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Reduced phagocytosis of colloidal carriers using soluble CD47.

PURPOSE: This study was designed to illustrate the feasibility of using soluble CD47 protein to antagonize phagocytosis of colloidal drug carriers by macrophages. METHODS: Expression of CD47-streptavidin (CD47-SA) fusion protein was achieved in B21CodonPlus host cells following IPTG induction. Murine macrophage cell line J774A.1, expressing high levels of SIRPalpha, was selected as the biologic model system for phagocytosis. FITC-labeled perfluorocarbon (PFC) emulsions were used as the colloidal carriers to trigger phagocytosis. Microscopy (inverted light and UV-fluorescence) and flow cytometry were used to qualitatively and quantitatively determine the degree of phagocytosis, respectively. RESULTS: The bacterially expressed, purified CD47-SA had neither cytotoxic nor cytostatic effects when incubated with J774A.1 cells up to a concentration of 400 nM for 24 h. Phagocytosis of FITC-labeled PFC emulsions was significantly diminished when macrophages were pretreated with 100 nM CD47-SA for 1 h. CONCLUSIONS: We demonstrated that soluble CD47-SA antagonized phagocytosis of colloidal carriers to a significant degree by interaction with macrophage SIRPalpha.

Animals↗

Fluorescence enhancements on silver colloid coated surfaces.

We observed a strong, more than 16-fold, enhancement of Texas Red-labeled BSA fluorescence emission when deposited on silver colloid coated surfaces (SCCS). The same labeled protein deposited on silver island films (SIFs) showed an approximate 8-fold fluorescence enhancement. The lifetimes of Texas Red-BSA fluorescence are significantly shorter on silvered surfaces than on uncoated quartz substrate indicating a strong change in radiative decay rate of the dyes. We also observed a 36-fold increased brightness of overlabeled fluorescein-HSA deposited on silver colloid coated surface. Stronger enhancement observed for overlabeled Fl-HSA protein indicates that presence of silver particles partially decreased self-quenching. Our results indicate that surfaces coated with silver colloids are valuable substrates for metal-enhanced fluorescence.

Algorithms↗

Albumin extravasation and tissue washout of hyaluronan after plasma volume expansion with crystalloid or hypooncotic colloid solutions.

BACKGROUND: Intravascular volume expansion is followed by loss of fluid from the circulation. The extravasation of albumin in this readjustment is insufficiently known. METHODS: Twelve male volunteers participated, each in three separate sessions, in a controlled, randomised, open fashion. They received one of the following: albumin 40 g/L,(7.1 mL/kg, i.e. 500 mL per 70 kg); Ringer's acetate (21.4 mL/kg), or dextran 30 g/L (7.1 mL/kg). The fluids were infused during 30 min and the subjects were followed for 180 min. ECG, arterial oxygen saturation and non-invasive arterial pressure were recorded. Haemoglobin, haematocrit, serum albumin and osmolality, plasma colloid osmotic pressure and hyaluronan concentration were determined in venous samples. RESULTS: The serum albumin concentration decreased (P < 0.05, anova) following Ringer's acetate or dextran, whereas serum osmolality was unchanged in all groups. The colloid osmotic pressure decreased (P < 0.05) after the Ringer solution. The blood volume increase was estimated from the decrease in haemoglobin concentration and did not differ between the three fluids. The cumulated extravasation of albumin was largest following albumin (10.4 +/- 5.4 g, mean +/- SD), less following dextran (5.6 +/- 5.0 g) and negligible in the Ringer group (0.5 +/- 10.0 g; P < 0.05 against albumin). However, the Ringer solution increased the plasma concentration of hyaluronan drastically. CONCLUSIONS: Infusion of hypotonic colloidal solutions entails net loss of albumin from the vascular space. This is not the case after Ringer's acetate. Increased interstitial hydration from the latter fluid is followed by lymphatic wash out of hyaluronan.

Adult↗

Development of a novel gene delivery scaffold utilizing colloidal gold-polyethylenimine conjugates for DNA condensation.

