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Journal of Animal Science Aug 2022Beta-adrenergic agonists (β-AAs) are widely used supplements in beef and pork production to improve feed efficiency and increase lean muscle mass, yet little is known...
Beta-adrenergic agonists (β-AAs) are widely used supplements in beef and pork production to improve feed efficiency and increase lean muscle mass, yet little is known about the molecular mechanism by which β-AAs achieve this outcome. Our objective was to identify the influence of ractopamine HCl and zilpaterol HCl on mitochondrial respiratory activity in muscle satellite cells isolated from crossbred beef steers (N = 5), crossbred barrows (N = 2), Yorkshire-cross gilts (N = 3), and commercial weather lambs (N = 5). Real-time measurements of oxygen consumption rates (OCRs) were recorded using extracellular flux analyses with a Seahorse XFe24 analyzer. After basal OCR measurements were recorded, zilpaterol HCl, ractopamine HCl, or no β-AA was injected into the assay plate in three technical replicates for each cell isolate. Then, oligomycin, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, and rotenone were injected into the assay plate sequentially, each inducing a different cellular state. This allowed for the measurement of OCR at these states and for the calculation of the following measures of mitochondrial function: basal respiration, non-mitochondrial respiration, maximal respiration, proton leak, adenosine triphosphate (ATP)-linked respiration, and spare respiratory capacity. Incubation of bovine cells with either zilpaterol HCl or ractopamine HCl increased maximal respiration (P = 0.046) and spare respiratory capacity (P = 0.035) compared with non-supplemented counterparts. No difference (P > 0.05) was observed between zilpaterol HCl and ractopamine HCl for maximal respiration and spare respiratory capacity in bovine cell isolates. No measures of mitochondrial function (basal respiration, non-mitochondrial respiration, maximal respiration, proton leak, ATP-linked respiration, and spare respiratory capacity) were altered by β-AA treatment in ovine or porcine cells. These findings indicate that β-AAs in cattle may improve the efficiency of oxidative metabolism in muscle satellite cells by modifying mitochondrial respiratory activity. The lack of response by ovine and porcine cells to β-AA incubation also demonstrates differing physiological responses to β-AA across species, which helps to explain the variation in its effectiveness as a growth supplement.
Topics: Adenosine Triphosphate; Adrenergic beta-Agonists; Animals; Cattle; Female; Myoblasts; Oxidative Phosphorylation; Phenethylamines; Protons; Sheep; Sheep, Domestic; Swine
PubMed: 35908785
DOI: 10.1093/jas/skac208 -
Addiction (Abingdon, England) Jun 2022To test (1) if there was a change in self-reported lifetime prevalence of meth/amphetamine use by birth cohort and (2) if the extent of under-reporting of... (Observational Study)
Observational Study
AIM
To test (1) if there was a change in self-reported lifetime prevalence of meth/amphetamine use by birth cohort and (2) if the extent of under-reporting of meth/amphetamine use was associated with the proportion of the population who nominated meth/amphetamine as a drug problem.
DESIGN
Observational study using seven waves of repeated cross-sectional nationally representative household surveys between 2001 and 2019.
SETTING
Australia.
PARTICIPANTS
Participants were from three birth cohorts: 1951-60 (age 68-77 at the 2019 survey; n = 29 458; 55% female), 1961-1970 (age 58-67; n = 29 859; 57% female) and 1971-1980 (age 48-57; n = 28 758; 59% female). Data were weighted to align the sample to the Australian population.
MEASUREMENTS
Past year meth/amphetamine use; under-reporting of lifetime meth/amphetamine use in each birth cohort, year and survey stratum (operationalised as the difference between self-reported lifetime prevalence in 2001 and that of each subsequent year); proportion of the population who nominated meth/amphetamine as a drug problem in each birth cohort, year and survey stratum. Under-reporting was regressed on the proportion of people holding negative attitude towards meth/amphetamine. Survey year and birth cohort were adjusted for.
