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Macromolecular organization of basement membranes. Characterization and comparison of glomerular basement membrane and lens capsule components by immunochemical and lectin affinity procedures.

The macromolecular components of bovine glomerular basement membrane (GBM) and lens capsules (anterior and posterior) solubilized by sequential extractions with denaturing agents were quantitated and characterized by polyacrylamide gel electrophoresis, CL-6B filtration, and DEAE-cellulose chromatography with the help of immunochemical techniques. Laminin, entactin, fibronectin, and heparan sulfate proteoglycan were primarily recovered (over 80%) from both basement membranes in a guanidine HCl extract which contained only a limited amount of the total protein (10-14%); most of the remainder of these noncollagenous components could be solubilized by the guanidine in the presence of reducing agent. Although a portion of the Type IV collagen could be obtained by these treatments, effective extraction of this protein depended on exposure to sodium dodecyl sulfate under reducing conditions. Immunoblot analysis revealed a remarkably similar pattern for GBM and lens capsule Type IV collagens with prominent bands of Mr = 390,000, 210,000, and 190,000 being evident. Fibronectin was present in much greater amounts in GBM than lens capsule while the reverse was true for entactin. In both GBM and lens capsules, the entactin (Mr = 150,000) exceeded laminin; the latter protein on immunoblotting was found to contain primarily the alpha-subunit (Mr = 200,000). The size of the heparan sulfate proteoglycan from anterior (Mr = 400,000) and posterior lens capsule (Mr greater than 500,000) was substantially larger than that from GBM (Mr = 200,000). During DEAE-cellulose chromatography under nonreducing conditions in a denaturing solvent, a portion of the Type IV collagen coeluted with the proteoglycan from these membranes. Considerable Bandeiraea simplicifolia I binding activity (alpha-D-galactose specific) was observed in GBM and lens capsule extracts and column fractions which could not be accounted for by laminin alone. Several components which reacted with this lectin were seen on transblots and among these Type IV collagen was identified. In contrast to the basement membranes from bovine tissues, the constituents from human GBM did not react with the B. simplicifolia I lectin.

Animals↗

Role of the capsule produced by Bacillus megaterium ATCC 19213 in the accumulation of metallic cations.

A study was undertaken to determine if the capsule produced by Bacillus megaterium ATCC 19213 was capable of binding metallic ions. For non-toxic metallic ions, this was accomplished by determining the relative concentrations of Fe2+, Ca2+, Zn2+, Mg2+, and Mn2+ removed from a chemically defined medium by the normally capsulated parent strain and two mutants with much smaller capsules. For toxic metals, the rates of respiration of the parent strain and a small capsule mutant in the presence of Cu2+, Hg2+, and Ag1+ were compared. It was found that the parent strain accumulated more Ca2+, Mg2+, and Mn2+. Accumulation of Fe2+ and Zn2+ was similar for the parent strain and the small capsule mutants. Respiration of the parent strain was less inhibited by Cu2+, Hg2+, and Ag1+, indicating that these metals are also bound to the capsule.

Bacillus megaterium↗

[Morphological study of capsules formed around various breast endoprostheses].

Silicone implants used in mammaplasty are often associated with constrictive capsule fibrosis, leading to induration and deformation of the prosthetic organs. In connection with this, there has been developed and is currently successfully applied in the clinical practice of the A. V. Vishnevsky Institute of Surgery an original method of mammary gland endoprosthesis with oily implants. The objective of this work was to make a comparative study of the late results of mammaplasty based upon the morphologic study of capsules formed around silicone and oily implants, removed during secondary surgical interventions. The dynamics of capsule formation around temporary organic glass endoprostheses has also been studied. The results showed that implantation of silicone prostheses results in a formation of a rough thick capsule, an active inflammatory reaction in the surrounding tissues and the development of constrictive fibrosis. Implantation of a temporary organic glass endoprosthesis that is filled with oil at the second stage of the operation, is followed by a thin capsule formation without signs of inflammation. The stability of the capsule structure up to 3 years has been noted. On the whole, this prosthesis provides a good cosmetic effect during long time after mammaplasty.

Adolescent↗

Histologic, histochemical, and ultrastructural studies of the hip joint capsule and ligamentum teres in congenital dislocation of the hip.

