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Iranian Journal of Allergy, Asthma, and... Apr 2024The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to...
The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 μg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics.
Topics: Humans; Albuterol; Asthma; Child; Male; Female; Bronchodilator Agents; Forced Expiratory Volume; Adolescent; Administration, Inhalation; Respiratory Function Tests; Inhalation Spacers; Plastics; Spirometry
PubMed: 38822517
DOI: 10.18502/ijaai.v23i2.15328 -
Neuroscience Letters Jun 2024Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the...
Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depression. Wistar rats, weighing between 250-300 g, were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. Depressive-like behaviors were assessed using the forced swim test (FST) on either day 7 or 14 post-surgery, to establish the presence of depressive symptoms. The impact of 25H-NBOMe treatment was then evaluated, focusing on the head-twitch response (HTR), performance in the FST, and GFAP expression in the prefrontal cortex. Treatment with 25H-NBOMe resulted in significant behavioral changes, demonstrated by decreased immobility and increased swimming times in the FST, along with a rise in the HTR. These outcomes indicate a reduction in depressive-like symptoms post-sepsis and the psychoactive effects of the compound. Furthermore, a notable decrease in GFAP expression in the study highlights the compound's impact on mitigating sepsis-induced astrogliosis. This study demonstrates the effectiveness of 25H-NBOMe, a psychedelic in the phenethylamine class, in treating post-sepsis depression and reducing astrogliosis. However, the psychedelic nature of 25H-NBOMe calls for further investigation into similar compounds with less psychoactive impact, crucial for advancing treatment options for neuropsychiatric symptoms following sepsis.
Topics: Animals; Rats, Wistar; Male; Sepsis; Depression; Rats; Hallucinogens; Phenethylamines; Prefrontal Cortex; Sepsis-Associated Encephalopathy
PubMed: 38821202
DOI: 10.1016/j.neulet.2024.137845 -
Cardiovascular Toxicology Jul 2024The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential...
The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.
Topics: Animals; Methamphetamine; Male; Rats, Wistar; Cardiotoxicity; Dietary Supplements; Physical Conditioning, Animal; Pyroptosis; Interleukin-18; Disease Models, Animal; Heart Diseases; Substance Withdrawal Syndrome; Caspase 1; Central Nervous System Stimulants; Interleukin-1beta; Myocardium; Rats; Amphetamine-Related Disorders; Time Factors
PubMed: 38816669
DOI: 10.1007/s12012-024-09871-4 -
ACS Synthetic Biology Jun 2024In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine -methyltransferase (PNMT) for the biosynthesis of both...
In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine -methyltransferase (PNMT) for the biosynthesis of both octopamine and synephrine. As most TBH and PNMT originate from eukaryotic animals and plants, the heterologous expression and identification of functional TBH and PNMT are critical for establishing the pathway in mode microorganisms like . Here, three TBHs were evaluated, and only TBH from was successfully expressed in the soluble form in . Its expression was promoted by evaluating the effects of different expression strategies. The specific enzyme activity of TBH was optimized up to 229.50 U·g, and the first step in the biosynthetic pathway was successfully established and converted tyramine to synthesize 0.10 g/L of octopamine. Furthermore, the second step to produce synephrine from octopamine was developed by screening PNMT, enhancing enzyme activity, and optimizing reaction conditions, with a maximum synephrine production of 2.02 g/L. Finally, based on the optimization of the reaction conditions for each individual reaction, the one-pot cascade reaction for synthesizing synephrine from tyramine was constructed by combining the TBH and PNMT. The synthetic synephrine reached 30.05 mg/L with tyramine as substrate in the two-step enzyme cascade system. With further optimization and amplification, the titers of octopamine and synephrine were increased to 0.45 and 0.20 g/L, respectively, with tyramine as substrate. This work was the first achievement of the biosynthesis of octopamine and synephrine to date.
Topics: Octopamine; Synephrine; Animals; Drosophila melanogaster; Escherichia coli; Phenylethanolamine N-Methyltransferase; Mixed Function Oxygenases; Tyramine; Biosynthetic Pathways; Metabolic Engineering
PubMed: 38815614
DOI: 10.1021/acssynbio.4c00082 -
ACS Applied Materials & Interfaces Jun 2024The growing number of acute drug abuse overdoses demands the development of innovative detoxification strategies for emergency purposes. In this study, an innovative...
