabled complete tumor regression at concentrations at which LPS solution was intolerable. The findings indicate that nanoparticles can serve as beyond carriers for the delivery of superficially decorated LPS molecules, but impact their overall efficiency and tolerability in cancer therapy.

Concentration, Chemical Composition and Origin of PM1: Results from the First Long-term Measurement Campaign in Warsaw (Poland)

This paper presents a 120-day-long variability of chemical composition of submicron particulate matter (PM1) over Warsaw. The content of the following components was examined in the PM1 mass: primary (POM) and secondary (SOM) organic matter, secondary inorganic matter (SIM), elemental carbon (EC) as well as Na and Cl ions (primary inorganic matter). The 24-hour concentrations of PM1 were subject to seasonal fluctuations which are typical of urban areas in Poland; their values averaged 11 µg m–3 in summer and 17 µg m–3 in winter. Most of the PM1 components and gaseous pollutants (SO2, NO2 and NOx) revealed higher mean concentrations in winter than in summer. A statistical analysis of meteorological parameters and 24-h concentrations of PM1, PM10, SO2, NO2 and NOx confirmed a significant influence of air temperature and precipitation on the concentration patterns of these pollutants over Warsaw. The highest concentrations of PM1 occurred in winter for the following wind directions: S, SE, N and NE; in summer for NE, E and S. The analysis of back trajectories demonstrated that on days with the highest 24-h concentration of PM1 polluted air masses arrived from S and SE and affected the concentration of PM1 over Warsaw. The submicron particulate matter, in as much as 62%, comprises secondary matter (SOM and SIM). The primary sources of its precursors and – to a smaller extent – of the primary matter as well – are traffic and combustion of various fuels for the purpose of heat and power generation. Their average contribution to the development of PM1 was 15% and 51%, respectively, for the entire period of observations.

Increased PD-1+CD154+ Tfh cells are possibly the most important functional subset of PD-1+ T follicular helper cells in adult patients with minimal change disease

T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)+ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1+, PD-1+CD154+, and PD-1+interleukin (IL)-21+ Tfh cells, and CD38+CD19+ and CD38+CD19+CD40+ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0.05). However, no significant difference was found in PD-1+BCL-6+ or PD-1+ICOS+ Tfh cells. Furthermore, the percentages of PD-1+ Tfh and PD-1+CD154+ Tfh cells were negatively correlated with the estimated glomerular filtration rate (eGFR), but positively correlated with the 24-h urinary protein concentration and serum IL-21 level. The percentages of PD-1+ Tfh and PD-1+CD154+ Tfh cells were positively correlated with the percentages of CD38+ plasma cells and active CD38+CD40+ plasma cells, respectively. After an 8–12-week treatment with prednisolone, the percentages of PD-1+, PD-1+CD154+, and PD-1+IL-21+ Tfh cells as well as the serum level of IL-21 were significantly reduced; in contrast, the serum levels of IL-4 and IL-10 were increased (P < 0.05). We conclude that increased PD-1+CD154+ Tfh cells are possibly the most important functional subset of PD-1+ Tfh cells and may contribute towards the pathogenesis of MCD.

Polyphenol-rich curry made with mixed spices and vegetables benefits glucose homeostasis in Chinese males (Polyspice Study): a dose-response randomized controlled crossover trial.

To investigate acute effects of two doses of a polyphenol-rich curry made with seven different spices and four base vegetables, eaten with white rice, on 24h glucose response, postprandial insulinemia, triglyceridemia and 24h urinary total polyphenol excretion (TPE). Randomized, controlled, dose-response crossover trial in healthy, Chinese men [n = 20, mean ± standard deviation (SD) age 23.7 ± 2.30years, BMI 23.0 ± 2.31kg/m2] who consumed test meals matched for calories, macronutrients and total vegetables content, consisting either Dose 0 Control (D0C) or Dose 1 Curry (D1C) or Dose 2 Curry (D2C) meal. 24h glucose concentration was measured using continuous glucose monitoring (CGM), together with postprandial plasma insulin and triglyceride for up to 7h. Total polyphenol content (TPC) of test meals and urinary TPE were measured using the Folin-Ciocalteu assay. TPC for D0C, D1C and D2C were 130 ± 18, 556 ± 19.7 and 1113 ± 211.6mg gallic acid equivalent (GAE) per portion served, respectively (p < 0.0001). Compared with D0C meal, we found significant linear dose-response reductions in the 3-h postprandial incremental AUC (iAUC) for CGM glucose of 19% and 32% during D1C and D2C meals respectively (p < 0.05) and non-significant linear dose response reductions in iAUC of insulin (p = 0.089). Notably, we found significant dose-dependent increases in postprandial triglyceride with increasing curry doses (p < 0.01). Significant increases in TPE with increasing curry doses were also observed (p < 0.01). Polyphenol-rich curry intake can improve postprandial glucose homeostasis. The longer term effects remain to be established.

Effect of cadmium exposure on hepatopancreas and gills of the estuary mud crab (Scylla paramamosain): Histopathological changes and expression characterization of stress response genes

Cadmium (Cd) is a heavy metal that accumulates easily in organisms and causes several detrimental effects, including tissue damage. Cd contamination from anthropogenic terrestrial sources flows into rivers, and through estuaries to the ocean. To evaluate the toxic effects of Cd on estuary crustaceans, we exposed the mud crab Scylla paramamosain to various Cd concentrations (0, 10.0, 20.0, and 40.0mg/L) for 24h. We also exposed mud crabs to a fixed Cd concentration (20.0mg/L) for various periods of time (0, 6, 12, 24, 48, and 72h). We observed that after exposure to Cd, the surfaces of the gill lamellae were wrinkled, and the morphologies of the nuclei and mitochondria in the hepatopancreas were altered. We analyzed the expression profiles of 36 stress-related genes after Cd exposure, including those encoding metallothioneins, heat shock proteins, apoptosis-related proteins, and antioxidant proteins, with quantitative reverse transcription PCR. We found that exposure to Cd altered gene expression, and that some genes might be suitable bioindicators of Cd stress. Gene expression profiles were organ-, duration-, and concentration-dependent, suggesting that stress-response genes might be involved in an innate defense system for handling heavy metal exposure. To the best of our knowledge, this study is the first one of histopathology and stress-response gene expression pattern of Scylla paramamosain after Cd exposure. Our work could increase our understanding of the effect of environmental toxins on estuary crustaceans.

Bacterial exposure to ZnO nanoparticles facilitates horizontal transfer of antibiotic resistance genes

Bacterial exposure to ZnO nanoparticles (nZnO) at sublethal concentrations (1 to 10mg/l) for 24h significantly increased the conjugative frequency of antibiotic resistance plasmid RP4. A 24.3-fold increase was observed in E. coli pure cultures, and an 8.3-fold increase occurred in a mixed culture of indigenous aquatic microbiota. In addition, nZnO increased by three fold the transformation efficiency of E. coli via the uptake of naked plasmid pGEX4T-1, which was confirmed by confocal fluorescence microscopy. Enhanced horizontal transfer of resistance plasmids was a nanoparticle-specific effect, since 5.3mg/l Zn2+ (representing the maximum release of Zn2+ from 10mg/l nZnO) did not enhance RP4 transfer or pGEX4T-1 uptake frequency. This phenomenon was attributed to increased bacterial cell permeability after exposure to nZnO (but not to Zn2+), which was confirmed by flow cytometry with propidium iodide staining. Overall, this study forewarns that accidental or incidental release of nZnO may facilitate environmental dissemination and propagation of antibiotic resistance genes through horizontal gene transfer.

Arginine reverses growth hormone resistance through the inhibition of toll-like receptor 4-mediated inflammatory pathway

ObjectiveGrowth hormone stimulates growth by increasing insulin-like growth factor 1 expression and secretion. In the presence of insufficient nutrients, GH increases, whereas IGF-1 expression becomes severely suppressed, leading to GH resistance. This study aimed to explore the effect of arginine (Arg) on GH resistance during malnutrition and to describe its underlying mechanism. MethodsC57BL/6J mice were injected intraperitoneally with Arg for 1h or subjected to caloric restriction with Arg supplement in drinking water for 18days. HepG2 cells were exposed to different Arg concentrations for 24h. Signaling pathway agonists/inhibitors, siRNA, and overexpression plasmids were used to investigate the underlying molecular mechanism. Liver-specific toll-like receptor (TLR4) knockout mice were utilized to clarify the role of TLR4 in Arg-induced IGF-I expression and secretion. ResultsArg inhibited the TLR4 downstream pathway by binding to TLR4 and consequently activated Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway. As a result, IGF-1 transcription and secretion increased. Arg activity was absent in liver-specific TLR4 knockout mice and was greatly suppressed in liver with overexpressed TLR4, suggesting that hepatic TLR4 was required and sufficient to induce GH resistance. By contrast, the mammalian target of rapamycin pathway was unnecessary for Arg activity. Arg not only significantly increased IGF-1 expression and secretion under acute fasting and chronic CR conditions but also attenuated body weight loss. ConclusionsOur results demonstrate a previously unappreciated pathway involving Arg that reverses GH resistance and alleviates malnutrition-induced growth restriction through the inhibition of TLR4-mediated inflammatory pathway.

