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Immunostimulatory colloidal delivery systems for cancer vaccines.

Cancer vaccine delivery is a multidisciplinary scientific field that is currently undergoing rapid development. An important component of cancer vaccines is the development of novel vaccine delivery strategies, such as colloidal immunostimulatory delivery systems. The importance of formulation strategies for cancer vaccines can be explained by the poor immunogenicity of tumour antigens. Colloidal vaccine delivery systems modify the kinetics, body distribution, uptake and release of the vaccine. This review explores recent research that is directed towards more targeted treatments of cancer through to colloidal vaccine delivery systems. Widely investigated carrier systems include polymeric micro- and nanoparticles, liposomes, archaeal lipid liposomes (archaeosomes), immune-stimulating complexes and virus-like particles. These systems are evaluated in terms of their formulation techniques, immunological mechanisms of action as well as the potential and limitations of such colloidal systems in the field of cancer vaccines.

Adjuvants, Immunologic↗

Protein concentration of the rat thyroid colloid during thyroxine treatment.

Sprague-Dawley rats were given daily doses of 20 mug thyroxine for varying periods between 1 and 21 days. Samples of colloid were obtained by micropuncture in vivo of follicles in the thyroid isthmus. The protein content of the samples was determined by gel electrophoresis and the volume by a technique based on radioactivity measurement. The relative volume of the follicle lumina was determined by light microscopy. Treatment with thyroxine resulted in an increase in the protein concentration of the colloid. This increase was statistically significant after 2 days and the concentration remained elevated throughout the experimental period. The size of the follicle lumina also increased, most rapidly during the first week. It is suggested that the increase in protein concentration of the colloid during thyroxine treatment is due to inhibition of endocytosis of colloid in combination with the discharge into the follicle lumen of highly concentrated protein.

Animals↗

Inhibitory effects of ionophore A23187 on the release of thyroid hormone and colloid reabsorption in mouse thyroid glands.

The effect of the ionophore A23187 on a. the release of thyroid hormone from perifused mouse thyroid glands and b. the morphological changes in follicular epithelial cells was evaluated. A23187 at a concentration of 5 mumol/l significantly inhibited both the TSH- and the forskolin-stimulated release of T3 and T4. In the presence of 3-isobutyl-1-methylxanthine or (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) RO 20-1724, A23187 did not affect the forskolin-stimulated release of cAMP, but did inhibit the release of T3 and T4 stimulated by forskolin. Light and electron microscopic evaluation of the follicular epithelial cells of mouse thyroid tissues following 1-h stimulation with forskolin showed numerous pseudopods engulfing luminal colloid of various size and the presence of reabsorbed colloid droplets in the apical cytoplasm. Quantitative electron microscopic analysis revealed that the addition of the ionophore A23187 reduced the number of reabsorbed colloid droplets to one eighth in follicular epithelial cells. These observations suggest that the increase in intracellular Ca2+ induced by the ionophore A23187 inhibits the TSH-stimulated thyroid hormone release independently of the cAMP level, and that the suppression of thyroid hormone release may be due to an inhibition of colloid reabsorption.

1-Methyl-3-isobutylxanthine↗

The importance of colloid osmotic pressure during open heart surgery in infants.

Fifty-five infants with transposition of the great arteries and with total anomalous pulmonary venous return underwent intracardiac repair under combined surface/perfusion hypothermia and total circulatory arrest in 1975 to 1983. Although cardiopulmonary bypass (CPB) time is limited when hypothermic circulatory arrest is employed, fluid balance derangement is one of the major postoperative complications. Fluid balance at the end of CPB averaged +299.5 ml (+63.4 ml/kg) when hemodilution with lactated Ringer's was utilized (Group A). Since colloid osmotic pressure (COP) plays an important role in regulating fluid balance, colloid hemodilution prime (whole blood and plasma) was employed in the last 3 years (Group B). COP and total protein concentration during CPB with colloid prime were maintained at around 19 mmHg and 5 g/100 ml, respectively. In Group B, fluid balance at the end of CPB averaged +81.1 ml (+16.3 ml/kg) and was significantly less than in Group A (p less than 0.01). The ICU stay period for survivors in Group B (average 10.9 days) was reduced to half the period in Group A (average 20.6 days) (p less than 0.05). The mortality rate in Group A was 42%, whereas 23% in Group B. It was concluded that well-maintained COP levels during CPB with colloid hemodilution prime reduced fluid accumulation in the body and made patient care easier following open heart surgery in infants.

Cardiopulmonary Bypass↗

Colloidal carbon blocks oestrogen-induced migration of eosinophils to the uterus and the uterine water imbibition response.

