Organocatalytic stereodivergent synthesis of β,β-disubstituted-α-aminoacids

In this work, we present an organocatalytic stereodivergent synthesis of β,β-disubstituted-α-aminoacids using arylidene azlactones as starting materials. The developed two step synthesis involves a sequential catalysis approach, in which two different catalysts act sequentially to control the absolute configuration of two different stereocenters. With an accurate selection of the catalysts absolute configuration it is possible to obtain all the stereoisomers of the product. The first synthetic step is a catalytic asymmetric transfer hydrogenation of the azlactone C=C double bond. A Jacobsen type thiourea and a Hantzsch ester were chosen as chiral catalyst and hydride donor, respectively. Different azlactones, Hantzsch esters and thioureas were synthetized and tested in the asymmetric transfer hydrogenation to achieve the best stereoselectivity. The second step involves a dynamic kinetic resolution on the reduced azlactone, through a nucleophilic addition to the carbonyl moiety promoted by a bifunctional chiral catalyst. A wide range of nucleophiles and organocatalysts were tested; the best results were reached with alcohols as nucleophiles and squaramide-based cinchona alkaloids as a chiral catalysts. With the optimized conditions two stereodivergent syntheses were then performed, enabling the selective obtainment of both diastereoisomeric product with high enantioselectivities

Antioxidant Activity of pomegranate (Punica granatum L.) Extracts in Cell-free and Cell culture Systems

Punica granatum L. (Punicaceae) fruits have been widely used in folk medicine; a number of therapeutic properties of pomegranate preparations has been reported (Duke and Ayensu, 1985), including vermifugal, taenicidal, astringent, antispasmodic, antihysteric, diuretic, carminative, emmenagogue and antiinflammatory. More recently, De Nigris et al. (2005) reported that pomegranate juice may exert a preventive role in atherosclerotic disease. These actions have been ascribed to the presence of anthocyanins, cyanidin, ellagitannins, punicalagin and vitamin C. It has been reported (Gil et al., 2000) that industrial pomegranate juice (obtained from both arils and rinds) displays antioxidant activity against reactive oxygen species; this activity has been found to be higher than that of red wine and green tea; arils-only juice seems to be less active than whole fruit juice. Further studies, including one from our group (Ricci et al., in press), dealt with the antioxidant activity of whole, arils or rinds pomegranate juices/extracts: however, these research works have been carried out exclusively in cell-free systems

Cyclic Vomiting Syndrome in Children

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CV

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Valutazione di Health Technology Assessment del sistema di sanificazione biologico a base di probiotici del genere Bacillus (PCHS)

Le infezioni correlate all’assistenza: priorità per la salute pubblica Epidemiologia delle infezioni correlate all’assistenza in Italia e loro impatto per la salute pubblica Sistemi di sanificazione attualmente disponibili in Italia Il Probiotic Cleaning Hygiene System (PCHS): caratteristiche della tecnologia, aspetti di efficacia e sicurezza Un sistema di sanificazione a base di probiotici per la riduzione delle infezioni correlate all’assistenza e la resistenza antimicrobica: analisi dell’impatto sul budget Impatto ambientale per la salute pubblica degli attuali sistemi di sanificazione di ambienti/superfici in setting assistenziale e comunitario e potenziali benefici dei nuovi sistemi innovativi Analisi delle principali raccomandazioni nazionali su sanificazione e disinfezione degli ambienti sanitari Valutazione etica dell’utilizzo del Probiotic Cleaning Hygiene System (PCHS) in Italia Elementi chiave per il processo decisional

Novel catalytic systems and methidologies for organocatalysis and photocatalysis

The thesis is divided into two main parts. In the first one organocatalysis is briefly introduced. Then, new enantiopure trityl pyrrolidines modified with an ionic tag are described. All the catalysts are tested in the benchmark Michael addition reaction to prove their activity and stereoselectivity. In the second part, photocatalysis is first introduced. Then, four different research projects are described. At first, the construction of a hybrid metal-organo-photoredox catalyst is described. The hybrid photocatalysts obtained were employed in the benchmark photoredox alkylation of aldehydes. Then, the use of visible light and a photocatalytic system for the cyclization of iodoaryl vinyl derivatives to tetrahydroquinoline structures is described. In addition, the reaction can also be performed using flow-chemistry. Finally, a mechanistic proposal based on some mechanistic studies is described. Third, a new photoredox catalyzed transformation for the synthesis of 2,3-dihydrofurans is reported. Depending on the involved starting materials, different pathways have arisen. A mechanistic proposal based on reported literatures and experimental data is described. At last, a new photoredox catalyzed transformation for the synthesis of 2-aminofurans is described. Electrophilic radical addition on allenamides and subsequential intramolecular cyclization are exploited. The reaction proceeds under very mild conditions and in 2-aminofurans are obtained in good to high yield. It represents one of the few applications of allenamides in photoredox catalysis. A mechanistic proposal is described. Finally, preliminary investigations on the applicability of the developed transformation under flow chemistry conditions

Silenzio di clausura e silenzio di corte : le donne nel Medioevo

A stretto contatto con fonti, specie di natura documentaria, si sono presi in considerazione alcune esempi di presenza femminile all'interno del mondo claustrale e di analoghe presenze negli ambienti di corte fino al 13. secolo

A base de dados bibliográficos de acervo como suporte para o processo de automação: uma experiência na UNESP- Universidade Estadual Paulista.

O processo de informatização das bibliotecas no Brasil passou a viver uma nova fase, caracterizada pela disponibilidade de recursos avançados - máquinas e softwares de nova geração, que chegaram ao País nos últimos anos. Foi criada a necessidade das bibliotecas colocarem rapidamente as informações de seus acervos em meio magnético, construindo suas bases de Dados. Recursos como RECON - Retrospective Conversion, são utilizados para agilizar a formação dessas bases. Critérios e requisitos devem ser observados para conferir qualidade à Base. A UNESP- Universidade Estadual Paulista, encontra-se vivenciando essa experiência

A supramolecular bifunctional iridium photoaminocatalyst for the enantioselective alkylation of aldehydes

The construction of a hybrid metal-organo-photoredox catalyst based on the conjugation of an imidazolidinone organocatalyst and Ir(ppy)2(bipy) (ppy = 2-phenylpyridine, bipy = bipyridine) is described. The introduction of the desired organocatalyst into the bipyridine moiety is quite modular, allowing the preparation of different hybrid photocatalysts, and is realized though a simple click reaction. The hybrid photocatalysts obtained were employed in the benchmark photoredox alkylation of aldehydes. Remarkably, the conjugation of a first-generation MacMillan catalyst produces an active and stereoselective hybrid photoredox catalyst