PubMed HealthSearch

Biomedical subjects

P Harmatz

Publications and source records attributed to P Harmatz.

7 recordsLinked to original sources

Elevated plasma ceruloplasmin in insulin-dependent diabetes mellitus: evidence for increased oxidative stress as a variable complication.

Ceruloplasmin (Cp) is an acute-phase-responsive oxidase enzyme. Prior reports suggest that Cp is increased in diabetes mellitus, perhaps reflecting greater oxidant stress. However, the situation in insulin-dependent diabetes mellitus (IDDM) per se remains unclear. Furthermore, vitamin C can interfere with one indirect assay for Cp, and vitamin C metabolism is altered in IDDM. We measured Cp levels by both a direct radial immunodiffusion (RID) assay and an indirect oxidase assay in 10 subjects with IDDM and 10 nondiabetics, both at baseline and after 30 days of vitamin C supplementation (100 or 600 mg daily, five subjects per group). Plasma copper level was measured independently also. Our data show that circulating levels of Cp are significantly increased in IDDM subjects as a group, and specifically that Cp is abnormally high in a subset of IDDM individuals. Vitamin C supplementation at either dose interfered with the oxidase assay for Cp in both groups, but vitamin C did not alter the RID assay. The observed increase in plasma copper suggests that circulating holo-Cp is increased. The finding of increased Cp in some individuals with IDDM supports the hypothesis of increased oxidant stress as a variable factor in the spectrum of chronic complications in diabetes. Measurements of Cp level by the oxidase assay must be considered unreliable for subjects taking vitamin C supplements of > or = 100 mg/d.

Acute-Phase Reaction

Prolactin is transported across the epithelium of the jejunum and ileum of the suckling rat.

Milk prolactin is transferred from the gastrointestinal tract to the circulation of the suckling rat. To identify the site of prolactin penetration and to determine the mechanism by which the hormone traverses the mucosal barrier, we followed the uptake of prolactin from ligated loops of jejunum or ileum in vivo by three methods: autoradiography, transport of prolactin-gold conjugates, and immunocytochemistry. Autoradiographic studies demonstrated specific binding sites for 125I-prolactin on apical membranes of the jejunum and ileum. Excess cold prolactin reduced radiolabel in apical and basal compartments. Gel autoradiography of portal sera showed the presence of intact prolactin and a prolactin fragment following jejunal transport but only a prolactin fragment following ileal transport. Uptake of prolactin-gold conjugates demonstrated that, in the jejunum, label was present at the luminal surface, within endosomal compartments and lysosomes, in basal coated and smooth vesicles, within basal coated pits, and beyond the basolateral surface. In the ileum, label was found at the luminal surface; within the tubulocisternae, endosomal vesicles, lysosomes, and basal smooth vesicles; and beyond the basolateral surface. Immunoreactive prolactin was present throughout the transepithelial pathways. This study demonstrates that prolactin is selectively and nonselectively absorbed in the jejunum and ileum and that the hormone is directed either to the lysosome for degradation or across the epithelium by means of a transcellular pathway.

Animals

Burn severity, copper dose, and plasma ceruloplasmin in burned children during total parenteral nutrition.

Copper (Cu) is an essential nutrient with known metabolic roles in wound healing. Ceruloplasmin (CP), the primary Cu-transport protein, responds as an acute-phase reactive protein after trauma. However, for severe burn trauma, this response is absent in the early catabolic phase despite Cu provision. We report data for 14 severely burned children receiving Cu in total parenteral nutrition (TPN-Cu) ranging from 7 to 26 micrograms Cu.kg-1 x day-1. All patients manifested low plasma levels of CP. The reduction in CP reflected burn severity but also appeared to be dependent on the Cu dose. Increasing Cu supplementation to improve CP raises a concern for hepatotoxicity, which is accompanied by an elevation in the plasma nonceruloplasmin Cu (nonCP-Cu). The calculated plasma nonCP-Cu in our series is consistent with a lack of increased risk and suggests that TPN-Cu at the general pediatric guideline of 20 micrograms.kg-1 x day-1 is safe and reasonable for severely burned children. Cu supplementation > 20 micrograms/kg may be beneficial; however, monitoring of both CP and total Cu should continue as standard practice in the management of these patients.

Burns