Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States

ObjectiveSeveral β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.MethodsThe exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.ResultsResults showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.ConclusionThe dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.

Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes (BTX) in BTX-Exposed Petrochemical Workers Cohort (BEPWC)

Background Ubiquitous benzene, toluene, and xylenes (BTX) frequently occur together. Exposure to single BTX component and BTX-rich mixtures could induce hematological effects. However, it still needs to clarify the hematological influences of long-term co-exposure to BTX components, and propose reference exposure levels (REL) base on their hematological effects. Objective We sought to evaluate the hematological effects of long-term BTX co-exposure and estimate REL based on these effects. Methods We established BTX-Exposed Petrochemical Workers Cohort (BEPWC), quantified long-term BTX exposure levels by calculating cumulative exposure doses (CED), and detected multiple hematologic parameters in both baseline and follow-up stages. Generalized weighted quantile sum (gWQS) regression models were used to evaluate the combined effects of BTX components and identify their contributions. Benchmark Dose (BMD) Software was used to calculate BMD and the lower confidence limits (BMDL). Results Most hematologic parameters were decreased after four-year follow-up (P<0.05). We found a positive association of benzene with the decline in monocyte counts (β = 0.012), and a negative association of toluene with the decline in mean corpuscular hemoglobin concentrations (β =-0.905) after false discovery rate (FDR) adjustment. The associations of BTX components with the decline in hematologic parameters were mostly significantly stronger in subjects with higher baseline parameters, males, drinkers, and overweighted subjects (FDR-adjusted Pinteraction <0.05). BTX components had positive combined effects on the decline in monocyte counts, red blood cell counts, and hemoglobin concentrations (Ptrend for WQS index <0.05). BMD (and BMDL) for CED levels of benzene, toluene, and xylene were estimated at 2.138 (1.559), 1.449 (1.325), and 2.937 (2.312) mg/m3×year, respectively. Conclusions Our study revealed complex hematological effects of long-term BTX occupational co-exposure, and proposed some REL-TWA around 0.01 ppm for BTX components based on their hematological effects. All these findings are worthy of further investigation.

Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2

Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2-1 kPa CO2 (2,000 - 10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 minutes, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ∼4 to ∼22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3− and pH, likely because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.

Screening for Noise-Induced Hearing Loss among Palm Oil Mill Workers in Peninsular Malaysia: A Comparison across Noise Exposure Levels

Background: Palm oil mill workers in Malaysia are exposed to hazardous levels of noise in the workplace, and thus are at risk of developing noise-induced hearing loss (NIHL). In 2019, Malaysia introduced a new noise regulation, which reduced the level of permissible noise exposure. Objectives: This study aims to determine the prevalence of NIHL among palm oil mill workers based on screening data and assess the effects of different noise exposure levels on NIHL. Methods: A cross-sectional study was conducted by analyzing data from noise risk assessment reports of selected mills and screening audiometric data from workers. NIHL was defined as bilateral high-frequency hearing loss. Results: The overall NIHL prevalence was 50.8%. Noise exposure level and age were significant predictors of NIHL among the workers. The risk of developing NIHL was high even for workers who were not categorized in the high-risk group. Conclusions: In view of the findings, a precautionary approach is needed when evaluating the risk of NIHL in the study population. Vulnerable groups of workers must be protected from occupational noise hazards through the implementation of effective hearing conservation programs in the workplace.

Estimating Sound Exposure Levels Due to a Broadband Source over Large Areas of Shallow Sea

3D sound propagation modeling in the context of acoustic noise monitoring problems is considered. A technique of effective source spectrum reconstruction from a reference single-hydrophone measurement is discussed, and the procedure of simulation of sound exposure level (SEL) distribution over a large sea area is described. The proposed technique is also used for the modeling of pulse signal waveforms at other receiver locations, and results of a direct comparison with the pulses observed in the experimental data is presented.

Personal Exposure to Fine Particles (PM2.5) in Northwest Africa: Case of the Urban City of Bamako in Mali

Personal exposure to particulate matter (PM) from anthropogenic activities is a major concern in African countries, including Mali. However, knowledge of particulates is scant. This study was undertaken to characterize personal exposure to PM2.5 microns or less in diameter (PM2.5) in the city of Bamako in Mali. The exposure to PM2.5, through daily activities was observed from September 2020 to February 2021. Participants wore palm-sized optical PM2.5 sensors on their chest during their daily activities. The exposure levels in four different groups of residents were investigated in relation to their daily activities. The variation in PM2.5 concentration was measured during different activities in different microenvironments, and the main sources of exposure were identified. The highest average 10 min concentrations were observed at home and in bedrooms, while the participants were using specific products typically used in Africa, Asia, and South America that included insecticides (IST; 999 µg/m3) and incense (ICS; 145 µg/m3), followed by traffic (216 µg/m3) and cooking (150 µg/m3). The lowest average 10 min concentrations were also observed in the same microenvironment lacking IST or ICS (≤14 µg/m3). With no use of specific products, office workers and students were the least exposed, and drivers and cooks were the most exposed. The concentrations are up to 7.5 and 3 times higher than the World Health Organization’s yearly and daily recommended exposure levels, respectively, indicating the need to promptly elaborate and apply effective mitigation strategies to improve air quality and protect public health. This study highlights the importance of indoor air pollution sources related to culture and confirms previous studies on urban outdoor air pollution sources, especially in developing countries. The findings could be applied to cities other than Bamako, as similar practices and lifestyles are common in different cultures.

