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排序方式: 共有81条查询结果,搜索用时 31 毫秒
1.
Rolando Barbucci Mario Casolaro Mila Nocentini Gianna Reginato Paolo Ferruti 《Macromolecular chemistry and physics.》1986,187(8):1953-1962
Two linear vinyl polymers carrying amido and primary amino groups in the side chains were synthesized and characterized. Their behaviour in aqueous solution was investigated by potentiometric, viscometric and calorimetric techniques. In both cases, the basicity constants show a linear dependence on the degree of protonation α, while the enthalpy values of protonation do not. The thermodynamic results demonstrate the important role of hydrophobic interactions on the protonation process. 相似文献
2.
Evaluation of the S-type of alpha-1-antitrypsin as an in vivo and in vitro inhibitor of neutrophil elastase 总被引:1,自引:0,他引:1
F Ogushi R C Hubbard G A Fells M A Casolaro D T Curiel M L Brantly R G Crystal 《The American review of respiratory disease》1988,137(2):364-370
S-type alpha 1-antitrypsin (alpha 1AT) is a deficiency haplotype that differs from the common normal M1 (val213) alpha 1AT haplotype by a single amino acid (glu264 to val264). To evaluate the adequacy of the antineutrophil elastase protection associated with the S homozygous state, alpha 1AT plasma and lung epithelial lining fluid (ELF) levels and antineutrophil elastase function were analyzed in 9 PISS subjects. The plasma alpha 1AT levels of SS subjects were intermediate between that of M1M1 and ZZ subjects (p less than 0.001, all comparisons) and the plasma neutrophil elastase inhibitory capacity paralleled the differences in alpha 1AT concentration (p less than 0.001, all comparisons). The association rate constant for neutrophil elastase of the purified S protein was less than that of the normal molecule (S-type, 7.1 +/- 0.1 X 10(6) M-1 s-1; M1-type, 9.6 +/- 0.2 X 10(6) M-1 s-1; p less than 0.001), but much greater than that for the Z molecule (p less than 0.001). Exposure of the purified S protein to increasing oxidant burdens resulted in a dose-dependent reduction in the ability of the molecule to inhibit neutrophil elastase in a fashion parallel to that of the M1 and Z proteins. Quantification of ELF alpha 1AT levels and antineutrophil elastase capacity demonstrated that the SS ELF parameters were, as in plasma, intermediate between M1 homozygotes and Z homozygotes. Using the association rate constant together with the quantification of ELF alpha 1AT levels, the "in vivo lung inhibition time" was estimated, yielding an assessment of the relative antineutrophil elastase screen of the PISS lower respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Muscelli E Casolaro A Gastaldelli A Mari A Seghieri G Astiarraga B Chen Y Alba M Holst J Ferrannini E 《The Journal of clinical endocrinology and metabolism》2012,97(8):2818-2826
Context: Dipeptidyl peptidase IV (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes. The underlying mechanisms (incretin effect, β-cell function, endogenous glucose production) are not well known. Objective: The aim of the study was to examine mechanisms of the antihyperglycemic effect of DPP-4 inhibitors. Design, Setting, and Patients: We administered a mixed meal with glucose tracers ([6,6-(2)H(2)]-glucose infused, [1-(2)H]-glucose ingested), and on a separate day, a glucose infusion matched the glucose responses to the meal (isoglycemic test) in 50 type 2 diabetes patients (hemoglobin A(1c) = 7.4 ± 0.8%) and seven controls; 47 diabetic completers were restudied after 6 wk. Glucose fluxes were calculated, and β-cell function was assessed by mathematical modeling. The incretin effect was calculated as the ratio of oral to iv insulin secretion. Intervention: We conducted a 6-wk, double-blind, randomized treatment with sitagliptin (100 mg/d; n = 25) or placebo (n = 22). Results: Relative to placebo, meal-induced changes in fasting glucose and glucose area under the curve (AUC) were greater with sitagliptin, in parallel with a lower appearance of oral glucose [difference (post-pre) AUC = -353 ± 915 vs. +146 ± 601 μmol · kg(-1) · 5 h] and greater suppression of endogenous glucose production. Insulin sensitivity improved 10%, whereas total insulin secretion was unchanged. During the meal, β-cell glucose sensitivity improved (+19[29] vs. 5[21] pmol · min(-1) · m(-2) · mm(-1); median [interquartile range]) and glucagon AUC decreased (19.6 ± 7.5 to 17.3 ± 7.1 ng · ml(-1) · 5 h), whereas intact glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 AUC increased with sitagliptin vs. placebo. The incretin effect was unchanged because sitagliptin increased β-cell glucose sensitivity also during the isoglycemic test. Conclusions: Chronic sitagliptin treatment improves glycemic control by lowering the appearance of oral glucose, postprandial endogenous glucose release, and glucagon response, and by improving insulin sensitivity and β-cell glucose sensing in response to both oral and iv glucose. 相似文献
5.
