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activation of these neurons increases dopamine and norepinephrine in these areas, and excites histaminergic tuberomammillary neurons increasing histamine levels there.
تفعيل هذه الخلايا العصبية يزيد مستويات الدوبامين ويزيد نورإبينيفرين في هذه الأجزاء الدماغية، ويثير histaminergic tuberomammillary neurons ردود الفعل العصبية المتزايدة الهستامين مستويات هناك.
loratadine, 1mg/1ml, syrup, oral, 100ml, bottle, non sedating, anti-histamine, clara
لوراتادين، ١مجم/١مل، شراب، عن طريق الفم ، ١٠٠مل، زجاجة، غير مهدئ، مضاد للحساسية، كلارا
just as there are inhibitors as yet undiscovered there could also be other histamine receptor agonists in decomposed fish. although not previously suggested, this is yet another possible explanation for the dose/response anomalies of scombroid poisoning, that the severity of the response is due to an increase of total histamine-like bioactivity. there is some precedence for this idea, since there is already one example of a free histidine-derived agonist active at one of the other histaminergic receptors. gizzerocine is a small peptide (okazaki et al., 1983) found in poor quality feed produced by overheating decomposed fish material. it is a potent h2 histamine receptor agonist, 200 more potent than histamine itself (masamura et al., 1985) and kills poultry by causing excessive excretion of digestive acids. although certainly not implicated in scombroid poisoning, gizzerocine provides an excellent example of a previously unknown and histidine-derived agonist active at a histamine receptor. based on this precedent there may be other histidine-derived compounds in scombroid poisoning-implicated fish that could bind to histaminergic receptors, and thus it is not possible to rule out the existence of other agonists without comparing the total histamine receptor bioactivity with the predicted activity based on known histamine concentrations in outbreak-implicated sample extracts. if there were other histaminergic receptor agonists for the various histaminergic receptors with activity comparable to that shown by gizzerocine for h2 receptors, low levels of bioactive compounds could be enough to cause illness. the application of activity-based assays, with observable end points triggered by receptor binding, would thus be very useful. a potentially powerful approach to exploring the possible mechanisms of scombroid poisoning and for discovering histaminergic bioactives would be a combination of lc-ms and an activity-based assay to screen for ‘‘scombrotoxins’’ in outbreak-implicated fish samples. indeed, one of the first methods officially approved for the detection of histamine was a biological method (aoac, 1954) based on the contraction of guinea pig ileum. this assay is actually responding to h1-agonist activity and this approach could be updated and extended by developing cell lines rich in the relevant histaminergic receptors. transvected cells could be used for this purpose since the h1 receptor has been cloned (fujimoto et al., 1993) as have the h2 (gantz et al., 1991), h3 (lovenberg et al., 1999) and h4 (liu et al., 2001) receptors. the viability of cell assays in the study of other seafood toxins in samples from outbreakimplicated sample extracts has been demonstrated (manger et al., 1995) and proved especially powerful when combined with analysis of individual lc-ms fractions (dickey et al., 1999; dickey, 2008); combined activity and structure information were easily obtained, even for toxins and toxin metabolites for which no purified standards were available. a similar approach to studying scombroid poisoning is much needed. any one of the above hypothesized explanations may apply to some cases of scombroid poisoning and not to others, since scombroid poisoning describes a collection of symptoms and circumstances and thus may not have a single specific mechanism of toxicity
وكما أن هناك مثبطات لم يتم اكتشافها بعد، فقد يكون هناك أيضًا ناهضات مستقبلات هيستامين أخرى في الأسماك المتحللة. على الرغم من أنه لم يتم اقتراحه سابقًا، إلا أن هذا تفسير محتمل آخر لشذوذ الجرعة/الاستجابة للتسمم بالسكومبرويد، وأن شدة الاستجابة ترجع إلى زيادة إجمالي الهيستامين مثل النشاط الحيوي. هناك بعض الأسبقية لهذه الفكرة، حيث يوجد بالفعل مثال واحد على ناهض مشتق من الهيستامين الحر نشط في أحد الهيستامينيات الأخرى