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排序方式: 共有783条查询结果,搜索用时 15 毫秒
91.
Rajani B. Athawale Darshana S. Jain Kamlinder K. Singh Rajiv P. Gude 《Biomedicine & Pharmacotherapy》2014
Poor solubility of etoposide and associated poor bioavailability of the drug was circumvented by developing solid lipid nanocarrier system. The objective of the research work was to prepare etoposide loaded solid lipid nanoparticles (SLN) for improved efficacy and therapy of metastasized cancers. Entrapment of drug into nanoparticulate system modifies the pharmacokinetic and biodistribution profile of the drug with improved therapeutic efficacy. Solid lipid nanoparticles of various triglycerides were prepared using hot homogenization technique. Further, the process and formulation parameters viz. homogenization cycle and pressure, type of lipid were optimized. Developed nanoparticles were characterised for particle size, in vitro dissolution studies, DSC thermogram, surface morphology and cytotoxicity assay. Pharmacokinetic and biodistribution study were performed to assess the distribution of the drug in vivo. Modulation of the therapeutic activity of the drug was studied by performing antimetastatic activity on a B16F10 melanoma mouse model. The obtained results exhibited suitability of trimysristin for fabrication of nanoparticles. Characterisation of nanoparticles depicted formation of homogenous, spherical particles entrapping approximately 50% of the drug. The results for the performed MTT assay suggested that the developed nanoparticles exhibited cytotoxicity in a time- and concentration-dependent fashion. These findings concord with the results of the in vitro dissolution profile. Pharmacokinetic parameters demonstrated increase in area under curve (AUC), t1/2 and mean residence time (MRT) for drug in plasma. Further there is enhancement in the ratio of the drug that reaches to the highly perfused organs (upon encapsulation into solid lipid nanoparticles). Generally, cancer cells metastasized through the blood or lymphatic system. Accumulation of the drug in the highly perfused organ suggests suitability of the developed nanoparticles for targeting metastasized tumors. This was proved by the findings of the in vivo B16F10 mouse melanoma model. Improvement in the tumoricidal activity and survival rate of the animals substantiates the application of nanoparticles for improved therapeutic activity of etoposide. 相似文献
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Ronak Rajani MD MRCP FSCCT Roberta L. Brum MRCP Edward Barden FRCR MRCP Sarah Drake MRCP Rebecca L. Preston FRCR MRCP Gerald Carr‐White PHD MRCP John B. Chambers MD FACC FESC 《Catheterization and cardiovascular interventions》2013,82(7):E952-E958
Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri‐ and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patient's selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector‐computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI. © 2012 Wiley Periodicals, Inc. 相似文献
94.
Steven N. Leonard Megan E. Supple Ronak G. Gandhi Meghna D. Patel 《Antimicrobial agents and chemotherapy》2013,57(6):2678-2683
Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility. 相似文献
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M S Parihar Madhulika Chaudhary Rajani Shetty Taruna Hemnani 《Journal of clinical neuroscience》2004,11(4):397-402
Diabetes mellitus is reported to impair the memory function in experimental animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role in a diverse set of cognitive functions, such as novelty detection and memory, we examined the vulnerability of cortex and hippocampus regions of the brain to oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the attenuating effect of extracts of Withania somnifera and Aloe vera on prevention of hippocampal and cortical cell degenerations. Doses of both plant extracts given to experimental animals were based on the evaluation of their total antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and observed the changes in memory and motor behavioral functions in diabetic and control mice. The results showed a significant (P < 0.05) increase in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also found a significant impairment in both motor and memory behavioral functions in diabetic mice. However, when diabetic mice were supplemented with the extracts of Withania somnifera and Aloe vera, the oxidative damage in both brain regions was reduced as marked by a significant (p < 0.05) declines in both LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was more effective in reducing oxidative damage in brain regions than the supplementation of single plant extract. The combination also lowered the blood glucose level in comparison to STZ diabetic mice. Memory impairment and motor dysfunction were also improved by the plant extracts supplementation. We conclude that impairments in the hippocampus and cortex in STZ diabetic mice are associated with an increased free radical mediated oxidative damage and that the supplementation of plant extracts showed preventive effects in attenuating oxidative damage in both brain regions possibly via antioxidative mechanisms. 相似文献
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100.
Guan N Korukonda R Hurh E Schmittgen TD Donkor IO Dalton JT 《International journal of oncology》2006,29(3):655-663
Calpain is a class of Ca(2+)-dependent cysteine proteases and has been suggested to be involved in several important signaling cascades. A series of novel aldehyde calpain inhibitors identified in our laboratory were more potent and specific than commercially available calpain inhibitors, and were used to assess the involvement of calpain in cancer. Our inhibitors demonstrated potent anti-proliferative activity in four cancer cell lines (PC-3, HeLa, Jurkat and Daudi) with IC(50)'s ranging from 2 to >30 microM. A non-cancer cell line (CV-1) was 4-7-fold less sensitive than the cancer cell lines. Apoptotic activity was determined and appeared to be inversely correlated to calpain expression levels in the different cell types. Leukemia cell lines (i.e., Daudi and Jurkat) with undetectable m-calpain were more susceptible to the apoptotic effects in response to calpain inhibition, while apoptosis was not detected in PC-3 prostate cancer cells, which highly express m-calpain. The extent of apoptosis in HeLa cells was moderate under identical conditions. Apoptosis induced by calpain inhibition was accompanied by caspase-3 activation. Furthermore, cell cycle analysis showed that aldehyde calpain inhibitors arrested cells at the G2/M boundary in a concentration-dependent manner. These results indicate that aldehyde calpain inhibitors exhibit their cytotoxic effects via induction of G2/M arrest and apoptosis. Importantly, the compounds failed to exert any inhibitory effects toward 20S proteasome. Collectively, our results suggest that calpain is a novel target for the treatment of a variety of cancer diseases and provide leads for further discovery and development of calpain inhibitors. 相似文献