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In vitro stability and in vivo absorption studies of colloidal particles formed from a solid dispersion system.

We investigated the physicochemical and pharmaceutical properties of a solid dispersion (SD) derived from a solution of the poorly water-soluble drug (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), hydroxypropylmethylcellulose 2910 (TC-5E) and polyoxyethylene hydrogenated caster oil 60 (HCO-60). Colloidal particles produced when the SD was dispersed into water had a mean diameter of 160 nm and contained 67-77% YM022. Powder X-ray diffractometry showed that YM022 existed in the colloidal particles in an amorphous state. The particle diameter and YM022 content remained unchanged during storage for 7 d, confirming that the colloidal solution was stable. On oral administration to rats, good absorption was observed for both the colloidal solution prepared immediately before and the sample stored for 7 d before administration. Thus, the stability of this colloidal solution of SD was confirmed by in vitro storage tests and by in vivo absorption experiments in rats.

Absorption↗

Characterization of T3 immunoreactivity release from thyroid gland in vitro a reflection of colloid droplet formation.

T3 immunoreactivity release from the thyroid gland in vitro was shown to be increased by TSH. In the present study, we sought to determine whether the T3 immunoreactivity release is an indicator of thyroid hormone secretion or due to hormone synthesis. When thyroid glands from mice were incubated with TSH, T3 immunoreactivity release was increased in parallel with intracellular colloid droplet formation in a dose related manner. When colchicine, a known inhibitor of colloid droplet formation, was added, both T3 immunoreactivity release and colloid droplet formation were inhibited, whereas MMI, an inhibitor of hormone synthesis, failed to influence both aspects. Thus T3 immunoreactivity release as a reflection of colloid droplet formation was demonstrated. The analysis of the released immunoreactivity by Sephadex column and subsequent radioimmunoassay suggested that the T3 immunoreactivity was, to a considerable extent, due to macromolecule instead of T3 itself. The effect of I- or Li+ to inhibit thyroid hormone secretion was shown to be on the step prior to, but not subsequent to, colloid droplet formation.

Animals↗

Neurons with strongly negative-charged surface-coats in adult rat brain as detected by staining with cationic iron colloid.

Light microscopy of tissue sections stained either with cationic iron colloid (pH 1.0-2.0) and nuclear fast red or with this colloid and thionin showed that the adult rat brain contains a considerable number of neurons which are strongly negative-charged by being coated with sulfated proteoglycans such as chondroitin sulfates. These neurons are distributed mainly in the cerebral cortex, hippocampus, zona incerta, medial and lateral cerebellar nuclei, ventral pontine nuclei and certain other areas. In the hippocampal formation, the strongly negative-charged cells seem identical with the GABAergic inhibitory interneurons reactive to the lectin Vicia villosa agglutinin. Neurons, including the GABAergic Purkinje's cells, of the cerebellar cortex showed no reaction to our cationic iron colloid at pH values of 1.0-2.0. Many non-GABAergic pyramidal cells in the lamina ganglionalis of cerebral cortex and many non-GABAergic large neurons of the ventral pontine nuclei were highly reactive to our colloid at pH values of 1.0-2.0. This suggests that our cationic iron colloid at pH values of 1.0-2.0 mainly stains certain subtypes of GABAergic neurons as well as some non-GABAergic neurons projecting long associational or commissural fibers.

Animals↗

Enhanced visualization of weak colloidal iron signals with Bodian's protein silver for demonstration of perineuronal nets of proteoglycans in the central nervous system.

The present study aimed for a clear visualization of faintly deposited colloidal iron in tissue sections for light microscopy. Paraffin blocks containing paraformaldehyde-fixed brain tissue from healthy adult mice were cut into sections 10-15 microm thick. After deparaffinization, the sections were stained with fine cationic iron colloid at a pH value of 1.0-1.5, and treated with a mixture of potassium ferrocyanide and hydrochloride for Prussian blue reaction. Some sections were further treated with Bodian's protein silver after the Prussian blue reaction. This sensitized development of Prussian blue reaction with Bodian's protein silver more clearly visualized the faintly deposited cationic colloidal irons than the demonstration by Prussian blue reaction alone, and allowed an enhanced visualization of the perineuronal nets of sulfated proteoglycans in the brain. Thus, such fine perineuronal sulfated proteoglycans as those in the CA3 field of the hippocampus, which are weakly stained with cationic iron colloid and usually overlooked by a demonstration with only a Prussian blue reaction, could be clearly visualized with striking contrast by the sensitized development with Bodian's protein silver after the Prussian blue reaction. Preliminary hyaluronidase digestion erased Bodian's protein silver development of perineuronal sulfated proteoglycans. Though some axonal fibers were also additionally stained with Bodian's protein silver itself, this sensitized development is useful to enhance such weak colloidal iron signals as are hardly detectable by only Prussian blue reaction.

