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1.
FASEB J ; 36(6): e22358, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35604751

RESUMEN

G protein-coupled receptors (GPCRs) are known to be involved in tumor progression and metastasis. The adenosine A1 receptor (A1 AR) has been detected to be over-expressed in various cancer cell lines. However, the role of A1 AR in tumor development is not yet well characterized. A series of A1 AR mutations were identified in the Cancer Genome Atlas from cancer patient samples. In this study, we have investigated the pharmacology of mutations located outside of the 7-transmembrane domain by using a "single-GPCR-one-G protein" yeast system. Concentration-growth curves were obtained with the full agonist CPA for 12 mutant receptors and compared to the wild-type hA1 AR. Most mutations located at the extracellular loops (EL) reduced the levels of constitutive activity of the receptor and agonist potency. For mutants at the intracellular loops (ILs) of the receptor, an increased constitutive activity was found for mutant receptor L211R5.69 , while a decreased constitutive activity and agonist response were found for mutant receptor L113F34.51 . Lastly, mutations identified on the C-terminus did not significantly influence the pharmacological function of the receptor. A selection of mutations was also investigated in a mammalian system. Overall, similar effects on receptor activation compared to the yeast system were found with mutations located at the EL, but some contradictory effects were observed for mutations located at the IL. Taken together, this study will enrich the insight of A1 AR structure and function, enlightening the consequences of these mutations in cancer. Ultimately, this may provide potential precision medicine in cancer treatment.


Asunto(s)
Neoplasias , Adenosina/farmacología , Animales , Línea Celular , Humanos , Mamíferos/metabolismo , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Receptor de Adenosina A1/genética , Receptor de Adenosina A1/metabolismo , Saccharomyces cerevisiae/genética
2.
Molecules ; 27(12)2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35744872

RESUMEN

Overexpression of the adenosine A1 receptor (A1AR) has been detected in various cancer cell lines. However, the role of A1AR in tumor development is still unclear. Thirteen A1AR mutations were identified in the Cancer Genome Atlas from cancer patient samples. We have investigated the pharmacology of the mutations located at the 7-transmembrane domain using a yeast system. Concentration-growth curves were obtained with the full agonist CPA and compared to the wild type hA1AR. H78L3.23 and S246T6.47 showed increased constitutive activity, while only the constitutive activity of S246T6.47 could be reduced to wild type levels by the inverse agonist DPCPX. Decreased constitutive activity was observed on five mutant receptors, among which A52V2.47 and W188C5.46 showed a diminished potency for CPA. Lastly, a complete loss of activation was observed in five mutant receptors. A selection of mutations was also investigated in a mammalian system, showing comparable effects on receptor activation as in the yeast system, except for residues pointing toward the membrane. Taken together, this study will enrich the view of the receptor structure and function of A1AR, enlightening the consequences of these mutations in cancer. Ultimately, this may provide an opportunity for precision medicine for cancer patients with pathological phenotypes involving these mutations.


Asunto(s)
Neoplasias , Receptor de Adenosina A1 , Adenosina/metabolismo , Adenosina/farmacología , Animales , Humanos , Mamíferos , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Estructura Secundaria de Proteína , Receptor de Adenosina A1/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
3.
J Dual Diagn ; 13(2): 91-100, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28418789

RESUMEN

OBJECTIVE: There is a reasonable theoretical base for understanding the possible causes and motivations behind substance misuse and its dependency. There is a need for a reliable and valid measure that delineates the markers of substance use from its initiation and identifies different motivations for drug use transitioning, maintenance, and dependency. We addressed this gap in the United Kingdom by examining and validating the Substance Transitions in Addiction Rating Scale (STARS). METHODS: For this review, 390 male prisoners were screened for conduct disorder and assessed with a clinical diagnostic interview for attention deficit/hyperactivity disorder (ADHD). They completed the four STARS subscales regarding their substance use. Exploratory structural equation modeling was performed to assess the STARS structure and to derive factors to assess validity against ADHD and conduct disorder diagnostic categories. RESULTS: Each of the subscales produced meaningful and reliable factors that supported the self-medication and behavioral disinhibition hypotheses of substance use motivation. The findings robustly show that ADHD is significantly associated with the need for coping as a way of managing primary and comorbid symptoms, but not conduct disorder. The findings were strongest for the combined ADHD type. DISCUSSION: STARS has a great potential to further the understanding of the motivation behind substance use and its dependency in different populations.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno de la Conducta/psicología , Motivación , Prisioneros/psicología , Trastornos Relacionados con Sustancias/psicología , Adaptación Psicológica , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno de la Conducta/diagnóstico , Diagnóstico Dual (Psiquiatría) , Conducta Exploratoria , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Escocia , Autoinforme , Trastornos Relacionados con Sustancias/diagnóstico
4.
J Pediatr ; 175: 224-7, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27215776

