Chronic Inhalation Research Articles

Modelling of constant and realistic chronic intake scenarios and their implications.

Chronic inhalation intake of radionuclides is possible for radiation workers in the nuclear industry. The International Commission on Radiological Protection (ICRP) provides organ retention fractions as well as daily urinary and fecal excretion for chronic intake of various radionuclides. In this study, organ retention fractions and daily urinary excretion for chronic intake were estimated for constant chronic intake (CCI) and realistic chronic intake (RCI) scenarios. CCI is a daily intake of 1Bq, and RCI is an intake of 1.4Bq for five working days followed by two days gap. Radiologically important radionuclides such as 239Pu, 60Co, 137Cs, 131I, and 3H having long, moderate, and short effective half-lives in the deposited organ or whole body were considered. The retention fractions and daily urinary excretion of all the radionuclides studied for RCI were found to converge with those for the CCI scenario at ~40 to 200days except for daily urinary excretion of 131I.

Chronic inhalation exposure to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) alters cardiac collagen in Wistar rats.

2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most used in the world and exposure to herbicides can affect animals and humans, causing toxic effects that include cardiotoxicity. This is the first study to evaluate cardiac remodeling after experimental simulation of environmental exposure by chronic inhalation (6months) to the herbicide 2,4-D. Thirty male Wistar rats were exposed to two different concentrations of the 2,4-D formulation (low - 187.17mg/m3; and high - 467.93mg/m3) and the control group exposed to nebulization of chloride solution 0.9% sodium. Inhalation exposure lasted 6months. Mice hearts were collected for histology. There was a difference between exposure concentrations in relation to the increase in cardiac collagen (P<0.0001). In mice exposed to a low dose of 2,4-D and a decrease in the fractal dimension of cardiac collagen in the high dose of 2, 4-D (P=0.010). This study shows that chronic inhalation exposure to 2,4-D induces cardiotoxicity in rats, characterized by extracellular matrix reorganization and changes in collagen levels, highlighting the impact of the exposure route on cardiac outcomes. There was no difference in relation to anatomical parameters, cardiomyocyte area, collagen types I and III and analysis of arteriole thickness. Chronic exposure at different doses to the 2,4D herbicide had the potential to cause damage to cardiac remodeling by altering cardiac collagen in rats.

Toxicological characterization of the insecticide metofluthrin and assessment of the carcinogenic risk to human health due to its chronic inhalation effect

The aim of the investigation is the toxicological characterization and analysis of the danger criteria of the insecticide metofluthrin with an assessment of the carcinogenic risk to health caused by chronic inhalation exposure to the substance at the level of the maximum possible concentrations in the air environment of human life. The analysis of scientific reports of the US Environmental Protection Agency (US EPA) and the European Chemicals Agency (ECHA) on the toxicological properties of metofluthrin was carried out. The assessment of the risk of the development of carcinogenic effects due to chronic inhalation exposure to metofluthrin was carried out taking into account the average daily dose of the substance that can enter the human body during the natural life span (LADD) and the carcinogenic potential factor (SF) in accordance with domestic guidelines. Classification of levels of carcinogenic risk was carried out using domestic and international approaches. It was established that the limiting criteria for the danger of metofluthrin are the average lethal concentration in air (LC50 =1080 mg/m³) and the size of the zone of chronic action (Zch=7.46), which characterizes the danger of occurrence of chronic intoxication due to long-term inhalation exposure. According to these indicators, metofluthrin is classified as a dangerous substance (hazard class 2). The key effects of the toxic action of metofluthrin are determined – neurotoxicity, hepatotoxicity and nephrotoxicity. The threshold non-genotoxic oncogenic potential of metofluthrin according to the phenobarbital type was established. Individual carcinogenic risk under different scenarios of chronic inhalation exposure to metofluthrin was calculated. The substance concentration of 3.54 mg/m³ leads to a high level of risk (1.5×10-3), which is considered unacceptable for production conditions and the population. At concentrations of 0.28 mg/m³ and 1.0 mg/m³, the risk is estimated as average and acceptable for production conditions (1.1-4.1×10-4). The risk of exposure to a concentration of 0.14 mg/m³ is classified as low and acceptable for the population (5.7×10-5). Thus, the results obtained in the study indicate that such concentrations of metofluthrin in the air as 0.14 – 0.28 – 1.0 mg/m³ are safe for human health, subject to compliance with medical and sanitary regulations at the stage of production and application of insecticides based on metofluthrin as prescribed.

