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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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S. Ramakrishnan MD DM Shyam S. Kothari MD DM FACC 《Catheterization and cardiovascular interventions》2008,72(3):413-415
We describe an unusual route and uncommon device use for the percutaneous closure of a modified Blalock–Taussig (BT) shunt. A 4‐year‐old male had presented with severe upper body swelling after a bidirectional Glenn shunt done one month earlier. The BT shunt which was clipped during the surgery was found to be patent. The BT shunt was finally closed from the bidirectional Glenn using an Amplatzer vascular plug, resulting in symptom relief. © 2008 Wiley‐Liss, Inc. 相似文献
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Rohini Sharma Ravinder K. Kaundal Shyam Sunder Sharma 《Pulmonary pharmacology & therapeutics》2009,22(3):183-189
Airway dysfunction and pulmonary neutrophilic inflammation are the major characteristics of inflammatory conditions of lungs like chronic obstructive pulmonary disease (COPD). Lipopolysaccharide (LPS), a constituent of cigarette smoke, has been identified as the most important risk factor for COPD development. Inhalation exposure to LPS or cigarette smoke elicits an inflammatory response accompanied by airway hyperresponsiveness, elevated proinflammatory mediators and inflammatory cells similar to COPD. In the present study, we have evaluated the effects of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, in LPS-induced pulmonary dysfunction, inflammatory changes and oxidative stress in guinea pigs. Inhalation exposure to nebulised LPS (30 μg ml?1) resulted in significant increase in the breathing frequency and bronchoconstriction accompanied with a significant decrease in tidal volume. Our results demonstrated that the LPS-induced pulmonary dysfunction was temporally associated with neutrophil infiltration as evident from heavy neutrophilia, increased TNFα in bronchoalveolar lavage fluid (BAL), elevated myeloperoxidase (MPO) level and histology of the lung tissue. Exposure to LPS also produced significant increase in tissue malondialdehyde (MDA) level indicating underlying oxidative stress. The results also reveal that pioglitazone (3, 10 and 30 mg kg?1, p.o.) is effective in abrogating the pulmonary dysfunction by attenuating neutrophilia, TNFα release and oxidative stress in LPS-induced model of acute lung inflammation. Results from the present study have added to the emergent body of evidence that PPARγ agonists are effective in the therapy of inflammatory disease of the lungs. 相似文献
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Sex pheromone of the pink hibiscus mealybug, Maconellicoccus hirsutus, contains an unusual cyclobutanoid monoterpene
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Zhang A Amalin D Shirali S Serrano MS Franqui RA Oliver JE Klun JA Aldrich JR Meyerdirk DE Lapointe SL 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(26):9601-9606
Two compounds that together constitute the female sex pheromone of the pink hibiscus mealybug (PHM), Maconellicoccus hirsutus, were isolated, identified, and synthesized. They are (R)-2-isopropenyl-5-methyl-4-hexenyl (S)-2-methylbutanoate [common name is (R)-lavandulyl (S)-2-methylbutanoate] and [(R)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoate [which we refer to as (R)-maconelliyl (S)-2-methylbutanoate]. Maconelliol is an unusual cyclobutanoid monoterpene, and its structure has been established by enantioselective synthesis from precursors of known structure and configuration. A 1:5 synthetic mixture of the two RS esters (1 microg per rubber septum) proved to be a potent attractant of males in field bioassays. The pheromone component, maconelliyl 2-methylbutanoate, represents a heretofore undescribed natural product. 相似文献
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A 5-year-old boy with stenosed left pulmonary artery following total correction of tetralogy of Fallot underwent surgical pulmonary arterioplasty through a left anterolateral thoracotomy on a normothermic perfused heart under cardiopulmonary bypass. We found this to be a convenient approach, and recommend it for correction of this lesion in the absence of gross pulmonary regurgitation and right ventricular outflow tract dilatation. 相似文献