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At least 235 records · Page 13Linked to original sources

PubMed2001

Ultrastructural anatomy of contracted capsules around textured implants in augmented breasts.

The development of a capsule around an implant is part of the physiological response to a foreign body. Capsular contracture is the most specific and frustrating complication of augmentation mammaplasty, and a lot of studies have been devoted to it. The aim of the current study is to examine the fine architecture of the contracted capsule around textured implants in humans. Eight capsules from augmented and contracted breasts with gel-filled, textured-surface silicone implants were studied after standard preparation for light and scanning electron microscopy, and after partial digestion in sodium hydroxide. Two capsules from contracted breasts around smooth implants and two noncontracted capsules around textured implants were prepared and studied in the same fashion as controls. A multilayer structure of the contracted capsule was seen, and the architecture of the various layers is described. The inner surface presents irregular craterlike depressions. The arrangement of collagen fibers varies in capsule layers. The effect of a textured-surface implant on the mechanism of capsule contraction based on the observed capsular architecture is that only part of the capsule is effective mechanically in producing a contracting force. A thin vascular layer was identified near the inner surface in contracted capsules around textured implants, and the authors' think that this layer is probably the key structure in the histological development and growth of the capsule.

Adult↗

PubMed2003

Induction of capsule growth in Cryptococcus neoformans by mammalian serum and CO(2).

The pathogenic fungus Cryptococcus neoformans has a polysaccharide capsule that is essential for virulence in vivo. Capsule size is known to increase during animal infection, and this phenomenon was recently associated with virulence. Although various conditions have been implicated in promoting capsule growth, including CO(2) concentration, osmolarity, and phenotypic switching, it is difficult to reproduce the capsule enlargement effect in the laboratory. In this study, we report that serum can induce capsule growth, and we describe the conditions that induce this effect, not only by serum but also by CO(2). Capsule enlargement was dependent on the medium used, and this determined whether the strain responded to serum or CO(2) efficiently. Serum was most effective in inducing capsule growth under nutrient-limited conditions. There was considerable variability between strains in their response to either serum or CO(2), with some strains requiring both stimuli. Sera from several animal sources were each highly efficient in inducing capsule growth. The cyclic AMP (cAMP) pathway and Ras1 were both necessary for serum-induced capsule growth. The lack of induction in the ras1 mutant was not complemented by exogenous cAMP, indicating that these pathways act in parallel. However, both cAMP and Ras1 were dispensable for inducing a partial capsule growth by CO(2), suggesting that multiple pathways participate in this process. The ability of serum to induce capsule growth suggests a mechanism for the capsular enlargement observed during animal infection.

Animals↗

PubMed1976

Mechanical properties of the dog renal capsule.

The renal capsule is an important determinant of whole kidney volume/pressure relationships. To gain further insights into its possible role we examined the mechanical properties of the dog renal capsule using standard materials testing procedures. From each of four locations on the kidney surface, the following mechanical properties of the renal capsule were determined: elastic modulus (force/unit of cross-sectional area theoretically required to double the length of the specimen), tensile stiffness (force/unit width theoretically required to double the length of the specimen), ultimate strength (stress at time of fracture of the specimen), and maximum strain (percent strain at time of the fracture of the specimen). We found that the elastic modulus of the renal capsule from all capsular sites was substantially greater than values previously reported for dog aorta. The stiffness of the capsule covering the anterior-posterior surface of the kidney was found to be about 50% greater than the stiffness of the capsule covering the lateral and polar surfaces of the kidney. The ultimate strength of the anterior-posterior capsule was significantly greater than that of the lateral or polar capsule. This finding may explain the clinical observation that the spontaneous rupture of the renal capsule and parenchyma associated with the acute swelling of transplant rejection is confined almost exclusively to the lateral and polar portions of the renal capsule and cortex. The mean maximum strain at each capsular site was about 35%. This degree of circumferential expansion corresponds to about a doubling of kidney volume. Thus, this observation suggests that the renal capsule is at risk to undergo spontaneous rupture when renal volume increases of this magnitude are observed.

