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151.
Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock 总被引:1,自引:0,他引:1
Giacometti A Cirioni O Ghiselli R Mocchegiani F Viticchi C Orlando F D'Amato G Del Prete MS Kamysz W łLukasiak J Saba V Scalise G 《Peptides》2003,24(11):1747-1752
The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach. 相似文献
152.
Chronic hypothyroidism is frequently associated with atherosclerosis due to increased cholesterol plasma levels; nevertheless, the contribution of impaired reverse cholesterol transport (RCT) in this process has not been completely elucidated. The aim of this study was to evaluate the effect of thyroidectomy (Htx) upon the main stages of RCT in rats. Plasma lipid alterations induced by thyroidectomy showed a slight, but significant, reduction of total plasma triglycerides, a 300% increase of LDL-cholesterol and a 25% decrease in HDL-cholesterol compared to control rats. We evaluated the first stage of RCT determining 3H-cholesterol efflux in Fu5AH cells. The capacity of HDL obtained from Htx rats to promote cholesterol efflux was similar to that of controls. Lecithin:cholesterol acyltransferase (LCAT) activity, the second stage and the driving force of RCT was 30% lower in Htx animals compared to controls, as determined by reconstituted HDL used as an external substrate. Lipoproteins are remodeled by hepatic lipase; the mean activity of this enzyme in postheparin plasma of Htx animals was reduced by 30% compared to controls, thus suggesting an impaired HDL remodeling by this enzyme in the hypothyroid status. In contrast, lipoprotein lipase activity in the Htx group was unchanged. In summary, this study demonstrates that chronic hypothyroidism in the rat induced an impaired RCT mainly at the cholesterol esterification, and HDL remodeling mediated by hepatic lipase. The latter probably results in an abnormal HDL structure, i.e. phospholipid enrichment, which contributes to decrease HDL-apo AI fractional catabolic rates. 相似文献
153.
Fiorenza G Bottasso OA Rateni L Farroni MA Dlugovitzky D 《FEMS immunology and medical microbiology》2003,38(2):159-164
Our study investigated whether the respiratory burst (RB) of polymorphonuclear neutrophils from tuberculosis (TB) patients was related with the disease severity or treatment, as well as the circulating levels of TNF-alpha. The sample comprised 57 patients with moderate (n=21) or advanced disease (n=36, 13 of them with HIV coinfection, TB-HIV) and 12 controls. Patients were newly diagnosed (n=27) or under treatment (moderate=14, advanced=10, TB-HIV=6). Cytometric analysis showed that untreated patients had a depressed RB in response to Candida albicans, being more pronounced in the advanced group and nearly absent in TB-HIV cases. A recovered RB was observed in treated patients, except for the TB-HIV cases that continued to show a poor response. TNF-alpha serum levels were increased in untreated patients, mostly in the advanced and TB-HIV groups, and showed an inverse and significant correlation with the RB. Disease severity and anti-TB therapy exerted negative and positive influences on the reactive oxygen intermediates production, respectively. 相似文献
154.
In Saccharomyces cerevisiae pseudohyphae formation may be triggered by nitrogen deprivation and is stimulated by cAMP. It was observed that even in a medium with an adequate nitrogen supply, cAMP can induce pseudohyphal growth when S. cerevisiae uses ethanol as carbon source. This led us to investigate the effects of the carbon source and of a variety of stresses on yeast morphology. Pseudohyphae formation and invasive growth were observed in a rich medium (YP) with poor carbon sources such as lactate or ethanol. External cAMP was required for the morphogenetic transition in one genetic background, but was dispensable in strain 1278b which has been shown to have an overactive Ras2/cAMP pathway. Pseudohyphal growth and invasiveness also took place in YPD plates when the yeast was subjected to different stresses: a mild heat-stress (37 °C), an osmotic stress (1 m NACl), or addition of compounds which affect the lipid bilayer organization of the cell membrane (aliphatic alcohols at 2%) or alter the glucan structure of the cell wall (Congo red). We conclude that pseudohyphal growth is a physiological response not only to starvation but also to a stressful environment; it appears to require the coordinate action of a MAP kinase cascade and a cAMP-dependent pathway. 相似文献
155.
