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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 - 400â¯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.
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Dermatoglifia , Refractometría , Sudor , Humanos , Sudor/química , Masculino , Femenino , Adulto , Glándulas Ecrinas , Detección de Abuso de Sustancias/métodos , Guantes ProtectoresRESUMEN
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.
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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.
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Enfisema , Enfisema Pulmonar , Humanos , Porcinos , Animales , Elastasa Pancreática/efectos adversos , Microtomografía por Rayos X , Pulmón , Enfisema/patología , Agua , Modelos Animales de EnfermedadRESUMEN
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.
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Animales Salvajes , Medicina Legal , Animales , Humanos , Medicina Legal/métodos , Ciencias Forenses/métodos , ADN , Crimen , Conservación de los Recursos NaturalesRESUMEN
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.
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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/metabolismoRESUMEN
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.
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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/genéticaRESUMEN
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.
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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 TándemRESUMEN
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.
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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 , TecnologíaRESUMEN
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.
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Cocaína , Alcaloides Opiáceos , Adulto , Anfetamina , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Detección de Abuso de SustanciasRESUMEN
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 (â§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.
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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 , PorcinosRESUMEN
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.
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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 , ViscosidadRESUMEN
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.
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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 JovenRESUMEN
Objective: The objective of the study is to quantify the extent of specific polysubstance use, drug transitions to current substances, and describe the association with alcohol use disorders among inmates with ADHD. We also examined health risk behaviors and patterns of offending in relation with ADHD. Method: A total of 387 male British prison inmates were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2). Results: Male prisoners with ADHD endorse more methadone and amphetamine use. There was a significantly higher linear trend among those with ADHD for the number of substances ever used. ADHD was positively associated with increasing levels of alcohol use disorder severity, and with alcohol dependence. Transition along the pathways of substance misuse and persistence of drug misuse was better explained by the presence of conduct disorder/antisocial personality traits. Conclusion: Higher rates of alcohol dependence and stimulant-cocaine misuse suggest these inmates have maladaptive coping mechanisms, such as self-medication behaviors.
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Alcoholismo , Trastorno por Déficit de Atención con Hiperactividad , Preparaciones Farmacéuticas , Prisioneros , Trastornos Relacionados con Sustancias , Adulto , Alcoholismo/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Humanos , Masculino , Prisiones , Escalas de Valoración Psiquiátrica , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
Boldenone (1-dehydrotestosterone) is an exogenous anabolic-androgenic steroid (AAS) but is also known to be endogenous in the entire male horse and potentially formed by microbes in voided urine, the gastrointestinal tract, or feed resulting in its detection in urine samples. In this study, equine fecal and urine samples were incubated in the presence of selected stable isotope labeled AAS precursors to investigate whether microbial activity could result in 1-dehydrogenation, in particular the formation of boldenone. Fecal matter was initially selected for investigation because of its high microbial activity, which could help to identify potential 1-dehydrogenated biomarkers that might also be present in low quantities in urine. Fecal incubations displayed Δ1-dehydrogenase activity, as evidenced by the use of isotope labeled precursors to show the formation of boldenone and boldione from testosterone and androstenedione, as well as the formation of Δ1-progesterone and boldione from progesterone. Unlabeled forms were also produced in unspiked fecal samples with Δ1-progesterone being identified for the first time. Subsequent incubation of urine samples with the labeled AAS precursors demonstrated that Δ1-dehydrogenase activity can also occur in this matrix. In all urine samples where labeled boldenone or boldione were detected, labeled Δ1-progesterone was also detected. Δ1-progesterone was not detected any non-incubated urine samples or following an administration of boldenone undecylenate to one mare/filly. Δ1-progesterone appears to be a candidate for further investigation as a suitable biomarker to help evaluate whether boldenone present in a urine sample may have arisen due to microbial activity rather than by its exogenous administration.