Animals↗

PubMed2006

[Evaluation of diagnostic yield and clinical impact of capsule endoscopy in patients with obscure gastrointestinal bleeding].

BACKGROUND AND AIMS: The major indication of small bowel capsule endoscopy is the diagnostics of obscure gastrointestinal bleeding. The present retrospective study was aimed to analyze the diagnostic yield, positive and negative predictive values and clinical impact of capsule endoscopy in patients with obscure gastrointestinal bleeding. PATIENTS AND METHODS: During a 36 month period at two workplaces 66 capsule endoscopy studies were performed in 62 patients with gastrointestinal bleeding who had undergone non-diagnostic upper endoscopy and colonoscopy. Capsule video recordings were evaluated by two investigators at both workplaces. Capsule endoscopy findings were divided into 3 groups according to the bleeding source: definitive bleeding source (48 patients), uncertain bleeding potential (5 patients), and negative finding (8 patient). Patients after capsule endoscopy were followed-up until a mean of 20 (1-41) months. RESULTS: A definitive small bowel bleeding source was detected in 78.7% of the cases studied by capsule endoscopy. Definitive bleeding sources included angiodysplasia (28 cases), small bowel Crohn's disease (5 cases), small bowel tumor (5 cases), small bowel stenosis (2 cases), NSAID therapy related ulcer (1 case), non-specific inflammation (1 case) and helminthiasis (1 case) respectively. The positive and negative predictive values of capsule endoscopy studies were 95.8% and 84.6% respectively. In cases with definitive bleeding sources 72% of patients received therapy in accordance with capsule endoscopy findings (surgery in 18 patients, medical treatment modification in 16 patients, chemoembolisation in 1 patient). During the follow-up period 17.7% of the patients had rebleeding. CONCLUSIONS: Capsule endoscopy is a useful and effective diagnostic method in cases with obscure gastrointestinal bleeding. Effective therapy may be introduced in accordance with the majority of positive capsule endoscopy results.

Angiodysplasia↗

PubMed1998

Comparative assessment of hepatic Glisson's capsule and bovine pericardium in heart valve bioprostheses.

BACKGROUND AND AIM OF THE STUDY: The optimal material for heart valve bioprostheses remains disputable. This investigation was initiated to compare the properties of hepatic Glisson's capsule, clinical experience of which in cardiovascular surgery is minimal, with those of bovine pericardium. METHODS: Hepatic Glisson's capsule was harvested from bull calves and used to create composite pulmonary arterial monocusp grafts and bioprostheses. Comparison of the strength and elastic properties of Glisson's capsule and bovine pericardium, as well as the hydrodynamic characteristics of valves made from these materials, was performed. Late results of operations using these materials were estimated echocardiographically. RESULTS: Although Glisson's capsule tissue is thinner than the bovine pericardium, its elasticity modulus is greater. However, the hydrodynamic characteristics of heart valves made from either tissue are similar. Moreover, valves made from Glisson's capsule have a lower systolic pressure gradient on the prosthesis and a higher effective orifice area. Composite pulmonary arterial xenopericardial grafts with a monocusp of Glisson's capsule were used in 30 patients during tetralogy of Fallot repair. Glisson's capsule was also used for tricuspid valve reconstruction and as a bioprosthesis in six patients with Ebstein's anomaly. At 1-2 years after surgery, the Glisson's capsule tissue remained thin and flexible, with no calcification. CONCLUSIONS: Although the hydrodynamic properties of hepatic Glisson's capsule and the bovine pericardium are similar, the capsule tissue is thinner and has a greater elasticity modulos. Thus, Glisson's capsule may be used for bioprosthesis construction both independently and in combination with bovine pericardium.

Animals↗

PubMed1986

Multidimensional column-switching liquid chromatographic method for dissolution testing of enprostil soft elastic gelatin capsules.