RESUMEN

The ventilatory response of infants of mothers who smoke and misuse substances and controls to carbon dioxide was assessed at 6-12 weeks and the perinatal period. Infants of mothers who smoke and misuse substances had a dampened response at the peak age of sudden infant death syndrome, greater than in the perinatal period.


Asunto(s)
Dióxido de Carbono/fisiología , Conducta Materna , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Respiración , Fumar , Trastornos Relacionados con Sustancias , Femenino , Estudios de Seguimiento , Humanos , Hipercapnia/fisiopatología , Lactante , Recién Nacido , Masculino , Embarazo , Pruebas de Función Respiratoria , Factores de Riesgo , Muerte Súbita del Lactante/etiología , Contaminación por Humo de Tabaco/efectos adversos
5.
J Obstet Gynaecol ; 36(4): 468-72, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26467264

RESUMEN

In this ten-year retrospective study we were able to show that Maltese substance-misusing mothers (SMMs) have significantly different socio-biological characteristics from mothers in the general population which seem to impact on neonatal outcomes. Significant differences from the general population were noted in the SMM's age, age at first pregnancy, marital status, educational background, number of cigarettes smoked, number of offspring and weight gained in pregnancy. SMMs booked their pregnancy in hospital later than the general population. On the other hand their infants had a lower mean birth weight and head circumference, had lower Apgar scores, were of lesser gestational age and premature. They were less breast-fed and stayed longer in hospital after their birth.


Asunto(s)
Complicaciones del Embarazo/inducido químicamente , Resultado del Embarazo , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Factores de Edad , Estudios de Casos y Controles , Escolaridad , Femenino , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Malta , Embarazo , Nacimiento Prematuro/inducido químicamente , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversos , Factores Socioeconómicos , Adulto Joven
6.
Analyst ; 140(18): 6254-9, 2015 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-25977942

RESUMEN

Latent fingerprints provide a potential route to the secure, high throughput and non-invasive detection of drugs of abuse. In this study we show for the first time that the excreted metabolites of drugs of abuse can be detected in fingerprints using ambient mass spectrometry. Fingerprints and oral fluid were taken from patients attending a drug and alcohol treatment service. Gas chromatography mass spectrometry (GC-MS) was used to test the oral fluid of patients for the presence of cocaine and benzoylecgonine. The corresponding fingerprints were analysed using Desorption Electrospray Ionization (DESI) which operates under ambient conditions and Ion Mobility Tandem Mass Spectrometry Matrix Assisted Laser Desorption Ionization (MALDI-IMS-MS/MS) and Secondary Ion Mass Spectrometry (SIMS). The detection of cocaine, benzoylecgonine (BZE) and methylecgonine (EME) in latent fingerprints using both DESI and MALDI showed good correlation with oral fluid testing. The sensitivity of SIMS was found to be insufficient for this application. These results provide exciting opportunities for the use of fingerprints as a new sampling medium for secure, non-invasive drug detection. The mass spectrometry techniques used here offer a high level of selectivity and consume only a small area of a single fingerprint, allowing repeat and high throughput analyses of a single sample.