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Anabolizantes/orina , Heces/química , Caballos/orina , Testosterona/análogos & derivados , Anabolizantes/análisis , Anabolizantes/metabolismo , Animales , Cromatografía Liquida , Doping en los Deportes , Caballos/fisiología , Masculino , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Testosterona/análisis , Testosterona/metabolismo , Testosterona/orinaRESUMEN
The licensed pharmaceutical industry and regulators use many approaches to control counterfeiting, but it remains a very difficult task to differentiate between counterfeit and real products. Moreover, there is a lack of techniques available for providing a batch specific molecular bar code for tablets that has the required traceability, specificity and sensitivity to be fit for purpose. The aim of this study was to evaluate DNA molecular tags as a potential anti-counterfeiting technology in tablets. Lactose tablets (400â¯mg) were used as a model to investigate incorporation DNA molecular tag into a solid dosage form: DNA authentication was carried out on an Applied DNA SigNify® qPCR instrument. Tablet batches were subjected to accelerated stability conditions (40⯰C and 75% RH) for up to 6â¯months. All batches passed the monograph specifications of the British Pharmacopoeia (hardness, friability and mass uniformity) throughout the storage period. In all of recovery plots, the number of cycles required for DNA detection (Cq values) increased as a function of storage time, which indicated a reduction in tag levels, but it should be noted for all storage experiments the tag was clearly detected. It would appear that DNA molecular tags could feasibly be applied within the pharmaceutical development cycle when a new solid dosage form is brought to the market so as to mitigate the risk and dangers of counterfeiting.
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Medicamentos Falsificados/análisis , Sondas de ADN/aislamiento & purificación , Composición de Medicamentos/métodos , Fraude/prevención & control , Coloración y Etiquetado/métodos , Composición de Medicamentos/normas , Excipientes/química , Estudios de Factibilidad , Lactosa/química , ComprimidosRESUMEN
Boldenone is an anabolic-androgenic steroid that is prohibited in equine sports. Urine from the uncastrated male horse contains boldenone that is thought to be of endogenous origin and thus a threshold ('cut-off') concentration has been adopted internationally for free and conjugated boldenone to help distinguish cases of doping from its natural production. The testis is likely to be a source of boldenone. Qualitative analysis was performed on extracts of equine testicular homogenates (nâ¯=â¯3 horses) incubated non-spiked and in the presence of its potential precursors using liquid chromatography tandem mass spectrometry (LC-MS/MS) and LC high resolution mass spectrometry (LC-HRMS). Samples were analysed both underivatised and derivatised to increase the certainty of identification. In addition to previously reported endogenous steroids, analysis of non-spiked testicular tissue samples demonstrated the presence of boldenone and boldienone at trace levels in the equine testis. Incubation of homogenates with deuterium or carbon isotope labelled testosterone and androstenedione resulted in the matching stable isotope analogues of boldenone and boldienone being formed. Additionally, deuterium and carbon labelled 2-hydroxyandrostenedione was detected, raising the possibility that this steroid is a biosynthetic intermediate. In conclusion, boldenone and boldienone are naturally present in the equine testis, with the biosynthesis of these steroids arising from the conversion of testosterone and androstenedione. However, additional work employing larger numbers of animals, further enzyme kinetic experiments and pure reference standards for 2-OH androstenedione isomers would be required to better characterize the pathways involved in these transformations.
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Testículo/metabolismo , Testosterona/análogos & derivados , Animales , Caballos , Masculino , Testosterona/biosíntesis , Testosterona/química , Testosterona/metabolismoRESUMEN
Lactose, a disaccharide is a ubiquitous excipient in many pharmaceutical formulations which exists in two anomeric forms; either as α- or ß-lactose. The anomers have different properties which can affect their application. Nevertheless, batches of lactose products are widely produced by many manufacturers, and is available in many grades. However, the anomeric content of these batches has not been accurately characterized and reported previously. Therefore, the aim of this study was to analyse a set of 19 commercially available samples of lactose using a novel H1-NMR technique to establish a library showing the anomeric content of a large range of lactose products. The lactose samples were also analysed by DSC. The anomeric content of the α-lactose monohydrate samples were found to vary by more than 10%, which might influence bioavailability from final formulations. The data showed that there is a need to determine and monitor the anomeric content of lactose and this should be a priority to both the manufacturers and the formulators of medicines.
