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Journal of Neurovirology Feb 2022Macrophages are key elements of the innate immune system. Their HIV-1 infection is a complex process that involves multiple interacting factors and various steps and is...
Macrophages are key elements of the innate immune system. Their HIV-1 infection is a complex process that involves multiple interacting factors and various steps and is further altered by exposure of infected cells to methamphetamine (Meth), a common drug of abuse in people living with HIV. This is reflected by dynamic changes in the intracellular and secreted proteomes of these cells. Quantification of these changes poses a challenge for experimental design and associated analytics. In this study, we measured the effect of Meth on expression of intracellular and secreted galectins-1, -3, and -9 in HIV-1 infected human monocyte-derived macrophages (hMDM) using SWATH-MS, which was further followed by MRM targeted mass spectrometry validation. Cells were exposed to Meth either prior to or after infection. Our results are the first to perform comprehensive quantifications of galectins in primary hMDM cells during HIV-1 infection and Meth exposure a building foundation for future studies on the molecular mechanisms underlying cellular pathology of hMDM resulting from viral infection and a drug of abuse-Meth.
Topics: HIV Infections; HIV Seropositivity; HIV-1; Humans; Macrophages; Methamphetamine
PubMed: 35175539
DOI: 10.1007/s13365-021-01025-4 -
Molecules (Basel, Switzerland) Oct 2020New developments in the synthesis, resolution, and synthetic applications of chiral 1-phenylethylamine (α-PEA) reported in the last decade have been reviewed. In... (Review)
Review
New developments in the synthesis, resolution, and synthetic applications of chiral 1-phenylethylamine (α-PEA) reported in the last decade have been reviewed. In particular, improvements in the synthesis of α-PEA and its derivatives and chiral resolution, as well as their applications in the resolution of other compounds, were discussed. α-PEA was used as a chiral auxiliary in the diastereoselective synthesis of medicinal substances and natural products. Chiral ligands with α-PEA moieties were applied in asymmetric reactions, and effective modular chiral organocatalysts were constructed with α-PEA fragments and used in important synthetic reactions.
Topics: Chemistry Techniques, Synthetic; Phenethylamines; Stereoisomerism
PubMed: 33114098
DOI: 10.3390/molecules25214907 -
Biological Psychiatry. Cognitive... Sep 2022Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity as measured by resting-state functional magnetic resonance...
BACKGROUND
Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging. Specifically, thalamic intrinsic functional connectivity is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal limbic cortices (hypoconnectivity). Psychedelics such as lysergic acid diethlyamide (LSD) elicit similar thalamocortical hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical hypoconnectivity with prefrontal limbic cortices, because current findings are equivocal. Thalamocortical hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic-induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics.
METHODS
We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic intrinsic functional connectivity with 2 brain networks (auditory-sensorimotor and salience networks, corresponding to sensorimotor and prefrontal limbic cortices, respectively), using a double-blind, placebo-controlled, crossover design.
RESULTS
All active substances elicited auditory-sensorimotor-thalamic hyperconnectivity compared with placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with the salience network, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns.
CONCLUSIONS
Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.
Topics: Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Hallucinogens; Humans; Lysergic Acid; Lysergic Acid Diethylamide; N-Methyl-3,4-methylenedioxyamphetamine
PubMed: 35500840
DOI: 10.1016/j.bpsc.2022.04.003 -
The International Journal on Drug Policy Jun 2022Wastewater-based epidemiology (WBE) is a complementary epidemiological data source to monitor stimulant consumption. The aims were to: (i) study intra- and inter-year...
BACKGROUND AND AIMS
Wastewater-based epidemiology (WBE) is a complementary epidemiological data source to monitor stimulant consumption. The aims were to: (i) study intra- and inter-year temporal changes in stimulant use in Belgium during the first wave of the COVID-19 pandemic; and (ii) evaluate the effect of COVID-19 restrictive measures on stimulant consumption.
METHODS
The study population corresponded to the catchments of four wastewater treatment plants corresponding with four Belgian cities (i.e., Antwerp-Zuid, Boom, Brussels, Leuven). Daily 24-h composite influent wastewater samples collected over one week in September 2019 and March through June 2020 during the first wave of the COVID-19 pandemic were analyzed for biomarkers of amphetamine, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Measured concentrations were converted to population-normalized mass loads by considering the daily flow rate and the catchment population size. Mobile network data was used to accurately capture population movements in the different catchment areas. Temporal changes were assessed with multiple linear regression models, and the effect of the COVID-19 interventions on stimulant consumption were investigated.
