OTC product: SudaCare Shower Soothers.
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Camphor↗
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Results for “Menthol”
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Letter: The effect of the vapors of a commonly used remedy for colds on pulmonary antibacterial defenses.
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Animals↗
Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation.
Transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are ion channels that detect cold and hot sensations, respectively. Their activation depolarizes the peripheral nerve terminals resulting in action potentials that propagate to brain via the spinal cord. These receptors also play a significant role in synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons. Here, we show that TRPM8 is functionally downregulated by activation of protein kinase C (PKC) resulting in inhibition of membrane currents and increases in intracellular Ca2+ compared with upregulation of TRPV1 in cloned and native receptors. Bradykinin significantly downregulates TRPM8 via activation of PKC in DRG neurons. Activation of TRPM8 or TRPV1 at first sensory synapse between DRG and DH neurons leads to a robust increase in frequency of spontaneous/miniature EPSCs. PKC activation blunts TRPM8- and facilitates TRPV1-mediated synaptic transmission. Significantly, downregulation is attributable to PKC-mediated dephosphorylation of TRPM8 that could be reversed by phosphatase inhibitors. These findings suggest that inflammatory thermal hyperalgesia mediated by TRPV1 may be further aggravated by downregulation of TRPM8, because the latter could mediate the much needed cool/soothing sensation.
Animals↗
A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels.
Temperature transduction in mammals is possible because of the presence of a set of temperature-dependent transient receptor potential (TRP) channels in dorsal root ganglia neurons and skin cells. Six thermo-TRP channels, all characterized by their unusually high temperature sensitivity (Q10 > 10), have been cloned: TRPV1-4 are heat activated, whereas TRPM8 and TRPA1 are activated by cold. Because of the lack of structural information, the molecular basis for regulation by temperature remains unknown. In this study, we assessed the role of the C-terminal domain of thermo-TRPs and its involvement in thermal activation by using chimeras between the heat receptor TRPV1 and the cold receptor TRPM8, in which the entire C-terminal domain was switched. Here, we demonstrate that the C-terminal domain is modular and confers the channel phenotype regarding temperature sensitivity, channel gating kinetics, and PIP2 (phosphatidylinositol-4,5-bisphophate) modulation. Thus, thermo-TRP channels contain an interchangeable specific region, different from the voltage sensor, which allows them to sense temperature stimuli.
Analysis of Variance↗
Repellency of oils of lemon eucalyptus, geranium, and lavender and the mosquito repellent MyggA natural to Ixodes ricinus (Acari: Ixodidae) in the laboratory and field.
MyggA Natural (Bioglan, Lund, Sweden) is a commercially available repellent against blood-feeding arthropods. It contains 30% of lemon-scented eucalyptus, Corymbia citriodora (Hook.) K. D. Hill & L. A. S. Johnson (Myrtaceae), oil with a minimum of 50% p-menthane-3,8-diol. MyggA Natural also contains small amounts of the essential oils of lavender, Lavandula angustifolia Mill. (Lamiaceae), and geranium, Pelargonium graveolens L'Her. (Geraniaceae). In laboratory bioassays, MyggA Natural and C. citriodora oil exhibited 100% repellency against host-seeking nymphs of Ixodes ricinus (L.) (Acari: Ixodidae). Lavender oil and geranium oil, when diluted to 1% in 1,2-propanediol, had weak repellent activities on I. ricinus nymphs, but when diluted to 30% in 1,2-propanediol had 100% repellencies. 1,2-Propanediol (100%) had no significant repellent activity in comparison with that of the control. In field tests in tick-infested areas in central Sweden, tick repellency of MyggA Natural and C. citriodora oil was tested by the blanket-dragging technique for 4 d during a 6-d period. The repellencies (74 and 85%, respectively) on day 1 are similar (89%) to that of blankets treated in a similar manner with 19% diethyl-methyl-benzamide, based on previous work. Repellencies declined significantly from day 1 to day 6 (74 to 45% for MyggA Natural; 85 to 42% for C. citriodora oil).
Animals↗
Repellency of IR3535, KBR3023, para-menthane-3,8-diol, and deet to black salt marsh mosquitoes (Diptera: Culicidae) in the Everglades National Park.
IR3535, KBR3023, para-Menthane-3,8-diol (PMD), and deet were evaluated in controlled studies with human subjects (n = 5) for repellency to black salt marsh mosquitoes (Ochlerotatus taeniorhynchus Wiedemann), in the Everglades National Park, FL. In tests of 6-h duration, with an average mosquito biting pressure on exposed forearm skin of 19.5 (+/- 13.7) bites per minute, the mean percent repellencies (SE) for IR3535, KBR3023, PDM, and deet was 88.6 (3.2), 97.5 (1.7), 89.2 (2.9), and 94.8 (2.5), respectively. Mean complete protection times (SE) for IR3535, KBR3023, PMD), mean deet were 3.0 (1.0), 5.4 (0.6), 3.8 (1.4), and 5.6 (0.5) h, respectively. Untreated (ethanol) controls provided 0% repellency. When mosquito biting rates on the untreated forearm skin of repellent-treated subjects were compared with biting rates on the forearm skin of control subjects, the former were 23%-40% lower early in tests and as much as 22% higher late in tests. These differences cast doubt on the technical merit of test designs comprising evaluation of more than one repellent at a time on the same human subject while underscoring the importance of untreated subjects as negative controls in field repellent bioassays.
