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American Journal of Ophthalmology Case... Sep 2024This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly...
PURPOSE
This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly used weight loss medication.
OBSERVATIONS
A 49-year-old woman presented with acute painless vision loss in her right eye and was found to have a branch retinal artery occlusion after taking prescribed dosages of phentermine for weight loss therapy. Fundus examination revealed retinal whitening in the distribution of the superior temporal branch retinal artery, and spectral domain optical coherence tomography demonstrated macular edema. Systemic evaluation was negative for cardiovascular, infectious, or autoimmune etiologies. Based on the retinal findings, the patient was diagnosed with phentermine associated branch retinal artery occlusion. She was followed for nine years with no further complications and her vision remained stable in the right eye.
CONCLUSIONS AND IMPORTANCE
This case highlights that phentermine, a commonly used weight loss medication, could be associated with ischemic retinopathies. Thus, clinicians should be aware that retinal vascular occlusions may not only occur in those who use recreational amphetamines but also in patients taking the prescribed dosages of a weight loss medication like phentermine.
PubMed: 38884112
DOI: 10.1016/j.ajoc.2024.102013 -
Progress in Neuro-psychopharmacology &... Jun 2024Adolescent stress (AS) has been associated with higher vulnerability to psychiatric disorders such as schizophrenia, depression, or drug dependence. Moreover, the...
Adolescent stress (AS) has been associated with higher vulnerability to psychiatric disorders such as schizophrenia, depression, or drug dependence. Moreover, the alteration of brain catecholamine (CAT) transmission in the medial prefrontal cortex (mPFC) has been found to play a major role in the etiology of psychiatric disturbances. We investigated the effect of adolescent stress on CAT transmission in the mPFC of freely moving adult rats because of the importance of this area in the etiology of psychiatric disorders, and because CAT transmission is the target of a relevant group of drugs used in the therapy of depression and psychosis. We assessed basal dopamine (DA) and norepinephrine (NE) extracellular concentrations (output) by brain microdialysis in in the mPFC of adult rats that were exposed to chronic mild stress in adolescence. To ascertain the role of an altered release or reuptake, we stimulated DA and NE output by administering either different doses of amphetamine (0.5 and 1.0 mg / kg s.c.), which by a complex mechanism determines a dose dependent increase in the CAT output, or reboxetine (10 mg/kg i.p.), a selective NE reuptake inhibitor. The results showed the following: (i) basal DA output in AS rats was lower than in controls, while no difference in basal NE output was observed; (ii) amphetamine, dose dependently, stimulated DA and NE output to a greater extent in AS rats than in controls; (iii) reboxetine stimulated NE output to a greater extent in AS rats than in controls, while no difference in stimulated DA output was observed between the two groups. These results show that AS determines enduring effects on DA and NE transmission in the mPFC and might lead to the occurrence of psychiatric disorders or increase the vulnerability to drug addiction.
PubMed: 38879069
DOI: 10.1016/j.pnpbp.2024.111055 -
The American Journal on Addictions Jun 2024Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT)...
Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.
BACKGROUND AND OBJECTIVES
Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada.
METHODS
Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation).
RESULTS
Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05).
CONCLUSION AND SCIENTIFIC SIGNIFICANCE
This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.
PubMed: 38877969
DOI: 10.1111/ajad.13619 -
Analytical Methods : Advancing Methods... Jun 2024Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system...
Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system depressant, helps lose weight by disrupting hormone regulation, stimulating sympathetic nerves, and suppressing appetite. However, some unethical businesses fail to properly handle raw materials in foods like apple cider vinegar, leading to residual methyl parathion in apples or illegal excessive addition of sibutramine. Therefore, it is imperative to develop an immunoassay for the rapid detection of methyl parathion and sibutramine. The corresponding two haptens were prepared and coupled with the carrier proteins according to methyl parathion-sulfur-bovine serum protein (BSA)/chicken ovalbumin (OVA)-sibutramine (20 : 1 : excess, 15 : 1 : excess, 10 : 1 : excess, and 5 : 1 : excess), and sibutramine-BSA/OVA-methyl parathion (20 : 1 : excess, 10 : 1 : excess: 5 : 1 : excess, and 0 : 1 : excess). The result shows that the inhibition rate of the antibody obtained by methyl parathion-BSA/OVA-sibutramine (20 : 1 : excess) was higher than that of sibutramine-BSA/OVA-methyl parathion, which was 67.93%, and the concentration of methyl parathion was 8.65 ng mL at this inhibition rate. Thus, methyl parathion-BSA/OVA-sibutramine (8.65 : 1 : excess) and the corresponding antibodies were selected for subsequent method establishment. By changing the concentration of the coating and antibody, the inhibition rate was found when the coating was 0.125 ng mL and the antibody was diluted 4000 times. The antibody was used to develop a standard curve for the detection of sibutramine at the half-maximum inhibitory concentration (IC) is 4.59 ng mL, the limit of detection (IC) is 2.21 ng mL, the detection range is 2.89 to 7.28 ng mL, methyl p-phosphorus at the half-maximum inhibitory concentration (IC) is 15.34 ng mL, the limit of detection (IC) is 0.42 ng mL, the detection range is ng mL. Under these conditions, the recovery rate was between 88% and 102%, within reasonable limits, indicating the successful establishment of a rapid enzyme-linked ELISA assay.
Topics: Cyclobutanes; Enzyme-Linked Immunosorbent Assay; Malus; Methyl Parathion; Acetic Acid; Appetite Depressants; Food Contamination; Animals; Limit of Detection
PubMed: 38873980
DOI: 10.1039/d4ay00879k -
Legal Medicine (Tokyo, Japan) Jun 2024Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of...
Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.
PubMed: 38870841
DOI: 10.1016/j.legalmed.2024.102469 -
Journal of Addiction Medicine Jun 2024Addressing the methamphetamine epidemic will require a more complete understanding of its effect on healthcare systems and of the populations at risk. The objective of...
OBJECTIVES
Addressing the methamphetamine epidemic will require a more complete understanding of its effect on healthcare systems and of the populations at risk. The objective of the study was to assess the impact of methamphetamine use on psychiatric emergency services outcomes and on Asian American (AA) and Pacific Islander (PI) populations, a historically overlooked population in substance use research.
METHODS
A retrospective chart review was performed for all visits to a large level I trauma center in urban Hawaii from 2007 to 2019 that required psychiatric emergency services and in which urine drug screening was completed (N = 44,658). Demographic characteristics and emergency room courses were compared between amphetamine-positive and amphetamine-negative visits.
RESULTS
The proportion of amphetamine-positive visits approximately doubled from 13.3% in 2007 to 25.5% in 2019. Amphetamine-positive visits were more likely to involve arrival by law enforcement (38.3% vs 27.2.%, P < 0.001), require intramuscular psychotropic medications (17.3% vs 12.3%, P < 0.001), and have longer emergency department lengths of stay (median, 420 vs 372 minutes, P < 0.001). Visits by Native Hawaiian and Hispanic/Latino patients had the highest rate of amphetamine positivity, while visits by Chinese and Korean patients had the lowest.
CONCLUSIONS
The findings reveal a concerning rise in amphetamine positivity that is associated with increased resource utilization. There was also significant variability in the rate of amphetamine positivity within the AA and PI population, a group of ethnicities often analyzed as a single entity in previous studies. Culturally sensitive interventions may curb the methamphetamine epidemic's effect on healthcare systems and vulnerable populations.
PubMed: 38869174
DOI: 10.1097/ADM.0000000000001335 -
Clinical Case Reports Jun 2024An interesting case that shows the importance of identifying a pathogenic TTN gene mutation through genetic assessment in unexplained cardiomyopathy, especially with...
KEY CLINICAL MESSAGE
An interesting case that shows the importance of identifying a pathogenic TTN gene mutation through genetic assessment in unexplained cardiomyopathy, especially with family history. This case highlights the need for genetic counseling and testing for at-risk relatives, and advocates for personalized management considering both genetic and lifestyle factors.
