Faculty Bibliography

Because mesangial expansion is considered a precursor of focal glomerulosclerosis, we studied whether morphine can cause mesangial expansion. We used radiolabeled human immunoglobulin G aggregates (125I-ahIgG) to study mesangial kinetics in control and experimental (morphine-treated) rats. Control and experimental rats were administered 125I-ahIgG by tail vein. Serum levels of 125I-ahIgG and uptake of 125I-ahIgG by liver, spleen, and mesangium were determined at 4, 8, 12, 24, and 36 h after 125I-ahIgG administration. Mesangial 125I-ahIgG levels were higher (P < 0.05) at 4 h and at later periods in morphine-treated vs. control rats. Naloxone, an opioid antagonist, did not attenuate the morphine-induced mesangial accumulation of 125I-ahIgG. The mean uptake of IgG aggregates was lower in the liver and spleen of morphine-treated rats at 36 h (P < 0.05). In both in vivo and in vitro experiments, ultrastructural studies showed accumulation of IgG-coated gold particles in vesicles, endosomes, and lysosomes. Morphine may have increased the accumulation of 125I-ahIgG in the glomeruli either by increasing the delivery of macromolecules into the mesangium or by altering the exit of macromolecules from the mesangium.

Focal glomerular sclerosis is the predominant renal lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the uptake of immunoglobulin G (IgG) complexes by cultured mesangial cells (MC) and macrophages (MP). Pre-incubation of morphine (10(-6) M) decreased uptake of IgG complexes [morphine, 66,577 +/- 6,248 vs. control, 95,735 +/- 5,227 counts.min-1 (cpm).mg protein-1; P < 0.02] by MC. Morphine (10(-4)-10(-6) M) also inhibited (P < 0.01) uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-labeled low-density lipoprotein by MC. MP pretreated with morphine (10(-6) M) also showed significantly (P < 0.02) lower uptake of IgG complexes (control 94,959 +/- 4,980 vs. morphine, 58,360 +/- 11,608 cpm/mg protein). Binding studies carried out at 4 degrees C on MC and MP indicated that morphine did not modulate surface binding of IgG complexes. Naloxone, a morphine antagonist, also produced a rather decreased (P < 0.05) uptake of IgG complexes by both MP and MC and did not inhibit the effect of morphine on the uptake of IgG complexes. In vivo studies indicated that morphine-treated rats had a higher (P < 0.05) accumulation of aggregated human IgG complexes (125I-labeled ahIgG) in their glomeruli when compared with untreated rats (control rats, 256,929 +/- 40,008 cpm/g protein vs. experimental rats, 398,317 + 51,512 cpm/g). Increased accumulation of 125I-ahIgG in the glomeruli from morphine-treated rats may either be related to increased delivery of 125I-ahIgG into the mesangium or be a result of decreased drainage of 125I-ahIgG from the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)

Considerable controversy exists concerning the assessment of thyroidal state in critically ill patients with decreased serum T4 and T3 concentrations, in part because serum free T4 values are often low in such patients no matter what method of measurement is used. We developed an ultrafiltration method to measure free T4 and free T3 in undiluted serum and compared the results with those obtained using a standard equilibrium dialysis method to measure free T4 and T3. In 30 consecutive intensive care unit (ICU) patients, serum free T4 values were similar to or higher than those in 12 normal subjects by both methods in most patients and were clearly distinguishable from those in hypothyroid patients. The serum total T4 concentrations in these patients ranged from 12.9-131.3 nmol/L (mean, 68.2; normal mean, 115.8). Free T4 by equilibrium dialysis was highly correlated with free T4 by ultrafiltration in the ICU group (r = 0.91; P less than 0.001). Serum free T3 levels, however, whether measured by equilibrium dialysis or ultrafiltration, were decreased in the ICU patients, confirming other reports of lowered free T3 in critically ill clinically euthyroid patients. Our findings suggest that the use of equilibrium dialysis of undiluted serum or ultrafiltration to measure serum free T4 concentrations will distinguish euthyroid hypothyroxinemic ICU patients from those with hypothyroidism.