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[Results of the UFT sensitivity test using human urogenital cancers transplanted subcutaneously and under the subrenal capsule of nude mice].

Experimental chemotherapy with UFT was performed against human urogenital cancers, transplanted subcutaneously and under the subrenal capsule (SRC) of nude mice. The tumor take with subcutaneous assay was confirmed in 21 cell lines of human neoplasms, which consisted of 9 renal cell carcinomas, 5 renal pelvic carcinomas, 1 ureteral carcinoma, 3 carcinomas of the urinary bladder, 2 prostatic carcinomas and 1 testicular tumor. On the other hand, the tumor take with subrenal capsule assay was confirmed in 17 of the neoplasm, which consisted of 7 renal cell carcinomas, 4 renal pelvic carcinomas, 4 carcinomas of urinary bladder, 1 prostatic carcinoma and 1 testicular tumor. UFT was administered, starting on Day 14 for subcutaneous transplantation and starting on Day 0 for SRC assay. The dose of UFT was the same as clinical dose for both subcutaneous transplantation and subrenal capsule assays. Treatment with UFT was performed for 6 weeks in subcutaneous transplantation assay and for 4 weeks in subrenal capsule assay. Effect of UFT was evaluated by the inhibition rate (IR) calculated by the mean tumor weights of both treated and untreated groups. Responses to the treatment in subcutaneous transplantation and subrenal capsule assays were judged as effective when the IR were higher than 58% and 20%, respectively. Responses rates of UFT in subcutaneous transplantation and subrenal capsule assays were 43% and 82%, respectively.

Animals↗

[The release of immobilized substances from Symplex capsules].

A new procedure of microencapsulation was studied with regard to substance release and quantification of diffusion processes on the capsule membrane. The permeability behaviour on the capsule membrane was especially studied in metabolites, which are essential for immobilized biological objects (i.g. preimplantative mammal embryos). Peptide and proteohormones, cyanmethemoglobin and proteins were enclosed in simple and multiple Symplex Capsules. All substances examined are able to pass the Symplex membrane. The speed of release is influenced by the size of the capsule, the ion force, temperature, concentration of immobilized substances as well as their linear and globular structur. Compared with simple capsules the release of substances from multiple capsules was delayed. Corresponding to the results found under the experimental design described the Symplex membrane can be considered as coating for the compartmentation of cells, that allows the passage of essential substances for the immobilized objects. The method of microencapsulation used and described has various ways of application.

Capsules↗

Studies on a single-dose capsule preparation of Poliomyelitis vaccine.

In view of certain difficulties involved in the administration of poliomyelitis vaccine in liquid form on sugar or in syrup in mass campaigns, trials have been conducted with a new single-dose preparation of live attenuated poliovaccine (Sabin strain) in an emulsion in a gelatin capsule. Each capsule contained a standard dose of vaccine which was shown to be stable in this form. It has been demonstrated that the capsule vaccine was as effective as liquid vaccine both in children and in adults. The capsules were acceptable to adults and children over the age of 5 years, but between 6% and 7% of 4-5-year-old children refused the vaccine in this form owing to difficulty in swallowing the capsules.The authors consider that the capsule may be recommended for the routine immunization of older children and adults and for mass vaccination campaigns. It is suggested that the vaccine could be administered to young children and babies in the course of such campaigns by opening the capsule and mixing the contents with water or sweetened liquid in a spoon.

Adolescent↗

[Effect of the antibiotic granulation method on the quality of semisynthetic penicillin capsules (e.g., the sodium salt of dicloxacillin)].

A procedure for dry granulation of antibiotics consisting in dry compacting of a powder-like composition followed by its grinding to granules was developed. The advantages of dicloxacyllin capsules manufactured by dry granulation over the capsules manufactured by moist granulation are shown with respect to the content of the light absorbing admixtures during the capsule manufacture and storage. The conditions for estimation of the antibiotic dissolution from the capsule were developed with the use of a "Rotating Basket" apparatus. Comparative evaluation of disintegration and dissolution of the capsules prepared by dry or moist granulation showed practical equivalence of both types of the capsules with respect to these characteristics.

