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PubMed2005

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week.

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6 mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4-12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h. The mean maximal serum drug concentration (mean C(max)) of MTX attained at 1-2 h after ingestion of the first capsule was 0.215 and 0.252 microM, respectively, in the first and the follow-up week. The mean C(max) after ingestion of the third capsule was 0.223 microM and 0.357 microM. The mean C(max) of 7-OH MTX was 0.0334 and 0.0289 microM for the first capsule, and 0.0495 and 0.0672 microM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6 mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5 mg per week.

Journal Article↗
PubMed1979

Foreign material in the capsules around breast prostheses and the cellular reaction to it.

Thirteen capsules which had formed around breast prostheses were examined, using the technique of splitting the capsule wall. A foreign material in droplet form was present in all the capsules. The foreign material was taken up by phagocytes, and the cytological evidence is that it has cytotoxic activity. It was shown that the material migrates to the vessels in the outer layer of the capsule and may reach the lumen of those vessels. On the basis of the microscopic appearance and the results of infrared spectrum analysis, the foreign material in the capsules was assumed to be silicone.

Breast↗
PubMed1984

Immediate postabortal contraception with Norplant: levonorgestrel, gonadotropin, estradiol, and progesterone levels over two postabortal months and return of fertility after removal of Norplant capsules.

Six Silastic levonorgestrel-releasing capsules, Norplant, were introduced subcutaneously into the ventral aspect of the left forearm or upper arm of thirteen patients immediately after first trimester pregnancy termination. Blood samples were taken twice a week over two months after abortion and from one subject over one month after removal of Norplant capsules. Plasma concentrations of levonorgestrel were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. If removal of Norplant capsules took place because of planning pregnancy, the subjects were asked to inform us if they had become pregnant. During the first month after abortion the mean levonorgestrel concentration (489 pg/ml) was statistically significantly higher than during the second month (237 pg/ml). The mean estradiol values fell to prefollicular levels within four days, remaining a little suppressed. The mean progesterone concentrations were below 2 ng/ml three days after abortion. Three subjects had a transient increase in plasma progesterone concentrations nine days after abortion. Thereafter no ovulatory progesterone concentrations were seen. The LH concentrations ranged within normal values of the follicular phase and FSH values were just beneath the lower limit of follicular phase FSH values, apart from a few peaks, indicating mild suppression. After removal of Norplant capsules, progesterone concentrations increased to ovulatory levels fifteen days after removal. The Norplant capsules were removed from two subjects because of planning pregnancy and they delivered healthy babies 9.5 and 12.5 months after removal.

Abortion, Induced↗
PubMed1990

Sequence and developmental expression of the mRNA encoding the seleno-protein of the sperm mitochondrial capsule in the mouse.

We have characterized cDNA clones encoding the selenium-containing polypeptide of the keratinous mitochondrial capsule in mouse sperm. The longest open reading frame encodes a polypeptide 143 amino acids long which contains 21% cysteine and 27% proline and closely resembles the size and amino acid composition of bull mitochondrial capsule seleno-protein (V. Pallini, B. Baccetti, and A. G. Burrini, 1979, in "The Spermatozoon," D. W. Fawcett and J. M. Bedford, Eds., pp. 141-151, Urban & Schwartzenberg, Baltimore/Munich). The reading frame encoding the mitochondrial capsule seleno-protein ends with an amber stop codon suggesting that selenium is not incorporated cotranslationally into the protein by an opal suppressor selenocysteyl-tRNA as has been found for several eukaryotic and bacterial proteins. Northern blots using RNA extracted from purified spermatogenic cells and staged prepuberal mice suggest that the mitochondrial capsule seleno-protein mRNA is first transcribed in late meiotic cells and that the levels of the mRNA increase after meiosis in early haploid cells. Southern blots demonstrate that there is one copy of the gene in the mouse genome. The identification of this cDNA clone, in combination with previous work (K. C. Kleene, 1989, Development 106, 367-373) demonstrates that the mRNA for the mitochondrial capsule seleno-protein is translationally repressed with long homogenous poly(A) tracts in round spermatids and translationally active with shortened heterogenous poly(A) tracts in elongating spermatids.

Amino Acid Sequence↗
PubMed1989

Location of a synergistic factor in the capsule of a granulosis virus of the armyworm, Pseudaletia unipuncta.

