The [Tc(N)(PNP)]2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging: in vitroand in vivo studies

The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8), by using the metal fragment [99mTc(N)(PNP3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylamine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable in aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37 degrees C. Binding properties give Kd (19.0 +/- 4.6 nmol/l) and Bmax (approximately 10(6) sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors

Seasonal differences of corticosterone metabolite concentrations and parasite burden in northern bald ibis (Geronticus eremita): The role of affiliative interactions

The reproductive season is energetically costly as revealed by elevated glucocorticoid concentrations, constrained immune functions and an increased risk of infections. Social allies and affiliative interactions may buffer physiological stress responses and thereby alleviate associated effects. In the present study, we investigated the seasonal differences of immune reactive corticosterone metabolite concentrations, endoparasite burden (nematode eggs and coccidian oocysts) and affiliative interactions in northern bald ibis (Geronticus eremita), a critically endangered bird. In total, 43 individually marked focal animals from a freeranging colony were investigated. The analyses included a description of initiated and received affiliative interactions, pair bond status as well as seasonal patterns of hormone and endoparasite levels. During the reproductive season, droppings contained parasite eggs more often and corticosterone metabolite levels were higher as compared to the period after reproduction. The excretion rate of endoparasite products was lower in paired individuals than in unpaired ones, but paired animals exhibited higher corticosterone metabolite concentrations than unpaired individuals. Furthermore, paired individuals initiated affiliative behaviour more frequently than unpaired ones. This suggests that the reproductive season influences the excretion patterns of endoparasite products and corticosterone metabolites and that affiliative interactions between pair partners may positively affect endoparasite burden during periods of elevated glucocorticoid levels. Being embedded in a pair bond may have a positive impact on individual immune system and parasite resistance

Qualit\ue0 di vita in donne con tumore al seno: influenza delle variabili socio-demografiche

L\u2019obiettivo di questo studio \ue8 quello di individuare le relazioni significative tra elementi socio-demografici e qualit\ue0 di vita nelle donne affette da tumore al seno, sottoposte a trattamento chirurgico e/o chemioterapico . MATERIALI: Studio quantitativo su un campione di 99 donne in cura presso IOV di Padova. Nel periodo tra luglio e agosto 2008, \ue8 stato somministrato il questionario validato EORTC QLQ-30 Ve 3.0 e il modulo EORTC-BR23, specifico per carcinoma mammario, con lo scopo di valutare l\u2019influenza sulla QOL di variabili demografiche ( l\u2019et\ue0, lo stato civile, il n. di figli, il ruolo sociale) e variabili cliniche (la diagnosi, la stadiazione, la fatigue, il tipo di intervento e/o trattamento), attraverso test non parametrici ed il successivo confronto dei risultati con altri studi sull\u2019argomento. RIASSUNTO: I risultati dello studio indicano una buona QOL nel complesso, eccetto che per variabili quali: preoccupazione per il futuro, fatigue, disagio per la perdita dei capelli. Inoltre, le donne pi\uf9 giovani dispongono di una migliore funzionalit\ue0 fisica in confronto alle anziane, e se single di una migliore immagine corporea e funzionalit\ue0 sociale, rispetto alle sposate. Le donne anziane, indicano una migliore QOL sul piano dell\u2019immagine corporea e della funzionalit\ue0 sociale in particolare rispetto alle recidive e/o ai trattamenti chemioterapici successivi al primo. CONCLUSIONI: La programmazione degli interventi infermieristici, in questo ambito, non pu\uf2 prescindere dalla valutazione delle variabili influenti la QOL e l\u2019utilizzo di strumenti ad hoc per la sua valutazione

Angiosarcoma of the breast: a case report

Angiosarcoma of the breast is a rare and highly aggressive vascular cancer. Here we describe a case of a 36-year-old woman with angiosarcoma of the left breast who presented with breast enlargement and a bluish red discoloration in the overlying skin. The mammographic and sono-graphic findings were aspecific and due to the color doppler findings and the discoloration of the overlying skin, an angiosarcoma was suspected. A biopsy of the area identified at the color doppler sonography was performed and the histological examination showed the presence of a low-grade angiosarcoma. Systemic examinations (CT, total body bone scintigraphy) showed no evidence of metastasis. A left modified radical mastectomy was performed and pathological examination confirmed the presence of a grade I angiosarcoma. Immunohistochemistry showed that the neoplastic cells were positive for factor VIII, CD 31 and CD 34 confirming the tumor vascular origin. The patient presents no evidence of disease 3 years after surgery. Eur. J. Oncol., 14 (4), 217-221, 200