Oestrogen induces a migration of eosinophil leukocytes to the uterus where, it is suggested, these cells mediate several responses to hormone stimulation. To investigate the mechanism of the recognition of the uterus by the eosinophils, the present study describes the effect of a blockade of the rat reticulo-endothelial system with colloidal carbon on oestrogen-induced uterine eosinophilia, and other responses to oestrogen stimulation that, it has been suggested, are mediated by eosinophils. In the absence of oestrogen colloidal carbon induced an increase in the number of eosinophils in mesometrium but not in endometrium with myometrium, and a slight oedematous reaction in deep endometrium. Colloidal carbon abolished the oestrogen-induced increase in the number of eosinophils in endometrium with myometrium and drastically decreased the oestrogen-induced increase in uterine wet weight and the endometrial oedematous responses 6 h after the administration of oestrogen. The present results agree with the hypothesis that most uterine water imbibition is mediated by eosinophils and suggest a possible mechanism for the interaction of colloidal carbon with eosinophil migration to the uterus.

Animals↗

A modified method of fine-granular cationic iron colloid preparation: its use in light and electron microscopic detection of anionic sites in the rat kidney glomerulus and certain other tissues.

Ferric chloride, when boiled with hydrazine hydrate and cacodylic acid, is converted into a fine cationic iron (ferric hydroxide) colloid which consists of 0.5-1.5 nm electron-dense granules, and gives a distinct Prussian blue reaction. This colloid allows light and electron microscopic detection of ionized anionic sites in tissues at a wide pH range of 0.8-7.6. It is smaller in size and more stable, and assures longer and greater staining of tissues, especially at low pH levels, than the iron colloid prepared with sodium or ammonium cacodylate by Seno and his associates (1983, 1984, 1985). Some light and electron micrographs of the rat kidney, spleen and other organs stained with our colloid are presented as examples. These micrographs confirm that the glomerular podocyte end-foot surface facing the Bowman's capsular space is strongly negative-charged. They also show that almost all lymphoid cells around the arteries in the splenic white pulp and thymic cortex contain strongly negative-charged nuclei and that the distal convoluted and collecting urinary tubules are more negative-charged than the proximal convoluted tubules.

Animals↗

Negative charges bound to collagen fibrils in the rabbit articular cartilage: a light and electron microscopic study using cationic colloidal iron.

Negative charged sites in the normal rabbit articular cartilage were investigated using cationic colloidal iron methods. In light microscopy of the cartilage stained with the colloidal iron at pH 1.5, a distinct Prussian blue reaction was observed in the pericellular matrix, and a weak blue reaction in the territorial and interterritorial matrices. At pH 7.0, a diffuse Prussian blue reaction was observed in the pericellular and interterritorial matrices. Digestion with chondroitinase ABC, hyaluronidase and keratanase could not erase the Prussian blue reaction. However, the sections digested with collagenase followed by chondroitinase ABC showed significant elimination of the Prussian blue reaction. Electron microscopy of ultrathin sections stained with the colloidal iron at pH 1.5 revealed that the cationic colloid particles were deposited abundantly in the pericellular matrix and dotted along collagen fibrils in the territorial and interterritorial matrices. The present results suggest that negatively charged sites in the articular cartilage derive mostly from chondroitin sulfate, whose proteoglycans firmly bind to collagen fibrils. Such an ultrastructure may maintain the electrostatic microenvironment in the collagen plexus, holding much water in the cartilage matrix, and also producing biomechanical properties such as tensile strength and elasticity of the cartilage.

Animals↗

Intensely positively charged perineuronal nets in the adult rat brain as detected by staining with anionic iron colloid.

Ferric chloride, when boiled with ammonium thiocyanate, ammonia and cacodylic acid, is converted into a fine anionic iron colloid which consists of 1.0-1.5 nm electron dense granules and gives a distinct Prussian blue reaction (OHTSUKA and MURAKAMI, 1986). Light microscopy of tissue sections stained with this fine anionic iron colloid at pH values of 6.0, 7.0 and 8.0 showed that the healthy adult rat brain contains a considerable number of neurons which possess an intensely positively charged perineuronal net. This net was most clearly demonstrable by staining with the anionic iron colloid at a pH value of 8.0, at which ionizations of almost all cationic sites of the tissue elements were obliterated. Transmission electron microscopy of ultrathin sections stained at a pH value of 8.0 showed that the anionic iron colloid was preferentially deposited in the perineuronal tissue spaces. These findings indicate that the intensely positively charged perineuronal net contains some strongly basic substances such as guanidino compounds, and occupies the perineuronal (perisynaptic) tissue space.

Animals↗

Impact of activated sludge-derived colloidal organic carbon on behavior of estrogenic agonist recombinant yeast bioassay.

