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Effect of left atrial size on the oesophageal transit of capsules.

The oesophageal transit time of barium sulphate capsules was measured using X ray fluoroscopy in 20 patients with mitral valve disease and 12 control patients in the erect and supine positions when swallowed with both 15 ml and 60 ml of water. An erect barium swallow was performed, and from a lateral radiograph the area of indentation of the oesophagus caused by the cardiac impression was measured. Left atrial diameter was derived from M mode echocardiography. In 19 patients with mitral valve disease one or more capsules remained in the oesophagus for five minutes and disintegrated there, whereas this occurred in only six control patients. Capsule transit time was significantly slower in the study patients than in the control patients in the supine position with 15 ml water. There was a significant correlation between the area of indentation and mean capsule transit time and supine 15 ml transit time. The area of indentation closely correlated with the left atrial diameter. When capsules were delayed in the oesophagus, this occurred mainly at the level of the left atrial impression in the study patients and at the lower oesophageal sphincter in the control patients. Patients with mitral valve disease are more likely than control patients to have delayed oesophageal transit of capsules because of the anatomical deformity caused by enlargement of the left atrium.

Adult↗

Nitrate induced coronary vasodilatation: differential effects of sublingual application by capsule or spray.

BACKGROUND: Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. OBJECTIVE: To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography. DESIGN: 96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puffs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation. RESULTS: There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, + 17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, + 13%, p < 0.001; group 4, 0.47 mm, + 13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, + 5%, p = 0.3). CONCLUSIONS: Sublingual ISDN spray may be more efficacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures.

Acute Disease↗

Capsules of Escherichia coli, expression and biological significance.

Escherichia coli may cause intestinal or extraintestinal infections. Generally, extraintestinal E. coli are encapsulated. The capsules are important virulence determinants, which enable the pathogenic bacteria to evade or counteract the unspecific host defense during the early (preimmune) phase of infection. They interfere with the action of complement and phagocytes. This effect is generally transient and overcome by capsule-specific antibodies in the immune phase of the host defense. In some cases, capsules are not or only poorly immunogenic, as a result of structural relationship or identity with host material. Strains with such capsules (e.g., K1 or K5) are very virulent. Bacterial capsules consist of acidic polysaccharides, which are made up from oligosaccharide repeating units. The capsules of E. coli are divided into two groups, which differ in chemistry, biochemistry, and genetic organization. All capsular polysaccharides are chromosomally determined: those of group I close to his and those of group II close to serA. The biosynthesis and surface expression have been extensively studied with representatives of group II capsular polysaccharides. It could be shown that their biosynthesis is directed from a gene block that determines the synthesis of the polysaccharide, its translocation across the cytoplasmic membrane, as well as its surface expression in a coordinate process. The chemical nature of group II capsular polysaccharides, as well as the mechanism(s) of their biosynthesis and expression, is presented.

Animals↗

Crohn disease of the small bowel: preliminary comparison among CT enterography, capsule endoscopy, small-bowel follow-through, and ileoscopy.

PURPOSE: To prospectively compare four diagnostic small-bowel imaging techniques for depiction of abnormal findings in the same patients known to have or suspected of having Crohn disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Patients known to have or suspected of having nonobstructive Crohn disease were recruited. Each patient underwent capsule endoscopy, computed tomographic (CT) enterography, colonoscopy with ileoscopy, and small-bowel follow-through (SBFT). Findings consistent with Crohn disease were tabulated for each imaging examination (diagnostic yield). The proportions of patients with positive findings at each examination were compared, and any significant differences between the tests were calculated by using the exact McNemar test. RESULTS: Seventeen patients (nine women, eight men; mean age, 49 years; range, 18-78 years) completed the study out of 20 patients enrolled. Crohn disease was depicted by capsule endoscopy in 12 patients (71%), ileoscopy in 11 (65%), CT enterography in nine (53%), and SBFT in four (24%). Ileoscopy was incomplete in four patients, and capsule endoscopy was incomplete in two patients. Capsule endoscopy had the highest diagnostic yield for Crohn disease, and SBFT had the lowest, but these differences were not statistically significant (P = .02). SBFT failed to depict a stricture in one patient, which resulted in surgical removal of the capsule. CT enterography and SBFT depicted extraintestinal findings (eg, mesenteric adenopathy in two patients, perianal and enterocolic fistulas in one patient) not detected endoscopically. CONCLUSION: This preliminary study demonstrates capsule endoscopy and CT enterography may depict nonobstructive Crohn disease when techniques such as ileoscopy and SBFT have negative or inconclusive findings.

Adolescent↗

Anterior joint capsule of the normal hip and in children with transient synovitis: US study with anatomic and histologic correlation.

