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1.
Giorgia Del Favero Silvio Sosa Mark Poli Aurelia Tubaro Orfeo Sbaizero Paola Lorenzon 《Toxicology letters》2014
Palytoxins (PLTXs) are known seafood contaminants and their entrance into the food chain raises concern about possible effects on human health. The increasing number of analogs being identified in edible marine organisms complicates the estimation of the real hazard associated with the presence of PLTX-like compounds. So far, 42-OH-PLTX is one of the few congeners available, and the study of its toxicity represents an important step toward a better comprehension of the mechanism of action of this family of compounds. From this perspective, the aim of this work was to investigate the in vivo and in vitro effect of 42-OH-PLTX on skeletal muscle, one of the most sensitive targets for PLTXs. Our results demonstrate that 42-OH-PLTX causes damage at the skeletal muscle level with a cytotoxic potency similar to that of PLTX. 42-OH-PLTX induces cytotoxicity and cell swelling in a Na+-dependent manner similar to the parent compound. However, the limited Ca2+-dependence of the toxic insult induced by 42-OH-PLTX suggests a specific mechanism of action for this analog. Our results also suggest an impaired response to the physiological agonist acetylcholine and altered cell elasticity. 相似文献
2.
One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. 总被引:73,自引:0,他引:73
One hundred and twenty-seven cultured human tumor cell lines produced tumors after sc inoculation of 1-20 million cells into nude mice. They included 56 carcinoma lines, 14 sarcoma lines, and 57 lines from miscellaneous tumors and were all glucose-6-phosphate dehydrogenase type B. Twenty-nine percent of the lines produced tumors of 1 cm3 size within 1 month and 41% in the second month after inoculation. The histopathology correlated with the human tumor of origin in all cases. 相似文献
3.
P A Ades P G Gunther W L Meyer T C Gibson J Maddalena T Orfeo 《The American journal of cardiology》1990,66(5):591-596
Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning. 相似文献
4.
Carlo Di Bello Adriana Lucchiari Orfeo Buso Mauro Tonellato 《Chemical biology & drug design》1984,23(1):61-71
The S-peptide of the enzyme bovine pancreatic ribonuclease has been used as a model for covalent semisynthesis. Methods for side-chain protection, enzymatic cleavage of the peptide chain at the level of the single arginine-10 and for selective deprotection of the α-carboxyl function of this residue, have been examined. The partially protected [1–10] sequence has been coupled to a solid-phase generated [11–15] sequence attached to the polymer. After deblocking from the solid-support, the [1–15] semisynthetic peptide was complexed with native S-protein to give a complex with high biological activity. 相似文献
5.
Scuor N Gallina P Panchawagh HV Mahajan RL Sbaizero O Sergo V 《Biomedical microdevices》2006,8(3):239-246
Micromechanical systems are increasingly being used as tools in biological applications, since their characteristic dimensions
permit to operate at the same length scale of the structures under investigation. Here, we present a methodology for the design,
fabrication and operation of a tool for the assessment of mechanical properties of single cells. In particular, we describe
a microsystems platform to study bio-mechanical response of single living cells to in-plane biaxial stretching. The proposed
device employs a new linkage design in order to obtain the displacement of the quadrants of a sliced circular plate in mutually-orthogonal
directions using just one linear actuator. With this linkage geometry, the whole device has only one degree of freedom. This
results in a very predictable and reliable mechanical behaviour, thereby allowing use a simple and easily available control
electronics. Results of this study have relevance for the design of a powerful yet simple BioMEMS platform for the characterization
of living cells as in-plane bi-axial loading simulated the conditions experienced by cells in vivo more realistically than a uniaxial stretching. 相似文献
6.
14 patients with primary and recurrent herpetic keratitis were treated with continuous usage of human leukocyte interferon (HLI) at low concentration using therapeutic contact lenses. All patients recovered in a medium-short time of 7 days, including some who had not benefited by previous treatments (idoxuridine, etc.). We conclude that continuous application of HLI increases its effectiveness. 相似文献
7.