A synergistic factor (SyF), which enhanced the infection of nuclear polyhedrosis viruses, was purified from capsules of a Pseudaletia unipuncta granulosis virus (Hawaiian strain) by immune affinity chromatography. The isolated SyF consisted primarily of a protein with molecular mass 98 kDa. The recovery rate depended on the alkali used to dissolve the capsules: the highest rate occurred with 0.05 M Na2CO3-0.05 M NaCl, followed in turn with 0.02-0.05 M NaOH and 0.04 M NaOH-0.05 M glycine. The solubilized components from untreated capsules contained 98- and 100-kDa proteins in addition to the matrix protein (29 kDa) and its decomposed products, while those from heat-treated capsules contained only the 100-kDa protein. Virons liberated from the capsules with the glycine buffer contained three proteins (33, 98, and 100 kDa) serologically related to the SyF. Immunoelectron microscopy of infected tissue and purified virions revealed the localization of the SyF antigens on the viral envelope.

Animals↗
PubMed1988

Exocrine contamination impairs implantation of pancreatic islets transplanted beneath the kidney capsule.

The effect of exocrine contamination on islets implanted under the kidney capsule has been studied by histological examination of pure or exocrine-contamination human, monkey, or rat islets transplanted to the kidney capsule of the nude rat, monkey, or rat, respectively. Exocrine contamination resulted in an appearance suggestive of impaired islet implantation, due to tissue necrosis and subsequent fibrosis. The effect of exocrine contamination was examined quantitatively in a rat islet isograft model in which handpicked DA rat islets were transplanted under the kidney capsule of normal DA rats. The islets were either pure or deliberately recontaminated with exocrine tissue (50 or 90% contamination). Four hundred pure islets were placed under one kidney capsule and 400 islets (of similar size and from the same islet preparation) were contaminated and then placed under the contralateral kidney capsule. After 2 weeks the kidneys were removed and extracted for insulin content. The insulin content of kidneys bearing islets contaminated by either 50 or 90% exocrine tissue was significantly reduced when compared to the contralateral kidney bearing pure islets. These findings support the view that exocrine contamination of islets resulted in impaired islet implantation when transplanted to a confined site such as the kidney subcapsule.

Animals↗
PubMed1988

Feasibility of using hard gelatin capsules for the packaging and deep-freezing of bull semen.

Various packaging systems have been used for deep freezing of semen. In this study, feasibility of using hard gelatin capsules was established. Of the four types of capsules developed and tested, polymer-treated capsules were found to be suitable for the purpose, and were therefore used subsequently. French medium (0.5 ml) straws were used for control. Five semen samples from each of 12 bulls were processed and included for study. Semen was frozen by fast-freezing. Parameters studied after thawing of semen were comparable for the two methods. Upon analysis, the percentages of progressive motile spermatozoa, live spermatozoa and morphologically abnormal spermatozoa obtained for semen frozen in hard gelatin capsules and French medium straws were found to be nonsignificant. The percentage of intact acrosomes was found to be significantly higher (P < 0.05) for semen frozen - thawed in straws as compared to semen in capsules.

Journal Article↗
PubMed1994

Visualization of capsule formation by Erwinia amylovora and assays to determine amylovoran synthesis.

Exopolysaccharide (EPS) synthesis by Erwinia amylovora depends on environmental and genetic predispositions. To measure the amount of the acidic EPS amylovoran synthesized by E. amylovora cell cultures, a turbidity assay using cetylpyridinium salt was developed. The EPS produced by bacteria grown on solid media was additionally characterized by its water content. The amylovoran capsules were visualized in situ by staining with fluorescein isothiocyanate (FITC)-labelled lectin from Abrus precatorius, which reacts with the galactose residue of the EPS side chain. The staining and the turbidity assays were applied to suspension cell cultures or to cells from colonies and did not require any purification steps. Lectin staining was superior to electron microscopic (EM) techniques for visualization of capsules. For EM, the capsule was stabilized with polycationic ferritin. In contrast to lectin staining, only a small fraction of the cells was found to be EPS-coated in the EM assay. An increase in capsulation and in amylovoran production was found in conjunction with mutations in a ribosomal protein conferring resistance to streptomycin. Furthermore, the presence of sorbitol in the growth environment resulted in high synthesis of amylovoran. Cells in the stationary growth phase continued to produce amylovoran. Apparently, the strong dependence of the fireblight pathogen on capsules requires the capacity for EPS synthesis in all growth stages in order to escape plant defence reactions.