Enprostil (methyl 7-[(1 R,2R,3R)-3-hydroxy-2-[(E)-(3R)-3-hydroxy-4- phenoxy-1-butenyl]-5-oxocyclopentyl]-4,5-heptadienoate), an E-type prostaglandin exhibiting anti-ulcer activity, is formulated as a propylene carbonate solution filled into soft elastic gelatin (SEG) capsules. Enprostil SEG capsules were maintained for timed intervals at 50 degrees C, 30 degrees C, and room temperature, and the quantity of drug released upon complete capsule dissolution was determined as a function of storage condition. The dissolution test adhered to USP XXI guidelines (paddle method) and used a multidimensional HPLC technique to provide a sensitive and selective enprostil assay. Parallel HPLC assays determined the enprostil concentration in the propylene carbonate fill that was physically expressed from initially manufactured and from aged capsules. This corrected for any enprostil loss via chemical degradation on storage. The study included six different aged samples (six replicates each), and for all six samples, the enprostil recovered from dissolved capsules averaged 104 +/- 1.4% of the enprostil physically expressed from the capsules. Similarly, the enprostil recovered from dissolved, aged capsules averaged 103 +/- 5% of the enprostil physically expressed from capsules at the initial time point. These findings exclude the possibility that interactions with the SEG capsule wall reduce drug availability during storage under normal conditions. The multidimensional HPLC technique should generally extend to analysis of other noncationic drugs formulated into soft gelatin capsules.

Capsules↗

PubMed2005

Alkaline phosphatase encapsulated in gellan-chitosan hybrid capsules.

Alkaline phosphatase (ALP) was encapsulated in gellan-chitosan polyion complex (PIC) capsules using a convenient procedure. The recovery of ALP was about 50% when the capsules were prepared by dropping a solution of ALP and gellan mixture (ALP/gellan) into a chitosan solution. When p-nitrophenyl phosphate (p-NPP) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP) were incubated with ALP/gellan-chitosan capsules as substrates for ALP, the transparent colorless capsules changed to yellow and blue, respectively. The encapsulation of ALP into the PIC capsules was also confirmed by SDS-PAGE and immunoblot analyses. The ALP and polypeptides of more than 30 kDa remained without release even after incubation at 4 degrees C for 14 d. The biochemical properties of the encapsulated ALP activity were similar to those of the intact enzyme. When the solution containing p-NPP was loaded on a column packed with ALP/gellan-chitosan capsules at 27 degrees C, approximately 75% of p-NPP was hydrolyzed by passing through the column. No significant leakage of ALP was observed during the procedure, indicating that the capsules were resistant to pressure in the chromatographic operation. Furthermore, 70% of the hydrolytic activity of the packed capsules remained after storage at 4 degrees C for one month. These results suggest that the polyion complex capsules could be useful materials for protein fixation without chemical modification. [Diagram: see text] Encapsulation of ALP into PIC capsules and the morphological changes seen in the absence of the ALP substrate and in the presence of p-NPP and BICP.

Alkaline Phosphatase↗

PubMed2006

Clinical application of wireless capsule endoscopy in pediatric patients for suspected small bowel diseases.

Capsule endoscopy (CE) has been demonstrated to be safe and well tolerated in adults with suspicion of small intestinal diseases with negative results of gastroscopy and colonoscopy. However, its value in pediatric patients has not yet been well studied. This study aimed to evaluate the results and safety of CE in pediatric patients with suspicion of small bowel disorders. There were 16 consecutive children and adolescents (12 boys, 4 girls) and 15 adults (9 men, 6 women) referred to us for suspected small bowel diseases from August 2002 to September 2005. Among the pediatrics, six patients were less than 10 years old. Technique for capsule placement, gastric transit time, small bowel transit time, excretion time of capsule endoscopy, capsule findings, and complications were recorded. All 16 pediatric patients described that the capsule was easy to swallow except for three children. Finally we delivered the capsule under gastroscopy with overtube for these three children. No capsule retention occurred during our study. Median recording time was 7 h 44 min (range 6 h 51 min-9 h 11 min). Median gastric transit time was 83.5 min (range 4-296 min). Median small bowel transit time was 270 min (range 142-484 min). Median excretion time of capsule was 33.9 h (range 12-96 h). There was no significant difference in excretion time of capsule, gastric transit time and small bowel transit time between pediatric patients and adult patients (P > 0.05). CE was positive in 12 patients, including Crohn's disease (4), hemangioma (2), angiodysplasia (2), Meckel diverticulum (1), polyp (1), aphthous ulcer in ascending colon (1), and cobblestone appearance of ileal mucosa. CE has been performed safely in a small series of pediatric patients after ingestion or endoscopic placement of the capsule. The high yield of abnormal findings was comparable to those of adult patients.