The impact of size-fractionated colloidal organic carbon (COC) originating from a biological wastewater treatment facility on the sensitivity of the yeast estrogen screen (YES) bioassay containing the human estrogen receptor (hER) gene was evaluated. Dose-response curves of serially diluted 17beta-estradiol (E2), both in the presence and absence of COC, were generated by the YES bioassay. The concentration of E2 leading to a 50% YES response (effective concentration 50%, or EC50) was used to evaluate quantitatively the estrogenic activity of the different COC-E2 mixtures. The EC50 values for all COC size fractions, including COC-free samples (<1 kD), were statistically greater than the controls using Milli-Q water. Normalized EC50 values significantly increased as a function of COC concentration for the larger size fractions (>0.22 microm), but were not significantly affected by smaller COC material at environmental levels (1-5 mg/L), while both colloidal polysaccharide concentrations and colloidal fluorophores (measured at an excitation/emission wavelength pair of 350 nm/450 nm) appear to have an important role in the sensitivity of the YES bioassay. Estimates of the colloid-associated E2 fraction did not predict accurately increases in EC50 values. Matrix effects of the specific environment being tested with the YES bioassay need to be evaluated closely due to the sensitivity of the hER and reporter plasmid.

Biological Assay↗

Amperometric hydrogen peroxide biosensor based on horseradish peroxidase-labeled nano-Au colloids immobilized on poly(2,6-pyridinedicarboxylic acid) layer by cysteamine.

A sensitive hydrogen peroxidase (H2O2) amperometric sensor based on horseradish peroxidase (HRP)-labeled nano-Au colloids has been proposed. Nano-Au colloids were immobilized by the thiol group of cysteamine, which was associated with the carboxyl groups of poly(2,6-pyridinedicarboxylic acid) (PPDA). With the aid of the hydroquinone, the sensor displayed excellent electrocatalytical response to the reduction of H2O2. Compared with the non-Au-colloid modified electrode, i.e., PPDA/HRP, the Au-colloid modified electrode exhibited better performance characteristics, including stability, reproducibility, sensitivity and accuracy. The biosensor shows a linear response to H2O2 in the range of 3.0 x 10(-7) - 2 x 10(-3) M. The detection limit was 1.0 x 10(-7) M.

Biosensing Techniques↗

Colloidal silica-coated tissue culture dishes for primary cell cultures: growth of rabbit renal proximal tubule cells.

The use of colloidal silica as a substratum for primary cultures of differentiated cells has significant advantages over classic tissue culture polystyrene. In this report, the growth and the level of expression of differentiated function of primary rabbit renal proximal tubule (RPT) cell cultures on colloidal silica is examined, using hormonally defined serum-free medium. Primary RPT cells grew to confluence more rapidly on colloidal silica than on tissue culture polystyrene (TC+). Moreover, following three passages, the RPT cells increased in number threefold more than parallel cultures on TC+. The morphology of primary RPT cells on colloidal silica were found by means of transmission electron microscopy to possess a polarized morphology with a brush border, and differentiated markers were retained even after passaging, including the Na+/glucose cotransport system and Glut 7.

Animals↗

Colloidal speciation of heavy metals in runoff and interstitial waters of a retention/infiltration pond.

The thickness of non-saturated zone and physico-chemical conditions are important parameters to assess the impact of infiltration ponds on water resources with respect to heavy metals transfer. As changes in physico-chemical parameters of solutions have a strong impact on the mobility of colloidal phases in sediments and soils, the colloidal facilitated transfer of heavy metals has to be investigated. Therefore, this study focuses on the characterization of runoff, surface and interstitial waters in a retention/infiltration pond collecting runoff waters of a bridge near Nantes. Physico-chemical parameters and chemical analyses were performed on the waters during about one year. The separation of dissolved and colloidal fractions was carried out by filtration and ultrafiltration for one sample of surface and interstitial waters. Until now, the runoff waters were only filtered at 0.45 microm. The comparison of physico-chemical data shows that the minor variations of runoff water parameters are mitigated in basin and in soils but strong variations impact the composition of interstitial waters. High concentrations of zinc, copper and still of lead are measured in runoff. Lead and cadmium seem to be associated to colloidal and particulate fractions while zinc, copper, nickel and chromium are distributed in all fractions.

Colloids↗

Improved detection of upper abdominal abscesses by combination of 99mTc sulfur colloid and 111In leukocyte scanning.

