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Biomedical subjects

V Mani

Publications and source records attributed to V Mani.

At least 37 records · Page 2Linked to original sources

Mesalazine release from coated tablets: effect of dietary fibre.

Delayed-release mesalazine formulations relay on pH-dependent coat dissolution to ensure delivery of 5-aminosalicylic acid (5-ASA) to the colon. As dietary fibre acidifies the colonic lumen we have studied the effect of fibre supplementation in 10 patients with quiescent colitis. Greater intake of dietary fibre was associated with a decrease in stool pH and an increase in stool frequency and faecal mass. However, the 24 h faecal and urinary excretion of 5-ASA and N-acetyl-5-ASA was unchanged. The percentage of total faecal ASA excreted as N-acetyl-5-ASA correlated with whole-gut transit time, suggesting that prolonged transit may be disadvantageous to patients with colitis as N-acetyl-5-ASA appears to be inactive.

Adult↗

Ring oxidized retinals form unusual bacteriorhodopsin analogue pigments.

Three ring oxidized retinal analogues have been isolated from the exhaustive oxidation of all-trans retinal. All-trans 4-oxoretinal and 2,3-dehydro-4-oxoretinal have similar absorption maxima to that of all-trans retinal and have been shown to be in the 6-s-cis conformation in solution. Pigments formed with bacterioopsin exhibit absorption maxima (520 nm) blue-shifted from that of bacteriorhodopsin (bR), indicating a disturbance of the external point charge by the electronegative carbonyl moiety at the 4 position. The third analogue contains a ring contracted to a cyclopentenyl-alpha,beta-dione. Unlike the majority of retinals, this analogue displays a 6-s-trans conformation in solution and has a red-shifted absorption maximum at 435 nm. The resulting bR analogue pigment (515 nm) is formed five times faster than the other oxoretinal pigments. All three oxoretinal pigments show an irreversible 20 nm blue shift upon exposure to white light. The 4-oxo and 2,3-dehydro-4-oxoretinal pigments, after irradiation, undergo a small reversible blue shift (4-8 nm) on dark adaptation. These two pigments pump protons, although with slowed photocycle kinetics, demonstrating that these structural changes (addition of the carbonyl at the C-4 and insertion of a double bond in the ring) do not block the function of the pigment. Extraction of the C-15 tritiated analogue retinals from illuminated and non-illuminated pigments of all three oxoretinals yield identical results. Therefore, any crosslinking of these oxoretinals to the protein is by linkages which are unstable to the extraction procedures.

Bacteriorhodopsins↗

Microscopic activity in ulcerative colitis: what does it mean?

To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse.

Adult↗

Transduction noise induced by 4-hydroxy retinals in rod photoreceptors.

New visual pigments were formed with 4-hydroxy retinals in isolated vertebrate rod photoreceptors by exposing bleached rods from the tiger salamander, Ambystoma tigrinum, to lipid vesicles containing the analogues. Formation of physiologically active pigment was demonstrated by the restoration of sensitivity and by a shift of approximately 50 nm in the peak of both the visual pigment absorptance spectrum and rod spectral sensitivity spectrum from approximately 520 to approximately 470 nm for 11-cis 4-hydroxy retinal. Membrane current recordings from the inner segments of isolated rods revealed excess fluctuations in membrane current after formation of the new pigment in bleached cells or after exposure of unbleached cells to flashes in the presence of the analogue. The excess current fluctuations are similar to the fluctuations elicited by steady light producing a few discrete responses per second, a rate approximately 100 times greater than the normal rate of spontaneous events in darkness. These results suggest that analogues of retinal can produce alterations in the frequency of production of discrete responses in darkness in rod photoreceptors.

Ambystoma↗

Why do patients with ulcerative colitis relapse?

To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Adolescent↗

Spin trapping of the superoxide anion: complications in the use of the water-soluble nitroso-aromatic reagent DBNBS.

Sodium 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS) is reported to be a useful spin trap for the measurement of superoxide anions in aqueous solution. However, the signal observed arises from interaction of the spin trap with some species other than the superoxide radical or hydrogen peroxide, a product of its dismutation, as the addition of both superoxide dismutase and catalase to a superoxide generating system failed to attenuate the signal. Therefore caution must be employed in the interpretation of results obtained using this spin trap.

Benzenesulfonates↗

A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis.