Asunto(s)
Cocaína/análogos & derivados , Cocaína/análisis , Dermatoglifia , Espectrometría de Masas/métodos , Detección de Abuso de Sustancias/métodos , Presión Atmosférica , Humanos , Propiedades de Superficie , Factores de Tiempo
7.
Am J Drug Alcohol Abuse ; 40(2): 137-42, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24521141

RESUMEN

BACKGROUND: Alcohol use is common among injecting drug users. The coexistence of alcohol consumption and injecting risk behaviour has the potential to increase harms among intravenous drug users (IDUs). OBJECTIVE: This study aimed to determine whether the level of alcohol use is a risk factor for injecting paraphernalia sharing behaviours. METHODS: A total of 637 treatment-seeking IDUs were assessed for injecting paraphernalia sharing behaviours and drinking risk level as defined by the National Institute for Health and Care Excellence (NICE). Multivariate analyses were performed to identify alcohol risk factors associated with injecting paraphernalia sharing behaviours. RESULTS: After adjusting for the effects of ethnicity, employment and drug used, the odds ratio of higher risk drinking for injecting paraphernalia sharing behaviours was 1.92 (95% CI 1.31-2.83). CONCLUSION: Higher-risk drinking in IDUs is associated with higher rates of injecting paraphernalia sharing behaviours. It is important to take alcohol use into account when evaluating these patients for treatment and designing intervention strategies.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Consumidores de Drogas/psicología , Compartición de Agujas/psicología , Asunción de Riesgos , Abuso de Sustancias por Vía Intravenosa/psicología , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Adulto Joven
8.
Subst Use Misuse ; 49(10): 1349-52, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24708427

RESUMEN

BACKGROUND: Dokha is a mixed tobacco product, smoked through a pipe, traditional in Arabic culture and popular in the UAE. User forums suggest this product may contain higher levels of nicotine and potentially psychoactive properties. However, there have been few published studies on dokha prevalence and health effects. The present study provides initial data on prevalence of use among high school students resident in Dubai, UAE. METHODS: 416 students were recruited from five English curriculum schools. Respondents completed a questionnaire measuring current and lifetime use of tobacco in the form of cigarettes, water-pipes and dokha. Current tobacco users completed the 'Hooked on Nicotine Checklist for signs of dependency. RESULTS: Data from 394 subjects were analyzed with mean age 16.9 years. Regular use (weekly or daily) of tobacco had relatively high prevalence (23.4%) compared to international data and was driven by use of the local tobacco, dokha. CONCLUSION: Dokha forms a commonly used tobacco product among young people in the UAE from both Arab and Western national groups. Little is currently known about the health and dependence risks of this product. The paper adds to the few studies calling for timely research into this and other emerging tobacco products.


Asunto(s)
Nicotiana , Fumar/epidemiología , Tabaquismo/epidemiología , Adolescente , Femenino , Humanos , Masculino , Prevalencia , Instituciones Académicas , Estudiantes , Encuestas y Cuestionarios , Emiratos Árabes Unidos/epidemiología , Adulto Joven
9.
Soc Stud Sci ; : 3063127241226829, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38270094

RESUMEN

In this article I follow the mystery of millions of tons of materials washed out to sea by the March 2011 Japan tsunami: a massive wave of lost materials expected to reach North American shores that never seems to officially arrive. I bring Gordon's conceptualization of haunting together with STS conversations about absence and invisibility to build on feminist approaches that do not take as given what is missing or what should be done. I begin by situating efforts to respectfully distinguish materials survivors call 'floating things' amidst a sea of concern for ocean plastic pollution. These efforts are then contrasted with what I initially perceived as the institutional erasure of floating things at sea, re-counting how some practices work to ensure materials can be ignored, cleaned-up, or used for other kinds of ocean science research. Yet, floating things refuse to disappear completely, as potential traces wash up on beaches, trajectories are modeled back into existence, and individual practices exceed institutional obligations. I argue that attending to hauntings by listening to ghosts and drifting with them is necessary for justice-oriented forms of care for absences. In the case of floating things, this means honoring survivor relations while resisting the perpetuation of Pacific narratives of danger from the outside.