Assessment of disorders of metabolic process on the base of quantification of target proteins under aerogenic influence of aluminum oxide in children

Introduction. The study of the mechanisms of the occurrence of adverse events at the molecular level, followed by the study of biological processes at the cellular, tissue, and organ level, allows further investigating the mechanism of the toxic action of chemicals to predict the development of adverse effects in humans. The purpose of the study is to evaluate disturbances in the signal-transporter pathways of metabolic processes on the base of the quantification of identified target proteins under aerogenic exposure to aluminum oxide in children. Materials and methods. Using the methods of chemical-analytical, statistical, proteomic, biochemical, histological research, and bioinformation analysis, the adverse effects were assessed in 4–7 years children and Wistar rats exposed to aerogenic and inhalation exposure to aluminum oxide (Al2O3). A comparative analysis of the results obtained in the experiment and natural conditions was carried out. Results. In children under conditions of long-term aerogenic exposure to Al2O3 at the level of 0.1–1.0 RfC, the urine concentration of the studied substance was found to be up to 2 times higher than the average comparison value and the reference value. In the experiment with chronic inhalation of Al2O3 at a dose equivalent to the real one, the aluminum urine content in rats was 3.5 times higher than the control value. Comparative analysis of proteomic maps in children revealed 23 significantly different protein spots, 8 of which had a relationship between intensity changes and an increase in Al urine concentration. In rats, 15 significantly different protein spots were found between the groups, 13 of which had a reliable relationship with the exposure marker. In natural and experimental studies, only two identical proteins were found: apolipoprotein A-I and transthyretin; increased levels of ALAT, ASAT and alkaline phosphatase, total and direct bilirubin, gamma-aminobutyric and glutamic acids, lipid hydroperoxide in the blood serum; increased MDA and decreased AOA in the blood plasma. Pathomorphological changes in the tissues of the brain, heart, and liver were confirmed in the experiment. Limitations. The research conducted allows drawing a conclusion about the effect of Al2O3 on the body only through the aerogenic route of entry. Conclusion. Based on the bioinformational analysis of the results obtained and assessment of the cause-and-effect relationships of the transformation of the proteomic profile of blood plasma under natural conditions, verified in the experiment, the leading molecular-cellular events in the development of adverse effects in the form of oxidation, imbalance of lipoprotein and neurotransmitter metabolism, and decreased neurogenesis activity were identified. Metabolic disorders are predicted in the tissues of the heart, blood vessels, liver, and brain under continued conditions of aerogenic exposure to Al2O3. The study of the cascade of events of adverse responses (from the molecular to the organ level) expands knowledge about the pathogenetic mechanisms of metabolic processes of dysregulation of signal-transporter pathways in the human body in response to the influence of a chemical factor, including Al2O3. This increases the effectiveness of early prediction of the occurrence of the disease and the development of targeted measures to prevent adverse consequences.

Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications.

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under "M1. Manipulation of Blood and Blood Components" and therefore could be considered a prohibited method if used as a non-diagnostic tool.

Assessment of the risk to the health of the population living in the zone influenced by atmospheric emissions from the engineering industry

