ABSTRACT
Dalbergia pinnata (Lour.) Prain (D. pinnata) is a valuable medicinal plant, and its volatile parts have a pleasant aroma. In recent years, there have been a large number of studies investigating the effect of aroma on human performance. However, the effect of the aroma of D. pinnata on human psychophysiological activity has not been reported. Few reports have been made about the effects of aroma and sound on human electroencephalographic (EEG) activity. This study aimed to investigate the effects of D. pinnata essential oil in EEG activity response to various auditory stimuli. In the EEG study, 30 healthy volunteers (15 men and 15 women) participated. The electroencephalogram changes of participants during the essential oil (EO) of D. pinnata inhalation under white noise, pink noise and traffic noise stimulations were recorded. EEG data from 30 electrodes placed on the scalp were analyzed according to the international 10-20 system. The EO of D. pinnata had various effects on the brain when subjected to different auditory stimuli. In EEG studies, delta waves increased by 20% in noiseless and white noise environments, a change that may aid sleep and relaxation. In the presence of pink noise and traffic noise, alpha and delta wave activity (frontal pole and frontal lobe) increased markedly when inhaling the EO of D. pinnata, a change that may help reduce anxiety. When inhaling the EO of D. pinnata with different auditory stimuli, women are more likely to relax and get sleepy compared to men.
Subject(s)
Dalbergia , Oils, Volatile , Male , Humans , Female , Sound , Anxiety , Electroencephalography , Oils, Volatile/pharmacologyABSTRACT
Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/drug therapy , Administration, Inhalation , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/drug therapy , Respiratory TherapyABSTRACT
The United States Transuranium and Uranium Registries (USTUR) is a unique resource of data and materials for studying biokinetics of uranium in the human body. In this study, bioassay data and post-mortem organ activities from a female whole-body USTUR donor who was exposed to highly enriched uranium were analyzed using the IMBA Professional Plus® software to derive the best estimate of the total intake. The resulting radiation doses delivered to this individual's whole body and major target organs were calculated from estimated intake based on case-specific dose coefficients derived using the AIDE® software. Both intake and dose calculations were carried out using the biokinetic and dosimetric models recommended by the International Commission on Radiological Protection (ICRP) in its Occupational Intakes of Radionuclides publication series. Different exposure scenarios including chronic and acute inhalation intakes were tested. A combination of a chronic inhalation intake and two acute inhalation intakes appears to best describe the bioassay data. To fit this female individual's autopsy data, the transfer rate from the liver to the blood was increased by a factor of 8 and the transfer rate from the kidneys to the blood was decreased by a factor of 2.2. This resulted in the best fit to all data (p = 0.519). The total intake was estimated to be 44.1 kBq, and the committed effective dose was 211 mSv with 96.8% contributed by 234U. 96.6% of the committed effective dose was contributed by the lungs. The remaining 3.4% of the committed effective dose was contributed by all systemic tissues and organs with the highest contribution (0.40%) from the red bone marrow. It is concluded that the current ICRP models, with the adjustment for smoking status, adequately describe uranium biokinetics for this individual except retention in the liver and kidneys. However, this study was based on a single case and may not be sufficient to identify any apparent sex-specific differences in uranium biokinetics.
Subject(s)
Occupational Exposure , Uranium , Male , Humans , Female , Follow-Up Studies , Radiometry , Radioisotopes , Software , Occupational Exposure/analysis , Radiation DosageABSTRACT
PURPOSE OF REVIEW: The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature. RECENT FINDINGS: Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace.
