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[Importance of an intact posterior capsule for the vitreous body. Complication of posterior capsulotomy].

The various extracapsular cataract surgery techniques keep the anatomy and physiology of the eye largely untouched, since both the intact posterior capsule and the crystalline lens form a diaphragm between the aqueous humour and the vitreous. If the posterior capsule opacifies--which occurs in up to 50% within five years postoperatively--a capsulotomy becomes necessary. This increases the rate of retinal detachment and cystoid macular edema. To date no pharmacologic or immunologic means exist to prevent posterior capsule opacification. Implanting the IOL into the capsule bag and the biconvex lens design by itself reduce the incidence of opacification. The biconvex optic of the IOL seals the gap in the capsule, if a capsulotomy has been performed; fluorophotometry shows us that the diaphragm function remains intact after in the bag implantation as compared to sulcus fixated IOL.

Cataract↗

Transplantation of tracheal epithelial cells onto a prefabricated capsule pouch with fibrin glue as a delivery vehicle.

OBJECTIVE: The purpose of this study was to investigate whether in vitro cultured tracheal epithelial cells can be transplanted onto a prefabricated capsule surface in vivo for possible use in tracheal reconstruction. METHODS: Tracheal epithelial cells from 12 donor inbred rats were harvested for culture and expansion. In 16 recipient inbred rats, 2 sterile cylinders made of silicone rubber were implanted in each rat bilaterally in the folds of both the left and right anterior rectus sheath by wrapping the sheaths around the cylinders to induce a capsule formation. Ten days later, the cell cultures were divided and suspended in 1 of 2 delivery vehicles (standard culture medium or fibrin glue) and implanted onto the capsule surface. To compare the 2 delivery vehicles, we used fibrin glue on one side and the standard culture medium on the other. RESULTS: After 2 (group 1, n = 8) and 4 (group 2, n = 8) weeks, histologic findings, immunohistochemical staining, and electron microscopy demonstrated the capsule to be covered with a tracheal neoepithelium in group 1 and additional ciliated cells and secretory cells in a confluent layer in group 2 but only on the side with fibrin glue as the delivery vehicle. No viable epithelial cells were identified on the side with the standard culture medium in either group. CONCLUSION: We conclude that cultured epithelial cells can be successfully transplanted onto a prefabricated capsule surface with fibrin glue, which will differentiate into morphologic, nearly normal epithelium, showing potential for tracheal reconstruction.

Animals↗

Retrovirus-mediated transfer of a suicide gene into lens epithelial cells in vitro and in an experimental model of posterior capsule opacification.

PURPOSE: The most common complication of cataract surgery is the development of posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification and was found to be an important feature contributing to opacification of the posterior capsule. We investigated the feasibility of killing the residual lens epithelial cells by retroviral-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, a well-studied suicide gene, into rabbit lens epithelial cells followed by ganciclovir (GCV) treatment. METHODS: The capacity of retroviral vectors to transfer genes into rabbit lens epithelial cells was determined either in vitro (culture of rabbit lens epithelial cells) or in vivo (experimental model of PCO in rabbits) using cDNA encoding the beta-galactosidase (LacZ) reporter gene. To evaluate the efficiency of suicide gene therapy (infection with retroviral vectors encoding the HSV-tk gene followed by GCV treatment) we determined the sensitivity of HSV-tk infected lens epithelial cells to different concentrations of GCV in vitro. Then, in an experimental model of PCO, rabbits were treated with HSV-tk retroviral vectors at the end of the surgery and they received repeated intracameral and intravitreal injections of GCV at the concentration determined by the in vitro experiments. RESULTS: Infection efficiency using LacZ retroviral vectors was about 29% in vitro and 10% in vivo. After infection of the HSV-tk cDNA in vitro, the cell killing effect of GCV was evaluated. A significant enhancement (four- to five-fold) of the cell sensitivity to GCV was shown in FLY-DFGtk as compared with mock infected (P < 0.01) cells even without selection of the HSV-tk positive cells. The GCV concentration leading to 50% reduction in cell number (IC50) was 50 microg/ml. In vivo infection with a HSV-tk vector led to the tk gene transfer into lens epithelial cells. Despite this local HSV-tk gene expression, we could not prevent capsule opacification. CONCLUSIONS: Lens epithelial cells were successfully infected both in vitro and in vivo by beta-galactosidase and HSV-tk genes via retroviral vectors. In vitro infected lens epithelial cells displayed a strong sensitivity to GCV treatment. In vivo, we could not prevent capsule opacification in the rabbit model, very likely due to the limited level of the HSV-tk gene expression. However, our results suggest that virus-mediated suicide gene therapy might be a feasible treatment strategy to prevent capsule opacification with a more powerful vector.

