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101.
Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases. 相似文献
102.
A single-site mutant (M5) of native urokinase plasminogen activator (prouPA) induces effective thrombolysis in dogs with venous or arterial thrombosis with a reduction in bleeding complications compared to tPA. This effect, related to inhibition of two-chain M5 (tcM5) by plasma C1-inhibitor (C1I), thereby preventing non-specific plasmin generation, was augmented by the addition of exogenous C1I to plasma in vitro. In the present study, tPA, M5 or placebo +/- C1I were administered in two rat stroke models. In Part-I, permanent MCA occlusion was used to evaluate intracranial hemorrhage (ICH) by the thrombolytic regimens. In Part II, thromboembolic occlusion was used with thrombolysis administered 2 h later. Infarct and edema volumes, and ICH were determined at 24 h, and neuroscore pre (2 h) and post (24 h) treatment. In Part I, fatal ICH occurred in 57% of tPA and 75% of M5 rats. Adjunctive C1I reduced this to 25% and 17% respectively. Similarly, semiquantitation of ICH by neuropathological examination showed significantly less ICH in rats given adjunctive C1I compared with tPA or M5 alone. In Part-II, tPA, M5, and M5+C1I induced comparable ischemic volume reductions (>55%) compared with the saline or C1I controls, indicating the three treatments had a similar fibrinolytic effect. ICH was seen in 40% of tPA and 50% of M5 rats, with 1 death in the latter. Only 17% of the M5+C1I rats showed ICH, and the bleeding score in this group was significantly less than that in either the tPA or M5 group. The M5+C1I group had the best Benefit Index, calculated by dividing percent brain salvaged by the ICH visual score in each group. In conclusion, adjunctive C1I inhibited bleeding by M5, induced significant neuroscore improvement and had the best Benefit Index. The C1I did not compromise fibrinolysis by M5 in contrast with tPA, consistent with previous in vitro findings. 相似文献
103.
Elisa Bellei Stefania Bergamini Emanuela Monari Luca Isaia Fantoni Aurora Cuoghi Tomris Ozben Aldo Tomasi 《Amino acids》2011,40(1):145-156
In clinical and pharmaceutical proteomics, serum and plasma are frequently used for detection of early diagnostic biomarkers
for therapeutic targets. Although obtaining these body fluid samples is non-invasive and easy, they contain some abundant
proteins that mask other protein components present at low concentrations. The challenge in identifying serum biomarkers is
to remove the abundant proteins, uncovering and enriching at the same time the low-abundance ones. The depletion strategies,
however, could lead to the concomitant removal of some non-targeted proteins that may be of potential interest. In this study,
we compared three different methods aimed to deplete high-abundance proteins from human serum, focusing on the identification
of non-specifically bound proteins which might be eventually removed. A Cibacron blue-dye-based method for albumin removal,
an albumin and IgG immunodepletion method and an immunoaffinity column (Multiple Affinity Removal System) that simultaneously
removes a total of six high-abundance proteins, were investigated. The bound proteins were eluted, separated by two-dimensional
gel electrophoresis and identified by Nano LC-CHIP-MS system. Flow-through fractions and bound fractions were also analysed
with the ProteinChip technology SELDI-TOF-MS. Our results showed that the methods tested removed not only the targeted proteins
with high efficiency, but also some non-targeted proteins. We found that the Multiple Affinity Removal Column improved the
intensity of low-abundance proteins, displayed new protein spots and increased resolution. Notably, the column showed the
lowest removal of untargeted proteins, proved to be the most promising depletion approach and a reliable method for serum
preparation prior to proteomic studies. 相似文献
104.
105.
106.
Artur Junio Togneri Ferron Bruno Barcellos Jacobsen Paula Grippa Sant’Ana Dijon Henrique Salomé de Campos Loreta Casquel de Tomasi Renata de Azevedo Mello Luvizotto Antonio Carlos Cicogna André Soares Leopoldo Ana Paula Lima-Leopoldo 《PloS one》2015,10(9)
Obesity has been shown to impair myocardial performance. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them beta-adrenergic (βA) system, an important mechanism of regulation of myocardial contraction and relaxation. The objective of present study was to evaluate the involvement of βA system components in myocardial dysfunction induced by obesity. Thirty-day-old male Wistar rats were distributed in control (C, n = 25) and obese (Ob, n = 25) groups. The C group was fed a standard diet and Ob group was fed four unsaturated high-fat diets for 15 weeks. Cardiac function was evaluated by isolated papillary muscle preparation and βA system evaluated by using cumulative concentrations of isoproterenol and Western blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats and several comorbidities; however, were not associated with changes in systolic blood pressure. Obesity caused structural changes and the myocardial responsiveness to post-rest contraction stimulus and increased extracellular calcium (Ca2+) was compromised. There were no changes in cardiac function between groups after βA stimulation. The obesity was not accompanied by changes in protein expression of G protein subunit alpha (Gsα) and βA receptors (β1AR and β2AR). In conclusion, the myocardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to βAR system impairment at the receptor-signalling pathway. 相似文献
107.
The cellular composition and certain functional characteristics of murine Peyer's patches (PP) were examined and compared with other lymphoid tissues. The composition of PP resembled most closely that of the spleen with the exception of a significant decrease in the number of adherent and phagocytic cells. Very few cells with dendritic morphology could be identified in Peyer's patches. Whole PP (and the nonadherent population) were capable of presenting antigen ovalbumin, human gammaglobulin, and purified protein derivative in a T proliferative assay to sensitized lymph node cells and to an antigen-specific T-cell clone. The antigen-presenting cell in both the spleen and PP was concentrated in the low-density population which floated on 1.080 bovine plasma albumin. However, equal numbers of whole and PP floaters were deficient in their capacity to present antigen compared with similar populations from spleen. Moreover, in PP the antigen-presenting cell appeared in the nonadherent rather than the adherent population as found with other lymphoid tissues. Similar results were obtained with (B6A)F1, CBA, A.TFR-1 and B10.S (12R) mice, suggesting that the inability of adherent cells from PP to present antigen effectively was not genetically determined. Whole and nonadherent PP contained cells capable of stimulating an allogeneic MLR, although again they were generally inferior to those of the spleen when comparable numbers of cells were employed. The adherent population of PP did not elicit an MLR. However, whole PP contained accessory cells needed for mitogen-induced proliferation since passage over nylon-wool columns resulted in a nonadherent fraction which did not respond to concanavalin A or phytohemagglutinin and the addition of adherent peritoneal exudate cells restored the lectin response. The differences noted in the accessory cell function in PP and other lymphoid tissues suggest the possibility that quantitative or qualitative differences in the function of these cells may explain some of the previously observed characteristics of PP, such as the inability to detect a primary antibody response in this tissue. The possibility that the development of gut-associated suppressor cells and their migration to peripheral tissues may be involved in the systemic tolerance that follows oral immunization and that these may be related to numerical and/or functional differences in macrophages or accessory cells is discussed. 相似文献
108.
Bazin MA Le Lamer AC Delcros JG Rouaud I Uriac P Boustie J Corbel JC Tomasi S 《Bioorganic & medicinal chemistry》2008,16(14):6860-6866
Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and in the PTS deficient CHO-MG cells. In addition, alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor known to indirectly enhance the activity of the PTS and consequently increase the cytotoxicity of cytotoxic drugs entering cells via the PTS, had no effect on the activity of the polyamine derivatives. The more active derivative (1,8-diaminooctane derivative) displayed similar activities on all cancer cell lines studied and induced apoptosis. 相似文献
109.
C Griffoni E Spisni M Orlandi S Santi M Riccio V Tomasi 《Nucleosides & nucleotides》1999,18(6-7):1673-1676
Recent studies suggest that antisense phosphorothioate oligonucleotides (APO) are useful tools not only to impair gene expression, but also to modify the splicing of pre-mRNA, as the classical view that they act by suppressing the translation of mature mRNA has been challenged by several examples showing their nuclear site of action. In this work we show that an APO directed against cytosolic phospholipase A2 (cPLA2) mRNA localises in the nucleus and interacts with a specific nuclear protein. 相似文献
110.
Elisabeth APM Romme David A McAllister John T Murchison Edwin JR Van Beek George S Petrides Cameron OS Price Erica PA Rutten Frank WJM Smeenk Emiel FM Wouters William MacNee 《Respiratory research》2013,14(1):129