Subject(s)
Petroleum , Humans , Petroleum/toxicity , Hydrocarbons/toxicityABSTRACT
BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has major implications for rehabilitation, motor recovery, activities of daily living, social and interpersonal functioning, and mortality. In view of the side effects of antidepressants, aromatherapy, a widely used non-pharmacological therapy, has received growing attention in recent years for its benefits of reduced complications, accessibility, and effectiveness. This study was designed to assess the effects of inhalation aromatherapy with lavender essential oil on depression and sleep quality in patients with PSD. MATERIALS AND METHODS: Forty patients with PSD were enrolled and randomized into experimental and placebo groups. Experimental-group patients inhaled microencapsulated lavender essential oil every night at bedtime over a period of 4 weeks. A nonwoven bag containing 2.3 g of microcapsules with about 1.5 g of lavender essential oil was placed on or under the patient's pillow, depending on the patient's scent sensitivity. Placebo-group patients used the empty nonwoven bags for the same period as the experimental group. The 17-item Hamilton Rating Scale for Depression (HAMD-17), the Zung Self-Rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure outcomes. RESULTS: The HAMD-17 score, SDS score, and PSQI score showed statistically significant differences between both groups before and after intervention (P ≤ 0.01). The improvement in the experimental group was more marked than in the placebo group (P < 0.05). CONCLUSION: Lavender essential oil inhalation aromatherapy may help reduce depression and improve sleep quality in patients with PSD.
Subject(s)
Aromatherapy , Lavandula , Oils, Volatile , Humans , Sleep Quality , Activities of Daily Living , Single-Blind Method , Depression/drug therapy , Depression/etiology , Oils, Volatile/therapeutic use , Plant Oils/therapeutic useABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a highly debilitating and fatal chronic lung disease that is difficult to cure clinically. IPF is characterized by a gradual decline in lung function, which leads to respiratory failure and severely affects patient quality of life and survival. Oxidative stress and chronic inflammation are believed to be important pathological mechanisms underlying the onset and progression of IPF, and the vicious cycle of NOX4-derived ROS, NLRP3 inflammasome activation, and p38 MAPK in pulmonary fibrogenesis explains the ineffectiveness of single-target or single-drug interventions. In this study, we combined astragaloside IV (AS-IV) and ligustrazine (LIG) based on the fundamental theory of traditional Chinese medicine (TCM) of "tonifying qi and activating blood" and loaded these drugs onto nanoparticles (AS_LIG@PPGC NPs) that were inhalable and could penetrate the mucosal barrier. Our results suggested that inhalation of AS_LIG@PPGC NPs significantly improved bleomycin-induced lung injury and fibrosis by regulating the NOX4-ROS-p38 MAPK and NOX4-NLRP3 pathways to treat and prevent IPF. This study not only demonstrated the superiority, feasibility, and safety of inhalation therapy for IPF intervention but also confirmed that breaking the vicious cycle of ROS and the NLRP3 inflammasome is a promising strategy for the successful treatment of IPF. Moreover, this successful nanoplatform is a good example of the integration of TCM and modern medicine.