ABSTRACT
This case report examines a 33-year-old Hispanic male with bipolar disorder, schizophrenia, and a history of substance use, presenting with acute respiratory failure and cardiac arrest. The patient's nonischemic dilated cardiomyopathy (DCM) highlights the critical role of genetic factors, particularly titin gene (TTN) mutations, in cardiomyopathy pathogenesis. Through genetic analysis, we explore the intersection of lifestyle factors and genetic predisposition in DCM, underscoring the importance of comprehensive genetic testing for accurate diagnosis and targeted therapy. This case contributes to the evolving understanding of DCM etiology, emphasizing the necessity of considering both environmental and genetic factors in clinical assessment and management.
PubMed: 38868113
DOI: 10.1002/ccr3.9069 -
Der Nervenarzt Jun 2024Consumption of stimulant drugs, a heterogeneous group of addictive substances, has significantly increased in recent years with rising numbers of stimulant-associated... (Review)
Review
BACKGROUND
Consumption of stimulant drugs, a heterogeneous group of addictive substances, has significantly increased in recent years with rising numbers of stimulant-associated intoxication and deaths.
OBJECTIVE
To provide an overview of recent scientific evidence of the diagnosis and treatment of stimulant use disorders.
MATERIAL AND METHODS
A literature review of the neuropathology, clinical presentation, diagnostic criteria and evidence-based treatment for stimulant use disorders.
RESULTS
The chronic use of stimulant drugs is associated with significant physical (e.g., hypertension, tachycardia and dyspnoea) and psychological harm (e.g., dependence, psychotic disorders and affective disorders). Despite major advances in the research of the neuropathology of stimulant use disorder and the refinement of diagnostic criteria, the disorder still presents a challenge, not least because of the lack of effective treatments. There are currently no approved pharmacotherapeutic interventions for stimulant use disorder and meta-analyses show that the efficacy of behavioural interventions is low to moderate, similar to cognitive behavioural treatment.
CONCLUSION
Despite growing insights into the neuropathology associated with stimulant use disorder, treatment remains a challenge. The lack of effective interventions makes it difficult to give clear recommendations for the clinical practice. Further scientific research is thus warranted.
PubMed: 38867056
DOI: 10.1007/s00115-024-01687-5 -
Human Genomics Jun 2024Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single...
Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single nucleotide variants (SNV) have been found in patients with schizophrenia and metabolic disorders. However, the frequency of variants in geographically diverse populations and the functional effects of such variants are unknown. In this study, we aimed to characterise the distribution of TAAR1 SNVs in five different WHO regions using the Database of Genotypes and Phenotypes (dbGaP) and conducted a critical computational analysis using available TAAR1 structural data to identify SNVs affecting ligand binding and/or functional regions. Our analysis shows 19 orthosteric, 9 signalling and 16 micro-switch SNVs hypothesised to critically influence the agonist induced TAAR1 activation. These SNVs may non-proportionally influence populations from discrete regions and differentially influence the activity of TAAR1-targeting therapeutics in genetically and geographically diverse populations. Notably, our dataset presented with orthosteric SNVs D103N (found only in the South-East Asian Region and Western Pacific Region) and T194A (found only in South-East Asian Region), and 2 signalling SNVs (V125A/T252A, found in African Region and commonly, respectively), all of which have previously demonstrated to influence ligand induced functions of TAAR1. Furthermore, bioinformatics analysis using SIFT4G, MutationTaster 2, PROVEAN and MutationAssessor predicted all 16 micro-switch SNVs are damaging and may further influence the agonist activation of TAAR1, thereby possibly impacting upon clinical outcomes. Understanding the genetic basis of TAAR1 function and the impact of common mutations within clinical populations is important for the safe and effective utilisation of novel and existing pharmacotherapies.
Topics: Humans; Receptors, G-Protein-Coupled; Polymorphism, Single Nucleotide; Structure-Activity Relationship; Genotype; Ligands; Trace Amine-Associated Receptors
PubMed: 38863077
DOI: 10.1186/s40246-024-00620-w -
The AAPS Journal Jun 2024Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities...
Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of β-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption.
Topics: Humans; Hepatocytes; Tandem Mass Spectrometry; Propiophenones; Chromatography, Liquid; Substance Abuse Detection; Methamphetamine; Psychotropic Drugs; Metabolomics; Alkaloids; Illicit Drugs
PubMed: 38862871
DOI: 10.1208/s12248-024-00940-8