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Biomedical subjects

B S Ramakrishna

Publications and source records attributed to B S Ramakrishna.

At least 19 recordsLinked to original sources
PubMed2006

Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea.

BACKGROUND: Oral rehydration solution (ORS) for treatment of diarrhea relies on enhancement of small intestinal sodium and fluid absorption to correct dehydration. Amylase-resistant starch added to ORS significantly reduced the duration and severity of diarrhea in adults with cholera, presumably by generation of short-chain fatty acids in the colon and enhancement of colonic sodium and fluid absorption. The present study was initiated to determine whether addition of amylase-resistant starch to standard World Health Organization glucose-ORS (G-ORS) would reduce the duration of diarrhea and fecal fluid losses in children with acute diarrhea. METHODS: One hundred eighty-three children (6 months to 3 years) with acute watery diarrhea were randomized to receive either standard treatment with G-ORS or G-ORS with additional amylase-resistant starch, HAMS (HAMS-ORS, 50g/L). Stool weight and consistency were monitored serially until development of formed stool or development of treatment failure defined as either the need for unscheduled intravenous fluid therapy or diarrhea longer than 72 hours. RESULTS: Five of the subjects were lost to follow up. In 178 remaining children (87 HAMS-ORS and 91 G-ORS) with evaluable data, time from enrolment to last unformed stool was significantly less in children receiving HAMS-ORS (median, 6.75 hours; 95% confidence interval, 4.27-9.22) than in children treated with G-ORS (12.80 hours, 8.69-16.91) (P = 0.0292). Time to first formed stool was also significantly shorter in children receiving HAMS-ORS (median, 18.25 hours; 95% confidence interval, 13.09-23.41) compared with children receiving G-ORS (median, 21.50 hours; 95% confidence interval, 17.26-25.74) (P = 0.0440). The total amount of ORS consumed was similar in both groups. There was a trend toward lower mean stool weight in first 24 hours (P = 0.0752) as well as total diarrheal stool weight (P = 0.0926) in patients in the HAMS group compared with the G-ORS group. CONCLUSION: In children with acute diarrhea, the addition of amylase-resistant starch to glucose ORS significantly shortened duration of diarrhea compared with standard treatment.

Acute Disease↗
PubMed2006

Tropical malabsorption.

Malabsorption is an important clinical problem both in visitors to the tropics and in native residents of tropical countries. Infections of the small intestine are the most important cause of tropical malabsorption. Protozoal infections cause malabsorption in immunocompetent hosts, but do so more commonly in the setting of immune deficiency. Helminth infections occasionally cause malabsorption or protein-losing enteropathy. Intestinal tuberculosis, chronic pancreatitis and small-bowel bacterial overgrowth are important causes of tropical malabsorption. In recent years, inflammatory bowel disease and coeliac disease have become major causes of malabsorption in the tropics. Sporadic tropical sprue is still an important cause of malabsorption in adults and in children in South Asia. Investigations to exclude specific infective, immunological or inflammatory causes are important before considering tropical sprue as a diagnosis. This article briefly reviews the management of tropical sprue and presents an algorithm for its investigation and management.

Bacterial Infections↗
PubMed2005

Characterization of soluble FAS, FAS ligand and tumour necrosis factor-alpha in patients with chronic HCV infection.

