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[...]an ingredient [GAMMA]-butyrolactone (GBL) is readily converted into [GAMMA]-hydroxybutyrate (GHB), which has well-known toxic effects. Conditioning nail polish remover pads contain the following as principal ingredients: GBL (84%), butoxyethanol (10%), diethylene glycol (2%), panthenol (1%) and propylene glycol (1%).

European surveys estimate an ever-in-lifetime use of 3%, increasing to 19% in some groups, such as people attending nightclubs.5 GBL toxicity should be considered in any patient who presents with rapid onset of coma of unknown cause. Since there is only a short time frame (<12 h) for chemical detection of GBL,3 blood or urine samples should be analysed as soon as possible.

Background Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have been profiled as 'party drugs' used mainly at dance parties and in nightclubs on weekend nights. The purpose of this study was to examine the frequency of injecting drug use among GHB/GBL overdose patients and whether there are temporal differences in the occurrence of GHB/GBL overdoses of injecting drug and recreational drug users. Methods In this retrospective study, the ambulance and hospital records of suspected GHB- and GBL overdose patients treated by the Helsinki Emergency Medical Service from January 1 st 2006 to December 31 st 2007 were reviewed. According to the temporal occurrence of the overdose, patients were divided in two groups. In group A, the overdose occurred on a Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. Group B consisted of overdoses occurring on outside this time frame. Results Group A consisted of 39 patient contacts and the remaining 61 patient contacts were in group B. There were statistically significant differences between the two groups in (group A vs. B, respectively): history of injecting drug abuse (33% vs. 59%, p = 0.012), reported polydrug and ethanol use (80% vs. 62%, p = 0.028), the location where the patients were encountered (private or public indoors or outdoors, 10%, 41%, 41% vs. 25%, 18%, 53%, p = 0.019) and how the knowledge of GHB/GBL use was obtained (reported by patient/bystanders or clinical suspicion, 72%, 28% vs. 85%, 10%, p = 0.023). Practically all (99%) patients were transported to emergency department after prehospital care. Conclusion There appears to be at least two distinct groups of GHB/GBL users. Injecting drug users represent the majority of GHB/GBL overdose patients outside weekend nights.

γ-Butyrolactone (GBL) is a popular drug of abuse which is easily available over the internet. Following a UK classification change to a class C drug in January 2010, internet supply has become difficult. Some of the effects have resulted in sourcing GBL from industrial solvents. We report a case of a 24-year-old man who was admitted for detoxification from GBL. He reported having sourced the GBL by diluting the contents of nail varnish remover pads with water. During his admission he developed a severe withdrawal delirium and acute renal failure. He required admission to the intensive care unit. Physicians and psychiatrists should be aware of toxic sources of GBL leading to renal failure and consider GBL in those presenting with agitation, psychosis or coma.

Gamma-hydroxybutyrate (GHB) is a compound used in the treatment of alcohol withdrawal, narcolepsy, and for induction of anaesthesia. It is also contained in many products illegally marketed as “dietary supplements” and is increasingly being recognised as a potential drug of abuse. We report the case of a 44-year-old man who suffered coma and life-threatening respiratory depression following an accidental overdose of the GHB prodrug, gamma-butyro-lactone (GBL), contained in a “health drink”. He made a full recovery following appropriate supportive treatment. GHB toxicity should be included in the differential diagnosis of patients with altered mental state, particularly where there is a history of recreational drug abuse.

Drug abuse affects a significant number of individuals of all ages. Health care practitioners must be knowledgeable about both the physiological effects of such drugs and the impact of drug-seeking behavior on their patients.

Products containing gamma-butyrolactone (GBL) are marketed for many claimed purposes, including to induce sleep, release growth hormone, enhance sexual activity and athletic performance, relieve depression, and prolong life. GBL is converted by the body into gamma-hydroxybutyrate (GHB), a drug banned outside of clinical trials approved by the Food and Drug Administration (FDA). Recognized manifestations of GHB toxicity include bradycardia, hypothermia, central nervous system depression, and uncontrolled movements. This report describes seven cases of GBL toxicity involving the product \"Revivarant,\" which is labeled as containing 1.82 g of GBL per fluid ounce, reported from two hospital emergency departments (EDs) in Minnesota during October-December 1998 and summarizes an additional 34 cases of GBL toxicity reported to poison centers in New Mexico and Texas during October 1998-January 1999.