PURPOSE: To study the anatomic components of the anterior joint capsule of the normal hip and in children with transient synovitis. MATERIALS AND METHODS: Six cadaveric specimens were imaged with ultrasonography (US) with special attention to the anterior joint capsule. Subsequently, two specimens were analyzed histologically. These anatomic findings were correlated with the US findings in 58 healthy children and 105 children with unilateral transient synovitis. RESULTS: The anterior joint capsule comprises an anterior and posterior layer, mainly composed of fibrous tissue, lined by only a minute synovial membrane. Both fibrous layers were identified separately at US in 98 of 116 (84%) hips of healthy subjects and in all hips with transient synovitis. Overall, the anterior layer was thicker than the posterior layer. In transient synovitis compared with normal hips, no significant thickening of both layers was present (P = .24 and .57 for the anterior and posterior layers, respectively). Normal variants include plicae, local thickening of the capsule, and pseudodiverticula. CONCLUSION: Increased thickness of the anterior joint capsule in transient synovitis is caused entirely by effusion. There is no US evidence for additional capsule swelling or synovial hypertrophy.

Adult↗

Histologic evaluation of the shoulder capsule in normal shoulders, unstable shoulders, and after failed thermal capsulorrhaphy.

BACKGROUND: Attenuation of the shoulder capsule has been noted during revision surgery for failed thermal capsulorrhaphy. HYPOTHESIS: The attenuated capsule seen in patients who have undergone failed thermal capsulorrhaphy will show histologic characteristics distinguishing it from the capsule of normal shoulders and dislocating shoulders. STUDY DESIGN: Case control study. METHODS: The shoulder capsules were studied in 12 patients with traumatic anterior instability and in 7 patients who experienced recurrent instability after a thermal capsulorrhaphy. The capsules of six fresh-frozen cadavers with no shoulder lesions were used as controls. RESULTS: Among patients who had a history of traumatic instability, a denuded synovial layer was present in 58%, subsynovial edema in 58%, increased cellularity in 25%, and increased vascularity in 83%. At the time of surgery, five of seven shoulders in the failed thermal capsulorrhaphy group (71%) were subjectively felt to be thin and attenuated. Denuded synovium was found in 100% of these patients, subsynovial edema in 43%, and changes in the collagen layer in 100%. Changes in the collagen layer in these patients included a "hyalinization" appearance in five cases (71%), increased collagen fibrosis in two cases (29%), and increased cellularity in two cases (29%). CONCLUSIONS: There was no one characteristic observable on histologic evaluation that would explain the attenuation of the capsule in cases of failed thermal treatment. Morphologic collagen structure can be histologically abnormal for up to 16 months after thermal capsulorrhaphy.

Adolescent↗

Analysis of collagen and elastic fibers in shoulder capsule in patients with shoulder instability.

This study examined collagen cross-links, collagen fibril diameter and density, amino acid composition, and elastic fibers in shoulder capsule and skin in four patient groups: 1) unidirectional anterior instability (N = 8); 2) multidirectional instability/primary surgery (N = 6); 3) multidirectional instability/revision surgery (N = 6); and 4) no history of instability (N = 5). Compared with normal capsule, capsule from groups 1 and 2 had more stable and reducible collagen cross-links, significantly greater mean collagen fibril diameter, more cysteine, and a higher density of elastin staining. Compared with shoulder capsule in groups 1 and 2, shoulder capsule from group 3 contained significantly more reducible cross-links, smaller-diameter collagen fibrils, decreased collagen fibril density, and an increased density of elastin staining. There were no significant differences in any parameters between groups 1 and 2. We hypothesized that repeated capsular deformation in patients with shoulder instability results in changes in the capsule that increase its strength and resistance to stretching. Skin analyses demonstrated a significantly smaller mean collagen fibril diameter in skin from group 2 compared with group 1, suggesting the possibility of an underlying connective tissue abnormality.

Adolescent↗

In vitro release characteristics of hard shell capsule products coated with aqueous- and organic-based enteric polymers.