BACKGROUND: There are limited reports on the role of the cell surface receptor Fas and its ligand molecule in mediating apoptosis during infection with the hepatitis C virus (HCV). OBJECTIVES: The aims of this study were (1) to assess the susceptibility of the Fas antigen expressed on peripheral blood mononuclear cells to Fas ligand-induced-death in patients with chronic HCV infection and (2) to investigate the correlation between the plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumour necrosis factor-alpha (TNF-alpha), alanine amino transferase (ALT), and HCV viral load. STUDY DESIGN: The susceptibility of peripheral blood mononuclear cells from 17 subjects with chronic HCV infection to Fas ligand induced cell death was assessed using a water soluble tetrazolium assay. The plasma levels of associated markers such as sFas, sFasL, and TNF-alpha were quantified using immunoassays. ALT values were obtained from hospital records. Viral loads were quantified using a commercially available quantitative assay--the Amplicor Monitor (version 2.0). Controls for comparison included a group of healthy individuals and individuals infected with the human immunodeficiency virus 1. RESULTS: The percentage of cell death induced in hepatitis C virus infected individuals was lower than that seen in the healthy control group. Patients infected with HCV had higher average values of sFas and TNF-alpha as compared to both control groups. Plasma levels of sFas in patients with chronic HCV infection showed significant positive correlations to ALT and TNF-alpha levels. TNF-alpha levels also showed a significant positive correlation with ALT levels. CONCLUSIONS: PBMC in HCV infection exhibit decreased susceptibility to Fas ligand induced cell death. This may signify a means by which HCV escapes immune surveillance. This phenomenon merits further investigation. The strong correlations observed between plasma sFas, ALT and TNF-alpha suggest a potential role for these markers as an alternative to an invasive liver biopsy.

Acquired Immunodeficiency Syndrome↗
PubMed2004

HCV genotype 4--an emerging threat as a cause of chronic liver disease in Indian (south) patients.

BACKGROUND: Hepatitis C virus (HCV) genotyping is relevant for the delivery of effective antiviral therapy. HCV genotypes are geographically restricted with genotype 4, which is resistant to therapy, traditionally considered to be confined to the Middle East and Africa. We report here on the occurrence of HCV genotype 4 in Indian (South) patients. OBJECTIVES: 1) To highlight the occurrence of HCV genotype 4 in the patient population attending a tertiary care hospital in south India. 2) To ascertain the difference in HCV viral loads and alanine aminotransferase (ALT) values between patients infected with HCV genotype 4 and those infected with the other two most commonly detected genotypes in this patient population viz., HCV genotypes 1 and 3. 3) To assess the genetic relatedness of the Indian strains to Genbank sequences, which we report for the first time. STUDY DESIGN: The study group consisted of 125 HCV infected, untreated patients who had been genotyped using type specific primers. Eight of the nine samples classified as HCV genotype 4 by this technique were subjected to nucleotide sequencing. Viral load estimations were carried out. Information on possible risk factors and ALT values were obtained from hospital records. Statistical analyses were carried out to compare viral loads and ALT values across genotypes. A phylogenetic tree was constructed and the genetic relatedness of the strains was assessed through sequence analysis. RESULTS: HCV genotype 4 was detected in nine of 125 (7.2%) patients. Eight of the nine were subjected to nucleotide sequencing and all strains were confirmed as HCV genotype 4. Six of the eight strains were closely related, with two strains being phylogenetically diverse. CONCLUSIONS: HCV genotype 4 is detected in a significant minority of HCV infected patients in India. This finding should be considered in designing strategies prior to initiation of therapy in Indian patients infected with HCV.

Adult↗
PubMed2003

Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB.

Butyrate enemas have been demonstrated to ameliorate inflammation in ulcerative colitis. The mechanism of this protective effect of butyrate is not known, and this study examines the effect of butyrate on epithelial function, inducible heat shock protein 70 (HSP70) expression, and NF-kappaB activation in experimental colitis. Colitis was induced in rats by oral dextran sulfate sodium (DSS) and by butyrate or saline enemas. Mucosal barrier function was assessed by electrical resistance and [14C]mannitol permeability. HSP70 production was determined by [35S]methionine labeling, Western blot analysis, and immunohistochemistry. Activation of heat shock factors (HSFs) and NF-kappaB was evaluated by EMSA. Butyrate showed a significant protection against the decrease in cell viability, increase in mucosal permeability, and polymorphonuclear neutrophil infiltration seen in DSS colitis. Butyrate inhibited HSP70 expression in DSS colitis and also inhibited the activation of HSF and NF-kappaB. Thus butyrate enema was found to be cytoprotective in DSS colitis, an effect partly mediated by suppressing activation of HSP70 and NF-kappaB.

Animals↗
PubMed2003

Distribution of the different genotypes of HCV among patients attending a tertiary care hospital in south India.

