Immunohistochemical demonstration of the distribution of chloroquine (CQ) and its metabolites in CQ-poisoned mice.

Chloroquine (CQ) distribution in tissues of acutely poisoned mice was demonstrated by immunohistochemistry using anti-CQ polyclonal antibodies (PAC). PAC recognized 4-amino-7-chloro-quinoline structure and sufficiently reacted with CQ and CQ's metabolite bisdesethyl-chloroquine. In the brain, CQ and its metabolites (CQs) localized in the region of the choroids plexus, indicating an important role in the blood-cerebrospinal barrier system. In the heart, most regions showed diffused positive staining, and relatively strong reaction was observed in Purkinje cells, indicating an important role in acute CQ toxicity. In the lungs, CQs were observed in the bronchial epithelium, type II pneumocytes, and on the surface of alveolar walls. It was suggested that CQs were excreted to the alveolar wall with surfactant phospholipids, which are produced by type II pneumocytes. In the liver, CQs were concentrated in the centrolobular area rather than in the periportal area, in agreement with CQ's metabolic pathway. In the kidneys, tubular cells were strongly stained compared to glomerular capsules, and the distal part of renal tubules was better stained than the proximal tubules. These findings suggested that CQs were predominantly excreted or reabsorbed through the distal tubules and the collecting duct. Distribution of CQs in tissues presented here were mostly consistent with the physico-chemical properties of CQ and its metabolites. However, the elucidation of CQs' localization in Purkinje cells remains open. Further experimental studies at the level of microorganella will be needed to clarify the present result.

[Two cases of diphenhydramine related suicide].

Two suicidal cases associated with ingestion of diphenhydramine (DPH) were reported. Case 1 is a typical DPH overdose case of a young man with the blood DPH concentration of 12.2 microg/ mL. Case 2 is a double suicide of a man and a woman. They ingested DPH and fell asleep in a vehicle which had a cooking clay charcoal stove. Their blood DPH concentrations were 0.4 and 0.7 microg/mL, which were high enough to make them sleep. Their cause of death, however, was carbon monoxide poisoning with blood CO-Hb concentration of 14 and 19%. DPH is a low toxic agent and is available as an OTC drug in Japan. Similar fatal cases can be expected to happen in Japan.