The histology, histochemistry, and ultrastructure were investigated in 12 ligamentum teres and 11 hip joint capsule biopsies obtained at open reduction of 9 patients with congenital dislocation of the hip (CDH) and of 2 normal hips. The ages of the patients ranged from 2 months to 4 years and 2 months. In the joint capsule of the dislocated hips, the cells were irregularly distributed, had different shapes, and appeared to be in different stages of functional activity. The collagen fiber bundles were thicker than in the normal capsule, distributed and of varied thickness. The collagen fibrils in the younger patients were thinner than in the normal hip and their diameter increased slightly with age. In the ligamentum teres of the dislocated hips the elastic fibers were thicker and more numerous than in the normal hip, whereas the cells and collagen fibrils showed changes similar to those observed in the capsule. Fibrocartilaginous metaplasia was found in both the capsule and the ligamentum teres in areas compressed by the femoral head. The morphologic and histochemical changes observed in the joint capsule in CDH appeared to be secondary to the mechanical stresses caused by the dislocation.

Cartilage, Articular↗

Sampling intestinal content with a sequestering capsule. A noninvasive technique for determining bile acid kinetics in man.

A noninvasive technique for determining bile acid kinetics by isotope dilution in man features the intravenous injection of a radiolabeled bile acid, together with daily oral administration, for several days, of capsules of dialysis membrane containing cholestyramine and colored beads for dating. The cholestyramine traps conjugated bile acids during transit of the small intestine. Capsules are recovered from stool by sieving, sequestered bile acid is eluted, conjugated bile acids are isolated chromatographically, and their specific activity is determined. The precision and validity of this sequestering capsule technique were assessed by comparing the specific activity decay curve of chenodeoxycholyl conjugates obtained from capsule samples with that obtained from duodenal samples in seven healthy volunteers in whom the bile acid pool had been labeled with [14C]chenodeoxycholic acid. Estimates of pool size by the two methods correlated well (r = 0.98), as did the daily fractional turnover rate (r = 0.96). The mean (+/-SD) percentage differences for the kinetic parameters of pool size (8.3 +/- 13.6), fractional turnover rate (-15.2 +/- 11.5), and synthesis rate (-4.3 +/- 11.4) were fairly small, indicating that the noninvasive method has validity. However, agreement between simultaneously administered capsules was only fair, especially when the amount of bile acid trapped was small, suggesting that the precision of the capsule technique may be less than that of the conventional duodenal sampling technique; the latter probably obtains a more valid sample of the bile acid pool.

Administration, Oral↗

[Motor paresis with cheiro-oral topography due to small infarct in the internal capsule or the corona radiata].

We reported five patients having presented only with clumsy hand and dysarthria which resulted from motor paresis confined to one side of the fingers and the ipsilateral face and tongue. All of them were right-handed, and their manifestation was transient. They had no abnormalities of muscle tonus and sensation, and no ataxia. The features of these cases differed from those of the dysarthria-clumsy hand syndrome because of absence of ataxia, and could be distinguished from pure motor hemiplegia by a motor paresis with cheiro-oral topography. MRI examinations showed a localized lesion at the border between internal capsule and corona radiata (two cases), or in the corona radiata just over this region (three cases). In the former cases in which the internal capsule was involved, we confirmed the lesion in the genu and anterior half of the posterior limb of the internal capsule. The lesion was on the left side in all five patients. It has been known that the pyramidal tract consists of the large and small fibers. The large ones are localized in the posterior part of the posterior limb of the internal capsule, and the damage of them produces sustained and serious motor paralysis. The small ones are widely distributed in the genu and the posterior limb of the internal capsule. The findings of our study suggest that the small fibers have adjacent somatotopy for the hand and mouth in the region of the genu and the anterior part of the posterior limb of the internal capsule, and that the damage of them may lead to mild, transient motor paresis without spasticity.

Adult↗

[Effect of refined xuefu capsule on mRNA expression of nitric oxide synthase of hypoxic ischemic myocytes evaluated by northern blotting].