Study of PM10, PM2.5, and PM1 levels in during dust storms and local air pollution events in urban and rural sites in Tehran

ABSTRACTThe aim of this study is to survey the PM10, PM2.5, and PM1 concentrations in rural and urban areas in Tehran province during cold, warm and dust storm days from December 22, 2016 to June 5, 2017 using Grimm Model aerosol spectrometer. During the study period, daily PM10, PM2.5, and PM1 concentrations ranged from 27.2 to 244.96, 8.4 to 77.9, and 6.5 to 56.8 μg/m3 in urban sites, and 22.8 to 286.4, 6 to 41.1, and 2.1 to 20.2 μg/m3 in rural parts, respectively. Particularly, both daily WHO limits for outdoor PM10 (50.0 μg/m3) and PM2.5 (25.0 μg/m3) exceeded in 95% and 83% of the outdoor measurements in winter and 82% and 58% in total sampled days in urban site, respectively. The 24-h average PM10 and PM2.5 concentrations also exceeded by 59% and 18% in winter and by 36% and 14% of all sampling days in rural site, respectively. During the dust storm, the 24-h average PM10, PM2.5, and PM1 concentrations were, respectively 4.7, 2, and 1.96 times higher than those in urban site and 2, 1.7, and 1.3 times more than those in rural site in all sampled days.

Outdoor air 1,3-butadiene monitoring near a petrochemical industry (Tarragona region) and in several Catalan urban areas using active multi-sorbent bed tubes and analysis through TD-GC/MS

1,3-Butadiene is a carcinogenic compound that can be emitted to the atmosphere from several sources, such as the combustion of organic matter or traffic. However, petrochemical industry is one of the main origins of this compound. Several campaigns (2013–2017) were conducted in twelve Catalan urban areas to determine 1,3-butadiene concentrations in outdoor air, five of which were close to Tarragona petrochemical region. 1,3-Butadiene was dynamically sampled in multi-sorbent bed tubes (Carbotrap, Carbopack X and Carboxen 569) using portable pump equipment. The analysis was performed by automatic thermal desorption coupled with capillary gas chromatography/mass spectrometry detector. El Morell, Perafort and Puigdelfí, located near petrochemical facilities, were the most impacted locations, with average concentrations up to 15±33, 33±41 and 27±39μgm−3, respectively. Maximum 24h concentrations of 125μgm−3 were observed in Puigdelfí. However, 1,3-butadiene average and maximum concentrations in the Tarragona petrochemical region diminished significantly (p≤0.05) in a drastic way (40–80%) since the first monitoring program in 2013. On the other hand, average concentrations in the rest of studied Catalan urban areas generally presented average values below 1μgm−3, ranging from 0.07–1.1μgm−3. Spain does have neither a monitoring strategy nor standard regulations related to 1,3-butadiene. Taking into account that relevant values can be found in locations near petrochemical facilities, a regulation should be implemented as soon as possible, at least in this specific areas.

Automated time-lapse microscopy a novel method for screening of antibiotic combination effects against multidrug-resistant Gram-negative bacteria

ObjectivesAntibiotic combinations are often used for carbapenemase-producing Enterobacteriaceae (CPE) but more data are needed on the optimal selection of drugs. This study aimed to evaluate the feasibility of a novel automated method based on time-lapse microscopy (the oCelloScope, Philips BioCell A/S, Allerød, Denmark) to determine in vitro combination effects against CPE and to discuss advantages and limitations of the oCelloScope in relation to standard methods. MethodsFour Klebsiella pneumoniae and two Escherichia coli were exposed to colistin, meropenem, rifampin and tigecycline, alone and in combination. In the oCelloScope experiments, a background corrected absorption (BCA) value of ≤8 at 24 h was used as a primary cut-off indicating inhibition of bacterial growth. A new approach was used to determine synergy, indifference and antagonism based on the number of objects (bacteria) in the images. Static time–kill experiments were performed for comparison. ResultsThe time–kill experiments showed synergy with 12 of 36 regimens, most frequently with colistin plus rifampin. BCA values ≤8 consistently correlated with 24-h bacterial concentrations ≤6 log10 CFU/mL. The classification of combination effects agreed with the time–kill results for 33 of 36 regimens. In three cases, the interactions could not be classified with the microscopy method because of low object counts. ConclusionsAutomated time-lapse microscopy can accurately determine the effects of antibiotic combinations. The novel method is highly efficient compared with time–kill experiments, more informative than checkerboards and can be useful to accelerate the screening for combinations active against multidrug-resistant Gram-negative bacteria.