Introduction. During operation, machine-building enterprises emit pollutants that can negatively affect the health of the population. The study aims to determine the impact of emissions from a machine–building plant, as well as background atmospheric pollution, on the health risk of the population of Novokuznetsk. Materials and methods. The work used data from the volume of maximum permissible emissions of a machine-building plant. The researchers calculated the maximum and average concentrations of pollutants using the "ECOcenter – Standard" program at 36 exposure points selected on the city map. Experts determined the maximum permissible concentrations of pollutants in the atmosphere in accordance with SanPiN 1.2.3685-21. The authors calculated the risks to public health in accordance with the Guidelines R 2.1.10.1920-04. The classification of risk levels was carried out on the basis of MP 2.1.10.0156-19. 2.1.10. Scientists also made a risk assessment considering background atmospheric pollution. Results. Specialists carried out a risk assessment from exposure to nitrogen dioxide, carbon monoxide, sulfur dioxide, carbon (soot), inorganic dust, hexavalent chromium. The maximum and average concentrations of pollutants, as well as the maximum concentrations calculated taking into account background pollution, did not exceed the maximum permissible level. The average concentrations of nitrogen dioxide and hexavalent chromium, taking into account the background, exceeded the hygienic standard. The values of the hazard indices for acute and chronic exposures without taking into account the background, as well as for acute exposures taking into account the background, corresponded to the minimum (target) risk level. The values of the hazard indices for chronic inhalation effects, considering the background, corresponded to the alarming risk level at five points, amounting to 3.084–3.800. With chronic exposure, taking into account the background, an alarming level of risk was revealed for the effect on the respiratory organs (at four points the hazard index was 3.117 to 3.616) and blood (at three points the hazard index was in the range from 3.090 to 3.433). The total individual carcinogenic risk, excluding background, did not exceed the permissible level, ranging from 1.08×10–8 to 2.43×10–7 at different points, taking into account the background, amounted to 1.79×10–4–2.26×10–4, which corresponds to an alarming level. Hexavalent chromium makes the main contribution to the formation of carcinogenic risk. Limitations. Calculated concentrations of pollutants were used to assess the risks. Conclusion. The risks from exposure to atmospheric emissions from the machine-building plant correspond to the minimum (target) level. Background concentrations of toxic substances in chronic inhalation exposures determine an alarming level of non-carcinogenic risk at five points, as well as an alarming level of carcinogenic risk at all points of exposure. Ethics. This study did not require the conclusion of the Ethics Committee.

Neurotoxic effects associated with chronic inhalation and oral exposure to glyphosate-based herbicide IN adult rats.

The use of glyphosate-based herbicides (GBHs) for agricultural production has increased substantially around the world, as have their residues in the environment. Its effects on the central nervous system and neurotoxicity pathways are still not fully understood. The aim of this study was to evaluate the neurotoxic effect of chronic exposure to a GBH in adult rats. Sixty adult male albino Wistar rats were allocated into 6 groups, 2 control groups, and four GBH exposure groups (n=10/group). The animals were exposed to two concentrations of GBH, orally and by inhalation: 2.99 × 10-3grams of active ingredient per hectare (g.a.i./ha) and 7.48 × 10-3g.a.i./ha. The animals were exposed for six months. Behavioral studies were performed. Brain tissue was collected for histopathological, immunohistochemical, and oxidative stress analyses. Animals exposed by inhalation to GBH spent more time in the central area of the open field test, whereas animals exposed to a high oral concentration of GBH spent less time in the open arms in the elevated plus-maze test. Tissue hyperemia occurred only in animals exposed to high concentrations of GBH. There was a greater thickness of the cerebral cortex and an increase in the expression of the BCL-2 in the animals exposed by inhalation to GBH. There was no difference in the doses of malonaldehyde and protein carbonylation between exposed and unexposed groups. The exposure to GBH caused increased levels of anxiety, regardless of the route, high concentrations caused hyperemia and inhalation exposure cause increased cortex thickness and increased BCl-2 expression.

Качество атмосферного воздуха и риск развития болезней системы кровообращения у населения крупного города европейского севера