BACKGROUND: Genotyping of the hepatitis C virus (HCV) and assessment of viral load is important for designing therapeutic strategies and region specific diagnostic assays. OBJECTIVES: To determine the distribution of HCV genotypes among patients attending a tertiary care hospital in south India, and to correlate this with viral load. STUDY DESIGN: Ninety HCV RNA positive patients were recruited for the study. HCV genotyping was carried out using type-specific primers from the core region of the viral genome [J. Clin. Microbiol. 35 (1997) 201]. Viral load estimations were carried out using the Amplicor HCV Monitor (Versions 1.5 and 2, Roche Diagnostics, Branchburg, NJ, USA). Clinical details were elicited from patients' hospital records. RESULTS: Genotype 3 was detected most frequently (62.2%) followed by infection with HCV genotype 1 (18.8%). There was no significant difference seen in alanine aminotransferase (ALT) values between the two genotypes. Genotype 1 was associated with a significantly higher viral load as compared with genotype 3 (P=0.001). Parenteral transmission accounted for 61% of all infection caused. Infection with genotype 1 was significantly associated with a history of haemodialysis (P=0.01). Genotype 3 was detected more frequently in patients from east India, as compared with its detection in patients from south India (P=0.004). Similarly, genotype 1 was detected with greater frequency in individuals from south India as compared with patients from east India (P=0.004). The concordance between Ohno's genotyping assay and nucleotide sequencing, for genotypes 1 and 3, was 75%. CONCLUSIONS: HCV genotypes 1 and 3 accounted for 81% of HCV infections in patients from this geographical region. HCV genotype distribution showed regional differences and genotype 1 was associated with higher viral loads. Parenteral transmission was the major route for acquisition of HCV infection. Ohno's type-specific primer based genotyping assay can be used for distinguishing between HCV genotype 1 and non-1 HCV genotypes in laboratories that do not possess nucleotide sequencing facilities.

Adolescent↗
PubMed2003

Faecal lactoferrin as a predictor of positive faecal culture in south Indian children with acute diarrhoea.

Faecal lactoferrin, an iron-based glycoprotein found concentrated in secondary granules of neutrophils, may serve as a surrogate marker of inflammation in the intestine. We evaluated the usefulness of faecal lactoferrin as a predictor of infection with invasive enteropathogens in 262 children with diarrhoea. Lactoferrin at a dilution of 1:50 had the highest sensitivity for detection not only of conventionally cultured invasive enteropathogens but also of all other enteropathogens. Neither individual clinical symptoms nor the identification of faecal leucocytes by microscopy significantly predicted isolation of invasive enteropathogens from the faeces of children with diarrhoea. Faecal lactoferrin is a simple test which showed promise in predicting which children with diarrhoea are likely to be infected with invasive pathogens and can be incorporated as a screening test before faecal cultures are undertaken in this population.

Acute Disease↗
PubMed2002

Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon.

Short chain fatty acids, particularly butyrate, stimulate electroneutral NaCl absorption from the colon. Their effect in colonic epithelia lacking basal electroneutral NaCl absorption is unknown. Butyrate is also reported to inhibit active Cl- secretion in the colon. The present studies were undertaken to investigate the inter-relationships between the effects of butyrate on active Na+ and Cl- transport in the colon. Studies were carried out in rabbit distal colon (known to have predominant electrogenic Na+ absorption), rat distal colon (characterised by electroneutral Na+ absorption), and hyperaldosteronaemic rat distal colon (characterised by electrogenic Na+ absorption). The effect of cholera toxin (CT) was also noted. Potential difference, short-circuit current (I(SC)) and fluxes of Na+ and Cl- were measured in stripped mucosa under voltage-clamp conditions. Butyrate stimulated electroneutral Na+ and Cl- absorption in distal colon of normal and salt-depleted rats, and stimulated Na+ absorption in rabbit distal colon. Amiloride (10(-4) M) or CT did not inhibit this process. In rabbit distal colon, stimulation of Na+ absorption by butyrate was not dependent on the presence of Cl- in the medium. Butyrate significantly decreased conductance, decreased flux of sodium from serosa to mucosa (particularly in rabbit distal colon), and decreased I(SC). Net Cl- secretion, induced by CT, was completely inhibited by butyrate. Stimulation of Na+ absorption was independent of exposure to CT. Bumetanide reversed net Cl- secretion to net absorption, but did not alter Na+ or Cl- fluxes in tissues exposed to butyrate. Thus butyrate stimulates active Na+ absorption in colonic epithelia, with or without expression of basal Na+-H+ exchange. Independently, butyrate inhibits active Cl- secretion induced by cAMP in these epithelia.

