Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway

The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

Obtenção das isotermas de sorção e modelagem matemática para a pêra bartlett (Pyrus sp.) Com e sem desidratação osmótica

Este trabalho aborda o estudo teórico-experimental da atividade de água de pêras in natura e desidratadas osmoticamente a 55ºBrix e 40ºC. As isotermas foram construídas para três níveis de temperatura (40ºC, 60ºC e 80ºC) e ajustadas pelos modelos mais usuais: Langmuir, BET, BET linear, GAB, Halsey, Oswin, Peleg, Chung e Henderson. O desvio relativo entre os valores experimentais e os valores estimados foi calculado para cada curva, a fim de se avaliar qual equação melhor se ajustou aos dados experimentais. O modelo que melhor tratou os resultados das isotermas de dessorção da pêra foi o de Henderson entre os modelos que englobam a temperatura. Em relação aos modelos que tratam as isotermas isoladamente, os modelos de Peleg, GAB e Oswin apresentaram o melhor ajuste para a pêra desidratada e in natura.

Efeito do abacate (Persea americana Mill) variedade hass na lipidemia de ratos hipercolesterolêmicos

Os fitonutrientes podem ser encontrados em muitas frutas, sendo o abacate o mais rico em beta-sitosterol (fitoesterol) e glutationa. O fitoesterol é uma substância de origem vegetal cuja estrutura é muito similar a do colesterol e seu mecanismo de ação envolve a inibição intestinal de absorção do colesterol e diminuição da síntese de colesterol hepático. O efeito é exercido sobre os valores de colesterol plasmático total e LDL, sem afetar os níveis de HDL e triglicérides sanguíneos. O presente trabalho teve como objetivo analisar a influência do consumo de farinha de abacate variedade Hass nos níveis séricos de colesterol total, HDL, LDL, triglicérides, colesterol hepático e excretado. Estes parâmetros foram investigados em ratos Wistar hipercolesterolêmicos durante 30 e 60 dias de experimento. Ao final de 30 dias, a dieta com 15% de abacate mostrou ser mais efetiva para reduzir os níveis de colesterol total e LDL e aumentar o HDL em comparação ao controle. Foi observado que para o teor de colesterol excretado a melhor dieta foi a de 25% de abacate, pois quanto maior a concentração de abacate, maior a excreção de colesterol. A dieta com 15% e 25% de abacate, foram as que mais influenciaram nos níveis de colesterol hepático.

Of empty thoughts and blind intuitions Kant's answer to McDowell

This paper examines the relation between intuition and concept in Kant in light of John McDowell's neo-Kantian position that intuitions are concept-laden.2 The focus is on Kant's twofold pronouncement that thoughts without content are empty and that intuitions without concepts are blind. I show that intuitions as singular representations are not instances of passive data intake but the result of synthetic unification of the given manifold of the senses by the power of the imagination under the guidance of the understanding. Against McDowell I argue that the amenability of intuitions to conceptual determination is not due some pre-existing, absolute conceptuality of the real but to the "work of the subject."3 On a more programmatic level, this paper seeks to demonstrate the limitations of a selective appropriation of Kant and the philosophical potential of a more comprehensive and thorough consideration of his work. Section 1 addresses the unique balance in Kant's philosophy between the work on particular problems and the orientation toward a systematic whole. Section 2 outlines McDowell's take on the Kantian distinction between intuition and concept in the context of the Kant readings by Sellars and Strawson. Section 3 exposes McDowell's relapse into the Myth of the Given. Section 4 proposes a reading of Kant's theoretical philosophy as an epistemology of metaphysical cognition. Section 5 details Kant's original account of sensible intuition in the Inaugural-Dissertation of 1770. Section 6 presents the transition from the manifold of the senses to the synthesis in the imagination and the unification through the categories in the Critique of pure reason (1781 and 1787). Section 7 addresses Kant's formalism in epistemology and metaphysics.

Nietzsche como destino da filosofia e da humanidade? interpretação contextual do § 1 do capítulo "por que sou um destino", de ecce homo

The following translation is a reduced and revised version of the paper Schicksal Nietzsche? Zu Nietzsches Selbsteinschätzung als Schicksal der Philosophie und der Menschheit (Ecce Homo, Warum ich ein Schicksal bin §1)" - originally published in Nietzsche-Studien 37 (2008) - which was specially prepared to be presented in lecture organized by the Grupo de Pesquisa Spinoza & Nietzsche (Spinoza & Nietzsche research group - SpiN), in the Universidade Federal do Rio de Janeiro (Rio de Janeiro's Federal University), on September 14, 2009. In the text, the autor employs his own philological-hermeneutical methodology, which is called contextual interpretation, in the purpose to clarify the concepts of the first aphorism from "Why I am a destiny", from Ecce Homo, in its own context, in the context of Ecce Homo and in the context of the entire work from Nietzsche.

Nietzsche como destino da filosofia e da humanidade? interpretação contextual do § 1 do capítulo "por que sou um destino", de ecce homo

A tradução que se segue é uma versão resumida e revisada do artigo "Schicksal Nietzsche? Zu Nietzsches Selbsteinschätzung als Schicksal der Philosophie und der Menschheit (Ecce Homo, Warum ich ein Schicksal bin §1)" - publicado originalmente em Nietzsche-Studien 37 (2008) - que foi especialmente preparada para ser apresentada em palestra organizada pelo Grupo de Pesquisa Spinoza & Nietzsche (SpiN), na Universidade Federal do Rio de Janeiro, em 14/09/2009. No texto, o autor faz uso de sua própria metodologia filológico-hermenêutica, denominada interpretação contextual, com vistas a esclarecer os conceitos do primeiro aforismo de "por que sou um destino", de Ecce Homo no seu contexto próprio, no contexto de Ecce Homo e no contexto da obra de Nietzsche como um todo.