We have developed a novel gene delivery scaffold based on DNA plasmid condensation with colloidal gold/polyethylenimine conjugates. This scaffold system was designed to enable systematic study of the relationships between DNA complex physical properties and transfection efficiency. Using an enhanced green fluorescent protein-coding reporter plasmid and a Chinese hamster ovary cell line, we have measured the transfection efficiencies of our complexes using flow cytometry and their cytotoxicities using the trypan blue assay. We have also assayed complex particle morphologies using atomic force microscopy, photon correlation spectroscopy, and a novel plasmon absorbance peak position analysis. We achieved comparable rates of transfection relative to the commonly used polycationic condensation agents calcium phosphate and LipofectAMINE, with comparably low cytotoxicities. In addition, by manipulating colloidal gold concentration, we could partially decouple complex physical properties including charge ratio, size, DNA loading, and polyethylenimine concentration. Our morphological analyses showed that complexes with a diameter of a few hundred nanometers and a charge ratio of approximately 8 perform best in our transfection efficiency assays. The use of colloidal gold as a component in our delivery system provides a versatile system for manipulating complex properties and morphology as well as a convenient scaffold for planned ligand conjugation studies.

Animals↗

Optical barcoding of colloidal suspensions: applications in genomics, proteomics and drug discovery.

The enormous amount of information generated through sequencing of the human genome has increased demands for more economical and flexible alternatives in genomics, proteomics and drug discovery. Many companies and institutions have recognised the potential of increasing the size and complexity of chemical libraries by producing large chemical libraries on colloidal support beads. Since colloid-based compounds in a suspension are randomly located, an encoding system such as optical barcoding is required to permit rapid elucidation of the compound structures. We describe in this article innovative methods for optical barcoding of colloids for use as support beads in both combinatorial and non-combinatorial libraries. We focus in particular on the difficult problem of barcoding extremely large libraries, which if solved, will transform the manner in which genomics, proteomics and drug discovery research is currently performed.

Colloids↗

Analytical electron microscopy as a tool for accessing colloid formation process in natural waters.

Analytical electron microscopy was used to characterize aquatic iron-rich colloids. We focused our attention on a redox transition medium in the drainage water of a peat soil. In the anoxic peat water, observations by transmission electron microscopy and associated energy dispersive analyses (TEM-EDS) highlight the presence of spherical entities (approximately 100-600 nm), containing only traces of iron. The increase of dissolved oxygen concentration favours the formation of iron oxy(hydr)oxides. In the oxygenated drain, particles with the same morphology and size range are present. Statistical TEM-EDS analyses show that they represent the only colloidal form of iron in the drain samples. Nevertheless, although Fe-K peaks appear clearly on EDS spectra, the proportion of iron in these colloids reaches at most 4% at. (whereas C + O > 90% at.). Structural information completes this study. Both electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) reveal the disparity between element distributions within the drain entities. Iron and calcium are preferably distributed on the outer sphere of the particle, whereas carbon and oxygen follow the theoretical variation of the signal intensity within a plain sphere. The implication of organic matter as nucleation site for iron precipitation is spectacularly demonstrated by the presence of nanometre-sized iron-rich phases highlighted by EELS line scans.

Colloids↗

[The value of colloid scintigraphy and erythrocyte scintigraphy in detecting acute or intermittent gastrointestinal hemorrhages].

PURPOSE: In a retrospective analysis the diagnostic value of two scintigraphic methods was compared with each other. METHOD: 104 patients with acute or intermittent gastrointestinal haemorrhage were examined with 121 scintigraphic studies. We compared scintigraphic results with surgical findings, endoscopic results or final clinical diagnosis. We used two scintigraphic methods, colloid scintigraphy and in vivo/vitro red blood cell scintigraphy. RESULTS: Our scintigraphic findings reached a sensitivity of 72% and a specificity of 100%. We calculated a sensitivity of 68% for colloid scintigraphy and a sensitivity of 79% for red blood cell scintigraphy. The correct localisation of bleeding was successful in 52 (98%) cases. CONCLUSIONS: Our results demonstrate that red blood cell scintigraphy is the method of choice in detecting intermittent gastrointestinal hemorrhage. We believe that with new preparation kits for in vivo labelling red blood cell scintigraphy will become seriously competitive for the colloid scintigraphic method.