Capsules↗

Synthesis of lens capsule in long-term culture of human lens epithelial cells.

PURPOSE: This study examined the extent to which human lens epithelial (HLE) cells in tissue culture retain the potential for differentiation, expression of lens-specific marker proteins, and the synthesis of lens capsule, the major characteristics of lens epithelium in vivo. METHODS: Primary cultures of HLE cells were maintained for up to 450 days. Transmission and immunoelectron microscopy were used to study the thickness of the synthesized capsule and the formation of type IV collagen and laminin, two major protein components of the basement membrane of lens capsule in vivo. RESULTS: In a long-term HLE culture system, without subcloning, lens fiber differentiation and capsular synthesis were maintained over a period of 450 days. In these cultures, the cell sheet showed three distinct zones: (1) a central zone with tight monolayer; (2) a mild peripheral zone with irregularly aggregated multilayer; and (3) a peripheral zone with loose monolayer. The basement membrane-like material was synthesized in the central zone and lentoids, which serve as a model for fiber differentiation, developed primarily in the mid peripheral zone. No capsular material or lentoids were observed in the peripheral zone. The capsule-like material was 2 to 2.5 microns thick and showed the presence of type IV collagen and laminin, as detected by antibody reaction. CONCLUSION: This study demonstrates for the first time that HLE cells in long-term cultures synthesize a continuous sheet of capsule-like material. The findings also suggest that reformation of a tight cell-to-cell relationship or generation of high cell density similar to that found in vivo may be an important factor for the synthesis of lens capsule.

Basement Membrane↗

[Comparison of detection methods for the Staphylococcus aureus capsule].

Eleven methods for capsule detection of Staphylococcus aureus were compared. The most suitable of them were transmission electron microscopy, determination of the presence of clumping factor, determination of colonial morphology in serum-soft agar, estimation of cell volume and staining with safranine. The determination of clumping factor is a fast and effective method for presumptive diagnosis of capsulated strains, but need to be confirmed by another method. The cell volume estimation is useful for determination of capsule production in liquid cultures, while staining with safranine is suitable for genetic studies of capsule production. The other methods analyzed in this work (Indian ink staining, use of anticapsular antisera, determination of virulence for mice, lisostaphin susceptibility, resistance to phages and resistance to phagocytosis) were laborious, too slow, or need components and/or equipment not available in all laboratories. In addition, two methods of induction of capsule production were assayed, one in vitro by several passages in broth with 10% bovine serum and the other in vitro by intraperitoneal inoculation in mice. Both methods induced capsule production.

Agglutination Tests↗

Esophageal passage of iodine-131 capsules.

UNLABELLED: The purpose of this study was to determine the orogastric transit time of standard 131I capsules and the incidence of transit delay. METHODS: We studied 58 consecutive subjects receiving outpatient diagnostic and therapeutic 131I dosages. A standard ion chamber survey meter, placed over the left upper quadrant of the abdomen, monitored orogastric transit. Each subject had ample water to subjectively swallow their capsule. Orogastric transit times, volume of water ingested, capsule size, and demographic and historical data were recorded for each subject. RESULTS: Seventeen subjects (29%) had delayed transit, with an orogastric transit time > 90 sec (median 140 sec, range 100-930 sec). Forty-one subjects had normal transit (median 14 sec, range 4-51 sec). We identified delayed transit in 7 of 37 women (19%) and 10 of 21 men (48%) (p = 0.035). Age, capsule size and initial water volume ingested did not differ significantly between subject groups. CONCLUSION: Men were more likely than women to have prolonged orogastric transit of standard 131I capsules. Other than sex, we found no identifiable clinical feature or medical history to predict delayed orogastric transit. A standard survey meter can identify adherent capsules to minimize esophageal radiation exposure.

Adhesiveness↗

Demonstration of a capsule on Mycoplasma ovipneumoniae.

