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Real-time visualization and quantitation of vascular permeability in vivo: implications for drug delivery.
Pink DB, Schulte W, Parseghian MH, Zijlstra A, Lewis JD
(2012) PLoS One 7: e33760
MeSH Terms: Animals, Capillary Permeability, Cell Line, Chick Embryo, Chorioallantoic Membrane, Doxorubicin, Drug Delivery Systems, Evans Blue, Humans, Interleukin-2, Microscopy, Neoplasms, Neovascularization, Pathologic, Time-Lapse Imaging, Transplantation, Heterologous, Tumor Microenvironment, Vascular Endothelial Growth Factor A
Show Abstract · Added December 30, 2013
The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors.
1 Communities
1 Members
0 Resources
17 MeSH Terms
The importance of recognizing postural pseudoanemia.
Goldner F, Jacob G, Raj SR, Robertson D
(2006) Compr Ther 32: 51-5
MeSH Terms: Adult, Anemia, Blood Volume, Coloring Agents, Evans Blue, Female, Hematocrit, Hemoglobins, Hospitalization, Humans, Injections, Intravenous, Male, Posture, Radiopharmaceuticals, Serum Albumin, Radio-Iodinated, Tilt-Table Test
Show Abstract · Added December 10, 2013
The determination of the packed red cell volume and the hemoglobin level has been paramount for monitoring anemia and blood loss for patients in the hospital setting. Recently, these variables have been studied during various control conditions including changes in posture. It has been found that the hematocrit changes markedly with alteration of body posture, in such a way that shifts of estimated blood volume of 1 pint can commonly be elicited by a simple change of posture from supine to upright or vice versa. Therefore, it is important to recognize that in addition to the numerous pathological conditions that may affect the value of the packed cell volume, certain physiological maneuvers may have an equal impact and may confound the accurate assessment of true pathological changes in these variables. Thus, changes in posture can lead to substantial changes in hematocrit, which may be attributed mistakenly to blood loss or acute anemia and may result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention.
Zhang H, Zhang A, Kohan DE, Nelson RD, Gonzalez FJ, Yang T
(2005) Proc Natl Acad Sci U S A 102: 9406-11
MeSH Terms: Aldosterone, Animals, Biological Transport, Body Weight, Coloring Agents, Diabetes Mellitus, Type 2, Evans Blue, Gene Deletion, Genotype, Heterozygote, Hypoglycemic Agents, Immunohistochemistry, Integrases, Kidney, Kidney Tubules, Collecting, Mice, Mice, Knockout, Mice, Transgenic, Microscopy, Fluorescence, Microscopy, Phase-Contrast, Nephrons, PPAR gamma, Promoter Regions, Genetic, Radioimmunoassay, Rosiglitazone, Sodium, Thiazolidinediones
Show Abstract · Added September 9, 2013
The peroxisome proliferator-activated receptor subtype gamma (PPARgamma) ligands, namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have demonstrated great potential in the treatment of type II diabetes. However, their clinical applicability is limited by a common and serious side effect of edema. To address the mechanism of TZD-induced edema, we generated mice with collecting duct (CD)-specific disruption of the PPARgamma gene. We found that mice with CD knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPARgamma in the CD. RGZ reduced urinary sodium excretion in control and not in conditional knockout mice. Furthermore, RGZ stimulated sodium transport in primary cultures of CD cells expressing PPARgamma and not in cells lacking this receptor. These findings demonstrate a PPARgamma-dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention.
0 Communities
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1 Resources
27 MeSH Terms
Postural pseudoanemia: posture-dependent change in hematocrit.
Jacob G, Raj SR, Ketch T, Pavlin B, Biaggioni I, Ertl AC, Robertson D
(2005) Mayo Clin Proc 80: 611-4
MeSH Terms: Adult, Anemia, Coloring Agents, Evans Blue, Female, Follow-Up Studies, Hematocrit, Humans, Injections, Intravenous, Male, Plasma Volume, Posture, Radiopharmaceuticals, Reference Values, Retrospective Studies, Serum Albumin, Radio-Iodinated
Show Abstract · Added December 10, 2013
OBJECTIVE - To determine the magnitude of posture-related changes in blood components.
SUBJECTS AND METHODS - Twenty-eight healthy subjects were studied between 1995 and 2004 at the Vanderbilt Autonomic Dysfunction Center, Nashville, Tenn. Lying and standing plasma volume (PV) and hematocrit (Hct) values were determined for each subject.
RESULTS - Individual PV decreases on standing ranged from 6% to 25%. The absolute mean +/- SD PV shift was 417+/-137 mL (range, 149-717 mL). The mean +/- SD change in Hct was from 37.7%+/-2.8% while supine to 41.8%+/-3.2% within 30 minutes of standing. This absolute increase in Hct of 4.1%+/-1.3% represents a relative increase of 11.0%+/-3.6% from lying to standing.
CONCLUSIONS - Changes in posture can lead to substantial changes in Hct, which may be attributed mistakenly to blood loss or acute anemia and result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying (and vice versa).
0 Communities
2 Members
0 Resources
16 MeSH Terms
Plasma extravasation in the rat trachea induced by cold air is mediated by tachykinin release from sensory nerves.
Yoshihara S, Chan B, Yamawaki I, Geppetti P, Ricciardolo FL, Massion PP, Nadel JA
(1995) Am J Respir Crit Care Med 151: 1011-7
MeSH Terms: Air, Animals, Cold Temperature, Evans Blue, Extravasation of Diagnostic and Therapeutic Materials, Neurokinin B, Neurons, Afferent, Parainfluenza Virus 1, Human, Rats, Rats, Inbred F344, Respiration, Artificial, Trachea, Tracheitis, Virus Diseases
Show Abstract · Added March 5, 2014
Cold air was delivered to anesthetized, artificially ventilated, pathogen-free F344 rats via a tracheal cannula. Inhalation of cold air increased Evans blue dye extravasation in the trachea in a time-dependent (1 to 10 min) manner. Plasma extravasation increased after 3 min exposure to cold air and reached a maximum after 10 min exposure. The neutral endopeptidase inhibitor, phosphoramidon (2.5 mg/kg, intravenously), increased by 84% the plasma extravasation induced by inhalation of cold air for 1 min. The plasma extravasation evoked by 5 min exposure to cold air was abolished by the NK1 tachykinin receptor antagonist, CP-99,994 (4 mg/kg, intravenously); was reduced 30% by the B2 bradykinin receptor antagonist, HOE140 (0.1 mumol/kg, intravenously); and was not affected by H1 (pyrilamine, 10 mg/kg, intraperitoneally) or H2 (cimetidine, 10 mg/kg, intraperitoneally) histamine receptor antagonists or the cyclooxygenase inhibitor indomethacin (5 mg/kg, intravenously). In rats infected with Sendai virus, plasma extravasation evoked by inhalation of cold air was greater than in pathogen-free rats. Pretreatment with CP-99,994 (4 mg/kg, intravenously) inhibited completely the plasma extravasation induced by cold air in virus-infected rats. These findings indicate that cold air increases plasma extravasation in the rat trachea by a neurogenic mechanism that involves the release of tachykinins from sensory nerves. Kinin release may also play a role in this neurogenic inflammatory response.
0 Communities
1 Members
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14 MeSH Terms