Cardiac arrest by inhalation of deodorant spray.

Drug abuse by inhalation of volatile household product substances is uncommon, however, it can have devastating consequences. This case report describes the fatal outcome of deodorant inhalation by a 19-year-old patient in a detoxification clinic who developed a cardiac arrest after inhaling butane from a deodorant spray. Despite initial successful resuscitation, he developed a postanoxic encephalopathy with a status epilepticus resistant to extensive treatment. Inhalant abuse can be a cause of death in young patients.

Understanding emerging forms of cannabis use through an online cannabis community: An analysis of relative post volume and subjective highness ratings.

BACKGROUND: Legalization of medical and recreational cannabis has coincided with an increase in novel forms of cannabis use and a burgeoning cannabis product industry. This research seeks to understand the occurrence of discussions about these emerging and traditional forms of use in an online social media discussion forum. METHODS: We analyzed posts to a cannabis-specific forum on the Reddit social media platform posted from January 2010-December 2016. For each of various keywords describing smoking, vaping, edibles, dabbing, and butane hash oil (BHO) concentrate use, we analyzed (1) relative prevalence of posts mentioning these cannabis forms of use; (2) user-reported subjective ratings of "highness" on a scale of 1-10; (3) the ten most common words mentioned in posts; and (4) the frequency of adverse health effect terms. RESULTS: Form of use was mentioned in approximately 17.7% of 2.26 million posts; smoking was the most commonly mentioned form of cannabis use. From 2010-2016, relative post volume increased significantly for posts mentioning dabbing (3.63/1000 additional posts per year, p < .001), butane hash oil terms (3.16/1000, p < .001), and edible terms (2.84/1000, p = .002). Mean subjective highness was significantly greater for posts mentioning dabbing (mean = 7.8, p < .001), butane hash oil terms (mean = 7.5, p < .001), and edible terms (mean = 7.2, p < .001) but not significantly different for vaping (mean = 6.7, p = .19), when compared to smoking (mean = 6.8). CONCLUSIONS: Despite limitations in representativeness, findings indicate a significant increase in online discussion of emerging cannabis forms of use over time and greater subjective effects of dabbing, butane hash oil, and edible use.

Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease.

In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-ß-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months. At 16.5 months of age animals were killed and brains dissected. Analyses were carried out on the hippocampus and frontal cortex for glycolytic and TCA (Tricarboxylic Acid) cycle intermediates, amino acids, oxidized lipids and proteins, and enzymes. There were higher concentrations of d-ß-hydroxybutyrate in the hippocampus of KE-fed mice where there were also higher concentrations of TCA cycle and glycolytic intermediates and the energy-linked biomarker, N-acetyl aspartate compared to controls. In the hippocampi of control-fed animals the free mitochondrial [NAD+ ]/[NADH] ratio were highly oxidized, whereas, in KE-fed animals the mitochondria were reduced. Also, the levels of oxidized protein and lipids were lower and the energy of ATP hydrolysis was greater compared to controls. 3xTgAD mice maintained on a KE-supplemented diet had higher concentrations of glycolytic and TCA cycle metabolites, a more reduced mitochondrial redox potential, and lower amounts of oxidized lipids and proteins in their hippocampi compared to controls. The KE offers a potential therapy to counter fundamental metabolic deficits common to patients and transgenic models. Read the Editorial Highlight for this article on page 162.

Forensic medical evaluation of deaths resulting from inhalation of cigarette lighter refill fuel in Turkey.

Voluntary inhalation/abuse of volatile substances is an important public health problem which especially affects adolescent and young populations worldwide and may be encountered in all socioeconomic and cultural levels. Lighter gas abuse-related death is still an important health problem in Turkey. In this study, 25,265 case files and final reports submitted to the Institute of Forensic Medicine of the First Specialization Board between January 2011 and December 2015 were evaluated retrospectively. In 56 of these cases, lighter gas inhalation (n-butane, propane, isobutane) was recorded as the cause of death. All subjects were male with a mean age of 16.8years. According to eyewitness and crime scene investigation reports, in 48 (85.7%) of the cases, a lighter refill container was found at the scene. It was determined that 21.4% of the cases used a plastic bag to increase the effects of lighter gas and 76.8% inhaled the lighter gas via their mouth and nose. The toxicological analysis of the samples taken while hospitalized showed no lighter refill components (n-butane, propane, isobutane) in 66% of the cases, n-butane in 32.1% of the cases, and n-butane+propane+isobutane in 1.9% of the cases. The importance of lighter gas inhalation-related deaths in Turkey has been increasing. Strict measures against the abuse of these very dangerous substances should be undertaken by the mutual efforts of medical specialists and legislators.

Drug vaping applied to cannabis: Is "Cannavaping" a therapeutic alternative to marijuana?

Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoids forms can be used. Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas, and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of "cannavaping," defined as the "vaping" of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids. The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively. Conversely, "therapeutic cannavaping" could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.

Magnetic resonance spectroscopy for detection of choline kinase inhibition in the treatment of brain tumors.

Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both preclinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines. In vivo MRS studies of rats with intracranial F98-derived brain tumors showed a significant decrease in tumor total choline concentration after treatment with MN58b. High-resolution MRS of tissue extracts confirmed that this decrease was due to a significant reduction in phosphocholine. Concomitantly, a significant increase in poly-unsaturated lipid resonances was also observed in treated tumors, indicating apoptotic cell death. MRI-based volume measurements demonstrated a significant growth arrest in the MN58b-treated tumors in comparison with saline-treated controls. Histologically, MN58b-treated tumors showed decreased cell density, as well as increased apoptotic cells. These results suggest that inhibition of choline kinase can be used as an adjuvant to chemotherapy in the treatment of brain tumors and that decreases in total choline observed by MRS can be used as an effective pharmacodynamic biomarker of treatment response.

The somatostatin receptor 4 agonist J-2156 reduces mechanosensitivity of peripheral nerve afferents and spinal neurons in an inflammatory pain model.

Somatostatin (SST) is a peptide hormone that regulates the endocrine system and affects neurotransmission via interaction with G protein-coupled SST receptors and inhibition of the release of different hormones. The aim of this study was to investigate whether the analgesic properties of the selective SSTR4 agonist J-2156 are mediated via peripheral and/or spinal receptors. Effect on mechanical hyperalgesia in the Complete Freund׳s Adjuvant (CFA) model was measured after intraperitoneal application of J-2156. Electrophysiological neuronal recordings were conducted 24 h after injection of CFA or vehicle into the paw of Wistar rats. Mechanosensitivity of peripheral afferents of the saphenous nerve as well as of spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were measured after systemic or spinal application of J-2156. In CFA animals J-2156 dose dependently reduced hyperalgesia in behavioral studies. The minimal effective dose was 0.1 mg/kg. Mechanosensitivity of peripheral afferents and spinal neurons was significantly reduced by J-2156. NS neurons were dose dependently inhibited by J-2156 while in WDR neurons only the highest concentration of 100 µM had an effect. In sham controls, J-2156 had no effect on neuronal activity. We demonstrated that J-2156 dose-dependently reduces peripheral and spinal neuronal excitability in the CFA rat model without affecting physiological pain transmission. Given the high concentration of the compound required to inhibit spinal neurons, it is unlikely that the behavioral effect seen in CFA model is mediated centrally. Overall these data demonstrated that the analgesic effect of J-2156 is mediated mainly via peripheral SST4 receptors.

The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia through HIF1A accumulation and enhanced angioneurogenesis.

Only a minority of stroke patients receive thrombolytic therapy. Therefore, new therapeutic strategies focusing on neuroprotection are under review, among which, inhibition of the proteasome is attractive, as it affects multiple cellular pathways. As proteasome inhibitors like bortezomib have severe side effects, we applied the novel proteasome inhibitor BSc2118, which is putatively better tolerated, and analysed its therapeutic potential in a mouse model of cerebral ischaemia. Stroke was induced in male C57BL/6 mice using the intraluminal middle cerebral artery occlusion model. BSc2118 was intrastriatally injected 12 h post-stroke in mice that had received normal saline or recombinant tissue-plasminogen activator injections during early reperfusion. Brain injury, behavioural tests, western blotting, MMP9 zymography and analysis of angioneurogenesis were performed for up to 3 months post-stroke. Single injections of BSc2118 induced long-term neuroprotection, reduced functional impairment, stabilized blood-brain barrier through decreased MMP9 activity and enhanced angioneurogenesis when given no later than 12 h post-stroke. On the contrary, recombinant tissue-plasminogen activator enhanced brain injury, which was reversed by BSc2118. Protein expression of the transcription factor HIF1A was significantly increased in saline-treated and recombinant tissue-plasminogen activator-treated mice after BSc2118 application. In contrast, knock-down of HIF1A using small interfering RNA constructs or application of the HIF1A inhibitor YC1 (now known as RNA-binding motif, single-stranded-interacting protein 1 (RBMS1)) reversed BSc2118-induced neuroprotection. Noteworthy, loss of neuroprotection after combined treatment with BSc2118 and YC1 in recombinant tissue-plasminogen activator-treated animals was in the same order as in saline-treated mice, i.e. reduction of recombinant tissue-plasminogen activator toxicity through BSc2118 did not solely depend on HIF1A. Thus, the proteasome inhibitor BSc2118 is a promising new candidate for stroke therapy, which may in addition alleviate recombinant tissue-plasminogen activator-induced brain toxicity.

Use of gas combination cryosurgery for treating ameloblastomas of the jaw.

This study evaluated the results of curettage followed by spray propane, butane, and isobutane gas combination cryosurgery in 10 patients with ameloblastoma. The patients' age ranged from 7 to 87 years (mean, 31 years), with equal prevalence in both men and women. Five cases were diagnosed as solid ameloblastomas and 5 as unicystic ameloblastomas. Before enucleation and cryosurgery, the unicystic lesions received marsupialisation to decrease their size. No patient showed evidence of clinical or radiographic recurrence, pathologic fracture, or infection after treatment with enucleation and cryosurgery. The most common complication was wound dehiscence, which was observed in all cases. The average follow-up period was 60.5 months (range 48-108 months). These results show that enucleation followed by cryosurgery is an effective therapy for managing ameloblastomas.

[Myocardial infarction in a 16-year old following inhalation of butane gas]. / Myocardinfarct bij een 16-jarige na inhalatie van butaangas.

BACKGROUND: Butane gas is inhaled by young people with the aim of getting 'high'. This can cause coronary spasm with myocardial infarction and ventricular fibrillation as a result. CASE DESCRIPTION: We report on a 16-year-old male who collapsed at home after sniffing butane. His father, together with a paramedical emergency team that had found ventricular fibrillation, started basic and advanced life support. ECG showed exaggerated ST-elevations and an echocardiography showed a hypokinetic anterior ventricular wall and ventricular septum. After treatment with dobutamine, nitroglycerine, acetylsalicylic acid and dalteparine, the ECG and left ventricular function improved. He was admitted to a pediatric intensive care unit where he was artificially ventilated for 4 days and treated for cardiogenic shock. In the following days his cardiovascular condition improved. Magnetic resonance imaging showed no ischaemic damage of the brain. At 6 weeks his general condition was not as before, but ECG and cardiac function had almost recovered. CONCLUSION: Young people who experiment with inhalation of volatile substances generally do not know how dangerous this is. Provision of information about the possible consequences will have a preventive effect.

Partition of bispyridinium oximes (trimedoxime and K074) administered in therapeutic doses into different parts of the rat brain.

The penetration of acetylcholinesterase reactivators (oximes) into the central nervous system is typically restricted by the blood-brain barrier. Although oximes are highly hydrophilic compounds, some contradictory results confirming permeation into the brain exist. The aim of this study is to verify the penetration of oximes through the blood-brain barrier and to detect their levels achieved in different brain regions 60 min after the administration. It was confirmed that oximes are able to penetrate into the brain after injection of therapeutic doses corresponding with 5% of LD(50). The level in whole brain was 0.58% for trimedoxime and 0.85% for the experimental drug oxime K074 as the percentage of their plasma concentration. The highest concentration was found in frontal cortex (trimedoxime 2.27%; oxime K074 0.95%) and lowest in basal ganglia (trimedoxime 0.86%; oxime K074 0.42%). Entry of oximes into the brain is minimal, but some low reactivation effect should be expected. The reactivation potency of oximes might be higher or lower, depending on the real oxime concentration in a given area.

NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models.

BACKGROUND AND PURPOSE: We previously reported that NCX 2057, a compound comprising a nitric oxide (NO)-releasing moiety and the natural antioxidant, ferulic acid (FA), inhibits pro-inflammatory mediators through NO-mediated gene regulation. Here, we have assessed the activities of NCX 2057 in models of inflammatory and neuropathic pain, and characterized its effects on cyclooxygenase (COX)-1 and COX-2. EXPERIMENTAL APPROACH: Anti-nociceptive and anti-inflammatory activities of NCX 2057 were measured in vitro and in vivo in models of inflammatory (carrageenan) and neuropathic (chronic constriction injury; CCI) pain. Effects of NCX 2057 were measured on COX-1 and COX-2 activities in RAW 264.7 macrophages. KEY RESULTS: NCX 2057 dose-dependently inhibited single motor unit responses to noxious mechanical stimulation (ID(50)= 100 micromol kg(-1)) and wind-up responses in rats with paw inflammation induced by carrageenan. Moreover, NCX 2057 inhibited allodynic responses following CCI of the sciatic nerve [ipsilateral Paw Withdrawal Threshold (g): vehicle: 41.4 +/- 3.3; NCX 2057: 76.3 +/- 4.8 FA: 37.9 +/- 15.5 at 175 micromol kg(-1)]. NCX 2057 reversed carrageenan-induced hyperalgesic responses in mice and inhibited prostaglandin E(2) formation in paw exudates. Finally, NCX 2057 competitively inhibited COX-1 and COX-2 activities in whole RAW macophages (IC(50)= 14.7 +/- 7.4 and 21.6 +/- 7.5 microM, respectively). None of these properties were exhibited by equivalent treatments with FA or standard NO donor compounds. CONCLUSIONS AND IMPLICATIONS: These studies indicate that NCX 2057 is effective in chronic inflammatory and neuropathic pain models, probably because of its particular combination of anti-COX, antioxidant and NO-releasing properties.

