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At least 397 records · Page 22Linked to original sources

A bladder-cooling reflex in the anaesthetised guinea-pig: a model of the positive clinical ice-water test.

INTRODUCTION: In patients with detrusor hyperreflexia, intravesical instillation of ice-cold water results in the development of involuntary bladder contractions at volumes less than normal cystometric capacity. This is referred to as a positive ice-water test (+IWT) and can be reversed by vanilloid receptor agonists and potentiated by menthol. The present study was designed to investigate the existence of an analogous cooling reflex in the guinea-pig bladder that could be used as a small animal model in order to test the effects of drugs on the reflex. METHODS: Bladder pressure and external urethral sphincter electromyogram (EUS EMG) were recorded in alpha-chloralose/urethane anaesthetised guinea-pigs during rapid infusion of cold or warm saline into the bladder with or without prior intravesical exposure to menthol or resiniferatoxin (RTX). RESULTS: The mean control micturition threshold volume (TV) of 2.58 ml at 38 degrees C was reduced to 1.52 ml in response to saline infusion at 3 degrees C (P=0.001). The cold-induced reduction in TV was reproducible during several subsequent repeat infusions at 38 degrees C and 3 degrees C and was accompanied by decreases in bladder voiding pressure. The duration of the micturition reflex was markedly increased following cold compared with warm saline infusion (mean 24.5 s at 3 degrees C, 10.2 s at 38 degrees C, P=0.001) and was associated with oscillations in bladder pressure and concomitant bursting activity in the EUS EMG. During step-wise decreases in infusate temperature from 38 degrees C to 23 degrees C, 15 degrees C, 7 degrees C and 3 degrees C, the threshold infusate temperature to elicit a significant reduction in TV was 15 degrees C. The reduction in TV at 3 degrees C was potentiated by intravesical infusion of 0.6 mM menthol whilst intravesical infusion of 500 nM RTX reversed the reduction in TV at 3 degrees C. DISCUSSION: These data suggest that a bladder-cooling reflex is present in the anaesthetised guinea-pig and represents a useful small animal model of the clinical +IWT.

Anesthesia↗

High-resolution microcoil NMR for analysis of mass-limited, nanoliter samples.

An improved nanoliter-volume NMR probe design places the microcoil and capillary at the magic angle (57.7 degrees) with respect to the external magnetic field. Using an NMR probe which requires a total sample volume of just 200 nL, high-resolution 300-MHz 1H-NMR spectra (line width, 0.6 Hz) are presented of 10 mM alpha-bag cell peptide for an observe quantity of 45 ng (50 pmol in 5 nL). For the volume of sample inside the microcoil (the observe volume, Vobs), the 3 sigma limit of detection (LOD) is 9 ng (10 pmol, 2mM) for data obtained in 15 h. To reduce the data acquisition time, a probe with a greater Vobs is developed. As an example of a rapid, mass-limited analysis, a concentration corresponding to 400 ng of menthol dissolved in Vobs = 31 nL (82.6 mM) yields a spectrum in 9 min (LOD = 6.9 ng, 44 pmol, 1.4 mM). To illustrate improvements in concentration sensitivity, a spectrum is acquired in 45 min for 400 ng of menthol dissolved in a total sample volume of 200 nL (12.8 mM). Compared to a commercial nanoprobe for the same mass of menthol, these two examples reduce data acquisition time by at least 95%. Both model compounds demonstrate substantially improved concentration LODs compared to those obtained in previous high-resolution, microcoil NMR work. These advances illustrate the utility of enhanced sensitivity provided by NMR microcoils applied to nanoliter volumes of mass-limited samples.

Indicators and Reagents↗

Identification of a cold receptor reveals a general role for TRP channels in thermosensation.

The cellular and molecular mechanisms that enable us to sense cold are not well understood. Insights into this process have come from the use of pharmacological agents, such as menthol, that elicit a cooling sensation. Here we have characterized and cloned a menthol receptor from trigeminal sensory neurons that is also activated by thermal stimuli in the cool to cold range. This cold- and menthol-sensitive receptor, CMR1, is a member of the TRP family of excitatory ion channels, and we propose that it functions as a transducer of cold stimuli in the somatosensory system. These findings, together with our previous identification of the heat-sensitive channels VR1 and VRL-1, demonstrate that TRP channels detect temperatures over a wide range and are the principal sensors of thermal stimuli in the mammalian peripheral nervous system.

Amino Acid Sequence↗

Factors influencing cotinine half-life during smoking abstinence in African American and Caucasian women.

