The window area constitutes a significant part of the façades of heritage buildings in French cities. An effective way to improve window performance as well as preserve the appearance of heritage ...buildings is to retrofit old single-glazed windows into supply-air double windows by putting a secondary window inside the existing window. For window renovation, the U-value is an important indicator. To accurately identify the U-values (i.e., the Ueq value, Uuse value and Uloss value) of supply-air double windows, a new guarded hot box (GHB) method was firstly proposed which improved the GHB setup and calibration/testing procedure. Based on GHB experiments, the thermal performance of different window configurations was identified and compared. The results showed that U-value reductions were in the range of 59.2%-80.8% by renovating a single-glazed window into a supply-air double window. Moreover, the window U-value was compared to the center-of-glass U-value, which is often used in building codes to simulate building energy consumptions. It was found that the deviations between the window U-value and the center-of-glass U-value were in the range of 21.6%-45.5% for different window configurations. The GHB experimental data were further utilized to validate a three-dimensional computational fluid dynamic (CFD) model. Based on the validated model, a parametric study was performed to investigate the impacts of different window configuration parameters on U-values. The results showed that the location of Low-E coating, coating emissivity and air flow rate had significant effects on U-values. In addition, it was found that improving the thermal conductivity performance of the internal window frame was more important than the external window frame.
Highlights • “Chemsex” describes the use of psychoactive substances in sexual settings. • There is evidence to suggest a rise in chemsex among gay men in London. • Our qualitative study examined harm ...reduction need for men engaged in chemsex. • Fears of judgment dissuade some men from accessing professional help when needed. • Generic drug services may not be sufficiently resourced in relation to this issue.
L’acide γ-amino-butyrique (GABA), principal neurotransmetteur inhibiteur du système nerveux central, se lie aux récepteurs GABAA et GABAB.
Les intoxications aigues par les agonistes des récepteurs ...GABAA (éthanol, benzodiazépines) sont très fréquentes et peuvent entraîner un coma calme et hypotonique. Le traitement du coma éthylique est symptomatique alors qu’il existe un antidote pour les intoxications par benzodiazépines, le flumazénil. Les intoxications par les agonistes des récepteurs GABAB (GHB, baclofène) sont rares mais en augmentation. Les intoxications par GHB peuvent entraîner un coma calme hypotonique associé à une bradycardie, une dépression respiratoire et des myoclonies. Les intoxications par baclofène peuvent entraîner des troubles neurologiques parfois associés à des complications respiratoires et hémodynamiques. Dans les deux cas, le traitement est symptomatique. Après une intoxication aiguë par des agonistes GABA, il peut survenir un syndrome de sevrage chez les utilisateurs chroniques peu de temps après la résolution des symptômes d’intoxication.
Les agonistes GABAergiques sont fréquemment rencontrés au cours des intoxications aiguës. Si les intoxications par les agonistes des récepteurs GABAA sont bien connus (éthanol, benzodiazépines), ces vingt dernières années ont vu émerger la survenue d’intoxications par les agonistes des récepteurs GABAB (GHB, baclofène).
γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system (CNS), binds to two types of receptors: the GABAA and GABAB receptors.
GABAA agonists poisonings (ethanol, benzodiazepines) are very common and may induce central nervous system depression. The treatment of ethanol poisoning is symptomatic while there is an antidote for benzodiazepines poisoning, the flumazenil. GABAB receptor agonists (GHB, baclofen) poisonings remain rare but are increasing. GHB poisonings can cause coma frequently associated with bradycardia, respiratory depression, myoclonus and hypothermia. Baclofene poisonings are mainly responsible for neurological complications that may be associated with respiratory and hemodynamic complications. Treatment of GABAB receptor agonists poisonings is symptomatic. After acute GABA agonists poisoning, withdrawal syndrome may occur in chronic users shortly after the resolution of poisoning symptoms.
GABAergic agonists are frequently responsibles for acute poisoning. Although GABAA receptor agonists poisonings are well described (ethanol, benzodiazepines), the last twenty years have seen the increase in GABAB receptor agonists poisonings (GHB, baclofen).