Subject(s)
Idiopathic Pulmonary Fibrosis , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , Medicine, Chinese Traditional , Inflammasomes/metabolism , Reactive Oxygen Species/metabolism , Quality of Life , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/metabolism , Lung/metabolism , Fibrosis , Inflammation/pathology , p38 Mitogen-Activated Protein KinasesABSTRACT
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Pulmonary Disease, Chronic Obstructive , Humans , Retrospective Studies , Drug Therapy, Combination , Administration, Inhalation , Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Muscarinic Antagonists , Adrenal Cortex Hormones , Respiratory TherapyABSTRACT
Exposure to a total of 51 targeted and non-targeted polycyclic aromatic hydrocarbons (PAHs) and their oxygenated and alkylated derivatives associated with size-segregated aerosol was investigated in rural kitchens using liquefied petroleum gas (LPG), mixed biomass (MB) and firewood (FW) fuels in northeastern India. The averaged PM10-associated parent-, alkylated-, and oxygenated-PAHs concentrations increased notably from LPG (257, 54, and 116 ng m-3) to MB (838, 119, and 272 ng m-3) to FW-using kitchens (2762, 225, and 554 ng m-3), respectively. PAHs were preferentially associated with the PM1 fraction with contributions increasing from 80 % in LPG to 86 % in MB and 90 % in FW-using kitchens, which in turn was dominated by <0.25 µm particles (54-75 % of the total). A clear profile of enrichment of low-molecular weight PAHs in cleaner fuels (LPG) and a contrasting enrichment of high-molecular weight PAHs in biomass-based fuels was noted. The averaged internal dose of Benzo[a]pyrene equivalent was the lowest in the case of LPG (19 ng m-3), followed by MB (161 ng m-3) and the highest in FW users (782 ng m-3). Estimation of incremental lifetime cancer risk (ILCR) from PAH exposure revealed extremely high cancer risk in biomass users (factors of 8-40) compared to LPG. The potential years of life lost (PYLL) and PYLL rate averaged across kitchen categories was higher for lung cancer (PYLL: 10.55 ± 1.04 years; PYLL rate: 204 ± 426) compared to upper respiratory tract cancer (PYLL: 10.02 ± 0.05 years; PYLL rate: 4 ± 7), and the PYLL rates for biomass users were higher by factors of 9-56 as compared to LPG users. These findings stress the need for accelerated governmental intervention to ensure a quick transition from traditional biomass-based fuels to cleaner alternatives for the rural population of northeastern India.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Lung Neoplasms , Petroleum , Polycyclic Aromatic Hydrocarbons , Humans , Rural Population , Air Pollution, Indoor/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Cooking , India , Cost of Illness , Particulate Matter/analysis , Air Pollutants/analysisABSTRACT
Increase of patients with hypertension in the world determines the search for new, accessible, easily applicable and mildly effective antihypertensive agents, particularly essential oils (EO). Currently available studies of the EO impact on blood pressure do not allow to assess the efficiency of such therapy. OBJECTIVE: To perform the comparative study of antihypertensive effects of inhalation with EO vapors of various composition. MATERIAL AND METHODS: The investigation included 849 women aged 55-89 years with hypertension. Two examination series were done: 10- and 20-minute duration procedures. Trial subjects were divided into control (psychorelaxation procedure) and experimental (psychorelaxation procedure combined with the EO inhalation of common basil, Italian immortelle, clove tree, common hyssop, cardamom, coriander, Caucasian nepeta, nepeta cataria, spicate lavender, bay laurel, the sort «Oxamitov¼ of brook-mint, the sorts «Prilutskaya¼, «Udaichanka¼, «Ukrainian¼ of pepper mint, the Siberian fir, Tauric wormwood, the sort «Crimean red¼ of rose, rosmarinus officinalis, Scotch pine, fennel, mountain savory, garden savory and clary sage; EO concentration in air - 1 mg/m3) groups. Systolic and diastolic blood pressure, heart rate were measured, as well as the coefficient of blood circulation efficiency and Robinson index were calculated before and after the examination in trial subjects. RESULTS: It has been established that the EO of clary sage, bay laurel, Caucasian nepeta and the sort «Oxamitov¼ of brook-mint have antihypertensive action at both 10-minute and 20-minute exposure. The antihypertensive action of EO of common basil, clove tree, coriander, nepeta cataria, the sort «Crimean red¼ of rose, rosmarinus officinalis, garden savory was found after 10-minute exposure. There was no antihypertensive action in EO application of Italian immortelle, common hyssop, spicate lavender, the sorts «Prilutskaya¼, «Ukrainian¼, «Udaichanka¼ of pepper mint, Siberian fir, tauric wormwood, Scotch pine and fennel. CONCLUSION: The EO vapors' inhalation of clary sage, bay laurel, Caucasian nepeta, the sort «Oxamitov¼ of brook-mint, common basil, clove tree, coriander, nepeta cataria, the sort «Crimean red¼ of rose, rosmarinus officinalis and garden savory can be a promising method to reduce blood pressure in patients with hypertension.
