A Lactobacillus casei Shirota probiotic drink reduces antibiotic-associated diarrhoea in patients with spinal cord injuries: a randomised controlled trial.

Certain probiotics may prevent the development of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD), but their effectiveness depends on both strain and dose. There are few data on nutritional interventions to control AAD/CDAD in the spinal cord injury (SCI) population. The present study aimed to assess (1) the efficacy of consuming a commercially produced probiotic containing at least 6·5 × 109 live Lactobacillus casei Shirota (LcS) in reducing the incidence of AAD/CDAD, and (2) whether undernutrition and proton pump inhibitors (PPI) are risk factors for AAD/CDAD. A total of 164 SCI patients (50·1 (sd 17·8) years) with a requirement for antibiotics (median 21 d, range 5-366) were randomly allocated to receive LcS (n 76) or no probiotic (n 82). LcS was given once daily for the duration of the antibiotic course and continued for 7 days thereafter. Nutritional risk was assessed by the Spinal Nutrition Screening Tool. The LcS group had a significantly lower incidence of AAD (17·1 v. 54·9%, P< 0·001). At baseline, 65% of patients were at undernutrition risk. Undernutrition (64·1 v. 33·3%, P< 0·01) and the use of PPI (38·4 v. 12·1 %, P= 0·022) were found to be associated with AAD. However, no significant difference was observed in nutrient intake between the groups. The multivariate logistic regression analysis identified poor appetite ( < 1/2 meals eaten) (OR 5·04, 95% CI 1·28, 19·84) and no probiotic (OR 8·46, 95% CI 3·22, 22·20) as the independent risk factors for AAD. The present study indicated that LcS could reduce the incidence of AAD in hospitalised SCI patients. A randomised, placebo-controlled study is needed to confirm this apparent therapeutic success in order to translate into improved clinical outcomes.

Protein phosphatase 2A, a negative regulator of the ERK signaling pathway, is activated by tyrosine phosphorylation of putative HLA class II-associated protein I (PHAPI)/pp32 in response to the antiproliferative lectin, jacalin.

Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including those mediated by extracellular signal-regulated kinase (ERK) signaling. While investigating the reversible antiproliferative effect of the dietary lectin, jacalin, which binds the Thomsen-Friedenreich antigen (galactose beta1-3 N-acetylgalactosamine alpha-), we have found that this lectin (30 microg/ml) induces rapid, transient, tyrosine phosphorylation of putative human HLA-DR-associated protein I (PHAPI, also known as the tumor suppressor pp32) in HT29 human colon cancer cells. This is accompanied by the release of PP2A from association with PHAPI, allowing increased phosphatase activity of PP2A (by 42 +/- 10% at 10 min) and consequent complete dephosphorylation of the ERK kinase, MEK1/2, by 10 min and of ERK1/2 by 60 min. PHAPI knockdown by RNA interference abolished the effects of jacalin on PP2A activation and MEK inhibition. Thus phosphorylation of PHAPI/pp32 is a critical regulatory step in PP2A activation and ERK signaling.

An N-terminal truncated form of Orp150 is a cytoplasmic ligand for the anti-proliferative mushroom Agaricus bisporus lectin and is required for nuclear localization sequence-dependent nuclear protein import.

Nuclear localization sequence-dependent nuclear protein import is essential for maintaining cell function and can be selectively blocked in epithelial cells by mushroom (Agaricus bisporus) lectin. Here we report that a major intracellular ligand for this lectin is an N-terminally truncated form of oxygen-regulated protein 150 (Orp150), which lacks the endoplasmic reticulum translocation signal peptide of full-length Orp150. This cytoplasmic form of Orp150 expresses the lectin carbohydrate ligand (sialyl-2,3-galactosyl-beta1,3-N-acetylgalactosamine-alpha) and is shown to be essential for nuclear localization sequence-dependent nuclear protein import.