排序方式: 共有27条查询结果,搜索用时 31 毫秒
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Coleman CI Reddy P Laster-Bradley NM Dorval S Munagala B White CM 《The Annals of pharmacotherapy》2003,37(7-8):956-961
OBJECTIVE: To determine whether a letter-based intervention program submitted to prescribers and pharmacists would improve drug therapy in users of high-dose beta(2)-agonists (HDBs). STUDY DESIGN: Retrospective drug utilization review. PATIENTS AND METHODS: The intervention group consisted of 135 asthmatic patients (identified through ICD-9-CM codes) in the Connecticut Medicaid Program who submitted >1 claim per month for short-acting beta(2)-agonists (over a 6-mo period). Patient-specific intervention packets were mailed to the patients' prescribers and pharmacists, and their use of long-term control agents and healthcare utilization was evaluated over 6 months. These variables were compared with a comparison group (n = 510) of asthmatics drawn from the same Medicaid program who were not considered to be high-dose users of short-acting beta(2)-agonists at baseline. RESULTS: Prior to the intervention, the intervention group used fewer long-term asthma control agents as compared with the comparison group (58% vs. 96%; p < 0.001); there was no significant difference after the intervention program (65% vs. 71%; p = 0.169). The acquisition of spacers was greater in the intervention group than in the control group after the intervention (7% vs. 2%; p = 0.007). At the end of the 6-month intervention period, 46% of patients in the intervention group were no longer HDB users (p < 0.001). The higher frequency of prescriber office visits in the intervention group than the comparison group before the intervention (0.46 +/- 0.82 vs. 0.25 +/- 0.66; p < 0.001) was not evident after the intervention program (0.24 +/- 0.63 vs. 0.18 +/- 0.60; p = 0.283). CONCLUSIONS: This intervention program had modest impact on improving the use of long-term control agents and reducing prescriber office visits. 相似文献
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Trichomonas vaginalis, a parasitic protozoan and the causative agent of trichomoniasis, lacks de novo purine nucleotide synthesis and possesses a unique purine salvage pathway, consisting of a bacterial type purine nucleoside phosphorylase and a purine nucleoside kinase. It is generally believed that adenine and guanine are converted to their corresponding nucleosides and then further phosphorylated to form AMP and GMP, respectively, as the main as well as the essential pathway of replenishing the purine nucleotide pool in the organism. Formycin A, an analogue of adenosine, inhibits both enzymes as well as the in vitro growth of T. vaginalis with an estimated IC(50) of 0.27 microM. This growth inhibition was reversed by adding adenine to the culture medium but not by adding guanine or hypoxanthine. Furthermore, T. vaginalis can grow in semi-defined medium supplemented with only adenine but not with guanine or hypoxanthine. Radiolabeling experiments followed by HPLC analysis of the purine nucleotide pool in T. vaginalis demonstrated incorporation of [8-14C]adenine into both adenine and guanine nucleotides, whereas [8-14C]guanine was incorporated only into guanine nucleotides. Substantial adenosine deaminase activity and significant IMP dehydrogenase and GMP synthetase activities were identified in T. vaginalis lysate, suggesting a pathway capable of converting adenine to GMP via adenosine. This purine salvage scheme depicts adenosine the primary precursor of the entire purine nucleotide pool in T. vaginalis and the purine nucleoside kinase one of the most pivotal enzymes in purine salvage and a potential target for anti-trichomoniasis chemotherapy. 相似文献
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Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania Somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ± 0.05 μM). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects. 相似文献
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Hina Kausar Radha Munagala Shyam S. Bansal Farrukh Aqil Manicka V. Vadhanam Ramesh C. Gupta 《Cancer letters》2013
