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High doses of d-chiro-inositol alone induce a pco-like syndrome and other alterations in mouse ovaries
Administration of 1000–1500 mg/day D-Chiro-Inositol (DCIns) or a combination of Myo-Inositol (MyoIns) and DCIns in their plasma molar ratio (40:1) for three or more months are among recommended treatments for metabolic syndrome and/or Polycystic Ovary Syndrome (PCOS). We previously confirmed the efficacy of this formulation (8.2 mg/day MyoIns and 0.2 mg/day DCIns for 10 days) in a mouse PCOS model, but also observed negative effects on ovarian histology and function of formulations containing 0.4–1.6 mg/day DCIns. We therefore analyzed effects of higher doses of DCIns, 5, 10 and 20 mg/day, administered to young adult female mice for 21 days, on ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. Five mg/day DCIns (human correspondence: 1200 mg/day) altered ovarian histology, increased serum testosterone levels and reduced the amount of aromatase of negative controls, suggesting the induction of an androgenic PCOS model. In contrast, 10–20 mg/day DCIns (human correspondence: 2400–4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Protection from experimental autoimmune encephalomyelitis (EAE): non-depleting anti-CD4 mAb treatment induces peripheral T-cell tolerance to MBP in PL/J mice.
Membrane form of TNF alfa induces both cell lysis and apoptosis in susceptible target cells.
Tumor necrosis factor α, in the secreted as well as membrane- associated (mTNFα) form, represents a cytotoxic effector mechanism of activated macrophages; in contrast, direct evidence of the mTNFα involvement in cytotoxic T lymphocyte (CTL)-mediated lysis has not yet been obtained. We observed that following activation with anti-CD3 monoclonal antibody (mAb), both cloned CTL and peritoneal exudate lymphocytes rapidly upregulated mTNFα; a similar effect was observed in the macrophage cell line J774 after stimulation with lipopolysaccharide endotoxin. Activated effector cells, which were fixed with paraformaldehyde before testing, exerted lyric activity against the TNF-sensitive WEHI 164 tumor cell line, but not against the TNF-resistant P-815 mastocytoma. This effect was completely inhibited in the presence of anti-mouse TNFα Ab. Moreover, both mTNFα-expressing macrophages and CTL induced nuclear DNA fragmentation in WEHI 164 cells, which was also blocked by anti-TNFα Ab and was accompanied by a morphologic degeneration characteristic of the apoptotic form of cell death. These data on the whole indicate a common mode of action for mTNFα expressed on different cell populations endowed with cytotoxic capability and also imply a role for this molecule in T-cell-mediated cytotoxicity
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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