Cardiovascular diseases are the most frequent causes of premature mortality associated with ambient air quality. In the Arkhangelsk region, population mortality caused by diseases of the circulatory system is higher than the national average. The aim of this study was to assess ambient air quality in Arkhangelsk and associated health harm in adult population. The study relied on using data of ambient air monitoring in Arkhangelsk collected over 2011–2022. We analyzed average annual levels of 23 pollutants and primary incidence of diseases of the circulatory system (CVD) and calculated hazard quotients under chronic inhalation exposure (HQ), hazard index (HI) for the cardiovascular system, and the number of attributable deaths associated with exposure to PM10 and PM2.5. Over the analyzed period, the average long-term concentrations of most pollutants met hygienic standards. Average levels of formaldehyde, chromium, copper and benzene were found to exceed the MPL by 1.5–2.3 times. Hazard coefficients for formaldehyde (HQ = 2.3), copper (HQ = 1.8) and PM2.5 (HQ = 1.7) were established to be above their permissible value. The risk of developing general toxic effects is determined to be high (HI = 6.6) for the cardiovascular system. The main contribution to the risk level is made by copper and PM2.5. Attributable outcomes of primary cardiovascular incidence among the adult population of Arkhangelsk associated with exposure to PM10 and PM2.5 equaled 10.7 and 2.9 ‰ cases per year. The greatest harm under exposure to PM2.5 is due to the development of coronary artery disease and amounts to 1.9 ‰ cases per year.

Ambient air quality and risk of circulatory diseases for population of a large city in the European north of Russia

Cardiovascular diseases are the most frequent causes of premature mortality associated with ambient air quality. In the Arkhangelsk region, population mortality caused by diseases of the circulatory system is higher than the national average. The aim of this study was to assess ambient air quality in Arkhangelsk and associated health harm in adult population. The study relied on using data of ambient air monitoring in Arkhangelsk collected over 2011–2022. We analyzed average annual levels of 23 pollutants and primary incidence of diseases of the circulatory system (CVD) and calculated hazard quotients under chronic inhalation exposure (HQ), hazard index (HI) for the cardiovascular system, and the number of attributable deaths associated with exposure to PM10 and PM2.5. Over the analyzed period, the average long-term concentrations of most pollutants met hygienic standards. Average levels of formaldehyde, chromium, copper and benzene were found to exceed the MPL by 1.5–2.3 times. Hazard coefficients for formaldehyde (HQ = 2.3), copper (HQ = 1.8) and PM2.5 (HQ = 1.7) were established to be above their permissible value. The risk of developing general toxic effects is determined to be high (HI = 6.6) for the cardiovascular system. The main contribution to the risk level is made by copper and PM2.5. Attributable outcomes of primary cardiovascular incidence among the adult population of Arkhangelsk associated with exposure to PM10 and PM2.5 equaled 10.7 and 2.9 ‰ cases per year. The greatest harm under exposure to PM2.5 is due to the development of coronary artery disease and amounts to 1.9 ‰ cases per year.

Uranium Body Clearance Kinetics-A Long-term Follow-up Study of Retired Nuclear Fuel Workers.