10.
Forensic Sci Int ; 361: 112124, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38971140

RESUMEN

Latent fingerprints (LFPs) are predominantly used for personal identification, but in recent years research has shown their potential for drug screening. Despite this there is no standardised collection method to allow accurate drug test interpretation. We sought to help address this by characterising different variables related to sweat deposition in LFPs as the knowledge is limited. A series of experiments were conducted firstly to validate a novel tool called the Ridgeway (Intelligent Fingerprint Ltd. UK) to quantify the amount of sweat deposited from a LFP using the refractive index (RI). A significant positive correlation was observed between the Ridgeway score (Rs) and LFP mass [r = 0.868, p < 0.01]. The Rs was used as means to investigate optimal sampling to characterise sample deposition for drug screening purposes. It was found with a consistent disposition pressure (300 - 400 g) and surface (glass slide) no significant difference was observed between the left and right index finger [left: p = 0.938; right: p = 0.838]. Significantly higher Rs [p<0.01] were obtained when 10 cumulative LFPs were deposited compared to a single LFP, suggesting a larger sweat quantity. We also wanted to investigate optimal eccrine sweat sampling to confirm drug ingestion over drug contamination of the fingerprint. We found that wearing gloves did not significantly improve mean difference in Rs when compared to no gloves [p = 0.239]. To produce eccrine only LFPs, external contamination (e.g. sebaceous sweat) needs to be removed. Soap with lint free tissue was significantly better for this compared to antibacterial hand gel [p<0.01]. Our findings showed that the Ridgeway tool effectively quantified LFPs at the point of deposition using a refractive index and enabled us to establish conditions for consistent LFP sampling.

11.
Prev Med ; 57 Suppl: S8-10, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23624111

RESUMEN

OBJECTIVES: There is evidence that smoking behaviour differs by ethnicity. This study aims to compare smoking behaviour characteristics between Caucasian and Malay smokers. METHODS: A cross sectional survey, involving 175 smokers attending smoking cessation clinics at the Institute of Psychiatry, London, United Kingdom and University Malaya, Kuala Lumpur, Malaysia between May 2005 and February 2007. Data on demographics, smoking history, nicotine dependence and smoking behaviour were collected. RESULTS: All participants were males, mean age 30.7 ± 10.3 years. Caucasians initiated smoking significantly earlier (mean age 14.8 ± 2.8 years) (p = 0.001) and smoked regularly significantly earlier (mean age 17.3 ± 3.5) (p = 0.003) than Malays (mean starting age 16.9 ± 4.4 years and mean age regular use 19.5 ± 4.5 years), respectively. Caucasians smoked less for social integration than Malays (p = 0.03) but smoked more for regulation of negative affect than Malays (p = 0.008) and smoked more for hedonism than Malays (p < 0.001). CONCLUSION: Malays smoke as a means of socially integrating. This has important public health implications. Social reasons and the social environment play a role in smoking uptake, smoking maintenance and smoking cessation and this should be borne in mind for strategies planning to promote smoking cessation.


Asunto(s)
Pueblo Asiatico/psicología , Fumar/etnología , Población Blanca/psicología , Adolescente , Adulto , Edad de Inicio , Pueblo Asiatico/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Fumar/epidemiología , Fumar/psicología , Cese del Hábito de Fumar/etnología , Cese del Hábito de Fumar/psicología , Cese del Hábito de Fumar/estadística & datos numéricos , Conducta Social , Reino Unido/epidemiología , Población Blanca/estadística & datos numéricos , Adulto Joven
12.
Forensic Sci Int ; 350: 111781, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37478729

RESUMEN

Wildlife forensics is defined as providing forensic evidence to support legal investigations involving wildlife crime, such as the trafficking and poaching of animals and/ or their goods. While wildlife forensics is an underexplored field of science, the ramifications of poaching can be catastrophic. The consequences of wildlife crime include disease spread, species and habitat loss, human injury, and cultural loss. Efforts to use forensic science to combat poaching are currently limited to DNA-based techniques. However, fingermark analysis for the identification of perpetrators of wildlife crimes has not been explored to the same extent, despite being a cost-effective, simple-to-use forensic method that is easy to deploy in-field. This review covers literature that has explored fingermark examination techniques used on wildlife-related samples, such as pangolin scales, ivory-based substances, bone, and eggs, as well as feathers and skins, among more obscure trafficked items. Useful preliminary work has been conducted in this subject area, demonstrating that commonly used fingermark analysis techniques can be applied to wildlife-based items. However, many of these studies suffer from limitations in terms of experimental design. More work should be done on creating studies with larger sample sizes and novel approaches should be validated under environmental conditions that mimic real crime scenes. Further research into determining the forensic fingermark analysis techniques that perform the most efficiently in the environmental conditions of the countries where they are needed would therefore benefit legal investigations and help to reduce instances of poaching.