Subject(s)
Hypertension , Oils, Volatile , Humans , Female , Oils, Volatile/therapeutic use , Oils, Volatile/pharmacology , Blood Pressure , Plant Oils/pharmacology , Hypertension/drug therapyABSTRACT
OBJECTIVE: The purpose of this systematic review is to ascertain the impact of inhalation aromatherapy on stress and anxiety in clinical settings. METHODS: A search strategy was developed using various databases. Randomised Controlled Trials (RCTs) as well as single and double-blind pilot clinical studies (non-RCT) using inhalation aromatherapy with an essential oil blend or a single essential oil were examined. All studies included a control intervention and use of a validated measurement tool. The time period under review was years 2000-2021. Due to the high level of heterogeneity and element of bias, a narrative synthesis was conducted. RESULTS: The search strategy initially retrieved 628 studies and through application of the selection criteria and the removal of duplicates, 76 studies were selected for review with a total of 6539 patients. In 42% of the RCTs, physiological measures including vital signs and/or salivary cortisol were used in addition to questionnaires. Over 70% of the studies reported a positive effect on anxiety levels in the aromatherapy intervention groups compared with the control. However, in many cases this is limited by the absence of safety data, imprecise reporting of plant species and dosage of essential oil. CONCLUSION: Inhalation aromatherapy has the potential to reduce stress and anxiety with data emerging to further support this result across a wide modality of clinical treatments. However, there is a clear need for the development of standard protocols for research in this area, generating measurable results which will create the opportunity for more rigorous evidence-based outcomes.
Subject(s)
Aromatherapy , Oils, Volatile , Humans , Aromatherapy/methods , Oils, Volatile/therapeutic use , Anxiety/therapy , Anxiety Disorders/drug therapy , Administration, Inhalation , Randomized Controlled Trials as TopicABSTRACT
Bis (2-chloro-1-methylethyl) ether (DCIP), one U.S. Environmental Protection Agency priority pollutant, could pose health and/or odor risk in water environment. In this study, odor characteristics, occurrence and source of DCIP in drinking waters of China were investigated based on sensory analysis and a nation-wide investigation covering 140 drinking water treatment plants. Then multi-risk integrated health and aesthetic aspects through oral and inhalation (showering) exposure by drinking water were first estimated. Sensory evaluation showed DCIP exhibited "solvent-like" odor with thresholds of 34.8 ng/L in air and 142.0 ng/L in water. DCIP was detected at comparable concentrations in raw and finished waters (<1280 ng/L) and was by-product from industrial production of epichlorohydrin/propylene oxide. Lifetime Average Daily Dose through oral exposure was 0-36.65 ng/day/kg, corresponding to odor activity values of 0-8.4 and hazard quotients of far < 1, indicating drinking tap water might cause odor issues rather than significant health hazard. The proportion of sensitive population to DCIP's odor was 6.1%. In contrast, residents rarely detect DCIP's odor by inhalation. The presence in drinking water as industrial by-product, poor removal using conventional water treatment and potential to be T&O issues, indicates urgent demand for pollutant source control to protect DCIP from entering source waters.