OBJECTIVE: To examine Mycoplasma ovipneumoniae for presence of a capsule and its potential role in adherence. SAMPLE POPULATION: 17 isolates of M ovipneumoniae and 2 isolates of M arginini, recovered from sheep with respiratory tract disease. PROCEDURE: Mycoplasmas were cultured in modified Fills broth medium, ovine fetal lung cells, or ovine tracheal ring explants. Pelleted mycoplasmas or ring cultures infected with mycoplasmas were treated with ruthenium red or polycationic ferritin and visualized by transmission electron microscopy. Reactivity of several lectins with the mycoplasmas was studied by use of a microtitration plate agglutination test. RESULTS: Electron microscopy revealed a large number of M ovipneumoniae cells covered with an electron dense-stained amorphous material suggesting that it was a capsule. Multiple passages of the microorganisms in modified Friis broth medium decreased thickness of the capsule, but not percentage of cells encapsulated. Marked differences were observed when M ovipeumoniae isolates grown in modified Friis broth medium or co-cultured with ovine fetal lung cells were compared for capsular thickness or percentage of encapsulation. In thin sections of ruthenium red-stained tracheal ring cultures, the mycoplasmas appeared to be in close contact with cilia through their capsule. All isolates of M ovipneumoniae reacted strongly with wheat germ agglutinin lectin. CONCLUSIONS: Mycoplasma ovipneumoniae produces a polysaccharide capsule with variable thickness that is dependent on culture conditions and strain. Morphologic observations suggest that this capsule facilitates adherence of the organism to ciliated epithelium.

Agglutination↗

Types I and III collagen in the tissue capsules of titanium and stainless-steel implants.

Collagen plays an important role in wound healing and as such is present in connective tissue capsules around implanted materials. The proportion of type I collagen to type III collagen is lower during wound healing than that found in normal dermis, but the amount of type I collagen gradually increases and type III decreases as healing continues. The intent of this research was to investigate a possible correlation between implant metals and type I and type III collagen formation in the ensuing soft-tissue capsules. Smooth implants of grade 4 commercially pure titanium and 316L stainless steel were placed via injection needle into the subcutaneous tissue of 12 rats for 6 weeks. The soft-tissue capsule that formed around each implant was evaluated histologically and by immunofluorescence. Although the two metal implant types differ in many respects, they were chosen for their differences in surface conductivity. Titanium oxide is semiconducting, whereas the oxide of stainless steel is conducting. Impedance spectroscopy was used for conductivity analysis of the surface. No qualitative differences were found in amount of type I or type III collagen in the capsules of the two metals. However, the capsules around titanium stained for type I collagen were thicker than capsules around stainless steel. In addition, type I collagen showed evidence of a greater association with densely packed, highly orientated collagen fibers.

Animals↗

Long- and short-term effects of biological hydrogels on capsule microvascular density around implants in rats.

Fibrous capsule formation around implants can inhibit solute exchange between implantable devices and the circulation. Parylene-n coated polycarbonate disks surrounded with growth factor reduced Matrigel (MG) or several gelatin-based matrices were implanted intramuscularly into rats for 21 or 50 days. MG supplemented with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) increased capsule microvascular density at 21 days (p < 0.05) when compared to bare parylene-coated polycarbonate disks (control). The increased microvascular density around VEGF- and bFGF-treated implants regressed by 50 days and was no longer significantly different from controls. The microvascular density induced by the gelatin-based matrices was not significantly different from controls at 21 days, but was increased at 50 days (p < 0.05), suggesting a slower, long-term effect. Disks treated with MG and gelatin-based matrices had thinner capsules at 21 days (p < 0.05). By 50 days, the capsule thicknesses around these implants were no longer statistically thinner than controls. The capsule thickness around implants treated with VEGF, bFGF, and essential gelatin-based matrix was thinner than controls at 50 days (p < 0.05). These results indicate that it is possible to increase functional microvascular density within fibrous capsules using angiogenic growth factors and gelatin-based matrices. However, this effect may be short-lived, requiring chronic administration of growth factors.

Animals↗

Highly stable and biocompatible nafion-based capsules with controlled permeability for low-molecular-weight species.