External exposure levels and fluoride content in the urine of workers at aluminium electrolysis

Introduction. In the context of large-scale modernization and intensification of aluminium production, it becomes relevant to assess the actual fluoride loads and the main factors that determine the occupational exposure of workers to fluorides for health risk analysis. Materials and methods. Monitoring studies of the content of hydrofluoride and aerosols of fluoride salts in the air of electrolysis shops were carried out with traditional and modernized technologies for producing aluminium and fluorine in urine in 108 workers of the primary professions and 35 people in the control group. Determination of the concentration of fluorides was carried out by photometric methods, and fluorine in urine - by ionometric methods. Results. The total concentration of fluoride compounds in the air of the modernized shops was 1.4-2.1 times lower than the values in traditional shops. The fluoride content in the urine of workers in these workshops ranged from 0.8 to 4.7 mg/l, 1.1-6.7 times higher than the level of the control group and 1.1-2.3 times the limit value of the biological exposure index. The highest external and internal fluoride loads and associated health risks are found in workers who maintain electrolyzers and anodes. A closer, noticeable (r = 0.644) correlation was found between the content of fluoride in urine and the levels of gaseous hydrofluoride in the air, indicating its predominant effect on workers compared to other determinants (total concentration of fluorides, seniority and age). Conclusion. The studies’ results indicate a high additional informative value and reliability of biomonitoring of fluoride in urine, which, combined with analysis of air pollution with fluorides, provides a completely objective assessment of the risk of exposure to workers. The presence of high levels of hydrofluoride in the air of electrolysis shops creates a higher occupational health risk for workers.

The use of Cohort Size Shrinkage Index (CSSI) to quantify regional famine intensity during the Chinese famine of 1959-61

There has been a growing interest in studying the causes and impact of the Great Chinese Famine of 1959-61. The Cohort Size Shrinkage Index (CSSI) is the most widely used measure to examine famine intensity and was used in at least 28 Chinese famine studies to date. We examined the potential impact of violations of three requirements for a valid CSSI measure: reliable information on cohort size by year of birth; a stable trend of cohort size by year of birth; and the absence of significant regional migration. We used data from the 1% China 2000 Census to examine the trend of cohort size over time and concentrated on the time window between 1950-70 to exclude policies and events with a large impact on birth trends other than the famine itself. Across China we established a significant difference in cohort size trends between pre-famine births and post-famine births, violating one of the main requirements for a valid CSSI measure. This leads to systematic differences in CSSI depending on what non-famine years are selected for comparison. At the province level, CSSIs estimated based on pre- & post-famine births tend to overestimate famine intensity at higher exposure levels and underestimate intensity at lower levels compared to CSSIs based on pre-famine births alone. This is problematic and demonstrates that the CSSI is not as robust an estimator of famine intensity as had been assumed previously. We recommend therefore that all CSSI should be based on pre-famine birth trends. Using data from Sichuan province, we demonstrate a less pronounced dose-response relation between famine intensity and tuberculosis outcomes using pre-famine based CSSI as compared to reported patterns based on pre- & post-famine based CSSI. We encourage researchers to re-examine their results of Chinese famine studies as local differences in cohort size of pre-famine and post-famine births may lead to significant discrepancies of CSSI estimation and change the interpretation of their findings.

The rationality of PM2.5 monitoring sites’ locations based on exposure level across eastern China

Due to the heterogeneity of PM2.5 and population distribution, the representativeness of existing monitoring sites is questionable when the monitored data were used to assess the population exposure. By comparing the PM2.5 concentration from a satellite-based dataset named the China High Air Pollutants (CHAP), population and exposure level in urban areas with monitoring stations (UWS) and without monitoring stations (UNS), we discussed the rationality of the current spatial coverage of monitoring stations in eastern China. Through an analysis of air pollution in all urban areas of 256 prefectural-level municipalities in eastern China, we found that the average PM2.5 concentration in UNS in 2015 and 2018 were 52.26 μg/m3 and 41.32 μg/m3, respectively, which were slightly lower than that in UWS (52.98 μg/m3 and 41.48 μg/m3). About 12.1% of the prefectural-level municipalities had higher exposure levels in certain UNS than those in UWS. With the faster growth of UNS population, the gap between exposure levels of UNS and UWS were narrowing. Hence, currently prevalent administration-based principle of site location selection might have higher risk of missing the non-capital urban areas with relatively higher PM2.5 exposure level in the future.