Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 199 records · Page 11Linked to original sources

PubMed2001

Purification and characterization of protein methylase II from Helicobacter pylori.

Protein methylase II (AdoMet:protein-carboxyl O-methyltransferase, EC 2.1.1.24) was identified and purified 115-fold from Helicobacter pylori through Q-Sepharose ion exchange column, AdoHcy-Sepharose 4B column, and Superdex 200 HR column chromatography using FPLC. The purified preparation showed two protein bands of about 78 kDa and 29 kDa molecular mass on SDS-PAGE. On non-denaturing gel electrophoresis, the enzyme migrated as a single band with a molecular mass of 410 kDa. In addition, MALDI-TOF-MS analysis and Superdex 200 HR column chromatography of the purified enzyme showed a major mass signal with molecular mass values of 425 kDa and 430 kDa, respectively. Therefore, the above results led us to suggest that protein methylase II purified from H. pylori is composed of four heterodimers with 425 kDa (4x(78+29)=428 kDa). This magnitude of molecular mass is unusual for protein methylases II so far reported. The enzyme has an optimal pH of 6.0, a K(m) value of 5.0x10(-6) M for S-adenosyl-L-methionine and a V(max) of 205 pmol methyl-(14)C transferred min(-1) mg(-1) protein.

Amino Acid Sequence↗

PubMed2001

Differential effects of annexins I, II, III, and V on cytosolic phospholipase A2 activity: specific interaction model.

Annexins (ANXs) are a family of proteins with calcium-dependent phospholipid binding properties. Although inhibition of phospholipase A2 (PLA2) by ANX-I has been reported, the mechanism is still controversial. Previously we proposed a 'specific interaction' model for the mechanism of cytosolic PLA2 (cPLA2) inhibition by ANX-I [Kim et al., FEBS Lett. 343 (1994) 251-255]. Here we have studied the cPLA2 inhibition mechanism using ANX-I, N-terminally deleted ANX-I (DeltaANX-I), ANX-II, ANX-II(2)P11(2), ANX-III, and ANX-V. Under the conditions for the specific interaction model, ANX-I, DeltaANX-I, and ANX-II(2)P11(2) inhibited cPLA2, whereas inhibition by ANX-II and ANX-III was negligible. Inhibition by ANX-V was much smaller than that by ANX-I. The protein-protein interactions between cPLA2 and ANX-I, DeltaANX-I, and ANX-II(2)P11(2) were verified by immunoprecipitation. We can therefore conclude that inhibition of cPLA2 by specific interaction is not a general function of all ANXs, and is rather a specific function of ANX-I. The results are consistent with the specific interaction model.

Animals↗

PubMed2001

Effects of nicotine on APP secretion and Abeta- or CT(105)-induced toxicity.

Several lines of evidence indicated that overexpression or aberrant processing of amyloid precursor protein (APP) is causally related to Alzheimer's disease (AD). Amyloid precursor protein is principally cleaved within the amyloid beta protein domain to release a large soluble ectodomain (APPs), known to have a wide range of trophic functions. The central hypothesis guiding this review is that nicotine may play an important role in APP secretion and protection against toxicity induced by APP metabolic fragments (beta-amyloid [Abeta], carboxyl terminal [CT]). Findings from our experiments have shown that nicotine enhances the release of APPs, which has neurotrophic and neuroprotective activities in concentration-dependent (>50 micromol/L) and time-dependent (>2 hours) manners. In addition, pretreatment of nicotine (>10 micromol/L for 24 hours) partially prevented Abeta or CT(105)-induced cytotoxicity in primary cultured neuron cells, and the effects of nicotine-induced protection were inhibited by the pretreatment with a nicotine alpha-bungarotoxin. Nicotine (>10 micromol/L for 24 hours) partially inhibited CT(105)-induced cytotoxicity when PC12 cells was transfected with CT(105). From these results, we proposed that nicotine or nicotinic receptor agonist treatment might improve the cognitive functions not only by supplementation of cholinergic neurotransmission, but also by protecting Abeta- or CT(105)-induced neurotoxicity probably through the increased release of APPs and the activation of nicotinic receptors.

Alzheimer Disease↗

PubMed2001

Cyclic AMP inhibits Akt activity by blocking the membrane localization of PDK1.

