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1.
Psychiatry Res ; 331: 115626, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38096722

ABSTRACT

While the legal status and public perception of cannabis are currently changing in many countries, one of the important considerations from a public health viewpoint is its potential association with adverse health outcomes such as the development of psychosis. We conducted an umbrella review of systematic reviews and meta-analyses using the AMSTAR-2 to assess the quality of included reviews. We further created an evidence map to visualize and facilitate the overview of the published evidence synthesis on the association between cannabis use and all psychosis-related outcomes and risk moderators in healthy, high-risk, and clinical populations. Overall, we found 32 systematic reviews and meta-analyses. Based on a synthesis of current evidence, cannabis use is associated with subclinical psychosis states (psychotic-like experiences) and traits (schizotypal personality) in the healthy population, as well as earlier onset and development of psychosis. An association with the clinical-high-risk state for psychosis, attenuated psychosis symptoms and transition to psychosis in this population could not be confirmed. An association between cannabis use and psychosis outcomes in patients with psychotic disorder could solely be confirmed regarding relapse. Whether causal effects underlie those associations has not sufficiently been addressed in the evidence synthesis to date.


Subject(s)
Cannabis , Psychotic Disorders , Schizotypal Personality Disorder , Humans , Personality , Psychotic Disorders/complications , Schizotypal Personality Disorder/diagnosis , Systematic Reviews as Topic , Meta-Analysis as Topic
2.
Am J Physiol Lung Cell Mol Physiol ; 323(1): L107-L120, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35670484

ABSTRACT

Despite decades of research, studies investigating the physiological alterations caused by an acute bout of inflammation induced by exposing the lung to lipopolysaccharide have yielded inconsistent results. This can be attributed to small effects and/or a lack of fitted physiological testing. Herein, a comprehensive investigation of lung mechanics was conducted on 270 male C57BL/6 mice at 24, 48, or 96 h after an intranasal exposure to saline or lipopolysaccharide at either 1 or 3 mg/kg (30 mice per group). Traditional techniques that probe the lung using small-amplitude perturbations (i.e., oscillometry) were used, together with less conventional and new techniques that probe the lung using maneuvers of large amplitudes. The latter include a partial and a full-range pressure-volume maneuvers to measure quasi-static elastance, compliance, total lung volume, vital capacity, and residual volume. The results demonstrate that lung mechanics assessed by oscillometry was only slightly affected by lipopolysaccharide, confirming previous findings. In contradistinction, lipopolysaccharide markedly altered mechanics when the lung was probed with maneuvers of large amplitudes. With the dose of 3 mg/kg at the peak of inflammation (48 h postexposure), lipopolysaccharide increased quasi-static elastance by 26.7% (P < 0.0001) and decreased compliance by 34.5% (P < 0.0001). It also decreased lung volumes, including total lung capacity, vital capacity, and residual volume by 33.3%, 30.5%, and 43.3%, respectively (all P < 0.0001). These newly reported physiological alterations represent sensitive outcomes to efficiently evaluate countermeasures (e.g., drugs) in the context of several lung diseases.


Subject(s)
Lipopolysaccharides , Positive-Pressure Respiration , Animals , Inflammation , Lipopolysaccharides/pharmacology , Lung/physiology , Lung Compliance , Male , Mice , Mice, Inbred C57BL , Positive-Pressure Respiration/methods , Respiratory Mechanics/physiology
3.
Am J Physiol Lung Cell Mol Physiol ; 322(2): L294-L304, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34936511

ABSTRACT

There are renewed interests in using the parameter K of Salazar-Knowles' equation to assess lung tissue compliance. K either decreases or increases when the lung's parenchyma stiffens or loosens, respectively. However, whether K is affected by other common features of respiratory diseases, such as inflammation and airway smooth muscle (ASM) contraction, is unknown. Herein, male C57BL/6 mice were treated intranasally with either saline or lipopolysaccharide (LPS) at 1 mg/kg to induce pulmonary inflammation. They were then subjected to either a multiple or a single-dose challenge with methacholine to activate ASM to different degrees. A quasi-static pressure-driven partial pressure-volume (P-V) maneuver was performed before and after methacholine. The Salazar-Knowles' equation was then fitted to the deflation limb of the P-V loop to obtain K, as well as the parameter A, an estimate of lung volume (inspiratory capacity). The fitted curve was also used to derive the quasi-static elastance (Est) at 5 cmH2O. The results demonstrate that LPS and both methacholine challenges increased Est. LPS also decreased A, but did not affect K. In contradistinction, methacholine decreased both A and K in the multiple-dose challenge, whereas it decreased K but not A in the single-dose challenge. These results suggest that LPS increases Est by reducing the open lung volume (A) and without affecting tissue compliance (K), whereas methacholine increases Est by decreasing tissue compliance with or without affecting lung volume. We conclude that lung tissue compliance, assessed using the parameter K of Salazar-Knowles' equation, is insensitive to inflammation but sensitive to ASM contraction.