Acute Disease↗

[Cessation of treatment in childhood acute lymphatic leukemia. Long-term observations after meningosis prevention with intrathecal gold colloid radioisotopes and methotrexate].

Cytostatic long-term treatment for about 36 months was administered to 18 children with acute lymphatic leukaemia who were in long-term remission (43-98 months). Prophylaxis of meningosis involved intrathecal 198Au colloid and methotrexate. Seven recurrences occurred during the long-term remissions: the bone marrow was involved six times, leukaemic meningosis occurred once. Five out of seven recurrences occurred within one year of cessation of treatment. There were no complications induced by intrathecal radio-gold, such as the apathy syndrome or leukoencephalopathy. Intrathecal methotrexate led to side effects before administration of radio-gold: encephalopathy twice, paraplegia once. Symptoms regressed completely in two children, one child with encephalopathy continues to have symptoms. All three children were given 198Au colloid intrathecally thereafter which was tolerated very well. 198Au colloid represents an alternative for prophylaxis of meningosis with 60Co telecobalt irradiation in leukaemias and non-Hodgkin lymphomas in childhood.

Adolescent↗

Interactions between spherical colloids mediated by a liquid crystal: a molecular simulation and mesoscale study.

Monte Carlo simulations and dynamic field theory (DyFT) are used to study the interactions between dilute spherical particles, dispersed in nematic and isotropic phases of a liquid crystal. A recently developed simulation method (expanded ensemble density of states) was used to determine the potential of mean force (PMF) between the two spheres as a function of their separation and size. The PMF was also calculated by a dynamic field theory that describes the evolution of the local tensor order parameter. Both methods reveal an overall attraction between the colloids in the nematic phase; in the isotropic phase, the overall attraction between the colloids is much weaker, whereas the repulsion at short range is stronger. In addition, both methods predict a new topology of the disclination lines, which arises when the particles approach each other. The theory is found to describe the results of simulations remarkably well, down to length scales comparable to the size of the molecules. At separations corresponding to the width of individual molecular layers on the particles' surface, the two methods yield different defect structures. We attribute this difference to the neglect of density inhomogeneities in the DyFT. We also investigate the effects of the size of spherical colloids on their interactions.

Biosensing Techniques↗

Smoluchowski equation and the colloidal charge reversal.

Smoluchowski equation and the Monte Carlo simulations are used to study the conditions leading to the reversal of the electrophoretic mobility. Zeta (zeta) potential is identified with the diffuse potential at the shear plane which, we argue, must be placed at least one ionic diameter away from the colloidal surface. For sufficiently strongly charged colloids, zeta potential changes sign as a function of the multivalent electrolyte concentration, resulting in a reversal of the electrophoretic mobility. This behavior occurs even for very small ions of 4 A diameter as long as the surface charge density of the colloidal particles is sufficiently large and the concentration of 1:1 electrolyte is sufficiently low.

Chemistry, Physical↗

Surface molecular view of colloidal gelation.

We investigate the phase behavior of surface-functionalized silica colloids at both the molecular and macroscopic levels. This investigation allows us to relate collective properties such as aggregation, gelation, and aging directly to molecular interfacial behavior. By using surface-specific vibrational spectroscopy, we reveal dramatic changes in the conformation of alkyl chains terminating submicrometer silica particles. In fluid suspension at high temperatures, the interfacial molecules are in a liquid-like state of conformational disorder. As the temperature is lowered, the onset of gelation is identified by macroscopic phenomena, including changes in turbidity, heat release, and diverging viscosity. At the molecular level, the onset of this transition coincides with straightening of the carbon-carbon backbones of the interfacial molecules. In later stages, their intermolecular crystalline packing improves. It is the increased density of this ordered boundary layer that increases the van der Waals attraction between particles, causing the colloidal gas to aggregate. The approach presented here can provide insights into phase transitions that occur through surface modifications in a variety of colloidal systems.