In this article, an overview of the rationale for the use of enteric coated (EC) dosage forms is presented. The benefits and disadvantages inherent in the use of aqueous dispersions and organic solutions of the various polymers to generate these products are discussed. The comparative dissolution stability of a hard shell capsule product coated with enteric polymers applied as either aqueous dispersions, or as organic solutions, were assessed under accelerated conditions of storage. Polymethacrylic acid methacrylate copolymer, cellulose acetate phthalate (CAP) and polyvinyl acetate phthalate (PVAP), along with the corresponding commercially available aqueous dispersions, Eudragit L30D, Aquateric, and Coateric, were employed in these studies as enteric polymers. Diethyl phthalate (DEP) was used as the plasticizer and procainamide HCl 250 mg capsules served as the substrate. Storage of the coated capsules at 37 degrees C/80% RH and at 45 degrees C for 2 months revealed that, while the stability of Eudragit L30D coatings are comparable or superior to the corresponding organic-based coatings, Coateric films are markedly unstable when compared with PVAP coatings applied through the use of organic vehicles. After storage at 37 degrees C/80% RH, Aquateric-based capsules demonstrated stability comparable to CAP organic-based coatings only when a protective seal coat was present. The performance failures of the capsules that occur upon storage primarily result in a loss of gastric resistance. Scanning Electron Microscopy (SEM) and thermomechanical analysis (TMA) of the different coatings revealed differences in the film-forming properties of the polymer films and provide an explanation for the changes that occur during storage of the coated capsules.

Capsules↗

Transplantation of xenogeneic cells secreting beta-endorphin for pain treatment: analysis of the ability of components of complement to penetrate through polymer capsules.

The permeation of component of complement and secreted peptides through polymer capsules (PM30, K6305, and K5708) were examined. To analyze permeability by complement, the degree of hemolysis of sensitized sheep erythrocytes (EA) (1 x 10(9)/ml) enclosed in each type of capsule was examined after 24-h incubation in culture medium containing 10% human serum. PM30 and K6305 prevented the permeation of complement well, while K5708 did not. EA suspended in alginate prevented hemolysis even in K5708. Peptide permeation through the capsules was assessed by measuring the concentration of ACTH secreted by proopiomelanocortin (POMC)-gene-transfected-Neuro2A in the culture medium on days 4, 7, 14, 21, and 28 after encapsulation. The ACTH levels in the culture medium remained high until day 28. Alginate appeared to prevent the secretion, because ACTH levels decreased in alginate-suspended cells after day 14. The PM30-K6306 double capsules containing cell lines, Neuro2A, BHK21 (hamster fibroblasts), L929 (mouse fibroblasts), and HF-SKFII (human fibroblasts) were transplanted into the cerebrospinal fluid (CSF) space of the monkeys in the lumber region. The morphological examination showed the partial survival of Neuro2A, and BHK21 and HF-SKFII, which were cells concordant with the monkeys. On the other hand, L929 cells, which were discordant with the monkeys, could not survive at all. Because these results suggest that the complement components penetrate the polymer capsules, concordant cells are preferable for xenografting with polymer capsules into the CSF space.

Adrenocorticotropic Hormone↗

Factors influencing the transit of a gelatin capsule in the esophagus.

The tendency of a gelatin capsule to lodge in the esophagus, dissolve, and release its contents, as a potential etiology of drug-induced esophageal injury, was studied in 18 asymptomatic volunteers. Their ages ranged from 21 to 81 years, with nine subjects over 70 years old. Esophageal transit time of liquids was measured in all subjects after which the esophageal transit time of a #00 gelatin capsule containing technetium (99mTc) sulfur colloid was measured with a 120 ml and a 15 ml water bolus. The capsule lodged in three subjects (17 percent) with the 120 ml bolus and in 11 subjects (61 percent) with the 15 ml bolus. Esophageal manometry demonstrated a lower mean amplitude of esophageal contractions in subjects in whom the capsule lodged with the 120 ml bolus and in the elderly subjects. We conclude that the esophageal transit time of a gelatin capsule is related to the volume of fluid chaser. Our findings that a lower amplitude of esophageal contractions was associated with elderly patients and those in whom the capsule lodged with the large fluid bolus are worthy of further investigation.

Adult↗

Bioavailability and diuretic effect of furosemide following administration of tablets and retarded capsules to human subjects.

Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

Absorption↗

Bioavailability of cyclandelate from capsules in beagle dogs and dissolution rate: correlations with bioavailability in humans.

The bioavailability in beagle dogs and the dissolution rates of cyclandelate from five capsule preparations commercially available in Japan were measured. One of the capsules that showed an extremely low bioavailability in humans also showed the lowest bioavailability in beagle dogs, although the difference in bioavailability with the highest preparation was smaller than in humans. A significant correlation was obtained between the results of the studies in humans and beagles. However, the power of the test using beagles was extremely low in comparison with that in the human study. Food enhanced the bioavailability of cyclandelate from the capsules having the highest and lowest bioavailability in the fasted state in beagles as observed in the human study previously. The bioinequivalence of the cyclandelate capsules detected in the fasted state disappeared in the fed state in the beagle dog study, while the bioinequivalence still remained in the non-fasted state in human subjects. Thus bioequivalence testing in the fed state led to different results in both species. The most poorly bioavailable capsule in both species in the fasted state showed a slow dissolution rate by several dissolution methods with moderate stirring. In order to obtain a good correlation with in vivo bioavailability, a large volume of test solution and addition of Tween 80 were required. Extensive growth of whiskers (needle-like crystals) was observed in the entire capsule mass having the lowest bioavailability.

