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Exposure to or ingestion of turpentine can alter the scent of urine, conferring it a flowery, violet-like scent. Turpentine's effect on urine was initially noticed after its use either as medicine or as a preservative in winemaking. Regardless of the source of exposure, the phenomenon requires metabolic conversion of turpentine component(s) to ionone, the molecule mainly responsible for the scent of violets. The purpose of this study was to identify the presence of ionone in the urine of rats that received β-pinene, and thus to demonstrate that the postulated conversion occurs. We treated rats intraperitoneally with normal saline (negative control), β-ionone (positive control), low-dose β-pinene (1/3 of LD50), and high-dose β-pinene (1/2 of LD50). Urine samples were collected up to 72 h after administration of the compounds, followed by gas chromatography/mass spectrometry identification of the presence of ionone. β-Ionone was found in the urine of rats exposed to both low and high doses of β-pinene. In contrast, α-ionone appears unlikely to have been formed in rats exposed to either low or high doses of β-pinene. β-pinene was converted to β-ionone, followed by partial excretion in the urine of rats. β-Ionone is a minor metabolite of β-pinene. [ABSTRACT FROM AUTHOR]

Sir Louis Francis Knuthsen (1869–1957), the physician who painstakingly listed almost all treatments known for obstinate hiccough, ascribes the holding of breath method to Philip Henry Pye-Smith, FRS (1840–1914), consultant at Guy's Hospital in London. In fact, the strategy is much older and was mentioned by greats such as Francis Bacon (1561–1626), Aristoteles (384–322 BC), and Eryximachus (late-fifth century bce). Hypoventilation to reduce central nervous system excitability was used in antiquity as evidenced by Cyriacus' treatment of Artemia, the daughter of Emperor Diocletian (≈ 244–311). She was suffering from (among others) seizures that Cyriacus was apparently controlling by tightening a scarf around her neck, as depicted by Mathias Grünewald (1460–1528) on a wing of the so-called Heller Altar now on display at the Historical Museum, Frankfurt, Germany. In modern times, around 1920, inducing hypercapnia by CO2 inhalation as therapy for hiccups was suggested and tried by a number of anesthetists, such as Americans Russel Firth Sheldon (1885–1960) and Brian Collins Sword (1889–1956) in Boston; Briton Christopher Langton Hewer (1896–1986) at St. Bartholomew's Hospital in London; Austrian Karl Doppler (1887–1947) in Vienna; and the German/Polish Arthur Dzialoszynski (1893–1977) in Berlin. Although various authors assign the scientific primate to any of them, the first mention of carbon dioxide inhalation as treatment of singultus in the scientific literature is of French origin and was made by Paris pharmacist Henri Bocquillon-Limousin (1856–1917) in his 1892 Formulaire des médicaments nouveaux et des médications nouvelles. [ABSTRACT FROM AUTHOR]

Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigatedin silicoandin vitroand compared with an experimental oxime (kamiloxime; K-27) and pralidoxime.In silicothe molecular interactions between AChE and oximes were examined and binding energies were assessed. LogP (predicted log of the octanol/water partition coefficient) was estimated.In vitrothe intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Molecular docking revealed that K378 and K727 bind to the peripheral site(s) with high binding energies in contrast to the central binding of K-27 and pralidoxime. LogP values indicating that the novel compounds are significantly less hydrophilic than K-27 or pralidoxime. IC50of K378 and K727 were comparable (0.9 and 1 µM, respectively) but orders of magnitude lower than comparators.R50values revealed their inability to reactivate paraoxon inhibited AChE. It is concluded that the novel oximes K378 and K727 are unlikely to be clinically useful. Thein silicoandin vitrostudies described allow avoidance of unnecessaryin vivoanimal work and contribute to the reduction of laboratory animal use. [ABSTRACT FROM PUBLISHER]

A multitude of nonpharmacological interventions to terminate hiccup belong to the public-domain hiccup “mythology” or have been described in the medical literature as case reports. While usually effective in terminating bouts of acute hiccup, they are mostly ineffective in cases of hiccupping that have been present for an extended period. The common denominator of most of these therapeutic maneuvers (some also used to terminate paroxysmal supraventricular tachycardia) is their ability to directly or indirectly increase efferent vagal activity. Among the best known “vagal maneuvers” are the oculo-cardiac reflex (Dagnini-Aschner), the carotid sinus massage, the Valsalva maneuver, stimulation of the ear/auditory canal, ice ingestion, and induction of emesis. This short report provides an overview on hiccups and attempts to identify the lesser known personalities who pioneered its treatment by vagal maneuvers. The recent introduction of electrical vagus nerve stimulation for therapy-resistant hiccup is the ultimate compliment to these pioneers. [ABSTRACT FROM PUBLISHER]