Colloids↗

Paired colloid cysts of the third and lateral ventricles.

We report the case of a man of aged 27 years who presented with obstructive hydrocephalus caused by a colloid cyst of the third ventricle. He was found to have an additional and larger colloid cyst lying adjacent to it, but within the lateral ventricle. The contents of the two cysts were of different consistency. We have been able to find only one previous report of more than one colloid cyst occurring in the same patient and none where one of the cysts lay within the lateral ventricle.

Adult↗

Crystalloid or colloid for partial exchange transfusion in neonatal polycythemia: a systematic review and meta-analysis.

AIMS: To determine whether crystalloid solutions are as effective as colloid solutions when a partial exchange transfusion is performed in newborns with polycythemia. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register of the Cochrane Library (1966-2004). Keywords used were: polycythemia, partial exchange transfusion, hyperviscosity, and limited to newborn. Randomized studies in newborns with polycythemia were selected for evaluation. Outcomes examined were: long-term neurodevelopment; short-term physiological effects; improvement in clinical symptoms; reduction in haematocrit at 4-6 h; haematocrit at 24 h; and frequency of serious complications. RESULTS: Four randomized controlled clinical trials, including 200 patients in total, with evaluable data, which satisfied our criteria, were found. There were no data on long-term outcomes. There is no reported important difference in short-term physiologic effects. Use of crystalloid was as effective as colloid in both correction of haematological values and reduction of clinical symptoms following partial exchange transfusion. CONCLUSION: Crystalloid solutions are as effective as colloid solutions for partial exchange transfusion. When crystalloid solutions are used for this purpose, there is no risk of transmission of blood-borne diseases, there is no risk of anaphylaxis, they are rapidly and easily available, and are less expensive. The use of crystalloid should become the standard for partial exchange transfusion.

Colloids↗

EPR investigation of the free radicals generated during the photosensitization of TiO2 colloid by hypocrellin B.

The cation radical of dye produced from the interfacial electron transfer from a surface chelated dye to the conduction band of the colloidal TiO2 was studied by laser flash photolysis and electron paramagnetic resonance (EPR) techniques. The study employed hypocrellin B (HB), a natural photodynamic pigment with strong absorption over the visible light region, as a sensitizer and titanium dioxide as a colloid semiconductor. HB formed a chelate with this colloid semiconductor and exhibited a red-shifted and strongly enhanced absorption in the visible spectrum. Laser photolysis indicated that the electron excitation in the visible absorption band of the chelate resulted in extremely rapid and efficient electron injection from the excited triplet state of the dye into the conduction band of the semiconductor. A transient absorption of cation radical of HB at 570 nm was observed. The appearance of cation radical of HB was characterized by EPR spectrometry: the photoinduced EPR signal was not quenched by oxygen and its intensity decreased in the presence of NaI, a typical hole scavenger. The generation of conduction band electrons in HB-sensitized TiO2 system was also verified by the spin elimination of a stable cyclic nitroxide, 2,2, 6,6-tetramethylpiperidine-1-oxyl (TEMPO), and by the reduction of methyl viologen (MV2+) to its radical MV+.

Animals↗

Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery.

Colloidal gold, a sol comprised of nanoparticles of Au(0), has been used as a therapeutic for the treatment of cancer as well as an indicator for immunodiagnostics. However, the use of these gold nanoparticles for in vivo drug delivery has never been described. This communication outlines the development of a colloidal gold (cAu) nanoparticle vector that targets the delivery of tumor necrosis factor (TNF) to a solid tumor growing in mice. The optimal vector, designated PT-cAu-TNF, consists of molecules of thiol-derivatized PEG (PT) and recombinant human TNF that are directly bound onto the surface of the gold nanoparticles. Following intravenous administration, PT-cAu-TNF rapidly accumulates in MC-38 colon carcinoma tumors and shows little to no accumulation in the livers, spleens (i.e., the RES) or other healthy organs of the animals. The tumor accumulation was evidenced by a marked change in the color of the tumor as it acquired the bright red/purple color of the colloidal gold sol and was coincident with the active and tumor-specific sequestration of TNF. Finally, PT-cAu-TNF was less toxic and more effective in reducing tumor burden than native TNF since maximal antitumor responses were achieved at lower doses of drug.

