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Bianchi BR El Kouhen R Neelands TR Lee CH Gomtsyan A Raja SN Vaidyanathan SN Surber B McDonald HA Surowy CS Faltynek CR Moreland RB Jarvis MF Puttfarcken PS 《The Journal of pharmacology and experimental therapeutics》2007,323(1):285-293
1-((R)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea (A-778317) is a novel, stereoselective, competitive antagonist that potently blocks transient receptor potential vanilloid-1 (TRPV1) receptor-mediated changes in intracellular calcium concentrations (pIC50 = 8.31 +/- 0.13). The (S)-stereoisomer, 1-((S)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea (A-778316), is 6.8-fold less potent (pIC50 = 7.47 +/- 0.07). A-778317 also potently blocks capsaicin and acid activation of native rat TRPV1 receptors in dorsal root ganglion neurons. A-778317 was tritiated ([3H]A-778317; 29.3 Ci/mmol) and used to study recombinant human TRPV1 (hTRPV1) receptors expressed in Chinese ovary cells (CHO) cells. [3H]A-778317 labeled a single class of binding sites in hTRPV1-expressing CHO cell membranes with high affinity (KD = 3.4 nM; Bmax = 4.0 pmol/mg protein). Specific binding of 2 nM [3H]A-778317 to hTRPV1-expressing CHO cell membranes was reversible. The rank-order potency of TRPV1 receptor antagonists to inhibit binding of 2 nM [3H]A-778317 correlated well with their functional potencies in blocking TRPV1 receptor activation. The present data demonstrate that A-778317 blocks polymodal activation of the TRPV1 receptor by binding to a single high-affinity binding site and that [3H]A-778317 possesses favorable binding properties to facilitate further studies of hTRPV1 receptor pharmacology. 相似文献
84.
El Kouhen R Surowy CS Bianchi BR Neelands TR McDonald HA Niforatos W Gomtsyan A Lee CH Honore P Sullivan JP Jarvis MF Faltynek CR 《The Journal of pharmacology and experimental therapeutics》2005,314(1):400-409
The vanilloid receptor transient receptor potential type V1 (TRPV1) integrates responses to multiple stimuli, such as capsaicin, acid, heat, and endovanilloids and plays an important role in the transmission of inflammatory pain. Here, we report the identification and in vitro characterization of A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel, potent, and selective TRPV1 antagonist. A-425619 was found to potently block capsaicin-evoked increases in intracellular calcium concentrations in HEK293 cells expressing recombinant human TRPV1 receptors (IC50 = 5 nM). A-425619 showed similar potency (IC50 = 3-4 nM) to block TRPV1 receptor activation by anandamide and N-arachidonoyl-dopamine. Electrophysiological experiments showed that A-425619 also potently blocked the activation of native TRPV1 channels in rat dorsal root ganglion neurons (IC50 = 9 nM). When compared with other known TRPV1 antagonists, A-425619 exhibited superior potency in blocking both naive and phorbol ester-sensitized TRPV1 receptors. Like capsazepine, A-425619 demonstrated competitive antagonism (pA2 = 2.5 nM) of capsaicin-evoked calcium flux. Moreover, A-425619 was 25- to 50-fold more potent than capsazepine in blocking TRPV1 activation. A-425619 showed no significant interaction with a wide range of receptors, enzymes, and ion channels, indicating a high degree of selectivity for TRPV1 receptors. These data show that A-425619 is a structurally novel, potent, and selective TRPV1 antagonist. 相似文献
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Charles Sabbagh Pierre Verhaeghe Abdennaceur Dhahri Olivier Brehant David Fuks Rachid Badaoui Jean-Marc Regimbeau 《Obesity surgery》2010,20(6):679-684
Background
Sleeve gastrectomy (SG) is an alternative to gastric bypass and laparoscopic adjustable gastric banding (GB).Methods
From January 2004 to January 2006, 111 patients with a follow-up longer than 24 months were prospectively followed. Three treatment groups were defined. Sleeve gastrectomy as first procedure (SGFP; n?=?50), sleeve gastrectomy after failure of GB (SG after GB; n?=?9) and GB (n?=?52). We compared morbidity, mortality, length of stay, number of procedures under general anaesthesia, excess weight loss (EWL) and quality of life.Results
Mean initial body mass index (BMI) was 50.4 (SG), 50.8 (SG after GB) and 43.8 (GB; p?=?0.000001). Mean operating time was 97.1 min (SGFP), 122.2 min (SG after GB) and 69.8 min (GB; p?<?0.0001). The reoperation rate under general anaesthesia was 2% (SGFP), 11% (SG after GB) and 30.76% (GB; p?=?0.00001).The fistula rate was 2% (SGFP), 0% (SG after GB) and 0% (GB). BMI at 24 months was 33.8 (SGFP), 35.3 (SG after GB) and 33.2 (GB; NS). EWL at 24 months was 67.4 (SGFP), 60.3 (SG after GB) and 58.6 (GB; NS). In the SGFP group and in the SG after GB group, the mean quality-of-life score was 1.1. In the GB group, the mean score was 0.95 (NS).Conclusions
Initial BMI was significantly higher in the SG group but was no longer significantly different from the BMI of the GB group at 12 and 24 months. Excess BMI loss was higher after SG than after GB. This reduction of BMI was considered to be a success for GB. Thus, results of SG should be considered as a success. Quality of life was not significantly different between the three groups. These results validated SG as first procedure or after failure of GB. 相似文献87.