Comparative study on effect of refined Xuefu capsule, Xuefu Zhuyu capsule and diltiazem on mRNA expression of nitric oxide synthase (NOS) and release of LDH-L, CK, GOT of hypoxic hypoglycemic cultured myocytes were studied by using the serum pharmacological method, reverse transcriptase-polymerase chain reaction (RT-PCR) and Northen blotting. It was shown that the three drugs can reduce release of LDH-L,CK,GOT of myocytes (P < 0.01), the effect of refined Xuefu capsule and diltiazem were obvious than that of Xuefu Zhuyu capsule in reducing LDH-L release and NOS mRNA expression (P < 0.01), and effect of refined Xuefu capsule was the strongest (P < 0.01). These findings indicated that all 3 drugs have significant effect in protecting myocytes which related to their effect on NO production of myocyte particularly the refined Xuefu capsule and diltiazem.

Animals↗

True exfoliation of the lens capsule.

True exfoliation or lamellar delamination of the lens capsule is a rare disorder in which the lens capsule is thickened and the superficial portion of the lens capsule splits from the deeper layer and extends into the anterior chamber. The pathogenesis of this disorder is not clear, but intense infrared radiation has been thought to be the main causative factor. We describe a patient with a history of heat exposure who had a cataract and was found to have bilateral delamination of the anterior lens capsule. Findings from light microscopy and scanning and transmission electron microscopy demonstrated a lamellar separation of the anterior portion of the lens capsule, confirming the diagnosis of true exfoliation.

Aged↗

Distribution of collagens and glycosaminoglycans in the joint capsule of the proximal interphalangeal joint of the human finger.

BACKGROUND: The capsule of the proximal interphalangeal joint consists of the central slip of the extensor tendon dorsally, the collateral ligaments at the sides and the palmar ligament ventrally. Fibrocartilaginous menisci have been reported extending into the joint cavity and the central slip has a sesamoid fibrocartilage articulating with the proximal phalanx. This study relates ECM composition in the joint capsule to function. METHODS: Each part of the capsule from 24 fingers amputated because of trauma, carcinoma, isthaemia, fixed-flexion deformities or Dupuytren's contracture, was dissected out. Sections were prepared for routine histology or immunolabelled with a panel of monoclonal and polyclonal antibodies against collagens and glycosaminoglycans using the avidin/biotin/peroxidase procedure. RESULTS: All parts of the capsule consistently labelled for types I, III and VI collagens and for dermatan and keratan sulphate, though labelling was more pericellular in fibrocartilaginous regions. In contrast, only certain regions of the capsule in some fingers labelled for type II collagen, chondroitin 4 or 6 sulphate. The sesamoid fibrocartilage in the central slip showed the greatest degree of fibrocartilage differentiation, especially in fixed-flexion deformity fingers, and the palmar ligament the least. CONCLUSIONS: The immunolabelling patterns suggest that there is an ordered sequence of matrix changes accompanying fibrocartilage differentiation. Chondroitin sulphate-containing proteoglycans accumulate first, and type II collagen appears later. The presence or absence of type II collagen probably relates to different levels of compressive loading. No fibrocartilaginous menisci were found in normal joints and those described previously are regarded as synovial folds.

Adolescent↗

Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules.

Twelve healthy fasting volunteers received two 0.2-mg digoxin capsules or tablets with 60 ml water, 60 ml Maalox, or 60 ml Kaopectate in a randomized, single-dose, six-way crossover study. Concentrations of digoxin in multiple plasma samples and in all urine collected during the 24 hours after each dose were determined by radioimmunoassay. Compared to the water treatment, administration of both tablets and capsules with Maalox or Kaopectate reduced the peak digoxin plasma concentrations but did not significantly influence the time of peak concentration. Neither Maalox nor Kaopectate influenced the area under the 24-hour plasma concentration--time curve for either tablets or capsules. However, 24-hour urinary recovery of digoxin from tablets tended to be reduced by Maalox and Kaopectate; this was not the case with capsules. Digoxin capsules may have an advantage over currently available tablets in clinical situations requiring digoxin coadministration with nonabsorbable gastrointestinal preparations.

Adult↗

Lens epithelial cell adhesion to lens capsule: a model system for cell-basement membrane interaction.

