Conventional and novel strategies in the treatment of adrenocortical cancer

Adrenocortical carcinoma is a highly malignant neoplasm with an incidence of two per million people per year. Several treatment strategies have resulted in temporary or partial tumor regression but very few cases have attained long survival. Surgical resection of the primary tumor and metastases is most effective. Several chemotherapeutic protocols have been employed with variable success. Mitotane (o,p'-DDD) is an adrenalytic drug effective in inducing a tumor response in 33% of patients treated. Mitotane requires metabolic transformation for therapeutic action. Tumors may vary in their ability to metabolize mitotane and the ability of tumors to transform mitotane may predict the clinical response to the drug. Preliminary data show a possible correlation between metabolic activity of neoplastic adrenocortical tissue and response to mitotane. We have attempted to develop mitotane analogs with enhanced adrenalytic effect. Compared to mitotane, a di-chloro compound, the bromo-chloro and di-bromo analogs appear to have a greater effect. Future approaches to the treatment of adrenocortical carcinoma are likely to be based on blocking or reversing the biological mechanisms of tumorigenesis. Angiogenic and chemotactic mechanisms may play a role in adrenal tumor growth and inhibition of these mechanisms may result in inhibition of tumor growth. New mitotane analogs with greater adrenalytic potential could be a promising approach to developing more effective and selective therapies for adrenal cancer. Alternative approaches should attempt to suppress tumor growth by means of compounds with anti-angiogenic and anti-chemotactic activity.

Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

Identification and characterisation of phenolic compounds extracted from Moroccan olive mill wastewater

Olive mill wastewater, hereafter noted as OMWW was tested for its composition in phenolic compounds according to geographical areas of olive tree, i.e. the plain and the mountainous areas of Tadla-Azilal region (central Morocco). Biophenols extraction with ethyl acetate was efficient and the phenolic extract from the mountainous areas had the highest concentration of total phenols' content. Fourier-Transform-Middle Infrared (FT-MIR) spectroscopy of the extracts revealed vibration bands corresponding to acid, alcohol and ketone functions. Additionally, HPLC-ESI-MS analyses showed that phenolic alcohols, phenolic acids, flavonoids, secoiridoids and derivatives and lignans represent the most abundant phenolic compounds. Nüzhenide, naringenin and long chain polymeric substances were also detected. Mountainous areas also presented the most effective DPPH scavenging potential compared to plain areas; IC50 values were 11.7 ± 5.6 µg/ml and 30.7 ± 4.4 µg/ml, respectively. OMWW was confirmed as a rich source of natural phenolic antioxidant agents.

Bulgakov's sophiology as philosopheme: non-ontology and ontogenesis

The text examines Sergej Nikolajeviè Bulgakov's description of the philosopheme as thoroughly "immanent" (viz., the immanence of man qua being, such that ontology in Bulgakov becomes a conceptual analogue for immanence) and the corollary that such immanence necessarily excludes the problematic of the "creation of the world." Because of this resolute immanence and the notion that the creation of the world in the form of creatio ex nihilo requires a non-immanent or non-ontological thought and concept, the problematic for Bulgakov is approached only by a theologeme. Appropriating this argument as material for a cursory philosopheme, the text attempts to transform Bulgakov's theologeme into a philosopheme through an elision of God and dogma that overdetermines the theologeme. This philosopheme (nascent within Bulgakov's work itself, in both his hesitation to the overdetermination of immanence and the commitment to the problem of creation) would be a thoroughly non-ontological philosopheme, one that allows for the treatment of the problematic of "creation" or singular ontogenesis, yet with the corollary that this philosopheme must rely on an "ontological zero" Such a philosopheme qua ontologically empty formula nevertheless remains ontologically significant insofar as it is to evince the limit of ontology, in the ontological zero's non-relationality to ontology.

"Chegou a hora de darmos a luz a nós mesmas": Situando-nos enquanto mulheres e negras

O artigo, ao analisar manifestações de mulheres negras, busca entender como se constituem cidadãs numa sociedade que discrimina seu grupo e etnia. À indagação sobre o que significa ser mulher e negra, formulada a mulheres militantes do Movimento Negro nos estados do sul do país, mostrou que o configurar-se como mulheres negras implica enfrentar atitudes e posturas discriminatórias, além de exigir combatividade, introspecção, auto-imagem positiva, crítica a relações sociais e propostas para transformá-las. Buscando elucidar sua presença na sociedade, o estudo mostra que lutam para superar a invisibilidade conferida aos descendentes de africanos, bem como para ter suas necessidades atendidas por políticas públicas que resolvam os problemas que os afligem e suprimam as opressões que lhes são impingidas. Assim, lutam por justiça para todos que são marginalizados pela sociedade. O artigo conclui com a afirmativa de que as fontes mais genuínas de conhecimento sobre as mulheres negras são elas mesmas, sendo necessário que estudos que as tomem por temática, considerem seus pontos de vista de mulheres e negras.