Cotinine, the proximate metabolite of nicotine, has been identified as an indicator of smoke constituent exposure. Higher cotinine levels in African American cigarette smokers have been identified. Because African Americans experience disproportionate smoking-related morbidity and mortality, it is important to examine potential factors influencing these higher levels of cotinine. The current study examined selected factors of ethnicity, menthol cigarette preference, body composition and alcohol-use history on cotinine half-life in 6 days of smoking abstinence in African American and Caucasian women. A 7-day inpatient protocol was conducted in the General Clinical Research Center, in which day 1 was ad lib smoking and days 2-7 were smoking abstinence (n = 32). Plasma cotinine was measured every 8 h throughout. Average cotinine half-life was 21.3 h, similar to previously reported 18-20 h. Three women exhibited >14 ng/ml cotinine after 136 h of smoking abstinence. Host factors explaining 52.0% of variance in cotinine half-life and associated with longer half-life were being an African American menthol smoker, fewer years of alcohol use and greater lean body mass. Among menthol smokers, baseline cotinine level and cotinine half-life were not significantly different in Caucasian and African American women. Intra-individual cotinine half-life variation and CYP2A6 genotype were examined in substudies. To improve accuracy in correctly classifying non-smokers with cotinine levels, a period of at least 7 days of smoking abstinence may be warranted.

Black or African American↗

Inhibition of rat mammary carcinogenesis by monoterpenoids.

We have previously demonstrated the cancer chemopreventive activities of the monocyclic unsaturated monoterpene d-limonene. In the present work we report data evaluating the chemopreventive effects of limonene and five other monoterpenes with various chemical structures using a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis model. The terpenes tested include: oxygenated [(-)-menthol] and non-oxygenated (d-limonene) monocyclic forms, oxygenated (1,8-cineole) and non-oxygenated [(+/-)-alpha-pinene] bicyclic forms and oxygenated [(+/-)-linalool] and non-oxygenated (beta-myrcene) acyclic forms. Dietary additions of each of the monocyclic terpenes, d-limonene or (-)-menthol resulted in a significant inhibition of mammary carcinogenesis. Furthermore, menthol was found to be a more potent chemopreventive agent than limonene during the DMBA initiation of rat mammary tumors. The acyclic and bicyclic terpenes had no significant chemopreventive activities at the dose levels used in these studies.

9,10-Dimethyl-1,2-benzanthracene↗

Trigeminal perception of odorant quality in congenitally anosmic subjects.

Twenty congenitally anosmic subjects and 50 normosmic controls were tested for their ability (i) to assign verbal labels from a list of trigeminal-type descriptors to six odorants believed to have a strong trigeminal component; and (ii) to discriminate between intensity-matched pairs of these odorants in an odd-ball paradigm. The following was found: normosmic controls judged menthol and cineole as distinctly cool and fresh, acetic acid as pungent and sour, and acetone as pungent, but showed no clear descriptive profile for ethanol and propanol. The descriptive profiles given by the anosmic subjects correlated significantly with those given by the controls for three of the six odorants (menthol, cineol and ethanol), confirming that the sensations described may indeed be mediated by the trigeminal system. In the odd-ball test, the control subjects correctly identified an average of eight out of the nine items presented, with most mistakes occurring in response to pairs with a similar trigeminal profile. With an average of 7.2 of nine items correct, the performance of the anosmic subjects was not significantly different to that of the normosmics, except in discriminating between acetic acid and menthol. Although additional tests are necessary to decide finally whether differences in stimulus intensity may have contributed to this good discriminatory performance, the present results suggest that the nasal trigeminal system may contribute significantly to the perception of odor quality.

1-Propanol↗

Preimaginal learning determines adult response to chemical stimuli in a parasitic wasp.

The behavioural responses of parasitic wasps to chemical cues from their hosts and host plants are known to be affected by genetic and environmental components. In a previous study of the codling moth ectoparasitoid Hyssopus pallidus, we found that the response of adult parasitoids to the frass of their host caterpillars depended on a learning process involving plant cues. In the present study, we investigated how and when learning takes place. A series of experiments was conducted involving exposure of parasitoids to fruit cues at different developmental stages. While parasitoids were not able to learn the fruit cues in the adult stage, exposure to fruit odour at early preimaginal stages significantly increased the adult response to frass from fruit-fed caterpillars. The olfactory memory persisted through metamorphosis, with a retention time of 14 days. Preimaginal learning was not confined to fruit cues but was also demonstrated for a host- and fruit-independent cue, menthol. Parasitoids exposed to menthol odour at the egg and larval stages no longer showed negative responses as adults. Sensitization to fruit cues and habituation to menthol are considered to be the mechanisms involved. This study provides evidence of true preimaginal learning of olfactory cues in a parasitic wasp.