Absorption↗
PubMed2001

Towards a better oral rehydration fluid.

Improvements in characteristics of solutions used for oral rehydration therapy, to provide significant reductions in amount and duration of diarrhea, are expected to contribute to wider use of these fluids. Recent studies suggest that these may come about from reducing the osmolality of the solution, and by providing short chain fatty acids for better fluid absorption from the colon. This article briefly reviews the physiology of intestinal and colonic absorption in diarrhea, and indicates the further studies that are needed to translate the above advances into universal practice for the treatment of diarrhea.

Child↗
PubMed2001

Epidemiological and laboratory investigations of outbreaks of diarrhoea in rural South India: implications for control of disease.

Two epidemics of acute, watery diarrhoea in villages in North Arcot district, India, were investigated. The attack rates were 10.03 and 15.53 per 100 population, the median duration was 5 days and enteric pathogens were present in 56.8% and 60.3% of specimens from the two villages, but no predominant pathogen was identified. Examination of stools from a 20% age-stratified random sample of the population of one of the villages after the epidemic found 22.9% of asymptomatic subjects excreted bacterial enteric pathogens. Despite the high background of enteric pathogen carriage, the isolation rates for shigellae, enteropathogenic Escherichia coli and Shiga-toxin producing E. coli were significantly higher (P < 0.001, P < 0.02, P < 0.05) during the epidemic. The epidemics may have been caused by faecal contamination of well water following rain. Point-of-use techniques for water disinfection may be most effective for preventing such outbreaks, but further research into the development of appropriate technology is required.

Adolescent↗
PubMed2000

Amylase-resistant starch plus oral rehydration solution for cholera.

BACKGROUND: Although standard glucose-based oral rehydration therapy corrects the dehydration caused by cholera, it does not reduce the diarrhea. Short-chain fatty acids, which are produced in the colon from nonabsorbed carbohydrates, enhance sodium absorption. We conducted a study to determine the effects of an orally administered, nonabsorbed starch (i.e., one resistant to digestion by amylase) on fecal fluid loss and the duration of diarrhea in patients with cholera. METHODS: We randomly assigned 48 adolescents and adults with cholera to treatment with standard oral rehydration therapy (16 patients), standard therapy and 50 g of rice flour per liter of oral rehydration solution (16 patients), or standard therapy and 50 g of high-amylose maize starch, an amylase-resistant starch, per liter of oral rehydration solution (16 patients). The primary end points were fecal weight (for every 12-hour period during the first 48 hours after enrollment) and the length of time to the first formed stool. RESULTS: The mean (+/-SD) fecal weights in the periods 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours after enrollment were significantly lower in the resistant-starch group (2206+/-1158 g, 1810+/-1018 g, and 985+/-668 g) than in the standard-therapy group (3251+/-766 g, 2621+/-1149 g, and 2498+/-1080 g; P=0.01, P= 0.04, and P=0.001, respectively). From 36 to 48 hours after enrollment, fecal weight was also significantly lower with the resistant-starch therapy than with the rice-flour therapy (985+/-668 g vs. 1790+/-866 g, P=0.01). The mean duration of diarrhea was significantly shorter with the resistant-starch therapy (56.7+/-18.6 hours) than with standard therapy alone (90.9+/-29.8 hours, P=0.001) or the rice-flour therapy (70.8+/-20.2 hours, P=0.05). Fecal excretion of starch was higher with the resistant-starch therapy (32.6+/-30.4) than with the standard therapy (11.7+/-4.1 g, P=0.002) or the rice-flour therapy (15.1+/-8.4 g, P=0.01). CONCLUSIONS: The addition of a resistant starch to oral rehydration solution reduces fecal fluid loss and shortens the duration of diarrhea in adolescents and adults with cholera.

