Inhalation of electronic cigarette aerosol induces reflex bronchoconstriction by activation of vagal bronchopulmonary C-fibers.

The electronic cigarette (e-cig) has been suggested as a safer alternative to tobacco cigarettes. However, the health effects of e-cigs on the airways have not been fully investigated. Nicotine, the primary chemical constituent of the e-cig aerosol, has been shown to stimulate vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit vigorous pulmonary defense reflexes, including airway constriction. In this study, we investigated the bronchomotor response to e-cig inhalation challenge in anesthetized guinea pigs and the mechanisms involved in regulating these responses. Our results showed that delivery of a single puff of e-cig aerosol into the lung triggered immediately a transient bronchoconstriction that sustained for >2 min. The increase in airway resistance was almost completely abolished by a pretreatment with either intravenous injection of atropine or inhalation of aerosolized lidocaine, suggesting that the bronchoconstriction was elicited by cholinergic reflex mechanism and stimulation of airway sensory nerves was probably involved. Indeed, electrophysiological recording further confirmed that inhalation of e-cig aerosol exerted a pronounced stimulatory effect on vagal bronchopulmonary C-fibers. These effects on airway resistance and bronchopulmonary C-fiber activity were absent when the e-cig aerosol containing zero nicotine was inhaled, indicating a critical role of nicotine. Furthermore, a pretreatment with nicotinic acetylcholine receptor antagonists by inhalation completely prevented the airway constriction evoked by e-cig aerosol inhalation. In conclusion, inhalation of a single puff of e-cig aerosol caused a transient bronchoconstriction that was mediated through cholinergic reflex and triggered by a stimulatory effect of nicotine on vagal bronchopulmonary C-fiber afferents.

Reflex bronchoconstriction evoked by inhaled nicotine aerosol in guinea pigs: role of the nicotinic acetylcholine receptor.

Inhaled cigarette smoke stimulated vagal bronchopulmonary C fibers via an action of nicotine on neuronal nicotinic acetylcholine receptor (nAChR). Recent studies have reported that nicotine at high concentrations can also activate the transient receptor potential ankyrin 1 receptor (TRPA1) expressed in these sensory nerves. This study was performed to characterize the airway response to inhaled nicotine aerosol and to investigate the relative roles of nAChR and TRPA1 in this response. Guinea pigs were anesthetized and mechanically ventilated; one tidal volume of nicotine aerosol (2% solution) was diluted by an equal volume of air and delivered directly into the lung via a tracheal cannula in a single breath. Our results showed the following: 1) Inhalation of nicotine aerosol triggered an immediate and pronounced bronchoconstriction; the increase in total pulmonary resistance reached a peak of 588 ± 205% (mean ± SE) in 10-40 s, which gradually returned to baseline after 1-5 min. 2) Pretreatment with either atropine (iv) or mecamylamine (aerosol) almost completely abolished the nicotine-induced bronchoconstriction; the mecamylamine pretreatment did not block the bronchoconstriction and bradycardia evoked by electrical stimulation of the distal end of one sectioned vagus nerve, indicating its minimal systemic effects. 3) Pretreatment with HC-030031, a selective TRPA1 antagonist, abolished the bronchoconstriction induced by allyl isothiocyanate, a selective TRPA1 agonist, but did not attenuate the nicotine-evoked bronchoconstriction. In conclusion, inhalation of a single breath of nicotine aerosol evoked acute bronchoconstriction mediated through the cholinergic reflex pathway. This reflex response was triggered by activation of nAChR, but not TRPA1, located in airway sensory nerves. NEW & NOTEWORTHY Recent reports revealed that nicotine at high concentration activated transient receptor potential ankyrin 1 receptor (TRPA1) expressed in vagal bronchopulmonary sensory nerves. This study showed that inhalation of a single breath of nicotine aerosol consistently evoked acute bronchoconstriction that was mediated through the cholinergic reflex pathway and triggered by activation of nicotinic acetylcholine receptor, but not TRPA1, located in these nerves. This is new and important information considering the recent rapid and alarming rise in the prevalence of e-cigarette use for nicotine inhalation.

Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults.

Cyclic Vomiting Syndrome (CVS) has been linked to episodic migraine, yet little is known about the precise brain-based mechanisms underpinning CVS, and whether these associated conditions share similar pathophysiology. We investigated the functional integrity of salience (SLN) and sensorimotor (SMN) intrinsic connectivity networks in CVS, migraine and healthy controls using brain functional Magnetic Resonance Imaging. CVS, relative to both migraine and controls, showed increased SLN connectivity to middle/posterior insula, a key brain region for nausea and viscerosensory processing. In contrast, this same region showed diminished SMN connectivity in both CVS and migraine. These results highlight both unique and potentially shared pathophysiology between these conditions, and suggest a potential target for therapeutics in future studies.