Adhesion of calf lens epithelial cells to lens capsule, their natural basement membrane was found to be considerably more rapid than either to plastic or to type I or type IV collagen coated surfaces. No polarity of the basement membrane was observed as the cells were able to attach to either side of the anterior or posterior lens capsule; a prerequisite for adhesion to the lenticular side of the anterior capsule was the prior removal of its epithelial cell layer. The attachment was energy-dependent and required calcium and magnesium ions, but was not enhanced by the presence of serum. Neither exogenous fibronectin nor laminin was able to stimulate attachment or spreading of lens cells to the capsule even when the cells had been treated with cycloheximide. Since rapid adhesion and spreading takes place in this lens cell-lens capsule system without requirement of exogenous macromolecules, it provides a favorable model for investigating the determinants in epithelial cell-basement membrane interactions.

Animals↗

Versatile unit for filling gelatin capsules with drugs or chemicals.

A new, inexpensive device was developed for making individually prepared capsules that can be administered to experimental animals. The device was designed for accurate and rapid production of large numbers of various capsule sizes and drug dosages. During 12 months of usage, 21 capsules were prepared weekly for each of 44 dogs (924 total capsules) in approximately 2.5 work-hours/week. Each capsule contained a precise amount of drug to administer a specific dosage to each individual dog. No difficulties were encountered in the manufacture or utilization of this device, and it can be operated by untrained personnel.

Animals↗

Bioavailability and pharmacokinetics of a new, slow-release potassium chloride capsule.

The bioavailability of a new, slow-release potassium chloride product consisting of coated beads in a hard gelatin capsule was compared with the bioavailability of two marketed products, an elixir and a slow-release tablet, by determining the urinary excretion of potassium. Twelve healthy male volunteers were dosed with a total of 80 mEq of potassium, in a single dose for the capsule and tablet and in three 26.6-mEq doses at 6-hr intervals for the elixir. Mean recoveries in 24-hr urine potassium levels from all three dosage forms after subtracting normal urine potassium excretion levels were 50.8% from the capsule, 53.9% from the elixir, and 63.1% from the tablet. Maximum excretion rates were reached at 2.0 hr for the elixir, 6.8 hr for the capsule, and 4.0 hr for the tablet. Fewer side effects were reported with the capsule than with the elixir and tablet.

Adult↗

Design of a slow-release capsule using laser drilling.

Conventional hard gelatin capsules were made GI-tract resistant by formalin vapor treatment. The residual formalin content was 80 micrograms/capsule 24 h after treatment, which decreased with increased storage time. An in vitro GI-tract resistance test was performed by exposing the capsules to simulated gastric fluid for 4 h and then to simulated intestinal fluid for 4 h at 37 degrees C. The resistance was further confirmed by in vivo X-ray studies in human volunteers. Minute pores were drilled on the hardened shells of the capsules with a carbon dioxide gas laser. This permitted the slow passage of the encapsulated tetracycline hydrochloride when subjected to 0.1 M HCl in in vitro dissolution studies. In vitro drug release from these capsules followed zero-order kinetics after an initial lag period of 30 min. The factors influencing the in vitro release rate of tetracycline hydrochloride from these capsules are discussed.

Capsules↗

Water migration from soft gelatin capsule shell to fill material and its effect on drug solubility.

The bioavailability of some poorly water-soluble drugs was reported to increase due to a change in dosage form from a tablet to a solution encapsulated in soft gelatin capsules. However, the objective of increasing the bioavailability may be defeated if the drug crystallizes from a solution inside the capsule. In this study, a water-insoluble drug [alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; REV 5901] was solubilized in both polyethylene glycol 400 (PEG 400) and a 6:1 mixture of Gelucire 44/14:PEG 400. The solutions were then encapsulated in soft elastic gelatin capsules with a fill weight of 700 mg (drug, 125 mg), and water migration from the capsule shell into the fill material and its effect on the solubility of the drug were investigated. Gelucire 44/14 is a mixture of hydrogenated fatty acid esters with a mp of 44 degrees C; PEG 400 was added to reduce the mp of solution to approximately 36 degrees C for easier encapsulation. After equilibration of capsules at ambient condition, the amount of water in the PEG 400 solution was 6.3%. This reduced the solubility of the drug by 45%, resulting in drug crystallization. The solubility decreased exponentially with the increase in water content. The water in the encapsulated Gelucire:PEG solution was only 1.1%, which did not affect the solubility significantly.