Animals↗

Effects of pseudophakic lens capsule opacification on optical coherence tomography of the macula.

PURPOSE: To report observations on the influence of posterior lens capsule opacification on optical coherence tomographic imaging quality and measurements of macular thickness. METHODS: The retrospective study included 13 eyes in 12 patients of which 2 eyes had a healthy macula and 11 eyes had maculopathy. In all eyes posterior lens capsule fibrosis was present. A clinical examination including biomicroscopy of the macula and an in-vivo macular optical coherence tomography (OCT) before and after YAG-laser membranotomy had been performed. RESULTS: Foveal retinal thickness before and after membranotomy were highly correlated (R = 0.98), and no systematic difference was found between values obtained before vs. after membranotomy (mean thickness 318.7 +/- 92.7 microm vs. 322.2 +/- 97.4 microm; p = 0.221). The signal-to-noise ratio increased in 11 out of 13 eyes after membranotomy (mean signal-to-noise ratio before 47.1 +/- 6.6 dB vs. 52.6 +/- 4.0 dB after; p = 0.004, the change ranging from -1.5 dB to 17 dB). CONCLUSIONS: The qualitative effect of the posterior lens capsule opacification on the OCT-scan consists primarily of a loss of signal and consequently of intraretinal detail, whereas total foveal retinal thickness seems to be reliably assessed even when posterior lens capsule opacification interfering with the biomicroscopic evaluation of retinal edema are present. YAG-laser membranotomy results in a measurable improvement in the OCT signal-to-noise ratio, but OCT seems to yield reliable measurements of foveal retinal thickness before treatment. Consequently the OCT seems to reliably diagnose a macular thickening although not the type of this until after removal of the posterior lens capsule opacification.

Adult↗

Analysis of transcriptional control mechanisms of capsule expression in Neisseria meningitidis.

The major virulence factor which contributes to the survival of Neisseria meningitidis in the blood stream and the cerebrospinal fluid is the capsular polysaccharide. Expression of the capsule genes of N. meningitidis serogroups B, C, W-135 and Y is controlled by an intergenic region separating the capsule biosynthesis operon (siaA-D) and the capsule transport operon (ctrA-D). To further investigate capsule expression in N. meningitidis we amplified and sequenced the intergenic region of 42 meningococcal isolates of different serogroups. Sequence variations were found mainly in a repeat region preceding the siaA start codon. Correlation between sequence variation and serogroup could not be observed. To measure the transcriptional and translational activity of the respective intergenic regions we performed transcriptional and translational fusions with the lacZ gene integrated into the chromosome of N. meningitidis. Sequence variations preceding the siaA start codon had no effect on beta-galactosidase activity. Different in vitro growth conditions such as temperature, glucose concentration, osmolarity, pH and iron concentration also did not influence beta-galactosidase activity. Sequential deletions of the intergenic region showed that an Up-like element adjacent to the predicted -35 box is necessary for full transcriptional activity. The deletion of the untranslated region preceding the siaA start codon led to a threefold higher beta-galactosidase activity compared with the full-length construct suggesting that the respective region may be involved in capsule regulation.

Bacterial Capsules↗

Clinical application of video capsule endoscopy.

BACKGROUND: Non-invasive imaging of the complete small bowel has become possible with the recently available video capsule endoscopy technique. The aim of this study was to review and assess the possibilities and limitations of the clinical application of video capsule endoscopy. METHODS: Literature review. RESULTS: Video capsule endoscopy is a new promising technique with good to excellent visualization of the mucosa of the small bowel. It has a high diagnostic yield in patients with occult gastrointestinal blood loss (OGIB) and Crohn disease (CD). Several other indications need further study. Compared to small-bowel X-ray and push enteroscopy, diagnostic yield appears to be superior. Video capsule endoscopy is very well tolerated by patients. Its most important limitation is the impossibility of taking biopsies and therapeutic interventions. CONCLUSION: Video capsule endoscopy is a promising new diagnostic tool for small-bowel disease.