Genetic parameters of body weight, egg production, and shell quality traits in the Shan Ma laying duck (Anas platyrhynchos).

Three hundred and four female ducks of the Chinese indigenous Shan Ma breed, progeny of 11 sires and 104 dams, were used to study laying traits. Among them, 264 ducks were used to study the egg shell quality traits of eggs laid at 300 days of age. The mean age at first egg was 109 days with an average egg weight of 49.6 ± 3.7 g. Between 210 and 300 days of age, egg weight increased from 65.0 ± 3.9 g to 67.0 ± 4.2 g and the mean of the number of eggs laid up to 300 days was 161 ± 15.0. Egg length was 59.57 ± 3.01 mm and egg width was 45.02 ± 1.98 mm, leading to a shape index of 1.32 ± 0.08. Egg shell thickness was about 0.31 mm whatever the shell region, and the breaking strength was 28.80 ± 8.29 N. The heritability's estimated using restricted maximum likelihood ( REML: ) methodology were high for egg weights (ranging from 0.43 to 0.61), intermediate for the number of eggs laid (ranging from 0.38 to 0.43), and low for the age at first egg (0.13). Heritability's for egg shell quality traits varied from 0.20 for the breaking strength to 0.44 for egg length, with in-between values of 0.28 for shell thickness and 0.34 for the shape index. The number of eggs laid was not genetically correlated with the age at first egg or egg weight, but was correlated with body weight (rg = +0.54 ± 0.23). High positive correlations were found between egg weight and body weight traits, and both of these traits (except egg weight at first egg) were highly and positively correlated with egg length and width. Breaking strength was genetically correlated with egg shell thickness (rg = +0.54 ± 0.19) and the shape index (rg = +0.71 ± 0.23). These results suggest that an efficient selection strategy could be implemented to improve the egg production of the pure Shan Ma duck line.

Selection and crossbreeding in relation to plumage color inheritance in three chinese egg type duck breeds (anas platyrhynchos).

In China and South East Asia, the duck (common duck) is important in egg production for human consumption. Plumage color is a breed characteristic and of economic importance, together with egg production. Our aim in this study was to investigate the inheritance of plumage color in three Chinese indigenous egg-type duck breeds, Shan Ma (S), Putian White (F) and Putian black (P), and some of their crossbreds. These three breeds have different plumage color and are used in crossbreeding. The crossbred laying ducks F×(P×S) and F×(S×P) showed highly improved laying ability but heterogeneous plumage color. Genotypes at four relevant loci were investigated by studying down color and pattern in ducklings after crossbreeding. F1 ducklings from the matings F×S and S×F, P×S, and S×P were classified into four classes of plumage color (the Shan Ma plumage color, black, white, or multicolored) over three generations. Parents were selected for the Shan Ma plumage color of their progeny. In the fourth generation, P male and P female ducks were selected according to the frequency of the desired class of plumage color (Shan Ma) of their F1 progeny to obtain the so-called "Brown Putian Ma duck". The Shan Ma duck genotype was identified as having the restricted mallard color pattern (M(R)M(R)), full expression of any of the patterns or colors (CC), no extended black (ee) and no brown dilution D (D). The Putian White genotype was recessive white (cc), no extended black (ee) and no brown dilution D (D). The Putian Black genotype exhibited full expression of extended black (E gene) and no brown dilution (CCEE D [D]). It was shown that F×S and S×F tests should be implemented to eliminate the recessive white c allele in the S line and the dominant extended black E allele in the F line. It was also shown that the Brown Putian Ma obtained from Putian Black, with no extended black genotype (ee), could be used to get rid of the black plumage (E gene) in the crossbred ducks. This could provide a solution for producing 3-way crossbred ducks Putian White×(Putian-Ma ×Shan Ma) and Putian White×(Shan Ma×Putian-Ma), with the desired Shan Ma feather color.

Infantile haemangiomas: a challenge in paediatric dermatology.

Infantile haemangiomas, common benign vascular tumours of childhood, are characterized by rapid growth during the first year of life and a slow regression that is usually completed at 7-10 years of age. These tumours are composed of endothelial cells with high mitotic rates and stromal components such as fibroblasts, mast cells and pericytes. Haemangiomas become a challenge when they are part of a syndrome, are located in certain areas of the body or when complications develop. The above-mentioned factors also influence the treatment modality used. However, although there remain many uncertainties regarding management, the beta-adrenergic receptor blocker propranolol is a promising new candidate for first-line systemic therapy. It produces such a dramatic and rapid response that the appearance of an infantile haemangioma should impart expeditious consideration of the risks and benefits of its use.

