Chemical Diversity of Citrus Leaf Essential Oils.

The essential oils from leaves of 20 commercial citrus accessions maintained by the University of California, Riverside Givaudan Citrus Variety Collection and selected on the basis of their odor profile were analyzed by GCMS/FID. The main components were quantified while the semi-quantitative percentage composition data was compiled with data from other publications for sample visualization, classification and comparison with leaf oils from other citrus accessions. Some compositional clusters aligned closely with the taxonomic clades of sweet orange, bitter orange, and C. hystrix while other clades like the mandarins and lemons showed distinct chemical sub-groups. Characteristic compounds for the clusters included linalyl acetate and linalool (bitter orange leaf), sabinene (sweet orange leaf), methyl N-methyl anthranilate (mandarin leaf), γ-terpinene (yuzu leaf), citronellal (C. hystrix), limonene, citronellal and citral (lemons and citrons). A chemometric approach combined with t-SNE cluster plots can be more informative than taxonomic assignments when considering flavor and fragrance characteristics.

Metal hypersensitivity in patients with orthopaedic implant complications-A retrospective clinical study.

BACKGROUND: Hypersensitivity to metals as a cause of implant-related complications has been a subject of controversy. Projections indicate an increase in the frequency of joint replacements of between 300% and 600% by the year 2030; therefore, this issue is of considerable interest. OBJECTIVE: To evaluate sensitization to implant materials in patients with implant-related complications, to identify allergens, and to clarify whether hypersensitivity is a relevant cause. METHODS: Patients with implant-related complications or a positive history of contact allergy and planned total joint replacements referred for allergological investigation between 2004 and 2017 were retrospectively analysed. RESULTS: In total, 311 patients were included. A positive patch test reaction to a metal was seen in 64.4% of preoperative patients and in 54.6% of patients with implant-related complications. Common alloy metals such as cobalt, chromium and titanium gave positive reactions in up to 2.9% of patients with implant-related complications. None of the patients with skin changes had a positive patch test reaction to an implant metal. CONCLUSION: Other factors, such as the type of replaced joint and mechanical stress, seem to be more relevant for implant-related complications. Sensitization to metals or other materials seems to rarely play a role, and is overestimated.

Novel menthol-derived cooling compounds activate primary and second-order trigeminal sensory neurons and modulate lingual thermosensitivity.

We presently investigated 2 novel menthol derivatives GIV1 and GIV2, which exhibit strong cooling effects. In previous human psychophysical studies, GIV1 delivered in a toothpaste medium elicited a cooling sensation that was longer lasting compared with GIV2 and menthol carboxamide (WS-3). In the current study, we investigated the molecular and cellular effects of these cooling agents. In calcium flux studies of TRPM8 expressed in HEK cells, both GIV1 and GIV2 were approximately 40- to 200-fold more potent than menthol and WS-3. GIV1 and GIV2 also activated TRPA1 but at levels that were 400 times greater than those required for TRPM8 activation. In calcium imaging studies, subpopulations of cultured rat trigeminal ganglion and dorsal root ganglion cells responded to GIV1 and/or GIV2; the majority of these were also activated by menthol and some were additionally activated by the TRPA1 agonist cinnamaldehyde and/or the TRPV1 agonist capsaicin. We also made in vivo single-unit recordings from cold-sensitive neurons in rat trigeminal subnucleus caudalis (Vc). GIV 1 and GIV2 directly excited some Vc neurons, GIV1 significantly enhanced their responses to cooling, and both GIV1 and GIV2 reduced responses to noxious heat. These novel cooling compounds provide additional molecular tools to investigate the neural processes of cold sensation.

Modulation of bitter taste perception by a small molecule hTAS2R antagonist.

Human bitter taste is mediated by the hTAS2R family of G protein-coupled receptors. The discovery of the hTAS2Rs enables the potential to develop specific bitter receptor antagonists that could be beneficial as chemical probes to examine the role of bitter receptor function in gustatory and nongustatory tissues. In addition, they could have widespread utility in food and beverages fortified with vitamins, antioxidants, and other nutraceuticals, because many of these have unwanted bitter aftertastes. We employed a high-throughput screening approach to discover a novel bitter receptor antagonist (GIV3727) that inhibits activation of hTAS2R31 (formerly hTAS2R44) by saccharin and acesulfame K, two common artificial sweeteners. Pharmacological analyses revealed that GIV3727 likely acts as an orthosteric, insurmountable antagonist of hTAS2R31. Surprisingly, we also found that this compound could inhibit five additional hTAS2Rs, including the closely related receptor hTAS2R43. Molecular modeling and site-directed mutagenesis studies suggest that two residues in helix 7 are important for antagonist activity in hTAS2R31 and hTAS2R43. In human sensory trials, GIV3727 significantly reduced the bitterness associated with the two sulfonamide sweeteners, indicating that hTAS2R antagonists are active in vivo. Our results demonstrate that small molecule bitter receptor antagonists can effectively reduce the bitter taste qualities of foods, beverages, and pharmaceuticals.

Activation of lumbar spinal wide-dynamic range neurons by a sanshool derivative.

The enigmatic sensation of tingle involves the activation of primary sensory neurons by hydroxy-alpha-sanshool, a tingly agent in Szechuan peppers, by inhibiting two-pore potassium channels. Central mechanisms mediating tingle sensation are unknown. We investigated whether a stable derivative of sanshool-isobutylalkenyl amide (IBA)-excites wide-dynamic range (WDR) spinal neurons that participate in transmission of chemesthetic information from the skin. In anesthetized rats, the majority of WDR and low-threshold units responded to intradermal injection of IBA in a dose-related manner over a >5-min time course and exhibited tachyphylaxis at higher concentrations (1 and 10%). Almost all WDR and low-threshold units additionally responded to the pungent agents mustard oil (allyl isothiocyanate) and/or capsaicin, prompting reclassification of the low-threshold cells as WDR. The results are discussed in terms of the functional role of WDR neurons in mediating tingle sensation.