Asunto(s)
Animales Salvajes , Medicina Legal , Animales , Humanos , Medicina Legal/métodos , Ciencias Forenses/métodos , ADN , Crimen , Conservación de los Recursos Naturales
13.
J Appl Physiol (1985) ; 135(5): 1001-1011, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37767558

RESUMEN

Emphysema is one of the pathological hallmarks of chronic obstructive pulmonary disease. We have recently reported that radiofrequency therapy improves lung function in rodent models of emphysema. However, preclinical data using large animals is necessary for clinical translation. Here, we describe the work performed to establish a unilateral porcine emphysema model. Different doses of porcine pancreatic elastase (PPE) were instilled into the left lung of 10 Yucatan pigs. Three additional pigs were used as controls. Six weeks after instillation, lungs were harvested. Lung compliance was measured by a water displacement method and plethysmography. Systematic uniform random sampling of the left and right lungs was performed independently to measure alveolar surface area using micro-computed tomography (micro-CT) and histology. In pigs instilled with 725-750 U/kg of PPE (PPE group, n = 6), the compliance of the left lung was significantly higher by 37.6% than that of the right lung (P = 0.03) using the water displacement method. With plethysmography, the volume of the left lung was significantly larger than that of the right lung at 3, 5, and 10 cmH2O. Measurements from either micro-CT or histology images showed a significant decrease in alveolar surface area by 14.2% or 14.5% (P = 0.031) in the left lung compared with the right lung of the PPE group. A unilateral model for mild emphysema in Yucatan pigs has been established, which can now be used for evaluating novel therapeutics and interventional strategies.NEW & NOTEWORTHY For clinical translation, preclinical data using large animal models is necessary. However, papers describing an emphysema model in pigs, which are anatomically and physiologically similar to humans, are lacking. Here, we report success in creating a unilateral mild-emphysema model in pigs with only one single dose of porcine pancreatic elastase. This model will be useful in bringing novel technologies and therapies from small animals to humans with emphysema.


Asunto(s)
Enfisema , Enfisema Pulmonar , Humanos , Porcinos , Animales , Elastasa Pancreática/efectos adversos , Microtomografía por Rayos X , Pulmón , Enfisema/patología , Agua , Modelos Animales de Enfermedad
14.
J Anal Toxicol ; 46(1): 47-54, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33263738

RESUMEN

Sweat deposited via latent fingerprints (LFPs) was previously used to detect cocaine, opioids, cannabis and amphetamine via a point-of-care test (POCT). This screening method combined non-invasive sampling with a rapid result turnaround to produce a qualitative result outside of the laboratory. We report the novel application of a LFP drug screening test in a social care setting. Clients were tested on either an ad hoc or a routine basis using the POCT DOA114 (Intelligent Fingerprinting Ltd) drug screening cartridge. Screening cutoff values were 45, 35 and 95 pg/fingerprint for benzoylecgonine (BZE), morphine and amphetamine analytes, respectively. Confirmation LFP samples (DOA150, Intelligent Fingerprinting Ltd) and oral fluid (OF) were analyzed using ultra-performance liquid chromatography with tandem mass spectrometry. Thirty-six clients aged 36 ± 11 years participated (53% females). Individuals self-reported alcohol consumption (39%) and smoking (60%). Of 131 screening tests collected over 8 weeks, 14% tested positive for cocaine, 2% tested positive for opioids and 1% tested positive for amphetamine. Polydrug use was indicated in 10% of tests. Of 32 LFP confirmation tests, 63% were positive for cocaine and BZE. Opioids were also detected (31%), with the metabolite 6-monoacetylmorphine (6-MAM) being the most common (16%). In OF, cocaine was the dominant analyte (9%) followed by 6-MAM (5%). On comparing positive LFP screening tests with positive OF samples, we found that 39% and 38% were cocaine and opiate positive, respectively. Of the drugs screened for via the LFP POCT, cocaine was the most prevalent analyte in LFP and OF confirmation samples. The study is a step change in the routine drug screening procedures in a social care setting, especially useful for on-site cocaine detection in clients whose drug use was being monitored. Additionally, testing was easily accepted by clients and social care workers.


