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Biomedical subjects

S Somasundaram

Publications and source records attributed to S Somasundaram.

At least 19 recordsLinked to original sources
PubMed1998

Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.

BACKGROUND: The predicted gastrointestinal tolerability of specific cyclooxygenase-2 inhibitors could be due to either a lack of 'topical' irritation and/or lack of effect on cyclooxygenase-1. METHODS: Key pathophysiologic steps (in vitro and in vivo uncoupling, intestinal prostanoid levels (prostaglandin E, thromboxane B2, and 6-keto-prostaglandin F1alpha), intestinal permeability (51Cr-ethylenediaminetetraacetic acid), inflammation (faecal excretion of a granulocyte marker protein), and ulcer counts) in enteropathy induced by nonsteroidal anti-inflammatory drugs were assessed after administration of indomethacin, 10 mg/kg, and 15 (roughly equipotent), 30, and 60 mg/kg of the preferential cyclooxygenase-2 inhibitor nimesulide. RESULTS: Indomethacin uncoupled oxidative phosphorylation at lower concentrations than nimesulide in vitro. Indomethacin was associated with electron microscopy changes suggestive of uncoupling in 60%-70% of enterocytes examined, whereas nimesulide affected 10%-30% of enterocytes, depending on the dose. Indomethacin increased intestinal permeability and caused inflammation and ulcers with 71%-96% reductions in prostanoid levels. Nimesulide at 15 mg/kg caused no damage, whereas 30 and 60 mg/kg nimesulide were associated with significant decreases in mucosal prostanoids (46%-75%), but only the 60-mg/kg dose caused a transient increase in intestinal permeability. However, at none of the doses did nimesulide cause intestinal inflammation or ulcers. CONCLUSIONS: These results endorse the idea that selective cyclooxygenase-2 inhibitors may be associated with some gastrointestinal tolerance due to their selectivity for cyclooxygenase-2, inhibiting cyclooxygenase-1 at only very high doses, and reduced topical irritation.

Animals↗
PubMed1998

Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage by a non-prostaglandin (PG) dependent "topical" action and by inhibiting cyclooxygenase. AIMS: To discriminate between these two effects by studying some key pathophysiological steps in NSAID enteropathy following administration of (R)- and (S)-flurbiprofen, the racemic mixture, and an uncoupler, dinitrophenol. METHODS: The effects of dinitrophenol, racemic, (R)-, and (S)-flurbiprofen on mitochondria were assessed in vitro and on key pathophysiological features of small intestinal damage in vivo (ultrastructure by electron microscopy, mucosal prostanoid concentrations, intestinal permeability, inflammation, and ulcer count) in rats. RESULTS: All the drugs uncoupled mitochondrial oxidative phosphorylation in vitro, caused mitochondrial damage in vivo, and increased intestinal permeability. Dinitrophenol and (R)-flurbiprofen caused no significant decreases in mucosal prostanoid concentrations (apart from a decrease in thromboxane (TX) B2 concentrations following (R)-flurbiprofen) while racemic and (S)- flurbiprofen reduced mucosal prostanoids significantly (PGE, TXB2, and 6-keto-PGF1alpha concentrations by 73-95%). Intestinal inflammation was significantly greater following administration of (S)-flurbiprofen and racemate than with dinitrophenol and (R)-flurbiprofen. No small intestinal ulcers were found following dinitrophenol or (R)-flurbiprofen while both racemic and (S)-flurbiprofen caused numerous ulcers. CONCLUSIONS: Dinitrophenol and (R)-flurbiprofen show similarities in their actions to uncouple mitochondrial oxidative phosphorylation in vitro, alter mitochondrial morphology in vivo, increase intestinal permeability, and cause mild inflammation without ulcers. Concurrent severe decreases in mucosal prostanoids seem to be the driving force for the development of severe inflammation and ulcers.

Animals↗
PubMed1997

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗
PubMed1997

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗
PubMed1996

Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease.

BACKGROUND: The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown. AIMS: To design a non-invasive technique for the localisation of altered gastrointestinal permeability to 51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time profiles in serum of a series of simultaneously ingested indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA. SUBJECTS: Five normal controls, six patients with untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which entailed the simultaneous ingestion of the above four test substances followed, during the next 24 hours, by timed serial collection of urine and serum for marker analysis. RESULTS: Urinary excretion of 51CrEDTA was significantly increased in all patient groups. Analysis of serum appearances and profiles of the markers suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative colitis. CONCLUSION: A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.