Akt is a protein serine/threonine kinase that plays an important role in the mitogenic responses of cells to variable stimuli. Akt contains a pleckstrin homology (PH) domain and is activated by phosphorylation at threonine 308 and serine 473. Binding of 3'-OH phosphorylated phosphoinositides to the PH domain results in the translocation of Akt to the plasma membrane where it is activated by upstream kinases such as (phosphoinositide-dependent kinase-1 (PDK1). Over-expression of constitutively active forms of Akt promotes cell proliferation and survival, and also stimulates p70 S6 kinase (p70S6K). In many cells, an increase in levels of intracellular cyclic AMP (cAMP) diminishes cell growth and promotes differentiation, and in certain conditions cAMP is even antagonistic to the effect of growth factors. Here, we show that cAMP has inhibitory effects on the phosphatidylinositol 3-kinase/PDK/Akt signaling pathway. cAMP potently inhibits phosphorylation at threonine 308 and serine 473 of Akt, which is required for the protein kinase activities of Akt. cAMP also negatively regulates PDK1 by inhibiting its translocation to the plasma membrane, despite not affecting its protein kinase activities. Furthermore, when we co-expressed myristoylated Akt and PDK1 mutants which constitutively co-localize in the plasma membrane, Akt activity was no longer sensitive to raised intracellular cAMP concentrations. Finally, cAMP was also found to inhibit the lipid kinase activity of PI3K and to decrease the levels of phosphatidylinositol 3,4,5-triphosphate in vivo, which are required for the membrane localization of PDK1. Collectively, these data strongly support the theory that the cAMP-dependent signaling pathway inhibits Akt activity by blocking the coupling between Akt and its upstream regulators, PDK, in the plasma membrane.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2001

Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. I. In vitro bone-marrow progenitor culture.

Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.

Analysis of Variance↗

PubMed2001

Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. II. Myelotoxicity associated with petroleum industrial wastes.

Various chemical mixtures exist in soil contaminated with petrochemical wastes, yet no comprehensive assessment of their impact on terrestrial ecosystems has been conducted. The purpose of this study was to evaluate hematotoxicity risks to wild populations of cotton rats (Sigmodon hispidus) residing in habitats previously contaminated by petroleum industrial wastes. Resident cotton rats were monitored on nine contaminated sites and nine ecologically matched reference sites in Oklahoma. The possible toxicological interactions of petrochemical wastes on bone marrow was investigated by using the assay of colony formation of granulocyte-macrophage progenitor cells. There was a consistent significant 21 to 39% decrease in the number of colony-forming units of granulocyte-macrophage (CFU-GM) in cotton rats from petrochemical-contaminated sites compared to matched reference sites, with no marked changes in hematological or histopathological parameters. These results suggest that bone-marrow progenitor cell culture is a sensitive indicator for the assessment of ecotoxicity risks associated with petrochemical wastes that are generated by the oil refining industry. Long-term exposure to hazardous wastes associated with the petroleum industry may represent a subtle risk to the hematopoietic system in humans.

Animals↗

PubMed2001

Widespread risks of dental fluorosis in cotton rats (Sigmodon hispidus) residing on petrochemical waste sites.

Fluoride has been identified as a ubiquitous contaminant of soils where petrochemical wastes have been disposed. The purpose of this study was to assess how widespread toxicity risks are to resident vertebrates from chronic exposure to fluoride in the soil of petrochemical-contaminated waste sites. In total, 573 wild cotton rats (Sigmodon hispidus) were examined. The rats that were seasonally collected from 12 contaminated and 12 ecologically matched reference sites across Oklahoma over a 3-yr period. The risks of cotton rats exposed to fluoride were analyzed by means of gross examination, histopathology, and scanning electron microscopy of rat incisors. Cotton rats from reference sites showed no pathologic changes in incisors (98%). In comparison, 46% of cotton rats from contaminated sites had various degrees of dental lesions. The prevalence and severity of dental lesions in cotton rats from contaminated sites were significantly influenced by season. There was a 45% increase in prevalence and a 65% increase in severity of dental lesions from summer to winter. This study demonstrated that cotton rats are very sensitive biomonitors for assessing toxicity risks from soils contaminated with fluoride and that such assessments should consider seasonal influences.

Animals↗

PubMed2001

Leucine zipper-mediated homodimerization of the p21-activated kinase-interacting factor, beta Pix. Implication for a role in cytoskeletal reorganization.