Exposure to fine particulate matter during pregnancy and risk of term low birth weight in Jinan, China, 2014-2016.

Existing studies exploring the association between low birth weight (LBW) and maternal fine particulate matter (aerodynamic diameter<2.5μm, PM2.5) exposure have presented equivocal results, and one of the possible reasons for this finding might be due to relatively low maternal exposures. In addition, relatively narrow maternal exposure windows to PM2.5 have not been well established for LBW. We employed a nested matched case-control design among 43,855 term births in a large maternity and child care hospital in Jinan, China. A total of 369 cases were identified, and four controls per case matched by maternal age were randomly selected among those with normal birth weight (n=1,476) from 2014 to 2016. Ambient air monitoring data on continuous measures of PM2.5, nitrogen dioxide (NO2), and sulfur dioxide (SO2) (24-h average concentrations) from 2013 to 2016 were collected from thirteen local monitoring stations. An inverse distance weighting method based on both home and work addresses was adopted to estimate the individual daily exposures to these air pollutants during pregnancy by weighting the average of the twelve nearest monitoring stations within 30km of each 100m×100m grid cell by an inverse squared distance, and then the average exposure concentrations for gestational months, trimesters and the entire pregnancy were calculated. Adjusted conditional logistic regression models were used to estimate the odds ratios (ORs) per 10μg/m3 increment in PM2.5 and by PM2.5 quartiles during different gestational periods. In this study, the estimated mean values of PM2.5, NO2, and SO2 exposure during the entire pregnancy were 88.0, 54.6, and 63.1μg/m3, respectively. Term low birth weight (TLBW) increased in association with per 10μg/m3 increment in PM2.5 for the 8th month [OR=1.13, 95% confidence interval (CI): 1.04, 1.22], the 9th month (OR=1.06, 95% CI: 0.99, 1.15), the third trimester (OR=1.17, 95% CI: 1.05, 1.29), and the entire pregnancy (OR=1.38, 95% CI: 1.07, 1.77) in models adjusted for one pollutant (PM2.5). In models categorizing the PM2.5 exposure by quartiles, comparing the second, third, and highest with the lowest PM2.5 exposure quartile, the PM2.5 was positively associated with TLBW during the 8th month (OR: 1.77, 95% CI: 1.09, 2.88; OR: 1.77, 95% CI: 1.03, 3.04; OR: 1.92, 95% CI: 1.04, 3.55, respectively) and for the 9th month, only association for exposure in the third versus the lowest quartile was significant (OR: 1.91, 95% CI: 1.02, 3.58). The study provides evidence that exposure to PM2.5 during pregnancy might be associated with the risk of TLBW in the context of very high pollution level of PM2.5, and the 8th and 9th months were identified as potentially relevant exposure windows.

Risk assessment of dietary lead exposure among First Nations people living on-reserve in Ontario, Canada using a total diet study and a probabilistic approach

Indigenous peoples have elevated risk of lead (Pb) exposure as hunted traditional food can be contaminated with lead-containing ammunition. Recent scientific consensus states that there is no threshold level for Pb exposure. The objective of this study was to estimate dietary exposure to Pb among First Nations living on-reserve in the province of Ontario, Canada. A total diet study was constructed based on a 24-h recall and Pb concentrations for traditional foods from the First Nations Food, Nutrition, and Environment Study (FNFNES) and Pb concentrations in market foods from Health Canada. A probabilistic assessment of annual and seasonal traditional food consumption was conducted. Results indicate that traditional foods, particularly moose and deer meat. are the primary source of dietary Pb intake (73%), despite providing only 1.8% of the average caloric intake. The average dietary Pb exposure (0.21μg/kg/d) in the First Nations population in Ontario was 1.7 times higher than the dietary Pb exposure in the general Canadian population. Pb intake was associated with an estimated average increase in systolic blood pressure of 1.2mmHg. These results indicate that consumption of foods hunted with Pb containing ammunition and shot puts the population at elevated risk of Pb toxicity.

