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1.
G M Pacifici A Viani M Franchi S Santerini A Temellini L Giuliani M Carrai 《British journal of clinical pharmacology》1990,30(3):427-435
1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
L Padeletti A Michelucci T Giovannini A Mezzani A Monopoli F Franchi 《Giornale italiano di cardiologia》1989,19(5):411-416
Programmed atrial stimulation at five atrial sites was performed to evaluate electrophysiologic atrial properties in 17 control patients (14 M, 3F, mean age 61 +/- 9 years) (Group A) and in 18 patients with paroxysmal atrial fibrillation (13 M, 5 F, mean age 61 +/- 5 years) (Group B) with normal sinus node function. The mean value of the P wave duration was similar in both groups. Programmed atrial stimulation was performed at five atrial sites: high, medium and low lateral wall, and high and low medial wall. We evaluated the following parameters: A) local conduction delay measured at the functional refractory period as the difference between A1-A2 and S1-S2 intervals; B) widening of local electrogram measured at the functional refractory period as the difference between A1-A2 interval measured at the end of each local electrogram and A1-A2 interval measured at the beginning of each local electrogram. We evaluated the mean and the maximum value of the two above-mentioned parameters; C) dispersion of effective refractory period and functional refractory period, determined as the longest minus the shortest refractory period from the range of refractory periods measured in each patient; D) the mean of effective refractory periods and functional refractory periods observed at five atrial sites. Mean and maximum local conduction delay, mean effective and functional refractory periods did not present significant differences in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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S. Stegemann F. Leveiller D. Franchi H. de Jong H. Lindn 《European journal of pharmaceutical sciences》2007,31(5):249-261
Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.
The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail. 相似文献
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M Franchi F Eppinger G F Filippini G Montanari 《Bulletin du Groupèment international pour la recherche scientifique en stomatologie & odontologie》1992,35(3-4):93-97
Premolars roots of humans were manually instrumented with K-type files and irrigated with different solutions to evaluate the rate of cleaning of endodontic surface. Root canals irrigated with 0.9% saline solution or H2O2 (10 volumes) showed the presence of predentin and amorphous smear layer. Thick smear layer was always present on endodontic walls rinsed with 5% solution of NaOCl. Specimens treated with 0.2% solution of EDTA showed partially clean dentinal tubules orifices and remnants of a thin smear layer. Occasional uninstrumented areas of the same roots presented smear layer remnants and predentin with calcified bacteria. The root canals irrigated with NaOCl and EDTA solutions alternated after each instrument showed at the dentin surface thick smear layer: only few dentinal tubules orifices were visible. Endodontic surface of root canals irrigated with NaOCl during instrumentation and finally rinsed with EDTA solutions showed the most homogeneous ultrastructural pictures: partially clean dentinal orifices were detectable in the whole canals. 相似文献
8.
Distribution of 2-naphthol sulphotransferase and its endogenous substrate adenosine 3′-phosphate 5′-phosphosulphate in human tissues 总被引:1,自引:0,他引:1
M. Cappiello M. Franchi L. Giuliani G. M. Pacifici 《European journal of clinical pharmacology》1989,37(3):317-320
The activity of sulphotransferase towards 2-naphthol and the concentration of its endogenous substrate, adenosine 3'-phosphate 5'-phosphosulphate (PAPS), have been measured in five specimens of human liver, lung, and kidney, and the mucosa from the ileum and the ascending, descending and sigmoid colon. The activity of 2-naphthol sulphotransferase (mean nmol.min-1.mg-1 protein) was 1.82 (liver); 0.034 (kidney); 0.19 (lung); 0.64 (ileum); 0.47 (ascending colon); 0.50 (descending colon); 0.40 (sigmoid colon). The concentration of PAPS (mean nmol.g-1 wet tissue) was 22.6 (liver); 4.8 (kidney); 4.3 (lung); 12.8 (ileum); 8.1 (ascending colon); 7.5 (descending colon); 6.2 (sigmoid colon). The concentration of PAPS and the activity of 2-naphthol sulphotransferase were higher in the liver than in the extrahepatic tissues. There was significant difference between ileum and ascending colon, both the activity of sulphotransferase and the concentration of PAPS being higher in the former. 2-Naphthol sulphotransferase activity and the concentration of PAPS have consistent distribution patterns. Differences between the tissues studied were more marked for sulphotransferase than for its endogenous substrate. 相似文献
9.
Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma 总被引:4,自引:0,他引:4
Massi D Franchi A Paglierani M Ketabchi S Borgognoni L Reali UM Santucci M 《Human pathology》2004,35(4):496-502
The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma. 相似文献
10.
Clustering of Y chromosome deletions in subinterval E of interval 6 supports the existence of an oligozoospermia critical region outside the DAZ gene. 总被引:4,自引:0,他引:4 下载免费PDF全文
L Stuppia V Gatta G Mastroprimiano F Pompetti G Calabrese P Guanciali Franchi E Morizio R Mingarelli M Nicolai R Tenaglia L Improta V Sforza S Bisceglia G Palka 《Journal of medical genetics》1997,34(11):881-883
Y chromosome molecular analysis was performed using the STS-PCR technique in 50 patients with oligozoospermia. Microdeletions of interval 6 of the Y chromosome were detected in seven patients, in six of whom subinterval E was affected. All patients retained the RBM1 and DAZ genes, while in one deletion involved the SPGY gene. The size of the deletion was not apparently related to the severity of the disease. These results suggest the presence of an oligozoospermia critical region on the Y chromosome within subinterval E of interval 6. 相似文献