RESULTS
An increase in amphetamine use was observed in three cities during governmental restrictions, with highest consumption predominantly during lockdown. Similarly, cocaine consumption was higher after the pandemic started, with highest consumption noted during the lockdown period in Boom and Leuven. Consumption of MDMA was similar in Antwerp-Zuid, Brussels and Leuven throughout the entire sampled period. In Boom, the highest consumption was observed during the full lockdown period.
CONCLUSIONS
The present study shows the potential of WBE to assess the impact of stringent lockdown measures on stimulant use in Belgium. This paper shows that strong restrictive measures did not have a profound effect on stimulant consumption.
Topics: Amphetamines; Belgium; COVID-19; Central Nervous System Stimulants; Cocaine; Communicable Disease Control; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Pandemics; Substance Abuse Detection; Wastewater
PubMed: 35427945
DOI: 10.1016/j.drugpo.2022.103679 -
JACC. Cardiovascular Imaging Nov 2019
Topics: Diastole; Dobutamine; Echocardiography, Stress; End Stage Liver Disease; Humans
PubMed: 30660550
DOI: 10.1016/j.jcmg.2018.11.020 -
Addictive Behaviors Jun 2024Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between... (Review)
Review
OBJECTIVE
Anxiety and depression are prevalent mental health problems in people who use illicit stimulants. Improved understanding of the temporal relationship between methamphetamine, ecstasy/MDMA, or cocaine use with anxiety or depression informs public health interventions and treatment options for those experiencing this co-occurrence. This narrative systematic review sought to examine associations and temporality between the use of methamphetamine, ecstasy/MDMA, or cocaine, with anxiety or depressive symptoms. Method Systematic searches of 4 electronic databases were conducted up to August 2023. Study eligibility included the measurement of anxiety and/or depressive symptoms, and frequency of illicit stimulant use (methamphetamine, cocaine, or ecstasy/MDMA) at two separate time points, with data analysis of the association between these variables. The Joanna Briggs Critical Appraisal Checklist was utilised to assess quality. Data was extracted, and a narrative synthesis incorporating an eight-criteria framework to assess associations was conducted. Results 4432 studies were screened for eligibility; 11 studies (3 RCTs and 8 prospective cohort studies) were included. Evidence for an association between depressive symptoms and methamphetamine use was demonstrated in six studies, with temporal evidence in three studies supporting methamphetamine use preceding depressive symptoms. Three studies reported an association between cocaine use and depressive symptoms. Evidence for associations with any of the illicit stimulants and anxiety symptoms was lacking.
CONCLUSIONS
There was some evidence to support a case for temporality, particularly for methamphetamine use and depressive symptoms. Investing in longitudinal studies is pivotal to understanding the dynamic and reciprocal relationship between illicit stimulant use and anxiety or depressive symptoms. A limitation of the study was the variation in the measurement and analysis of outcomes.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Methamphetamine; Depression; Prospective Studies; Anxiety; Cocaine; Central Nervous System Stimulants; Cocaine-Related Disorders
PubMed: 38394960
DOI: 10.1016/j.addbeh.2024.107988 -
Molecules (Basel, Switzerland) Oct 2023The aim of this study was to develop and optimize a chiral HPLC-MS/MS method for quantitative analysis of ()-/()-salbutamol and ()-/()-salbutamol-4'--sulfate in human...
Development of an HPLC-MS/MS Method for Chiral Separation and Quantitation of ()- and ()-Salbutamol and Their Sulfoconjugated Metabolites in Urine to Investigate Stereoselective Sulfonation.
The aim of this study was to develop and optimize a chiral HPLC-MS/MS method for quantitative analysis of ()-/()-salbutamol and ()-/()-salbutamol-4'--sulfate in human urine to allow for bioanalytical quantitation of the targeted analytes and investigations of stereoselectivity in the sulfonation pathway of human phase Ⅱ metabolism. For analytical method development, a systematic screening of columns and mobile phases to develop a separation via enantiomerically selective high performance liquid chromatography was performed. Electrospray ionization settings were optimized via multiple-step screening and a full factorial design-of-experiment. Both approaches were performed matrix-assisted and the predicted values were compared. The full factorial design was superior in terms of prediction power and knowledge generation. Performing a longitudinal excretion study in one healthy volunteer allowed for the calculation of excretion rates for all four targeted analytes. For this proof-of-concept, either racemic salbutamol or enantiopure levosalbutamol was administered perorally or via inhalation, respectively. A strong preference for sulfonation of ()-salbutamol for inhalation and peroral application was found in experiments. In previous studies phenol sulfotransferase 1A3 was described to be mainly responsible for salbutamol sulfonation in humans. Thus, in vitro and in silico investigations of the stereoselectivity of sulfotransferase 1A3 complemented the study and confirmed these findings.
