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      1. Author :
        Zhang, J.; Preda, D. V.; Vasquez, K. O.; Morin, J.; Delaney, J.; Bao, B.; Percival, M. D.; Xu, D.; McKay, D.; Klimas, M.; Bednar, B.; Sur, C.; Gao, D. Z.; Madden, K.; Yared, W.; Rajopadhye, M.; Peterson, J. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Am J Physiol Renal Physiol
      6. Products :
      7. Volume :
        303
      8. Issue :
        N/A
      9. Page Numbers :
        F593-603
      10. Research Area :
        N/A
      11. Keywords :
        ReninSense 680 FAST, FMT, Animal Feed/analysis; Animals; Cathepsin D; Cathepsin G; Female; Fluorescent Dyes/*pharmacology; Humans; Mice; Mice, Inbred C57BL; Peptides/*pharmacology; Peptidyl-Dipeptidase A/metabolism; Rats; Renin/*blood/*metabolism; Renin-Angiotensin System/physiology; Sensitivity and Specificity; Sodium, Dietary
      12. Abstract :
        The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22674025
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10572
      1. Author :
        Pan, Y.; Zhong, L. J.; Zhou, H.; Wang, X.; Chen, K.; Yang, H. P.; Xiaokaiti, Y.; Maimaiti, A.; Jiang, L.; Li, X. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Acta Pharmacol Sin
      6. Products :
      7. Volume :
        33
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, 14-3-3 Proteins/*genetics; Animals; Anticoagulants/pharmacology/*therapeutic use; Antineoplastic Agents/pharmacology/*therapeutic use; Apoptosis/drug effects; Cadherins/genetics; Cell Cycle/drug effects; Cell Line, Tumor; Cell Proliferation/*drug effects; Gene Expression Regulation, Neoplastic/drug effects; Heparin/pharmacology/*therapeutic use; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis/drug therapy/genetics; Neoplasms/*drug therapy/genetics; Prostate/drug effects/metabolism; Prostatic Neoplasms/drug therapy/genetics; Transforming Growth Factor beta/genetics; Vimentin/*genetics
      12. Abstract :
        AIM: To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin. METHODS: Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 mug/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10-luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-beta, E-cadherin, and alpha(v)-integrin was measured by RT-PCR. RESULTS: Heparin 25 and 125 mug/mL significantly inhibited the proliferation, arrested the cells in G(1) phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down-regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 mug/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of alpha(v)-integrin. Heparin 125 mug/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-beta mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells. CONCLUSION: Heparin inhibited PC-3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and alpha(v)-integrin expression.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22669117
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10534
      1. Author :
        Smith, B. R.; Kempen, P.; Bouley, D.; Xu, A.; Liu, Z.; Melosh, N.; Dai, H.; Sinclair, R.; Gambhir, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nano Lett
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; *Disease Models, Animal; Ear Neoplasms/*blood supply/pathology; Humans; Mice; Microscopy, Fluorescence; Nanoparticles/*chemistry; *Nanotechnology; Nanotubes, Carbon/chemistry; Neoplasms, Experimental/*blood supply/pathology; Particle Size; Quantum Dots; Surface Properties
      12. Abstract :
        Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22650417
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10439
      1. Author :
        Subbarayan, P. R.; Sarkar, M.; Nagaraja Rao, S.; Philip, S.; Kumar, P.; Altman, N.; Reis, I.; Ahmed, M.; Ardalan, B.; Lokeshwar, B. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Ethnopharmacol
      6. Products :
      7. Volume :
        142
      8. Issue :
        N/A
      9. Page Numbers :
        523-30
      10. Research Area :
        N/A
      11. Keywords :
        BxPC-3, BxPC-3-luc2, IVIS, Achyranthes; Animals; Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use; Apoptosis/*drug effects; Caspase 3/genetics/metabolism; Gene Expression/drug effects; Humans; Injections, Intraperitoneal; Medicine, Ayurvedic; Mice; Mice, Nude; Pancreatic Neoplasms/*drug therapy/genetics/metabolism; Phosphorylation; *Phytotherapy; Plant Extracts/pharmacology/*therapeutic use; Plant Leaves; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/metabolism; Xenograft Model Antitumor Assays
      12. Abstract :
        ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes aspera (Family Amaranthacea) is used for cancer therapy by ayurvedic medical practitioners in India. However, due to the non formal nature of its use, there are no systematic studies validating its medicinal properties. Thus, it's utility as an anti cancer agent remains anecdotal. Earlier, we demonstrated A. aspera to exhibit time and dose-dependent preferential cytotoxicity to cultured human pancreatic cancer cells. In this report we validate in vivo anti tumor properties of A. aspera. MATERIALS AND METHODS: The in vivo anti tumor activity of leaf extract (LE) was tested by intraperitoneal (IP) injections into athymic mice harboring human pancreatic tumor subcutaneous xenograft. Toxicity was monitored by recording changes in behavioral, histological, hematological and body weight parameters. RESULTS: Dosing LE to athymic mice by I.P. injection for 32 days showed no adverse reactions in treated mice. Compared to the control set, IP administration of LE to tumor bearing mice significantly reduced both tumor weight and volume. Gene expression analysis using Real time PCR methods revealed that LE significantly induced caspase-3 mRNA (p<0.001) and suppressed expression of the pro survival kinase Akt-1 (p<0.05). TUNEL assay and immunohistochemistry confirmed apoptosis induction by activation of caspase-3 and inhibiting Akt phosphorylation in treated sets. These results are in agreement with RT PCR data. CONCLUSION: Taken together, these data suggest A. aspera to have potent anti cancer property.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22640722
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10484
      1. Author :
        Noberini, R.; Rubio de la Torre, E.; Pasquale, E. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cell Adh Migr
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc-C6, PC-3M-luc, IVIS, Bioware, Prostate cancer, Bioluminescence, Animals; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Ephrins/genetics/*metabolism; Humans; Mass Spectrometry/*methods; Mice; Receptor, EphA1/genetics/*metabolism
      12. Abstract :
        The Eph receptor tyrosine kinase family includes many members, which are often expressed together in various combinations and can promiscuously interact with multiple ephrin ligands, generating intricate networks of intracellular signals that control physiological and pathological processes. Knowing the entire repertoire of Eph receptors and ephrins expressed in a biological sample is important when studying their biological roles. Moreover, given the correlation between Eph receptor/ephrin expression and cancer pathogenesis, their expression patterns could serve important diagnostic and prognostic purposes. However, profiling Eph receptor and ephrin expression has been challenging. Here we describe a novel and straightforward approach to catalog the Eph receptors present in cultured cells and tissues. By measuring the binding of ephrin Fc fusion proteins to Eph receptors in ELISA and pull-down assays, we determined that a mixture of four ephrins is suitable for isolating both EphA and EphB receptors in a single pull-down. We then used mass spectrometry to identify the Eph receptors present in the pull-downs and estimate their relative levels. This approach was validated in cultured human cancer cell lines, human tumor xenograft tissue grown in mice, and mouse brain tissue. The new mass spectrometry approach we have developed represents a useful tool for the identification of the spectrum of Eph receptors present in a biological sample and could also be extended to profiling ephrin expression.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22568954
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10538
      1. Author :
        Abdelwahab, M. G.; Fenton, K. E.; Preul, M. C.; Rho, J. M.; Lynch, A.; Stafford, P.; Scheck, A. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        GL261-luc2, IVIS, 3-Hydroxybutyric Acid/metabolism; Animals; Blood Glucose/metabolism; Brain/metabolism/pathology; Combined Modality Therapy; Disease Models, Animal; Glioma/*diet therapy/*radiotherapy; Humans; Kaplan-Meier Estimate; *Ketogenic Diet; Ketones/blood; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Time Factors
      12. Abstract :
        INTRODUCTION: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal(R) (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2x4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of beta-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22563484
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10485
      1. Author :
        Ale, A.; Ermolayev, V.; Herzog, E.; Cohrs, C.; de Angelis, M. H.; Ntziachristos, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Methods
      6. Products :
      7. Volume :
        9
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bone Remodeling; Disease Models, Animal; Equipment Design; Female; Fluorescence; Head and Neck Neoplasms/pathology/radiography; Image Processing, Computer-Assisted/*methods; Lung Neoplasms/pathology/radiography; Mammary Neoplasms, Experimental/pathology/radiography; Mice; Osteogenesis Imperfecta/pathology/radiography; Tomography, Optical/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360 degrees imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22561987
      14. Call Number :