Animals↗

Stability of esomeprazole capsule contents after in vitro suspension in common soft foods and beverages.

STUDY OBJECTIVE: To determine the in vitro stability of esomeprazole pellets from an opened capsule after suspension in various common soft foods and beverages. DESIGN: In vitro study. SETTING: Pharmaceutical company research laboratory. MEASUREMENTS AND MAIN RESULTS: Pellets from opened esomeprazole 20-mg capsules were suspended in 100 ml of tap water, milk (1.5% fat), orange juice, apple juice, yogurt, or cultured milk for 30 minutes, then added to 500 ml of hydrochloric acid to simulate gastric acid exposure. After a 2-hour incubation, the mixture was filtered through a sieve, and the collected pellets were dissolved in an alkaline solution. Esomeprazole concentrations were measured using reverse-phase liquid chromatography The stability of the esomeprazole pellets exceeded 98% in all beverages and soft foods except milk. CONCLUSION: Administration of the pellets from an opened esomeprazole capsule shortly after suspending them in tap water, yogurt, cultured milk, orange juice, or apple juice may be a practical alternative for patients who cannot swallow an intact capsule. Bioavailability studies comparing esomeprazole administered as an intact capsule to that of the pellets from an opened capsule suspended in these beverages or soft foods are recommended to confirm these findings.

Animals↗

Evaluation of esophageal transit of tablets and capsules in 30 cats.

We have reported tablet-induced focal esophagitis and esophageal stricture formation in cats. The proposed mechanism is thought to be abnormal esophageal tablet retention resulting in focal esophagitis with subsequent stricture formation. The objective of this study was to evaluate the passage of tablets and capsules when given alone (dry swallow) and when followed by a water bolus (wet swallow) to determine if this could, in part, explain the esophageal stricture formation we have observed in cats. Fluoroscopy was used to evaluate tablet or capsule passage after administration. The percentage of dry tablet swallows that successfully passed into the stomach was 0.0% at 30 and 60 seconds, 6.7% at 90 seconds, 13.3% at 120 seconds, 26.7% at 180 and 240 seconds, and 36.7% at 300 seconds. Wet tablet swallows successfully passed 90.0% of the time at 30 seconds, 93.3% of the time at 60 seconds, and 100.0% of the time thereafter. The percentage of dry capsule swallows that successfully passed was 16.7% at each time interval. Wet capsule swallows successfully passed 96.7% of the time at 30 seconds and 100% of the time thereafter. For each time interval, wet swallows achieved significantly greater percentage passage into the stomach when compared to dry swallows (P < .05). This study shows that tablets or capsules given by dry swallow have prolonged retention in the esophagus compared to those given by wet swallow. On the basis of this study, we recommend the routine administration of a water bolus to cats receiving tablets or capsules PO to facilitate esophageal clearance. This practice may help prevent medication-associated esophagitis or stricture formation.

Administration, Oral↗

Esophageal transit of capsules in clinically normal cats.

OBJECTIVE: To evaluate the esophageal passage of capsules in clinically normal cats and determine the incidence of prolonged transit or entrapment. ANIMALS: 12 clinically normal adult cats. PROCEDURE: Esophageal transit of barium sulfate-filled capsules was evaluated fluoroscopically. Each cat was examined 3 times (36 examinations). Esophageal transit times were classified as normal (< or = 30 seconds) or prolonged (> 30 but < or = 240 seconds). Capsules were considered entrapped when transit times were > 240 seconds. RESULTS: Transit times were normal in 10 of the 36 (27.8%) examinations, whereas times were prolonged in 7 (19.4%) examinations. Capsules became entrapped in the midcervical region of the esophagus during 19 (52.8%) examinations. Following termination of each examination, cats with entrapped capsules were fed a small amount (0.5 to 1 ounce) of food; this resulted in passage of the capsule to the stomach. CONCLUSIONS AND CLINICAL RELEVANCE: The possibility of medication-induced esophagitis should be considered when orally administering ulcerogenic drugs to cats. It is recommended that a small volume of food be given following medications to ensure complete esophageal clearance.

Administration, Oral↗

The roles of laminin and fibronectin in the development of the lens capsule.