During intrauterine life, hiccups are universally present, their incidence peaking in the third trimester. Alfons Mermann (1852–1908), a gynecologist from Mannheim, Germany, best known for having established the Luisenheim Woechnerinnenasyl [lying-in asylum] there in 1887, is viewed as the first physician to name and describe singultus foetalis [fetal hiccups] in a modern peer-reviewed scientific publication. This short report attempts to shed some light on the work of Dr. Mermann and to explore whether or not he was indeed the first to recognize this phenomenon. [ABSTRACT FROM AUTHOR]

One important risk gene in schizophrenia is neuregulin-1 ( NRG1), which is expressed in different isoforms in the brain. To determine if alterations of NRG1 are present in schizophrenia, we measured gene expression of NRG1 and its main isoforms as well as the impact of genetic variation of NRG1 in an exploratory study examining three brain regions instead of only one as published so far. In all, we examined post-mortem samples from 11 schizophrenia patients and eight normal subjects. We investigated gene expression of total NRG1 and isoforms I, II and III by real-time PCR in the prefrontal cortex (Brodmann areas 9 and 10) and right hippocampal tissue. For the genetic study, we genotyped the NRG1 polymorphism SNP8NRG221533, which is within the core haplotype of the original publication. Compared to controls, gene expression of the NRG1 isoform I was decreased and isoform II increased in the prefrontal cortex (BA10) of schizophrenia patients. There were no statistically significant differences between individuals carrying at least one C allele of SNP8NRG221533 compared to individuals homozygous for the T allele. The decreased expression of NRG1 isoform I and overexpression of isoform II may be related to deficits in receptor function as well as abnormal migration and myelination. However, our study sample was small and results of this exploratory study should be verified in a larger sample. [ABSTRACT FROM AUTHOR]

A simple and reliable reversed-phase TLC method was used to determine the lipophilicity of ACE inhibitors. The TLC silica plates were saturated with paraffin using continuous development with 10% paraffin in hexane for 18 hours. The TLC silica particles covered with the paraffin are used as an inexpensive substituent of the usual RP-18 TLC stationary phase. [ABSTRACT FROM AUTHOR]

The chemical structures of certain drug candidates give only a minimum of lipophilicity. Investigation of their elution on reversed-phase materials was difficult, even when the water content of the mobile phase was changed. The dominative role of lipophilicity, either in the drugs' penetration or in the receptorial drug binding, is considered to be valid solely in the same chemical group of the various drugs. In the cases of extremely lipophobic (i.e., hydrophilic) compounds, both the determination or calculation of lipophilicity was difficult or impossible. This is the reason that a novel index, the TLC hydrophilicity parameter, should be introduced as a substitute for lipophilicity. Hydrophilicity can be preferrably determined using a planar stationary phase and an aqueous-organic mobile phase. Numerical data of hydrophilicity on silica stationary phase can be calculated using RM values, similar to the lipophilicity indices. [ABSTRACT FROM AUTHOR]

Presents a study which examined the utility of paraoxon sensitive phenylvalerate hydrolase to assess the severity of acute poisoning of paraoxon, an organosphophorous compound. Materials and methods; Results; Discussion.

We examined the influence of an experimental venous and arterial air embolism on the hearing level in laboratory mini pigs. Before and after the injection of air a threshold ABR was measured in anaesthetized mini pigs (n=15). A venous air embolism was performed in 6 animals: no changes in the hearing level or in the interpeak latencies Jewett wave V-I were observed in any of the animals before, during or after the application of air. In 9 animals the arterial embolism was done, 2 animals died and had to be excluded. In 6 animals out of 7 a hearing loss was observed starting after the injection of 40 ml air and finally ending in deafness for these 6 animals. The detected hearing loss is probably of cochlear origin, as no prolongations of the interpeak latencies of Jewett wave V-I at 90 dB HL were observed prior to the deafness. Our results show that air bubbles in the arterial circulation lead to cochlear damage ending in deafness. Our research indicates that decompression sickness, which is comparable to the arterial air embolism, is more often the cause of a sensorineural hearing loss after diving than previously believed. [ABSTRACT FROM AUTHOR]

A response from Dietrich E. Lorke and colleagues to a letter to the editor on their article "Efficacy of two new asymmetric bispyridinium oximes (K-27 and K-48) in rats exposed to diisopropylfluorophosphate: Comparison with pralidoxime, obidoxime, trimedoxime, methoxime, and HI6," is presented.