8.
Mariana Vigiola Cruz Jenna N. Luker Bonnie C. Carney Kathleen E. Brummel-Ziedins Maria-Cristina Bravo Thomas Orfeo Jason H. Chen Lauren T. Moffatt Jeffrey W. Shupp 《Thrombosis journal》2017,15(1):31
Background
A functional coagulation assay was used to investigate the extrinsic pathway of coagulation on citrated whole blood samples from healthy adult male Sprague Dawley rats using the mini cup and pin system.Methods
Reference values for coagulation parameters from forty-three animals were calculated using data obtained from the ROTEM® delta hemostasis analyzer with the EXTEM test.Results
The following ranges, presented as the 2.5–97.5 percentiles, were established: CT [18–77], CFT [20–80], α [73–86], MCF [53–70], and ML [1–22], along with others.Conclusions
These reference ranges can be used in future studies in rats to identify clinically significant coagulopathies.9.
G Del Favero C Florio B Codan S Sosa M Poli O Sbaizero J Molgó A Tubaro P Lorenzon 《Chemical research in toxicology》2012,25(9):1912-1920
Palytoxin (PLTX) is one of the most toxic seafood contaminants ever isolated. Reports of human food-borne poisoning ascribed to PLTX suggest skeletal muscle as a primary target site. Primary cultures of mouse skeletal muscle cells were used to study the relationship between Ca(2+) response triggered by PLTX and the development of myotoxic insult. Ca(2+) imaging experiments revealed that PLTX causes a transitory intracellular Ca(2+) response (transient phase) followed by a slower and more sustained Ca(2+) increase (long-lasting phase). The transient phase is due to Ca(2+) release from intracellular stores and entry through voltage-dependent channels and the Na(+)/Ca(2+) exchanger (reverse mode). The long-lasting phase is due to a massive and prolonged Ca(2+) influx from the extracellular compartment. Sulforhodamine B assay revealed that the long-lasting phase is the one responsible for the toxicity in skeletal muscle cells. Our data analyzed, for the first time, pathways of PLTX-induced Ca(2+) entry and their correlation with PLTX-induced toxicity in skeletal muscle cells. The cellular morphology changes induced by PLTX and the sensitivity to gadolinium suggest a role for stretch-activated channels. 相似文献
10.
Previous studies of factor (F)Va inactivation on human umbilical vein endothelial cells have shown that alpha-thrombin cleaves the heavy chain near the COOH-terminus to produce a M(r) 97,000 fragment containing the NH(2)-terminal portion of the heavy chain and a M(r) 8,000 peptide containing the rest of the molecule. The alpha-thrombin cleavage appeared to occur between amino acid residues 586 and 654 of FV. This region contains a consensus sequence for alpha-thrombin cleavage located at residues 640-644 (S-S-P-R-S). To test the hypothesis that alpha-thrombin cleaves the FVa heavy chain at Arg(643) and to evaluate the functional importance of this cleavage for FVa inactivation, site-directed mutagenesis was used to create recombinant FV molecules with mutations R(643) --> Q (FV(R643Q)) and R(643) --> A (FV(R643A)). All recombinant molecules were purified to homogeneity and assayed for activity following extended activation with alpha-thrombin. Under similar experimental conditions, appearance of the M(r) 97,000 heavy chain fragment in the plasma and wild-type FVa molecules correlated with partial loss of cofactor activity, while following extended incubation of FV(R643Q) and FV(R643A) with alpha-thrombin no cleavage of the heavy chain at Arg(643) was detected and no presence of the M(r) 97,000 heavy-chain fragment was noticed. Further, no loss in cofactor activity was observed using these mutant recombinant FVa molecules. Our data demonstrate that cleavage of FVa at Arg(643) by alpha-thrombin results in a partially inactive cofactor molecule and provides for an activated protein C (APC)-independent anticoagulant effect of alpha-thrombin. 相似文献