Alopecia areata in children: treatment with diphencyprone.

We assessed the efficacy of diphencyprone (DPCP) treatment in a total of 26 children with alopecia areata (AA). Sixteen children had alopecia areata totalis (AAT) and 10 had alopecia areata localis (AAL). DPCP is an absolute contact sensitizer. Twenty-five children could be sensitized with a 2% DPCP solution, whereas one child could not be sensitized. Patients were treated, once a week for at least 3 months, for up to 1 year. Twenty-one of the 25 (84%) children showed hair regrowth to a greater or lesser extent after DPCP treatment. Eight of the 25 (32%) children showed cosmetically acceptable hair regrowth. Cosmetically acceptable regrowth at the end of the study was seen in four of the 15 (27%) children with AAT and in four of the 10 (40%) children with AAL. These results are comparable with those reported in an earlier study in children with AA. Our opinion is that DPCP is a beneficial therapeutic agent in children with severe AAT and AAL showing no spontaneous remission.

Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea-pigs.

1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, cardiac M2 receptor function in vitro and bronchial responsiveness to histamine in vivo were evaluated. 2. Sensitivity to inhaled histamine was increased 3.1 fold and 1.6 fold after the early and late allergic reactions (i.e. at 5 h and 23 h after a single ovalbumin challenge), respectively. At 23 h after the last of four allergen challenges, executed on four consecutive days, bronchial hyperresponsiveness to histamine was diminished to 1.3 fold. 3. After the early response, there was no change in cardiac muscarinic M2 receptor function, since in left atria pD2 (-log EC50) and Emax values of pilocarpine and pKB values of AQ-RA 741, a selective M2 receptor antagonist, were not significantly different from controls (unchallenged sensitized animals), and this also applied to methacholine pD2 values for muscarinic M3 receptors in tracheal smooth muscle. 4. Prejunctional inhibitory muscarinic M2 autoreceptors in airway smooth muscle were markedly dysfunctional after the early allergic response, since potentiation of electrically evoked twitch contractions of tracheal preparations by low concentrations of the M2-selective muscarinic receptor antagonists, gallamine, methoctramine, AQ-RA 741 and AF-DX 116, which is the result of M2 receptor blockade, was clearly and significantly diminished compared to controls. However, after the late response, both in single and repeatedly challenged animals, twitch potentiation was not significantly different from and similar to controls, indicating restoration of M2 receptor function during the late allergic reaction.5. It is concluded that dysfunction of muscarinic M2 autoreceptors in the airways of sensitized and challenged guinea-pigs is already present after the early allergic reaction, and that it has recovered after the late response. Since histamine-induced bronchoconstriction involves vagal pathways, the present results suggest that bronchial hyperresponsiveness to histamine is partly due to M2 auto receptor dysfunction, leading to increased release of acetylcholine.

Selectivity profile of some recent muscarinic antagonists in bovine and guinea-pig trachea and heart.

The functional affinities of some recently developed subtype-selective muscarinic antagonists towards bovine tracheal smooth muscle muscarinic M3 receptors were established and compared to binding affinities for bovine cardiac M2 and functional affinities for guinea-pig tracheal smooth muscle M3 receptors; functional affinities towards bovine or guinea-pig cardiac M2 receptors were determined when the M2/M3 selectivity in bovine tissues deviated from reported guinea-pig data. It was found that the M2-selective antagonist AQ-RA 741 showed similar high affinities in bovine and guinea-pig heart (8.27-8.41); the affinity in bovine trachea, however, was almost 10-fold higher than in guinea-pig trachea (7.51-6.63). The M3-selective antagonist DAC 5945 displayed functional affinities that were similarly high in bovine and guinea-pig trachea (8.16-8.24) and approximately a 100-fold lower in bovine and guinea-pig heart (6.15-6.36); with this compound, the binding affinity in bovine cardiac membranes (6.92) was clearly higher than the functional affinity, as has meanwhile also been reported for the guinea-pig. With the M3-selective muscarinic antagonists p-fluorohexahydrosiladifenidol and UH-AH 371, affinities towards bovine tracheal muscarinic M3 receptors were 0.3 log units higher than in guinea-pig trachea (7.36-7.09 and 8.43-8.13, respectively), and, in case of p-fluorohexahydrosiladifenidol, both were lower than previously reported for the guinea-pig ileum (typically 7.8). In some instances, especially AQ-RA 741 in bovine trachea and p-fluorohexahydrosiladifenidol in bovine and guinea-pig trachea, the M3 receptor affinities found here correlated better to the reported M1 than to the M3 receptor affinities. It is concluded that small, but occasionally clear species and tissue differences exist with regard to the affinities of muscarinic receptor antagonists for smooth muscle M3 receptors, and it is suggested that this may be due to small, but potentially important differences in their amino acid sequences.