The regulation exerted by ammonium and other nitrogen sources on amino acid utilization was studied in swollen spores of Penicillium chrysogenum. Ammonium prevented the L-lysine, L-arginine and L-ornithine utilization by P. chrysogenum swollen spores seeded in complete media, but not in carbon-deficient media. Transport of L-[14C]lysine into spores incubated in presence of carbon and nitrogen sources was fully inhibited by ammonium ions (35 mM). However, in carbon-derepressed conditions (growth in absence of sugars, with amino acids as the sole carbon source) L-[14C]lysine transport was only partially inhibited. Competition experiments showed that L-lysine (1 mM) inhibits the utilization of L-arginine, and vice versa, L-arginine inhibits the L-lysine uptake. High concentrations of L-ornithine (100 mM) prevented the L-lysine and L-arginine utilization in P. chrysogenum swollen spores. In summary, ammonium seems to prevent the utilization of basic amino acids in P. chrysogenum spores by inhibiting the transport of these amino acids through their specific transport system(s), but not through the general amino acid transport system that is operative under carbon-derepression conditions. 相似文献
156.
Artificial endosperm of Cleopatra tangerine zygotic embryos: a model for somatic embryo encapsulation 总被引:1,自引:0,他引:1
Nieves Nadina Lorenzo Jose C. Blanco Maria de los A. González Justo Peralta Hipólito Hernández Martha Santos Ramón Concepción Oscar Borroto Carlos G. Borroto Eduviges Tapia Raúl Martinez Marcos E. Fundora Zaida González Alfredo 《Plant Cell, Tissue and Organ Culture》1998,54(2):77-83
Synthetic seed technology may be of value in breeding programs and allow the propagation of many elite genotype-derived plants
in a short time. In this work, a range of artificial endosperm treatments of Cleopatra tangerine zygotic embryos were evaluated
for suitability for encapsulation of somatic embryos. Different complexing ions in the form of alginate capsules, zeolite
as an ion exchanger and the relationship between capsule-nutrient gel on germination of zygotic embryos, were evaluated. Artificial
endosperm assays showed that abscisic acid (1 μM) and mannitol (0.25 M) delayed germination and conversion of zygotic embryos,
whereas amino acid supplements (proline, glutamic acid and arginine) accelerated the conversion process. An artificial endosperm
was used to encapsulate somatic and zygotic embryos. After encapsulation, zygotic embryos germinated after four days of culture
while somatic embryos germinated asynchronously after 20 days. Somatic embryo-derived plantlets showed greater vigour than
zygotic embryo-derived plantlets. Results showed that this artificial endosperm is adequate for Cleopatra tangerine somatic
embryo germination and conversion into plants.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
157.
Yong-Chun Li ;Jiang-Ping Ren ;Myeong-Je Cho ;Su-Mei Zhou ;Yong-Bum Kim ;Hong-Xiang Guo ;Joshua H. Wong ;Hong-Bin Niu ;Hyun-Kyung Kim ;Susumu Morigasaki ;Peggy G. Lemaux ;Oscar L. Frick ;Jun Yin ;Bob B. Buchanan 《植物生理学报》2009,(3):430-441
Work with cereals (barley and wheat) and a legume (Medicago truncatula) has established thioredoxin h (Trx h) as a central regulatory protein of seeds. Trx h acts by reducing disulfide (S-S) groups of diverse seed proteins (storage proteins, enzymes, and enzyme inhibitors), thereby facilitating germination. Early in vitro protein studies were complemented with experiments in which barley seeds with Trx h overexpressed in the endosperm showed accelerated germination and early or enhanced expression of associated enzymes (α-amylase and pullulanase). The current study extends the transgenic work to wheat. Two approaches were followed to alter the expression of Trx h genes in the endosperm: (1) a hordein promoter and its protein body targeting sequence led to overexpression of Trx hS, and (2) an antisense construct of Trx h9 resulted in cytosolic underexpression of that gene (Arabidopsis designation). Underexpression of Trx h9 led to effects opposite to those observed for overexpression Trx h5 in barley--retardation of germination and delayed or reduced expression of associated enzymes. Similar enzyme changes were observed in developing seeds. The wheat lines with underexpressed Trx showed delayed preharvest sprouting when grown in the greenhouse or field without a decrease in final yield. Wheat with overexpressed Trx h5 showed changes commensurate with earlier in vitro work: increased solubility of disulfide proteins and lower aUergenicity of the gliadin fraction. The results are further evidence that the level of Trx h in cereal endosperm determines fundamental properties as well as potential applications of the seed. 相似文献
158.