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Química Farmacéutica/métodos , Excipientes/química , Lactosa/química , Espectroscopía de Resonancia Magnética/métodos , Rastreo Diferencial de CalorimetríaRESUMEN
BACKGROUND & OBJECTIVE: Substance misuse has been a major health and social issue worldwide and has become an important public health issue in China over the past two decades. Methadone maintenance treatment (MMT) has been proved worldwide by large bodies of research to be one of the most effective practices for illicit drug users. The Treatment Outcome Profile (TOP) was developed in 2007 by the UK National Treatment Agency (NTA). It has been proved to be a reliable instrument for outcome measure. This study aim to develop the Chinese version of the Treatment Outcome Profile (TOP), and to assess whether TOP is a reliable outcome measure that can be recommended for use in Chinese MMT program. METHODS: The Chinese version of TOP was translated and revised based on the English version of TOP. Psychometric properties of TOP were evaluated through face-to-face interviews in 197 patients who had been attending methadone maintenance treatment clinics in Kunming city, Yunnan Institute for Drug Abuse, for less than three months. Patients were interviewed by 3 trained interviewers. Reliability and validity of the instrument were analyzed by measures including test-retest and inter-rater reliability, concurrent validity and change sensitivity. Concurrent validity was assessed by comparing the scores from TOP with scores obtained from validated clinometric instruments. Self-reported opiate use was compared with results of urine analysis. Change sensitivity was judged by t-tests and chi-square tests. RESULTS & CONCLUSIONS: About 67% of the 197 interviewers were male and 33% were female. Test-retest reliability of TOP scores (after 10 days interval) were good (K=0.65 to 0.95), inter-rater correlations (ICC) ranged from 0.7 to 0.9, and the criterion validity ranged from 0.72 to 0.88. TOP covers a large scope of problems encountered by drug users needed for treatment. The Chinese version of TOP is a reliable and valid assessment tool.
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Metadona/administración & dosificación , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/rehabilitación , Evaluación de Resultado en la Atención de Salud/métodos , Adulto , China , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Psicometría , Reproducibilidad de los Resultados , Autoinforme , Detección de Abuso de Sustancias , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
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/diagnósticoRESUMEN
OBJECTIVES: To determine at the peak age for sudden infant death syndrome (SIDS) the ventilatory response to hypoxia of infants whose mothers substance misused in pregnancy (SM infants), or smoked during pregnancy (S mothers) and controls whose mothers neither substance misused or smoked. In addition, we compared the ventilatory response to hypoxia during the neonatal period and peak age of SIDS. WORKING HYPOTHESIS: Infants of S or SM mothers compared to control infants would have a poorer ventilatory response to hypoxia at the peak age of SIDS. STUDY DESIGN: Prospective, observational study. PATIENT-SUBJECT SELECTION: Twelve S; 12 SM and 11 control infants were assessed at 6-12 weeks of age and in the neonatal period. METHODOLOGY: Changes in minute volume, oxygen saturation, heart rate, and end tidal carbon dioxide levels on switching from breathing room air to 15% oxygen were assessed. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines. RESULTS: The S and SM infants had a greater decline in minute volume (P = 0.037, P = 0.016, respectively) and oxygen saturation (P = 0.031) compared to controls. In all groups, the magnitude of decline in minute volume in response to hypoxia was higher in the neonatal period compared to at 6-12 weeks (P < 0.001). CONCLUSIONS: Both maternal substance misuse and smoking were associated with an impaired response to a hypoxic challenge at the peak age for SIDS. The hypoxic ventilatory decline was more marked in the neonatal period compared to the peak age for SIDS indicating a maturational effect. Pediatr Pulmonol. 2017;52:650-655. © 2016 Wiley Periodicals, Inc.