Animals↗

In situ preparation of colloidal iron by microwave irradiation for transmission electron microscopy.

We attempted to prepare colloidal iron within tissues by means of microwave irradiation. Mouse tissue blocks were fixed with a mixture of paraformaldehyde and ferric chloride in a cacodylate buffer, immersed in a cacodylate buffered ferric chloride solution, and irradiated in a microwave processor. Colloidal iron was prepared within tissues or cells, and was observed in the form of electron dense fine granules (1-2 nm in diameter) by transmission electron microscopy. Collagen fibrils in the connective tissue showed colloidal iron deposition at regular periodical intervals. Cells in the splenic tissue showed that fine colloidal granules were deposited on the ribosomes but not on the nuclear chromatin. This finding suggests that ferric ions could not diffuse into the nucleus, which was surrounded by the nuclear envelope. The podocyte processes of the renal glomerulus were stained diffusedly. Though this microwave in situ colloidal iron preparation method has some limitations, it is convenient for use in biomedical specimen preparation in transmission electron microscopy.

Animals↗

Positron tomographic imaging of the liver: 68 Ga iron hydroxide colloid.

A new radiopharmaceutical, 68Ga ion hydroxide colloid, for hepatic imaging by positron emission tomography was prepared from the eluate of a 68Ge-68Ga solvent extraction generator. In rats, 84% of the administered dose of colloid localized in the liver and 4.6% accumulated in the spleen. Initial imaging studies in normal dogs showed close correspondence of the findings by positron tomography and transmission computed tomography. Emission tomography with 68Ga-colloid was performed in 10 patients with hepatic metastases demonstrated by conventional 99mTc sulfur colloid scintigraphy. All focal defects noted on the conventional scintigrams were easily identified and generally were seen more clearly by positron tomography. In one patient, additional lesions not identified on the initial 99mTc sulfur colloid images were demonstrated. The positron tomographic images were compared with those obtained by transmission computed tomography in seven patients; the two studies showed comparable findings in five patients, whereas positron tomography more clearly showed multiple lesions in two. Our results suggest that positron emission tomography is a suitable technique for obtaining high contrast, cross-sectional images of large abdominal organs.

Animals↗

Accumulation of technetium-99m sulfur colloid by hepatocellular adenoma: scintigraphic-pathologic correlation.

It is currently believed that hepatocellular adenoma is photon deficient on technetium-99m sulfur colloid scintigraphy because these tumors lack Kupffer cells. In a retrospective review of 13 pathologically proven cases of hepatocellular adenoma with technetium-99m sulfur colloid scintigrams, Kupffer cells were present in all 13 cases. We observed uptake of the radiocolloid by the hepatocellular adenoma in three cases (23%), and there were no histologic differences between the tumors with uptake and the ones without it. We conclude that the currently accepted reason for the lack of technetium-99m sulfur colloid uptake within hepatocellular adenoma is incorrect, and an explanation other than a lack of Kupffer cells is responsible for the photon-deficient appearance in the majority of cases of hepatocellular adenoma. Further, because hepatocellular adenoma may have technetium-99m sulfur colloid uptake in a significant percentage of cases, it should be added to focal nodular hyperplasia in the differential diagnosis of a hepatic mass with uptake by technetium-99m sulfur colloid.

Adolescent↗

Colloid osmotic pressure in decompensated cirrhosis. A 'mirror image' of portal venous hypertension.