Subject(s)
Lipopolysaccharides , Lung , Airway Resistance , Animals , Inflammation , Lipopolysaccharides/pharmacology , Lung Compliance , Male , Methacholine Chloride/pharmacology , Mice , Mice, Inbred C57BL , Muscle Contraction , Respiratory Mechanics
4.
Sci Rep ; 11(1): 7777, 2021 04 08.
Article in English | MEDLINE | ID: mdl-33833346

ABSTRACT

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research. The one induced by a single lipopolysaccharide (LPS) exposure is practical. However, whether it is preferable to administer LPS intranasally or intratracheally remains an open question. Herein, female C57Bl/6 J mice were exposed intranasally or intratracheally to one dose of either saline or 3 mg/kg of LPS. They were studied 24 h later. The groups treated with LPS, either intranasally or intratracheally, exhibited a pronounced neutrophilic inflammation, signs of lung tissue damage and protein extravasation into the alveoli, and mild lung dysfunction. The magnitude of the response was generally not different between groups exposed intranasally versus intratracheally. However, the variability of some the responses was smaller in the LPS-treated groups exposed intranasally versus intratracheally. Notably, the saline-treated mice exposed intratracheally demonstrated a mild neutrophilic inflammation and alterations of the airway epithelium. We conclude that an intranasal exposure is as effective as an intratracheal exposure in a murine model of ARDS induced by LPS. Additionally, the groups exposed intranasally demonstrated less variability in the responses to LPS and less complications associated with the sham procedure.


Subject(s)
Inflammation/chemically induced , Lipopolysaccharides/adverse effects , Lung/pathology , Respiratory Distress Syndrome/chemically induced , Administration, Intranasal , Animals , Disease Models, Animal , Female , Inflammation/pathology , Lipopolysaccharides/administration & dosage , Mice , Mice, Inbred C57BL , Proteins/analysis , Respiratory Distress Syndrome/pathology
5.
Physiol Rep ; 7(10): e14093, 2019 05.
Article in English | MEDLINE | ID: mdl-31140749

ABSTRACT

Electronic cigarette uses propylene glycol and glycerol to deliver nicotine and flavors to the lungs. Given the hundreds of different brands, the thousands of flavors available and the variations in nicotine concentrations, it is likely that electronic cigarette settings and e-liquid composition affect the size distribution of particles emitted and ultimately pulmonary deposition. We used the inExpose e-cigarette extension to study two separate modes of operation of electronic cigarettes, namely power-controlled and the temperature-controlled. We also assessed several e-liquids based on propylene glycol and glycerol concentrations, nicotine content, and selected monomolecular flavoring agents (menthol, vanillin, and maltol). Particle size distribution was measured using a Condensation Particle Counter and a Scanning Mobility Particle Sizer spectrometer. Lung deposition was predicted using the International Commission on Radiological Protection model. For all resistance coils, increase in power delivery generated larger particles while maintaining a higher coil temperature generated smaller particles. Increase in glycerol concentration led to the generation of larger particles. With regard to flavors, we showed that despite minor effect of menthol and maltol, vanillin dramatically increased particle size. Presence of nicotine also increased particle size. Finally, particles emitted by the electronic cigarette were predicted to mainly deposit in the alveoli and conditions generating larger particle sizes led to a reduction in predicted lung deposition. This study shows that coil temperature, propylene glycol and glycerol concentrations, presence of nicotine, and flavors affect the size of particles emitted by an electronic cigarette, directly affecting predicted lung deposition of these particles.


Subject(s)
Electronic Nicotine Delivery Systems , Lung/metabolism , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Temperature , Vaping , Administration, Inhalation , Aerosols , Equipment Design , Flavoring Agents/administration & dosage , Flavoring Agents/chemistry , Flavoring Agents/metabolism , Glycerol/administration & dosage , Glycerol/chemistry , Glycerol/metabolism , Humans , Models, Biological , Nicotine/chemistry , Nicotine/metabolism , Nicotinic Agonists/chemistry , Nicotinic Agonists/metabolism , Particle Size , Propylene Glycol/administration & dosage , Propylene Glycol/chemistry , Propylene Glycol/metabolism
6.
J Vis Exp ; (137)2018 07 10.
Article in English | MEDLINE | ID: mdl-30059019

ABSTRACT

Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to non-invasively assess some features of the respiratory function in humans as well as in laboratory animals. The present article focuses on the application of the double-chamber plethysmography (DCP) in small animals. It provides background information on the methodology as well as a detailed step-by-step procedure to successfully assess respiratory function in conscious, spontaneously breathing animals in a non-invasive manner. The DCP can be used to monitor the respiratory function of multiple animals in parallel, as well as to identify changes induced by aerosolized substances over a chosen time period and in a repeated manner. Experiments on control and allergic mice are used herein to demonstrate the utility of the technique, explain the associated outcome parameters, as well as to discuss the related advantages and shortcomings. Overall, the DCP provides valid and theoretically sound readouts that can be trusted to evaluate the respiratory function of conscious small animals both at baseline and after challenges with aerosolized substances.


Subject(s)
Plethysmography/methods , Respiration , Animals , Consciousness , Mice
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