Pix, a p21-activated kinase-interacting exchange factor, is known to be involved in the regulation of Cdc42/Rac GTPases. The 85-kDa betaPix-a protein contains an Src homology 3 domain, the tandem Dbl homology and Pleckstrin homology domains, a proline-rich region, and a GIT1-binding domain. In addition to those domains, betaPix-a also contains a putative leucine zipper domain at the C-terminal end. In this study, we demonstrate that the previously identified putative leucine zipper domain mediates the formation of betaPix-a homodimers. Using in vitro and in vivo methodologies, we show that deletion of the leucine zipper domain is sufficient to abolish betaPix-a homodimerization. In NIH3T3 fibroblast cells, expression of wild type betaPix-a induces the formation of membrane ruffles. However, cells expressing the leucine zipper domain deletion mutant could not form membrane ruffle structures. Moreover, platelet-derived growth factor-mediated cytoskeletal changes were completely blocked by the leucine zipper domain deletion mutant. The results suggest that the leucine zipper domain enables betaPix-a to homodimerize, and homodimerization is essential for betaPix-a signaling functions leading to the cytoskeletal reorganization.

3T3 Cells↗

PubMed2001

Stable expression of human immunodeficiency virus type 1 Nef confers resistance against Fas-mediated apoptosis.

To investigate the effect of Nef on Fas-mediated apoptosis, we compared T cells, both population and subclones stably expressing Nef from HIV-1(NL432), with Nef(-) control cells. Fas-mediated apoptosis was significantly delayed in Nef(+) cells as determined by annexin V staining and the percentage of apoptotic cells was lower in all Nef-expressing cells than in the control cells by a maximum of 10-fold. Next we measured cell surface levels of Fas to test whether the delayed apoptosis in Nef(+) cells was due to reduced cell surface expression of Fas. We found that there was no significant difference in the surface level of Fas between the Nef(+) and Nef(-) cells. To further define the steps affected by Nef in the Fas signaling pathway, the activation of caspase-3 and caspase-8 was investigated. A reasonable correlation was found between the magnitude of apoptosis measured by annexin V staining and the enzymatic activity of caspase-3. The overall level of caspase-8 activity in Nef(+) cells was also lower than in Nef(-) cells, although the extent of inhibition was not as significant as seen for caspase-3. Overall, our results indicate that long-term stable expression of Nef, which mimicks persistent or latent infection in vivo, confers resistance against anti-Fas Ab-induced apoptosis through inhibition of caspase-3 and caspase-8 activation.

Annexin A5↗

PubMed2001

Interferon gamma (IFNgamma ) and tumor necrosis factor alpha synergism in ME-180 cervical cancer cell apoptosis and necrosis. IFNgamma inhibits cytoprotective NF-kappa B through STAT1/IRF-1 pathways.

We investigated the molecular mechanism of the synergism between interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) documented in a variety of biological occasions such as tumor cell death and inflammatory responses. IFNgamma/TNFalpha synergistically induced apoptosis of ME-180 cervical cancer cells. IFNgamma induced STAT1 phosphorylation and interferon regulatory factor 1 (IRF-1) expression. Transfection of phosphorylation-defective STAT1 inhibited IFNgamma/TNFalpha-induced apoptosis, whereas IRF-1 transfection induced susceptibility to TNFalpha. Dominant-negative IkappaBalpha transfection sensitized ME-180 cells to TNFalpha. IFNgamma pretreatment attenuated TNFalpha- or p65-induced NF-kappaB reporter activity, whereas it did not inhibit p65 translocation or DNA binding of NF-kappaB. IRF-1 transfection alone inhibited TNFalpha-induced NF-kappaB activity, which was reversed by coactivator p300 overexpression. Caspases were activated by IFNgamma/TNFalpha combination; however, caspase inhibition did not abrogate IFNgamma/TNFalpha-induced cell death. Instead, caspase inhibitors directed IFNgamma/TNFalpha-treated ME-180 cells to undergo necrosis, as demonstrated by Hoechst 33258/propidium iodide staining and electron microscopy. Taken together, our results indicate that IFNgamma and TNFalpha synergistically act to destroy ME-180 tumor cells by either apoptosis or necrosis, depending on caspase activation, and STAT1/IRF-1 pathways initiated by IFNgamma play a critical role in IFNgamma/TNFalpha synergism by inhibiting cytoprotective NF-kappaB. IFNgamma/TNFalpha synergism appears to activate cell death machinery independently of caspase activation, and caspase activation seems to merely determine the mode of cell death.

Apoptosis↗

PubMed2001

A strategy to identify differentially expressed genes using representational difference analysis and cDNA arrays.