Nuclear industry workers exposed to uranium aerosols may risk kidney damage and radiation-induced cancer. This warrants the need for well-established dose and risk assessments, which can be greatly improved by using material-specific absorption parameters in the ICRP Human Respiratory Tract Model. The present study focuses on the evaluation of the slow dissolution rate ( s s , d -1 ), a parameter that is difficult to quantify with in vitro dissolution studies, especially for more insoluble uranium compounds. A long-term follow-up of urinary excretion after the cessation of chronic inhalation exposure can provide a better estimate of the slow-rate dissolution. In this study, two workers, previously working for >20 y at a nuclear fuel fabrication plant, provided urine samples regularly for up to 6 y. One individual had worked at the pelletizing workshop with the known presence of uranium dioxide (UO 2 ) and triuranium octoxide (U 3 O 8 ). The second individual worked at the conversion workshop where multiple compounds, including uranium hexafluoride (UF 6 ), uranium dioxide (UO 2 ), ammonium uranyl carbonate, and AUC [UO 2 CO 3 ·2(NH 4 ) 2 CO 3 ], are present. Data on uranium concentration in urine during working years were also available for both workers. The daily excretion of uranium by urine was characterized by applying non-linear least square regression fitting to the urinary data. Material-specific parameters, such as the activity median aerodynamic diameter (AMAD), the respiratory tract absorption parameters, rapid fraction ( f r ,), rapid dissolution rate ( s r , d -1 ), and slow dissolution rate ( s s , d -1 ) and alimentary tract transfer factor ( f A ) acquired from previous work along with default absorption types, were applied to urine data, and the goodness of fit was evaluated. Thereafter intake estimates and dose calculations were performed. For the ex-pelletizing worker, a one-compartment model with a clearance half-time of 662 ± 100 d ( s s = 0.0010 d -1 ) best represented the urinary data. For the ex-conversion worker, a two-compartment model with a major [93% of the initial urinary excretion (A 0 )] fast compartment with a clearance half-time of 1.3 ± 0.4 d ( s r = 0.5 d -1 ) and a minor (7% of A 0 ) slow compartment with a half-time of 394 ± 241 d ( s s = 0.002 d -1 ) provided the best fit. The results from the data-fitting of urinary data to biokinetic models for the ex-conversion worker demonstrated that in vitro derived experimental parameters (AMAD = 20 μm, f r = 0.32, s r = 27 d -1 , s s = 0.0008 d -1 , f A = 0.005) from our previous work best represented the urinary data. This resulted in an estimated intake rate of 0.66 Bq d -1 . The results from the data-fitting of urinary data to biokinetic models for the ex-pelletizing worker indicated that the experimental parameters (AMAD = 10 μm and 20 μm, f r = 0.008, s r = 12 d -1 , f A = 0.00019) from our previous dissolution studies with the slow rate parameter step-wise optimized to urine-data ( s s = 0.0008 d -1 ) gave the best fit. This resulted in an estimated intake rate of 5 Bq d -1 . Experimental parameters derived from in vitro dissolution studies provided the best fit for the subject retired from work at the conversion workshop, where inhalation exposure to a mix of soluble (e.g., AUC, UF 6 ) and relatively insoluble aerosol (e.g., UO 2 ) can be assumed. For the subject retired from work at the pelletizing workshop, which involved exposure to relatively insoluble aerosols (UO 2 and U 3 O 8 ), a considerably higher s s than obtained in dissolution studies provided a better representation of the urinary data and was comparable to reported s s values for UO 2 and U 3 O 8 in other studies. This implies that in vitro dissolution studies of insoluble material can be uncertain. When evaluating the results from the retrospective fitting of urine data, it is evident that the urine samples acquired after cessation of exposure provide less fluctuation. Long-term follow-up of uranium excretion after cessation of exposure is a good alternative for determining absorption parameters and can be considered the most viable way for determining the slow rate for more insoluble material.

Withdrawal from chronic alcohol impairs the serotonin-mediated modulation of GABAergic transmission in the infralimbic cortex in male rats

The infralimbic cortex (IL) is part of the medial prefrontal cortex (mPFC), exerting top-down control over structures that are critically involved in the development of alcohol use disorder (AUD). Activity of the IL is tightly controlled by γ-aminobutyric acid (GABA) transmission, which is susceptible to chronic alcohol exposure and withdrawal. This inhibitory control is regulated by various neuromodulators, including 5-hydroxytryptamine (5-HT; serotonin). We used chronic intermittent ethanol vapor inhalation exposure, a model of AUD, in male Sprague-Dawley rats to induce alcohol dependence (Dep) followed by protracted withdrawal (WD; 2 weeks) and performed ex vivo electrophysiology using whole-cell patch clamp to study GABAergic transmission in layer V of IL pyramidal neurons. We found that WD increased frequencies of spontaneous inhibitory postsynaptic currents (sIPSCs), whereas miniature IPSCs (mIPSCs; recorded in the presence of tetrodotoxin) were unaffected by either Dep or WD. The application of 5-HT (50 μM) increased sIPSC frequencies and amplitudes in naive and Dep rats but reduced sIPSC frequencies in WD rats. Additionally, 5-HT2A receptor antagonist M100907 and 5-HT2C receptor antagonist SB242084 reduced basal GABA release in all groups to a similar extent. The blockage of either 5-HT2A or 5-HT2C receptors in WD rats restored the impaired response to 5-HT, which then resembled responses in naive rats. Our findings expand our understanding of synaptic inhibition in the IL in AUD, indicating that antagonism of 5-HT2A and 5-HT2C receptors may restore GABAergic control over IL pyramidal neurons. Significance statementImpairment in the serotonergic modulation of GABAergic inhibition in the medial prefrontal cortex contributes to alcohol use disorder (AUD). We used a well-established rat model of AUD and ex vivo whole-cell patch-clamp electrophysiology to characterize the serotonin modulation of GABAergic transmission in layer V infralimbic (IL) pyramidal neurons in ethanol-naive, ethanol-dependent (Dep), and ethanol-withdrawn (WD) male rats. We found increased basal inhibition following WD from chronic alcohol and altered serotonin modulation. Exogenous serotonin enhanced GABAergic transmission in naive and Dep rats but reduced it in WD rats. 5-HT2A and 5-HT2C receptor blockage in WD rats restored the typical serotonin-mediated enhancement of GABAergic inhibition. Our findings expand our understanding of synaptic inhibition in the infralimbic neurons in AUD.