Adult↗
PubMed1995

Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

Adult↗
PubMed1994

Comparison of enteral feeding and total parenteral nutrition after liver transplantation.

Total parenteral nutrition is used for nutritional support in patients undergoing orthotopic liver transplantation but is associated with complications. We compared the efficacy and tolerability of early enteral feeding with total parenteral nutrition after liver transplantation. 24 patients were studied: 14 received enteral feeding and 10 total parenteral nutrition. A double-lumen enteral tube was used to deliver the feed directly into the jejunum with the second lumen of the tube being used for gastric aspiration. Enteral feeding was started post-operatively within 18 h, was well-tolerated, and of comparable efficacy to total parenteral nutrition. The median number of days for patients to start eating (4) and to achieve 70% of estimated requirements orally (5) did not differ significantly between the two groups. Mid-arm circumference, triceps skinfold thickness, and biceps skinfold thickness were, by comparison with pre-operative values, maintained on the tenth postoperative day in both groups. Early postoperative absorptive capacity, as assessed by a combined carbohydrate test, was reduced significantly in both groups but insufficiently to be of nutritional concern. Intestinal mucosal integrity, as assessed by an intestinal permeability test, was maintained throughout. We conclude that the practical aspects of enteral feeding after liver transplantation are surmountable and that enteral feeding is as effective at maintaining nutritional status as total parenteral nutrition, and has potential benefits in terms of reduced complications and costs.

3-O-Methylglucose↗
PubMed1994

The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass.

BACKGROUND/AIMS: Mean arterial pressure is reduced during hypothermic cardiopulmonary bypass. The aim of this study was to assess whether this was associated with intestinal hypoperfusion and whether it affected intestinal absorption and permeability. METHODS: Twenty-six patients undergoing coronary artery bypass grafting underwent an intestinal absorption-permeability test involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler blood flow were measured perioperatively in eight patients. RESULTS: Hypothermic (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6% reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose) carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose) transport in the immediate postoperative period, respectively. The differential urine excretion of lactulose/L-rhamnose increased sixfold. All parameters returned to control levels by the fifth postoperative day. CONCLUSIONS: Cardiopulmonary bypass, while maintaining generally acceptable levels of hemodynamic performance, is associated with significant intestinal hypoperfusion and malabsorption of monosaccharides, which may have implications for enteral drug treatment in the immediate postoperative period.

Adult↗
PubMed1993

Cardiopulmonary bypass impairs small intestinal transport and increases gut permeability.

Gastrointestinal damage occurs in 0.6% to 2% of patients after cardiopulmonary bypass (CPB), and carries a mortality of 12% to 67%. The incidence of subclinical gastrointestinal damage may be much greater. We examined the effects of nonpulsatile, hypothermic CPB on intestinal absorption and permeability in 41 patients. Bowel mucosal saccharide transport and permeation were evaluated using 100 mL of an oral solution containing 3-O-methyl-D-glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and lactulose (5.0 g) to assess active carrier-mediated, passive carrier-mediated, transcellular, and paracellular transport, respectively, with a 5-hour urine analysis. Patients were studied before, immediately after, and 5 days after CPB. Immediately after CPB there was a decrease in urinary excretion of 3-O-methyl-D-glucose (from 34% +/- 2.2% to 5.2% +/- 0.7%; p < 0.0001), D-xylose (from 25.4% +/- 1.4% to 4.1% +/- 0.8%; p < 0.0001), and L-rhamnose (from 8.3% +/- 0.6% to 2.6% +/- 0.4%; p < 0.0001). The permeation of 3-O-methyl-D-glucose and D-xylose returned to normal levels 5 days after CPB, but that of L-rhamnose remained significantly below pre-CPB values at 6.6% +/- 0.5% (p = 0.004). However, the permeation of lactulose increased after CPB (from 0.35% +/- 0.04% to 0.59% +/- 0.1%; p = 0.018), and the lactulose/L-rhamnose gut permeability ratio increased markedly (from 0.045 +/- 0.04 to 0.36 +/- 0.08; normal = 0.06 to 0.08; p = 0.004). Patients who had a CPB time of 100 minutes or more had a greater increase in gut permeability (p = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1988

Density and radioactivity distribution of respirable range human serum albumin aerosol.

Dry human serum albumin (HSA) aerosol in the respirable size range was generated using the BARC nebulizer. The aerosol was sampled using Lovelace Aerosol Particle Separator (LAPS) and the density of HSA was determined. Labelling of HSA with 99mTcO4- was done, both in HSA solution and with dry denatured HSA particles, to study the distribution of radioactivity in both cases. The results are discussed in the paper.

