Long-term functional evaluation of the treated kidney in a prospective series of patients who underwent laparoscopic partial nephrectomy for small renal tumors.

Background: Renal scintigraphy may allow long-term monitoring of ischemic damage after partial nephrectomy (PN). Objective: Evaluate use of renal scintigraphy for evaluating long-term effects of warm ischemia on renal function in patients with a normal contralateral kidney. Design, setting, and participants: We prospectively examined kidney function of 54 patients who underwent laparoscopic PN (LPN). Minimum follow-up time was 4 yr. Intervention: LPN was performed with warm ischemia by transperitoneal or retroperitoneal approach. Measurements: Demographic, perioperative, and pathologic data and postoperative complications were registered. Split renal function (SRF) and effective renal plasma flow (ERPF) were evaluated by renal scintigraphy preoperatively, at 3 and 12 mo postoperatively, then yearly. Baseline weighted differentials (b-WDs) of both SRF and ERPF in the affected kidney were calculated between baseline condition and every time point. Multivariate linear regression was used to find independent variables for increased b-WDs at 3 and 48 mo. P values<0.05 were considered significant. Results and limitations: The SRF and ERPF of kidneys treated by LPN decreased significantly at month 3 and subsequently remained stable through the duration of follow-up. Conversely, neither serum creatinine nor estimated glomerular filtration rate changed significantly during follow-up. The regression model showed statistical significance at month 3 for warm ischemia time (WIT) and age, whereas at 48 mo, statistical significance was reached by WIT alone. No new onset of cardiovascular disease was registered. No evidence of local recurrence was recorded with computed tomography scan. Our study may be underpowered due to small sample size; however, this is one of the largest long-term prospective series using renal scintigraphy to evaluate the renal function after LPN. Conclusions: WIT contributes to irreversible kidney damage observed at month 3 that does not appear to worsen

Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.

Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonu-cleotides to deoxyribonucleotides, we have now prepared and evaluated 5′-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 μM for the UDP analogue 5′-deoxy-5′- N-(phosphon-acetyl)uridine sodium salt (amide) to 600 μM for the CDP analogue 5′- O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100–500 μM concentrations, whereas ADP analogue 5′- N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5′-deoxy-5′- N-(phos-phon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 μM) against HSV-2 and a modest inhibitory activity (EC50: 110 μM) against HIV-1, respectively

Hindered nucleoside analogs as antiflaviviridae agents

Abstract Flaviviridae are an important family of viruses, responsible for widely spread diseases such as dengue and West Nile fever and hepatitis C. Despite the severity of the related diseases, no effective antiviral treatments for infection are available. Following our discovery of adenosine-hindered analogs as potent antiflaviviridae agents, we have continued our investigation on guanosine and inosine derivatives, which were evaluated for activity against BVDV, YFV, DENV, and WNV viruses in cell-based assays. The present study allowed us to identify some newer features that led to improve the antiviral potency (down to the µM range) and to selectively inhibit BVDV and YFV viruses. The molecular modeling results were consistent with the hypothesis that test analogs act as RNA-dependent RNA polymerase (RdRp) inhibitors by interacting with a surface allosteric binding pocket

Anti-flavivirus activity of different tritylated pyrimidine and purine nucleoside analogues

A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′-O-tritylated and the 5′-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5′O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV

The antioxidants and pro-antioxidants network: an overview.

Living beings have evolved over the past two billion years through adaptation, to an increasing atmospheric oxygen concentration, by both taking advantage of oxygen activating function and developing a complex control network. In these regards, potentially damaging species (reactive oxygen, nitrogen and chlorine species) arise as by-products of metabolism and also work as physiological mediators and signalling molecules. Oxidative stress may be an important factor in numerous pathological conditions, i.e. infection if micronutrients are deficient. Levels of these species are controlled by the antioxidant defence system, which is composed by antioxidants and pro-antioxidants. Several components of this system are micronutrients (e.g. vitamins C and E), are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide dismutase) or are produced by specific endogenous pathways. The antioxidant defences act, to control levels of these species, as a coordinated system where deficiencies in one component may affect the efficiency of the others. In this network some of the components act as direct antioxidants whereas others act indirectly (pro-antioxidants) either by modulation of direct agents or by regulation of the biosynthesis of antioxidant proteins. Thus, entities usually not considered as antioxidants, also act efficiently counteracting damaging effects of oxidative species. In this contest, the design of new molecules that take into account synergistic interactions among different antioxidants, could be useful both to address mechanistic studies and to develop possible therapeutic agents. In this review the principal categories of antioxidants and pro-antioxidants that goes from vitamins through phyto-derivatives to minerals, are critically reviewed, with particular emphasis on structure-function considerations, together with the perspective opened, in the design of possible therapeutic agents, by the antioxidants interplay

Metodo per associare una immagine a una sequenza di pressioni di tasti inserita tramite una tastiera

In un telefono cellulare provvisto di un display e di una tastiera, una immagine viene associata a una sequenza di pressioni di tasti inserita tramite la tastiera e viene visualizzata tramite il display. La associazione tra l’immagine e la sequenza di pressioni di tasti è realizzata definendo una area di immagine, associando a ciascun tasto della tastiera una rispettiva porzione di area dell’area di immagine, associando, a ciascuna coppia di successive pressioni di tasti, una rispettiva linea, la quale è definita nell’area di immagine e passa per le porzioni di area associate ai tasti subenti la coppia di pressioni successive, in modo da definire un insieme di linee associato alla sequenza di pressioni di tasti, e determinando l’immagine sulla base dell’insieme di linee