Air pollution and admissions due to ST elevation myocardial infarction—a time-series study from northwest of Iran

We investigated the association between the levels of air pollutants and the number of daily admissions due to ST segment elevation myocardial infarction (STEMI) in a metropolitan in the northwest of Iran. Daily concentrations of common air pollutants were obtained for the greater city of Tabriz for a period of 2years. These reports included sulfur dioxide (SO2), nitrogen dioxide (NO2), nitric oxide (NO), nitrogen byproducts (NOx), carbon monoxide (CO), ozone (O3), and particulate matters <10μm (PM10). The census of admissions for STEMI was retrieved for the same period from hospital registries. The association of daily variations in air pollutant levels and the daily number of STEMI admissions were investigated in a time-series analysis. In the multi-pollutant model adjusting for long-term trend, seasonality, and temperature, a significant association was found for 1-h [NO2] and 24-h [CO]. A marginally significant association was observed for 24-h [NO2] and 8-h [CO]. The 24-h [CO] had the strongest association with the number of admissions with STEMI. Maximum 1-h concentrations of NO2 on the same day and on the prior day as well as 24-h concentrations of CO on the prior day were independently associated with increased number of STEMI admissions. However, daily concentrations of SO2, NO, O3, and PM10 were not associated with the frequency of hospital admissions for STEMI.

Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

IntroductionTo investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy.MethodsThis was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study.ResultsA total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000–0600). A severe hypoglycemic episode was not observed in either group.ConclusionVildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women.

Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet. A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium. At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group. A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

Lead induces apoptosis in mouse TM3 Leydig cells through the Fas/FasL death receptor pathway

The study was aimed to investigate the effect of Pb toxicity on mouse Leydig cells and its molecular mechanism. The TM3 cells were cultured in vitro and exposed to Pb at different concentrations for 24h. The effects of Pb on cell proliferation and apoptosis were analyzed with MTT and Annexin V-FITC/PI via flow cytometry, respectively. Expression levels of Fas, Fas-L and caspase-8 in TM3 cells were determined by western blot. As well as the inhibitory effect of the caspase-8 inhibitor Z-IETD-FMK on cell apoptosis. We found that Pb treatment significantly decreased the cellar viability (P<0.05), increased the apoptosis (P<0.01) and the Fas, FasL, and caspase-8 expression levels in Pb-treated cells as compared to the control cells (P<0.05 or P<0.01). Furthermore, the caspase-8 inhibitor effectively block the Pb-induced cell apoptosis. Taken together, our data suggest that Pb-induced TM3 cell toxic effect may involve in the Fas/FasL death receptor signaling pathway.

A method to measure the absorbed dose of the thyroid during I-131 therapy, using a collar detector system and a SPECT acquisition.

Due to variations in biological half-life, accurate thyroid dosimetry for I-131 therapy is not trivial in clinical practice. In recent publications, systems are described to measure the uptake of I-131 in the thyroid repeatedly over time. In this work, we present a method to calculate patient specific pharmacokinetics and absorbed dose using such a collar detector system (CoTI) in combination with a SPECT acquisition and a two-compartment model fit. For three patients receiving I-131 therapy for benign thyroid conditions, the complete uptake profile is measured over a period of 15 to 25 days after administration. A SPECT measurement is performed to assess the functional volume of the thyroid and the amount of I-131 in the thyroid. The uptake profile measured in counts-per-second is converted to absolute activity in MBq using the absolute quantification of the SPECT. A two-compartment model is used as a fit to the uptake data of the thyroid and to estimate the activity in the blood-pool. The estimated absorbed dose to the thyroid is then calculated from the integral of the activity. The assessed parameters from the method (6- and 24-h uptake, thyroid volume and I-131 uptake concentration) are compared with the values as determined in clinical practice. Furthermore, the convergence of the calculated absorbed dose as a function of measurement series duration is determined to assess the required measurement duration of the uptake profile. The two-compartment model fit shows a good agreement with the measured data points. Resulting dynamic uptake profiles of the three patients differ from each other. The uptake percentages differ from the pretherapy I-123 uptake measurements that are used in usual clinical practice, which shows the potential added value of the proposed method. The duration of the required measurement series appears to be patient dependent and therefore needs to be determined for each patient individually. The proposed method allows for a basic investigation of the individual dynamic uptake profile of I-131 in the thyroid and the calculation of the absorbed dose. The proposed measurement method is feasible and easily implementable given a system that can measure the uptake of I-131 in the thyroid repeatedly over time. The observed differences in dynamic uptake profiles and the differences in the absorbed thyroid dose as calculated with our method and the parameters of the usual clinical care support the relevance of the proposed method. In future studies, this approach may possibly be used for outcome prediction and therapeutic activity optimization.

Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.

Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups—lean, overweight/obese (OW/OB), and OW/OB with T2DM—in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty-eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups—for example, phospholipids showed maximal difference at 5:00 AM (lean vs. OW/OB) and at 5:00 PM (OW/OB vs. T2DM). Metabolites that were identified with both robust 24-h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.—Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.