Heroin body packing: three fatal cases of intestinal perforation.

Death from heroin body packing has been well described in the forensic literature. Most fatalities are due to drug leakage and consequent acute heroin toxicity. Recently, drug traffickers have become more sophisticated in their packaging, and the risk of rupture of drug packets is more remote. Though intestinal obstruction is a recognized risk of body packing, rarely has this resulted in death. We describe four cases of heroin body packing presenting to the Regional Medical Examiner Office in New Jersey. Death in three of these cases was due to intestinal obstruction, with resultant intestinal rupture and peritonitis. Toxicologic evaluation in these three cases was negative for opiates or other drugs of abuse. In one case, death was due to acute heroin toxicity, validated by toxicologic analysis. We briefly discuss the differing drug packaging found in these four cases and the ramifications of packaging as it relates to intestinal obstruction.

Distribution of codeine, morphine, and 6-acetylmorphine in vitreous humor.

Two hundred and twenty-three vitreous humor specimens, which were obtained from a medical examiner's office, were found to be opiate positive (cutoff, 50 ng/mL) by fluorescence polarization immunoassay. All samples were analyzed for their free codeine, morphine, and 6-acetylmorphine contents by a gas chromatography-mass spectrometry protocol. 6-Acetylmorphine was found (cutoff, 10 ng/mL) in 41 specimens in the concentration range of 10-125 ng/mL. Twenty specimens had a free codeine-free morphine concentration ratio > or = 1. Eighty-five samples that were found to contain 50 ng/mL free morphine were further analyzed for their total codeine and total morphine contents. Total codeine-total morphine concentration ratios in 8 (of the 85 samples) were > or = 1, whereas this ratio in the others (only those with a codeine concentration high than 15 ng/mL were included) was significantly lower than 1. The codeine-morphine concentration ratio in vitreous humor appears to resemble that reported for blood and urine and can be used as the basis for differentiating between codeine- and morphine- (heroin-) induced fatalities.

Clinical manifestations of bronchogenic carcinoma.

A retrospective clinical study was carried out on 227 pathologically proven cases of bronchogenic carcinoma from eastern Taiwan, between October 1986 and March 1990. The ratio of males to females was low (2.15:1). The most common cell type was adenocarcinoma (39.2%), with squamous cell carcinoma (36.1%) being the second most common. Adenocarcinoma contributed to 51.4% of the bronchogenic carcinoma in women and 33.5% in men. History of cigarette smoking was strongly associated with squamous cell carcinoma and small cell carcinoma. The most common symptom was a cough (69%). The majority of small cell carcinoma and squamous cell carcinoma appeared to be of the central type in location while most adenocarcinoma appeared to be of the peripheral type. Bronchoscopic examination was the most valuable method for confirming the diagnosis of bronchogenic carcinoma. Most patients presented late and only 19 cases (8.4%) underwent surgery. Aborigines have a lower risk of developing bronchogenic carcinoma. The clinical manifestations of bronchogenic carcinoma in eastern Taiwan are similar to those found in Taiwan as a whole.

Is ethanol the unknown toxin in smoke inhalation injury?

Of the 12,000 fire-related deaths occurring annually in the United States, it is estimated that 60 to 80 per cent are due to smoke inhalation. Plastic and synthetic materials which have been introduced in home construction and furnishings produce a more toxic smoke when burned. Efforts to identify a "supertoxin" in this smoke have been unsuccessful to date. An alternative approach is to examine why victims are unable to escape, and become exposed to smoke for lethal periods of time. The authors examined the circumstances of death in 39 fire victims (27 adults, 12 children) over a 25-month period. Detailed examination of the fire scene, autopsy studies, and toxicologic analysis were carried out. Position of the victim, and escape efforts were noted. Carbon monoxide was elevated in all victims, with "lethal" levels (= greater than 50%) in 21/39 victims. Cyanide was detected in 24/29 victims, but none had lethal (3 mg/L) levels present. Ethanol was detected in 21/26 adults (80%) and 0/12 children (0%). 18/26 adult victims had ethanol levels above the statutory level of intoxication (10 mg%). Victims found in bed (no escape attempt) had a mean blood ethanol level of 268 mg%, compared with a mean level of 88 mg% in those victims found near an exit (P = .006). Ethanol intoxication significantly impairs the ability to escape from fire and smoke and is a contributory factor in smoke-related mortality.