Background: The term 'chemsex' was coined to indicate the voluntary intake of
psychoactive and non psychoactive drugs in the context of recreational settings to facilitate and/or to
enhance sexual ...intercourses mostly among men who have sex with other men (MSM).
Objective: The authors aimed to review the mechanisms of action, the toxicity and the pattern of use
and abuse of substances involved in 'chemsex' practice together with the sociocultural background
underlying it and the health-related consequences that they may have.
Results: Gamma-hydroxybutyrate, gamma-butyrolactone,1,4-butanediol, mephedrone, methamphetamine,
sildenafil, tadalafil, vardenafil and alkyl nitrites have been described in their role of 'chemsex drugs'
including pharmacological action and in their implication to impair capacities to chose sexual
partners and consensual sex. Moreover, it has been demonstrated that sexual activity over protracted
length of time under the influence of chemsex drugs can result in rectal trauma or penile abrasions and a
significant increase of the risk of transmission of sexual transmitted diseases, especially in case of
condomless intercourses, which are frequent in this context, representing therefore a serious health
threat.
Conclusion: One of the major problems to establish health policy priority interventions for chemsex
is the lack of available epidemiological data on the issue. Finally, social actions should be taken in
order to break down the barriers that currently exist among chemsex drug users in accessing services,
including the shame and stigma often associated with drug use. In conclusion, more specific
resources to face high risks of infections and HIV transmission are required in bisexual and
homosexual individuals having SUID: sex under the influence of drugs.
The small-molecule ligand (E)-2-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo7annulen-6-ylidene)acetic acid (NCS-382) is an analogue of γ-hydroxybutyric acid (GHB) and is widely used for probing the ...brain-specific GHB high-affinity binding sites. To reach these, brain uptake is imperative, and it is therefore important to understand the molecular mechanisms of NCS-382 transport in order to direct in vivo studies. In this study, we hypothesized that NCS-382 is a substrate for the monocarboxylate transporter subtype 1 (MCT1) which is known to mediate blood-brain barrier (BBB) permeation of GHB. For this purpose, we investigated NCS-382 uptake by MCT subtypes endogenously expressed in tsA201 and MDA-MB-231 cell lines in assays of radioligand-based competition and fluorescence-based intracellular pH measurements. To further verify the results, we measured NCS-382 uptake by means of mass spectrometry in Xenopus laevis oocytes heterologously expressing MCT subtypes. As expected, we found that NCS-382 is a substrate for MCT1 with half-maximal effective concentrations in the low millimolar range. Surprisingly, NCS-382 also showed substrate activity at MCT4 as well as uptake in water-injected oocytes, suggesting a component of passive diffusion. In conclusion, transport of NCS-382 across membranes differs from GHB as it also involves MCT4 and/or passive diffusion. This should be taken into consideration when designing pharmacological studies with this compound and its closely related analogues. The combination of MCT assays used here exemplifies a setup that may be suitable for a reliable characterization of MCT ligands in general.
Display omitted
•Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL.•The most common features were reduction in consciousness.•Patients with ethanol co-ingestion had a higher ...frequencies of arrivals by ambulance, reduction in consciousness, need for treatment in the ED, use of sedatives, admission to critical care units, and prolonged hospital stay.
Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use.
We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 – December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs.
A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003).
Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay.
Narcolepsy is a chronic and debilitating sleep disorder characterized by cataplexy and excessive daytime sleeping. Gamma-hydroxybutyrate (GHB) has been widely used to treat narcolepsy, and new ...findings have been published in recent years.
A meta-analysis was conducted to assess the efficacy and tolerability of GHB treatment in adults with narcolepsy.
A systematic search of PubMed, Cochrane, Embase, Web of Science, and clinical-trials.gov from inception to June 2018 was performed. Change in daily diaries and polysomnographic data of narcoleptic patients were defined as the efficacy outcomes. The tolerability and acceptability outcomes were the rates of adverse events and dropping out for adverse effects or other reasons.
