966 resultados para Panzani, Gregorio, -1662


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Manuscrito encuadernado con: Concilia Magnae Britanniae et Hiberniae a Synodo Verolamiensi... (XVIII/68-TG)

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Manuscrito encuadernado con: Concilia Magnae Britanniae et Hiberniae a Synodo Verolamiensi...(XVIII/68-TG)

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Lidocaine bears in its structure both an aromatic ring and a terminal amine, which can be protonated at physiological pH, linked by an amide group. Since lidocaine causes multiple inhibitory actions on nicotinic acetylcholine receptors (nAChRs), this work was aimed to determine the inhibitory effects of diethylamine (DEA), a small molecule resembling the hydrophilic moiety of lidocaine, on Torpedo marmorata nAChRs microtransplanted to Xenopus oocytes. Similarly to lidocaine, DEA reversibly blocked acetylcholine-elicited currents (IACh) in a dose-dependent manner (IC50 close to 70 μM), but unlike lidocaine, DEA did not affect IACh desensitization. IACh inhibition by DEA was more pronounced at negative potentials, suggesting an open-channel blockade of nAChRs, although roughly 30% inhibition persisted at positive potentials, indicating additional binding sites outside the pore. DEA block of nAChRs in the resting state (closed channel) was confirmed by the enhanced IACh inhibition when pre-applying DEA before its co-application with ACh, as compared with solely DEA and ACh co-application. Virtual docking assays provide a plausible explanation to the experimental observations in terms of the involvement of different sets of drug binding sites. So, at the nAChR transmembrane (TM) domain, DEA and lidocaine shared binding sites within the channel pore, giving support to their open-channel blockade; besides, lidocaine, but not DEA, interacted with residues at cavities among the M1, M2, M3, and M4 segments of each subunit and also at intersubunit crevices. At the extracellular (EC) domain, DEA and lidocaine binding sites were broadly distributed, which aids to explain the closed channel blockade observed. Interestingly, some DEA clusters were located at the α-γ interphase of the EC domain, in a cavity near the orthosteric binding site pocket; by contrast, lidocaine contacted with all α-subunit loops conforming the ACh binding site, both in α-γ and α-δ and interphases, likely because of its larger size. Together, these results indicate that DEA mimics some, but not all, inhibitory actions of lidocaine on nAChRs and that even this small polar molecule acts by different mechanisms on this receptor. The presented results contribute to a better understanding of the structural determinants of nAChR modulation.

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Photostat copy of a petition from ferrymen Francis Hudson and John Burrage requesting the General Court coin twopenny and fourpenny pieces for change so the ferrymen could accommodate customers attempting to pay with larger currency denominations.

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This unbound commonplace book was kept by John Holyoke during 1662 and 1663. The volume contains chiefly religious quotations and sermon notes (possibly of sermons preached by Holyoke himself), in English, Latin and Greek. Both ends of the volume were used to begin writing: the front page reads “Johannes Holyoke, adjunctu occupatu, May-1663” and the rear page reads “Johannes Holyoke [illegible] 1662.” The texts do not follow a straight tête-bêche model, where one text is upside down in relation to the other; rather, the texts change direction several times within the volume. The volume also includes part of letter sent to Holyoke’s grandfather Pynchon, September 16, 16?? [date illegible], as well as a series of alphabetically arranged quotations.

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Mode of access: Internet.

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At head of t.-p.: Colecção sociologica [XXI].