[Ventricular fibrillation following deodorant spray inhalation]. / Fibrillation ventriculaire par inhalation de spray déodorant.

We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

Bithalamic lesions of butane encephalopathy.

Butane inhalation can cause serious medical complications and is particularly toxic to the nervous system. This is a report of an acutely encephalopathic youth with prominent abulia. MRI revealed severe bithalamic injury attributed to butane toxicity. Clinical issues, including particular radiologic findings, related to butane inhalation are reviewed.

Inhalant abuse in New Zealand.

AIM: To describe patterns of inhalant abuse in New Zealand and discuss management. METHODS: Calls to the National Poisons Centre (NPC) from January 1 2003 to December 31 2004 were analysed. In addition, deaths following inhalational abuse were identified from the Institute of Environmental Science and Research Limited (ESR) database for 2001 and 2002 and available data for 2003. RESULTS: Seventy calls were classified as relating to inhalational abuse incidents. In abusers whose age was known, 83% were between 11 and 20 years, and 61% were male. Over half (44/70) of the calls involved abuse of propane or butane, either alone or in combination with a synthetic pyrethroid. ESR coronial data identified 11 inhalant abuse related deaths, most commonly attributed to cardiac effects. 73% of deaths were in teenagers and all but one fatality involved propane and/or butane. CONCLUSIONS: Inhalant abuse is a persisting problem in New Zealand. NPC and ESR data demonstrate that teenagers are more likely to abuse inhalants than other age groups and butane and propane are the inhalants of choice. Acute management can be difficult, with significant mortality and morbidity. Continued education and other preventive measures are essential to help curb an extremely dangerous practice.

Hemodynamic effects of di-sec-butyl phenol, an anesthetic substituted phenol.

Dose- and age-related hemodynamic effects were determined for an anesthetic substituted phenol, 2,6-di-sec-butyl phenol (DSB). DSB, 7.5 mg/kg, induced hypnosis in young rabbits and increased mean blood pressure to 170 +/- 14% and heart rate to 150 +/- 21% of control values. In elderly rabbits, 7.5 mg/kg DSB induced hypnosis, had no effect on blood pressure, but increased the heart rate to 130 +/- 2% of control. After ganglionic blockade with hexamethonium, 7.5 mg/kg DSB caused a decline in mean blood pressure (71 +/- 5% of control) without change in heart rate. DSB increased norepinephrine release from SH-SY5Y cells, a human neuroblastoma cell line (5.4 +/- 1.7% vs. 3.5 +/- 0.3%). DSB produced age-dependent elevation of mean blood pressure in rabbits, probably by causing release of catecholamines from the sympathetic nervous system.

Autoerotic accident by inhalation of propane-butane gas mixture.

We present a case of an accidental autoerotic death involving the inhalation of a propane-butane gas mixture, also known as LPG (liquefied petroleum gas). A 19-year-old male was found dead in supine position in his bed in a residential accommodation one day after he was last seen alive. On a personal computer at the end of the bed, a pornographic movie was still running. On his left shoulder, an empty rubber balloon and on the bedside 2 empty "Kisag-Gas" cartridges were found. Toxicologic investigations revealed an intoxication with propane and butane, together with a recent consumption of cannabis. This case report compares the toxicologic findings with other recently published cases, and the theories of the toxic effects are discussed.

Determination of antagonism between cyhalofop-butyl and other rice (Oryza sativa) herbicides in barnyardgrass (Echinochloa crus-galli).

Herbicide antagonism is defined as the reduction of control of certain weeds as the result of applying mixtures of two or more herbicides. Cyhalofop-butyl, a graminicide used for postemergence grass weed control in rice, is antagonized by some rice herbicides when applied simultaneously. The result of this type of antagonism usually results in decreased control of grass weeds. Research has shown that herbicide antagonism between graminicides and other herbicides may be caused by different mechanisms as the result of activity of the tank-mix partner. Using HPLC, the objective of this experiment was to analyze the fate of cyhalofop-butyl in barnyardgrass tissue when applied alone and in combination with halosulfuron, propanil, or triclopyr. Results indicated that absorption of cyhalofop-butyl and hydrolysis to its phytotoxic metabolite, cyhalofop-acid, was rapid and that halosulfuron and triclopyr had no effect. Because of a likely interaction of propanil with an apoplastic esterase enzyme, increased levels of cyhalofop-butyl and cyhalofop-acid were detected in barnyardgrass tissue, indicating that cyhalofop-butyl metabolism was hindered by propanil.