Sucralfate is well established in the treatment of upper gastrointestinal inflammation and ulceration, and preliminary evidence suggests it may be of benefit in active colitis. We have therefore undertaken a clinical trial to compare enemas of sucralfate (4 g) and prednisolone metasulphobenzoate (20 mg) in the treatment of active distal ulcerative colitis. Forty-four patients were entered into a 4-week study. Two patients were withdrawn because of non-compliance, and five were unable to complete the study: two developed constipation (both allocated to sucralfate) and three were unable to retain the enemas (two prednisolone and one sucralfate). Intention-to-treat analysis showed significant within-treatment improvement in rectal bleeding, sigmoidoscopic grade, and histologic grade in the prednisolone-treated group, and in stool frequency, rectal bleeding, and sigmoidoscopic grade in the sucralfate-treated group. Between-treatment comparisons, however, showed greater resolution of rectal bleeding and more marked improvements in histologic grade in patients treated with prednisolone metasulphobenzoate enemas. Further studies using higher doses of sucralfate would be useful.

Adult↗

Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis.

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.

Adult↗

Delayed-release mesalazine (5-aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

1. Delayed-release mesalazine has been formulated to deliver 5-aminosalicylic acid to the colon. We have therefore studied the ileostomy excretion and coat dissolution of this preparation. 2. Following ingestion of a single tablet 88% (range 69-114%) of the 400 mg dose appeared unchanged in the ileosomy effluent over the subsequent 12 h. 3. Ileostomy effluent pH appeared to be a major determinant of 5-aminosalicylic acid release. 4. In vitro studies revealed rapid coat dissolution above pH 7.0, slow dissolution between pH 6.0 and 7.0 and non-dissolution at pH 2.0 and 4.0.

Adult↗

Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.

Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function.

Adult↗

Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution.

Seminal abnormalities are commonly found during sulphasalazine treatment. Although these changes appear reversible after drug withdrawal this may result in colitis relapse. Animal studies suggest that 5-aminosalicylic acid, the active component of sulphasalazine, does not impair fertility. Sixteen patients with quiescent ulcerative colitis were studied. Each patient produced three samples of semen at weekly intervals. Of the 48 samples analysed 39.6% showed oligospermia, 41.7% showed an increased number of abnormal forms and 91.7% showed impaired motility. Nine patients substituted enteric coated mesalazine (5-aminosalicylic acid) for sulphasalazine for a minimum period of three months. During this time one patient developed a salmonella associated colitis relapse; the others remained well. Improvement in sperm count (p less than 0.02), motility (p less than 0.001) and morphology (p less than 0.02) occurred in all cases. To date, four successful pregnancies have resulted, three in couples complaining of long term infertility. Treatment with enteric-coated mesalazine allows the recovery of seminal abnormalities induced by sulphasalazine in patients with colitis.

Adult↗

Colonic involvement in salmonellosis.

Although small intestine is generally regarded as the principal site involved in human salmonella infection of food-poisoning type, the pathophysiology of salmonella diarrhoea remains obscure. A sigmoidoscopic and biopsy study of 23 hospital inpatients with acute salmonella infection revealed presence of active colitis in 21. It is suggested that colonic involvement is common in human salmonellosis and probably plays an important role in the causation of diarrhoea.

Adolescent↗

Treatment of ulcerative colitis with oral disodium cromoglycate. A double-blind controlled trial.

Twelve patients with ulcerative protocolitis were treated for six months with each of oral disodium cromoglycate (2 g/day) and placebo in a double-blind cross-over trial. The active drug significantly improved the patients' sense of well-being and the signoidoscopic and rectal biopsy appearances. Orally administered disodium cromoglycate may have a place in the long-term management of colitis.

Administration, Oral↗

Mast cells and immunoglobulin E in inflammatory bowel disease.

The numbers of mast cells and of IgE-containing immunocytes in the bowel wall of patients suffering from Crohn's disease of ulcerative colitis have been estimated and the results compared with those found in normal control specimens. In ulcerative colitis there is a slight rise in the number of mast cells and it appears that these participate in the inflammatory process in a non-specific manner; the number of IgE-containing immunocytes is not significantly altered. In Crohn's disease there is an almost total absence of stainable mast cells in affected areas of the bowel, together with a marked decrease in IgE-containing immunocytes. It is suggested that these findings are due to degranulation of mast cells and consumption of IgE as a result of an immediate hypersensitivity reaction in the bowel wall, this being one component of the protein inflammatory and immunological response to the entry of a variety of antigenic material.

Antibody-Producing Cells↗