Bullous Eruption Associated With Dihydropyridines With Cross Reactivity.

The spectrum of cutaneous eruptions associated with dihydropyridines is extensive, varying from exanthemas to severe adverse events. We report a case of bullous eruption, one month after starting nicardipine and lercanidipine. The same symptoms recurred few days after taking nitrendipine.

Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis.

Antibodies to malondialdehyde (MDA)-modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde, which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with MDA adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA-modified proteins were able to be inhibited by a chemical analogue, hexyl-MAA. Also, MDA-MAA adducts were detected in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These studies determined that commercially available antibodies to MDA predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and the aortic tissue. Therefore, the immune response to MDA-modified proteins is most probably to the dihydropyridine structure (predominant epitope in MAA), which suggests that MAA adducts may play a role in the development and/or progression of atherosclerosis.

[Obtaining antibodies to 1,4-dihydropyridine calcium channel blockers].

Immunization of rabbits with amlodipine conjugated with horseradish peroxidase resulted in raising polyclonal antibodies that allowed group determination of 1,4-dihydropyridine calcium channel blockers in aqueous solutions by ELISA with a sensitivity of 0.1 to 1.0 ng/ml for amlodipine, felodipine, nifedipine, and isradipine.

Affinity purification of antibodies specific for 1,4-dihydropyridine Ca2+ channel blockers.

High-affinity antibodies specific for the 1,4-dihydropyridine Ca2+ channel blockers have been produced in sheep and affinity purified using a dihydropyridine-Sepharose affinity column. Dihydropyridine-Sepharose affinity matrix was synthesized by reaction of aminohexyl-Sepharose with an affinity analogue of nifedipine, dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridine-dicarbo xylate. Residual amine groups were then blocked by carbodiimide-catalyzed acetylation. [3H]Nitrendipine-binding activity in serum was specifically absorbed by the dihydropyridine-Sepharose affinity column. The bound antibody was eluted with diethylamine (pH 11.5) in 10% dioxane or with a low-affinity dihydropyridine ligand (diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate), pH 7.4. Thirty-six milligrams of highly pure IgG antibody, as demonstrated by sodium dodecyl sulfate-gel electrophoresis, was isolated from 50 ml hyperimmune sheep serum. The affinity-purified anti-dihydropyridine antibodies have been shown to have high affinity (Kd approximately 0.1 nM) and specificity for the 1,4-dihydropyridine Ca2+ channel blockers and, therefore, exhibit dihydropyridine-binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+ channel blockers. Immunoblot staining of an azidopine-bovine serum albumin conjugate with affinity-purified antidihydropyridine antibodies demonstrated that the anti-dihydropyridine antibodies recognize the 1,4-dihydropyridine Ca2+ channel blockers when covalently coupled to protein and, therefore, should be useful in the identification and purification of receptors covalently labelled with 1,4-dihydropyridine Ca2+ channel blockers.