Nur Alam | Universitas Tadulako (original) (raw)

Papers by Nur Alam

Research paper thumbnail of Time Course of Bacterial Diversity in Stool Samples of Malnourished Children With Cholera Receiving Treatment

Journal of Pediatric Gastroenterology and Nutrition, 2009

Recent nutritional interventions have targeted colonic functions in patients with infectious diar... more Recent nutritional interventions have targeted colonic functions in patients with infectious diarrhea during rehydration and during recovery from malnutrition, with the assumption that the effects will be influenced by metabolism of complex carbohydrates by colonic bacteria. However, the diversity of colonic bacteria in patients with cholera is not known. To study the diversity of colonic bacteria in malnourished children with cholera before and during treatment with oral rehydration salt solutions containing 1 of these 3 substrates: glucose, rice, or amylase-resistant starch. Serial fecal samples were collected from 30 malnourished children with cholera until completion of rehydration and partial nutritional recovery; 11 malnourished children without diarrhea; and 6 better nourished children. Polymerase chain reaction, using universal primers for 16S rDNA, was performed on chromosomal DNA extracted from the stool samples, and the products were separated by temporal temperature gradient gel electrophoresis. The Vibrio cholerae band was detected in all children at enrollment and disappeared within 2 days. On day 2, a rapid and significant increase in the band numbers was observed, which was followed by a steady increase until day 28. After full recovery from cholera and partial recovery from malnutrition, the number of bands (11.5+/-2.8) was lower than in healthy children (22.2+/-1.3). On day 3, the number of bands was greater with rice or amylase-resistant starch than with glucose (P<.05). Bacterial diversity was markedly but transiently altered in severely malnourished children with cholera receiving therapy.

Research paper thumbnail of Safety of Rapid Intravenous Rehydration and Comparative Efficacy of 3 Oral Rehydration Solutions in the Treatment of Severely Malnourished Children With Dehydrating Cholera

Journal of Pediatric Gastroenterology and Nutrition, 2009

Assess the safety of rapid intravenous rehydration of severely malnourished children and compare ... more Assess the safety of rapid intravenous rehydration of severely malnourished children and compare the efficacy of 3 formulations of oral rehydration salts solutions. A group of 175 severely malnourished children of either sex (weight/length <70% of National Center for Health Statistics median), ages 6 to 36 months with cholera, were randomly assigned to receive 1 of 3 oral rehydration solutions (ORSs): glucose-ORS (n=58), glucose-ORS plus 50 g/L of amylase-resistant starch (n=59), or rice-ORS (n=58). Severely dehydrated children at enrollment were administered 100 mL/kg of an intravenous solution for 4 to 6 hours before randomisation, and those with some dehydration were randomised on enrollment. The electrolytes of the 3 ORSs were identical. In acute and convalescence phases, treatment was similar other than the nature of the ORSs. Intravenous fluid (mean) administered to 149 study children was 103 mL/kg (95% confidence interval [CI] 96-109), and all were rehydrated within 6 hours. None of them developed overhydration or heart failure. During the first 24 hours, stool output (31%; 95% CI 14%-42%; P=0.004) and the ORS intake (26%; 95% CI 12%-37%; P=0.002) of children receiving rice-ORS were significantly less compared with children receiving glucose-ORS. The mean duration of diarrhoea in all children (66 hours; 95% CI 62-71), and time to attain 80% of median weight/length (7.15+/-2.81 days) were not different. Dehydration in severely malnourished children can safely be corrected within 6 hours. All study ORSs were equally efficient in correcting dehydration. Rice-ORS significantly reduced the stool output and ORS intake, confirming previous reports.

Research paper thumbnail of Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: A randomized controlled clinical trial

Journal of Pediatrics, 2001

Objective: We evaluated and compared the efficacy of the World Health Organization (WHO) oral reh... more Objective: We evaluated and compared the efficacy of the World Health Organization (WHO) oral rehydration solution (ORS) and 2 different formulations of reduced osmolarity ORSs in infants with persistent diarrhea. Study design: Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO-ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30), or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of ongoing stool losses for up to 7 days. Major outcome measures were stool volume and frequency, ORS intake, and resolution of diarrhea. Results: Although there were variations from one study day to another, the stool volume was approximately 40% less in the reduced osmolarity ORS groups; consequently, these children required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion of children in the RORS-R groups also had resolution of diarrhea during the study period. No children in any of the treatment groups had hyponatremia. Conclusion: Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be advantageous for use in the treatment of children with persistent diarrhea. (J Pediatr 2001;138:532-8)

Research paper thumbnail of Lactobacillus paracasei Strain ST11 Has No Effect on Rotavirus but Ameliorates the Outcome of Nonrotavirus Diarrhea in Children From Bangladesh

Background. Previous studies have shown that selected strains of lactobacilli that are administer... more Background. Previous studies have shown that selected strains of lactobacilli that are administered orally result in a modest reduction of diarrhea duration. However, duration alone is not considered optimal for therapeutic evaluation of any agent in diarrhea.