Asunto(s)
Cocaína , Alcaloides Opiáceos , Adulto , Anfetamina , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Detección de Abuso de Sustancias
15.
Drug Test Anal ; 14(8): 1482-1490, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35514245

RESUMEN

Human oral fluid is well established as a matrix for drug screening, particularly in the workplace. The need to synthesise synthetic oral fluid (SOF) has been recognised in order to overcome human oral fluid's composition variability. We have used SOF spiked with six common drugs of abuse or their primary metabolites: morphine, amfetamine, benzoylecgonine, cocaine, diazepam, and (-)-Δ9 -tetrahydrocannabinol (THC) in order to assess the suitability of this matrix for quality assurance purposes. For confirmation of a drug screening test, controls and spiked standards are normally required. All our analytes were detected by LC-MS/MS using a quick and easy "dilute and inject" sample preparation approach as opposed to relatively slower solid-phase extraction. The limit of detection (LOD) was 10 ng/ml for diazepam and THC and 5 ng/ml for morphine, amfetamine, benzoylecgonine and cocaine. Validation results showed good accuracy as well as inter- and intra-assay precision (CV [%] < 5). Our work highlighted the importance of adding Tween® 20 to the SOF and calibrants to reduce losses when handling THC. Furthermore, drug stability was tested at various temperatures (5°C, 20°C and 40°C), for a number of days or after freeze-thaw cycles. Recommendations regarding storage are provided, the spiked SOF being stable at 5°C for up to 1 week without significant drug concentration loss.


Asunto(s)
Cocaína , Detección de Abuso de Sustancias , Anfetamina , Cromatografía Liquida , Cocaína/análisis , Diazepam , Dronabinol/análisis , Humanos , Derivados de la Morfina/análisis , Saliva/química , Detección de Abuso de Sustancias/métodos , Espectrometría de Masas en Tándem
16.
Drug Test Anal ; 14(4): 613-621, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34766468

RESUMEN

To date, a specific point-of-care test (POCT) for 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, 'E') in latent fingerprints (LFPs) has not been explored. Other POCTs identify MDMA in sweat by detecting the drug as a cross-reactant rather than target analyte, thus decreasing the test's sensitivity. The study's aim was to design a sensitive POCT for the detection of MDMA in LFPs using surface plasmon resonance (SPR) and lateral flow immunoassay (LFA) technology. A high-affinity antibody binding pair was identified using the former technique, deeming the pair suitable for a LFA. Titrations of fluorescently labelled antibody and antigen concentrations were tested to identify a sharp drop-in signal upon the addition of MDMA to allow a clear distinction between negative and positive outcomes. We trialled the LFA by producing dose response curves with MDMA and a group of drugs that share a similar chemical structure to MDMA. These were generated through spiking the LFA with increasing levels of drug (0-400 pg/10 µl of MDMA; 0-10,000 pg/10 µl of cross-reactant). Fluorescent test signals were measured using a cartridge reader. The cut-off (threshold) 60 pg/10 µl calculated better cartridge performance (1.00 sensitivity, 0.95 specificity and 0.98 accuracy), when compared with 40 pg/10 µl. The biggest cross-reactant was PMMA (250%), followed by MDEA (183%), MBDB (167%), MDA (16%) and methamphetamine (16%). A sensitive LFP screening tool requiring no sample preparation was successfully designed.