Influenza Vaccination Effectiveness in Paediatric ‘Healthy’ Patients: A Population-Based Study in Italy

Background: Seasonal influenza can cause serious morbidity, mortality, and financial burden in pediatric and adult populations. The influenza vaccine (IV) is considered the most effective way to prevent influenza and influenza-like-illness (ILI) complications. Objective: To assess the effectiveness of the IV in a cohort of healthy children in Italy. Methods: From the Pedianet database, all healthy children aged six months–14 years between 2009–2019 were enrolled. Cox proportional-hazards models were fitted to estimate hazard ratios and the 95% confidence interval for the association between IV exposure during each season of interest (from October to April of each year) with incident influenza/ILI. Exposure was considered as a time-varying variable. Vaccine effectiveness (VE) was calculated as (1-HR) × 100. The additive and prolonged effects of IV were evaluated across the seasons. Results: We found a high IV effectiveness among healthy children. No additional or prolonged effects were found. Conclusion: Our data indicates that IV was effective in preventing influenza/ILI in healthy children. Therefore, IV should be encouraged and provided free of charge to healthy children in all the Italian regions every year, reducing disease spread and lowering the burden on the pediatric population

Central nervous system abnormalities in vaginismus

Objective: To investigate possible altered CNS excitability in vaginismus. Methods: In 10 patients with primary idiopathic lifelong vaginismus, 10 with vulvar vestibulitis syndrome accompanied by vaginismus and healthy controls we recorded EMG activity from the levator am (LA) and external anal sphincter (EAS) muscles and tested bulbocavernosus reflex (BCR). Pudendal-nerve somatosensory evoked potentials (SEPs) were tested after a single stimulus. Pudendal-nerve SEP recovery functions were assessed using a paired conditioning-test paradigm at interstimulus intervals (ISIs) of 5, 20 and 40 ms. Results: EMG in patients showed Muscular hyperactivity at rest and reduced inhibition during straining. The BCR polysynaptic R2 had larger amplitude (p < 0.01) and longer duration (p, < 0.01) in patients from both groups than in controls. In controls, paired-pulse SEPs were suppressed at the 5 ms ISI for N35-P40 (p < 0.05) and P40-N50 ms (p < 0.001) and facilitated at the 20 ms ISI for N35-P40 (p < 0.05) and P40-N50 (p < 0.05). No significant differences were found in the paired-pulse N35-P40 in patients and controls but the cortical P40-N50 at 20 ISI was facilitated in patients (p < 0.05). Conclusions: EMG activity is enhanced and the cortical SEP recovery cycle and BCR are hyperexcitable in vaginismus. Significance: The neurophysiological abnormalities in patients with vaginismus indicate concomitant CNS changes in this disorder. (C) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved

Antitumor/Antifungal Celecoxib Derivative AR-12 is a Non-Nucleoside Inhibitor of the ANL-Family Adenylating Enzyme Acetyl CoA Synthetase

AR-12/OSU-03012 is an antitumor celecoxib-derivative that has progressed to Phase I clinical trial as an anticancer agent and has activity against a number of infectious agents including fungi, bacteria and viruses. However, the mechanism of these activities has remained unclear. Based on a chemical-genetic profiling approach in yeast, we have found that AR-12 is an ATP-competitive, time-dependent inhibitor of yeast acetyl coenzyme A synthetase. AR-12-treated fungal cells show phenotypes consistent with the genetic reduction of acetyl CoA synthetase activity, including induction of autophagy, decreased histone acetylation, and loss of cellular integrity. In addition, AR-12 is a weak inhibitor of human acetyl CoA synthetase ACCS2. Acetyl CoA synthetase activity is essential in many fungi and parasites. In contrast, acetyl CoA is primarily synthesized by an alternate enzyme, ATP-citrate lyase, in mammalian cells. Taken together, our results indicate that AR-12 is a non-nucleoside acetyl CoA synthetase inhibitor and that acetyl CoA synthetase may be a feasible antifungal drug target