Adolescent↗

PubMed2006

Effects of food on the single-dose pharmacokinetics/pharmacodynamics of tizanidine capsules and tablets in healthy volunteers.

BACKGROUND: A multiparticulate capsule formulation of the alpha2-adrenergic agonist tizanidine has been developed to decrease C(max), AUC, and associated somnolence, while maintaining efficacy. OBJECTIVE: The purpose of this study was to compare the pharmacokinetics and impact of somnolence on cognitive function after single doses of the tablet and capsule formulations of tizanidine under fed and fasted conditions in healthy volunteers. METHODS: This Phase I, single-dose, randomized, open-label, 4-way crossover study was conducted at MDS Pharma Services, Belfast, United Kingdom. Healthy male and female adult subjects received tizanidine (8 mg) as tablets and capsules under fasting and nonfasting conditions. Blood samples were collected to determine plasma tizanidine pharmacokinetic profiles, and computerized cognitive function tests were performed that yielded a validated composite score, Power of Attention, an index of sedation. RESULTS: Ninety-six patients were enrolled in the study (54 men, 42 women; mean [SD] age, 27 [8] years [range, 18-52 years]; mean [SD] body weight, 71.7 [12.4] kg [range, 46-102 kg]). Tizanidine tablets and capsules were found to be bioequivalent after fasting. In the fed state, mean C(max) and AUC(0-t) were substantially decreased, by 33.8% and 15.4%, comparing the capsules and tablets, respectively. The median T(max) increased significantly from 1.41 to 3.0 hours (P < 0.001). Administration of the capsules with food resulted in <20% difference in mean C(max) and AUC(0-t) compared with the fasting state, whereas mean C(max) and AUC(0-t) were 22.6% and 45.2% higher when the tablet formulation was administered with food. The onset of impairment in Power of Attention was significantly delayed from 0.75 to 1.5 hours postdose when capsules were administered with food compared with the other conditions (P < 0.001). The most commonly reported adverse events were asthenia, somnolence, and orthostatic hypotension. A significantly lower adverse event rate was observed in the combined capsules group compared with the tablets, suggesting that differences in tolerability may exist. CONCLUSIONS: The results of this study in healthy volunteers suggest that the capsule and tablet formulations of tizanidine were bioequivalent only in the fasted state. The capsule formulation exhibited a food effect that reduced C(max) and AUC(0-t), and significantly increased T(max), which was associated with a delay in cognitive impairment. The large interpatient variability in plasma profiles most likely dampened the ability to fully elucidate the differences between the 2 formulations.

Adolescent↗

PubMed2003

Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles.

The objective of this study was to develop and evaluate a rupturable pulsatile drug delivery system based on soft gelatin capsules with or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug after a lag time (rupturing of the external polymer coating). The swelling of the gelatin capsule itself was insufficient to rupture the external polymer coating, an additional swelling layer was applied between the capsule and the polymer coating. Croscarmellose sodium (Ac-Di-Sol) was more effective as a swelling agent than low and high molecular weight hydroxypropylmethyl cellulose (HPMC; E5 or K100M). Brittle polymers, such as ethyl cellulose (EC) and cellulose acetate propionate (CAPr), led to a better rupturing and therefore more complete drug release than the flexible polymer coating, Eudragit RS. The lag time of the release system increased with higher polymer coating levels and decreased with the addition of a hydrophilic pore-former, HPMC E5 and also with an increasing amount of the intermediate swelling layer. The water uptake of the capsules was linear until rupture and was higher with CAPr than with EC. Soft gelatin capsule-based systems showed shorter lag times compared to hard gelatin capsules because of the higher hardness/filling state of the soft gelatin capsules. The swelling pressure was therefore more directed to the external polymer coating with the soft gelatin capsules. Typical pulsatile drug release profiles were obtained at lower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAPr-coated capsules resulted in a more complete release than EC-coated capsules.