Topics: Humans; Albuterol; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Levalbuterol; Administration, Inhalation; Stereoisomerism
PubMed: 37894685
DOI: 10.3390/molecules28207206 -
Respiratory Care Aug 2022
Topics: Administration, Inhalation; Aerosols; Albuterol; Bronchodilator Agents; Equipment Design; Humans; Nebulizers and Vaporizers
PubMed: 35882446
DOI: 10.4187/respcare.10347 -
PloS One 2023Crystal methamphetamine ('ice') use is a large and growing worldwide problem, yet few research studies have explored the impact of crystal methamphetamine use on...
BACKGROUND
Crystal methamphetamine ('ice') use is a large and growing worldwide problem, yet few research studies have explored the impact of crystal methamphetamine use on affected friends and family members. We explored the experiences and narratives of family members and friends of people who use methamphetamine to inform the development of a Family and Friend Support Program.
METHODS
This paper reports on a subset of findings from a mixed method study, which sought to better understand the experiences of family members and friends of people who use methamphetamine. Participants were recruited via Facebook advertising and asked to complete a survey outlining their experiences. At the end of the survey, participants were invited to be interviewed by a clinical psychologist on the research team, to discuss their experiences in greater depth; seventeen people agreed to be interviewed. This paper is based on a qualitative thematic analysis of these interviews using Braun and Clarke's 6-stage approach to identify key areas of concern for friends and family members of people who use methamphetamine.
RESULTS
Through thematic analysis, five key themes were developed, namely: (1) loss, (2) stigma, (3) support (or lack thereof), (4) ways of coping, and (5) the value in sharing personal experiences. The results of this study revealed the profound sadness, frustration and loss friends and family members experienced when caring for a loved one who uses methamphetamine. This loss was further complicated by societal stigma surrounding the use of methamphetamine, which often extended to friends and family members themselves. Since experiences of grief and loss were interwoven across the three themes, concepts of ambiguous loss, disenfranchised grief, and narrative constructivist approaches to understanding loss, were applied to the discussion of results.
CONCLUSION
This study provides a more complete picture of family and caregiver experiences when caring for a loved one using methamphetamine, which may further help inform the design of intervention programs. Implications for future research and practice with this population are considered.
Topics: Humans; Methamphetamine; Family; Grief; Adaptation, Psychological; Caregivers; Qualitative Research
PubMed: 37043501
DOI: 10.1371/journal.pone.0284156 -
Journal of Aerosol Medicine and... Jan 2022A new real-time method for assessing factors determining aerosol delivery is described. A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier...
A new real-time method for assessing factors determining aerosol delivery is described. A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. Tc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer. A shielded gamma ratemeter was oriented to count radioaerosol accumulating on an inhaled mass (IM) filter at the airway opening of a test lung. Radioactivity measured at 2-10-minute intervals was expressed as % nebulizer charge (bolus) or % syringe activity per minute infused. All circuit parts were measured and imaged by gamma camera to determine mass balance. Ratemeter activity quantitatively reflected immediate changes in IM: 3 and 6 mL bolus IM% = 16.1 and 18.8% in 6 and 14 minutes, respectively; infusion IM% = 0.64 + 0.13 (run time, min), 0.999. Effect of nebulizer priming and system anomalies were readily detected in real time. Mass balance (basis = dose infused in 90 minutes): IM 39.2%, breath-enhanced jet nebulizer residual 35.5%, circuit parts including humidifier 23.4%, and total recovery 98.1%. Visual analysis of circuit component images identified sites of increased deposition. Real-time ratemeter measurement with gamma camera imaging provides operational feedback during testing procedures and yields a detailed analysis of the parameters influencing drug delivery during mechanical ventilation. This method of analysis facilitates assessment of device function and influence of circuit parameters on drug delivery.
Topics: Administration, Inhalation; Aerosols; Albuterol; Bronchodilator Agents; Drug Delivery Systems; Equipment Design; Nebulizers and Vaporizers; Respiration, Artificial
PubMed: 34227873
DOI: 10.1089/jamp.2021.0019