Capsules↗

Colonic drug delivery: influence of cross-linking agent on pectin beads properties and role of the shell capsule type.

For colonic delivery, pectin beads obtained by ionotropic gelation method have been already reported as an interesting approach. This study investigated the influence of the cross-linking agent (calcium or zinc) and the type of shell capsule used (classical or enteric capsules) on pectin beads properties and on their performance to target the colon (in vitro dissolution studies with subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate beads seemed to be relatively similar to calcium's ones in morphological point, except on the surface aspect. When beads were introduced in classical hard capsules, ketoprofen release was not significantly different between CPG and ZPG beads, and it was too premature and too quick due to a chemical erosion of the pectinate matrix (acid + basic attacks). However, zinc pectinate beads showed slower ketoprofen release compared with calcium pectinate beads when enteric hard capsules were used. This interesting finding could be due to the strength of the network formed during the process between the zinc cations and the LM-pectin following the "egg-box" model. This network was stronger and induced a reduction of swelling and hydration when contact with dissolution medium, then subsequently a decrease of drug release. Thus, the zinc pectinate beads could protect sufficiently drug entrapped from the upper gastro-intestinal conditions and drug release will be controlled by pectin degradation with colonic microflora. Finally, these zinc pectinate beads in enteric hard capsules are promising as a carrier for specific colonic delivery of drugs after oral administration.

Administration, Oral↗

Reliability and validity of the pressure pain thresholds (PPT) in the TMJ capsules by electronic algometer.

Pressure pain thresholds (PPT) of 39 normal subjects (20 males and 19 females) and 30 female patients with temporomandibular joint (TMJ) capsulitis (21 lateral and 25 posterior capsulitis) were examined by an electronic algometer. In normal subjects, statistically significant correlation coefficients were obtained from the values of intra-examiners and inter-examiners in both lateral and posterior TMJ capsules (p < 0.01). A comparison with data obtained from contralateral sides failed to demonstrate significant differences. Statistically significant differences were found between the PPT of normal female subjects and female patients with capsulitis in both lateral and posterior TMJ capsules (p < 0.01).

Adult↗

Local spermicidal contraception: a comparative study of the acceptability and safety of a new pharmaceutical formulation of benzalkonium chloride, the vaginal capsule, with a reference formulation, the pessary.

OBJECTIVE: To evaluate comparatively the acceptability and safety of a new pharmaceutical form of benzalkonium chloride, the vaginal capsule, with the pessary form. METHODS: Eighty-nine women were randomized to receive either a benzalkonium chloride vaginal capsule or a benzalkonium chloride pessary prior to sexual intercourse according to an open cross-over design over a 2-month study period. RESULTS: The discomfort caused by delayed leakage or discharge was mild. The mean scores for subjective signs (burning, itching, vulvar pruritus) were also mild and were comparable for the two formulations. The capsule appeared to be slightly superior to the pessary regarding discomfort caused by immediate discharge or leakage, ease of use and acceptance by the woman's partner. Local safety was generally good. Adverse events consisted chiefly of vulvar pruritus and a vaginal or vulvar burning sensation, with a higher incidence being associated with the pessary than the capsule. All symptoms regressed spontaneously after the end of treatment. CONCLUSIONS: This study demonstrated good acceptability and good local safety for the benzalkonium chloride vaginal capsule. It is essential to take these parameters into consideration in the evaluation of any local spermicidal contraceptive, since they play a large part in compliance with, and thus in the efficacy of, the product under assessment.

Administration, Intravaginal↗

Stability study of hard gelatin capsules containing retinoic acid.