Bacteriological Techniques↗
PubMed1984

Sex and strain differences in mouse kidney: Bowman's capsule morphology and susceptibility to chloroform.

Chloroform (CHCl3) produces liver damage in male and female mice but renal injury only in male mice. Previous reports demonstrated that the parietal epithelium of Bowman's capsule in female mice is composed of squamous cells, whereas the parietal cells of Bowman's capsule from male mice consist of a mixture of squamous and cuboidal cells or purely cuboidal cells. These data suggested that the factor(s) associated with these histological differences may similarly be associated with factors that determine susceptibility to tubular damage from chloroform. The susceptibility of male mice to chloroform nephrotoxicity varies with animal strain. In the present study, administration of CHCl3 to male C57BL/6J (C57) and male and female DBA/2J (DBA) mice produced dose-dependent kidney tubular damage in male C57 and male DBA mice. However, CHCl3 nephrotoxicity was considerably greater in male DBA mice than in male C57 mice. Female DBA mice failed to develop renal damage following administration of CHCl3. Male DBA mice had a higher percentage of cuboidal parietal epithelial cells in Bowman's capsule whereas male C57 mice had a higher percentage of squamous cells in the parietal epithelium. The parietal epithelium in Bowman's capsule of female DBA mice was predominantly squamous. Since morphological differences between sex and strain of mice occurred in the capsular epithelium, and the differences in susceptibility to CHCl3 appear to be a tubular phenomenon, it is unlikely that there is a causal relationship between the structure of Bowman's capsule and chloroform-induced renal tubular necrosis; rather, these two independent phenomena are regulated by some common factor(s), possibly testosterone.

Alanine Transaminase↗
PubMed1990

Detection of capsule in strains of Clostridium difficile of varying virulence and toxigenicity.

Nine toxigenic and six non-toxigenic strains of Clostridium difficile, of varying virulence in the hamster model of antibiotic-associated colitis, were examined for the presence of a capsule. Antibody stabilisation of the capsule with heterologous and/or homologous antiserum fixed in glutaraldehyde, or direct fixation in glutaraldehyde/diamine, were used with added ruthenium red to stain the capsular glycocalyx. All strains possessed a capsule which was either loose-knit or compact, sometimes with attached globular masses. Better capsule preservation was achieved in some strains with glutaraldehyde/diamine/ruthenium red fixative than with homologous or heterologous antibody stabilisation. The possession of a capsule following in vitro growth does not appear to correlate with the virulence status of these strains of C. difficile.

Animals↗
PubMed2004

Stage-specific formation of the equine blastocyst capsule is instrumental to hatching and to embryonic survival in vivo.

Early embryonic development in the horse is characterized by the formation of an unusual acellular glycoprotein "capsule" between the trophectoderm and the overlying zona pellucida. This structure is first detected between days 6 and 7 after ovulation and completely envelops the spherical conceptus until as late as day 23 of gestation. In the present study, a micromanipulator was used to remove the capsule from 15 embryos on day 6-7 after ovulation. None of these denuded embryos developed into ultrasonographically detectable pregnancies after surgical transfer into recipient mares whereas four of six control embryos handled and transferred similarly but without capsule removal developed normally, thereby demonstrating clearly a role for the capsule in embryonic survival. In addition, observation of the embryonic investments after embryo collection and during micromanipulation led to the hypothesis that hatching of the horse embryo from its zona pellucida is assisted by the force of the expanding capsule, which causes the attenuating zona to literally burst open.

Animals↗
PubMed2006

Adhesive capsulitis of the hip.