Capsules↗

PubMed2004

Water-mediated lysis of lens epithelial cells attached to lens capsule.

PURPOSE: To investigate the effect of distilled deionized water (DDW) on lens epithelial cells (LECs) attached to the lens capsule. SETTING: Wound Healing Research Laboratory, Center for Vision Research, Westmead Hospital, Sydney, NSW, Australia. METHODS: Anterior capsulotomy specimens taken during routine cataract surgery were divided in half. One half was immersed in DDW and the other half in culture medium (control) for 1 to 5 minutes and photographed at intervals by phase-contrast microscopy. In further experiments, the capsules were exposed to DDW for 1 or 2 minutes and placed in culture for 1 week to determine whether LECs survive treatment and are capable of repopulating the lens capsule. RESULTS: Distilled-deionized water induced marked swelling of the cytoplasm within 60 seconds of treatment. At 120 seconds, there was disruption of the plasma membranes, with few intact cells remaining. In the control capsules, confluent monolayers of LECs covered the entire capsule surface with a halo of LECs growing on the surrounding plastic well. Viable LECs were observed in 1 of 3 capsules treated for 1 minute with DDW. These did not reach confluence or grow off the capsule onto the surrounding well. No viable LECs were seen on capsules exposed to DDW for 2 minutes. CONCLUSIONS: Short exposure of LECs to DDW induced extensive and rapid cell lysis. Distilled-deonized water may be a useful agent for instillation in the capsular bag during sealed-capsule irrigation to prevent posterior capsule opacification.

Cataract Extraction↗

PubMed2004

Incidence of and risk factors for residual posterior capsule opacification after cataract surgery.

PURPOSE: To evaluate the incidence of and determine the risk factors for residual posterior capsule opacification (PCO). SETTING: University of New Mexico Health Sciences Center and the Veterans Administration Medical Center, Albuquerque, New Mexico, USA. METHODS: This study evaluated 194 uneventful cataract surgeries. Immature cataracts were graded for nuclear sclerosis (NS), posterior subcapsular cataract (PSC), and anterior cortical spokes on a 1 to 4 scale. Preoperative Snellen best corrected visual acuity was converted to the logMAR scale. The posterior capsule was examined after polishing and was classified as clear or as having residual opacity. Those with residual capsule opacity were evaluated 6 weeks postoperatively for the presence of visually significant PCO. RESULTS: The incidence of residual capsule opacity was 23% (44 eyes). Seven (54%) of 13 eyes with white mature cataract had residual capsule opacity. In contrast, 37 (20%) of 181 eyes with immature cataract had residual capsule opacity (P = .01). In eyes with immature cataract, the mean preoperative logMAR acuity was +1.14 +/- 0.60 (SD) in the residual capsule opacity group and +0.73 +/- 0.46 in the clear group (P<.001). In eyes with immature cataract, the adjusted odds ratio for each increasing grade of NS was 2.3 and of PSC, 1.8 (P = .002 and P<.001, respectively). Eleven percent (5 eyes) of residual capsule opacities resulted in visually significant PCO 6 weeks postoperatively. All 5 opacities were centrally located at surgery. CONCLUSIONS: Results indicate that aggressive polishing of peripheral or adherent residual capsule opacities is not advisable as only 5 eyes with central residual capsule opacities developed visually significant PCO.

Aged↗

PubMed2004

Anthrax capsule vaccine protects against experimental infection.