Biocompatible hollow capsules have been formed by electrostatic layer-by-layer self-assembly of a perfluorinated ionomer (Nafion) in alternation with ferric ions onto polystyrene latex particles or organic microcrystals, followed by dissolution of the cores by tetrahydrofuran or dimethylformamide. The stepwise growth of multilayers was followed by UV-visible spectroscopy and microelectrophoresis. The formation of hollow capsules was verified by confocal laser scanning microscopy and scanning force microscopy. The hollow Fe3+/Nafion capsules displayed high stability over a wide range of pH values and at high temperature. Fluorescein transport through the Fe3+/Nafion capsule wall was studied by means of photochemical bleaching and recovery (PBR) of the capsule interior. A diffusion model is suggested to calculate the diffusion coefficient for low-molecular-weight species, which was determined to be in the order of 10(-12) cm2s. The permeability can be manipulated by changing the wall thickness of the capsules.

Journal Article↗

Multiple-functional capsule catalysts: a tailor-made confined reaction environment for the direct synthesis of middle isoparaffins from syngas.

A capsule catalyst for isoparaffin synthesis based on Fischer-Tropsch reaction was designed by coating a H-ZSM-5 membrane onto the surface of the pre-shaped Co/SiO(2) pellet. Morphological and chemical analysis showed that the capsule catalyst had a core-shell structure. A compact, integral shell of H-ZSM-5 crystallized firmly on the Co/SiO(2) substrate without crack. Syngas passed through the zeolite membrane to reach the Co/SiO(2) catalyst to be converted, and all hydrocarbons formed with straight chain structure must enter the zeolite channels to undergo hydrocracking as well as isomerization in this tailor-made confined reaction environment. A narrow, anti-Anderson-Schultz-Flory law product distribution was observed on these capsule catalysts. Contrary to a mechanical mixture of H-ZSM-5 and Co/SiO(2), C(10+) hydrocarbons were suppressed completely on this novel capsule catalyst, and the selectivity of middle isoparaffins was considerably improved. The carbon number distribution of the products depended on the thickness of the zeolite membrane, and it was possible to selectively synthesize specified distillates, such as gasoline-range, or heavier hydrocarbons from syngas directly, by simply adjusting the thickness of the zeolite membrane of the capsule catalyst. This kind of capsule catalysts can be extended to various consecutive reaction systems as the shell and core components are independent catalysts for different reactions. At the same time, shape selectivity and space-confined effects can be expected for the reactant, intermediates and product of the sequential reactions.

Journal Article↗

Bone morphogenetic protein 4 (BMP4): a regulator of capsule chondrogenesis in the developing mouse inner ear.

Formation of the cartilaginous otic capsule is directed by otic epithelial-periotic mesenchymal interactions. In response to induction by otic epithelium, condensations of mesenchyme appear in the periotic region and form a chondrified otic capsule that serves as the template for the subsequent formation of the endochondral bony labyrinth. Previous studies indicate that members of the transforming growth factor beta superfamily, including transforming growth factor beta(1), participate in guiding these tissue interactions. In this study, we report the localization of bone morphogenetic protein 4 (BMP4) to the mesenchymal and epithelial-derived tissues of the mouse inner ear between 10.5 and 14 days of embryonic development. We demonstrate modulation of chondrogenesis in cultured mouse periotic mesenchyme by exogenous BMP4 protein and investigate the function of endogenous BMP4 in otic capsule chondrogenesis. We show that in the presence of the BMP antagonist, Noggin, otic capsule chondrogenesis is suppressed in culture in a dose-dependent manner. Consistent with this finding, addition of BMP4-specific antisense oligonucleotide to cultures of mouse periotic mesenchyme containing otic epithelium decreases levels of endogenous BMP4 protein and suppresses the chondrogenic response of the cultured periotic mesenchyme, providing evidence of the necessity for BMP4 in mediating otic capsule chondrogenesis. Supplementation of either Noggin- or BMP4 antisense oligonucleotide-treated cultures with BMP4 protein can restore the extent of chondrogenesis to normal levels. Our findings support BMP4 as an essential mediator of chondrogenesis in the developing otic capsule in situ.