Retinoic acid (RA) is employed in the therapeutic treatment of acute promyelocytic leukemia (APL). In this paper, the chemical stability and the most favorable storage conditions of RA in hard gelatin capsules containing alpha-lactose monohydrate, used in clinical experimentation, are reported. A secondary goal of this work was to show the usefulness of a robust regression technique, repeated median with replicates (RMWR) in a solid-state shelf life prediction by accelerated studies. The capsules were stored at room temperature and in the freezer. Their residual RA content was assayed for more than 3 years. RA chemical degradation was monitored by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) stability-indicating methods previously validated and able to detect various potential degradation products. Possible physical modifications were checked by dissolution tests and differential scanning calorimetry (DSC) of the content of the capsules. The shelf life was also predicted by an accelerated isothermal method to confirm room temperature results, and the activation energy estimated through this study was 12.5 +/- 1.1 kcal/mol (95% confidence interval). In the conditions of climatic zone II, the shelf life for the capsules stored at room temperature in light-resistant containers was equal to 678 days, while the capsules stored in the freezer retained the initial content of drug after 1289 days. From the results gathered in this study, the usefulness of RMWR for shelf life prediction in the presence of outliers is evident.

Calorimetry, Differential Scanning↗

An endogastric capsule for measuring tumor markers in gastric juice: an evaluation of the safety and efficacy of a new diagnostic tool.

BACKGROUND: In gastric juice, high levels of the carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9) have been found to correlate with precancerous lesions and gastric cancer. So far, sampling of gastric juice has required upper endoscopy. In place of this invasive procedure, we investigated a new tool for the quantitation of tumor markers in gastric juice. MATERIALS AND METHODS: The study population consisted of healthy controls and consecutive subjects with suspected gastric cancer or dyspepsia/epigastric distress. Patients were asked to swallow a small gelatine capsule (14 mm in length and 5 mm in diameter) containing a pierced plastic cover and surrounding a piece of absorbent paper. The capsule was left in the gastric cavity for 60 min to allow saturation of the absorbent paper with gastric juice. A 45-50 cm length of nylon thread connected to the inner capsule was used to remove the device from the gastric cavity. After processing the absorbent paper for radioimmunoassay, CEA and CA 19-9 levels were correlated to the findings of upper endoscopy and biopsies of gastric mucosa or suspected lesions. RESULTS: The endogastric capsule did not cause any side-effects and 62 participants were fully compliant to the procedure. Assessable gastric juice samples were taken from 23 patients with gastric cancer, 15 patients with intestinal metaplasia or dysplasia, 12 patients with gastritis and 12 controls without gastric diseases. In the 12 samples of gastric juice from control patients, mean values of CEA and CA 19-9 were 1.1 +/- 0.9 ng/ml and 16 +/- 7.5 ng/ml, respectively. The mean levels of both markers were found to increase according to the severity of gastric lesions and in patients with cancer, mean CEA and CA 19-9 levels were 513 +/- 627 ng/ml and 545 +/- 510 ng/ml, respectively. Patients with precancerous lesions and cancer showed higher levels of CEA and CA 19-9 than patients with normal findings or gastritis (P <0.001). CONCLUSIONS: The endogastric capsule is a simple, non-invasive tool for the measurement of CEA and CA 19-9 levels in gastric juice. These values may discriminate between normal or minor pathologic changes and precancerous lesions or carcinomas. Further investigations are warranted, since this may represent a new method for gastric cancer screening.

Adolescent↗

Myofibroblast numbers are elevated in human elbow capsules after trauma.

Elbow contractures, a frequent problem after injury, can be treated by excision of the joint capsule. However, the underlying changes in the joint capsule are poorly understood. Based on skin healing work, we examined the hypotheses that myofibroblast numbers and expression of a myofibroblast marker alpha-smooth muscle actin, are elevated in patients with posttraumatic joint contractures. Anterior capsules were obtained from six patients who had operative release of posttraumatic contractures greater than 5 months after injury and six elbows of organ donors free of contractures. Immunohistochemical studies revealed that myofibroblast numbers and percentage of total cells that were myofibroblasts were significantly elevated in the joint capsules from patients with contractures (326 +/- 61 cells per field, 36% +/- 4% total cells) when compared with similar tissues of the organ donors (69 +/- 41 cells per field, 9% +/- 4% total cells). Western blot analysis showed that protein levels of alpha-smooth muscle actin were significantly elevated in patients with posttraumatic joint contractures. However, analysis with reverse transcription-polymerase chain reaction determined that messenger ribonucleic acid levels for smooth muscle actin normalized to the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase were not significantly different between the two groups. An association between increased numbers of myofibroblasts and posttraumatic joint contractures has been established in the human elbow capsule. Additional work is required to determine whether myofibroblast regulators may be targets for adjuvant therapies of posttraumatic contractures.