Adolescent↗
PubMed2000

Increased permeability in dextran sulphate colitis in rats: time course of development and effect of butyrate.

BACKGROUND: Increased mucosal permeability is an important factor in the genesis of mucosal inflammation in inflammatory bowel disease. This study examined the time course of increased permeability and the effect of butyrate on permeability in experimental colitis in rats. METHODS: Colitis was induced in albino rats by administration of 4% dextran sulphate sodium (DSS) orally for up to 7 days. Rats were killed sequentially after 1-7 days of DSS feeding and compared with control animals. Distal colon sheets, from normal and DSS rats, were mounted in Ussing chambers. Electric resistance and passive permeation of 14C-mannitol were measured over 90 min. In control and 5-day DSS rats additional permeability measurements were made in the presence of butyrate (25 mmol/l) in the bathing solutions. The permeability of the normal distal colon was measured after addition of DSS in vitro. Sections of colon were examined by light microscopy. The viability of colonocytes, from normal and DSS rat colon, was measured by release of lactate dehydrogenase immediately and during a 60-min incubation after isolation. RESULTS: Focal mild inflammation and shedding of epithelium were noted after 2 days of DSS administration; crypt loss with flattened epithelium in adjacent areas after 5 days; and fibrosis after 7 days. Decreased epithelial cell survival after 60 min of incubation was noted after 1 day of DSS administration, whereas decreased viability at the time of isolation was noted after 2 days of DSS administration (viability, 72.7% +/- 1.4%; mean +/- standard error) compared with control (89.3% +/- 0.8%) (P < 0.01). Increased permeability was noted after 1 day of DSS administration. Electric resistance (mu omega/cm2/h) was significantly reduced after 1 day of DSS administration to 85.9 +/- 4.6 (mean +/- standard error) compared with control animals (117.2 +/- 2.2; P < 0.001). Serosa-mucosa flux of mannitol (micromol/cm2/h) was also significantly increased after 1 day of DSS feeding (0.169 +/- 0.01) compared with control (0.061 +/- 0.08) (P < 0.01). Electric resistance and mannitol permeability were significantly returned towards normal by the presence of butyrate. DSS added directly to the bathing solution did not significantly alter the colon permeability in vitro. CONCLUSIONS: Increased mucosal permeability is a very early change in colitis induced by DSS, is accompanied by decreased cell survival, and precedes detectable changes in histology. Reversal of increased mucosal permeability by butyrate may explain its utility in the therapy of inflammatory disease of the colon.

Animals↗
PubMed2000

Butyrate and glucose metabolism by colonocytes in experimental colitis in mice.

BACKGROUND/AIMS: Impaired colonocyte metabolism of butyrate has been implicated in the aetiopathogenesis of ulcerative colitis. Colonocyte butyrate metabolism was investigated in experimental colitis in mice. METHODS: Colitis was induced in Swiss outbred white mice by oral administration of 4% dextran sulphate sodium (DSS). Colonocytes isolated from colitic and normal control mice were incubated with [(14)C]butyrate or glucose, and production of (14)CO(2), as well as of intermediate metabolites (acetoacetate, beta-hydroxybutyrate and lactate), was measured. The effect of different substrate concentrations on oxidation was also examined. RESULTS: Butyrate oxidation (micromol/h per mg protein; mean (SEM)) was significantly reduced in DSS colitis, values on day 7 of DSS administration being 0.177 (0.007) compared with 0.406 (0.035) for control animals (p<0.001). Glucose oxidation (micromol/h per mg protein; mean (SEM)) on day 7 of DSS administration was significantly higher than in controls (0.06 (0.006) v 0.027 (0.004), p<0.001). Production of beta-hydroxybutyrate was decreased and production of lactate increased in DSS colitis compared with controls. Increasing butyrate concentration from 10 to 80 mM enhanced oxidation in DSS colitis (0.036 (0.002) to 0.285 (0.040), p<0.001), although it continued to remain lower than in controls. Surface and crypt epithelial cells showed similar ratios of butyrate to glucose oxidation. When 1 mM DSS was added to normal colonocytes in vitro, it did not alter butyrate oxidation. The initial histological lesion of DSS administration was very patchy and involved crypt cells. Abnormal butyrate oxidation became apparent only after six days of DSS administration, at which time histological abnormalities were more widespread. CONCLUSIONS: Colonocyte metabolism of butyrate, but not of glucose, is impaired in DSS colitis, and may be important in pathophysiology. Histological abnormalities preceded measurable defects in butyrate oxidation.

