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101.
ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats 总被引:2,自引:0,他引:2
Liebetrau M Burggraf D Wunderlich N Jäger G Linz W Hamann GF 《Neuroscience letters》2005,376(3):205-209
The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model of malignant hypertension which lead to secondary alterations of the extracellular matrix. Our aim was to determine ACE-inhibitor related changes of proteases involved in the reconstruction of the extracellular matrix in the brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated with either an antihypertensive dose of ramipril or placebo for 6 months. Brain tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP-9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p < 0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25% in the basal ganglia (p < 0.0001 each). No differences were observed in the amount of TIMP-1 or TIMP-2. These findings provide new insights into the biochemical mechanisms underlying extracellular matrix proliferation and its modulation by ACE inhibitors. Therapeutic alterations that influence the proteolytic systems might prove important in the prevention of extracellular matrix accumulation and secondary microvascular vessel wall changes. 相似文献
102.
Needle biopsy of renal allografts: comparison of two techniques 总被引:2,自引:0,他引:2
Bogan ML; Kopecky KK; Kraft JL; Holladay AO; Filo RS; Leapman SB; Thomalla JV 《Radiology》1990,174(1):273-275
Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications. 相似文献
103.
Andreas Schalhorn Michael Kühl Gabriele Stupp-Poutot Volkmar Nüssler 《Cancer chemotherapy and pharmacology》1990,25(6):440-444
Summary After the use of d,1-folinic acid (d,1-CHO-THF), pharmacokinetic measurements should take into account 1-CHO-THF and its metabolite 1-methyltetrahydrofolic acid (1-CH3-THF) as well as d-CHO-THF. For this purpose, we developed a simple and rapid assay by combining reversed-phase HPLC to determine total levels of d,1-CHO-THF and CH3-THF and chiral HPLC to separate the biologically active 1-CHO-THF from the inactive d-CHO-THF. We investigated the pharmacokinetics after short-term infusion of 300 mg d,1-CHO-THF in ten healthy volunteers. With a mean of 56.5 min, 1-CHO-THF exhibits a rapid body clearance of 222 ml/min, about 60% of which is caused by metabolism to CH3-THF and 40%, by renal excretion. CH3-THF has a terminal half-life of 208 min and a total body clearance of 88.9 ml/min, which is essentially the same as the renal clearance. Due to the lower clearance of CH3-THF, its AUC (2,132 M × min) exceeds that of 1-CHO-THF (1445 M × min) by approximately 50%. In contrast to that of the reduced 1-folates, the total body and renal clearance of d-CHO-THF is very low, with values of 13.2 and 12.9 ml/min, respectively. This results in a very high AUC of 24, 269 M × min, which is higher by factors of 17 and 11 than those of 1-CHO-THF and CH3-THF, respectively. The implications of the distinct kinetics of the reduced 1-folates and d-CHO-THF for the efficacy of folinic acid/5-fluorouracil therapy and adequate protocols for the treatment of advanced colorectal cancer are discussed.Abbreviations CH2-THF
N-5,N-10-methylenetetnahydrofolic acid
- CH3-THF
N-5-methyltetrahydrofolic acid
- CHO-THF
N-5-formyltetrahydrofolic acid
- 5-FU
5-fluorouracil
- FBAL
-fluoro--alanine
- FUH2
dihydrofluorouracil
- FUPA
-fluoroureidopropionic acid
Dedicated to Prof. Dr. W. Wilmanns on the occasion of his 60th birthdayThis study was carried out with the support of the Lederle Company, Wolfratshausen 相似文献
104.
Tanja Neupert Gabriele Ihorst Wilfried Karmaus Thomas Frischer Matthias Kopp Christel Ulmer Brigitte Schwöbel Johannes Forster Joachim Kühr 《Zeitschrift fur Gesundheitswissenschaften》1997,5(1):63-75
Conclusion
Geographical differences in morbidity of asthma and asthmalike complaints were ascertained and remained stable after adjustment for potential confounders. However, the choice of the way of presentation (relative risk versus deviation from the weighted mean of the prevalences) can provoke different suggestive effects. 相似文献105.
Letizia Mazzini Daniela Testa Carla Balzarini Gabriele Mora 《Journal of neurology》1994,241(4):223-227
Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS. 相似文献
106.
Borghese M Gabriele R Antoniozzi A Teneriello F Caporale A Giuliani A Lombardo F Rengo M 《Il Giornale di chirurgia》1999,20(1-2):35-40
The Authors, after a short introduction concerning the primary carcinoma of the cystic duct and the exact definition according to Farrar's criteria, report a case occurred to their observation, the 35th case of international literature. In particular the importance of some hemato-clinical parameters and instrumental investigation (ERCP, angio-CT) to underlined in order to surgical indication. In the case here reported cholecystectomy uses informed with partial resection of the hepato-choledochus and excision of some periductal and pericholedochus lymph nodes. Finally, the Authors discuss about clinical data and diagnostic and therapeutic trends, on the case of their experience and literature review. 相似文献
107.
108.
Polyamine metabolism in gliomas 总被引:2,自引:0,他引:2
Ralf-Ingo Ernestus Gabriele Röhn Roland Schröder Thomas Els Jin-Yul Lee Norfrid Klug Wulf Paschen 《Journal of neuro-oncology》1996,29(2):167-174
Summary Biosynthesis of the polyamines putrescine, spermidine, and spermine has been found to be activated in tissues with cellular proliferation. In the present study we have investigated polyamine levels and the activity of the first rate-limiting enzyme ornithine decarboxylase (ODC) in tumour samples obtained during operation of 202 patients with gliomas. Biochemical data were closely related to the grading of malignancy and to the morphological characteristics of each sample. Mean ODC activity was significantly higher in all gliomas as compared to peritumoural non-neoplastic brain. Furthermore, it was significantly higher (p 0.001) in anaplastic gliomas who grade III and IV (9.0 ± 9.6 nmol/g/h) than in gliomas WHO grade I and II (3.3 ± 4.2 nmol/g/h). Highest enzyme activity (58.5 nmol/g/h) was found in solid and vital parts of malignant tumours, whereas predominantly necrotic areas exhibited low ODC activity (< 1 nmol/g/h). Thus, intra- and interindividual variability of ODC activity corresponded well to histomorphological heterogeneity in high-grade gliomas. Putrescine levels also increased with rising grade of malignancy, whereas spermidine and spermine levels did not correlate with the histological grading. In conclusion, high ODC activity represents a biochemical marker of malignancy in gliomas, but low values do not prove benignity. The present study reinforces the need of further and more extensive tumour sampling closely related to follow-up investigations in the heterogeneous group of gliomas. 相似文献
109.
AIMS AND BACKGROUND: Isolated vaginal recurrences of endometrial carcinoma are rare, and prognostic factors that predict treatment outcome are still not well defined. The aim of the present study was to evaluate the results of brachytherapy in isolated vaginal recurrences from endometrial carcinoma. METHODS: Thirty-five patients with isolated vaginal recurrences were treated with brachytherapy with intravaginal ovoids or cylinders that were calculated to deliver 6000 to 7000 cGy at the surface. Patients were assessed for size and location of recurrence at presentation, response and complications from therapy. RESULTS: Treatment was well tolerated by most patients. Grade 2 toxicity occurred in 4 patients (3 cases of partial vaginal stenosis and one proctitis). Complete response to radiation was observed in all patients, and an overall 9 failures were observed (4 local, 4 distant and 1 local plus distant). Twenty patients (57%) were alive without evidence of disease at 3 to 11 years following treatment. Site of vaginal recurrence (upper third versus others) and long (more than 12 months versus less than 12 months) interval from hysterectomy were the only factors significantly related to local failures. CONCLUSIONS: Isolated vaginal recurrences following hysterectomy for endometrial carcinoma can be treated with brachytherapy with a low rate of severe toxicity. 相似文献
110.
Identification of an aflatoxin G1-serum albumin adduct and its relevance to the measurement of human exposure to aflatoxins 总被引:1,自引:0,他引:1
A major aflatoxin G1 (AFG1)-albumin adduct has been identifiedand characterized in rats following exposure to AFG1. The productisolated from a Pronase digest of in vivomodified albumin wasidentical by chromatographic retention time to the syntheticproduct obtained by the acylase-catalysed deacetylation productof N-acetyl-L-lysine with 8,9-dihydro- 8,9-dibromo-AFG1. Thein vitro product, AFG1-lysine, was characterized by UV, fluorescence,1H- and 13C-NMR spectroscopy and fast atom bombardment MS. Acompetitive enzyme-linked immunoassay for this adduct was establishedusing polyclonal antibodies to AFB, and this was used togetherwith an HPLC-fluorescence technique to quantitate the in vivoformation of AFG1albumin adducts in comparison to AFB1.A linear doseresponse relationship was observed in ratsfollowing single exposures to 0.1 3 mg AFG1/kg body wt.The levels of AFG1-albumin adducts were determined to be 5.7-and 2.8-fold lower than with equivalent doses of AFB1 as determinedby immunoassay and HPLC fluorescence respectively. The lowerbinding of AFG1 and the lower levels in the human food supplycompared to AFB, suggest that the newly identified adduct couldbe added as an internal standard for methods using the measurementof aflatoxin-albumin adducts to quantitate human exposure toaflatoxin. 相似文献