Activity Cycles↗
A study of a pre-brushing mouthrinse as an adjunct to oral hygiene.
A previous clinical screening study demonstrated that a cetylpyridinium chloride (CPC) essential oil mouthrinse inhibited plaque regrowth to a significantly greater extent than a negative control or a triclosan/copolymer rinse when used without toothbrushing. The purpose of this study was to evaluate the same ingredient combination as a pre-brushing rinse over a 6-week period. The study employed a 4 group parallel design with a minimum of 50 subjects per group. Subjects with a minimum baseline plaque index of 1.95 were recruited. The formulations employed were two variations of a CPC/essential oil rinse, a triclosan/copolymer product, and a hydroalcohol negative control. Subjects were rendered plaque free at baseline and then rinsed twice daily before toothbrushing with their allocated product. Plaque was scored at 6 days and 6 weeks. Plaque scores were reduced at 6 days compared to baseline but there were no significant differences between any of the groups. At 6 weeks, plaque scores were significantly lower in both CPC/essential oil groups compared to control. Although both CPC/essential oil groups showed plaque scores which were lower than the triclosan group, in only one of the groups was the difference significant. The triclosan product was not significantly different from control. The results support the previous findings that a CPC/essential oil rinse could be a useful adjunct to oral hygiene when used prior to normal toothbrushing.
Adolescent↗
Solubilizing efficiency of different gutta-percha solvents: a comparative study.
A study was conducted to comparatively evaluate the efficiency of different solvents for dissolving gutta-percha. Halothane, chloroform, xylene, acetone, isopropyl alcohol, turpentine, oil of mela-leuca and eucalyptol were used as solvents for dissolving standardized gutta-percha discs. Halothane, chloroform and xylene were markedly superior solvents of gutta-percha in comparison with the others. There was no significant difference among the three (p > 0.05). Eucalyptol, turpentine and oil of melaleuca were relatively less efficient. Acetone and isopropyl alcohol did not dissolve gutta-percha, being similar in this respect to distilled water.
2-Propanol↗
PMD, a registered botanical mosquito repellent with deet-like efficacy.
para-Menthane-3,8-diol(PMD) is a monoterpene spent product of the distillation of leaves of the Australian lemon-scented gum tree (updated nomenclature Corymbia citriodora ssp. citriodora). In April 2005, the U.S. Centers for Disease Control and Prevention (CDC) endorsed two non-deet mosquito repellents, including PMD. However, few mosquito professionals have in-depth familiarity with the history and efficacy of PMD. In this article, we describe the origin and development of PMD as a repellent and offer a comprehensive review of its performance against Aedes, Anopheles, Culex, and Ochlerotatus. In addition, we present original data from field and laboratory studies involving large numbers of subjects and comparisons with high-concentration deet and other repellents. We conclude that not only is the CDC endorsement warranted but also that it probably underestimates the value of PMD as a deet alternative for public health applications.
Aedes↗
Dental plaque pH in relation to intake of carbohydrate products.
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Adolescent↗
Short-term effects of local anaesthetic agents on the structure of the rat tympanic membrane.
Topical agents used in office procedures for tympanic membrane anaesthesia have been considered to cause damage to the membrane. Four different anaesthetic agents have been compared as regards their histopathological effects for a period of up to 2 weeks after application. An etching effect is obvious when using these clinically potent agents, but it seems reversible and does not leave remaining structural changes.
Aerosols↗
Metabolism of alpha- and beta-pinene, p-cymene and 1,8-cineole in the brushtail possum, Trichosurus vulpecula.
1. The nature of the non-conjugated metabolites of the Eucalyptus oil terpenoid components alpha-pinene, beta-pinene, p-cymene and 1,8-cineole in the urine and faeces of the brushtail possum was investigated. 2. alpha-Pinene was metabolized to myrtenic acid and trans-verbenol, beta-pinene to myrtenic acid, p-cymene to p-cresol and cumic acid, and 1,8-cineole to p-cresol, 9-hydroxycineole and cineol-9-oic acid.
Animals↗
Metabolism of a monoterpene ketone, R-(+)-pulegone--a hepatotoxin in rat.