Capsules↗

What happens to tablets and capsules in the stomach: endoscopic comparison of disintegration and dispersion characteristics of two microencapsulated potassium formulations.

Previously we investigated gastric emptying and distribution of a capsule formulation of microencapsulated KCl and found the drug was usually present in clumps of KCl crystals held in place by gastric mucus. We therefore investigated whether a tablet formulation of microencapsulated KCl would have improved dispersion. We characterized the intragastric disintegration of capsules and tablets of microencapsulated KCl in 12 subjects. The capsule formulation floated in the gastric pool; one end would adhere to the gastric mucosa and the motion of the tethered capsule would pull the end of the capsule off. The KCl crystals would then be deposited in a mass. In contrast, the tablet formulation sank to the anatomically most dependent portion of the stomach. The tablet rapidly became soft and fragile but, if allowed to remain in one place and minimally disturbed, required a median of 12 min to lose its shape. If allowed to reach the gastric antrum, the tablet was quickly ground by the antro-pyloric pump and widely dispersed. Once liberated in the stomach, the microencapsulated KCl crystals were bound into a more-or-less cohesive mass. The differences between KCl formulations, once the crystals were released, was minimal although the larger crystals from the tablet formulation appeared less adherent and cohesive; they dispersed more in a reticulated pattern when the stomach was distended. We conclude that formulation of a drug in a microencapsulated multiple-unit dosage form does not guarantee wide dispersion nor absence of high local concentration of drug.

Adult↗

Evaluation of the bioequivalence of tablet and capsule formulations of granisetron in patients undergoing cytotoxic chemotherapy for malignant disease.

Granisetron is a novel, highly specific 5-hydroxytryptamine receptor antagonist given prophylactically to patients undergoing chemotherapy. An open, randomized, crossover trial was performed with 37 patients (24 females and 13 males) undergoing cytotoxic chemotherapy for malignant disease to compare an oral tablet (1-mg tablet given twice daily) with a clinical-trial capsule (1-mg capsule given twice daily). Complete pharmacokinetic data were determined for 24 patients (14 females and 10 males). The concentration of granisetron in plasma was measured by HPLC; the limit of quantitation was 0.2 ng/mL. The bioavailability evaluation was based mainly on the area under the curve (AUC) (mean values: 52.1 ng.h/mL for the capsule and 54.2 ng.h/mL for the tablet) and the maximum concentration (Cmax) (mean values: 7.42 ng/mL for the capsule and 8.18 ng/mL for the tablet) measured at the steady state after 7 days of continuous therapy. Wide interpatient variability in plasma granisetron levels after oral administration was observed. The 90% standard confidence interval for the geometric mean ratio overlapped the critical range, 0.8-1.25. Point estimates for AUC and Cmax based on two one-sided t tests and log-transformed data showed that the upper limit of the confidence interval was not within 20% of the mean for the capsule; the corresponding power analysis values for AUC and Cmax were 0.89 and 0.81, respectively. Despite bioequivalence not being proven, any differences that exist between the two formulations are likely to be small. There was no difference in efficacy or safety between the two formulations assessed.

Adolescent↗

Use of in vitro release tests for the prediction of the in vivo behavior and the development of flucytosine controlled-release capsules.

The antifungal substance flucytosine (5-fluorocytosine) was chosen as a model drug for studying the development of a controlled-release capsule dosage form based mainly on in vitro drug release tests. A solution and various capsule formulations of flucytosine were orally administered to beagle dogs, and the resulting plasma concentration-time profiles were determined. Special attention was directed to multiple-unit hard-gelatin capsules that exhibited a controlled-release effect in vitro, but not in vivo. The respective plasma profile was treated by the technique of numerical deconvolution to obtain the corresponding in vivo release profile (i.e., the drug release from the dosage form in the gastrointestinal tract of the dog). The influence of different experimental conditions of the USP paddle method on the release profile was investigated. By adding surfactant to the dissolution medium and omission of the sinker device, which is used to prevent the capsule from floating, the in vitro release rate markedly increased and correlated well with the in vivo release. Based on this adjusted in vitro test, the formulation was modified to achieve a more pronounced controlled-release effect. The plasma profile resulting from the reformulated multiple-unit capsules was in good agreement with the predictions made by numerical convolution of the in vitro release profile.

Administration, Oral↗