This study examines the distribution of laminin and fibronectin in the rat lens capsule during development. Both these extracellular matrix glycoproteins are localised in the interspace between presumptive lens and presumptive retina as well as in their basal laminae. The lens capsule arises from multilayering of the basal lamina of the lens cells. Immunofluorescence localises both laminin and fibronectin in the capsule at 16 days of embryonic development, although reactivity for fibronectin is much weaker than for laminin. In the 19 day embryo only laminin is detected. This indicates that during embryonic development fibronectin becomes a minor component of lens cell ECM and is not accumulated in the developing capsule. The roles of laminin and fibronectin in promoting cell migration during development were analysed in explant cultures. Lens epithelial explants from 16, 17 and 19 day old embryos and neonatal rats were grown on a laminin or fibronectin substratum. Lens cells from all ages of rats migrated on the laminin substratum, whereas lens cells progressively lost the ability to migrate on a fibronectin substratum as the age of the donor increased. This developmental loss of ability to migrate on fibronectin in vitro coincides with the developmental loss of fibronectin from the lens capsule in vivo. Therefore, we propose that whilst both laminin and fibronectin may be important for promoting migration of lens cells on their substratum at early stages of lens morphogenesis, during development laminin takes over as the key molecule that promotes migration on the capsule.

Animals↗

Anterior lens capsule abnormalities in Alport syndrome.

Alport syndrome is a hereditary, progressive disease characterized by progressive nephritis, sensorineural deafness, and ocular abnormalities, including anterior lenticonus. The ultrastructure of the lens capsule abnormalities in Alport syndrome is reported. Four anterior lens capsules from 31-year-old patient and 26-year-old patient with lenticonus who were affected by the Alport syndrome were obtained at capsulectomy. And all four anterior lens capsules were examined by transmission electron microscopy. The histopathologic findings showed that the thickness of the anterior lens capsules was decreased (4-13 microm) and that there were many vascular dehiscences localized at the inner part of the lens capsule. There were large numbers of capsular dehiscences containing fibrillar materials and vacuoles. The anterior capsules were clearly fragile in this disease, forming the basis for the progressive lenticonus and anterior polar cataract.

Adult↗

Protective effect of Radix Acanthopanacis Senticosi capsule on colon of rat depression model.

AIM: To investigate the abnormity of rat colon caused by depression and the ameliorative effects of Radix Acanthopanacis Senticosi (RAS) capsule on colon and their mechanisms in rat depression model. METHODS: Chronic stress-induced model of depression of Wistar rats was produced. The experimental animals were randomly divided into model control, 5-aminosalicylic acid (5-ASA) therapy group and three RAS capsule therapy groups. These five groups were intracolonically treated daily (8:00 a.m.) for 2 wk with normal saline, 5-ASA (100 mg/kg) and RAS capsule at the doses of 300, 600 and 900 mg/kg, respectively. A normal control group of rats was also included in the study. Colonic activities of nitric oxide (NO) and superoxide dismutase (SOD), levels of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) were determined by ultraviolet spectrophotometry. The expression of cyclooxygenase-2 (COX-2) in colonic tissue was detected by immunohistochemistry. RESULTS: Enhanced colon inflammatory response and oxidative stress were observed in the chronic stress-induced rat depression model, which manifested as the significant increase of MDA, iNOS and NO levels, as well as the expressions of COX-2 in the colon tissue, but the colonic SOD activity was significantly decreased compared with the normal control (MDA: 10.34+/-2.77 vs 2.55+/-0.70; iNOS: 1.11+/-0.44 vs 0.25+/-0.16; COX-2: 53.26+/-8.16 vs 4.87+/-1.65; NO: 11.28+/-5.66 vs 4.76+/-1.55; SOD: 53.39+/-11.15 vs 84.45+/-22.31; P < 0.01). However, these parameters were significantly ameliorated in rats treated locally with RAS capsule at the doses of 300, 600 and 900 mg/kg (iNOS: 0.65+/-0.31, 0.58+/-0.22 and 0.64+/-0.33; NO: 5.99+/-2.73, 6.87+/-1.96 and 6.50+/-1.58; MDA: 2.92+/-0.75, 3.19+/-1.08 and 3.26+/-1.24; SOD: 70.81+/-12.36, 73.30+/-15.30 and 69.09+/-11.03, respectively). The expressions of COX-2 in the colon were significantly ameliorated (28.83+/-9.48 and 27.04+/-9.56, respectively) when RAS capsule was administered at the doses of 600 and 900 mg/kg. CONCLUSION: Administration of RAS capsule intracolonically may have significant therapeutic effects on the colon of rat depression model, which are probably due to its antioxidative action and inhibition of arachidonic acid metabolism.

Animals↗