Colloid osmotic pressure in plasma (IIP) and ascitic fluid (IIA) and hydrostatic pressures in the hepatoportal system were measured simultaneously in 20 patients with decompensated cirrhosis. IIP was significantly decreased (mean, 21 mm Hg, versus normal, 30 mm Hg; P less than 0.01), and IIA was significantly below that of plasma (average, 25% of IIP; P less than 0.01). Portal pressure (transmural), determined as wedged hepatic venous minus inferior vena caval pressure (WHV--IVCP), was significantly increased (mean, 18 mm Hg, versus normal, 3 mm Hg; P less than 0.01) and inversely correlated to IIA/IIP (r = -0.77, P less than 0.001). WHV--IVCP was in most patients in the same order as and closely correlated to effective colloid osmotic pressure (IIP--IIA) (r = 0.88, P less than 0.001). No relationship was found between WHV--IVCP and IIP. The results indicate that a fall in colloid osmotic pressure in the interstitial space and ascitic fluid is related to and most likely secondary to the elevated portal pressure in decompensated cirrhosis. Effective colloid osmotic pressure may therefore be regarded as a 'mirror image' of transmural portal pressure. The role of colloid osmotic pressure in the genesis and perpetuation of ascites should be reconsidered in the light of these findings.

Adult↗

An immunohistochemical study of neuroepithelial (colloid) cysts.

Monoclonal and polyclonal antisera were used against 12 cases of neuroepithelial (colloid) cysts to determine the specific antigenic profile of the cyst epithelium. Intermediate filament markers (cytokeratin, vimentin, neurofilament, and glial fibrillary acidic protein) and epithelial markers (epithelial membrane antigen and monoclonal antibody lu-5) demonstrated that colloid cyst epithelium has a unique antigenic profile in contrast to that of choroid plexus or glial tissue. Theories raised to explain the etiology of colloid cysts have included derivation from the embryonic paraphysis, detachments of developing neuroepithelium from the tela choroidea, and remnants of respiratory epithelium; a more recent theory suggests that these cysts are products of developing choroid plexus or ependyma. The present study shows that colloid cyst epithelium is distinct from that of choroid plexus or ependyma and therefore does not represent a product of their formation, nor does it represent a form of immature glia. This finding supports the conclusion that colloid cysts in any ventricular location represent a developmental anomaly of primitive neuroectoderm in the embryo, which remains unique from other products of neuroectodermal derivation.

Brain Diseases↗

Intrapontomesencephalic colloid cyst: an unusual location. Case report.

Colloid cysts appear most commonly in the third ventricle; the occurrence of a colloid cyst in the brainstem is very unusual. The authors report on a patient with an intrapontomesencephalic colloid cyst. This 15-year-old girl complained of a headache associated with diplopia. Her neurological examination revealed right-sided sixth nerve paresis and a mild left hemiparesis. Radiological investigations revealed an intraparenchymal pontomesencephalic cystic mass. Surgical removal of the lesion was achieved via the pterional transsylvian approach and the patient experienced an excellent recovery. Histopathological examination revealed that the lesion was a typical colloid cyst. To the best of the authors' knowledge, this is the first case in which an intraparenchymal upper brainstem colloid cyst was surgically excised totally. In addition to describing this case, the authors also review other brainstem neuroepithelial cysts described in the literature and briefly discuss the concept of their origin.

Adolescent↗

Size- and surface-dependent uptake of colloid particles into the lymphatic system.

PURPOSE: To examine the effect of particle size and surface characteristics on colloidal particle uptake from subcutaneous tissue into the lymphatic system. MATERIALS AND METHODS: Perfluorocarbon emulsion ZY13163 (median particle diameter, 0.08 micron; surfactant, egg yolk phospholipid), ZY13164 (median particle diameter, 0.36 micron; surfactant, egg yolk phospholipid), ZY13199 (0.18 micron, surfactants Tetronic904) and ZY14001 (0.11 micron, surfactant Pluronic L121) were individually injected into the dorsal skin of the hind foot of rabbits. Lymph flow rates and particle concentrations were determined in prenodal lymph fluid after injection, with and without massage of the skin over the injection site. RESULTS: In the first 24 hours after injection, the decreasing order of colloid flux without massage was as follows: ZY13199 > ZY14001 > ZY13163 > ZY13164. Lymph flow rates, lymph leukocyte concentrations and colloid concentrations increased substantially with mechanical skin massage. CONCLUSIONS: Transport of colloids into lymphatic vessels depends on particle size and surface characteristics. Without massage, colloids with egg yolk phospholipid exhibit size dependent decrease in uptake into lymphatics, while with massage only a weak correlation with particle size is present.

