Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons

BACKGROUND: Triptans, 5-HT(1B/ID )agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca(2+ )channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca(2+ )channels are not yet documented. RESULTS: In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca(2+ )channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba(2+ )currents (I(Ba)) passing through Ca(2+ )channels. Zolmitriptan (0.1–100 μM) reduced the size of I(Ba )in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT(1B/1D )antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca(2+ )channel blockers inhibited the inhibitory action of zolmitriptan on I(Ba), compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT(1B/1D )receptor linked to G(i/o )pathway. CONCLUSION: It is concluded that this zolmitriptan inhibition of HVA Ca(2+ )channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan

Tubulointerstitial Nephritis and Uveitis Syndrome Associated with Renal Tryptaseand Chymase-positive Mast Cell Infiltration

We report the clinical course and immunohistochemical analysis of a patient who presented with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome). The patient, a 40-year-old woman, was referred to our hospital with general fatigue and a slight fever from another hospital. Mast cells are closely related to the development of renal interstitial fibrosis in patients with glomerulonephritis. To determine the role of mast cells in renal interstitial injury in TINU patients, we performed immunohistochemical studies on renal biopsy specimens using anti-human tryptase and anti-human chymase antibodies specific for mast cells. Double immunostaining of tryptase and chymase was also performed in renal tissues. In double immunofluorescence, cells with both chymase and tryptase (MCtc) were marked in the regions of interstitial fibrosis in this patient. It appears that mast cells are one of the constitutive cells of interstitial fibrosis in patients with TINU syndrome

Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging

A new formulation of lateral imaging process of point-scanning optical coherence tomography (OCT) and a new differential contrast method designed by using this formulation are presented. The formulation is based on a mathematical sample model called the dispersed scatterer model (DSM), in which the sample is represented as a material with a spatially slowly varying refractive index and randomly distributed scatterers embedded in the material. It is shown that the formulation represents a meaningful OCT image and speckle as two independent mathematical quantities. The new differential contrast method is based on complex signal processing of OCT images, and the physical and numerical imaging processes of this method are jointly formulated using the same theoretical strategy as in the case of OCT. The formula shows that the method provides a spatially differential image of the sample structure. This differential imaging method is validated by measuring in vivo and in vitro samples

Automatic characterization and segmentation of human skin using three-dimensional optical coherence tomography

A set of fully automated algorithms that is specialized for analyzing a three-dimensional optical coherence tomography (OCT) volume of human skin is reported. The algorithm set first determines the skin surface of the OCT volume, and a depth-oriented algorithm provides the mean epidermal thickness, distribution map of the epidermis, and a segmented volume of the epidermis. Subsequently, an en face shadowgram is produced by an algorithm to visualize the infundibula in the skin with high contrast. The population and occupation ratio of the infundibula are provided by a histogram-based thresholding algorithm and a distance mapping algorithm. En face OCT slices at constant depths from the sample surface are extracted, and the histogram-based thresholding algorithm is again applied to these slices, yielding a three-dimensional segmented volume of the infundibula. The dermal attenuation coefficient is also calculated from the OCT volume in order to evaluate the skin texture. The algorithm set examines swept-source OCT volumes of the skins of several volunteers, and the results show the high stability, portability and reproducibility of the algorithm.This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?URI=oe-14-5-1862. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law

Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons

Abstract Background Triptans, 5-HT1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca2+ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca2+ channels are not yet documented. Results In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca2+ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba2+ currents (IBa) passing through Ca2+ channels. Zolmitriptan (0.1–100 μM) reduced the size of IBa in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca2+ channel blockers inhibited the inhibitory action of zolmitriptan on IBa, compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p 1B/1D receptor linked to Gi/o pathway. Conclusion It is concluded that this zolmitriptan inhibition of HVA Ca2+ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.</p

A total and practical synthesis of ergot alkaloid, (±)-aurantioclavine

The first synthesis of (±)-aurantioclavine by a convenient and practical five-step synthetic method, involving a new intra-molecular cyclization of nitro-olefin, is achieved starting from 3-formylindole with a 31% overall yield without using any protective groups

Airflow limitation and airway dimensions in chronic obstructive pulmonary disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and/or airway narrowing. Computed tomography has been widely used to assess emphysema severity, but less attention has been paid to the assessment of airway disease using computed tomography. Objectives: To obtain longitudinal images and accurately analyze short axis images of airways with an inner diameter 2 mm located anywhere in the lung with new software for measuring airway dimensions using curved multiplanar reconstruction. Methods: In 52 patients with clinically stable COPD (stage I, 14; stage II, 22; stage III, 14; stage IV, 2), we used the software to analyze the relationship of the airflow limitation index (FEV1, % predicted) with the airway dimensions from the third to the sixth generations of the apical bronchus (B1) of the right upper lobe and the anterior basal bronchus (B8) of the right lower lobe. Measurements and Main Results: Airway luminal area (Ai) and wall area percent (WA%) were significantly correlated with FEV1 (% predicted). More importantly, the correlation coefficients (r) improved as the airways became smaller in size from the third (segmental) to sixth generations in both bronchi (Ai: r = 0.26, 0.37, 0.58, and 0.64 for B1; r = 0.60, 0.65, 0.63, and 0.73 for B8). Conclusions: We are the first to use three-dimensional computed tomography to demonstrate that airflow limitation in COPD is more closely related to the dimensions of the distal (small) airways than proximal (large) airways