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61.
62.
Oleanolic acid promotes healing of acetic acid-induced chronic gastric lesions in rats. 总被引:7,自引:0,他引:7
Jaime A Rodríguez Luis Astudillo Guillermo Schmeda-Hirschmann 《Pharmacological research》2003,48(3):291-294
PURPOSE: Previous work demonstrates that oleanolic acid (OA), a triterpene widely distributed in plants, shows gastroprotective effect in the ethanol, aspirin and pilorous ligature-induced gastric ulcer in rats as well as in the ethanol/hydrochloric acid-induced ulcer in mice. The aim of this work was to assess the healing effect of OA in the acetic acid-induced chronic gastric ulcer model in rats. METHODS: Chronic gastric lesions were induced in male Sprague-Dawley rats with acetic acid. OA was administered orally during 14 days at 25, 50 and 100 mg/kg per day. Ranitidine (50 mg/kg) and the vehicle were used as controls. The ulcer area (mm2) and the curative ratio (%) were determined. Histological preparations were carried out for comparative purposes. RESULTS: The effect of OA was significantly different as compared to the control reducing the lesion area (in mm2) from 39+/-7 in controls to 17.8+/-1.9 and 9.4+/-1.1 at the doses of 50 and 100 mg/kg, respectively. The curative ratio was 54.5 and 76% for the compound at 50 and 100 mg/kg, while ranitidine at 50 mg/kg reduced the lesion area to 6.9+/-0.8 with a curative ratio of 84%. Mucosal thickness increased from 342 microm in controls to 540 microm in oleanolic acid- (100 mg/kg) and 945 microm in ranitidine-treated animals. Histological examination of the stomach showed regeneration of the lesions. CONCLUSIONS: OA improves healing of chronic gastric lesions in rats. The low toxicity and widespread occurrence of OA in plants suggest a potential for the development of the triterpene or their derivatives as a new antiulcer drug. 相似文献
63.
Antoinette R Tan Xiaowei Yang Stephen M Hewitt Arlene Berman Erin R Lepper Alex Sparreboom Allyson L Parr William D Figg Catherine Chow Seth M Steinberg Stephen L Bacharach Millie Whatley Jorge A Carrasquillo Jaime S Brahim Seth A Ettenberg Stan Lipkowitz Sandra M Swain 《Journal of clinical oncology》2004,22(15):3080-3090
PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients. 相似文献
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J. Jaime Caro MDCM K. Jack Ishak MSc Ingrid Caro MEd Kristen Migliaccio-Walle BS Wendy S. Klittich BS 《Value in health》2004,7(5):585-594
OBJECTIVES: Clinicians are told to use the number needed to treat (NNT) to compare the benefits of therapeutic strategies, and researchers are asked to report results this way, generally without considering differences among the studies from which these were derived. METHODS: The crude NNT currently advocated is compared to the NNT standardized for a common outcome, follow-up time, study population and comparator. An NNT model for cardiovascular disease is described as an example that addresses differences among studies of secondary prevention of cardiovascular disease. Crude NNTs are compared to those obtained from the model. RESULTS: Follow-up in the 18 trials identified varied from 1.0 to 6.2 years; rates of cardiovascular events in the untreated subgroups ranged from 4.8% to 45.9%. The crude NNTs were more variable (9.1-163.7) than those obtained from the model (9.1-75.2). The effect of standardization was substantial in some cases, with proportional changes ranging from a 91% decrease to a 223% increase. CONCLUSION: Using an NNT model to account for differences in study design allows for more meaningful comparisons. 相似文献
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Jaime Vengoechea Aditi S Parikh Shulin Zhang Flora Tassone 《European journal of human genetics : EJHG》2012,20(11):1197-1200
Loss-of-function due to expansion of a CGG repeat located in the 5''UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient. 相似文献
69.
The advent of dialytic therapy has enabled nephrologists to provide life‐saving therapy, but potassium balance continues to be an ever present challenge in the ESRD population. Although a small percent of patients are chronically hypokalemic, hyperkalemia is by far the most common abnormality in dialysis patients. It is associated with increased all‐cause mortality, cardiovascular mortality, and arrhythmogenic death. Although alterations of the dialysis bath may decrease predialysis potassium, potassium baths <2 mEq/l are associated with a higher risk of sudden cardiac death. Studies show that patients are aware of the risks of hyperkalemia, but adherence to a low potassium diet is suboptimal. ACEI, ARBs, and spironolactone may cause slight increases in potassium even in anuric patients, requiring increased surveillance. Fludrocortisone and potassium binders have not been proven to be beneficial in lowering interdialytic potassium levels. Frequent hemodialysis may be a viable option, and studies of prophylactic placement of implantable cardioverter/defibrillators are underway. 相似文献
70.
Michael B. Harbut Bhumit A. Patel Bryan K. S. Yeung Case W. McNamara A. Taylor Bright Jaime Ballard Frantisek Supek Todd E. Golde Elizabeth A. Winzeler Thierry T. Diagana Doron C. Greenbaum 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21486-21491
Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target. 相似文献