Animals↗

The efficacy of complement-mediated phagocytosis of Cryptococcus neoformans is dependent on the location of C3 in the polysaccharide capsule and involves both direct and indirect C3-mediated interactions.

Complement component 3 (C3) is the major opsonin for the pathogenic fungus Cryptococcus neoformans in the non-immune host. However, the efficiency of complement-mediated opsonization varies, depending on the strain, through mechanisms that are not understood. Analysis of complement-mediated phagocytosis for 12 strains grown in Sabouraud medium revealed that phagocytic indices were inversely correlated with capsule volume. In contrast, there was no correlation between phagocytic index and capsule volume for IgG1-opsonized cells. When capsule size was increased, the efficacy of complement-mediated phagocytosis decreased, whereas that of antibody-mediated phagocytosis increased. C3 localized inside the capsule and at the outer capsule edge for poorly phagocytozed and well-phagocytozed strains, respectively. Blocking experiments revealed that complement-mediated phagocytosis occurred through complement receptor 3 (CR3), without significant involvement of CR1 or CR4. Blocking experiments with antibodies to C3 did not completely abrogate yeast cell uptake, consistent with phagocytosis through glucuronoxylomannan-CR3 interactions. Our data explain how some large encapsulated cells avoid phagocytosis and suggest a novel strategy for immune evasion whereby a microbial capsule interferes with phagocytosis by modifying the location of C3 deposition.

Complement C3↗

A pharmacokinetic study of intravenous itraconazole followed by oral administration of itraconazole capsules in patients with advanced human immunodeficiency virus infection.

A randomized, open-label, comparative study was conducted in 30 male patients with moderately advanced human immunodeficiency virus (HIV) infection to examine the pharmacokinetics of an investigational intravenous preparation of itraconazole compared with pharmacokinetics after administration of itraconazole capsules. The study also assessed whether adequate plasma concentrations of itraconazole could be rapidly achieved with the intravenous formulation and then maintained after cessation of intravenous therapy with itraconazole capsules. All patients received 200 mg intravenous itraconazole as a 1-hour infusion in 40% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) vehicle twice daily for 2 days, and then 200 mg intravenously once daily for 5 days. Patients then received itraconazole capsules, either 200 mg twice daily or 200 mg once daily for 28 days. Steady-state plasma concentrations of itraconazole were reached by day 3 with intravenous infusion, a much shorter time than observed with administration of itraconazole capsules. Steady-state concentrations of itraconazole and hydroxyitraconazole were effectively maintained during the rest of the intravenous infusions of itraconazole. Oral follow-up with administration of 200-mg capsules once daily could not maintain the plasma concentrations of itraconazole and hydroxyitraconazole obtained at the end of the intravenous treatment, whereas twice-daily oral administration maintained or increased these concentrations. Mean plasma concentrations of itraconazole and hydroxyitraconazole on day 7 were similar to those on day 36 in the twice-daily group. Mean renal clearance was comparable to mean total body clearance, and approximately 93% to 101% of the HP-beta-CD was excreted unchanged in urine within 12 hours of administration. The HP-beta-CD was essentially eliminated through the kidney, and little accumulation in the body was observed in this patient population. Adverse events during the intravenous phase were most commonly associated with intravenous administration. Intravenous infusion of itraconazole for 7 days followed by administration of itraconazole capsules twice daily for 28 days is an effective dose regimen in patients with advanced HIV infection.

2-Hydroxypropyl-beta-cyclodextrin↗

Egg capsules of a parasitic turbellarian flatworm: ultrastructure of hatching sutures.