Animals↗

Characterization of cold sensitivity and thermal preference using an operant orofacial assay.

BACKGROUND: A hallmark of many orofacial pain disorders is cold sensitivity, but relative to heat-related pain, mechanisms of cold perception and the development of cold allodynia are not clearly understood. Molecular mediators of cold sensation such as TRPM8 have been recently identified and characterized using in vitro studies. In this study we characterized operant behavior with respect to individually presented cold stimuli (24, 10, 2, and -4 degrees C) and in a thermal preference task where rats chose between -4 and 48 degrees C stimulation. We also evaluated the effects of menthol, a TRPM8 agonist, on operant responses to cold stimulation (24, 10, and -4 degrees C). Male and female rats were trained to drink sweetened milk while pressing their shaved faces against a thermode. This presents a conflict paradigm between milk reward and thermal stimulation. RESULTS: We demonstrated that the cold stimulus response function was modest compared to heat. There was a significant effect of temperature on facial (stimulus) contacts, the ratio of licking contacts to stimulus contacts, and the stimulus duration/contact ratio. Males and females differed only in their facial contacts at 10 degrees C. In the preference task, males preferred 48 degrees C to -4 degrees C, despite the fact that 48 degrees C and -4 degrees C were equally painful as based on their reward/stimulus and duration/contact ratios. We were able to induce hypersensitivity to cold using menthol at 10 degrees C, but not at 24 or -4 degrees C. CONCLUSION: Our results indicate a strong role for an affective component in processing of cold stimuli, more so than for heat, which is in concordance with human psychophysical findings. The induction of allodynia with menthol provides a model for cold allodynia. This study provides the basis for future studies involving orofacial pain and analgesics, and is translatable to the human experience.

Animals↗

Olfactory and trigeminal thresholds and nasal resistance to airflow.

Nasal congestion associated with the common cold or allergy is associated with a decreased sensitivity of the sense of smell. This study was designed to detect any relationship between nasal resistance to airflow and the ability to detect odors presented to the nose. In particular we were interested to determine if the asymmetrical nasal resistance to airflow associated with the nasal cycle influenced nasal thresholds to menthol which is detected by trigeminal nerves and vanillin which is detected by olfactory nerves. Nasal resistance to airflow and the thresholds for L-menthol and vanillin were measured for each nasal passage in 17 normal volunteer subjects. Nasal resistance to airflow was asymmetrical due to the nasal cycle with a resistance on the high side of 0.94 +/- 0.15 Pa/cm3 s (mean +/- S.E. n = 17). and 0.48 +/- 0.04 Pa/cm3 s on the low side. The range of unilateral nasal resistances varied from 0.31-2.55 Pa/cm3 s. Despite these variations in nasal resistance to airflow no relationship was found between nasal resistance to airflow and thresholds for menthol or vanillin. Since threshold and nasal resistance are not related in normal subjects this may indicate that it is not the level of nasal congestion that affects the sense of smell in nasal infection and allergy, but some other factor related to the inflammatory response of the nasal mucosa.

Adult↗

Final report on the safety assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water.

Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, Mentha Piperita (Peppermint) Leaf Water are obtained from the Mentha piperita plant. The oil is currently used in cosmetic formulations as a fragrance component, but previously had been also described as a denaturant. The extract and leaves are described as biological additives, but only the extract is reported to be used. Peppermint Water is described as a flavoring agent or fragrance component, but is not currently in use. Peppermint Oil is used at a concentration of < or = 3% in rinse-off formulations and < or = 0.2% in leave-on formulations. Peppermint Oil is composed primarily of menthol and menthone. Other possible constituents include pulegone, menthofuran, and limone. Most of the safety test data concern Peppermint Oil. The oil is considered to present the "worst case scenario" because of its many constituents, so data on the oil were considered relevant to the entire group of ingredients. Peppermint Oil was minimally toxic in acute oral studies. Short-term and sub-chronic oral studies reported cystlike lesions in the cerebellum in rats that were given doses of Peppermint Oil containing pulegone, pulegone alone, or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognized hepatotoxin. Repeated intradermal dosing with Peppermint Oil produced moderate and severe reactions in rabbits, although Peppermint Oil did not appear to be phototoxic. Peppermint Oil was negative in the Ames test and a mouse lymphoma mutagenesis assay but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. In a carcinogenicity study of toothpaste and its components, no apparent differences were noted between mice treated with Peppermint Oil and those treated with the toothpaste base. Isolated clinical cases of irritation and/or sensitization to Peppermint Oil and/or its constituents have been reported, but Peppermint Oil (8%) was not a sensitizer when tested using a maximization protocol. It was expected that dermal absorption of Peppermint Oil would be rapid, following that of menthol, a major component, but in no case would be greater than absorption through the gastrointestinal tract. Because of the toxicity of pulegone, the safe concentration of this constituent was limited to < or = 1%. This concentration was achievable both by controlling the time of harvest and processing technique. There is evidence that menthol can enhance penetration of other agents. Formulators were cautioned that this enhanced penetration can affect the use of other ingredients whose safety assessment was based on their lack of absorption. With the limitation that the concentration of pulegone in these ingredients should not exceed 1%, it was concluded that Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Extract, Mentha Piperita (Peppermint) Leaves, Mentha Piperita (Peppermint) Water are safe as used in cosmetic formulations.