Research paper thumbnail of Differential expression of intestinal membrane transporters in cholera patients

Febs Letters, 2007

Vibrio cholerae causes the cholera disease through secretion of cholera toxin (CT), resulting in ... more Vibrio cholerae causes the cholera disease through secretion of cholera toxin (CT), resulting in severe diarrhoea by modulation of membrane transporters in the intestinal epithelium. Genes encoding membrane-spanning transporters identified as being differentially expressed during cholera disease in a microarray screening were studied by real-time PCR, immunohistochemistry and in a CaCo-2 cell model. Two amino acid transporters, SLC7A11 and SLC6A14, were upregulated in acute cholera patients compared to convalescence. Five other transporters were downregulated; aquaporin 10, SLC6A4, TRPM6, SLC23A1 and SLC30A4, which have specificity for water, serotonin (5-HT), magnesium, vitamin C and zinc, respectively. The majority of these changes appear to be attempts of the host to counteract the secretory response. Our results also support the concept that epithelial cells are involved in 5-HT signalling during acute cholera.

Research paper thumbnail of Broad Up-Regulation of Innate Defense Factors during Acute Cholera

Infection and Immunity, 2007

We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 di... more We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute-and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data.

Research paper thumbnail of Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139

Clinical and Vaccine Immunology, 2002

Investigations were carried out to study the production of factors associated with the innate imm... more Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1-and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO ⅐ ) metabolites (nitrite and nitrate [NO 2 ؊ and NO 3 ؊ ]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F 2␣ remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE 2 , LTB 4 , and NO ⅐ , as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.

Research paper thumbnail of Innate Immune Responses in Children and Adults with Shigellosis

Infection and Immunity, 2000

An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool... more An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E 2 , and leukotriene B 4 (LTB 4 ) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F 2␣ and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment. Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rectum. In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these molecules to the immunopathogenesis of severe colitis caused by shigellae.

Research paper thumbnail of Time Course of Bacterial Diversity in Stool Samples of Malnourished Children With Cholera Receiving Treatment

Journal of Pediatric Gastroenterology and Nutrition, 2009

Recent nutritional interventions have targeted colonic functions in patients with infectious diar... more Recent nutritional interventions have targeted colonic functions in patients with infectious diarrhea during rehydration and during recovery from malnutrition, with the assumption that the effects will be influenced by metabolism of complex carbohydrates by colonic bacteria. However, the diversity of colonic bacteria in patients with cholera is not known. To study the diversity of colonic bacteria in malnourished children with cholera before and during treatment with oral rehydration salt solutions containing 1 of these 3 substrates: glucose, rice, or amylase-resistant starch. Serial fecal samples were collected from 30 malnourished children with cholera until completion of rehydration and partial nutritional recovery; 11 malnourished children without diarrhea; and 6 better nourished children. Polymerase chain reaction, using universal primers for 16S rDNA, was performed on chromosomal DNA extracted from the stool samples, and the products were separated by temporal temperature gradient gel electrophoresis. The Vibrio cholerae band was detected in all children at enrollment and disappeared within 2 days. On day 2, a rapid and significant increase in the band numbers was observed, which was followed by a steady increase until day 28. After full recovery from cholera and partial recovery from malnutrition, the number of bands (11.5+/-2.8) was lower than in healthy children (22.2+/-1.3). On day 3, the number of bands was greater with rice or amylase-resistant starch than with glucose (P<.05). Bacterial diversity was markedly but transiently altered in severely malnourished children with cholera receiving therapy.

Research paper thumbnail of Safety of Rapid Intravenous Rehydration and Comparative Efficacy of 3 Oral Rehydration Solutions in the Treatment of Severely Malnourished Children With Dehydrating Cholera

Journal of Pediatric Gastroenterology and Nutrition, 2009

Assess the safety of rapid intravenous rehydration of severely malnourished children and compare ... more Assess the safety of rapid intravenous rehydration of severely malnourished children and compare the efficacy of 3 formulations of oral rehydration salts solutions. A group of 175 severely malnourished children of either sex (weight/length <70% of National Center for Health Statistics median), ages 6 to 36 months with cholera, were randomly assigned to receive 1 of 3 oral rehydration solutions (ORSs): glucose-ORS (n=58), glucose-ORS plus 50 g/L of amylase-resistant starch (n=59), or rice-ORS (n=58). Severely dehydrated children at enrollment were administered 100 mL/kg of an intravenous solution for 4 to 6 hours before randomisation, and those with some dehydration were randomised on enrollment. The electrolytes of the 3 ORSs were identical. In acute and convalescence phases, treatment was similar other than the nature of the ORSs. Intravenous fluid (mean) administered to 149 study children was 103 mL/kg (95% confidence interval [CI] 96-109), and all were rehydrated within 6 hours. None of them developed overhydration or heart failure. During the first 24 hours, stool output (31%; 95% CI 14%-42%; P=0.004) and the ORS intake (26%; 95% CI 12%-37%; P=0.002) of children receiving rice-ORS were significantly less compared with children receiving glucose-ORS. The mean duration of diarrhoea in all children (66 hours; 95% CI 62-71), and time to attain 80% of median weight/length (7.15+/-2.81 days) were not different. Dehydration in severely malnourished children can safely be corrected within 6 hours. All study ORSs were equally efficient in correcting dehydration. Rice-ORS significantly reduced the stool output and ORS intake, confirming previous reports.

Research paper thumbnail of Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: A randomized controlled clinical trial

Journal of Pediatrics, 2001

Objective: We evaluated and compared the efficacy of the World Health Organization (WHO) oral reh... more Objective: We evaluated and compared the efficacy of the World Health Organization (WHO) oral rehydration solution (ORS) and 2 different formulations of reduced osmolarity ORSs in infants with persistent diarrhea. Study design: Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO-ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30), or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of ongoing stool losses for up to 7 days. Major outcome measures were stool volume and frequency, ORS intake, and resolution of diarrhea. Results: Although there were variations from one study day to another, the stool volume was approximately 40% less in the reduced osmolarity ORS groups; consequently, these children required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion of children in the RORS-R groups also had resolution of diarrhea during the study period. No children in any of the treatment groups had hyponatremia. Conclusion: Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be advantageous for use in the treatment of children with persistent diarrhea. (J Pediatr 2001;138:532-8)

Research paper thumbnail of Lactobacillus paracasei Strain ST11 Has No Effect on Rotavirus but Ameliorates the Outcome of Nonrotavirus Diarrhea in Children From Bangladesh

Background. Previous studies have shown that selected strains of lactobacilli that are administer... more Background. Previous studies have shown that selected strains of lactobacilli that are administered orally result in a modest reduction of diarrhea duration. However, duration alone is not considered optimal for therapeutic evaluation of any agent in diarrhea.

Research paper thumbnail of Differential expression of intestinal membrane transporters in cholera patients

Febs Letters, 2007

Vibrio cholerae causes the cholera disease through secretion of cholera toxin (CT), resulting in ... more Vibrio cholerae causes the cholera disease through secretion of cholera toxin (CT), resulting in severe diarrhoea by modulation of membrane transporters in the intestinal epithelium. Genes encoding membrane-spanning transporters identified as being differentially expressed during cholera disease in a microarray screening were studied by real-time PCR, immunohistochemistry and in a CaCo-2 cell model. Two amino acid transporters, SLC7A11 and SLC6A14, were upregulated in acute cholera patients compared to convalescence. Five other transporters were downregulated; aquaporin 10, SLC6A4, TRPM6, SLC23A1 and SLC30A4, which have specificity for water, serotonin (5-HT), magnesium, vitamin C and zinc, respectively. The majority of these changes appear to be attempts of the host to counteract the secretory response. Our results also support the concept that epithelial cells are involved in 5-HT signalling during acute cholera.

Research paper thumbnail of Broad Up-Regulation of Innate Defense Factors during Acute Cholera

Infection and Immunity, 2007

We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 di... more We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute-and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data.

Research paper thumbnail of Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139

Clinical and Vaccine Immunology, 2002

Investigations were carried out to study the production of factors associated with the innate imm... more Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1-and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO ⅐ ) metabolites (nitrite and nitrate [NO 2 ؊ and NO 3 ؊ ]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F 2␣ remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE 2 , LTB 4 , and NO ⅐ , as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.

Research paper thumbnail of Innate Immune Responses in Children and Adults with Shigellosis

Infection and Immunity, 2000

An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool... more An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E 2 , and leukotriene B 4 (LTB 4 ) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F 2␣ and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment. Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rectum. In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these molecules to the immunopathogenesis of severe colitis caused by shigellae.