Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.

Background-The role of inflammatory markers is not well defined for either diagnosis or treatment of pericarditis. The aim of this study is to prospectively evaluate the frequency of high-sensitivity C-reactive protein (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. Key Words: C-reactive protein Ⅲ diagnosis Ⅲ pericarditis Ⅲ prognosis Ⅲ therapy T here are no universally accepted criteria for the diagnosis of pericarditis. In clinical practice, some criteria are usually adopted (chest pain, pericardial rubs, PR depression and diffuse ST-segment elevation on ECG, pericardial effusion; at least 2 of 4 should be present for the diagnosis), and the role of inflammatory markers (eg, C-reactive protein [CRP]) is not well defined. [1][2][3][4][5] Clinical Perspective on p 1097Pericarditis is an inflammatory disease, and evidence of elevated markers of inflammation could support the diagnosis. Moreover, the same length of therapy is empirical, and markers of inflammation (ie, CRP) may be a useful guide for treatment because it can be assumed that anti-inflammatory therapy should be continued until the inflammation is extinguished. On this basis, persistent elevation of inflammatory markers, as evidence of disease activity, could be associated with a worse prognosis.The aim of the present study is to prospectively evaluate the frequency of high-sensitivity CRP (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. Methods PatientsAll consecutive cases of acute pericarditis within 24 hours from symptom onset were screened for inclusion in a prospective cohort study from August 2005 to August 2007. A final diagnosis of idiopathic or viral acute pericarditis was reached at the end of the diagnostic assessment, which included chest x-ray, echocardiography, viral serology, and other specific testing according to the initial clinical presentation. Pericardiocentesis was done when a bacterial or neoplastic etiology was suspected or in case of cardiac tamponade or severe pericardial effusion without response to medical therapy after 1 week. Patients with a final diagnosis of viral and idiopathic pericarditis were included in the Received August 27, 2010; accepted January 10, 2011. Figure 1. The diagnosis of acute pericarditis was done according to available published criteria. [1][2][3][4][5][6][7][8] Diagnostic criteria included pericarditic typical chest pain, pericardial friction rubs, widespread ST-segment elevation or PR depressions not reported previously, and new or worsening pericardial effusion. A clinical diagnosis of acute pericarditis was made when at least 2 of these criteria were present. Criteria for the diagnosis of recurrence included recurrent pain and 1 or more of the following signs: fever, pericardial friction rub, ECG changes, echocardiographic evidence of pericardial effusion, and an elevation in th...

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Complex formation processes between the 39-mer residue peptide fragment of human prion protein, HuPrP(76-114), and copper(II) ions have been studied by potentiometric, UV-vis, circular dichroism (CD), electron paramagnetic resonance, and electrospray ionization mass spectrometry methods. This peptide consists of 39 amino acid residues and contains two histidines (His77 and His85) belonging to the octarepeat domain and two histidines (His96 and His111) outside this domain. It was found that HuPrP(76-114) is able to bind 4 equiv of metal ions and all histidyl residues are independent, except nonequivalent metal binding sites in the oligonuclear species. Imidazole nitrogen donor atoms are the primary and exclusive metal binding sites below pH 5.5 in the form of various macrochelates. The macrochelation slightly suppresses, but cannot prevent, the deprotonation and metal ion coordination of amide functions, resulting in the formation of (N(im),N(-)), (N(im),N(-),N(-)), and (N(im),N(-),N(-),N(-))-coordinated copper(II) complexes in the pH range from 5.5 to 9. CD spectroscopy results gave clear evidence for the differences in the metal binding affinity of the histidyl sites according to the following order: His111 > His96 >> His77 approximately His85. Among the oligonuclear complexes, the formation of di- and tetranuclear species seems to be favored over the trinuclear ones, at pH values beyond the physiological ones. This phenomenon was not observed in the complex formation reactions of HuPrP(84-114), a peptide fragment containing only one histidyl residue from the octarepeat. As a consequence, the data support the existence of cooperativity in the metal binding ability of this peptide probably due to the presence of two octarepeat sequences of the dimeric octarepeat domain of HuPrP(76-114) at basic pH values.