Synthesis and acid ionization constants of cyclic cystine peptides

Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-_n-Cys(Trt)-OBu^t] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK¹= 2.35–2.84) and to terminal amino group (pK₂= 5.61–6.93); pK₁, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK₂, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH⁺₃-) formation.     

Circulating Megakaryocytes and Platelet Release in the Lung

1. Megakaryocytes were demonstrated in central venous blood of each of23 patients who underwent cardiac catheterization. Cell counts ranged from0.7 to 5.9 megakaryocytes per ml. of blood; the equivalent of one-third ofthese cells were considered to contain a full complement of cytoplasm. It hasbecome evident that megakaryocytes are normal constituents of blood.

2. In an attempt to quantify megakaryocyte migration from the bone marrow it was calculated that from 20-50 per cent of the mature megakaryocytepopulation enters the blood and ultimately reaches the lungs. The possibilitythat all megakaryocytes migrate from the marrow is not precluded with certainty by these studies.

3. It was estimated that from 7-17 per cent of the body’s platelets are released in the pulmonary capillaries. If all megakaryocytes migrate from thebone marrow, then as much as 33 per cent of the platelet population is delivered to the blood in the lungs.

Submitted on January 15, 1965 Accepted on March 13, 1965     

Origin of Pulmonary Megakaryocytes

1. Evidence is presented which indicates that pulmonary megakaryocytesdo not originate in the lungs but elsewhere in the body and are carried tothe lungs in the venous blood.

2. Some megakaryocytes in the lungs evidently deliver platelets to theblood.

3. Surgery is a potent stimulus to megakaryocyte production; the numbersof megakaryocytes found in the lung postoperatively is significantly increased.

Submitted on July 3, 1964 Accepted on September 19, 1964     

Transferrin and the Absorption of Iron

A loop isolated in situ has been used to study iron absorption in the dog.An infusion of iron salt into the artery supplying the isolated loop fails tostop the absorption of iron from the lumen of the gut. Iron absorption appearsto be independent of the relative saturation of iron-binding protein.

Submitted on July 9, 1962 Accepted on July 26, 1962     

Fe59 Absorption in Human Subjects Using Total-Body Counting Technic

In most procedures utilizing total body counting to measure iron absorptionin humans, the assumption is made that iron located in the gastrointestinaltract is counted with the same efficiency as Fe⁵⁹ distributed throughout thebody. This assumption was found to be in error in a significant number ofsubjects.

Submitted on July 2, 1964 Accepted on August 6, 1965     

Iron Absorption: Effects of Sugars and Reducing Agents

The effect of the iron-chelating sugars, fructose, glucose and galactose, oniron absorption in rats has been examined. Fructose has an effect in increasing iron absorption. Glucose and galactose have no effect on iron absorption.These findings suggest that the metabolism of fructose is responsible forchanging iron absorption in the rat since it is metabolized during its absorption, while glucose and galactose are not.

Pyruvate and lactate, the final products of glycolysis, also increase ironabsorption in the rat. The effects of lactate and hydroquinone on iron absorption are additive, suggesting independent actions. The effects of cysteineand hydroquinone on iron absorption are additive, suggesting independentactions of these two reducing agents in increasing iron absorption. Alternativehypotheses are offered in explanation of these observations.

Submitted on December 20, 1963 Accepted on February 25, 1964