Indium-111-labeled leukocyte scanning is an excellent technique for detecting abdominal abscesses. However, since labeled leukocytes are normally taken up by the liver and spleen, diagnosing upper abdominal abscesses can be difficult. A prospective study was undertaken to see if having a technetium-99m sulfur colloid liver-spleen scan to compare with the 111In leukocyte scan would improve the reader's ability to diagnose or exclude upper abdominal abscesses. Ninety patients with suspected upper abdominal abscesses were examined with 111In leukocyte scans followed immediately by conventional 99mTc sulfur colloid liver-spleen scans in the same projections. In 57% of patients with upper abdominal abscesses and 26% of all patients studied, the 99mTc sulfur colloid scan was essential to diagnose or exclude an upper abdominal abscess. The liver-spleen scan was considered helpful in another 13%. The addition of a 99mTc sulfur colloid liver-spleen scan to the 111In leukocyte study is useful when evaluating patients with suspected upper abdominal abscesses.

Abdomen↗

Effect of hydroxyethyl starch infusion on colloid oncotic pressure in hypoproteinemic horses.

OBJECTIVE: To determine the effect of hydroxyethyl starch (HES) on colloid oncotic pressure (pi) during fluid resuscitation of hypoproteinemic horses and to evaluate the clinical usefulness of direct and indirect methods for determination of pi before and after infusion of a synthetic colloid. DESIGN: Prospective clinical study. ANIMALS: 11 hypoproteinemic horses. PROCEDURE: Horses received IV infusions of 8 to 10 ml of a 6% solution of HES/kg (3.6 to 4.5 ml/lb) of body weight during fluid resuscitation. Blood samples were obtained for determination of plasma measured colloid oncotic pressure (pi meas) and plasma total protein and albumin (A) concentrations. Plasma globulin concentration (G) was calculated as the difference between plasma total protein and albumin concentrations. Calculated values for colloid oncotic pressure (piA + G) were determined by use of a predictive nomogram previously developed for horses. RESULTS: There was no significant difference between the means of pi meas and piA + G at the beginning of HES infusion. After HES infusion, the mean of pi meas was increased significantly from baseline for 6 hours. Mean plasma total protein and albumin concentrations and piA + G were decreased significantly from baseline for 24 hours. Differences between mean pi meas and piA + G after HES infusion were significant for 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: There was good agreement between plasma pi meas and piA + G in blood samples obtained from hypoproteinemic horses immediately before infusion of HES. Use of a predictive nomogram did not, however, account for the oncotic effect of HES. Results of comparison of pi meas to piA + G after HES infusion suggest that a significant oncotic effect was maintained for 24 hours in the study horses.

Animals↗

Effects of cations on the colloidal stability of some oral bacteria.

The colloidal stability of seven strains of oral bacteria was studied at various concentrations of mono-, di-, and multi-valent metal counterions in the suspending media. Alterations in the concentration and the valency of the counterions were shown to influence the colloidal stability of the bacterial suspensions, as determined by their rate and time of initial sedimentation. The observations were in general in agreement with the accepted theories for colloidal stability. The results support previously made suggestions that under certain experimental conditions oral bacteria behave like colloidal particles.

Actinomyces↗

Influence of saliva from 'heavy' and 'light' plaque formers on the colloidal stability of bacterial suspensions.

The influence of parotid saliva on the colloid stability of suspensions of Streptococcus sanguis and S. salivarius was studied in groups of previously identified 'heavy' and 'light' plaque formers. For S. sanguis it was observed that addition of parotid saliva from light plaque formers had more pronounced negative influence on the colloid stability than addition of such saliva from heavy plaque formers. No differences were observed for S. salivarius. The results indicate that saliva and bacteria might be regarded as a biological colloidal system and that the individual rate of plaque formation can perhaps be partially related to the colloid-chemical properties of bacteria and saliva.

Chemical Phenomena↗

Interstitial fluid colloid osmotic pressure of the subcutaneous tissue in controls and patients before and after open-heart surgery: a comparison between the wick technique and the blister suction technique.

The purpose of this study was to compare the blister suction technique and the wick technique for measuring interstitial colloid osmotic pressure of subcutaneous tissue (COPif). Eight healthy volunteers and 14 patients undergoing aortocoronary bypass using extracorporal circulation (ECC) were included in the investigation. Colloid osmotic pressure was measured in fluid collected either from blisters (COPbl) developed by application of subatmospheric pressure to the chest skin, or from nylon wicks (COPw) implanted subcutaneously on the chest in the same area as the blisters were formed. Colloid osmotic pressure was then recorded on a colloid osmometer made for 5 microliter samples. In the patients, the measurements were performed 12-18 h pre-operatively (mean 15 h) and, on average, 4 h (range 1.5-7 h) following termination of extracorporal circulation. In the control subjects as well as in the patients, COPbl was significantly lower than COPw. However, the two types of measurements were found to change in the same direction, as a highly significant positive correlation exists between the two methods.

Adult↗

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