Animals↗

Particle size analysis of (99m)Tc-labeled and unlabeled antimony trisulfide and rhenium sulfide colloids intended for lymphoscintigraphic application.

UNLABELLED: Colloidal particle size is an important characteristic to consider when choosing a radiopharmaceutical for mapping sentinel nodes in lymphoscintigraphy. METHODS: Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were used to determine the particle size of antimony trisulfide and rhenium sulfide colloids, and membrane filtration (MF) was used to determine the radioactive particle size distribution of the corresponding (99m)Tc-labeled colloids. RESULTS: Antimony trisulfide was found to have a diameter of 9.3 +/- 3.6 nm by TEM and 18.7 +/- 0.2 nm by PCS. Rhenium sulfide colloid was found to exist as an essentially trimodal sample with a d(v(max1)) of 40.3 nm, a d(v(max2)) of 438.6 nm, and a d(v) of 650-2200 nm, where d(v) is volume diameter. (99m)Tc-antimony trisulfide by MF showed that more than 96% of radioactive particles were smaller than 100 nm; however, (99m)Tc-rhenium sulfide showed that more than 21% were smaller than 100 nm. These radioactive colloids were used with seven different membrane compositions and found not to adsorb significantly to any of them. CONCLUSION: MF was validated as a simple and reliable technique to estimate the percentage radioactive particle size distribution.

Antimony↗

[Study on the clinical use of alpha-fetoprotein (AFP) colloidal gold diagnostic strip].

OBJECTIVE: To test the sensitivity and specificity of alpha-fetoprotein (AFP) colloidal gold diagnostic strip as compared with RIA-AFP diagnostic kit. METHODS: Double blind method was used to test sera from 426 healthy people and 1567 patients selected in two general hospitals and a cancer hospital. Each serum was measured by RIA-AFP and AFP colloidal gold diagnostic strip on the same day. RIA-AFP diagnostic results was identified as true positive or negative. RESULTS: Among 426 healthy people, all the RIA-AFP test showed negative result (serum AFP concentration less than 25 IU/ml), but the AFP colloidal gold diagnostic strip had 1.88% false positive. When comparing the result from 1567 patients measured by RIA-AFP, the sensitivity and specificity of AFP colloidal gold diagnostic strip were 99.3%, and 97.2%, respectively. The crude correspondence rate between the two diagnostic regents was 97.6%. CONCLUSION: AFP colloidal gold diagnostic strip showed very good result and could be used as a screening diagnostic kit in clinic and hospital settings.

Biomarkers, Tumor↗

The effect of colloid stability of wastewater treatment plants effluent on nanofiltration performance.

Laboratory-scale filtration tests utilizing wastewater treatment plants (WWTP) effluent were conducted to investigate fouling and filtration behaviour, especially the influence of colloidal stability on nanofiltration performance. Acidification and coagulant dosage were used to create unstable colloidal conditions. Colloidal stability of the effluent was analysed on by zeta potential measurements. A statistical design method, full factorial design with blocking, has been used to account for effluent composition variations and to account for interaction between experimental parameters. The results show a high correlation between unstable colloidal natural organic matter and the formation of dense fouling layers. The reversibility of the fouling process was shown to be independent from colloidal stability. Irreversible fouling was show to be promoted by mild acidic (pH 5) effluent conditions, whereas coagulant addition showed an increase in the reversibility of the fouling.

Bioreactors↗

ACTH in bovine pituitary intraglandular colloid, the holocrine secretion of intermediate lobe cells.

The presence of bovine pituitary intermediate lobe peptides in intraglandular colloid, the holocrine secretion of intermediate lobe cells, is explored by ELISA. Intraglandular colloid collected immediately after sacrificing the animal, is placed in phosphate buffered saline, pH 7.6. This material is homogenized, centrifuged to remove extraneous tissue, lyophilized and stored at -20 degrees C. ACTH in intraglandular colloid is measured by competitive ELISA. Human ACTH (1-24) is used in the preparation of the solid phase antigen and as the standard for competition. The antibody is rabbit anti-human ACTH (1-24), and the alkaline phosphatase conjugate is goat anti-rabbit IgG with p-nitrophenyl phosphate as substrate. It is concluded that ACTH is present in bovine pituitary intraglandular colloid of intermediate lobe origin and that the colloid may serve as a transport medium for intermediate lobe materials.