Animals↗

Pulmonary lymphatic mapping in dogs: use of technetium sulfur colloid and isosulfan blue for pulmonary sentinel lymph node mapping in dogs.

Lung cancer is the most frequent cause of cancer death in the United States. The pattern of regional lymph node involvement is a major prognostic factor in a patient with nonsmall cell lung cancer. The accuracy of information obtained about the lymph node status of lung cancer patients can be potentially increased by sentinel node lymphatic mapping. This technique has been well studied in melanoma and breast cancer. It may be useful in increasing the detection of micrometastases and in decreasing the morbidity from complete mediastinal lymphadenectomy. We report an animal pilot study of pulmonary lymphatic mapping. The aim of our study was to gain experience in the surgical techniques for pulmonary sentinel node lymphatic mapping in an animal model prior to its application in humans. Technetium sulfur colloid and isosulfan blue dye were injected into different lobes of the lung followed by attempts to identify the sentinel node draining that specific portion of the lung. Technetium sulfur colloid identified the sentinel node in five of six dogs within 20 min after the radiotracer was injected into the lung parenchyma. Isosulfan blue dye identified the sentinel node in three of six dogs within 5 min. Both the agents are potentially useful, but we found greater technical ease in identifying the sentinel node with technetium sulfur colloid. Two single-institution pilot studies in humans have been performed. A multicentered study to validate and further refine this technique is necessary. Advanced pathologic techniques such as immunohistochemistry and reverse transcriptase-polymerase chain reaction can be used to enhance the accuracy of staging. This may facilitate proper application of novel therapeutic strategies to improve the current dismal prognosis of this disease.

Animals↗

The maintenance of blood colloid: passage of stored gum acacia from the cells to the circulation after plasmapheresis.

Removal of blood plasma by plasmapheresis from dogs made hypoproteinemic by injections of gum acacia over long periods of time, has resulted in the removal of more gum acacia than was originally present in the plasma. Gum acacia injections had been discontinued previous to the start of the experiments, and hence it must be concluded that the excess amounts of acacia were derived from deposits in the various organs. These observations verify the previous suggestion that the increase in blood acacia in the hypoproteinemic dog on a low protein diet is due to the transfer of acacia to the blood from its sites of deposit in the body. The experiments further suggest that the colloid content of the blood stream is maintained at the expense of tissue colloids, and support the idea that colloidal substances may pass in and out of cells.

Animals↗

Uteroplacental and fetal haemodynamics and cardiac function of the fetus and newborn after crystalloid and colloid preloading for extradural caesarean section anaesthesia.

We have studied the effects of randomized preloading with either a crystalloid (lactated Ringer's) 15 ml kg-1 or colloid (hydroxyethyl starch) 7.5 ml kg-1 solution in 20 parturients undergoing elective Caesarean section under extradural anaesthesia, on blood flow in maternal placental and non-placental uterine and placental arcuate arteries and in fetal umbilical, renal and middle cerebral arteries, using a pulsed colour Doppler technique. Simultaneously, fetal and neonatal myocardial function were investigated by pulsed Doppler and M-mode echocardiography. We found no changes in maternal or fetal blood velocity waveform indices after crystalloid preloading, but the pulsatility index of the maternal non-placental uterine artery increased significantly after colloid preloading. Fetal heart rate decreased after preloading with crystalloid solution. There were no differences in fetal or neonatal myocardial function between the groups, and the outcome of the newborn infants were uneventful in all cases. These results suggest that preloading with either a crystalloid or colloid solution may lead to different uterine and fetal haemodynamics but these solutions had only minimal effects on fetal and neonatal myocardial performance and no effect on the clinical condition of newborns in uncomplicated pregnancies.

Adult↗