Detailed imaging and genetic analysis reveal a secondary BRAFL505H resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib
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Inge Ubink Nicolle J. M. Besselink Mark Pieterse Wouter Veldhuis Marijn van Stralen Eelco F. J. Meijer Stefan M. Willems Michael A. Hadders Thomas Kuilman Oscar Krijgsman Daniel S. Peeper Marco J. Koudijs Edwin Cuppen Emile E. Voest Martijn P. Lolkema 《Pigment cell & melanoma research》2015,28(3):318-323
Resistance to treatment is the main problem of targeted treatment for cancer. We followed ten patients during treatment with vemurafenib, by three‐dimensional imaging. In all patients, only a subset of lesions progressed. Next‐generation DNA sequencing was performed on sequential biopsies in four patients to uncover mechanisms of resistance. In two patients, we identified mutations that explained resistance to vemurafenib; one of these patients had a secondary BRAF L505H mutation. This is the first observation of a secondary BRAF mutation in a vemurafenib‐resistant patient‐derived melanoma sample, which confirms the potential importance of the BRAF L505H mutation in the development of therapy resistance. Moreover, this study hints toward an important role for tumor heterogeneity in determining the outcome of targeted treatments. 相似文献
159.
160.
Cinzia Scambi Sara Ugolini T. Sakari Jokiranta Lucia De Franceschi Oscar Bortolami Valentina La Verde Patrizia Guarini Paola Caramaschi Viviana Ravagnani Guido Martignoni Chiara Colato Serena Pedron Fabio Benedetti Marco Sorio Fabio Poli Domenico Biasi 《PloS one》2015,10(2)
ObjectiveThe role of complement system in the pathogenesis of systemic sclerosis (SSc) has been debated during the last decade but an evident implication in this disease has never been found. We carried out an explorative study on SSc patients to evaluate the expression of soluble and local C5b-9 complement complex and its relation with a complement regulator, the Membrane Cofactor Protein (MCP, CD46) on skin vascular bed as target distinctive of SSc disease. We also analyzed two polymorphic variants in the complement activation gene cluster involving the MCP region.MethodsC5b-9 plasma levels of SSc patients and healthy subjects were analyzed by ELISA assay. Archival skin biopsies of SSc patients and controls were subjected to immunofluorescence analysis to detect C5b-9 and MCP on vascular endothelial cells. The expression of MCP was validated by immunoblot analysis with specific antibody. Polymorphic variants in the MCP gene promoter were tested by a quantitative PCR technique-based allelic discrimination method.ResultsEven though circulating levels of C5b-9 did not differ between SSc and controls, C5b-9 deposition was detected in skin biopsies of SSc patients but not in healthy subjects. MCP was significantly lower in skin vessels of SSc patients than in healthy controls and was associated with the over-expression of two polymorphic variants in the MCP gene promoter, which has been related to more aggressive phenotypes in other immune-mediated diseases.ConclusionsOur results firsty document the local complement activation with an abnormal expression of MCP in skin vessels of SSc patients, suggesting that a subset of SSc patients might be exposed to more severe organ complications and clinical evolution due to abnormal local complement activation. 相似文献