Risks assessment to the health of the population in the area of emissions pollutants influence of carbon graphite production enterprises

Risk assessment of the impact of the enterprise's activities on the environment includes risk assessment of the impact of the activity on the health of the population. Risk as the probability of undesirable events is an integral component of any person's life. Risk characterization integrates data on the danger of the analyzed chemical substances, the amount of exposure, parameters of "dose-response" dependence, with the aim of quantitative and qualitative assessment of risk, identification and assessment of the comparative significance of existing problems for the health of the population. In scientific terms, hazard identification is the process of establishing a causal relationship between the action of a chemical substance and the development of adverse effects on human health. The main goal of the hazard identification stage is the selection of priority, indicator chemical substances, the study of which allows to reliably characterize the sources of occurrence and the level of risk of public health impairment. Assessment of dose-response relationships is a process of quantitative characterization of toxicological information and establishment of a relationship between the likely influencing dose (concentration) of a pollutant and the incidence of adverse events in the exposed population. Characteristics of "dose-response" dependence, which are most often used to assess carcinogenic risk, have been sufficiently studied in epidemiological studies. Among them is the factor of carcinogenic potential (ICS), which reflects the probability of the development of a harmful reaction when the dose (concentration) increases by 1 mg/kg or 1 mg/m3 per exposure level, associated with a certain probability of effect (the indicators of this group are used for establishment of reference, i.e., reference doses and concentrations). The individual carcinogenic risk characterizes the upper limit of possible carcinogenic risk during the period corresponding to the average life expectancy of a person (70 years). Today, in the world, the classification and assessment of the acceptable risk to the health of the population caused by the chemical influence of chemical substances that pollute the environment is quite wide. the system of acceptance criteria recommended by WHO is used. In accordance with these criteria, the first range of risk (individual lifetime risk equal to or less than 1·10-6, which also corresponds to an additional case of serious illness or death per 1 million exposed persons) characterizes such levels of risk as are perceived by all strata population as quite small, which do not differ from ordinary everyday risks (De minimas level). Such risks do not require additional measures to reduce them and their levels are subject to periodic control. The second range (greater than 1·10-6 and less than 1·10-4) corresponds to the zone of conditionally accepted (acceptable) risk. It is at this level that most of the foreign and recommended by international organizations hygienic standards for the population as a whole are established. Levels of suitable risk belong to constant control. The third range (greater than 1·10-4 and less than 1·10-3) is suitable for professionals and unsuitable for the general population. The emergence of such a level of risk requires the development and implementation of planned health measures. The fourth range (equal to or greater than 1·10-3) is unsuitable neither for the population nor for professionals. This range is designated as De manifestis Risk, and when it is reached, it is necessary to carry out emergency health measures to reduce the risk on the part of the city authorities. During the assessment of the risk to the health of the population of Zaporizhzhia from the emissions of PJSC "Ukrgrafit", priority pollutants were identified: carbon oxides, nitrogen oxides, sulfur oxides, substances in the form of suspended solid particles of undifferentiated composition. Hazard indices were determined for individual HQ substances (non-carcinogenic risks) and in the case of combined exposure to HI, individual carcinogenic risks (ICR) and combined exposure (CRa) were calculated. Assessment of long-term effects (at the level of average annual concentration) on human health of the investigated substances. allowing to assess the chronic inhalation effect of the occurrence of negative effects in the health of the exposed population during the lifetime for the assessment and characterization of multistage risk showed that the hazard indices (HQ) do not exceed the norms.

Bletilla striata polysaccharide alleviates chronic obstructive pulmonary disease via modulating gut microbiota and NR1H4 expression in mice

Bletilla striata polysaccharide (BSP) is the main component of Bletilla striata and has been revealed to enhance immune responses. Chronic obstructive pulmonary disease (COPD) results from the chronic inhalation of toxic particles and gases, which initiates innate and adaptive immune responses in the lungs. This study aimed to evaluate whether the effects of BSP on COPD were related to the abundance of gut microbiota and explored the underlying mechanism. COPD mice were induced with cigarette smoke and human bronchial epithelial cells (HBEC) were subjected to cigarette smoke extract (CSE) for in vitro studies. BSP alleviated the inflammatory response and the inflammatory cell infiltration in lung tissues and promoted the recovery of respiratory function in COPD mice. BSP mitigated CSE-induced HBEC injury by repressing inflammation and oxidative stress. 16s rRNA sequencing revealed that BSP increased the abundance of Bacteroides intestinalis. Bacteroides intestinalis colonization enhanced the therapeutic effect of BSP in COPD mice by upregulating NR1H4 and its encoded protein FXR. Reduction of NR1H4 impaired the therapeutic impact of BSP and Bacteroides intestinalis in COPD. These data demonstrate that BSP inhibits COPD by upregulating NR1H4 through Bacteroides intestinalis, which underpins the application of BSP as a therapeutic agent for COPD.

Improving the reliability of internal dosimetry for uranium workers: Application of the ICRP/OIR uranium model to long-term occupational intakes

In the Occupational Intakes of Radionuclides (OIR) report series, the International Commission on Radiological Protection (ICRP) published updated biokinetic models and dosimetric data associated with the internal exposure of workers, which are consistent with the recommendations of ICRP Publication 103. The present study focused on the application of the new OIR uranium model published in ICRP Publication 137, which is relevant for the interpretation of measurements of activity in the body and in excreta, and for calculating the committed effective dose. The main objective of this study was to assess the impacts of the new OIR biokinetic models and dose coefficients compared with the old ones based on ICRP Publications 60/78/119. CIEMAT and the University of Salamanca in Spain have been working on re-interpreting in vitro bioassay data obtained from workers with long-term exposure to inhaling uranium oxides during the fabrication of nuclear fuel elements using low enriched uranium, which is now classified as OIR type M/S material. The effects on the retention/excretion models and dose coefficients were studied for 234U, 235U, 238U, and the uranium mixture. Committed effective doses were re-assessed using BIOKMOD code by applying the new OIR excretion model and dose coefficients considering acute and/or chronic inhalation intake scenarios. A reduction by roughly a factor of four was obtained compared with former doses based on ICRP Publications 60/78/119, which is an important effect to take into consideration.

Protective Effects of Coenzyme Q10 on Testicular Histology in Rats Exposed via Chronic Mosquito Coil Smoke Inhalation.

To determine the preventive effect of coenzyme Q10 (CoQ10) on the testicular histology of rats exposed chronically to mosquito coil smoke. Experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College/National University of Medical Sciences, Rawalpindi, Pakistan, from January to December 2020. Thirty male Sprague Dawley rats were divided into three groups of 10 rats each. Group A was the healthy control. Group B rats were exposed to allethrin-based mosquito coil smoke for 12 weeks (4 hours/day). Group C rats received coenzyme Q10 (CoQ10, 10mg/kg/day) through oral gavage, in addition to 12 weeks of mosquito coil smoke exposure (4 hours/day). At the end of the study, testicular histology was compared among three groups including the germinal epithelium height, seminiferous tubule diameter, and testicular capsule thickness, while adjusting for the body weight variations among rats. The rats in Group B, exposed only to mosquito coil smoke showed testicular disruption, characterised by dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.007), as compared to the control group rats. However, the germinal epithelium height (p = 0.73) and testicular capsule thickness (p = 0.31) of rats receiving CoQ10 in addition to mosquito coil smoke inhalation were not significantly different from the control group. Prolonged inhalation of allethrin-based mosquito coil smoke can cause testicular disruption among rats. The oral CoQ10 administration can effectively prevent the histomorphological adverse effects on the testis among rats exposed to mosquito coil smoke. Allethrin, Coenzyme Q10, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule.