Cucurbitacin B (CuB), has recently emerged as a potent anticancer agent; however, its efficacy in non-small-cell lung cancer (NSCLC) and the mechanism(s) initiating its biological effects remain largely unclear. In this study, CuB potently suppressed the growth of four NSCLC cells (H1299, A549, HCC-827 and H661) in vitro and the highly aggressive H1299 xenograft in vivo. CuB significantly altered the actin cytoskeletal assembly, induced G2/M cell-cycle arrest and mitochondrial apoptosis through the modulation of several key molecular targets mediating the aforementioned processes. Interestingly, all cellular effects of CuB were completely attenuated only by the thiol antioxidant N-acetylcysteine (NAC). Furthermore, pretreatment with glutathione synthesis inhibitor butithione-sulfoxime (BSO), significantly exacerbated CuB’s cytotoxic effects. To this end, cells treated with CuB revealed a rapid and significant decrease in the levels of protein thiols and GSH/GSSG ratio, suggesting disruption of cellular redox balance as the primary event in CuB’s cytotoxic arsenal. Using UV and FTICR mass spectrometry we also demonstrate for the first time a physical interaction of CuB with NAC and GSH in a cell-free system suggesting that CuB interacts with and modulates cellular thiols to mediate its anti-cancer effects. Collectively, our data sheds new light on the working mechanisms of CuB and demonstrate its therapeutic potential against NSCLC. 相似文献
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Gupta RC Bansal SS Aqil F Jeyabalan J Cao P Kausar H Russell GK Munagala R Ravoori S Vadhanam MV 《Carcinogenesis》2012,33(8):1608-1615
Many chemopreventive agents have encountered bioavailability issues in pre-clinical/clinical studies despite high oral doses. We report here a new concept utilizing polycaprolactone implants embedded with test compounds to obtain controlled systemic delivery, circumventing oral bioavailability issues and reducing the total administered dose. Compounds were released from the implants in vitro dose dependently and for long durations (months), which correlated with in vivo release. Polymeric implants of curcumin significantly inhibited tissue DNA adducts following the treatment of rats with benzo[a]pyrene, with the total administered dose being substantially lower than typical oral doses. A comparison of bioavailability of curcumin given by implants showed significantly higher levels of curcumin in the plasma, liver and brain 30 days after treatment compared with the dietary route. Withaferin A implants resulted in a nearly 60% inhibition of lung cancer A549 cell xenografts, but no inhibition occurred when the same total dose was administered intraperitoneally. More than 15 phytochemicals have been tested successfully by this formulation. Together, our data indicate that this novel implant-delivery system circumvents oral bioavailability issues, provides continuous delivery for long durations and lowers the total administered dose, eliciting both chemopreventive/chemotherapeutic activities. This would also allow the assessment of activity of minor constituents and synthetic metabolites, which otherwise remain uninvestigated in vivo. 相似文献
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The natriuretic peptides in cardiovascular medicine 总被引:13,自引:0,他引:13
Within the last five years, assay systems for measurement of plasma levels of brain natriuretic peptide (BNP) have been approved as a diagnostic aid for heart failure (HF). Similarly, nesiritide, a recombinant form of human BNP, has been approved for the treatment of acutely decompensated HF. Both BNP as a diagnostic test and a therapeutic modality are rapidly becoming integrated into clinical practice. The purpose of this review is to provide a brief overview of the physiology of the natriuretic peptides relevant to their informed clinical use. The current literature regarding the utility of measuring BNP for the diagnosis and management of HF is reviewed and practical recommendations regarding the interpretation of BNP levels are offered. The clinical literature regarding the use of recombinant BNP for the treatment of HF is reviewed, underscoring current gaps in our knowledge regarding the indications for and benefits of this novel agent. 相似文献
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Vikas Singh Rodrigo Mendirichaga Ghanshyambhai T. Savani Alexis P. Rodriguez Nitika Dabas Anish Munagala Carlos E. Alfonso Mauricio G. Cohen Sammy Elmariah Igor F. Palacios 《Journal of interventional cardiology》2017,30(5):405-414