The growing number of acute drug abuse overdoses demands the development of innovative detoxification strategies for emergency purposes. In this study, an innovative approach for the application of porous Zr-based metal-organic frameworks for the treatment of acute overdoses of popular drugs of abuse including amphetamine, methamphetamine, cocaine, and MDMA is presented. A comprehensive approach determining the efficacy and the kinetics of drug removal, considering dosage, adsorption time, and adsorption mechanisms, was tested and corroborated with density functional theory (DFT) modeling. The experimental results showed high removal efficiency reaching up to 90% in the case of the application of the NU-1000 metal-organic framework. The difference Raman spectroscopy method presented in this study corroborated with DFT-based vibrational analysis allows the detection of drug adsorbed in the MOF framework even with as low a concentration as 5 mg/g. Additionally, the drug adsorption mechanisms were modeled with DFT, showing the π-π stacking in a vast majority of considered cases. The performance and influence on the living organisms were evaluated throughout the and experiments, indicating that Zr-based MOFs could serve as efficient, organic, safe drug adsorbents.
Topics: Metal-Organic Frameworks; Adsorption; Zirconium; Density Functional Theory; Animals; Porosity; Methamphetamine
PubMed: 38815127
DOI: 10.1021/acsami.4c02450 -
The Journal of Clinical Psychiatry May 2024
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; United States; Hallucinogens; Amphetamine-Related Disorders
PubMed: 38814108
DOI: 10.4088/JCP.23com15224 -
Journal of Integrative Neuroscience May 2024Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and...
BACKGROUND
Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood.
METHODS
To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions.
RESULTS
In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation.
CONCLUSIONS
These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.
Topics: Humans; Amphetamine-Related Disorders; Male; Methamphetamine; Cognitive Dysfunction; Adult; Proteomics; Central Nervous System Stimulants; Female; Young Adult
PubMed: 38812388
DOI: 10.31083/j.jin2305107 -
Organic & Biomolecular Chemistry Jun 2024The synthesis of a biologically relevant 2-amino-3-alkylamido 4-quinazolinone has been accomplished in four steps from commercially available materials using design...
The synthesis of a biologically relevant 2-amino-3-alkylamido 4-quinazolinone has been accomplished in four steps from commercially available materials using design principles from both modular and divergent synthesis. 3-Alkylation of 2-chloro-4(3)-quinazolinone using methyl bromoacetate, followed by C2-amination produced a suitable scaffold for introducing molecular diversity. Optimization of alkylation conditions afforded full regioselectivity, enabling exclusive access to the -alkylated isomer. Subsequent C2-amination using piperidine, pyrrolidine, or diethylamine, followed by amide bond formation using variously substituted phenethylamines, generated fifteen unique 4-quinazolinones bearing C2-amino and 3-alkylamido substituents. These efforts highlight the reciprocal influence of C2 and 3 substitution on functionalization at either position, establish an effective synthetic pathway toward 2,3-disubstituted 4-quinazolinones, and enable preliminary bioactivity studies while providing an experiential learning opportunity for undergraduate student researchers.
PubMed: 38809109
DOI: 10.1039/d4ob00564c -
Ecotoxicology and Environmental Safety Jul 2024Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity...
Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.
Topics: Animals; Caffeic Acids; Phenylethyl Alcohol; Methamphetamine; Neuroprotective Agents; Mice; Male; Neurotoxicity Syndromes; Hippocampus; Mice, Inbred C57BL; Neurons
PubMed: 38805827
DOI: 10.1016/j.ecoenv.2024.116497 -
Molecular Biology Reports May 2024Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition,...
INTRODUCTION
Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition, attention and executive functions, but the underlying mechanisms are still unclear. Sirtuin 1 (SIRT1) is a post-translational regulator that is downregulated following METH neurotoxicity. Melatonin is a neuroprotective hormone that enhances mitochondrial metabolism. Here, we evaluated the effect of melatonin on METH-induced attention deficits disorder and the involvement of the miR-181/SIRT1 axis in melatonin neuroprotection.
METHODS AND RESULTS
METH at a dose of 5 mg/kg was injected for 21 consecutive days. The animals were assigned to receive either melatonin or the vehicle after METH injections. Attention levels were evaluated with abject-based attention test. In the prefrontal cortex, the expression levels of miR-181a-5p, SIRT1, p53 and CCAR2, as well as the mtDNA copy numbers were evaluated using qRT-PCR and western blotting. The outcomes revealed that melatonin treatment following METH injections improved METH-induced attention deficits. METH toxicity can be associated with changes in the miR-181/SIRT1 axis, elevated levels of p53 and COXII, and decreased levels of mtDNA in the prefrontal cortex of adult rats. Interestingly, administration of melatonin can improve the expression of these molecules and reduces the toxic effects of METH.
CONCLUSION
Melatonin ameliorated the neurotoxicity of METH in the prefrontal cortex and the miR-181/SIRT1 axis is involve in the protective effects of melatonin. However, melatonin can be potentially administrated to improve attention impairment in METH use disorders.
Topics: Melatonin; Methamphetamine; Prefrontal Cortex; Animals; Sirtuin 1; MicroRNAs; Male; Rats; Neuroprotective Agents; Attention; Rats, Wistar; Central Nervous System Stimulants
PubMed: 38796575
DOI: 10.1007/s11033-024-09631-1