Isotope Labeling↗
PubMed1986

The role of mitochondrial calcium transport during inflammation and the effect of anti-inflammatory drugs.

The effects of inflammation induced by the inoculation of rats with Freund's adjuvant on calcium transport by isolated rat liver mitochondria and on mitochondrial in vivo protein synthesis were investigated. Mitochondria isolated from the liver of inflamed rats exhibited (i) a reduction in 45Ca2+ uptake and, (ii) a reduction in protein synthesis. Addition of ATP to the calcium uptake medium stimulate the uptake in inflamed rat liver mitochondria. After inflammation was controlled by treatment with a mixture of Clerodendron inerme flavonoidal glycosides and indomethacin, rat liver mitochondria showed (i) an increase in 45Ca2+ uptake and, (ii) an increase in mitochondrial in vivo protein synthesis. The mechanism of mitochondrial calcium transport and the mitochondrial protein metabolism during inflammation and after treatment with anti-inflammatory drugs were discussed.

Adenosine Triphosphate↗
PubMed1986

Radium-226 body burden in U miners by measurement of Rn in exhaled breath.

Uranium miners were made to inhale Rn-free medical O2 and exhale through a 5.2-1 A1 chamber before reporting to work. The chamber was sealed and isolated from the sampling circuit. An electrostatic plate collected the freshly formed Rn-decay products. The subsequent programmed alpha counting of the plate yielded a Rn concentration in the exhaled breath. Assuming that the exhaled breath represents a certain fraction of the Rn produced inside the body, the body burden of 226Ra was calculated. Standardisation of this procedure and the data collected on 310 miners are discussed. The procedure is simple and applicable for routine measurements. The miner needs to be in the laboratory for only 10 min. The system is also portable for field application. For routine use, the minimum detectable concentration is 3.87 Bq X m-3 which corresponds to a body burden of 0.26 kBq in a typical miner, if one assumes the Rn release fraction from the body as 84%. The system offers a more convenient and sensitive alternative to whole-body counting of workers for 226Ra.

Body Burden↗
PubMed1986

Measurement of 220Rn in exhaled breath of Th plant workers.

The concentration of 220Rn in the exhaled breath of workers currently employed in a Th plant was measured using a double filter system. The results are expressed in terms of the equivalent activity of 224Ra freely emanating 220Rn at the mouth. Measurements performed on 176 subjects, without isolating them from day-to-day work, showed 220Rn levels having a median of 0.74 Bq, with the group consisting of sweepers and helpers showing the highest average level (1.68 Bq). Measurements performed on 15 selected workers, after isolating them from work for a minimum duration of 48 h yielded 220Rn levels which were consistently lower than those obtained in the first measurements. This is attributed to the material undergoing short term elimination from the body. It was also found from the latter measurements that the group consisting of workers engaged in radioactive work for more than 24 y has an average 220Rn level of 2.65 Bq which is significantly higher than that (1.27 Bq) found in the group that has worked for less than 12 y. A conversion factor of 0.09 deduced by earlier investigators is assumed to be valid for estimating the actual 224Ra burdens from the 220Rn data.

Body Burden↗
PubMed1984

Concentrations of four essential trace elements in breast milk of mothers from two socio-economic groups: preliminary observations.

Concentrations are reported for Cu, Mn, Mo and Zn in human milk samples obtained from mothers belonging to low and middle per capita family income groups. The trace element levels in milk of both groups are compared for samples obtained at two stages, viz. 3-5 days and 4-6 weeks post partum. Although the Mn level during the first stage appears to be lower in samples from the low income group, the difference is not statistically significantly (p less than or equal to 0.01). However, at 4-6 weeks post partum, Zn is significantly lower (p less than or equal to 0.01) in milk of mothers belonging to this group.

Copper↗
PubMed1983

In vitro absorption of [14C]leucine during inflammation and the effect of antiinflammatory drugs in the jejunum of rats.

1. Inflammation was induced in the hindlegs of rats by formalin injection and the in vitro absorption of [14C]leucine was studied. 2. Treatment of rats with formalin caused a reduction in the in vitro absorption of leucine from the mucosa of jejunum. 3. Oral administration of oxyphenbutazone or a herbal anti-inflammatory drug (Withania somnifera) prior to formalin injection resulted in no alteration in the jejunal absorption of [14C]leucine.

Animals↗