Effects of Bitter Receptor Antagonists on Behavioral Lick Responses of Mice

Bitter taste receptors TAS2Rs detect noxious compounds in the oral cavity. Recent heterologous expression studies reported that some compounds function as antagonists for human TAS2Rs. For examples, amino acid derivatives such as γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-Lysine (BCML) blocked responses to quinine mediated by human TAS2R4. Probenecid inhibited responses to phenylthiocarbamide mediated by human TAS2R38. In this study, we investigated the effects of these human bitter receptor antagonists on behavioral lick responses of mice to elucidate whether these compounds also function as bitter taste blockers. In short-term (10 s) lick tests, concentration-dependent lick responses to bitter compounds (quinine-HCl, denatonium and phenylthiourea) were not affected by the addition of GABA or BCML. Probenecid reduced aversive lick responses to denatonium and phenylthiourea but not to quinine-HCl. In addition, taste cell responses to phenylthiourea were inhibited by probenecid. These results suggest some bitter antagonists of human TAS2Rs can work for bitter sense of mouse

Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae

Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phospholipase Cβ2 (PLCβ2) and transient receptor potential channel M5 (TRPM5). Indeed, some gustducin-positive taste cells have been shown to respond to bitter compounds. However, there has been no systematic characterization of their response properties to multiple bitter compounds and the role of transduction molecules in these cells. In this study, we investigated bitter taste responses of gustducin-positive taste cells in situ in mouse fungiform (anterior tongue) and circumvallate (posterior tongue) papillae using transgenic mice expressing green fluorescent protein in gustducin-positive cells. The overall response profile of gustducin-positive taste cells to multiple bitter compounds (quinine, denatonium, cyclohexamide, caffeine, sucrose octaacetate, tetraethylammonium, phenylthiourea, L-phenylalanine, MgSO4, and high concentration of saccharin) was not significantly different between fungiform and circumvallate papillae. These bitter-sensitive taste cells were classified into several groups according to their responsiveness to multiple bitter compounds. Bitter responses of gustducin-positive taste cells were significantly suppressed by inhibitors of TRPM5 or PLCβ2. In contrast, several bitter inhibitors did not show any effect on bitter responses of taste cells. These results indicate that bitter-sensitive taste cells display heterogeneous responses and that TRPM5 and PLCβ2 are indispensable for eliciting bitter taste responses of gustducin-positive taste cells

Perioperative Care for Lung Transplant Recipients: A Multidisciplinary Approach

Lung transplantation has evolved as the gold standard for selective patients with end-stage lung disease since the first clinical lung transplant was performed in 1983 in the United States. Over the last few decades, lung transplantation volume has increased worldwide with steadily improving outcomes; however, access to lung transplantation remains limited due to the critical shortage of donor organs. Factors that have contributed to improved outcomes include a multidisciplinary management approach supported by advancements in surgical and anesthetic techniques, nursing and critical care, immunosuppressive therapy, transplant immunobiology, and the perioperative use of extracorporeal membrane oxygenation (ECMO) and ex vivo lung perfusion (EVLP). Excellent outcomes have been achieved in selective patients with high-risk comorbidities such as age over 65 years, concomitant severe coronary artery disease (CAD), and preexisting sensitization with donor-specific antibodies (DSAs). Such comorbidities are no longer considered absolute contraindications to lung transplantation. This chapter provides an overview of perioperative care of lung transplant recipients with focus on a multidisciplinary approach and highlights management strategies for patients with concomitant severe coronary artery disease and end-stage lung disease as well as those with preexisting sensitization with DSAs

Femoral Osteomyelitis due to Cladophialophora arxii in a Patient with Chronic Granulomatous Disease

Fungal infections in patients with chronic granulomatous disease (CGD) are a poor prognostic factor. We describe the first case of CGD with femoral osteomyelitis due to Cladophialophora arxii, which is a member of the dematiaceous group. The causative fungus was identified on the basis of its morphological characteristics, growth temperature profile, and nucleotide sequence on the internal transcribed space region of the ribosomal gene. The patient was successfully treated with surgical debridement, subsequent administration of itraconazolem and interferon-gamma.ArticleINFECTION. 37(5):469-473 (2009)journal articl

Oral Administration of L-Citrulline, but not L-Arginine or L-Ornithine, Acts as a Hypothermic Agent in Chicks

Some amino acids are important regulators of key metabolic pathways and necessary for several physiological functions. However, little is know about thermoregulatory functions of amino acids. In this study, therefore chicks were either centrally or orally administered with L-citrulline (L-Cit), L-arginine (L-Arg) or L-ornithine (L-Orn) to monitor changes in rectal temperature. In Experiment 1, the amino acids (L-Cit, L-Arg and L-Orn) were administered into the left ventricle of the chicks by intracerebroventricular (i.c.v.) injection at a dose of 1 μmol/10 μl to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period. In Experiment 2, chicks received the same amino acids by oral administration at a dose of 15 mmol/10 ml/kg body weight. In Experiment 3, chicks received three doses of L-Cit (3.75, 7.5 or 15 mmol/10 ml/kg body weight) by oral administration. I.c.v. injection with any of the amino acids studied did not alter body temperature, but oral administration of L-Cit significantly reduced body temperature. Importantly, the highest does effectively reduced body temperature. These results suggest that peripheral L-Cit has a hypothermic function in chicks, which may be a new candidate to minimize high body temperature in poultry during summer heat stress. Key words: body temperature, chick, L-arginine, L-citrulline, L-ornithin