An immunochromatographic dipstick as an alternate for monitoring of heroin metabolites in urine samples

Heroin use and addiction pose serious risks and side effects due to overdose. Quantification of heroin in biological samples is challenging due to rapid deacetylation of heroin to its active metabolites. In this study, we report the quantification of metabolic degradation of heroin by-products in biological urine samples. The presence of the drug was monitored after oral administration of heroin at different time intervals. Various biophysical techniques, such as high performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to evaluate the presence of the drug. A competitive fluorescence based immunoassay was developed with a limit of detection (LOD) up to 0.01 ng mL⁻¹ and the IC₅₀ value was 0.1 ng mL⁻¹, while the dipstick assay shows a LOD up to 5 ng mL⁻¹. Rapid detection of narcotic drugs was carried out for biological urine samples collected at various time points. Validation of the developed dipstick was carried out for the standard as well as the spiked urine samples by fluorescence based immunoassay (FIA), using anti-morphine antibodies. A strong correlation (R = 0.94) was obtained between the developed dipstick and FIA assay for biological urine samples collected at various time points. The developed immunochromatographic dipstick is highly sensitive, field applicable and cost effective, and can serve as a first choice for the monitoring of narcotic drugs in blood, urine and saliva in drug addicts and athletes.

Pathway of heroin degradation post oral administration in mice.     

The GLP-1 Receptor Agonist Liraglutide Increases Myocardial Glucose Oxidation Rates via Indirect Mechanisms and Mitigates Experimental Diabetic Cardiomyopathy

BackgroundType 2 diabetes (T2D) increases risk for cardiovascular disease. Of interest, liraglutide, a therapy for T2D that activates the glucagon-like peptide-1 receptor to augment insulin secretion, reduces cardiovascular-related death in people with T2D, though it remains unknown how liraglutide produces these actions. Notably, the glucagon-like peptide-1 receptor is not expressed in ventricular cardiac myocytes, making it likely that ventricular myocardium-independent actions are involved. We hypothesized that augmented insulin secretion may explain how liraglutide indirectly mediates cardioprotection, which thereby increases myocardial glucose oxidation.MethodsC57BL/6J male mice were fed either a low-fat diet (lean) or were subjected to experimental T2D and treated with either saline or liraglutide 3× over a 24-hour period. Mice were subsequently euthanized and had their hearts perfused in the working mode to assess energy metabolism. A separate cohort of mice with T2D were treated with either vehicle control or liraglutide for 2 weeks for the assessment of cardiac function via ultrasound echocardiography.ResultsTreatment of lean mice with liraglutide increased myocardial glucose oxidation without affecting glycolysis. Conversely, direct treatment of the isolated working heart with liraglutide had no effect on glucose oxidation. These findings were recapitulated in mice with T2D and associated with increased circulating insulin levels. Furthermore, liraglutide treatment alleviated diastolic dysfunction in mice with T2D, which was associated with enhanced pyruvate dehydrogenase activity, the rate-limiting enzyme of glucose oxidation.ConclusionsOur data demonstrate that liraglutide augments myocardial glucose oxidation via indirect mechanisms, which may contribute to how liraglutide improves cardiovascular outcomes in people with T2D.     

Preferences for Conditional Economic Incentives to Improve Pre-exposure Prophylaxis Adherence: A Discrete Choice Experiment Among Male Sex Workers in Mexico

AIDS and Behavior - Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV but requires sustained adherence. Conditional economic incentives (CEIs) can improve medication-taking...     

Pilot Randomized Controlled Trial of Motivational Interviewing with Sexual Minority Male Couples to Reduce Drug Use and Sexual Risk: The Couples Health Project

AIDS and Behavior - A randomized controlled trial evaluated the preliminary efficacy of a dyadically-delivered motivational interviewing (MI) intervention to reduce drug use and sexual risk in a...     

'Cold hand, ischemic heart': treatment by stenting of the left subclavian artery

A 59-year-old man presented with worsening angina and a cold, painful left hand, eight years after coronary artery bypass surgery. Coronary angiography showed extensive coronary atherosclerosis with blocked vein grafts to his left circumflex and right coronary arteries. There was a severe narrowing in the left subclavian artery before the origin of the left internal mammary artery (LIMA) which appeared patent. PTCA and stent implantation to the left subclavian artery stenosis restored normal flow to the left hand and the LIMA with abolition of his ischemic hand symptoms and marked improvement of his angina.     

Improving IR Ergonomics Using a Flexible C-Arm System

PurposeTo evaluate the impact of a versatile flexible ceiling-mounted C-arm on active table and gantry repositioning during interventions and its effect on operator discomfort, system usability, and patient safety compared with a traditional ceiling-mounted system.Materials and MethodsThere were 100 IR procedures studied: 50 in a traditional IR system (standard group) and 50 with a novel multiaxis ceiling-mounted system (test group). FlexArm was capable of multiple gantry rotation points allowing increased access to the patient in addition to 236 cm of lateral x-ray detector travel. For each procedure, both the table and the gantry repositioning were measured. Patient safety, patient/equipment repositioning effort, and physical discomfort were evaluated through an operator survey.ResultsTable repositioning was reduced from 42 to 16 instances per procedure (P < .001) in the test group compared with the standard group. The operators perceived less table and gantry repositioning effort (P < .0001) and decreased risks of equipment collisions, displacement of vascular access, and dislodgment of tubes/lines with the test group (P < .0001). Operator discomfort was reduced for all body areas in the test group over the standard group (P < .0001).ConclusionsThe FlexArm system geometry enhances operator ergonomics, as there was a decrease need to move the table, leading to a perceived decrease in patient risk and decrease operator physical discomfort when compared to a traditional imaging system.     

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development.SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca²⁺ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex.