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31.
Elisa Guazzelli Elena Masotti Manfred Kriechbaum Frank Uhlig Giancarlo Galli Elisa Martinelli 《Macromolecular chemistry and physics.》2023,224(3):2200360
Amphiphilic fluorinated copolymers PEGMAx-co-FAy and TEGMAx-co-FAy are prepared by activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). All polymers present a reversible thermoresponsive lower critical solution temperature-type behavior, and a cloud point temperature (Tc) in the range of 30–60 °C strictly dependent on the length of the oxyethylene side chain, the content of the hydrophobic counits, and the concentration of the solution. Combined small angle X-ray scattering (SAXS) and dynamic light scattering measurements are used to study the self-assembly behavior in water, organic solvents (tetrahydrofuran [THF] and dimethylformamide [DMF]), and a fluorinated solvent (hexafluorobenzene [HFB]). SAXS confirms the formation of compact-globular single-chain self-folded unimer micelles in water below Tc, which generally presents small hydrodynamic diameters (Dh ≤ 8 nm) as a result of the folding of the hydrophobic perfluorohexylethyl acrylate counits. The copolymers are also able to form reverse unimer micelle in HFB. The copolymers are not able to self-assemble in unimer micelles in THF or DMF solutions, in which they adopt conventional random coil conformations. 相似文献
32.
Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration 总被引:4,自引:0,他引:4
B. Falsini Sebastiano Serrao Antonello Fadda Giancarlo Iarossi Giovanni Porrello Francesco Cocco Erasmo Merendino 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1999,237(3):193-200
· Background: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer
retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological
lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. · Methods: Twenty-five patients (25 eyes)
with bilateral NE-AMD (visual acuity of the study eyes ≥0.4) as well as 10 age- and sex-matched control subjects (10 eyes)
were evaluated. FERGs were recorded from the macular region (9°) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude
and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides
according to the Wisconsin age-related maculopathy grading system [15]. Fluorescein angiograms were evaluated by an image
analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment
epithelial atrophy) within the macular (approximately 9°×9°) region. · Results: Compared to control eyes, NE-AMD eyes had
a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin
grading score (r=–0.63, P<0.001) or the percentage area of pathological hyperfluorescence (r=–0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score ≤6) and normal acuity had a lower mean amplitude (47% loss, P<0.05) than that of control eyes. · Conclusions: The results indicate that, in NE-AMD, the FERG is altered in parallel with
the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by
FERG losses, could precede morphological changes typical of more advanced disease.
Received: 6 March 1998 Revised version received: 5 June 1998 Accepted: 17 June 1998 相似文献
33.
Shader RI Granda BW von Moltke LL Giancarlo GM Greenblatt DJ 《Biopharmaceutics & drug disposition》1999,20(8):385-388
Zafirlukast is a cysteinyl leukotriene antagonist used to treat allergic and exercise-induced asthma. This in vitro study used human liver microsomes to evaluate the inhibitory activity of zafirlukast versus six human cytochrome P450 (CYP) isoforms. Zafirlukast (0-250 microM) was co-incubated with fixed concentrations of index substrates. Zafirlukast inhibited the hydroxylation of tolbutamide (CYP2C9; mean IC(50)=7.0 microM), triazolam (CYP3A; IC(50)=20.9 microM) and S-mephenytoin (CYP2C19; IC(50)=32.7 microM), and was a less potent inhibitor of phenacetin O-deethylation (CYP1A2; IC(50)=56 microM) and dextromethorphan O-demethylation (CYP2D6; IC(50)=116 microM). Zafirlukast produced negligible inhibition of CYP2E1. In vitro inhibition of CYP2C9 by zafirlukast is consistent with clinical studies showing impaired clearance of S-warfarin and enhanced anti-thrombotic effects, although the in vitro IC(50) value is higher than the usual range of clinically relevant plasma concentrations. Zafirlukast deserves further clinical study as an inhibitor of other CYP2C9 substrates such as nonsteroidal anti-inflammatory agents, tolbutamide, phenytoin and mestranol. Clinically important inhibition by zafirlukast of other CYP isoforms is not established. 相似文献
34.
Ferdinando Mannello GianDomenico Bocchiotti Rosario Troccoli Giancarlo Gazzanelli 《Breast cancer research and treatment》1992,24(2):167-170
Summary Benign mammary gross cystic disease is the most common breast lesion. Women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal female population. Sialic acid has drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the concentrations of lipid-associated sialic acid (LASA) in 62 breast cyst fluids and sera. Data analyses show a significant increase in the mean values of LASA in metabolically active apocrine cysts when compared to the cysts with Na+/K+>3 (flattened cysts) (p<0.001). The greater LASA levels in cyst fluids with lower intracystic Na+/K+ ratios could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface sialoglycolipid metabolism, providing a possible explanation of why women with apocrine cysts may be at greater cancer risk and being useful in further studies on functional stage changes in the cysts and their relationship to breast cancer. 相似文献
35.
Evaluation of the Maruyama Computer Program Accuracy for Preoperative Estimation of Lymph Node Metastases from Gastric Cancer 总被引:2,自引:0,他引:2
Guadagni S de Manzoni G Catarci M Valenti M Amicucci G De Bernardinis G Cordiano C Carboni M Maruyama K 《World journal of surgery》2000,24(12):1550-1558
Controversy still exists about the optimal lymph node (LN) dissection for potentially curable gastric cancer. For rational
LN dissection it is important to know the incidence of metastasis at each LN station. For this purpose a computer program
was developed using data from 4302 primary gastric cancers treated at the National Cancer Center Hospital in Tokyo between
1969 and 1989. To evaluate the accuracy of the computer program, the differences between the individual reports generated
by the computer and the stored data were investigated in 282 Italian patients submitted to curative gastrectomy and D2 or more extended LN dissections for gastric cancer. Receiver operating characteristic (ROC) analysis was used to assess the
sensitivity and specificity of the program for predicting LN metastases in each of the 16 regional LN stations. The computer
program showed good predictive ability for LN metastases in most of the 16 LN stations, as the areas under the curve ranged
from 0.741 (station 15) to 0.944 (station 8), with a mean of 0.856. A critical cutoff point of 18% of the program's expected
percentage was the value maximizing the validity of the prediction. Using an “absolute” cutoff point of 0%, the overall rate
of false-negative (FN) predictions in 176 N+ patients was 11.9%; of these, 11 (6.2%) were absolute FNs, in which the program
totally failed to estimate LN metastases; the remaining 10 cases (5.7%) were relative FNs because the specific prediction
was positive for a different depth of stomach invasion. The low number of D3/D4 lymphadenectomies in the historical database may affect the low estimate of metastases to N3/N4 nodes generated by the program. Based on these data, the program predicts with good accuracy the extent of LN metastases
from gastric cancer, but it is not recommended for directing the surgeon to perform more extensive lymphadenectomy. 相似文献
36.
Lamberto Re Cinzia Corneli Emanuele Sturani Giancarlo Paolucci Francesca Rossini Olga Sonia León Gregorio Martínez Marica Bordicchia Quintilio Tomassetti 《Pharmacological research》2003,48(1):55-60
The St. John's Wort (Hypericum perforatum) extract (Hp) represents one of the most useful natural therapeutic agents in the treatment of moderate and mild depression. The antidepressant effects of Hp are different, by a molecular mechanism point of view, when compared to those of other antidepressant drugs and, we think, a further pharmacological characterization is needed. It is suggested that the neurochemical effects of Hp could be bind either to its activity on the uptake of some mediators in the central nervous system or to the inhibition of some enzymatic activity at the receptor level. The present study carried out with the loose patch clamp (LPC) in the mouse neuromuscular junction, indicates a potentiation of the acetylcholine (ACh) action at the mouse neuromuscular junction. The spontaneous release of ACh was unaffected by Hp indicating that neither presynaptic nor postsynaptic function are modified by Hp. Indeed, both the frequency and the amplitude of the miniature end-plate currents (mepcs) were unmodified by Hp. Furthermore, the mepcs decay time (tau), i.e. the apparent cholinergic channel life time, was significantly increased after Hp treatment. The other parameter affected was the amplitude of the evoked end-plate currents (epcs) which was constantly and in a dose dependent manner increased by Hp. These findings suggest a possible action of Hp on the acetylcholinesterase (AChE) in terms of a reduction of the degradation rate of ACh. 相似文献
37.
Chiara Corsini Patrizia Mancuso Saki Paul Alessandra Burlini Giovanni Martinelli Giancarlo Pruneri Francesco Bertolini 《Clinical cancer research》2003,9(5):1820-1825
PURPOSE: Stroma cells play a relevant role in tumor development and progression. We investigated the activity of herceptin (HER), a humanized monoclonal antibody widely used for the treatment of HER2-overexpressing epithelial cancer, toward stroma cell lines L87/4 and L88/5. EXPERIMENTAL DESIGN: We studied the antiproliferative potential of HER and role of human serum in HER activity. We also investigated the ability of HER to alter ancillary functions of L87/4 and L88/5, such as support to long-term hematopoiesis, growth factor production, breast cancer cell adhesion, and proliferation. RESULTS: Flow cytometry showed that HER2 membrane expression in L87/4 and L88/5 stroma cells was intermediate between the expression in HER2-negative/dim MCF-7 breast cancer cells and HER2-bright SK-BC3 breast cancer cells. HER2 gene amplification was not detected by fluorescence in situ hybridization in either stromal cell lines. HER significantly inhibited L87/4 and L88/5 proliferation. Mean ID(50)s were found to be 2000 and 1700 micro g/ml for L87/4 and L88/5, respectively, after 3-day exposure and 800 micro g/ml for both cell lines after 9-day exposure. The presence of 10% human serum in the culture increased HER inhibitory activity. IC(50) of stroma cells was found to be intermediate between HER2-bright breast cancer cells (SK-BC3) and HER2-negative/dim breast cancer cells (MCF-7). The drug did not significantly affect the ability of stroma cells to support long-term hematopoiesis in the cobblestone area forming cell assay. In contrast, in coculture assay, MCF7 cells demonstrated a worse adhesion and growth capability on HER-treated stroma layers when compared with untreated stroma. Moreover, HER significantly reduced vascular endothelial growth factor production by L88/5 cells. CONCLUSIONS: Our data support the novel finding that HER may have a relevant activity against stroma cells. 相似文献
38.
Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. 总被引:15,自引:0,他引:15
Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC. 相似文献
39.
Giancarlo Colombo Carla Lobina Paola Maccioni M Francesca Mascia Alessandro Orrù Gian Luigi Gessa Mauro A M Carai 《Alcohol》2005,35(1):35-41
In the current study, we investigated the effect of the concurrent presentation of saccharin on the maintenance of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Rats were initially given access to alcohol [10% (volume/volume) in water] and water under the home cage, two-bottle, free-choice regimen, with unlimited access for 24 h/day for eight consecutive weeks. Next, a third bottle, containing saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], was concomitantly offered for an additional 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, with the 0.1% saccharin solution being the highest accepted. Alcohol intake was a U function of saccharin concentration, being reduced by 65%-95% in the group of rats exposed to the 0.1% saccharin solution. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin markedly reduced alcohol intake in alcohol-experienced sP rats and (2) the reducing effect of saccharin solutions on the alcohol intake in sP rats was positively related to their degree of acceptability. We hypothesized that saccharin solutions may have functioned as a reinforcer, partially substituting for alcohol reinforcement and rendering alcohol drinking less urgent. 相似文献
40.
Melina Verso Giancarlo Agnelli Sergio Bertoglio Franco C Di Somma Francesco Paoletti Walter Ageno Mario Bazzan Pasquale Parise Roberto Quintavalla Emanuele Naglieri Armando Santoro Davide Imberti Mariella Sorarù Stefano Mosca 《Journal of clinical oncology》2005,23(18):4057-4062
PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication. 相似文献