FINDINGS
Between 2001 and 2019, the lifetime prevalence of meth/amphetamine decreased from 6.1% (95% CI = 5.3-6.9) to 1.7% (95% CI = 1.2-2.2) in the 1951-1960 birth cohort (p < 0.001), from 13.0% (95% CI = 12.0-14.1) to 4.4% (95% CI = 3.7-5.2) in the 1961-1970 birth cohort (p < 0.001) and from 21.4% (95% CI = 19.9-22.9) to 11.2% (95% CI = 10.0-12.4) in the 1971-1980 birth cohort (p < 0.001). The proportion who nominated meth/amphetamine as a 'drug problem' increased significantly in all three cohorts (all p < 0.001) and the degree of under-reporting of meth/amphetamine use was significantly associated with proportion of people who nominated meth/amphetamine as the 'drug problem' (b = 0.09, SE = 0.01, p < 0.001).
CONCLUSION
In Australia, the actual prevalence of lifetime meth/amphetamine use may be two- to fourfold higher than that estimated in the most recent national household surveys (2019). The level of under-reporting is strongly associated with increasing negative attitudes towards methylamphetamine and d-amphetamine use over the same period.
Topics: Aged; Amphetamine; Amphetamine-Related Disorders; Australia; Cross-Sectional Studies; Female; Humans; Male; Methamphetamine; Middle Aged
PubMed: 34928522
DOI: 10.1111/add.15783 -
Analytical Methods : Advancing Methods... Jul 2022Reliable and feasible tools for detecting ()-methamphetamine [()-MAP] and ()-amphetamine [()-AP] are required for regulating their illicit circulation. Antibodies that...
Reliable and feasible tools for detecting ()-methamphetamine [()-MAP] and ()-amphetamine [()-AP] are required for regulating their illicit circulation. Antibodies that react equally to these stimulants are desirable for this purpose, but have been difficult to generate because of the crucial difference between their characteristic structures: ., -methylamino (MAP) and amino (AP) groups. Furthermore, their small molecular masses ( < 150) have hampered the generation of high-affinity antibodies. To overcome these problems, we converted ()-MAP and -AP into their 2-(trimethylsilyl)ethyl carbamate forms, Teoc-()-MAP and -AP, respectively, as surrogate analytes. The Teoc-derivatization not only increases their molecular masses, but also masks their structural differences. We generated a novel monoclonal antibody that showed a satisfactory affinity to Teoc-()-MAP residues ( = 13 nM as the IgG form) and developed a competitive enzyme-linked immunosorbent assay (ELISA) using microplates containing immobilized Teoc-()-MAP residues. Almost overlapping dose-response curves were obtained for Teoc-()-MAP and -AP, with the limit of detection of 0.078 and 0.10 ng per assay, respectively. A fixed amount of test powder sample (1 mg) was derivatized with Teoc--succinimidyl for 5 min, and subjected to ELISA using Teoc-()-MAP as the calibration standard. Under this protocol, ()-MAP and -AP were converted to their Teoc derivatives with 30% and 34% yield, respectively, determined using ELISA as "Teoc-()-MAP equivalent," being distinguished from the derivatization products of ()-MAP, ()-AP, ephedrine, ()-methylenedioxymethamphetamine, tyramine, dopamine, and β-alanine. This ELISA detected as little as 10 μg of ()-MAP and -AP, and ()-MAP in urine obtained from ()-MAP-administered rats. Immunochromatography devices were also developed using gold nanoparticles coated with the monoclonal antibody, with which 0.10 mg of ()-MAP and -AP was detected by the naked eye. We conclude that the present derivatization-assisted immunoassays may be useful for the detection of ()-MAP and/or -AP in early stage screening of suspicious substances.
Topics: Amphetamine; Animals; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Gold; Metal Nanoparticles; Methamphetamine; Rats
PubMed: 35785801
DOI: 10.1039/d2ay00940d -
Human Psychopharmacology Jan 2020The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances....
OBJECTIVE
The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances. We sought to determine and compare the subjective effects of various substances.
METHODS
We conducted in-depth interviews with 39 adults (75.4% male and 87.2% White) who reported experience using psychedelic phenethylamines and/or tryptamines. Participants described the effects of compounds they have used. We examined the subjective drug effects in a qualitative descriptive manner.
