Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus

Amadi, Beatrice; Fagbemi, Andrew O; Kelly, Paul; Mwiya, Mwiya; Torrente, Franco; Salvestrini, Camilla; Day, Richard M.; Golden, Michael; Eklund, Erik A.; Freeze, Hudson H.; Murch, Simon

doi:10.3945/ajcn.2008.27092

Cited by 55 publications

(91 citation statements)

References 46 publications

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“…However, it was similar to Gambian well-nourished children [38], and unaltered by nutritional recovery [37]. Both well-nourished and malnourished Gambian children had high levels of intestinal cytokine expression, but malnourished children had an increased ratio of cells expression pro-inflammatory to regulatory cytokines, compared to the well-nourished Gambian children [38].…”

Section: Resultsmentioning

confidence: 73%

“…However, the mucosal atrophy and functional changes did not only occur in malnourished children. Although sometimes found to be most severe in malnourished children [33] [35]–[36] [46]–[47], similar abnormalities were present in apparently well-nourished children from the same environment [38]–[40] [43] [50], and frequently persisted after nutritional recovery [34] [37] [51].…”

Section: Resultsmentioning

confidence: 95%

“…Autopsy-studies from as early as 1965 described a thin-walled intestine in malnourished children, and noted that “… the tissue paper intestine of kwashiorkor is well known to tropical pathologists.” [32]. Small-intestinal biopsies showed thinning of the mucosa [33]–[36], decrease in villous height [37]–[43], altered villous morphology [32] [40] [44] and infiltration of lymphocytes [32] [34]–[38]. Electron-microscopy studies found sparse brush border with shortened microvilli and sparse endo-plasmatic reticulum [42].…”

Section: Resultsmentioning

confidence: 99%

“…Two articles described immune cells in small intestinal biopsies from malnourished children in Gambia and Zambia: both reported increased lymphocyte infiltration, more T-cells, and cells expressing HLA-DR in malnourished children compared to English children [37]–[38]. However, it was similar to Gambian well-nourished children [38], and unaltered by nutritional recovery [37].…”

Section: Resultsmentioning

confidence: 99%

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The Immune System in Children with Malnutrition—A Systematic Review

et al. 2014

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BackgroundMalnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.ObjectivesTo review the scientific literature about immune function in children with malnutrition.MethodsA systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1–60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.ResultsThe literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.ConclusionThe immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Immune System in Children with Malnutrition—A Systematic Review

et al. 2014

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“…Reduced production of sulfated GAGs is associated with a form of severe malnutrition with high mortality characterized by edema and systemic abnormalities in children [22]. Undersulfated chondroitin sulfate is identified in neoplastic tissues [23].…”

Section: Introductionmentioning

confidence: 99%

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

Lan

et al. 2017

Cell Physiol Biochem

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Background/Aims: Bleomycin is a clinically used anti-cancer drug that produces DNA breaks once inside of cells. However, bleomycin is a positively charged molecule and cannot get inside of cells by free diffusion. We previously reported that the cell surface negatively charged glycosaminoglycans (GAGs) may be involved in the cellular uptake of bleomycin. We also observed that a class of positively charged small molecules has Golgi localization once inside of the cells. We therefore hypothesized that bleomycin might perturb Golgi-operated GAG biosynthesis. Methods: We used stable isotope labeling coupled with LC/MS analysis of GAG disaccharides simultaneously from bleomycin-treated and non-treated cancer cells. To further understand the cytotoxicity of bleomycin and its relationship to GAGs, we used sodium chlorate to inhibit GAG sulfation and commercially available GAGs to compete for cell surface GAG/bleomycin interactions in seven cell lines including CHO745 defective in both heparan sulfate and chondroitin sulfate biosynthesis. Results: we discovered that heparan sulfate GAG was significantly undersulfated and the quantity and disaccharide compositions of GAGs were changed in bleomycin-treated cells in a concentration- and time-dependent manner. We revealed that bleomycin-induced cytotoxicity was directly related to cell surface GAGs. Conclusion: GAGs were targeted by bleomycin both at cell surface and at Golgi. Thus, GAGs might be the biological relevant molecules that might be related to the bleomycin-induced fibrosis in certain cancer patients, a severe side effect with largely unknown molecular mechanism.

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Protein‐Losing Disorders of the Gastrointestinal Tract

Murch¹

2012

Textbook of Clinical Gastroenterology and Hepatology

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Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus

Cited by 55 publications

References 46 publications

The Immune System in Children with Malnutrition—A Systematic Review

The Immune System in Children with Malnutrition—A Systematic Review

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

Protein‐Losing Disorders of the Gastrointestinal Tract

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