Egg capsules of Syndisyrinx franciscanus, an intestinal parasite of sea urchins (Strongylocentrotus spp.), consist of a bulb, which contains the embryos, and a stalk-like filament. The wall of the bulb is about 12 microns thick and is composed of sclerotized proteins. The end of the bulb opposite the attachment of the filament bears a reticulum of hatching sutures. Transmission electron microscopy discloses that hatching sutures traverse the entire thickness of the capsule wall. The inner 9-10 microns of sutures are a uniform 20 nm in width and contain a trilaminar cementum. The outer 2-3 microns of sutures are 15 nm to more than 500 nm in width and contain an electron-lucent cementum. The latter may contain an irregular, median, electron-dense layer or, more commonly, electron-dense granules. The outside of some capsules is partially covered by a thin, electron-dense material. A previous study showed that sutures in intact capsules of Syndisyrinx franciscanus are not affected by host digestive fluids, but are severely weakened immediately prior to hatching owing to activities of the embryos. The hypothesis that the embryos secrete a hatching enzyme is supported by findings that sutures of intact capsules are not affected by externally applied trypsin, but become weakened when capsules are cut open and then incubated in trypsin. Scanning electron microscopy reveals that the outer parts of sutures often remain intact after hatching. We hypothesize that the ability of sutures to resist enzymatic attack from the outside, but not the inside, results from differences in the chemical properties of the cementums in outer and inner parts of sutures.

Animals↗

Phase-shift of polysaccharide capsule expression in group B streptococci, type III.

The type-specific polysaccharide capsule is an important virulence determinant in group B streptococci (GBS). The previously described inverse relationship between the buoyant density of a GBS-isolate and the capsular thickness was used to assess the frequencies of polysaccharide capsular phase-shift in clinical GBS, type III strains. Shift from intermediate density (ID) of parental strains, to high density (HD), i.e. shift from intermediate capsule thickness to poor encapsulation, was found to range from 1.2 x 10(-3) to 4.8 x 10(-6). Shift from ID to low density (LD), i.e. shift to abundant encapsulation, ranged from 1.9 x 10(-4) to 1.1 x 10(-7). Shifts were reversible in all cases, either directly (HD-->LD or vice versa) or through intermediate forms. Reversion frequencies were in some isolates as high as 10(-1). Phase-shift frequencies differed more than a thousand-fold between compared strains. Differences in phenotypic shift between strains were validated using flow cytometry. Possible modulation of capsule expression by changes in culture conditions was assessed. Variation of temperature, oxygen-tension, and presence of human serum did not affect capsule expression. However, growth at pH below 5.5 decreased the amount of capsule bound native type III polysaccharide, probably through phenotypic modification rather than genetic shift. IS861, an insertion sequence which has been proposed a regulatory function on the GBS capsule expression, was found in multiple copies in the isolates investigated. No differences in copy number or location of IS861 between the differently encapsulated phenotypes were found.

Animals↗

Attachment of blastocysts to lens capsule: a model system for trophoblast-epithelial cell interaction on a natural basement membrane.

The bovine lens capsule has previously been shown to provide an optimal surface for the examination of epithelial cell interaction with a basement membrane. This native substrate has been used to investigate some initial aspects of attachment of mouse blastocysts and trophoblastic cellular outgrowth. Mouse blastocysts were presented to the cell-free humoral side of the anterior lens capsule, incubated for 72 h, and examined by scanning and transmission electron microscopy. Blastocysts hatch and attach from their zonae pellucidae by 30 h. Trophoblastic cells proliferate rapidly in a coronal direction, display extensive surface microvilli, and advance by the extension of numerous filipodia, many of which terminate with bulbous projections. These projections were shown by transmission electron microscopy to contain numerous vacuoles and polysomes. To simulate further the initial blastocyst-uterine interaction, a suspension of lens epithelial cells was introduced to the capsule and permitted to form a monolayer prior to the addition of the blastocysts. At 72 h the monolayer of lens cells remained intact. We observed that: a) lens cells appear to recede from the advancing trophoblastic cells, and b) trophoblastic cells extend beneath the monolayer of lens cells and thereby dislodge the cells from the lens capsule substrate. No infiltration of the capsule by the advancing trophoblastic cells was observed. The lens capsule appears to offer a promising system for the study of trophoblast-epithelial cell interaction on a natural basement membrane.

Animals↗