RESULTS
Participants reported on the use of 36 compounds. The majority (64.1%) reported the use of 2C series drugs, with 2C-B use being most prevalent; 38.5% reported the use of NBOMe, and 25.6% reported the use of DOx. With regard to tryptamines, 46.2% reported use, and 4-AcO-DMT was the most prevalent drug used in this class. 2C-B was often described as being more favorable than other 2C series compounds with the effects described as being comparable with MDMA and LSD. NBOMe effects were generally described in an unfavorable manner, and the effects of DOx were often described as lasting too long (12-36 hr). The effects of 4-AcO-DMT were often described as mimicking psilocybin.
CONCLUSION
Knowing the effects of various compounds can inform education, prevention, and harm reduction efforts regarding the use of these drugs.
Topics: Adolescent; Adult; Drug Users; Female; Hallucinogens; Humans; Male; Phenethylamines; Qualitative Research; Self Report; Tryptamines; Young Adult
PubMed: 31909513
DOI: 10.1002/hup.2719 -
Journal of Analytical Toxicology Mar 2023Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and...
Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than amphetamines may have caused a false-positive amphetamine immunoassay screening result. Urine drug screens (12,250) in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false-positive results over a 6-year period (2015-2020). An additional 3,486 referred samples, for which confirmatory--mass spectrometry was requested, were also reviewed. About 86 in-house samples and 175 referral samples that were CEDIA false-positive screens were further analyzed by an LC-QTOF general unknown screen. Potential cross-reacting drugs were identified, and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false-positive specimens, on average, 6.8 drugs were detected by the LC-QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross-reacting drugs. False-positive amphetamine screens make up to 3.9-9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable.
Topics: Substance Abuse Detection; Amphetamines; Amphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Immunoassay; Mass Spectrometry
PubMed: 36367744
DOI: 10.1093/jat/bkac089 -
Clinical Toxicology (Philadelphia, Pa.) May 2023It is well known that cocaine increases the risk of acute coronary syndrome. However, it is uncertain if the use of other stimulants, such as amfetamines and cathinones,...
BACKGROUND
It is well known that cocaine increases the risk of acute coronary syndrome. However, it is uncertain if the use of other stimulants, such as amfetamines and cathinones, is also related to acute coronary syndrome.
OBJECTIVES
To identify all reported cases of acute coronary syndrome related to the use of amfetamines and cathinones, the type of acute coronary syndrome, the atherothrombotic aetiology, and the mortality rate.
METHODS
A systematic literature search in PubMed, Embase database, Cochrane library, PsycInfo and Web of Science was performed from inception until 31 August 2022. All original articles in English or Dutch describing adult patients with acute coronary syndrome after the use of amfetamines or cathinones were included. The main outcome was the occurrence of acute coronary syndrome associated with amfetamine-type stimulants or cathinones. Data were collected and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 11,605 articles were identified, 56 of which met the inclusion criteria. A total of 160 patients presented with acute coronary syndrome after five different types of amfetamines, namely, amfetamine ( = 48), metamfetamine ( = 98), 3,4-methylenedioxymetamfetamine ( = 11), fenethylline ( = 2), and 4-fluoroamfetamine ( = 1). Khat chewing was associated with acute coronary syndrome ( = 4234), as were three different types of synthetic cathinones, namely, non-defined cathinones ( = 1), 4-methylmethcathinone ( = 1), and α-pyrrolidinopentiophenone ( = 1). In patients with a known acute coronary syndrome type ( = 157), ST-segment elevation myocardial infarction was diagnosed in 53 patients (75%) and non-ST-segment elevation myocardial infarction in 18 patients (25%). Of the ST-segment elevation myocardial infarction patients, 36% were diagnosed with significant coronary stenosis or thrombus. The mortality rate for khat-associated acute coronary syndrome, with more often male and older patients with fewer cardiovascular risk factors, was higher compared to non-khat-associated acute coronary syndrome. For amfetamine, metamfetamine, and 3,4-methylenedioxymetamfetamine, mortality associated with ST--segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was 14% and 7%, respectively. Risk factors for acute coronary syndrome were infrequently reported, and risk stratification scores were not reported.
