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81.
Gitto R Damiano FM De Luca L Ferro S Vullo D Supuran CT Chimirri A 《Bioorganic & medicinal chemistry》2011,19(23):7003-7007
In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition. 相似文献
82.
Marco Barbero Roberto Gatti Loredana Lo Conte Fiona Macmillan Fiona Coutts Roberto MerlettiAuthor vitae 《Journal of electromyography and kinesiology》2011,21(5):827-833
The identification of the motor unit (MU) innervation zone (IZ) using surface electromyographic (sEMG) signals detected on the skin with a linear array or a matrix of electrodes has been recently proposed in the literature. However, an analysis of the reliability of this procedure and, therefore, of the suitability of the sEMG signals for this purpose has not been reported.The purpose of this work is to describe the intra and inter-rater reliability and the suitability of surface EMG in locating the innervation zone of the upper trapezius muscle.Two operators were trained on electrode matrix positioning and sEMG signal analysis. Ten healthy subjects, instructed to perform a series of isometric contractions of the upper trapezius muscle participated in the study. The two operators collected sEMG signals and then independently estimated the IZ location through visual analysis.Results showed an almost perfect agreement for intra-rater and inter-rater reliability. The constancy of IZ location could be affected by the factors reflecting the population of active MUs and their IZs, including: the contraction intensity, the acquisition period analyzed, the contraction repetition. In almost all cases the IZ location shift due to these factors did not exceed 4 mm. Results generalization to other muscles should be made with caution. 相似文献
83.
Context
Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.Objective
To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback.Design
Retrospective study.Setting
Academic hospital.Patients
1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.Measurements
TSH, FT4 and FT3 concentrations by immunoassays.Results
FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.Conclusions
Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients. 相似文献84.
Conte E Fruciano M Fagone E Gili E Caraci F Iemmolo M Crimi N Vancheri C 《PloS one》2011,6(10):e24663
Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease characterized by an accumulation of fibroblasts and myofibroblasts in the alveolar wall. Even though the pathogenesis of this fatal disorder remains unclear, transforming growth factor-β (TGF-β)-induced differentiation and proliferation of myofibroblasts is recognized as a primary event. The molecular pathways involved in TGF-β signalling are generally Smad-dependent yet Smad-independent pathways, including phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), have been recently proposed. In this research we established ex-vivo cultures of human lung fibroblasts and we investigated the role of the PI3K/Akt pathway in two critical stages of the fibrotic process induced by TGF-β: fibroblast proliferation and differentiation into myofibroblasts. Here we show that the pan-inhibitor of PI3Ks LY294002 is able to abrogate the TGF-β-induced increase in cell proliferation, in α- smooth muscle actin expression and in collagen production besides inhibiting Akt phosphorylation, thus demonstrating the centrality of the PI3K/Akt pathway in lung fibroblast proliferation and differentiation. Moreover, for the first time we show that PI3K p110δ and p110γ are functionally expressed in human lung fibroblasts, in addition to the ubiquitously expressed p110α and β. Finally, results obtained with both selective inhibitors and gene knocking-down experiments demonstrate a major role of p110γ and p110α in both TGF-β-induced fibroblast proliferation and differentiation. This finding suggests that specific PI3K isoforms can be pharmacological targets in IPF. 相似文献
85.
86.