Efficacy of a poly-gamma-D-glutamic acid anthrax capsule vaccine was assessed in a mouse model of infection. Capsule by itself was protective against lethal challenge with a toxin(-), capsule(+) Bacillus anthracis strain. Conjugation of capsule to bovine serum albumin resulted in enhanced IgG anti-capsule antibodies measured by ELISA, but completely abrogated the protection. The protective unconjugated capsule vaccine elicited significantly higher IgM titers and opsonic activity than did the non-protective capsule conjugate. When tested against a fully virulent toxin(+), capsule(+) B. anthracis strain, neither capsule nor protective antigen alone was protective. However, the combination of the two protected against a lethal challenge. These results suggest that capsule may enhance the protection afforded by protective antigen vaccines against anthrax if opsonizing antibodies are produced. Surprisingly, some protection was also observed when protective antigen was conjugated to itself.

Animals↗

PubMedDate not supplied

Cellular fibronectin, but not collagens, disappears in the central posterior capsules during healing after lens extraction and IOL implantation in rabbits.

PURPOSE: To investigate the nature of capsular opacification after cataract-intraocular lens (IOL) surgery in rabbit eyes, we immunohistochemically located extracellular matrix components in lens capsules after the surgery using light microscopy. The study was conducted also to compare the extracellular matrix components in rabbit capsules with those previously reported in the human eye. METHODS: Twenty-seven eyes of 17 Japanese albino rabbits were lensectomized by phacoemulsification, and IOLs were implanted. Using immunohistochemical methods, the lens capsules were examined immediately after surgery, and 1, 2, 4, and 8 weeks after surgery. RESULTS: In all cases at each time point, the edge of the anterior capsulotomy had contracted and was found to adhere to the inner surface of the posterior capsule, with both IOL haptics remaining in the capsular bag. Collagen types I and III were detected around the adhesion between the anterior capsulotomy edge and posterior capsule during all stages of healing and also observed on the central posterior capsules 1 or more weeks after surgery. Immunoreactivity for cellular fibronectin was seen around the adhesion between the anterior capsulotomy edge and posterior capsule during all stages of healing. It was also detected on the posterior capsules 2 and 4 weeks after surgery, but disappeared 8 weeks after surgery. CONCLUSION: Extracellular matrix components such as collagen types I and III and cellular fibronectin were expressed inside the residual lens capsular bag. Cellular fibronectin may play a role in the early wound healing process in the postoperative posterior capsule because the immunoreactivity in the central posterior capsule disappears in the later phase of healing.

Animals↗

PubMedDate not supplied

Management of posterior capsule tears.

Any breach in the continuity of the posterior capsule is defined as a posterior capsule tear. Posterior capsule tears can be preexisting (congenital or traumatic), spontaneous, or intrasurgical. Preexisting/congenital posterior capsule tears have been related to an intrauterine insult. Posterior capsule tears due to trauma may occur as a consequence of direct mechanical impact due to perforation or blunt injury. Depending on the duration of time between the posterior capsular trauma and the cataract surgery, these posterior capsule tears can have different features. Intrasurgical posterior capsule tears are the most common and can occur during any stage of cataract surgery. Also, they may be planned in the form of primary posterior capsulorhexis. The conventional management consists of prevention of mixture of cortical matter with vitreous, dry aspiration, and anterior vitrectomy, if required. In addition, during phacoemulsification low flow rate, high vacuum, and low ultrasound are advocated if a posterior capsule tear occurs. Dislocated nucleus or nuclear fragments require vitrectomy and the use of perfluorocarbon liquids. In the presence of a posterior capsule tear, the IOL can be placed in the sulcus, if the capsular rim is available, or in the bag, if the tear is small. Scleral fixated posterior chamber lenses and anterior chamber IOLs can be implanted when the posterior capsule tear is large.

Eye Injuries↗

PubMedDate not supplied

Comparative bioavailability of ceftibuten in capsule and suspension forms.