CONCLUSION
There is evidence that amfetamine-type stimulants and cathinones are associated with the occurrence of acute coronary syndrome. Khat chewing appears to be a risk factor for acute coronary syndrome. Amfetamine, metamfetamine, 3,4-methylenedioxymetamfetamine, fenethylline, 4-fluoroamfetamine, and synthetic cathinones were also reported in relation to acute coronary syndrome. However, this evidence is limited, of low quality and with a low number of reported cases. Further prospective studies need to be conducted.
Topics: Adult; Humans; Male; Acute Coronary Syndrome; Prospective Studies; Amphetamine; Central Nervous System Stimulants; Methamphetamine; Myocardial Infarction
PubMed: 37171152
DOI: 10.1080/15563650.2023.2191819 -
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 -
Journal of Analytical Toxicology Mar 2023Amphetamines (AMPs) in hair were investigated with thousands of workplace testing head and body hair samples collected and analyzed over 10 years and tabulated by year....
Amphetamines (AMPs) in hair were investigated with thousands of workplace testing head and body hair samples collected and analyzed over 10 years and tabulated by year. All samples were washed by a published extensive method prior to confirmation by liquid chromatography-mass spectrometry-mass spectrometry. Presented are concentrations of parent methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA) and methylenedioxyamphetamine as metabolite and AMP as metabolite and without the presence of parent drug. Some differences in METH concentrations from year to year were significant, and some ratios of metabolite to parent drug for both METH and MDMA also varied significantly. While rates of METH use may not have changed significantly, some aspects of the drugs ingested as demonstrated by hair analysis varied over the 10-year period.
Topics: N-Methyl-3,4-methylenedioxyamphetamine; Substance Abuse Detection; Amphetamines; Methamphetamine; Hair; Workplace
PubMed: 35900095
DOI: 10.1093/jat/bkac055 -
Cutaneous and Ocular Toxicology Dec 2023Amphetamines are the second most commonly used illicit drug worldwide. Amphetamine use can result in significant cutaneous morbidity. This review highlights the... (Review)
Review
Amphetamines are the second most commonly used illicit drug worldwide. Amphetamine use can result in significant cutaneous morbidity. This review highlights the dermatological manifestations of amphetamine abuse.
Topics: Humans; Amphetamine; Methamphetamine; Amphetamine-Related Disorders; Skin; Administration, Cutaneous
PubMed: 37450708
DOI: 10.1080/15569527.2023.2235425 -
Legal Medicine (Tokyo, Japan) Feb 2020The chemsex or slamsex phenomenon has attracted attention worldwide, with concerns also expressed by health professionals for the spread of sexually transmitted...
The chemsex or slamsex phenomenon has attracted attention worldwide, with concerns also expressed by health professionals for the spread of sexually transmitted diseases. Mephedrone or 4-methylmethcathinone, a substituted cathinone homolog of ephedrine, is one of the most popular substances used as a cheaper alternative to other traditional drugs. Fatal cases of chemsex are still rare. We present here the first case-report to the best of our knowledge of a mephedrone-related acute toxicity case in Parma (Italy) detected and quantitated in biological specimens (2.0 mg/L in urine sample, 1.1 mg/L in bile and 1.0 mg/L in central blood while 0.8 mg/L in peripheral blood). None of the other most common drugs of abuse could be detected. Autopsy findings such as facies edematosa, oedema and polyvisceral congestion, interstitial petechiae are compatible elements with a death from acute cardio-respiratory failure, with peri-mortem agony of few minutes in which the cardiac hypertrophy, the moderate aortocoronary sclerosis and mephedrone injection have played a substantial role in the evaluation of the final cause due to an accidental acute intoxication with mephedrone.
Topics: Autopsy; Fatal Outcome; Forensic Toxicology; Humans; Male; Methamphetamine; Middle Aged
PubMed: 31751794
DOI: 10.1016/j.legalmed.2019.101640