Effects of spatial variation in food availability on spacing behaviour and demography of Eurasian red squirrels 总被引:6,自引:0,他引:6
In heterogeneous habitats with limited resources, spacing behaviour will affect individual variation in breeding success and density of populations, and is thus of general interest to ecologists. We investigated how red squirrels Sciurus vulgaris adapt their social organisation to tine‐grained heterogeneity in habitat quality, studying spacing behaviour, habitat use and population dynamics in a forest in north Italy, characterised by a mosaic of high‐quality (chestnut‐pine) and poor‐quality patches. We compared the data with those from more homogeneous broadleaf and mixed woodlands with similar overall tree seed abundance (“stable” habitats). Squirrels lived at lower densities (pre‐breeding density 0.39‐0.58 ha‐1) than in “stable” habitats, although breeding rate was not reduced. Female breeding success was related to being primiparous as yearlings, and increased with body mass and proportion high‐quality habitat in the home range. Persistency rate of females was as in stable habitats, It was higher than male persistency, but immigration and recruitment rates were male biased, resulting in even sex‐ratio. All residents occupied high‐quality patches, and no subadults established a permanent home range in poor‐quality habitat. Home range and core‐area size was typically larger in males than in females and a male's core‐area overlapped those of other males and of females. Female core‐areas were overlapped by males but not. or very little, by other females (intrasexual territoriality). Home ranges, or core‐areas, were not smaller than in “stable” habitats, nor did we find a higher degree of core‐area overlap. We conclude that in patchy habitats dominant, resident red squirrels exclude dispersing animals from preferred, high‐quality habitat, producing a spacing pattern referred to as ideal despotic distribution, and that poor patches were only used temporarily by transient individuals, resulting in a reduction of density in comparison to populations in “stable” habitats. 相似文献
87.
A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate of iron(III) chloride, Fe(TDCPPS)Cl, was employed as a biomimetic catalyst in the oxidative coupling of terrestrial humic materials. High-performance size-exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance (CPMAS-(13)C NMR), electron paramagnetic resonance (EPR), and diffuse reflectance infrared spectroscopy (DRIFT) were used to follow conformational and structural changes brought about in different humic materials by the oxidative coupling. Increase in apparent weight-average molecular weight (Mw(a)) occurred invariably for all humic substances with the oxidative polymerization catalyzed by Fe(TDCPPS)Cl. HPSEC further showed that the polymerization reaction turned the loosely bound humic supramolecular structures into more stable conformations which could no longer be disrupted by the disaggregating effect of acetic acid. DRIFT spectroscopy suggested the formation of new alkyl and aromatic ethers following the oxidative coupling with the biomimetic catalyst. CPMAS-(13)C NMR and EPR spectra suggested a reduced molecular mobility of humic components and enhanced stabilization of free radicals in larger oxidized fragments. All findings concur in indicating that the biomimetic catalysis by Fe(TDCPPS)Cl increased the molecular mass and chemical rigidity of humic materials by formation of intermolecular covalent bonds via a free-radical mechanism. The development of a technology based on oxidative polymerization by biomimetic catalysis may be of importance in controlling the properties and reactivity of humic matter for industrial and environmental applications. 相似文献
88.
89.
Patriarca S Furfaro AL Domenicotti C Odetti P Cottalasso D Marinari UM Pronzato MA Traverso N 《Biochimica et biophysica acta》2005,1741(1-2):48-54
Rats were rendered diabetic with streptozotocin and supplemented or not with N-acetylcysteine (NAC) and taurine (TAU). The liver was examined for the quantity of glutathione (GSH), both total and oxidised (GSSG), by HPLC assay. Moreover, the liver expression of gamma-glutamyl-cysteine synthetase, cysteine dioxygenase and heme oxygenase 1 was evaluated. Streptozotocin-diabetic rats showed decreased levels of liver glutathione (GSH); dietary supplementation with the antioxidants NAC and TAU failed to restore liver GSH to the level of control rats. Gamma-glutamyl-cysteine synthetase expression was not reduced in the diabetic rats, so the low hepatic GSH level in the supplemented diabetic rats cannot be ascribed to decreased expression of the biosynthetic key enzyme. Moreover, the diabetic rats showed no evidence of increased expression of cysteine dioxygenase, which could have indicated that NAC-derived cysteine was consumed in metabolic pathways different from GSH synthesis. However, NAC+TAU treatment provided partial protection from glutathione oxidation in the liver of diabetic rats; moreover, the antioxidant treatment reduced the hepatic overexpression of heme oxygenase 1 (HO-1) mRNA which was detected in the diabetic rats. In conclusion, although NAC was not able to restore liver GSH levels, the antioxidant treatment restrained GSH oxidation and HO-1 overexpression, which are markers of cellular oxidative stress: diabetic rats probably exploit NAC as an antioxidant itself rather than as a GSH precursor. 相似文献
90.