Cava di Caldaccoli - Ipotesi di riuso e processi generativi

"Ipotesi di riuso e processi generativi". Secondo quanto suggerito dalla prima parte del titolo, la tesi affronta il tema del recupero funzionale di un'area estrattiva dismessa che, nella fattispecie, è sita nel comune di San Giuliano Terme, in provincia di Pisa. In questa parte saranno esposte le metodologie di indagine - dal rilievo all’analisi urbanistica e sociale - indispensabili per affrontare un tema di progettazione. La seconda parte del titolo attiene non già, o non solo, a quei processi mentali che si attivano all'atto della progettazione, ma, più in dettaglio, a quegli strumenti tecnici attraverso i quali è possibile collegare in maniera visuale i processi mentali alla costruzione finale

A interface entre o fazer teatral e a terapia ocupacional: reflexos no cotidiano

This study sought to identify how theater and Occupational Therapy are in the therapeutic scene aiming to promote health and potency of life of individuals served by this. For this, we created a theater group called “Trials Performing “ that happened at the Federal University of Santa Maria in 2013 and was composed of students aged between 20 and 25 years old. The methodology of action research was used and data analysis was based on content analysis. The results showed that the participants took the group as a place where they could have a moment of reflection on their daily lives, and also that the proposed activities were alternatives to self-knowledge, that is perception of the body, its limits and potential.O presente estudo buscou identificar como o teatro e a Terapia Ocupacional se encontram na cena terapêutica visando à promoção de saúde e a potencialização da vida dos sujeitos atendidos por esta. Para isso, criou-se um grupo de teatro denominado “Experimentações Cênicas” que aconteceu na Universidade Federal de Santa Maria no ano de 2013 e foi composto por universitários com faixa etária entre 20-25 anos. Utilizou-se como metodologia a pesquisa-ação e a análise dos dados foram baseadas na análise de conteúdo. Os resultados do trabalho mostraram que os participantes tomaram o grupo como um local onde podiam ter um momento de reflexão sobre seu cotidiano e, também, que as atividades propostas foram alternativas para o autoconhecimento, ou seja, percepção do próprio corpo, limites e potencialidades deste.

Catechols: a new class of carbonic anhydrase inhibitors

Catechols adopt a peculiar binding mode to the CA active site which involves both the zinc bound water molecule and the "deep water"

Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft

2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site.

2-Mercaptobenzoxazole represents an interesting lead compound alternative to the classical sulfonamides for the development of selective carbonic anhydrase inhibitors

Discovery of New Potential Anti-Infective Compounds Based on Carbonic Anhydrase Inhibitors by Rational Target-Focused Repurposing Approaches

In academia, compound recycling represents an alternative drug discovery strategy to identify new pharmaceutical targets from a library of chemical compounds available in house. Herein we report the application of a rational target-based drug-repurposing approach to find diverse applications for our in-house collection of compounds. The carbonic anhydrase (CA, EC 4.2.1.1) metalloenzyme superfamily was identified as a potential target of our compounds. The combination of a thoroughly validated docking screening protocol, together with in vitro assays against various CA families and isoforms, allowed us to identify two unprecedented chemotypes as CA inhibitors. The identified compounds have the capacity to preferentially bind pathogenic (bacterial/protozoan) CAs over human isoforms and represent excellent hits for further optimization in hit-to-lead campaigns

MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Fludarabine, is one of the most active single agents in the treatment of chronic lymphocytic leukemia (CLL). Over time, however, virtually all CLL patients become fludarabine-refractory. To elucidate whether microRNAs are involved in the development of fludarabine resistance, we analyzed the expression of 723 human miRNAs before and 5-days after fludarabine mono-therapy in 17 CLL patients which were classified as responder or refractory to fludarabine treatment based on NCI criteria.</p> <p>Results</p> <p>By comparing the expression profiles of these two groups of patients, we identified a microRNA signature able to distinguish refractory from sensitive CLLs. The expression of some microRNAs was also able to predict fludarabine resistance of 12 independent CLL patients. Among the identified microRNAs, miR-148a, miR-222 and miR-21 exhibited a significantly higher expression in non-responder patients either before and after fludarabine treatment. After performing messenger RNA expression profile of the same patients, the activation of p53-responsive genes was detected in fludarabine responsive cases only, therefore suggesting a possible mechanism linked to microRNA deregulation in non-responder patients. Importantly, inhibition of miR-21 and miR-222 by anti-miRNA oligonucleotides induced a significant increase in caspase activity in fludarabine-treated p53-mutant MEG-01 cells, suggesting that miR-21 and miR-222 up-regulation may be involved in the establishment of fludarabine resistance.</p> <p>Conclusions</p> <p>This is the first report that reveals the existence of a microRNA profile that differentiate refractory and sensitive CLLs, either before and after fludarabine mono-therapy. A p53 dysfunctional pathway emerged in refractory CLLs and could contribute in explaining the observed miRNA profile. Moreover, this work indicates that specific microRNAs can be used to predict fludarabine resistance and may potentially be used as therapeutic targets, therefore establishing an important starting point for future studies.</p

Consensus care recommendations for alfapump® in cirrhotic patients with refractory or recurrent ascites

BACKGROUND: The alfapump® is an implantable class III medical device that pumps ascitic fluid from the peritoneal space to the urinary bladder from where it is excreted. The pump reduces or abrogates the need for repeated paracentesis in patients with recurrent or refractory ascites. AIMS: To improve outcomes for alfapump® implantation and pre- and post-implant patient management in both clinical trial and real-world settings by development of consensus recommendations. METHODS: The alfapump® working group consisting of hepatologists and surgeons with extensive experience in implantation of the alfapump® and patient management met on two occasions: (1) to determine the key areas where recommendations should be made; and (2) to discuss the experiences of the working group within those areas and formulate draft statements. Developed statements were submitted to the group and consensus sought on relevance and wording through a collaborative iterative approach in order to consolidate the recommendations into consensus statements. Only recommendations agreed upon unanimously were included. RESULTS: Twenty-three consensus recommendations were developed in the areas of pre-implantation procedure, (three statements), surgical implant procedure (11 statements), immediate post-implant care (three statements) and long-term management (six statements). CONCLUSIONS: The consensus statements are a valuable reference resource for physicians managing patients with the alfapump® and for those considering management strategies for patients with refractory ascites

Consensus care recommendations for alfapump® in cirrhotic patients with refractory or recurrent ascites.

BACKGROUND The alfapump® is an implantable class III medical device that pumps ascitic fluid from the peritoneal space to the urinary bladder from where it is excreted. The pump reduces or abrogates the need for repeated paracentesis in patients with recurrent or refractory ascites. AIMS To improve outcomes for alfapump® implantation and pre- and post-implant patient management in both clinical trial and real-world settings by development of consensus recommendations. METHODS The alfapump® working group consisting of hepatologists and surgeons with extensive experience in implantation of the alfapump® and patient management met on two occasions: (1) to determine the key areas where recommendations should be made; and (2) to discuss the experiences of the working group within those areas and formulate draft statements. Developed statements were submitted to the group and consensus sought on relevance and wording through a collaborative iterative approach in order to consolidate the recommendations into consensus statements. Only recommendations agreed upon unanimously were included. RESULTS Twenty-three consensus recommendations were developed in the areas of pre-implantation procedure, (three statements), surgical implant procedure (11 statements), immediate post-implant care (three statements) and long-term management (six statements). CONCLUSIONS The consensus statements are a valuable reference resource for physicians managing patients with the alfapump® and for those considering management strategies for patients with refractory ascites

Inhibition of the newly discovered β‑carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with inorganic anions and small molecules

The protozoan pathogen Trichomonas vaginalis encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the β-class. One of these enzymes, T. vaginalis carbonic anhydrase 1 (TvaCA1), was recently cloned and characterized by our group, and its X-ray crystal structure reported. No inhibitors of this enzyme were reported up until now. Here we investigated the inhibition of TvaCA1 with inorganic anions and small molecules and observed that thiocyanate, cyanide, selenite, selenocyanate and divanadate are sub-millimolar inhibitors, whereas sulfamide, sulfate, phenylboronic acid and phenylarsonic acid are micromolar inhibitors. Finding effective TvaCA1 inhibitors may be useful for developing new antiprotozoan drugs.acceptedVersionPeer reviewe