Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron

Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE₂ induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as “teleantagonism”. We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: (i) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; (ii) a nonselective COX inhibitor was tested against PNN sensitization by IL-1β; (iii) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons.     

The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options

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Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.     

血液提取物在前牙软组织美学方面的应用

如何恢复前牙美学区退缩或缺损的软组织,是目前口腔医学的研究热点。血液提取物因制备技术简单、使用安全且含有高浓度生长因子,近年来被广泛应用于软硬组织增量技术。根据制备方法的不同,血液提取物可分为三代：第一代富血小板血浆、第二代富血小板纤维蛋白和第三代改良富血小板纤维蛋白、浓缩生长因子和注射型富血小板纤维蛋白。本文将介绍各种血液提取物的历史和制备方法,并对其在前牙软组织美学方面的研究及应用进展做一综述。     

Estrogen receptors and the regulation of neural stress responses

It is now well established that estrogens can influence a panoply of physiological and behavioral functions. In many instances, the effects of estrogens are mediated by the 'classical' actions of two different estrogen receptors (ERs), ERα or ERβ. ERα and ERβ appear to have opposing actions in the control of stress responses and modulate different neurotransmitter or neuropeptide systems. Studies elucidating the molecular mechanisms for such regulatory processes are currently in progress. Furthermore, the use of ERα and ERβ knockout mouse lines has allowed the exploration of the importance of these receptors in behavioral responses such as anxiety-like and depressive-like behaviors. This review examines some of the recent advances in our knowledge of hormonal control of neuroendocrine and behavioral responses to stress and underscore the importance of these receptors as future therapeutic targets for control of stress-related signaling pathways.     

Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial

Background  

Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn’s disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP.