Publications by authors named "Viola G"

A representative series of structural analogs of the antimitotic tripeptides hemiasterlins have been designed and synthesized, as potential inhibitors of tubulin polymerization. Relying also on a computational approach, we aimed to explore unknown extensive changes at the C-fragment, by incorporating the conformationally required double bond into five- and six-membered rings. Key steps of the synthetic strategy are a dynamic resolution affording the A-fragment in 97 % ee and the preparation of six new cyclic C fragments, all potentially able to interact with tubulin by means of H bonds.

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Aim: Psoriasis is a systemic inflammatory immune-mediated skin disease. Recently a relationship with metabolic syndrome in terms of psoriasis severity and response to therapy was observed.

Methods: We performed an open-label randomized controlled study to evaluate the role of a nutraceutical containing Q10 coenzyme, Krill-oil, lipoic acid, resveratrol, Vitis vinifera seed oil, vitamin E and selenium in addition to etanercept therapy for patients affected by psoriasis and metabolic syndrome.

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In search of new compounds with strong antiproliferative activity and simple molecular structure, we designed a novel series of agents based on the 2-amino-3-alkoxycarbonyl/cyano-5-arylethylthiophene scaffold. The presence of the ethyl spacer between the 2',5'-dimethoxyphenyl and the 5-position of the thiophene ring, as well as the number and location of methoxy substitutents on the phenyl ring, played a profound role in affecting the antiproliferative activity. Among the synthesized compounds, we identified the 2-amino-3-cyano-[2-(2,5-dimethoxyphenyl)ethyl] thiophene 2c as the most promising derivative against a wide panel of cancer cell lines (IC50=17-130 nM).

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Objectives: As infection is a severe complication of Ommaya reservoirs (OR), and existing data is limited, herein we describe the largest study of the clinical manifestations and treatment outcomes of Ommaya reservoir-related infections (ORRI).

Methods: We retrospectively reviewed the records of all patients at our institution who had an OR placed, and developed a definite device-related infection between 2001 and 2011.

Results: Among 501 OR placements, 40 patients (8%) developed an ORRI.

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Objective: The rate of postmastectomy tissue expander (TE) infection remains excessively high, ranging between 2% and 24%. We hypothesized that current perioperative antimicrobial regimens utilized for breast TE reconstruction may be outdated as a result of recent changes in microflora and susceptibility patterns.

Design And Methods: We reviewed the records of all patients who had a TE reconstructive procedure and developed a definite breast TE infection between 2003 and 2010 at MD Anderson Cancer Center.

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The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3',4',5'-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity.

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The East African Orogen, extending from southern Israel, Sinai and Jordan in the north to Mozambique and Madagascar in the south, is the world́s largest Neoproterozoic to Cambrian orogenic complex. It comprises a collage of individual oceanic domains and continental fragments between the Archean Sahara-Congo-Kalahari Cratons in the west and Neoproterozoic India in the east. Orogen consolidation was achieved during distinct phases of orogeny between ∼850 and 550 Ma.

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A small library of both [2,3-h] and [3,2-f] novel pyrroloquinolines equipped with an azolylmethyl group was designed and synthesized as nonsteroidal CYP19 aromatase inhibitors. The results showed that azolylmethyl derivatives 11, 13, 14, 21, and 22 exhibited an inhibitory potency on aromatase comparable to that of letrozole chosen as a reference compound. When assayed on CYP11B1 (steroid-11β-hydroxylase) and CYP17 (17α-hydroxy/17,20-lyase), compound 22 was found to be the best and most selective CYP19 inhibitor of them all.

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Meningitis is the main manifestation of cryptococcosis in adult systemic lupus erythematosus (SLE) patients, and other organs and systems, such as the lungs, are rarely affected in this fungal infection. To our knowledge, no case of pulmonary cryptococcosis has been described in the pediatric lupus population. Therefore, we report herein one patient with childhood SLE (C-SLE) and Sjögren's syndrome overlap that presented encapsulated Cryptococcus yeast cells in lung tissue.

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For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases.