Asunto(s)
3,4-Metilenodioxianfetamina , Metanfetamina , N-Metil-3,4-metilenodioxianfetamina , Anfetaminas , Cromatografía de Gases y Espectrometría de Masas , N-Metil-3,4-metilenodioxianfetamina/análisis , Pruebas en el Punto de Atención , Detección de Abuso de Sustancias/métodos , Resonancia por Plasmón de Superficie , Tecnología
17.
Drug Test Anal ; 13(3): 709-719, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33025712

RESUMEN

Quality assurance schemes for drug-screening programmes require access to large quantities of biological matrices for reference or control samples. This presents problems when the availability of a matrix, such as oral fluid (OF) for screening or for confirmatory purposes, limits the collection of large volumes. In such cases, synthetic alternatives of OF may provide a solution. The preparation of an artificial (synthetic) oral fluid (AOF) was conducted by dissolving its components (salts, surfactant, antimicrobial agent and mucin) in water. We characterised the physical properties of AOF to determine its suitability as a matrix for quality assurance purposes. The evaluation of pH, specific gravity (SG), conductivity (mS cm-1 ), freezing point depression (°C), light-scattering and kinematic viscosity (mm2 s-1 ) showed AOF to be a stable, reliable matrix. Synthetic OF was prepared using components (mucin, surfactants and so on) obtained from different suppliers and a comparison was performed. Our results suggest that AOF is a feasible matrix for the preparation of quality assurance samples for confirmatory or drug screening programmes.


Asunto(s)
Líquidos Corporales/química , Detección de Abuso de Sustancias/métodos , Antiinfecciosos/química , Humanos , Concentración de Iones de Hidrógeno , Mucinas/química , Garantía de la Calidad de Atención de Salud , Sales (Química)/química , Gravedad Específica , Tensoactivos/química , Temperatura de Transición , Viscosidad
18.
J Psychopharmacol ; 35(5): 547-555, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32538252

RESUMEN

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. AIM: To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. METHODS: Twenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. RESULTS: MDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. CONCLUSION: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.


Asunto(s)
Afecto/efectos de los fármacos , Empatía/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/farmacología , Confianza/psicología , Adulto , Teorema de Bayes , Conducta Cooperativa , Método Doble Ciego , Femenino , Alucinógenos/sangre , Alucinógenos/farmacología , Humanos , Masculino , Persona de Mediana Edad , N-Metil-3,4-metilenodioxianfetamina/sangre , Conducta Social , Adulto Joven
19.
Sci Rep ; 11(1): 20056, 2021 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-34625605

RESUMEN

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in "volume reduction" and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.


Asunto(s)
Tolerancia al Ejercicio , Condicionamiento Físico Animal , Enfisema Pulmonar/radioterapia , Fibrosis Pulmonar/prevención & control , Terapia por Radiofrecuencia/métodos , Animales , Rendimiento Pulmonar , Masculino , Ratones , Ratones Endogámicos C57BL , Elastasa Pancreática/administración & dosificación , Enfisema Pulmonar/etiología , Enfisema Pulmonar/metabolismo , Porcinos
20.
Anal Chem ; 82(22): 9150-4, 2010 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-20968301

RESUMEN

An immunoassay based technique is used for the detection of psychoactive substances in the sweat deposited within fingermarks of a narcotic drug user. Magnetic particles functionalized with antimorphine and antibenzoylecgonine antibodies were used for the detection of a metabolite of heroin (morphine) and a metabolite of cocaine (benzoylecgonine), respectively. The drug metabolites were detected individually as well as simultaneously from a single fingermark. The images of the fingermarks obtained using brightfield and fluorescence microscopy were of high evidential quality with resolution to enable identification of an individual in addition to providing information on drug usage.


Asunto(s)
Bioensayo/métodos , Dermatoglifia , Inmunoensayo/métodos , Narcóticos/análisis , Narcóticos/metabolismo , Detección de Abuso de Sustancias/métodos , Cocaína/análogos & derivados , Cocaína/análisis , Cocaína/inmunología , Cocaína/metabolismo , Humanos , Inmunoconjugados/química , Inmunoconjugados/inmunología , Magnetismo , Morfina/análisis , Morfina/inmunología , Morfina/metabolismo , Narcóticos/inmunología , Factores de Tiempo
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