The comparative bioavailability of ceftibuten, a new third-generation cephalosporin antibiotic given orally once daily, in capsule and suspension dosage forms, was assessed in healthy male subjects. In three separate studies, subjects received either a 400-mg dose as a suspension or one laboratory-batch, 400-mg capsule; one laboratory-batch, 400-mg capsule or two laboratory-batch, 200-mg capsules; or one production-batch, 400-mg capsule or two laboratory-batch, 200-mg capsules. Plasma samples were assayed for ceftibuten using high-performance liquid chromatography, and the data were assessed using pharmacokinetic and statistical methods. Confidence intervals for the maximum plasma concentration and the area under the plasma concentration-time curve extrapolated to infinity were within 80% to 125% of guidelines, demonstrating the bioequivalence of the two treatments within each of the three studies. One 400-mg capsule (laboratory or production batch) was bioequivalent to two 200-mg capsules used in a clinical efficacy trial; the 400-mg suspension was bioequivalent to a 400-mg capsule (laboratory batch). Thus we concluded that the capsule and the suspension dosage forms were bioequivalent.

Administration, Oral↗

PubMed2002

Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats.

The objective of this study was to achieve the colon-specific delivery of an anti-ulcerative colitis drug using chitosan capsules and to accelerate healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. The gastrointestinal transit of chitosan capsules was determined by counting the number of capsules in the gastrointestinal lumen by celiotomy at certain times after their oral administration to rats. The chitosan capsules reached the large intestine 3.5 h after oral administration in rats. We studied the release of 5-ASA from chitosan capsule by the Japan Pharmacopoeia (JP) rotating basket method. The release of 5-ASA from the chitosan capsule markedly increased in the presence of rat cecal contents. After oral administration of chitosan capsules containing 5-ASA, the concentrations of 5-ASA in the large intestinal mucosa were higher than those in the CMC suspension. For the treatment of colitis in rats, 5-ASA was orally administered using chitosan capsules or a carboxy methyl cellulose (CMC) suspension to TNBS-induced rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio and the damage score, respectively. When 5-ASA was orally administered using chitosan capsules in TNBS-induced colitis rats, we found better therapeutic effects with 5-ASA than with a 5-ASA CMC suspension, as evaluated by the MPO activities, C/B ratio and the damage score. In conclusion, chitosan capsules may be useful carriers for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and the healing of TNBS-induced colitis in rats.

Administration, Oral↗

PubMed2000

Genetic organisation of the capsule biosynthetic locus of Pasteurella multocida M1404 (B:2).

Capsules from a range of bacterial species have been shown to be major virulence determinants and capsule has been implicated in virulence in Pasteurella multocida. Moreover, capsular serogroup appears to be related to disease predilection. Haemorrhagic septicaemia strains belong to serogroup B and E, fowl cholera strains to serogroup A and atrophic rhinitis strains to serogroup D. The entire capsule biosynthetic locus of P. multocida A:1 has been cloned and its nucleotide sequence determined (Chung et al., 1998. FEMS Microbiol. Lett. 166, 289-296); however, nothing is known of the P. multocida B:2 capsule locus. In this work we have determined the nucleotide sequence and genetic organisation of the P. multocida M1404 (B:2) capsule locus. By analogy with the cap loci of other bacteria, the nucleotide sequence can be divided into three functional regions. Regions 1 and 3 comprise six genes involved in transport of the polysaccharide capsule to the cell surface. The deduced products of these genes show high similarity to proteins involved in capsule export in other bacteria. Region 2 comprises nine genes which are likely involved in biosynthesis of the polysaccharide capsule. The deduced products of three of these genes (bcbA, bcbB and bcbC) show significant similarity to proteins known to be involved in polysaccharide biosynthesis while the other six show no similarity to known proteins. However, their organisation indicates they are co-transcribed with bcbA, bcbB, bcbC and the Region 1 capsule export genes, suggesting strongly that they are also involved in capsule biosynthesis.

Amino Acid Sequence↗