Adult↗

Experimental anterior lens capsule transplantation for chronic corneal ulcers-Bowman's layer replacement?

PURPOSE: This study was designed to measure the value of allografted anterior lens capsule in the reepithelialization of recurrent corneal ulcers. METHODS: Mechanical ulcers of uniform size were created with a 6-mm corneal trephine in both eyes of four Chinchilla male rabbits at one-third corneal depth. Following initial epithelial regrowth, an identical injury was created in the same area of each cornea a second time. In four eyes (treated group), an anterior lens capsule from a healthy donor rabbit was sutured into the ulcer bed followed by antibiotic/steroid drops three times daily for 1 week. The remaining four control eyes were allowed to heal without surgical intervention using the same antibiotic/steroid drops only. Slit-lamp examination and histopathology findings were recorded over a 6-month follow-up period. RESULTS: The four treated eyes reepithelialized after the second injury at a faster rate than the control group eyes and had a lower percentage of corneal opacification at all follow-up exam dates. Histopathology revealed normal epithelium overlying the transplanted anterior lens capsule and no infiltration of inflammatory cells in the subepithelial stroma. CONCLUSIONS: In experimental conditions, allotransplantation of anterior lens capsule speeds up reepithelialization after repeated mechanical trauma to the cornea. To our knowledge, this is the first experimental transplantation of an anterior lens capsule to create an artificial Bowman's layer in recurrent corneal ulcerations to aid reepithelialization and minimize corneal scarring.

Animals↗

Radiolytic breakdown of sodium iodide (131I) in sodium iodide (131I) capsules.

Sodium iodide (131I) capsules are widely used for both diagnosis and therapy. The radiochemical purity of both diagnostic and therapeutic capsules in use in Australia was studied by gel chromatography, high voltage electrophoresis and paper chromatography. It was found that in two of the three bands of therapeutic capsules examined, significant quantities of a labelled high molecular weight component was produced with the result that these capsules failed to meet British Pharmacopoeia, BP, and United States Pharmacopoeia, USP, requirements for radiochemical purity well before their quoted expiry time. The nature of the impurity has not been identified but it is thought to be either iodinated gelatin or an iodinated capsule component.

Capsules↗

Mechanoreceptor evaluation of hip joint capsule and ligamentum capitis femoris in developmental hip dysplasia: a preliminary study.

We aimed to determine if there are mechanoreceptors in the hip joint capsule and ligamentum capitis femoris (LCF) of patients with developmental dysplasia of the hip (DDH). We took capsule and LCF biopsies from 20 hips of 20 patients who were operated on because of DDH. The mean age was 10.2 months (range 6-20 months) at the time of surgery. There were 12 girls and eight boys. Teratologic and secondary hip dislocations were not included in this study. Full thickness, 0.5 x 0.5 cm anterior capsule and LCF portions were taken for biopsy specimen. Specimens were stained with hemotoxylin eosin and examined immunohistochemically using monoclonal antibody against S-100 protein. In both analyses no mechanoreceptor was found in any samples of capsule or LCF. In this preliminary study we could not find mechanoreceptors in the local anterior joint capsule and LCF of the hip in children with DDH. We think that additional studies are necessary in order to understand the mechanoreceptor characteristics of the hip joint in children not only with DDH but also in children with healthy hips.

Biopsy, Needle↗

Immune reactions to Bacteroides fragilis populations with three different types of capsule in a model of infection.

