**6. References**

84 Biomarker

**4. Inorganic signatures of life: Can metal ion distributions be biomarkers of** 

The key to more insightful interpretations from much of this imaging is linking it to known physiological pathways. Much of what we know about cell function, and many therapeutic targets, is because of the specificity of proteins. Unleashing the potential of this tool calls for matching our developing understanding of the role of metal ions themselves in biology with

Can the distribution of metal ions be diagnostic? Can these metal ions, or at least their signature distribution and quantity in subcellular compartments, serve as biomarkers?

Thus, while it seems entirely possible that the distributions of metals may be used as a signature diagnostic of a pathological state in the future, the development of metalloproteomics and other methods of identifying their partner biomolecules is essential

**4.2 Need for higher resolution imaging to better define subcellular compartments** 

A need exists for higher-resolution X-ray fluorescence imaging, to better identify the specific cellular compartments where metals are distributed. Many examples highlighted here look at changes in metal distributions that are either 'in' vs. 'out' of the cell, 'near' or 'away' from the nucleus. At the advent of the age of nano-scale imaging of biological samples, imaging

Fig. 2. Copper localizes peripherally to the nucleus in a cell

**4.1 A need to link metal ion fluxes with other biomolecules** 

 Inorganic signatures can identify specific physiological processes Intervention, clinical diagnostics require targeting associated proteins

to therapeutic intervention in these metal-related disease processes.

our greater understanding of physiology in general.

Metal ions are essential to many processes

**physiological state?** 

Consider this:


**5** 

*Japan* 

**Urinary Water-Soluble Vitamins as Nutritional** 

The traditional approach of nutritional assessment is to survey the amount of nutrients consumed by dietary assessment. Although this method can provide approximate intake, this approach often makes misreporting, and can't determine nutritional status. Especially, to determine micronutrient intake by dietary assessment is difficult because of high variations in habitual micronutrient intake. A nutritional biomarker can be an indicator of nutritional status with respect to intake or metabolism of dietary constituents. The nutritional biomarkers can be designated into one or more of three categories, 1) a means of validation of dietary instruments, 2) surrogate indicators of dietary intakes, or 3) integrated measures of nutritional status for a nutrient (Potischman & Freudenheim, 2003). Recent validation studies have developed the urinary compounds as nutritional biomarkers to estimate nutrient intakes. For example, 24-hr urinary nitrogen has been established as a biomarker for protein intake (Bingham, 2003), same as urinary potassium and potassium intake (Tasevska et al., 2006), and urinary sugars for sugar intake (Tasevska et al., 2005).

Water-soluble vitamins are absorbed from the digestive tract after ingestion, stored in the liver, delivered to peripheral, and then excreted to urine (Food and Nutrition Board, Institute of Medicie, 1998). Urinary water-soluble vitamins or their metabolites decrease markedly as vitamin status declines, and they are affected by recent dietary intake (Food and Nutrition Board, Institute of Medicie, 1998). Urinary excretion of water-soluble vitamins such as thiamin, riboflavin and niacin has been used for setting Dietary Reference Intakes (DRIs) in USA and Japan (Food and Nutrition Board, Institute of Medicie, 1998; The Ministry of Health, Labour, and Welfare, 2009). Although pharmacological dose of watersoluble vitamin intake such as vitamin B2 (Zempleni et al., 1996), nicotinamide (Shibata & Matsuo, 1990) and biotin (Zempleni & Mock, 1999) dramatically increase urinary vitamin levels, a few study had studied about the relationship between several oral dose correspond to dietary intake and urinary excretion of vitamin C (Levine et al., 1996, 2001). Thus, little attention had been paid to assess the quantitative relationships between intakes and urinary excretion of water-soluble vitamins. However, only a single study had investigated urinary vitamin as a possible marker for intake until 2007. Individuals' 30-day means of thiamin intake are highly correlated with their mean 24-hr urine thiamin levels under strictly controlled condition, showing 24-hr urinary thiamin as a useful marker for thiamin intake

under strictly controlled conditions (Tasevska et al., 2007).

**1. Introduction**

**Biomarker to Estimate Their Intakes** 

Tsutomu Fukuwatari and Katsumi Shibata

*The University of Shiga Prefecture,* 