Fifteen randomized controlled trials involving 2104 participants were identified. GHB was found to improve cataplexy attacks (P = 0.001), subjective daytime sleepiness (P < 0.0001), daytime sleep latency (P < 0.0001), inadvertent naps/sleep attacks (P < 0.00001), effective rates (Clinical Global Impression of change) (P < 0.00001), hypnagogic hallucinations (P = 0.004), sleep paralysis (P = 0.004), stage 1 sleep (P = 0.04), slow wave sleep (P = 0.003), REM sleep (P = 0.0006), sleep shifts (P = 0.005), nocturnal awakenings (P = 0.004), quality of nocturnal sleep (P < 0.00001), chin muscle activity, and quality of life, but had no effect on stage 2 sleep (P = 0.88). GHB was less well tolerated than placebo because of side effects that occurred in a dose-dependent fashion (RR = 6.08; 95% CI = 2.18 to 16.97; P = 0.0006).
GHB was effective in improving narcolepsy-cataplexy and related symptoms in adults but was less well tolerated than placebo because of dose-dependent side effects.
•GHB was effective in adults with narcolepsy and its effects on many aspects of narcolepsy were dose- and/or time-related.•Only treatment with 9 g/night GHB resulted in a significant reduction of both cataplexy and objective daytime sleepiness.•The greatest reduction in cataplexy achieved at 4 weeks of 9 g/night GHB treatment.•GHB was less well tolerated than placebo because of dose-dependent side effects.
Introduction
Many patients with cluster headache report use of illicit drugs. We systematically assessed the use of illicit drugs and their effects in a well-defined Dutch cluster headache ...population.
Methods
In this cross-sectional explorative study, 756 people with cluster headache received a questionnaire on lifetime use and perceived effects of illicit drugs. Results were compared with age and sex-matched official data from the Dutch general population.
Results
Compared to the data from the general population, there were more illicit drug users in the cluster headache group (31.7% vs. 23.8%; p < 0.01). Reduction in attack frequency was reported by 56% (n = 22) of psilocybin mushroom, 60% (n = 3) of lysergic acid diethylamide and 50% (n = 2) of heroin users, and a decreased attack duration was reported by 46% (n = 18) of PSI, 50% (n = 2) of heroin and 36% (n = 8) of amphetamine users.
Conclusion
In the Netherlands, people with cluster headache use illicit drugs more often than the general population. The question remains whether this is due to an actual alleviatory effect, placebo response, conviction, or common pathophysiological background between cluster headache and addictive behaviours such as drug use.
•GHB related acids increased after intake of GHB.•Analysis on related acids increase detection window.•cut-offs to distinguish from endogenous levels recommended.
GHB related acids (3,4-dihydroxy ...butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.
The high frequency of drug‐facilitated sexual assaults (DFSA) and other criminal acts perpetrated by the adulteration of drinking water or other beverages with γ-hydroxybutyrate (GHB) compels ...researchers to develop spot tests for its rapid detection, on site, by the broad public. We report a BODIPY-metal complex (1·Fe3+) as a simple colorimetric and fluorimetric indicator based on a ligand displacement design for the sensitive determination of GHB. Assays were developed to detect the presence of GHB in the complex matrices of a broad range of spiked alcoholic and non-alcoholic beverages. The complex enables rapid qualitative spot tests and quantitative assays, and works in both solution and practical solid-state indicator strips.
The high frequency of drug‐facilitated sexual assaults (DFSA) and other criminal acts perpetrated by the adulteration of drinking water or other beverages with γ-hydroxybutyrate (GHB) compels researchers to develop spot tests for its rapid detection, on site, by the broad public. We report a BODIPY-metal complex (1·Fe3+) as a simple colorimetric and fluorimetric indicator based on a ligand displacement design for the sensitive determination of GHB. Assays were developed to detect the presence of GHB in the complex matrices of a broad range of spiked alcoholic and non-alcoholic beverages. The complex enables rapid qualitative spot tests and quantitative assays, and works in both solution and practical solid-state indicator strips. Display omitted
•A simple colorimetric and fluorimetric indicator 1·Fe3+ for the rapid detection of GHB is developed.•The assay is simple, fast (<5 s), and highly sensitive (LOD = 0.25 μg/mL (absorption) and 0.01 μg/mL (emission)) for GHB.•The assay exhibits high-contrast color and fluorescence responses for GHB in various alcoholic and non-alcoholic beverages.•Low-cost polymeric test-strips made from 1·Fe3+ confer the assay further simplicity as a portable field test kit for GHB.
PDF