Ferrali M Bambagioni S Ceccanti A Donati D Giorgi G Fontani M Laschi F Zanello P Casolaro M Pietrangelo A 《Journal of medicinal chemistry》2002,45(26):5776-5785
Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalized from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, postischaemic reperfusion, xenobiotic intoxications, etc.). In the present work, we appropriately modified an iron chelator of the hydroxychromene family in order to obtain a tridentate chelator that would inactivate the iron redox cycle after its complexation, with a view to using this molecule in human therapy and/or in disease prevention. We synthesized such a chelator for the first time and show, by different physicochemical analysis, its tridentate nature and, importantly, its capacity to chelate iron with enough strength to inhibit both iron-dependent H(2)O(2) generation and lipid peroxidation in in vitro biological systems. 相似文献
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The study assessed the activity of promestrien administered by a local vaginal route in 16 rats castrated 60 days previously. The dose used was 5 mg per day for 10 days. Following treatment, animals were sacrificed and histological analyses revealed a remarkable proliferation of the vaginal epithelium, inhibition and restored trophism of the strome, whereas no estrogen stimulus was observed at the level of uterine mucous. This confirms the exclusively local action of promestrien which does not provoke undesirable side effects on other segments of the genital tract, and allows the therapeutic use of the hormone in different gynaecological pathologies. 相似文献
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9.
F Monzani N Caraccio G Meucci F Lombardo G Moscato A Casolaro M Ferdeghini L Murri E Ferrannini 《European journal of endocrinology / European Federation of Endocrine Societies》1999,141(4):325-331
OBJECTIVE: Interferon-beta (IFN-beta) is a widely used therapy for multiple sclerosis (MS), a demyelinating disease of the central nervous system. This study has evaluated the effect on thyroid function and autoimmunity of a 1-year treatment with IFN-beta1b in patients with MS. PATIENTS: We studied 31 patients (age 34+/-7 years, 21 women) with relapsing-remitting MS during IFN-beta1b treatment of 1 year duration. Systematic thyroid assessment and measurements of serum interleukin-6 (IL-6) levels were performed at baseline and every 3 months during treatment. RESULTS: Sixteen percent of the patients had autoimmune thyroiditis before IFN-beta1b, all positive for anti-peroxidase antibodies. The overall incidence of thyroid dysfunction was 33% over 1 year (10% hyperthyroidism, 23% hypothyroidism). Thyroid autoimmunity developed in 5/26 patients (19%), in one case without dysfunction. In addition to autoantibody positivity at baseline, female gender and the presence of an ultrasound thyroid pattern suggestive of thyroiditis were identified by multiple logistic regression as additional risk predictors for the development of thyroid dysfunction. During IFN-beta1b treatment, serum IL-6 levels rose in a consistent biphasic pattern; there was, however, no difference between patients with or without incident thyroid abnormalities. CONCLUSIONS: We conclude that IFN-beta1b therapy can induce multiple alterations in thyroid function, some of which are unrelated to thyroid autoimmunity. IL-6 measurement is not useful to identify patients prone to develop thyroid abnormalities. Though thyroid dysfunction is generally subclinical and often transient, systematic thyroid assessment should be performed during IFN-beta1b treatment. 相似文献
10.
In this paper we investigated the interaction processes occurring at the protein-solvent interface for prednisolone-albumin and prednisone-albumin systems, using an approach based on the analysis of proton selective relaxation rate enhancements of the ligand in the presence of the macromolecule. The contribution from the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index[A]L(T) and the normalized affinity index [AI(N)]L(T) which removes the effects of motional anisotropies and different proton densities, and isolates the contribution due to a decrease in the ligand dynamics caused by the binding with the protein. This approach allowed the comparison of the binding ability of prednisolone and prednisone towards albumin. 相似文献