Adrenocorticotropic Hormone↗

Crystalloid versus colloid fluid resuscitation: a meta-analysis of mortality.

Controversy persists over the best choice of fluid to use for resuscitation. A number of published articles promote the use of either colloid or crystalloid fluids. Most of the arguments for use of one fluid or the other are based on cardiopulmonary data collected during and after fluid resuscitation. Although many studies report the mortality rate of patients treated with both fluids, none have critically analyzed this most important aspect of therapy. Meta-analysis is a relatively new statistical method whereby data from a number of clinical trials can be pooled to produce more reliable data. In this study meta-analysis was used to pool mortality data from reports of eight previously published, randomized, clinical trials, in which the efficacy of crystalloid and colloid fluid resuscitation was compared. The overall treatment effect when the data from all the clinical trials were pooled showed a 5.7% relative difference in mortality rate in favor of crystalloid therapy. When the data from only those studies using trauma patients were pooled, the overall treatment effect showed a 12.3% difference in mortality rate in favor of crystalloid therapy. However, when data from studies that used nontrauma patients were pooled, there was a 7.8% difference in mortality rate in favor of colloid treatment. In patients with trauma who are septic and in whom the capillary leak syndrome leads to adult respiratory distress syndrome, it may be assumed that colloid resuscitation would be no better than crystalloid resuscitation. In this study the meta-analysis of published data showed that this form of treatment is deleterious. In patients who are nonseptic or having elective surgery, however, the basement membrane is intact, and meta-analysis of data in this setting showed that treatment with colloids would be efficacious.

Colloids↗

Experimental septic shock: relative effects of treatment with antibiotics, crystalloid or colloid solution infusions and corticosteroids.

This study evaluates the relative effects of 2 combined antibiotics, a crystalloid solution, 4 3% colloid solutions, and a pharmacologic dose of corticosteroids, given alone and in combination for the treatment of Escherichia coli-induced septic shock. All treatments began 5.5 h after bacterial injection. Untreated septic rats had a mean survival time of 9.9 h. Antibiotics (trimethophrim and sulfamethoxazole) alone did not significantly increase mean survival time (11.0 h). No rats in either of these two groups survived 24 h. When antibiotics and dexamethasone were combined, 40% (4/10) rats lived longer than 24 h (p less than .05). With Ringer's solution infusion, the mean survival time was 8.7 h and 30% (3/10) lived longer than 24 h. When a 3% colloid solution was given, 50% (20/40) lived more than 24 h and 20% (8/40) lived more than 7 days. There was no significant difference between the 4 colloid solutions (albumin, dextran-40, dextran-70, hydroxyethyl starch). When Ringer's solution was combined with dexamethasone and antibiotics, 80% (8/10) lived more than 24 h and 20% (2/10) were long-term survivors. When the antibiotic drug was combined with a colloid solution and dexamethasone, all animals lived more than 24 h and 90% (9/10) lived more than 7 days. This study demonstrates the therapeutic value of an effective antibiotic drug for control of the infective organism, a colloid solution infusion to maintain blood volume and circulation, and corticosteroids for still largely unknown reasons.

Animals↗

A new formulation of Tc-99m minimicroaggregated albumin for marrow imaging: comparison with other colloids, In-111 and Fe-59.

The biodistributions of five Tc-99m colloids were compared with the 24-hr distributions of Fe-59 and In-111 in dogs by direct radioassay 1 hr after intravenous injection. One formulation of Tc-99m minmicroaggregated albumin (particle size 30-100 mn), produced the highest marrow concentration, approximately six times that of Tc-99m sulfur colloid, with similar blood, and liver concentrations and a lower splenic uptake. Nevertheless, the best colloid marrow uptake was lower than the 24-hr value for In-11 and much lower than that for Fe-59. The marrow concentration of minimicroaggregated albumin was also higher than that of sulfur colloid in rats at 30 min after injection. The principal disadvantage of Tc-99m antimony sulfide colloid was its slow blood clearance. Clinical evaluation of Tc-99m minimicroaggregated albumin for marrow imaging appears warranted, although its hepatic activity will obscure overlying and immediately adjacent marrow.

Animals↗