Subject(s)
Drinking Water , Environmental Pollutants , Water Pollutants, Chemical , Drinking Water/analysis , Ether/analysis , Solvents , Water Pollutants, Chemical/analysis , Ethers , Ethyl Ethers , Environmental Pollutants/analysis , Risk Assessment , China , Environmental MonitoringABSTRACT
INTRODUCTION: Medical cannabis is an increasingly prevalent treatment for a wide variety of indications, yet there is still no uniformly accepted protocol for the titration of cannabinoid doses. We aimed to develop a model to predict the stable THC and CBD dosages after six months of treatment using available baseline patient characteristics. METHODS: In this prospective study, we included all consecutive adult patients (age 18 and above) who exclusively used a single method of cannabis delivery. Telephone interviews were conducted six months post-treatment initiation to assess changes in symptoms and side effects. We prospectively analyzed THC and CBD dosages with respect to demographic variables and patient characteristics in two main groups divided according to cannabis administration method - inhalation or sublingual oil. RESULTS: A total of 3,554 patients were included in the study (2,724 exclusively inhaled cannabis and 830 exclusively consumed cannabis as sublingual oil). The daily THC and CBD doses were significantly higher in the inhalation group than in the sublingual group (p<.001). None of the four models predicting THC and CBD doses in the two groups had satisfactory prediction ability (adjusted R-squared between 0.007 and 0.09). Male gender, unemployed status, tobacco smoking and a lack of concern about cannabis treatment were associated with a higher inhaled THC dose (p<.001). CONCLUSION: Models based on patient characteristics failed to accurately predict the final titration doses of CBD and THC for both inhalation and sublingual administration. Clinical guidelines should maintain a highly individual approach for cannabinoid dosing.
Subject(s)
Cannabinoids , Cannabis , Medical Marijuana , Adult , Humans , Male , Adolescent , Prospective Studies , Dronabinol , Medical Marijuana/adverse effectsABSTRACT
Objective: Aromatherapy has been used for patients on maintenance hemodialysis (MHD), but the outcomes are still controversial. Thus, we conducted this study to systematically evaluate the effect of aromatherapy on the quality of life of patients on MHD.Methods: We searched the PubMed, Embays, Scopus, Web of Science, and CNKI databases for randomized controlled trials that evaluated the use of aromatherapy in dialysis patients and reported at least one outcome of interest.Results: Twenty-two relevant studies were included in the meta-analysis. The meta-analysis revealed that aromatherapy significantly increased subjective sleep quality (a lower score indicates better sleep quality) [standardized mean difference (SMD) = -1.52, 95% CI (-2.38, -0.67), p < 0.01] and reduced fatigue [SMD = -1.14, 95% CI (-1.95, -0.33), p = 0.01], anxiety [SMD = -1.38, 95% CI (-2.09, -0.67), p < 0.01], symptoms of restless legs syndrome [RLS; SMD = -1.71, 95% CI (-2.09, -1.33), p < 0.01], and arteriovenous fistula puncture pain [SMD= -1.56, 95% CI (-2.60, -0.52), p < 0.01].Conclusions: Aromatherapy may be used as a novel complementary and alternative therapy to improve sleep quality and reduce fatigue, anxiety, symptoms of RLS, and arteriovenous fistula puncture pain in patients on MHD.
Subject(s)
Aromatherapy , Humans , Quality of Life , Pain , Renal Dialysis , FatigueABSTRACT
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. PATIENTS AND METHODS: This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. RESULTS: We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. CONCLUSION: Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.
Subject(s)
East Asian People , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Muscarinic Antagonists/therapeutic use , Lung , Administration, Inhalation , Drug Therapy, Combination , Adrenal Cortex Hormones/therapeutic use , Respiratory Therapy , Bronchodilator Agents/therapeutic useABSTRACT
BACKGROUND: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure-efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. METHODS: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. RESULTS: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. CONCLUSION: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.