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Forkhead transcription factors (FOXO) are downstream targets of the phosphoinositol-3-kinase (PI3K) protein kinase B (PKB) signaling cascade and play a pivotal role in cell differentiation, cell cycle and apoptosis. We found that cells from prednisone-resistant T-acute lymphoblastic leukemia (T-ALL) patients showed cytoplasmic localization of FOXO3 in comparison to prednisone-sensitive patients suggesting its inactivation. To determine the impact of FOXO3, T-ALL cells were infected with a 4OH-tamoxifen-regulated, phosphorylation-independent FOXO3(A3)ERtm allele.

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Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.

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Article Synopsis
  • The use of cardiac implantable electronic devices (CIED) has surged, but infections related to these devices have also significantly increased despite preventive measures.
  • An in vitro study examined how well bacteria adhere to CIED surfaces made of polyurethane and titanium using common infectious microorganisms.
  • Results showed that bacteria adhered more to polyurethane than titanium, suggesting that using more titanium in CIED construction could help reduce infection rates, especially right after implantation; further animal studies are needed to confirm these findings.
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TR-644 is a novel combretastatin A-4 (CA-4) analogue endowed with potent microtubule depolymerizing activity superior to that of the lead compound and it also has high affinity to colchicines binding site of tubulin. We tested TR-644 anti-angiogenic effects in human umbilical endothelial cells (HUVEC). It showed no significant effects on the growth of HUVEC cells at concentrations below 1,000 nM, but at much lower concentrations (10-100 nM) it induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the disruption of the microtubule network.

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Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level.

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About 20 species of rapidly growing mycobacteria species that are capable of infecting human beings and causing bloodstream infections have been identified. Many more of these species are being discovered worldwide, especially in resource-poor settings. These microorganisms have been known to cause outbreaks and pseudo-outbreaks.

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Rapidly growing mycobacteria (RGM) are environmental organisms capable of causing a wide spectrum of diseases. We identified 116 cancer patients with RGM. Mycobacterium mucogenicum was the leading cause of disease.

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The serine/threonine kinase AMP-activated protein kinase (AMPK) and its downstream effectors, including endothelial nitric oxide synthase and BCL-2, are hyperactivated in B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) cells with MLL gene rearrangements. We investigated the role of activated AMPK in supporting leukemic cell survival and evaluated AMPK as a potential drug target. Exposure of leukemic cells to the commercial AMPK inhibitor compound C resulted in massive apoptosis only in cells with MLL gene rearrangements.

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Antitumor agents that bind to tubulin and disrupt microtubule dynamics have attracted considerable attention in the last few years. To extend our knowledge of the thiazole ring as a suitable mimic for the cis-olefin present in combretastatin A-4, we fixed the 3,4,5-trimethoxyphenyl at the C4-position of the thiazole core. We found that the substituents at the C2- and C5-positions had a profound effect on antiproliferative activity.

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Psoriasis and tuberculosis (TB) are 2 conditions with high prevalence in the general population, often present simultaneously in the same patient. The crucial cytokine involved in the pathogenesis of psoriasis, tumor necrosis factor alpha (TNF-alpha), also is important in defending against mycobacteria. Therefore, it is important to screen patients for a latent TB infection (LTBI) while they are undergoing treatment with TNF-alpha antagonists.

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The ν=5/2 anti-Pfaffian state and the ν=2/3 state are believed to have an edge composed of counterpropagating charge and neutral modes. This situation allows the generation of a pure thermal bias between two composite edge states across a quantum point contact as was experimentally established by Bid et al. [Nature 466, 585 (2010)].

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Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia and is an important risk factor for mortality and morbidity related mainly to an increased risk of cerebrovascular events and heart failure.An observational cross-sectional study was performed to evaluate the use of healthcare resources (including hospital and outpatient care) by patients with AF in the Lazio region (central Italy), from 1 January 2006 to 31 December 2008.Atrial fibrillation is an important source of healthcare resource utilization because of repeated emergency room visits, hospital admissions, outpatient consultations and procedures and extensive use of laboratory tests and pharmacological treatments.

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