The survival and growth of populations of the obligately anaerobic pathogenic bacterium Bacteroides fragilis enriched for large capsules (LCs), small capsules (SCs) or an electron-dense layer (EDL; non-capsulate by light microscopy) were examined in a mouse model of infection over a minimum period of 20 d. Chambers which allowed the influx of leukocytes, but not the efflux of bacteria, were implanted in the mouse peritoneal cavity. The LC and EDL populations consistently attained viable cell densities of the order of 10(8)-10(9) c.f.u. ml-1 within 24 h, whereas the SC population did not. However, after 3 d, all three bacterial populations maintained total viable numbers of 10(8)-10(9) c.f.u. ml-1 within the chambers. LC expression was selected against within 24 h in the model, the populations becoming non-capsulate by light microscopy, whereas in the SC population expression of the SC was retained by approximately 90% of the population. The EDL population remained non-capsulate by light microscopy throughout. Lymphocytes infiltrated the chambers to an equal extent for all three B. fragilis populations and at approximately 1000 times higher concentration than chambers which contained only quarter-strength Ringer's solution. The presence of neutrophils within the chambers did not cause a decrease in the total viable bacterial count. Each population elicited antibodies specific for outer-membrane proteins and polysaccharide, as detected by immunoblotting, which cross-reacted with the other populations. Differences were observed in the immunogenicity of the outer-membrane proteins within the three populations. Neutrophils were initially the predominant cell type in the chambers, but as the total leukocyte count increased with incubation time, neutrophils were outnumbered by other leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immobilization-based isolation of capsule-negative mutants of Streptococcus pneumoniae.

The capsular polysaccharide (CPS) is the most important identified virulence factor of Streptococcus pneumoniae, a human pathogen of the upper respiratory tract. One limitation in studies of S. pneumoniae surface virulence factors is the lack of a reliable procedure for isolation of capsule-negative mutants of clinical strains. This paper presents an approach, based on the immobilization of pneumococci in semi-liquid (0.04 % agar) medium, to easily distinguish and select for non-capsulated mutants. A clinical S. pneumoniae type 37 strain was used as a model to show that CPS production results in bacterial immobilization in semi-liquid agar medium and restricts cell sedimentation. Descendants of CPS(-) mutants sedimented faster under these conditions and therefore could be separated from immobilized parental cells. The CPS(-) phenotype of the obtained mutants was confirmed by both immunoagglutination and immunostaining experiments using specific type 37 capsular antibodies. Complementation of immobilization with the cloned tts gene, encoding type 37 CPS synthase, confirmed that faster sedimentation of mutants was specifically due to loss of the capsule. DNA sequence determination of three independent mutants revealed a point mutation, a 46 nt deletion and a heptanucleotide duplication in the tts gene. Immobilization of strains producing other CPSs (type 2, 3 and 6) also resulted in the appearance of CPS(-) mutants, thus showing that immobilization-based isolation is not restricted to type 37 pneumococci. Bacterial growth in semi-liquid medium proved to be a useful model system to identify the genetic consequences of immobilization. The results indicate that immobilization due to CPS may impose selective pressure against capsule production and thus contribute to capsule plasticity.

Agglutination Tests↗

Bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) and Ursofalk capsules measured by plasma pharmacokinetics and biliary enrichment.

BACKGROUND: Ursodeoxycholic acid is an approved therapy for hepatobiliary disorders but in infants and children compliance is compromised because it is formulated exclusively as capsules, or tablets. AIM: To determine the pharmacokinetics and bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) with a standard capsule (Ursofalk) in a randomized, unblinded, crossover designed study of 24 healthy adults. METHODS: Equivalence was based on single bolus oral plasma pharmacokinetics and biliary ursodeoxycholic acid enrichments after repeat doses. Biliary bile acid composition and hydrophobicity index were also compared. Ursodeoxycholic acid was measured in duodenal bile by high-performance liquid chromatography and in plasma by mass spectrometry. RESULTS: The mean percentage biliary ursodeoxycholic acid enrichment after administration of the suspension was not significantly different from that obtained with capsules (44.2 +/- 11.7% vs. 46.9 +/- 10.2%, respectively). The equivalence ratio was 0.94 (95% CI: 0.8-1.1), establishing bioequivalence between suspension and capsules. Both formulations reduced the biliary hydrophobicity index and no differences in bile acid composition were observed between formulations. The plasma pharmacokinetics of both formulations was similar and the tolerability of the suspension was excellent. CONCLUSIONS: A new liquid formulation of ursodeoxycholic acid suitable for paediatric patients is pharmacologically bioequivalent to capsules when given as single, or repeated oral doses.

Adolescent↗