Middle molecule hypothesis

Vanholder R, Van Laecke S, Glorieux G (2008) The middle-molecule hypothesis 30 years after lost and rediscovered in the universe of uremic toxicity J Nephrol 21(2) 146-160... 

B32. Brunner, H and Mann, H What remains of the middle molecule hypothesis today Contrib. Nephrol. 44, 14-39 (1985). 

The first hemodialysis devices utilized natural cellulose (cuprophan) membranes, which possessed predominantly small pores. These membranes permitted the removal of excess fluid, ions, and small molecules, but prohibited the removal of substances above approximately 1200 Da in size. Larger molecules, such as P2-microglogulin (P2M, ll.SkDa), accumulated in the blood and were thought to contribute to many of the additional health problems and high mortality of patients on dialysis. This idea, coined the middle molecule hypothesis by Bapp et al. [342], led to the development of new synthetic polysulfone or polyacrylonitrile dialysis membranes that possessed larger pores and, in combination with equipment to control transmembrane pressure, permitted more efficient elimination of middle molecules. 

The hairpin-DNA transporter (Table 24.1) was 30 bases long (30-mer) and contained a thiol substituent at the 5 end that allowed it to be covalently attached to the inside walls of the Au nanotubes [6]. The first six bases at each end of this molecule are complimentary to each other and form the stem of the hairpin, and the middle 18 bases form the loop (Table 24.1). The permeating DNA molecules were 18-mers that are either perfectly complementary to the bases in the loop, or contain one or more mismatches with the loop (Table 24.1). A second thiol-terminated DNA transporter was investigated (Table 24.1). This DNA transporter was also a 30-mer, and the 18 bases in the middle of the strand were identical to the 18 bases in the loop of the hairpin-DNA transporter. However, this second DNA transporter does not have the complementary stem-forming bases on either end and thus cannot form a hairpin. This linear-DNA transporter was used to test the hypothesis that the hairpin-DNA... 

Barke, Doerfler and Knoop [18] planned lectures according to the second hypothesis in middle school classes 14-16 years old students were supposed to understand acids, bases and neutralization. Instead of taking the usual equation HC1 + NaOH —> NaCl + H20 for the reaction, H + (aq) ions for acidic solutions and OII (aq) ions for basic solutions were introduced, the ionic equation of the formation of water molecules was explained H + (aq) ions + OH (aq) ions > H20 molecules . Later it was related that, with regard to neutralization, other students think of a formation of salt because NaCl is a product of this neutralization . Students discussed this idea with the result that no solid salt is formed by neutralization, Na + (aq) ions and Cl (aq) ions do not react but only remain by the neutralization. These ions are therefore often called spectator ions . 

The compositional paradigm proved very successful when reinforced by John Dalton s atomic hypothesis. By the middle of the nineteenth century, the definition of a compound by the nature and proportion of its constituents was being challenged by a structural paradigm that took into account the arrangement of atoms in molecules. Nevertheless, structural formulas do not respect the either/or condition any more than the compositional approach, but instead displace it. On this model, it is the physical arrangement of the constituent elements that accounts for the properties of the compound. 

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