The general toxicology unknown. I. The systematic approach.

The general toxicology unknown often presents challenges and interests to toxicologists. A systematic analytical approach to search for drugs or poisons is presented here. The preliminary screening analyses were as follows: alcohol by gas chromatography (GC), ethchlorvynol colorimetric analysis, enzyme multiplied immunoassay technique (EMIT), basic drug screening by GC, and neutral and weakly acidic drug screening by GC. Other additional analyses were performed depending on the special circumstance of each individual case and the results of these preliminary analyses. Positive findings were confirmed by computerized gas chromatography/mass spectrometry when practical. Quantitation was performed by GC whenever possible.

The general toxicology unknown. II. A case report: doxylamine and pyrilamine intoxication.

A general toxicology unknown case is presented to demonstrate our systematic approach. A 20-year-old male was found dead with multiple suicide notes. Overdose was suspected but substances were not known. Blood alcohol was negative. Urine was analyzed by enzyme-multiplied immunoassay technique and was negative for all drugs assayed. Urine was then extracted with ethyl acetate:hexane (1:1) at pH 10 and back-extracted into 1.0N sulfuric acid. The acidic layer was adjusted to pH 10, and re-extracted with ethyl acetate:hexane (1:1). The residue was analyzed by gas chromatography (GC) on a 3% OV-101 column. It was found to be negative for all commonly screened substances. However, several unknown peaks were observed. Electron impact mass spectra of these unknown peaks were obtained and searched for in our computer library of more than 25000 mass spectra. These unknown peaks were identified as doxylamine and pyrilamine by gas chromatography/mass spectrometry. The base peak and molecular ion for pyrilamine were at m/z 121 and 285, respectively. The base peak for doxylamine was at m/z 58. No molecular ion was observed for doxylamine. Both doxylamine and pyrilamine are antihistamines, but are promoted and used in the management of insomnia. Quantitation was performed on a GC using dexbrompheniramine as an internal standard. Blood concentrations for doxylamine and pyrilamine were 0.7 and 7.0 mg/L, respectively. Concentrations in other tissues were determined. Death was caused by combined doxylamine and pyrilamine intoxication; the manner of death was suicide.

Spontaneous live birth with a maternal history of intravenous use of pentazocine and tripelennamine (T's and blues).

A 24-year-old black female presented a live birth of six-months gestation. The 700-g neonate survived for 11 h. After toxicology revealed the presence of pentazocine and tripelennamine (T's and Blues), the mother admitted to using this combination intravenously 9 h previous to admission. Concentrations of pentazocine and tripelennamine were simultaneously determined by gas-liquid chromatography (GLC) combined with nitrogen selective detection. Analyses were performed on a 3% OV-101 column, with the added internal standard, dexbrompheniramine. Both pentazocine and tripelennamine were qualitatively confirmed by their electron impact mass spectra. Concentrations of pentazocine and tripelennamine in various fluids and tissues were determined.

Analysis of blood and tissue for amoxapine and trimipramine.

A method for the identification and quantitation of two tricyclic antidepressants, amoxapine (Asendin) and trimipramine (Surmontil) is presented here. Samples were extracted with hexane at pH 10, back-extracted with 1.0N sulfuric acid. The acidic layer was adjusted to pH 10 and re-extracted with hexane. Electron impact mass spectra were obtained. The base peak and molecular ion for amoxapine were at m/z 245 and 313, respectively. The base peak and molecular ion for trimipramine were at m/z 58 and 294, respectively. There were three forensic toxicology cases involving amoxapine in Cook County, IL, in 1980 and 1981. The concentrations of amoxapine in blood for these three cases were 1.66 mg/L, 7.16 mg/L, and 2.95 mg/L, respectively.

Simultaneous quantitation of morphine and codeine in biological samples by electron impact mass fragmentography.

A method was developed for the quantitative determination of free morphine and codeine utilizing multiple ion detection mass fragmentography. Samples were spiked with nalorphine (internal standard), extracted and converted to pentafluoropropionyl (PFP) derivatives prior to GC/MS analysis. The PFP derivatives were separated chromatographically on a 5% OV-1 column. The base peak and molecular ion of the El mass spectra were at m/e 414 and 577; 282 and 445; and 440 and 603, for morphine-PFP, codeine-PFP and nalorphine-PFP, respectively. These multiple ions were monitored and the peak area ratio relative to nalorphine-PFP was used as the basis for quantitation. Other drugs studied were found not to interfere with this method.