Animals↗

Effect of cyclic monoterpenes on percutaneous absorption in the case of a water-soluble drug (diclofenac sodium).

The promoting effect of cyclic monoterpenes on the percutaneous absorption of diclofenac sodium (DFS), a water-soluble drug, from gel ointments was investigated in rats. Of five cyclic monoterpenes examined, l-menthol was most effective. Plasma concentrations of diclofenac (DF) increased with increasing amounts of l-menthol in the gel ointment. L-menthol had no effect on the solubility and partition coefficient of DFS, suggesting that the thermodynamic nature of DFS in the formulation was not greatly affected. Plasma concentrations of DF arising from application of ointments containing varying amounts of the terpene were predicted from found pharmacokinetic parameters and the steady-state flux of DFS obtained from in vitro permeation experiments. Experimentally determined plasma concentration of DF agreed well with the predictions, indicating that steady-state flux in vitro well reflects percutaneous absorption in vivo.

Animals↗

Antibacterial and antifungal activity of aromatic constituents of essential oils.

Five aromatic constituents of essential oils (cineole, citral, geraniol, linalool and menthol) were tested for antimicrobial activity against eighteen bacteria (including Gram-positive cocci and rods, and Gram-negative rods) and twelve fungi (three yeast-like and nine filamentous). In terms of antibacterial activity linalool was the most effective and inhibited seventeen bacteria, followed by cineole, geraniol (each of which inhibited sixteen bacteria), menthol and citral aromatic compounds, which inhibited fifteen and fourteen bacteria, respectively. Against fungi the citral and geraniol oils were the most effective (inhibiting all twelve fungi), followed by linalool (inhibiting ten fungi), cineole and menthol (each of which inhibited seven fungi) compounds.

Acyclic Monoterpenes↗

Williopsis californica, Williopsis saturnus, and Pachysolen tannophilus: novel microorganisms for stereoselective oxidation of secondary alcohols.

A screening of 416 microorganisms from different taxonomical groups (bacteria, actinomycetes, yeasts, and filamentous fungi) has been performed looking for active strains in the stereoselective oxidation of secondary alcohols. The working collection was composed of 71 bacterial strains, 45 actinomycetes, 59 yeasts, 60 basidiomycetes, 33 marine fungi, and 148 filamentous fungi. All microorganisms selected were mesophilic. Yeasts were the most active microbial group in the whole-cell-catalyzed oxidation. Williopsis californica, Williopsis saturnus, and Pachysolen tannophilus were the strains of greatest interest, both as growing cells and as resting cells. The oxidation of the alcohols takes place when cells are in the stationary growth phase (after 48 h of culture). These three strains are S-stereoselective for the oxidation of racemic secondary alkanols and show stereospecificity in the oxidation of menthol or neo-menthol, whereas iso-menthol is not oxidized. In the case of the 1-tetrahydronaphtol enantiomers, only the S-enantiomer is oxidized. The three strains were immobilized by entrapment using agarose and agar from algae of the Gracilaria genus. The agarose derivatives displayed significant improvement in the stereospecificity of the reactions.

Alcohols↗

Two-phase system membrane reactor with cofactor recycling.

For the purpose of constructing a two-phase system reactor the enzymatic process of l-menthol production with cofactor recycling was studied as a model. The half-life of the menthone reductase immobilized onto activated carbon was 4 times as high as that of the free enzyme. The enzyme was capable of regenerating NADH when methyl isobutyl carbinol was used as a second substrate. Continuous production of l-menthol was achieved by using a reactor equipped with a hydrophobic microfiltration membrane. It was found that both NAD(H) and the enzyme could be retained in the reactor and the products, l-methanol and methyl isobutyl ketone, passed through the membrane. The production of l-methanol was maintained for 270 h at a rate of 46.1 g l-1 d-1, and had decreased by one-half at 607 h. The recycling number of NAD(H) was 2500 (max. 3020) during the operation. The number of theoretical plates was calculated to be 40 for the separation of l-menthol from other reactants.

