The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Nutritional Therapy with Vitamin K1 Is Effective in the Improvement of Vitamin K Status and Bone Turnover Markers in Patients with Severe Motor and Intellectual Disabilities.

We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 µg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.

Gastric and Jejunal Enteral Feeding Differently Affect Vitamin B12 Status in Subjects with Severe Motor and Intellectual Disabilities.

The absorption of vitamin B12 is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B12 status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B12, folate, vitamin B6, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B12, folate, and vitamin B6 than those with oral ingestion (OI). Serum folate and vitamin B6 concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B12 concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B12 intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B6, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B12.

Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction.

The immunological properties of rat S100A8 (r-S100A8) and S100A9 (r-S100A9) in immune cells are poorly understood. Enzyme-linked immunosorbent assay (ELISA) for r-S100A9 enabled us to discuss the differential functional roles of the two proteins, and their localization in the cells was observed microscopically. Recombinant human S100A8 (rh-S100A8) or S100A9 (rh-S100A9) were intravenously administrated into rats with LPS-induced liver damage. ELISA was used to measure the serum concentration of S100A9 in the rats. Western blotting and a preparative ELISA were used to prove specificity and avidity of monoclonal antibodies for r-S100A8 and r-S100A9. Immunohistochemical staining was carried out to visualize intracellular localization of the two proteins in the immune cells using the antibodies. When rh-S100A8 was intravenously injected in the rats (B group), the serum concentration of r-S100A9 apparently decreased as compared with that of the positive control rats (A group). The activities of AST, ALT, and LD in the rat sera (B group) also significantly went down in comparison with those of the rats (A group). Although both the S100A8 and S100A9 were abundantly expressed in activated immune cells, quite difference of not only their intracellular localization but also distribution of the cells expressing the two proteins was microscopically observed. In the rats (B group), less number of the immune cells or less amount of r-S100A8 and r-S100A9 in the cells than those of the rats (A group) was also seen. The r-S100A8 could serve as a regulator of acute inflammatory reaction in the rats with LPS-induced damage.

Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9: clinical significance of using proteins for monitoring the postoperative condition of liver recipients.

BACKGROUND: Serum proteins that non-specifically bind with human S100A8/A9 (h-S100A8/A9) have been proposed. Our aim was to isolate and identify these proteins, and verify their clinical significance for monitoring the postoperative condition of liver recipients, and further to discuss the transportation of human fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo. METHODS: To isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9 affinity columns were used. Proteins were identified by mass spectrometry. Two enzyme-linked immunosorbent assays (ELISA) were used to measure h-S100A8/A9 and h-FN in the sera of liver recipients. Flow cytometry was employed to detect h-S100A8/A9 and h-FN on immunological cells. Western blotting was used to confirm serum constituents using antibodies specific to each constituent. RESULTS: One of the proteins was identified with h-FN, and its fluctuation pattern in the serum of the recipient was in contrast to that of CRP. Flow cytometry showed a positive reaction for h-S100A8/A9 and h-FN on neutrophils and monocytes, indicating that both proteins exist on these cells. CONCLUSIONS: The h-FN could be transported with S100A8/A9 in blood and/or on immunological cells, and effectively prevent further attack by various internal oxidants or repair damaged liver tissue in vivo.