Flupyradifurone and sulfoxaflor present novel insecticide chemistries with particular efficacy against aphids, and the recent emergence of sugarcane aphid, Melanaphis sacchari (Zehntner), as a pest of sorghum in the United States has resulted in their widespread use. We examined their toxicity to Hippodamia convergens Guerin-Meneville, an important aphid biocontrol agent. We exposed beetles to topical applications of the field rate (FR) of these insecticides, fed them contaminated food (eggs of Ephestia kuehniella Zeller), and gave firstinstar larvae 24-h exposures to leaf residues. More than half of fourth-instar larvae receiving topical applications of sulfoxaflor at FR survived, whereas flupyradifurone at 0.1× FR caused 90% mortality. Adults survived topical treatments better than larvae and without measurable mortality, except flupyradifurone at FR, which killed more than 80% of beetles. Survivors of all treatments had fertility similar to controls, whether treated as larvae or adults. Ingestion of contaminated food caused significant mortality in all treatments (15–40% for adults and 55–85% for larvae), with no significant differences between insecticides at FR. Leaf residues of sulfoxaflor at 1.0 and 2.0× FR caused approximately 60 and 80% mortality of first instars, respectively, whereas flupyradifurone at 0.1 and 1.0× FR caused > 90% mortality. Although sulfoxaflor was less toxic to H. convergens than flupyradifurone, the tested FR of flupyradifurone has now been reduced by half. We conclude that neither insecticide appears as toxic as other nicotinic acetylcholine receptor agonists, and that both materials are compatible with integrated pest management programs for M. sacchari.

The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a homoserine lactonase (HSL) activity that is undetectable in PTE (kcat/km values of up to 2 × 104), with only a minor decrease in PTE paraoxonase activity. In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant. The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT) enzyme. pKa calculations for the enzyme (the WT and the variant) showed a significant pKa shift from WT standard values (ΔpKa = 3.5 units) for the His254residue (in the Arg254 variant). Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL) with a large aliphatic chain to site in the channels easily. Thence the expanding of the active pocket is beneficial to C4-HSL binding and has a little effect on paraoxon binding. Our results provide a new theoretical contribution of loop remodeling to the rapid divergence of new enzyme functions.

Doc number: 203 Abstract Background: The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was derived by partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba . Considering the good trypanosomicidal activity of HK and recalling that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the (anti) mutagenic... genotoxic activities of HK. Methods: The mutagenic... genotoxic activities were evaluated by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, and the comet assay, so as to assess the safe use of HK in the treatment of Chagas' disease. The antimutagenic ...antigenotoxic potential of HK were also tested against the mutagenicity of a variety of direct and indirect acting mutagens, such as 4- nitro-o -phenylenediamine (NOPD), sodium azide (SA), mitomycin C (MMC), benzo[a ]pyrene (B[a ]P), aflatoxin B1 (AFB1 ), 2-aminoanthracene (2-AA) and 2-aminofluorene (2-AF), by the Ames test, and doxorubicin (DXR) by the comet assay. Results: The mutagenicity...genotoxicity tests showed that HK did not induce any increase in the number of revertants or extent of DNA damage, demonstrating the absence of mutagenic and genotoxic activities. On the other hand, the results on the antimutagenic potential of HK showed a strong inhibitory effect against some direct and indirect-acting mutagens. Conclusions: Regarding the use of HK as an antichagasic drug, the absence of mutagenic effects in animal cell and bacterial systems is encouraging. In addition, HK may be a new potential antigenotoxic ... antimutagenic agent from natural sources. However, the protective activity of HK is not general and varies with the type of DNA damage-inducing agent used.