1. R-(+)-Pulegone was administered orally to rats and the urinary metabolites were investigated. Six metabolites were isolated and purified using column and thin layer chromatographic techniques. Metabolites were identified by i.r., n.m.r. and mass spectral analyses. 2. The neutral metabolites isolated from urine of rats treated with pulegone (I) were: pulegone (II), 2-hydroxy-2(1'-hydroxy-1'-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a-hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (V) and menthofuran (VII). Metabolites II and III were also excreted in conjugated form. 3. Acidic metabolites isolated from urine of rats treated with pulegone (I) were: 5-methyl-2(1'-methyl-1'-carboxyethylidene)cyclohexanone (IV) and 5-methyl-5-hydroxy-2(1'hydroxy-1'-carboxyethyl)cyclohexanone (VI).
Administration, Oral↗
Investigations of mechanisms of reactive metabolite formation from (R)-(+)-pulegone.
1. (R)-(+)-Pulegone is a monoterpene that is oxidized by cytochromes P-450 to reactive metabolites that initiate events in the pathogenesis of hepatotoxicity in mice, rats and humans. 2. Selective labelling of (R)-(+)-pulegone with deuterium revealed that menthofuran was a proximate hepatotoxic metabolite formed by oxidation of the allylic methyl groups of pulegone. Incubations of pulegone with mouse liver microsomes in an atmosphere of 18O2 resulted in the formation of menthofuran that contained only oxygen-18 in the furan moiety. These results are consistent with oxidation of pulegone to an allylic alcohol that reacts intramolecularly with the ketone moiety to form a hemiketal that subsequently dehydrates to generate menthofuran. 3. Studies on the metabolism of menthofuran revealed that it is oxidized by cytochromes P-450 to an electrophilic gamma-ketoenal that reacts with nucleophilic groups on proteins to form covalent adducts. In addition, diastereomeric mintlactones are formed. Investigations with H2(18)O and 18O2 are indicative of a furan epoxide intermediate, or a precursor, in the formation of the gamma-ketoenal and mintlactones.
Animals↗
Studies on the metabolism of a monoterpene ketone, R-(+)-pulegone--a hepatotoxin in rat: isolation and characterization of new metabolites.
1. The metabolic disposition of R-(+)-pulegone (I) was examined in rats following four daily oral doses (250 mg/kg). 2. Six metabolites, namely pulegol (II), 2-hydroxy-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a-hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (IV), menthofuran (V), 5-methyl-2-(1-methyl-1-carboxyethylidene)cyclohexanone (VI), and 5-methyl-5-hydroxy-2-(1-hydroxy-1-carboxyethyl)cyclohexanone (VII) have previously been isolated from rat urine, and identified (Moorthy et al. (1989a). Eight new metabolites have now been isolated from rat urine, namely, 5-hydroxy-pulegone (VIII), piperitone (IX), piperitenone (X), 7-hydroxy-piperitone (XI), 8-hydroxy piperitone (XII), p-cresol (XIII), geranic acid (XIV) and neronic acid (XV). These were identified by n.m.r., i.r. and mass spectrometry. 3. Based on these results, metabolic pathways for the biotransformation of R-(+)-pulegone in rat have been proposed.
Animals↗
The Microsponge Delivery System (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives.
The Microsponge Delivery System (MDS) is a unique technology for the controlled release of topical agents and consists of macroporous beads, typically 10-25 microns in diameter, loaded with active agent. When applied to the skin, the MDS releases its active ingredient on a time mode and also in response to other stimuli (rubbing, temperature, pH, etc). MDS technology is being used currently in cosmetics, over-the-counter (OTC) skin care, sunscreens and prescription products. By delivering the active gradually to the skin, MDS-benzoyl peroxide formulations, for example, have excellent efficacy with minimal irritation. These are typical benefits from the use of the MDS.
Acne Vulgaris↗
Mechanisms of the formation and disposition of reactive metabolites that can cause acute liver injury.
Acetaminophen and pulegone are just two examples for many agents that can form reactive metabolites that can cause acute liver injury. Two other classic organic compounds that have been extensively studied are carbon tetrachloride (for a recent review see Ref. 159, and for other discussions see Refs. 8 and 9) and bromobenzene (for review see Ref. 160). Different kinds of protein adducts of reactive metabolites of bromobenzene have been partially characterized [161], and specific antibodies to these adducts are now being used to isolate and identify the proteins that are modified (162). In contrast, carbon tetrachloride and other agents, such as the herbicide diquat, may form radicals that bind to and/or oxidize lipids and proteins in causing liver injury (163, 164). Therefore, the recent development [165] of antibodies to detect oxidative damage to proteins will be important in the identification and characterization of macromolecules that do not form adducts with reactive metabolites but are damaged oxidatively. Thus, some major challenges in the coming years are to identify hepatocellular macromolecules that are modified by reactive metabolites, and then approach the more difficult task of integrating this information into a time course and sequence of events leading to lethal hepatocellular injury.
Acetaminophen↗