PURPOSE: It is postulated that adhesive capsulitis of the hip is more common than suggested in the published literature, which recounts only a few isolated cases, and that this condition shares many of the same characteristics seen in the shoulder. The purpose of this study was to investigate and report the findings of the first clinical case series on this condition. TYPE OF STUDY: Clinical case series, retrospective review of prospectively collected data. METHODS: Since 1993, all hip arthroscopy cases have been prospectively assessed with a 100-point rating system. In 1999, adhesive capsulitis was first recognized as a causative factor. Since then, 9 patients have been identified with this condition with at least 1 year of follow-up. RESULTS: There was 100% follow-up at an average of 17.3 months. The average age was 43.7 years. There were 8 women and 1 man. Radiographs were normal in 8 cases and revealed mild degenerative disease in the 1 male patient. Magnetic resonance imaging/arthrography failed to reveal evidence of adhesive capsulitis. Examination under anesthesia revealed an average loss of 25 degrees of rotational motion (19.4 external, 5.6 degrees internal). Full range of motion was regained with manipulation. Arthroscopy revealed characteristic findings of adhesive capsulitis in all cases and coexistent pathology in 6 cases (5 articular lesions, 3 labral tears, and 1 ruptured ligamentum teres). The 8 women with normal radiographs all improved with an average of 32 points (preoperative, 56.4; postoperative, 88.4). The 1 man with degenerative changes showed negligible improvement. There were no complications. CONCLUSIONS: Adhesive capsulitis of the hip is not as rare as suggested by the paucity of available literature. The clinical characteristics are similar to the shoulder, principally consisting of painful restricted motion and a clear predilection for middle aged women. It may occur with or without associated intra-articular pathology. Arthroscopy can be beneficial in the treatment of recalcitrant cases, but may assume less of a role with improved diagnostic skills essential to implementing a proper management strategy. LEVEL OF EVIDENCE: Level IV.

Arthroscopy↗
PubMed2005

A novel solvent-free method for the manufacture of biodegradable antibiotic-capsules for a long-term drug release using compression sintering and ultrasonic welding techniques.

This report was to develop a novel solvent-free method for the manufacture of biodegradable capsules for a long-term drug delivery. To manufacture an antibiotic capsule, polylactide-polyglycolide copolymers were pre-mixed with vancomycin. The mixture was then injection compression molded to form a cylinder with a cover of 8mm in diameter. After the addition of gentamicin sulfate into the core, an ultrasonic welder was used to seal the capsule. An elution method and an high-performance liquid chromatography assay were employed to characterize the in vitro release rates of the antibiotics over a 30-day period. It was found that biodegradable capsules released high concentration of vancomycin and gentamicin (well above the minimum inhibition concentration) in vitro for the period of time needed to treat bone infection; i.e., 2-4 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 3 to 18 mm, which is equivalent to 16.7-100% of relative activity. By adopting this novel technique, we will be able to manufacture biodegradable capsules of various medicines for long-term drug delivery.

Anti-Bacterial Agents↗
PubMed2005

Complications, limitations, and failures of capsule endoscopy: a review of 733 cases.

BACKGROUND: Although a variety of technical and clinical problems of capsule endoscopy have been reported, their incidence and clinical importance are unknown. The objective was to evaluate the incidence and the type of such events. METHODS: This was a retrospective analysis of 733 consecutive examinations at 4 large referral centers. The main outcome measurements were that the problems were classified as "technical," i.e., related to the functioning of the equipment, and "clinical," i.e., related to patient characteristics. For each type of event, the causes and the impact on the ability to reach a diagnosis were examined. RESULTS: A total of 183 problems were recorded in 174 patients (23.7%): one problem occurred in 165 patients, two in 9 patients. In 8.46% of patients, technical limitations or failures, or clinical complications prevented or hampered diagnosis. Technical problems (e.g., gaps in the recordings, short duration of capsule batteries, failure of downloading) occurred in the early phase of capsule use in 8.6% of examinations and prevented or hampered diagnosis in 2.9%. Clinical problems (difficulty/inability to swallow the capsule, incomplete small-bowel examination) occurred in 16.4% of examinations and hampered or prevented diagnosis in 6.4%. Capsule retention that required surgical or endoscopic retrieval occurred in 1.9% of cases. CONCLUSIONS: Technical problems were rare and hampered or prevented the diagnosis in a very small number of cases. The majority of clinical failures were related to an incomplete small-bowel examination.

Adolescent↗
PubMed2005

Impact of capsule endoscopy in obscure small-bowel bleeding: defining strict diagnostic criteria for a favorable outcome.