        PKI @ kd.modi @ 29
      15. Serial :
        10363
      1. Author :
        Ale, A.; Ermolayev, V.; Herzog, E.; Cohrs, C.; de Angelis, M. H.; Ntziachristos, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Methods
      6. Products :
      7. Volume :
        9
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Remodeling; Disease Models, Animal; Equipment Design; Female; Fluorescence; Head and Neck Neoplasms/pathology/radiography; Image Processing, Computer-Assisted/*methods; Lung Neoplasms/pathology/radiography; Mammary Neoplasms, Experimental/pathology/radiography; Mice; Osteogenesis Imperfecta/pathology/radiography; Tomography, Optical/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360 degrees imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22561987
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10468
      1. Author :
        Herzog, E.; Taruttis, A.; Beziere, N.; Lutich, A. A.; Razansky, D.; Ntziachristos, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Radiology
      6. Products :
      7. Volume :
        263
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adenocarcinoma/*diagnosis; Animals; Colonic Neoplasms/*diagnosis; Contrast Media/pharmacokinetics; Disease Models, Animal; Female; Fluorescent Dyes/pharmacokinetics; Gold/pharmacokinetics; Image Processing, Computer-Assisted; Indocyanine Green/pharmacokinetics; Mammary Neoplasms, Experimental/*diagnosis; Mice; Nanoparticles; Spectrum Analysis/methods; Tomography, Optical/*methods
      12. Abstract :
        PURPOSE: To investigate whether multispectral optoacoustic tomography (MSOT) can reveal the heterogeneous distributions of exogenous agents of interest and vascular characteristics through tumors of several millimeters in diameter in vivo. MATERIALS AND METHODS: Procedures involving animals were approved by the government of Upper Bavaria. Imaging of subcutaneous tumors in mice was performed by using an experimental MSOT setup that produces transverse images at 10 frames per second with an in-plane resolution of approximately 150 mum. To study dynamic contrast enhancement, three mice with 4T1 tumors were imaged before and immediately, 20 minutes, 4 hours, and 24 hours after systemic injection of indocyanine green (ICG). Epifluorescence imaging was used for comparison. MSOT of a targeted fluorescent agent (6 hours after injection) and hemoglobin oxygenation was performed simultaneously (4T1 tumors: n = 3). Epifluorescence of cryosections served as validation. The accumulation owing to enhanced permeability and retention in tumors (4T1 tumors: n = 4, HT29 tumors: n = 3, A2780 tumors: n = 2) was evaluated with use of long-circulating gold nanorods (before and immediately, 1 hour, 5 hours, and 24 hours after injection). Dark-field microscopy was used for validation. RESULTS: Dynamic contrast enhancement with ICG was possible. MSOT, in contrast to epifluorescence imaging, showed a heterogeneous intratumoral agent distribution. Simultaneous imaging of a targeted fluorescent agent and oxy- and deoxyhemoglobin gave functional information about tumor vasculature in addition to the related agent uptake. The accumulation of gold nanorods in tumors seen at MSOT over time also showed heterogeneous uptake. CONCLUSION: MSOT enables live high-spatial-resolution observations through tumors, producing images of distributions of fluorochromes and nanoparticles as well as tumor vasculature.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22517960
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10365
      1. Author :
        Alsaadi, M.; Italia, J. L.; Mullen, A. B.; Ravi Kumar, M. N.; Candlish, A. A.; Williams, R. A.; Shaw, C. D.; Al Gawhari, F.; Coombs, G. H.; Wiese, M.; Thomson, A. H.; Puig-Sellart, M.; Wallace, J.; Sharp, A.; Wheeler, L.; Warn, P.; Carter, K. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Control Release
      6. Products :
      7. Volume :
        160
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Aerosols; Amphotericin B/*administration & dosage; Animals; Antifungal Agents/*administration & dosage; Cricetinae; Disease Models, Animal; Drug Carriers/*administration & dosage; Female; Firefly Luciferin/administration & dosage; Leishmaniasis/*drug therapy/metabolism/microbiology; Liver/metabolism/microbiology; Lung/metabolism/microbiology; Mesocricetus; Mice; Mice, Inbred BALB C; Pulmonary Aspergillosis/*drug therapy/metabolism/microbiology; Rats; Rats, Sprague-Dawley; Surface-Active Agents/*administration & dosage
      12. Abstract :
        Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p<0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p<0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p<0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p<0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22516093
      14. Call Number :
        PKI @ kd.modi @ 15
      15. Serial :
        10528
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