Representational difference analysis (RDA) combined with cDNA arrays is an effective approach to identify differentially expressed genes. To identify differentially expressed genes in c-Myc transgenic mouse liver, we compared the virtues of probing commercially available cDNA arrays with either radiolabeled cDNA pools or radiolabeled difference products (DP2) derived from RDA using c-Myc transgenic and normal mouse liver. Probing commercial and custom arrays with DP2 products led to the identification of transcripts of low abundance that were missed when the arrays were initially probed with PCR-amplified cDNA pools. Although DP2 probes also detected abundant transcripts that are highly differentially expressed, they failed to identify abundant transcripts with low differential expression that were detected with cDNA pools. The combined use of radiolabeled cDNA and DP2 products to probe arrays allows a more comprehensive identification of differentially expressed transcripts that are abundant or rare. Our method has the additional benefit of eliminating false-positive transcripts that lack true differential expression and frequently contaminate DP2 pools. Using this method we identified 16 differentially expressed genes in c-Myc transgenic liver, one of which is novel.

Animals↗

PubMed2001

Nuclear translocation of the N-terminal prodomain of interleukin-16.

Interleukin-16 (IL-16) is a pleiotropic cytokine that functions as a chemoattractant factor, a modulator of T cell activation, and an inhibitor of human immunodeficiency virus (HIV) replication. These diverse functions are exclusively attributed to the secreted C-terminal peptide of 121 amino acids (mature IL-16), which is cleaved from the precursor protein (pro-IL-16) by caspase-3. Human pro-IL-16 is comprised of 631 amino acids with three PDZ domains, one of which is present in secreted mature IL-16. No cellular localization or biologic functions have been ascribed to the unusually large and highly conserved N-terminal prodomain formed as a result of proteolytic release of the third PDZ domain of pro-IL-16. Here we show that the N-terminal prodomain of pro-IL-16 translocates into the nucleus following cleavage of the C-terminal segment. The nuclear localization signal of pro-IL-16 consists of a classical bipartite nuclear targeting motif. We also show that the nuclear targeting of the IL-16 prodomain induces a G(0)/G(1) arrest in the cell cycle. Taken together, the high degree of conservation of the prodomain among species, the presence of two PDZ motifs, and the nuclear localization and subsequent inhibitory effect on cell cycle progression suggest that pro-IL-16 is cleaved into two functional proteins, a C-terminal-secreted cytokine and an N-terminal product, which affects the cell cycle.

Animals↗

PubMed2001

Effects of combination of ACE inhibitor and angiotensin receptor blocker on cardiac remodeling, cardiac function, and survival in rat heart failure.

BACKGROUND: The mechanism and treatment of diastolic heart failure are poorly understood. We compared the effects of an ACE inhibitor, an angiotensin receptor blocker (ARB), and their combination on diastolic heart failure in Dahl salt-sensitive (DS) rats. METHODS AND RESULTS: DS rats fed an 8% NaCl diet from 7 weeks of age were treated with benazepril 10 mg/kg alone, valsartan 30 mg/kg alone, or combined benazepril and valsartan at 5 and 15 mg/kg, respectively, or at 1 and 3 mg/kg, respectively. At 16 weeks of age, DS rats exhibited prominent concentric left ventricular (LV) hypertrophy and diastolic dysfunction with preserved systolic function, as estimated by echocardiography. Despite comparable hypotensive effects among all drug treatments, the combination of benazepril 5 mg/kg and valsartan 15 mg/kg improved diastolic dysfunction and survival in DS rats more effectively than ACE inhibitor or ARB alone. Furthermore, the increase in LV endothelin-1 levels and hydroxyproline contents in DS rats was significantly suppressed only by combined benazepril and valsartan, and LV atrial natriuretic peptide mRNA upregulation in DS rats was suppressed to a greater extent by the combination therapy than monotherapy. CONCLUSIONS: The combination of ACE inhibitor and ARB, independently of the hypotensive effect, improved LV phenotypic change and increased LV endothelin-1 production and collagen accumulation, diastolic dysfunction, and survival in a rat heart failure model more effectively than either agent alone, thereby providing solid experimental evidence that the combination of these 2 agents is more beneficial than monotherapy for treatment of heart failure.

Angiotensin Receptor Antagonists↗

PubMed2001

Cycloplegic refractions in healthy children aged 1 through 48 months.

OBJECTIVES: To provide a description of refractive errors in healthy, term-born children, aged 1 through 48 months, and to test the hypotheses that spherical equivalent becomes significantly less hyperopic and less variable with increasing age. METHODS: Following a prospective, cross-sectional design, cycloplegic retinoscopy was used to measure the refractive error in both eyes of 514 healthy, term-born children in 12 age groups. Three hundred were aged 12 months or younger. Spherical equivalent and cylindrical power and axis were analyzed as a function of age. Prediction limits for spherical equivalent were calculated. RESULTS: Spherical equivalents of right and left eyes did not differ at any age. Hyperopia declined significantly with increasing age. The variability in spherical equivalent also decreased significantly with age. Cylindrical error of 1 diopter or more was found in 25% of the children; the proportion with astigmatism was highest in infancy and then waned. Myopia and anisometropia were rare, occurring in 3% and 1% of the sample, respectively. CONCLUSIONS: Significant declines in hyperopia and variability of spherical equivalent appear to be features of emmetropization. The normal prediction limits provide guidelines against which data from individual patients can be compared.

