Approaches towards C-10-hydroxylated analogues of narciclasine

Discussed in this thesis is the synthesis of a C10-benzyloxy unnatural derivative of narciclasine. The described approach involves the use of homochiral cyclohexadiene diols, products of the biocatalytic transformation of aromatic compounds, as precursors to ring C, and of highly oxygenated aromatic molecules to construct ring A. The document also reports a detailed account of the protocols studied for the intramolecular formation of ring B. Experimental data and spectral data are provided for the novel compounds

Transcriptional Stress Induces Chromatin Relocation of the Nucleotide Excision Repair Factor XPG.

Endonuclease XPG participates in nucleotide excision repair (NER), in basal transcription, and in the processing of RNA/DNA hybrids (R-loops): the malfunction of these processes may cause genome instability. Here, we investigate the chromatin association of XPG during basal transcription and after transcriptional stress. The inhibition of RNA polymerase II with 5,6-dichloro-l-β-D-ribofuranosyl benzimidazole (DRB), or actinomycin D (AD), and of topoisomerase I with camptothecin (CPT) resulted in an increase in chromatin-bound XPG, with concomitant relocation by forming nuclear clusters. The cotranscriptional activators p300 and CREB-binding protein (CREBBP), endowed with lysine acetyl transferase (KAT) activity, interact with and acetylate XPG. Depletion of both KATs by RNA interference, or chemical inhibition with C646, significantly reduced XPG acetylation. However, the loss of KAT activity also resulted in increased chromatin association and the relocation of XPG, indicating that these processes were induced by transcriptional stress and not by reduced acetylation. Transcription inhibitors, including C646, triggered the R-loop formation and phosphorylation of histone H2AX (γ-H2AX). Proximity ligation assay (PLA) showed that XPG colocalized with R-loops, indicating the recruitment of the protein to these structures. These results suggest that transcriptional stress-induced XPG relocation may represent recruitment to sites of R-loop processing

Substâncias administradas para a indução da Doença de Alzheimer em ratos

Estimates of the progressive expansion of Alzheimer's disease (AD) worldwide indicate the need for constant studies on this pathology, still without cure. Studies have investigated AD in non-human animal models using substances that induced AD. The present study aimed to review the literature on the substances and procedures used in laboratory to reproduce AD in rats. We selected 44 of 111 studies analyzed, keeping only papers that induced AD by chemical substances. The identified substances were aluminum, beta-amyloid, colchicine, d-galactose, scopolamine, streptozocin and homocysteine. It was verified that of the 44 articles, the most used substance was beta-amyloid, the main biomarker of AD. Although different studies have replicated results that simulate the occurrence of AD in rats and the treatments performed with rats in the laboratory appear promising, no cure has yet been found.Las estimaciones sobre la expansión de los casos de la enfermedad de Alzheimer (EA) en el mundo indican la necesidad de constantes estudios sobre esta patología aún sin cura. Los estudios han investigado la EA en modelos animales no humanos utilizando sustancias químicas que inducen a la EA. El presente estudio tuvo como objetivo realizar una revisión de la literatura sobre las sustancias usadas en laboratorio para reproducir la EA en ratas. Se seleccionaron 44 de 111 estudios analizados, manteniendo sólo los artículos que indujeron a EA por sustancias químicas. Las sustancias identificadas fueron el aluminio, la beta-amiloide, la colchicina, la d-galactosa, la escopolamina, la estreptozocina y la homocisteína. Se comprobó que de los 44 artículos, la sustancia más utilizada fue la beta-amiloide, principal biomarcador de la EA. Aunque diferentes estudios han replicado resultados que simulan la ocurrencia de EA en ratas y los tratamientos realizados con ratas en laboratorio parecen prometedores, no se ha encontrado ninguna cura.As estimativas sobre a expansão dos casos da Doença de Alzheimer (DA) no mundo indicam a necessidade de constantes estudos sobre essa patologia ainda sem cura. Os estudos têm investigado a DA em modelos animais não-humanos utilizando substâncias químicas que induzem à DA. O presente estudo teve por objetivo realizar uma revisão da literatura sobre as substâncias usadas em laboratório para reproduzir a DA em ratos. Foram selecionados 44 de 111 estudos analisados, mantendo apenas os artigos que induziram a DA por substâncias químicas. As substâncias identificadas foram o alumínio, a beta-amiloide, a colchicina, a d-galactose, a escopolamina, a estreptozocina e a homocisteína. Verificou-se que dos 44 artigos, a substância mais utilizada foi a beta-amiloide, principal biomarcador da DA. Embora diferentes estudos tenham replicado resultados que simulam a ocorrência de DA em ratos e os tratamentos realizados com ratos em laboratório pareçam promissores, nenhuma cura foi encontrada ainda

Promoción de exportación para las PyMEs

El presente trabajo tiene por finalidad revelar la incidencia que tienen las pequeñas y medianas empresas argentinas en el mercado internacional y los instrumentos con los que cuentan para acceder a dicho mercado. Para ello, se analizó el comercio exterior en su conjunto, principalmente, sus actores, operatoria, incoterms, entre otros. Se aplicaron métodos cuantitativos a través de la presentación de gráficos con datos estadísticos para conocer los porcentajes de exportación de las PyMEs en la Argentina. Los resultados obtenidos por un lado, indican la gran importancia que tienen estas empresas en las operaciones de extracción de mercadería que se realizan en nuestro país y por el otro, la falta de formación para insertarse al comercio exterior de una manera más competitiva. El objetivo de este informe es dar a conocer herramientas existentes que provocan beneficios y facilitan la introducción al mercado externo para las pequeñas y medianas empresas.Fil: Gazze, Omar Carim. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Naranjo Vega, Ana Victoria Lourdes. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Ticli, Brunela Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Efeitos do Tributil-estanho (TBT) no aparelho reprodutor masculino, hepático e renal de ratos Wistar

O presente estudo investigou os efeitos do TBT no aparelho reprodutor, no fígado e rim de ratos Wistar, por meio de análises histopatológicas. Utilizou-se de 10 animais por grupo (tratado e controle). Os resultados histopatológicos demonstraram que os ratos expostos ao TBT apresentaram alterações nos túbulos seminíferos e no espaço intertubular. Conclui-se que os efeitos da exposição ao TBT causa impactos importantes na saúde humana e ambiental

Biological and Pathological Studies of Rosmarinic Acid as an Inhibitor of Hemorrhagic Trimeresurus flavoviridis (habu) Venom

In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA’s neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible