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Bronwen J. Mayo Kate R. Secombe Anthony D. Wignall Emma Bateman Daniel Thorpe Claudio Pietra Dorothy M. Keefe Joanne M. Bowen 《Cancer chemotherapy and pharmacology》2020,85(4):793-803
Lapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine. We used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib. Rats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide. Elsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea. 相似文献
13.
4-Aminopyridine derivatives with antiamnesic activity 总被引:3,自引:0,他引:3
Andreani A Leoni A Locatelli A Morigi R Rambaldi M Pietra C Villetti G 《European journal of medicinal chemistry》2000,35(1):77-82
Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam. 相似文献
14.
Hudaib M Speroni E Di Pietra AM Cavrini V 《Journal of pharmaceutical and biomedical analysis》2002,29(4):691-700
Capillary GC/MS analysis based on polar and non-polar columns has been applied to evaluation of the volatile oils hydrodistilled from thyme (Thymus vulgaris L.) plants. The adopted methodology has been used to monitor seasonal variations in the composition of the oil obtained from thyme herbs harvested at different periods during the plant vegetative and life cycles. Oils from thyme plants of young (2 years) and old (5 years) cultivations have been evaluated from four and two collections, respectively, effected throughout May/December growth period. Generally, the oil was found to be rich in the active monoterpene phenols (thymol and carvacrol) and their corresponding monoterpene hydrocarbon (HC) precursors (p-cymene and gamma-terpinene), which collectively showed synchronized patterns of variation during the different collection periods and in different seasons. The oil from old plant collected in May/June period (0.15% v/w) was characterized by significantly lower levels of monoterpene HCs (mainly gamma-terpinene) and the highest levels of the oxygenated monoterpenes (linalool and borneol), monoterpene phenols (mainly thymol) and their derivatives (mainly carvacrol methyl ether), sesquiterpenes (mainly beta-caryophyllene) and their oxygenated derivatives (e.g. caryophyllene oxide) in comparison with all other samples. A characteristic presence of camphor and thymodihydroquinone was also observed in the old plant oils. On the other hand, the young plant, collected in June/July just before the end of the vegetative cycle, provided the best oil yield (1.2%) with also the highest % content of the monoterpene phenols (thymol: 51.2% and carvacrol: 4%). This latter growth period can represent the best harvest time of young thyme plants in order to obtain an essential oil with better quality and quantity. 相似文献
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Extracts of Monascusus Purpureus beyond Statins——Profile of Efficacy and Safety of the Use of Extracts of Monascus Purpureus 下载免费PDF全文
BIANCHI Antonio 《中国结合医学杂志》2005,(4)
Monascus purpureus is a fungus that has been tradi-tionally used in China for thousands of years to produce ricewine . Traditionally the fungus is used to ferment non-gluti-nous cooking of rice ,to produce a kind of famous red ricewine .Its main traditional indications consist of disordersdue to the accumulation of fats (nosologically linked withthe problems of stasis of circulation in traditional Chinesemedicine) ,liver disorders and some forms of tumor as ithelps i mprove the circulation of … 相似文献
17.
With the advent of the T cell activation inhibitors such as cyclosporine, heart transplant success rates for pediatric patients have improved to the point that the initially restricted ages and indications have expanded considerably. Currently the half-life (50% still alive) for children transplanted in the early 1980s is approximately 12-14 years. Decades-long survival seems likely. Components and functions of the immune system are na?ve and change during postnatal development. Maturation occurs not only in the first years of life, but well through adolescence and even into adult life. These age-dependent changes within the immune system greatly complicate any attempt to assess immune implications for the use of immunosuppression in children. Since the introduction of cyclosporine, immunosuppression regimens have been virtually unchanged through the 1990s. Recently, there have been significant new immune pharmacological agents which are now commercially available, or still in investigational stages of development. The new maintenance immunosuppressive drugs are either inhibitors of de novo synthesis of nucleotides (purines or pyrimidines), or are immunophilin-binding drugs that inhibit signal transduction in lymphocytes. The newer inhibitors of de novo nucleotide synthesis include mycophenolate mofetil, mizoribine, brequinar and leflunomide. The immunophilin-binding drugs are cyclosporine, tacrolimus and rapamycin. Antibody preparations such as ATG, ATGAM and OKT3, as well as the newer biological agents, which specifically bind to the IL-2 receptor, basiliximab and daclizumab, are discussed. The potential for biologicals which inhibit co-stimulation are also discussed. There may be dramatic changes in protocols used clinically as a result of these new agents over the next decade. The increasing understanding of the alloimmune response as well as the clinical use of these newer drugs promise even better long-term results. 相似文献
18.
A specific high-performance liquid chromatographic (HPLC) procedure suitable as a stability-indicating assay for the methenolone esters (the acetate and enanthate) analysis in pharmaceutical formulations was investigated. The analysis was carried out under isocratic and reversed-phase conditions using a UV detector (240 nm). A RP8-HPLC system was of choice for the methenolone enanthate analysis. 相似文献
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Spontaneous regression of pulmonary leiomyomas during pregnancy. 总被引:6,自引:0,他引:6
Multiple pulmonary nodular densities simulating metastastic cancer were discovered in a routine chest roentgenogram of a 30-year-old pregnant woman. Lung biopsy revealed nodules composed of smooth muscle and collagenous tissue containing entrapped glandular elements. The lesions were initially interpreted as multiple pulmonary fibroleiomyomatous hamartomas (MPFLH). During pregnancy and the post-partum period, the pulmonary nodules regressed spontaneously. Critical analysis of the published cases as well as our own case indicates that multiple pulmonary fibroleiomyomatous hamartomas (MPFLH) cannot be distinguished from benign metastasizing leiomyoma (BML) by either clinical, roentgenographic, or pathologic criteria and that all represent pulmonary metastases from a primary uterine neoplasm. The spontaneous regression of the pulmonary nodules in the present case as well as the increased risk for development of progressive pulmonary insufficiency in the pre-menopausal patients indicates an apparent hormonal dependence. Total abdominal hysterectomy and bilateral salpingo-oophorectomy appears to be the treatment of choice. 相似文献