Age Distribution↗

PubMed2001

Response of experimental retinal neovascularization to thiazolidinediones.

OBJECTIVE: To determine the effect of thiazolidinediones (TZDs) on experimental retinal neovascularization. METHODS: The ability of the TZDs troglitazone and rosiglitazone maleate (1-20 micromol/L) to inhibit retinal endothelial cell (REC) proliferation, migration, tube formation, and signaling was determined in response to vascular endothelial growth factor (VEGF). In vivo studies were performed using the oxygen-induced ischemia model of retinal neovascularization. Neonatal mice were treated with intravitreous injection of 0.5 microL of troglitazone (100 micromol/L) or rosiglitazone maleate (100 micromol/L), or vehicle, and retinal neovascularization was assayed qualitatively and quantitatively by means of angiography and histological examination. RESULTS: Expression of the TZD receptor, peroxisome proliferator-activated receptor gamma, was confirmed in RECs by means of Western immunoblotting. Rosiglitazone and troglitazone inhibited VEGF-induced migration (P< .05), proliferation (P< .05), and tube formation (P< .01) by RECs in vitro beginning at 10 micromol/L. Rosiglitazone and troglitazone inhibited phosphorylation of extracellular signal-regulated mitogen-activated protein kinase 1 in RECs. Intravitreous injection of rosiglitazone or troglitazone inhibited development of retinal neovascularization (P< .01) but did not significantly inhibit VEGF overexpression in the ganglion cell layer of the ischemic retina. CONCLUSION: The TZDs inhibit experimental retinal neovascularization with an effect that is primarily downstream of VEGF expression. CLINICAL RELEVANCE: The TZDs are widely prescribed and should be evaluated for their potential to inhibit the progression of diabetic retinopathy.

Animals↗

PubMed2001

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Adult↗

PubMed2001

Tissue-engineered growth of bone by marrow cell transplantation using porous calcium metaphosphate matrices.

In this study we investigated not only osteoblastic cell proliferation and differentiation on the surface of calcium metaphosphate (CMP) matrices in vitro but also bone formation by ectopic implantation of these cell-matrix constructs in athymic mice in vivo. Interconnected porous CMP matrices with pores 200 microm in size were prepared to use as scaffolds for rat-marrow stromal-cell attachment. Cell-matrix constructs were cultured in vitro, and cell proliferation and ALPase activities were monitored for 56 days. In addition to their being cultured in vitro, cell-matrix constructs were implanted into subcutaneous sites of athymic mice. In vitro these porous CMP matrices supported the proliferation of osteoblastic cells as well as their differentiation, as indicated by high ALPase activity. In vivo the transplanted marrow cells gave rise to bone tissues in the pores of the CMP matrices. A small amount of woven bone formation was detected first at 4 weeks; osteogenesis progressed vigorously with time, and thick lamellar bones that had been remodeled were observed at 12 weeks. These findings demonstrate the potential for using a porous CMP matrix as a biodegradable scaffold ex vivo along with attached marrow-derived mesenchymal cells for transplantation into a site for bone regeneration in vivo.

Alkaline Phosphatase↗

PubMed2001

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children.

BACKGROUND: Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. OBJECTIVES: In children with acute diarrhoea, to compare reduced osmolarity glucose-based oral rehydration salt solution with international WHO formulation. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: Randomised controlled trials comparing reduced osmolarity ORS solution with the WHO formulation. Outcomes sought were unscheduled intravenous fluid infusion therapy and measures of clinical illness. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. We tested for heterogeneity using the chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. MAIN RESULTS: The primary outcome was reported in 12 trials. In a meta-analysis of nine trials, reduced osmolarity ORS was associated with fewer unscheduled infusions compared with standard WHO ORS (Mantel Haenzel odds ratio 0.61, 95% confidence interval 0.47 to 0.81) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Thirteen trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. REVIEWER'S CONCLUSIONS: In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO ORS is associated with fewer unscheduled intravenous infusions, smaller stool volume post randomisation, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO ORS was detected.

Bicarbonates↗