Animals↗
PubMed1999

Stimulation of sodium chloride absorption from secreting rat colon by short-chain fatty acids.

Inhibition of electroneutral NaCl absorption by cyclic adenosine monophosphate (cAMP) results in fluid malabsorption in cholera. Short-chain fatty acids (SCFA) stimulate electroneutral NaCl absorption from the colon. The present study investigated effects of elevated cAMP on SCFA-stimulated NaCl absorption in rat distal colon. The effect of SCFA on fluxes of 22Na and 36Cl was studied under voltage-clamp conditions, in the presence and absence of secretagogues inducing mucosal cAMP elevation [ie, theophylline, cholera toxin (CT) and forskolin]. The effect of butyrate concentration on Na absorption in CT- and theophylline-treated mucosa was compared with control normal mucosa. cAMP was measured in isolated colonocytes in the presence of secretagogues with and without SCFA using a radioassay method. All secretagogues were noted to inhibit net Na absorption and to induce net Cl secretion. In the presence of SCFA, net Na absorption was normal, and net Cl secretion was partly reversed. The flux data indicated that NaCl absorption from secreting colon was stimulated by SCFA and that Cl secretion was partially inhibited. The effects of SCFA on NaCl absorption were similar regardless of the secretagogue used. The kinetics of butyrate-stimulated Na absorption were altered by theophylline and CT, which decreased Km (6.87 and 7.17, respectively, compared to 10.75 mM for control) and increased Vmax (4.55 and 8.33 compared to 3.45 mM/eq/cm2/hr for control). cAMP production by colonocytes in response to secretory stimuli was significantly reduced (34.4%) by butyrate but not by acetate or propionate. In conclusion, SCFA-stimulated Na absorption is up-regulated by cAMP and may be an absorptive pathway that can be utilized in the therapy of cholera. Effects of butyrate on cAMP generation are also likely to be useful in secretory diarrhea.

Animals↗
PubMed1999

Butyrate hastens restoration of barrier function after thermal and detergent injury to rat distal colon in vitro.

BACKGROUND: Epithelial migration restores barrier function after superficial injury to any mucosa. The present study aimed to determine whether butyrate, important to colonic epithelial physiology in diverse ways, influences restoration of barrier function in the injured rat colon. METHODS: Rat distal colon was transiently exposed in vitro to heat (55 degrees C for 10 sec) or to detergent (deoxycholic acid, 7.5 mM, for 15 min), and tissue damage was verified histologically. Epithelial barrier function was assessed, in colon tissue mounted in Ussing chambers, by measuring electric resistance and passive serosa-to-mucosa fluxes of 22Na and of 14C PEG 4000 under voltage clamp conditions. Studies were done in the absence and presence of 25 mM butyrate in the bathing solutions. RESULTS: Heat exposure induced superficial epithelial damage, and the electric resistance decreased significantly. This was accompanied by increase in flux of 14C PEG and increased passive flux of 22Na. Electric resistance was significantly higher, and PEG flux significantly lower, in tissues bathed with butyrate. Exposure to deoxycholic acid also induced superficial epithelial damage, reduced tissue electric resistance, and increased passive flux of Na and PEG. Electric resistance was significantly higher, and PEG flux significantly lower, in injured tissues bathed in butyrate, than in injured tissues bathed in butyrate-free solution. The effect of butyrate on restoration of electric resistance towards normal was seen in colon both from adult rats and from younger rats that were 2 or 6 weeks old. CONCLUSIONS: Butyrate enhanced restoration of mucosal barrier function in rat distal colon in response to heat and detergent injury.

Animals↗