Subject(s)
Biopharmaceutics , Medicine, Chinese Traditional , Animals , Mice , Administration, Intravenous , Injections, Intravenous , LungABSTRACT
Depression and anxiety are common diseases that endanger the physical and mental health of individuals. Agarwood incense inhalation has been used as a traditional Chinese medicine for relaxation and to improve sleep for centuries. In a previous study by the authors it was demonstrated that agarwood essential oil (AEO) injection exerted anxiolytic and antidepressant effects. Therefore the present study further investigated the anxiolytic and antidepressant effects of AEO inhalation on anxiolytic mice induced by M-chlorophenylpiperazine and depressive mice induced by chronic unpredictable mild stress. The results demonstrated that AEO exerted a significant anxiolytic effect, whereby autonomous movements were inhibited during the light dark exploration test and open field test. Furthermore, the tail suspension test and the forced swimming test demonstrated that AEO also exerted an antidepressant effect, whereby the immobility times were decreased. Moreover, AEO was determined to increase the levels of 5-hydroxytryptamine, γ-aminobutyric acid (GABA) A receptor (GABAA) and glutamate (Glu) in anxiolytic mice and inhibit the levels of GABAA and Glu in depressive mice. Further investigations into how AEO affected the Glu/GABA system demonstrated that AEO markedly increased the protein expression levels of GABA transaminase (GABAT), glutamate metabotropic receptor 5 (GRM5), glutamate ionotropic receptor AMPA type subunit 1 (GluR1) and vesicular glutamate transporter 1 (VGluT1). Furthermore, AEO reduced the expression levels of GABAT, glutamate ionotropic receptor NMDA type subunit 2B and GRM5, and enhanced the expression levels of GluR1 and VGluT1. These results demonstrated that AEO potentially possesses antianxiety and antidepressant properties. The present study determined that the mechanism was related to the regulation of Glu/GABA neurotransmitter system homeostasis.
ABSTRACT
Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG's drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-ß pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of -25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFß pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFß signalling in cell-based studies and thus holds promise as a potential treatment for PAH.
ABSTRACT
BACKGROUND: The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) Consumer tool was developed to fill in a methodology gap for a high throughput, screening level tool to support industry compliance with the European Union's Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. OBJECTIVE: To evaluate if the TRA Consumer tool has met its design of being a screening level tool (i.e., one which does not under-predict potential exposures). METHODS: The TRA Consumer tool algorithms and defaults were reviewed and performance benchmarked vs. other consumer models and/or empirical data. Findings from existing reviews of the TRA consumer tool were also considered and addressed. RESULTS: TRA predictions based on its default inputs exceeded measured exposures when available, typically by orders of magnitude, and were generally greater than or similar to those of other consumer exposure tools. For dermal exposure from articles, there was no evidence that a diffusivity approach would provide more appropriate exposure estimates than those of the TRA. When default values are refined using more specific data, the refined values must be considered holistically to reflect the situation being modeled as some parameters may be correlated. SIGNIFICANCE: This is the first evaluation of the ECETOC TRA consumer tool in its entirety, considering algorithms, input defaults, and associated predictions for consumer products and articles. The evaluation confirmed its design as a screening level tool. IMPACT STATEMENT: The ECETOC TRA Consumer tool has been widely applied to generate exposure estimates to support chemical registrations under the EU REACH regulation. This evaluation supports the appropriateness of the TRA as a screening level exposure assessment tool. It also warrants additional measurements of consumer exposure, especially for article use scenarios, to aid the development of consumer exposure tools and chemical risk assessment.
Subject(s)
Ecotoxicology , Occupational Exposure , Humans , Occupational Exposure/analysis , Algorithms , Risk Assessment/methods , IndustryABSTRACT
Tennessee Eastman Corporation workers were exposed to uranium dust resulting in high-linear energy transfer (LET) irradiation to lung tissue. In this work, radiation lung doses were reconstructed for 26 650 men and women working at the plant between 1942 and 1947. Site air monitoring data of uranium concentrations and payroll records were used to determine the daily inhaled activities and annualized lung doses. Variations in the activity median aerodynamic diameter of the uranium dust, the solubility of particulate matter in the lungs and the sex-specific breathing rate were investigated as part of a sensitivity analysis. Male and female mean lung doses of 18.9 and 32.7 mGy, respectively, from high-LET alpha irradiation, and there was general agreement with evaluations from previously published epidemiological studies. Annual lung dose estimates and sensitivity analysis for the 26 650 workers in the TEC cohort have been archived on the United States Department of Energy Comprehensive Epidemiologic Data Resource.