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

Membranous Fibrosis of the Lung

Membranous fibrosis of the lung depicts a morphological feature of the fibrous tissue which covers alveolar duct walls. Membranous sheets of fibrous tissue usually bridge and obstruct the mouths of alveoli, and attach only at the tips of the septa; i.e., the alveolar duct walls, and often provoke a collapse of alveolar spaces. There seem to be two types of membranous fibrosis. The first type is, in fact, a fibrous replacement of pre-existing hyaline membrane, while the second is a de novo formation of membranous fibrous tissue which has little or no preceding hyaline membrane. We consider that both of these changes result from damage to the alveolar duct walls and may constitute forms of the fibrosing alveolar ductitis syndrome. Recognition of this type of fibrosis gives us a better understanding of the morphogenesis of so-called diffuse alveolar damage

The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats

(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague-Dawley rats under urethane-chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested

New Stepwedge for Bootstrap Sensitometry in Medical Radiography

A new stepwedge has been developed for bootstrap sensitometry, which is used for determining the characteristic curve of radiographic screen/film systems. Since each step of the stepwedge is separated by the lead septum, flare generated under one step will not penetrate the region of another step. The metal of the stepwedge can be changed with various materials. Characteristic curves obtained with new stepwedge bootstrap (NSB) and conventional stepwedge bootstrap (CSB) techniques were compared with those obtained for screen/film systems with inverse sqare sensitometry. The inverse square method was used as the reference standard for accuracy. The NSB method provided characteristic curves that agreed well with those obtained using the inverse square method. The slope of the curve in the CSB method was lower than that in the inverse square or NBS method, because of scatter radiation. The shape of the characteristic curve from the NSB method did not vary with the materials of step metals (aluminum and copper). The cumulative error involved when using the bootstrap method is also discussed

Serum Concentration of Flomoxef in Administration of One Hour Infusion Every Eight Hours a Day

Flomoxef (FMOX) is a new, parenteral oxacephem antibiotic with strong, broad-spectrum antimicrobial activity. To compensate for short half time of this drug, multi-divided administration of the drug was attempted, and the concentrations of FMOX in the blood were determined. The treatment by dripping intravenous infusion of FMOX thrice daily or one hour infusion every eight hours were carried out in six patients with an indwelling intravenous catheter. Four patients had pneumonia and the other two suffered from respiratory infections with lung cancer. With the patient\u27s permission, six blood samples were drawn from each patient just before and after infusions, and the concentration of FMOX was determined by bioassay. The mean serum concentration in the six patients ranged between three troughs just before infusion and three peaks just after infusion, being 1.40 μg/ml, 2.59 μg/ml and 1.84 μg/ml, and 47.32 μg/ml, 52.17 μg/ml and 50 μg/ml, respectively. These concentrations, even troughs, were higher than the MIC90 of almost all bacteria considered to be sensitive to FMOX. In fact, five out of six patients showed a good response to this treatment. No side effects were observed, except mild and transient elevation of transaminase in one case. In conclusion, we recommend the administration of FMOX thrice daily for patients with severe pulmonary infections, especially from the standpoint of its blood concentration

Postnatal development of inhibitory synaptic transmission to superior salivatory neurons in rats

The primary parasympathetic center of the submandibular and sublingual salivary glands is the superior salivatory (SS) nucleus, and its neurons receive excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) synaptic transmissions in rats. In the present study, we focused on the postnatal development of inhibitory transmission to SS neurons. Gramicidin-perforated whole-cell patch-clamp recordings were performed in rat brainstem slices on postnatal day 2 (P2)-P14. Developmental changes in the intracellular Cl- concentration ([Cl-]in) were examined based on the reversal potentials of total inhibitory postsynaptic currents (GABAergic plus glycinergic), which were evoked by electrical stimulation near the recording neuron. The [Cl-]in in the P8-P14 groupwas significantly lower than in the P2-P7 group. The effect of GABA application at the resting potentials changed from depolarization to hyperpolarization around P8, suggesting that SS neurons acquired mature inhibitory systems around P8. The period at which GABA responses change from excitatory to inhibitory in SS neurons was discussed compared with those of the forebrain, brainstem, and spinal neurons

Clinical characteristics of tuberculosis patients in a tertiary hospital

　We retrospectively assessed the clinical characteristics of tuberculosis patients in a tertiary hospital. The subjects consisted of 80 patients who Mycobacterium tuberculosis was isolated from clinical specimens and who received a definite diagnosis of tuberculosis in our tertiary hospital without isolated bedrooms between January 2010 and June 2018. The average age of the 80 patients was 68.3 years old, consisting of 43 males and 37 females (6 non-Japanese). Sixty-eight patients had underlying diseases, and malignant diseases were most frequently recognized. Seven patients were diagnosed as outpatients and the remaining patients were diagnosed after admission. The final diagnose consisted of 56 patients with pulmonary tuberculosis and 35 patients with extrapulmonary tuberculosis (tuberculous lymphadenitis, tuberculous pleurisy, miliary tuberculosis, etc.). Concerning the results of interferon-γ release assays (IGRAs), while the positive response rate of QFT was 75%, that of T-SPOT was 81%. The clinical specimens used to diagnose tuberculosis were as follows: expectorated sputum, 26 patients; bronchoscopic specimens, 32; biopsy tissue, 17; and others, 5. The interval from the first consultation to diagnosis was three months at the maximum and within one month in most patients. Regarding radiological findings, pulmonary lesions including miliary tuberculosis showed various atypical findings: 39 of 66 patients with bilateral lesions; 50 with no cavity lesion; and 13 with the extent of the lesion exceeding the unilateral lung field. 　Tuberculosis patients in our tertiary hospital had many underlying diseases such as malignant or autoimmune diseases and were receiving immunosuppressive treatment. Therefore, because IGRAs do not always show a positive response and radiological findings also do not show typical findings, it is important to investigate acid-fast bacilli for various clinical specimens and actively perform diagnostic methods including bronchoscopy in order to prevent nosocomial infection

Cevimeline enhances the excitability of rat superior salivatory neurons

Cevimeline, a therapeutic drug for xerostomia, is an agonist of muscarinic acetylcholine receptors (mAChRs), and directly stimulates the peripheral mAChRs of the salivary glands. Since cevimeline is distributed in the brain after its oral administration, it is possible that it affects the central nervous system. However, it is unknown how cevimeline affects the superior salivatory (SS) neurons, which control submandibular salivation. In the present study, we examined the effects of cevimeline on the SS neurons using the whole-cell patch-clamp technique in brain slices. In Wistar rats (6-10 days), the SS neurons were retrogradely labeled by Texas Red applied to the chorda-lingual nerve. Two days after injection, whole-cell recordings were obtained from the labeled cells, and miniature excitatory postsynaptic currents (mEPSCs) were examined. Cevimeline induced the inward currents dose-dependently and increased the frequency of mEPSCs. Therefore, it is suggested that cevimeline enhances the excitability via post- and presynaptic muscarinic receptors in the rat SS neurons. In conclusion, cevimeline may enhance the excitability of the SS neurons