BACKGROUND: The most frequent indication for capsule endoscopy is to diagnose the cause of obscure GI bleeding. The objective of the study was to determine the impact of capsule endoscopy on the outcome of patients with GI bleeding of obscure origin. METHODS: Ninety-six patients (53 men, 43 women; mean [standard deviation] age, 60.84 years [16.55 years]) were enrolled in the study. All patients have been subjected to gastroscopy, colonoscopy, small-bowel barium follow-through or enteroclysis, and push enteroscopy; no bleeding site had been identified. Capsule endoscopy was performed with the Given M2A video capsule system. By using strict criteria, studies were classified as having positive findings, findings of uncertain significance, and no findings. Outcome was defined as continued or complete resolution of bleeding. RESULTS: Positive findings, findings of uncertain significance, and no findings were identified in 41.7%, 20.8%, and 37.5% of our study population, respectively. The most common lesions seen were angiodysplasias of the small intestine. Therapeutic intervention was possible in 82.5% of patients with positive findings and in 35.0% of patients with findings of uncertain significance. Complete resolution of bleeding, after a median (interquartile range) follow-up period of 14 months (9-17 months), occurred significantly more often in patients with positive findings (68.4%) compared with patients with findings of uncertain significance and no findings (40.8%, p = 0.009). CONCLUSIONS: Capsule endoscopy increases the diagnostic yield in the workup of patients with obscure small-bowel bleeding. Strictly defined positive findings are associated with a favorable outcome.

Endoscopes, Gastrointestinal↗
PubMed2025

Reversible phenotypic resistance to phage infection via capsule downregulation in Klebsiella pneumoniae.

Capsule loss is a major mechanism by which bacteria evade phage infection. This has traditionally been attributed to mutations in capsule biosynthesis genes. Here, we investigated phage resistance in Klebsiella pneumoniae, a medically relevant encapsulated bacterium. Phage infection rapidly selected for resistant acapsular cells. As expected, transcriptomic analysis revealed a marked downregulation of capsule biosynthesis genes. However, full genome sequencing showed that capsule loss occurred without evidence of mutations, and acapsular phage-resistant cells were able to rapidly restore their capsule once phage pressure was removed. These findings highlight that phage-driven selective pressure can act on non-heritable variation in gene expression, providing a faster and more flexible resistance mechanism compared to the traditional mutation-selection process. This reversible resistance may complicate predictability and limit the long-term efficacy of phage therapy.

Cell biology↗
PubMed2005

Clinical application of 11-deoxycortisol in visualizing prolapsed vitreous body after posterior capsule rupture in cataract surgery.

PURPOSE: To evaluate the clinical usefulness of 11-deoxycortisol, a precursor of cortisol in steroid metabolism, in visualizing the vitreous body in the anterior chamber after posterior capsule rupture during cataract surgery. SETTING: Department of Ophthalmology, Tsukuba University Hospital, Ibaraki, Japan. METHODS: Eight eyes had anterior vitrectomy during cataract surgery using this new technique. A suspension of 11-deoxycortisol was prepared by dilution in balanced salt solution without preservatives or emulsifying agents. After a posterior capsule rupture, the suspension was injected into the anterior chamber. The visual and anatomical outcomes of surgery were evaluated during a follow-up of 7 to 9 months. RESULTS: After the 11-deoxycortisol injection, the vitreous body that had prolapsed through the torn posterior capsule, with white particles entrapped on its surface, became clearly visible. Complete removal of the prolapsed vitreous body was achieved easily and safely using an anterior vitrectomy system. No postoperative complications related to the use of 11-deoxycortisol were observed. CONCLUSION: Injection of 11-deoxycortisol helped visualize the vitreous body in the anterior chamber after posterior capsule rupture. The technique minimized intraoperative and postoperative complications related to posterior capsule rupture and vitreous loss during cataract surgery [corrected]

Aged↗
PubMedDate not supplied

Adhesive capsulitis of the shoulder in human immunodeficiency virus-positive patients during highly active antiretroviral therapy.

Many adverse events have been described in patients treated with highly active antiretroviral therapy (HAART). Recently, among these, adhesive capsulitis of the shoulder has been described in some patients using protease inhibitors. We report our experience with 6 human immunodeficiency virus-positive patients in whom adhesive capsulitis of the shoulder developed during HAART. All 6 patients were treated with the same antiretroviral drug combination (HAART) including nucleoside reverse transcriptase (stavudine and lamivudine) and protease inhibitors (indinavir). The clinical pattern of adhesive capsulitis during HAART is similar to the classical form of adhesive capsulitis. Examining our case studies, we postulate a correlation between HAART and adhesive capsulitis. Discontinuation or reduction of the dosage of protease inhibitors associated with conventional conservative treatment is effective in reducing the symptoms and resolving the disease.

Adult↗