Pulmonary Alveolar Proteinosis Secondary to Chronic Ethylene Oxide Occupational Inhalation

In this case report, a 40-year-old male patient with a persistent and productive cough lasting over 2 weeks, accompanied by dyspnea, who received an anti-tuberculosis drug regimen for 12 months without any clinical improvement at a different hospital before being referred to Persahabatan Central General Hospital was presented. In-depth clinical, and radiological investigations, the periodic acid-Schiff (PAS)-positive related to pulmonary alveolar proteinosis (PAP) confirmed through transbronchial biopsy (TBB). PAP is a rare lung disease with exceptionally low prevalence and incidence, Notably, the patient’s occupational environment played a crucial role in the diagnosis, as we identified occupational PAP secondary to chronic inhalation of ethylene oxide in a poorly ventilated work setting and inadequate respiratory protection. The patient was administered inhaled filgrastim (1 vial) at four intervals over 30 days, yielding favorable and satisfactory clinical as well as radiological outcomes.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Impact of Pharmacist-led Interventions on Medication Adherence and Inhalation Technique in Adult Patients with COPD and Asthma

Introduction: Inhalation technique and medication adherence are essential prerequisites for achieving optimal therapeutic effects in patients with chronic obstructive pulmonary disease (COPD) and asthma. Although there are various effective treatments for respiratory disorders, disease control in these patients is still sub-optimal because of incorrect inhalation techniques and poor medication adherence. Pharmacist-led interventions have demonstrated a positive impact on improving inhalation technique, better medication adherence, and thus subsequently improving the quality of life of patients. Methods: Search engines such as PubMed, Google Scholar, and Science Direct were used to identify the relevant information using keywords: Chronic Obstructive Pulmonary Disease, Asthma, Pharmaceutical care, Pharmacist Intervention, Medication Adherence and Inhalation Technique. The relevant articles that were published between 2005 to 2021 were included and reviewed for the Pharmacist-led interventions to improve medication adherence, inhalation technique, and quality of life of patients with COPD and asthma. Results: Of the 300 articles screened, a total of 14 articles met the inclusion criteria and were included for review. Pharmacist-led interventions help to improve the medication adherence, inhalation technique, and quality of life of patients with COPD and asthma. Similarly, the articles mentioned in this review found that the interventions provided by the pharmacist to COPD and asthma patients were cost-effective in terms of reducing hospitalization rates and severe exacerbation rates. Conclusion: Our review concluded that the pharmacists’ interventions have a significant improvement in medication adherence and inhalation techniques with the enhancement of therapeutic effects in adult patients with COPD and asthma.

Chronic inhalation of H2S in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Insight into hematological parameters of petrol station workers.

Benzene is one of the major carcinogenic factors that can affect liver, kidneys, and lungs. Chronic inhalation of benzene vapor by petrol stations workers has been shown to have an impact on hematological parameters; thus, the present study aimed to investigate the effect of benzene exposure on petrol station workers. The study involved 99 participants, 50 of whom have been exposed to benzene and 49 of whom have not (control). A 5 ml blood sample in an ethylenediaminetetraacetic acid (EDTA) anticoagulant tube was collected from each subject, and a complete blood count test was used to test hematological parameters. The current study showed a significant decrease in red blood cells, packed cell volume, and hemoglobin in the exposed group compared to the control group. However, the amount of white blood cells was significantly increased (p < 0.0001) in the exposed group compared to the control group. Notably, there was no significant difference in platelet counts between the two groups. In terms of exposure time, subjects who have been exposed to benzene for more than a year and fewer than 10 years showed a significant decrease (p < 0.05) in RBCs indices and a significant increase (p < 0.0001) in WBCs compared to those in the control group CONCLUSIONS: Thus, the findings indicated that significant differences in hematological parameters were found in workers who were exposed to benzene compared to those who had not been exposed.