Chafik A Benjelloun A Bouchentouf R Mikou I Ehirchiou A 《Asian cardiovascular & thoracic annals》2010,18(6):579-580
We describe a rare case of retrosternal goiter that developed on the left side of the trachea, squeezing between the trachea and the left supra-aortic vessels, and causing signs of compression and acute left upper limb ischemia in a 35-year-old woman. Her symptoms disappeared after an emergency total thyroidectomy was performed. 相似文献
88.
Samira Rostom Karima Benbouaaza Bouchra Amine Rachid Bahiri Yousra Ibn Yacoub Sanae Ali Ou Alla Redouane Abouqal Najia Hajjaj-Hassouni 《Clinical rheumatology》2010,29(7):781-788
The objectives of this study are to translate, adapt in the Moroccan cultural context, and validate in patients with ankylosing
spondylitis (AS) the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity
Index (BASDAI). The cross-cultural adaptation of the BASFI and BASDAI was obtained in accordance with the guidelines for translation
of the health status measures. Eighty-five patients with AS were included in the study. The test–retest reliability and the
internal consistency were analyzed, and both questionnaires were assessed for external construct validity. Structural validity
was analyzed with correlation matrix. Twenty-four-hour test–retest reliability was good: BASFI intraclass correlation coefficient
(ICC) = 0.96 (confidence interval (CI) at 95%, 0.93–0.97), BASDAI ICC = 0.93 (CI at 95%, 0.90–0.95). Cronbach’s alpha was
0.90 for the BASFI and 0.86 for BASDAI. The construct validity of the instruments was evaluated. The BASFI showed a strong
validity when correlating its results with Schober’s test (r = −0.56), occipital wall distance (r = 0.46), chest expansion (r = −0.46), BASDAI (r = 0.54), Bath Ankylosing Spondylitis Metrology Index (r = 0.70), Bath Ankylosing Spondylitis Global Score (BAS-G; r = 0.58), Bath Ankylosing Spondylitis Radiology Index (r = 0.61), and the radiological changes in sacroiliac joints (r = 0.54). A good correlation was observed between the BASDAI and the spinal pain (r = 0.53), the number of nocturnal awakenings (r = 0.57), the morning stiffness (r = 0.65), the enthesic index (r = 0.47), the BAS-G (r = 0.53), the BASFI (r = 0.54), and the erythrocyte sedimentation rate (r = 0.41; for all p < 0.001). The correlation matrix showed an intermediate correlation between items. The Moroccan version of the BASFI and
the BASDAI showed adequate reliability and validity. These instruments can be used in the clinical evaluation of Moroccan
and Arabic-speaking patients with AS. 相似文献
89.
90.
Crépeaux G Bouillaud-Kremarik P Sikhayeva N Rychen G Soulimani R Schroeder H 《Toxicology letters》2012,211(2):105-113
Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants originated from incomplete combustion processes. Ingestion of contaminated food is the main route of exposure for humans. These molecules are able to cross the placental barrier and are also found in breast milk. Since PAHs are neurotoxic agents, the potential adverse effects of a perinatal exposure of the developing brain is a key issue for public health especially concerning PAH mixture. In this study, female rats were exposed trough diet to a mixture of 16 PAHs, at doses of 2 μg/kg/day or 200 μg/kg/day during gestation and 1.5 μg/kg/day or 150 μg/kg/day during breast-feeding period. To assess late neurotoxic effects in male offsprings, behavioural and cognitive tests were carried out and histochemical analyses using cytochrome oxidase as a cerebral metabolism marker were performed on adult animals. Results showed that anxiety-related behaviours significantly increased in exposed animals, but there was no significant alteration of motor activity and learning and memory abilities. Several brain areas of the limbic system showed a neuronal hypometabolism in exposed animals. This work highlights that exposure to PAHs at early stages of brain development can cause later troubles on behaviour and that PAHs are able to partly alter the central nervous system metabolism on adulthood. 相似文献