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PubMed1990

Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population.

This study was designed to explore the incidence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) and their relationship to each other in a healthy population of 499 blood donors. Plasma samples were tested for LA activity and IgG, IgM and polyvalent ACA. Prolongation of the kaolin clotting time of a mixture of 80% normal plasma and 20% test plasma compared to the normal (dKCT) was used to detect LA activity. A normal distribution of dKCT was found with the mean 3.5 seconds +/- SD 10.6 seconds. Forty subjects (8%) were greater than 10% of the normal control; among these, 18 (3.6%) were outside the 95% confidence limits. The median age (29.3) and sex (M = 12, F = 28) of the 40 subjects with prolonged KCT were significantly different (p less than 0.001) from the group as a whole, younger females predominating. The frequency distribution of IgG, IgM and polyvalent ACA was skewed and the majority did not have detectable levels. ACA concentration falling within 95% of the population group were regarded as normal. Applying this definition, abnormal IgG ACA was greater than 4.33 U/ml, IgM ACA greater than 3.55 U/ml and polyvalent ACA greater than 4.55 U/ml with a prevalence of 4.6%, 4.6% and 5.6% respectively. Of the subjects with positive ACA of any class there was no significant association with either age or sex or the presence of LA. Only three plasma samples had both activities. Neither ACA nor LA were associated with antinuclear antibodies (ANA) or rheumatoid factor (Rh factor). Thus, in a healthy population LA is found predominantly in younger females and neither LA or ACA appear to identify subjects with other autoimmune parameters such as ANA or Rh factor or, for that matter, each other.

Adult↗
PubMed1991

Modulation of neonatal rat myeloid kinetics resulting in peripheral neutrophilia by single pulse administration of Rh granulocyte-macrophage colony-stimulating factor and Rh granulocyte colony-stimulating factor.

Rh granulocyte-macrophage (GM) colony-stimulating factor (CSF) and rh granulocyte (G) CSF have been demonstrated to induce proliferation and maturation of myeloid stem cells and release of mature polymorphonucleocytes (PMNs) from human and animal adult bone marrows. Unfortunately, reduced bone marrow progenitor cells, neutrophil storage pool (NSP) depletion and peripheral neutropenia are characteristic of human and animal newborn bone marrows. We investigated the effect of administering intraperitoneal rhGM-CSF and rhG-CSF to Sprague-Dawley newborn rats (less than 36 h). Newborn rats treated with intraperitoneal CSF (3.0 micrograms/kg) demonstrated significant leukocytosis at 6 and 24 h: rhGM-CSF vs. control, WBC (10(3)/mm3), at 6 h, 8.0 +/- 0.5 vs 4.3 +/- 0.9 (p less than or equal to 0.003), and at 24 h, 7.7 +/- 1.7 vs. 3.8 +/- 0.2 (p less than or equal to 0.008); rhG-CSF vs. control WBC (10(3)/mm3) at 6 h, 6.6 +/- 1.2 vs 4.3 +/- 0.1 (p less than or equal to 0.03), and at 24 h, 8.1 +/- 0.2 vs. 3.75 +/- 0.2 (p less than or equal to 0.003). The absolute neutrophil count was also significantly elevated at 6 h following intraperitoneal CSF (3.0 micrograms/kg): RhGM-CSF vs. control 1,827 +/- 25 vs. 379 +/- 10 (p less than or equal to 0.001); rhG-CSF vs. control, 1,698 +/- 40 vs. 371 +/- 10.1 (p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Nicardipine hydrochloride suppresses DNA synthesis in human mesangial cells stimulated with recombinant human (rh) platelet-derived growth factor AA, rh interleukin-1 alpha, or rh tumor necrosis factor-alpha.

In order to define the role of cytokines in mesangial cell pathophysiology, we measured the mitogenic activity of recombinant human platelet-derived growth factor AA (rhPDGF-AA), rh interleukin-1 alpha (rhIL-1 alpha) and rh tumor necrosis factor-alpha (rhTNF-alpha) in cultured human mesangial cells, and investigated the effect of the calcium channel blocker nicardipine hydrochloride on their cell mitogenic activity. DNA synthesis in mesangial cells, stimulated by rhPDGF-AA, rhIL-1 alpha or rhTNF-alpha, was measured using [3H]TdR up take and similar investigations, with nicardipine hydrochloride added to the above, were conducted. The results showed DNA synthesis in cultured human mesangial cells were stimulated by rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha, and this effect was reduced by the addition of nicardipine hydrochloride. Since rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha are released by the inflammatory cells which infiltrate glomeruli, these cytokines may be involved in the mechanisms of mesangial cell proliferation observed in immune-mediated mesangial proliferative glomerulonephritis. Nicardipine hydrochloride reduced DNA synthesis in cultured human mesangial cells in response to these cytokines, suggesting possible application in medical therapy for immune-mediated mesangial proliferative glomerulonephritis.

Calcium Channel Blockers↗
PubMed1996

Pharmacokinetics and interspecies scaling of recombinant human factor VIII.

Recombinant human (rh) factor VIII is a glycoprotein consisting of multiple polypeptides with relative mobilities (M(r)) ranging from 80,000 to 210,000. It is produced in mammalian cells. Single-dose intravenous pharmacokinetic studies were conducted with rh factor VIII (Kogenate rh Antihemophilic Factor, Miles, Inc.) in male mice (21.0-25.8 g) and rats (252.0-254.2 g). Each species received 400 IU/kg, and blood was collected up to 12 hr (mice) or 32.5 hr (rats) post-dose. Immunoreactive factor VIII concentrations in plasma were quantified by a sensitive and specific ELISA. In both species, the disposition profiles were described by the sum of two exponentials. The pharmacokinetics of rh factor VIII in mouse were as follows: clearance, 27.7 ml/hr/kg; initial volume of distribution, 72 ml/kg; steady-state volume of distribution, 148 ml/kg; and terminal half-life, 4.1 hr. In rat, the mean estimates were as follows: clearance, 16.0 ml/hr/kg; initial volume of distribution, 41 ml/kg; steady-state volume of distribution, 125 ml/kg; and terminal half-life, 5.5 hr. These pharmacokinetic parameters for rh factor VIII in animals and human rh factor VIII pharmacokinetic parameters from the literature were evaluated to determine if the parameters can be represented by the allometric relationship, Y = aWb, where Y is the pharmacokinetic parameter, and W is body weight. The following allometric relations were obtained for rh factor VIII: clearance (ml/hr) = 10.4W0.69, half-life (hr) = 7.5 W0.18, initial volume of distribution (ml) = 43.6 W1.04, and steady-state volume of distribution (ml) = 99.1 W0.84. The allometric exponents for each parameter conformed to theory and were within the range of values commonly observed for xenobiotics and therapeutic proteins. These studies suggest that the pharmacokinetics of rh factor VIII in laboratory animals are predictive of the disposition in humans despite the complex nature of its biological interactions and the chemical diversity of the purified material.

Animals↗