Coenzymes↗

Antimicrobial and antiplasmid activities of essential oils.

The antimicrobial and antiplasmid activities of essential oils (orange oil, eucalyptus oil, fennel oil, geranium oil, juniper oil, peppermint oil, rosemary oil, purified turpentine oil, thyme oil, Australian tea tree oil) and of menthol, the main component of peppermint oil, were investigated. The antimicrobial activities were determined on the Gram (+) Staphylococcus epidermidis and the Gram (-) Escherichia coli F'lac K12 LE140, and on two yeast Saccharomyces cerevisiae 0425 delta/1 and 0425 52C strains. The antiplasmid activities were investigated on E. coli F'lac bacterial strain. Each of the oils exhibited antimicrobial activity and three of them antiplasmid action. The interaction of peppermint oil and menthol with the antibiotics was studied on the same bacterial strain with the checkerboard method. Peppermint oil and menthol displayed additive synergy with oxytetracycline. A new mechanism of plasmid curing was established for one of the oil components.

Anti-Bacterial Agents↗

Transdermal absorption of L-dopa from hydrogel in rats.

To improve compliance in administration of l-dopa, transdermal absorption of the agent was investigated in rats in vitro employing two-chamber diffusion cells in which the excised rat abdominal skin was mounted, and in vivo using an alcoholic hydrogel containing l-menthol. The in vitro study revealed that in presence of l-menthol (2%, W/W), ethanol (20 and 40%, V/V) accelerated transdermal penetration of l-dopa with an increase of its percentages. The in vivo study showed that when the l-dopa-hydrogel containing 2% l-menthol and 40% ethanol was attached on the skin, plasma levels of l-dopa and norepinephrine increased with the time elapsed; the level of dopamine increased and reached a plateau thereafter; and the level of epinephrine was unchanged. These in vitro and in vivo findings indicated that the hydrogel formulation of l-dopa provides new direction in treating Parkinson's disease.

Administration, Cutaneous↗

Central to Axial Transfer of Chirality in Menthone or Camphor-Derived 2,2'-Biphenols.

A study aimed at defining a molecular arrangement where a chiral fragment derived from menthone or camphor transfers its central chirality to a 2,2'-biphenol residue, inducing an axial chirality, is reported. The menthol or isoborneol groups are attached at the two benzylic positions at 3,3' in order to maximize efficiency in practical applications. A reliable and high-yielding procedure for the synthesis of such C(2)-symmetric molecules substituted at the 3,3'-positions has been developed. The procedure entails Mannich condensation with paraformaldehyde and morpholine, protection of the hydroxylic functions, chlorination, metalation, and addition to (-)-menthone and (+)-camphor. The use of samarium diiodide is essential in the latter step for optimum selectivity and efficiency. The tetrols exhibit intramolecular hydrogen bonding between phenolic and alcoholic hydroxy functions within each monomeric unity, so that they retain their rotational freedom. NOEDS and COSY experiments show that the tetrols are present in more than one rotamer. The tetrols react with tetrachlorosilane to afford siloxanes as pure diastereoisomers, showing that the metal is able to induce preferential helicity at the biphenyl residue; i.e., the central chirality of menthol or isoborneol auxiliary is totally transfered to the axial chirality of the biphenyl. The configurations could be determined by NOEDS and heterocorrelated HMQC experiments. Remarkably, while the menthol derivative induces total M helicity, the camphor induces complementary P helicity. These results suggest that these tetrols may be useful as ligands in catalysts for asymmetric synthesis.

Journal Article↗

Effects of solvents on skin permeation of formoterol fumarate.

Effects of various chemicals applied as penetration enhancers on the permeation of formoterol fumarate (FF) across excised rat skin were investigated. Remarkable enhancement was noted with terpenes, fatty acid esters, and higher alcohols, whereas no significant influence was observed in the case of lower alcohols, pyrrolidones, and amines. At high concentration, a cineole/N-methyl-2-pyrrolidone (NMP) mixed solvent system slightly enhanced the skin permeation of FF compared with cineole alone, and a l-menthol/NMP mixed solvent system caused significant further increase. Maximum skin permeation of FF was seen when the ratio of l-menthol/NMP was 60/40 w/w. From the present results, l-menthol/NMP and isopropyl myristate (IPM)/NMP mixed solvent systems can be considered effective for augmenting skin permeation of FF, with potential applications in transdermal delivery of the drug.

Administration, Cutaneous↗