1 The e ects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. 2 Similar to SP (K i =0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high a nity [ 3 H]-substance P (SP) binding to human NK 1 receptor (K i =0.175 nM) while its a nity for [ 125 I]-neurokinin A (NKA) binding at human NK 2 receptor was markedly lower (K i =560 nM). 3 In isolated bioassays HEK-1 was a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively. 4 The responses to HEK-1 were antagonized by GR 82334 in RUB (pK B =5.6+0.07), by nepadutant in RPA (pK B =8.6+0.04) and by SR 142801 in GPI (pK B =9.0+0.2) with apparent a nities comparable to that measured against tachykinin NK 1 , NK 2 and NK 3 receptor-selective agonists, respectively. 5 Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guineapigs (ED 50 =0.1 nmol kg 71 ) and salivary secretion in anaesthetized rats (ED 50 =6 nmol kg 71 ) with potencies similar to that of SP. All these e ects were blocked by the selective tachykinin NK 1 receptor antagonist, SR 140333. 6 We conclude that HEK-1 is a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors, possesses a remarkable selectivity for NK 1 as compared to NK 2 or NK 3 receptors and acts in vivo experiments with potency similar to that of SP.

BackgroundInforming health systems and monitoring hospital performances using administrative data sets, mainly hospital discharge data coded according to International-Classification-Diseases-9edition-Clinical-Modifiers (ICD9-CM), is now commonplace in several countries, but the reliability of diagnostic coding of acute ischemic stroke in the routine practice is uncertain. This study aimed at estimating accuracy of ICD9-CM codes for the identification of acute ischemic stroke and the use of thrombolysis treatment comparing hospital discharge data with medical record review in all the six hospitals of the Florence Area, Italy, through 2015.MethodsWe reviewed the medical records of all the 3915 potential acute stroke events during 2015 across the six hospitals of the Florence Area, Italy. We then estimated sensitivity and Positive Predictive Value of ICD9-CM code-groups 433*1, 434*1 and thrombolysis code 99.10 against medical record review with clinical adjudication. For each false-positive case we obtained the actual diagnosis. For each false-negative case we obtained the primary and secondary ICD9-CM diagnoses.ResultsThe medical record review identified 1273 acute ischemic stroke events. The hospital discharge records identified 898 among those (true-positive cases),but missed 375 events (false-negative cases), and identified 104 events that were not eventually confirmed as acute ischemic events (false-positive cases). Code-group specific Positive Predictive Value was 85.7% (95%CI,74.6–93.3) for 433*1 and 89.9% (95%CI, 87.8–91.7) for 434*1 codes. Thrombolysis treatment, as identified by ICD9-CM code 99.10, was only documented in 6.0% of acute ischemic stroke events, but was 13.6% in medical record review.ConclusionsHospital discharge data were found to be fairly specific but insensitive in the reporting of acute ischemic stroke and thrombolysis, providing misleading indications about both quantity and quality of acute ischemic stroke hospital care. Efforts to improve coding accuracy should precede the use of hospital discharge data to measure hospital performances in acute ischemic stroke care.

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A series of cyclic pseudopeptides of the formula cyclo(Leu psi[CH2NH]Xaa-Gln-Trp-Phe-beta Ala), where Xaa represents the residue of an alpha-amino acid, has been synthesized in order to establish the role of the Xaa side chain for tachykinin NK-2 receptor antagonist activity. Syntheses have been carried out in solid phase with either Fmoc or Boc strategy. The antagonist potency on NK-2 receptors in the hamster isolated trachea (HT) and the rabbit isolated pulmonary artery (RPA) bioassays increases with Xaa lipophilicity; cyclo(Leu psi[CH2NH]Cha-Gln-Trp-Phe-beta Ala) and cyclo(Leu psi[CH2NH]Asp(NHBzl)-Gln-Trp-Phe-beta Ala) resulted in being the two most active antagonists (pA2 = 9.06 and 9.26 on HT, respectively). A significant linear correlation was found between pA2 values determined in HT and RPA bioassays and capacity factors measured in reversed phase HPLC. The comparison between the biological activities of cyclic hexapeptides containing or not containing the aminomethylene moiety proved the crucial role of the pseudopeptide bond for determining high antagonist potency at the NK-2 receptor.