Severe hypoglycemia caused by a small dose of repaglinide and concurrent use of nilotinib and febuxostat in a patient with type 2 diabetes.

Repaglinide, an oral hypoglycemic agent, is a short-acting insulin secretagogue. We describe a case, in which an extremely low dose of repaglinide caused severe hypoglycemia and novel drug interactions are suggested. A 71-year-old man with type 2 diabetes was taken to the hospital due to consciousness disorder caused by severe hypoglycemia. He was taking repaglinide 0.25 mg once in the morning with nilotinib 400 mg/day and febuxostat 20 mg/day. Endogenous insulin secretion was not suppressed even in hypoglycemia. Detection of plasma repaglinide 10 h after administration in this case indicates delayed elimination of the agent, which might be derived from reduced hepatocyte uptake due to inhibitory effects of nilotinib on OATP1B1 and reduced oxidation of the agents by inhibitory effects of nilotinib, mainly on CYP3A4 activities, and of febuxostat on CYP2C8 activities. Repaglinide is eliminated by the liver, and is a short-acting insulin secretagogue with a good safety profile in patients with type 2 diabetes complicated by renal impairment, including elderly patients; however, its delayed elimination due to drug-drug interactions should be noted.

Correction to: Severe hypoglycemia caused by a small dose of repaglinide and concurrent use of nilotinib and febuxostat in a patient with type 2 diabetes.

[This corrects the article DOI: 10.1007/s13340-020-00434-w.].

Japanese young adults' attitudes toward suicide and its influencing factors.

This study investigated young Japanese adults' attitudes toward suicide and factors affecting them. Results revealed that 28.78% of respondents had serious suicidal ideation history; 18.53% knew suicidal others; and 15.29% took suicide-prevention training. A t-test showed that respondents' "Right to suicide" and "Common occurrence" scores were higher with suicidal ideation history, but "Unjustified behavior" was lower than in those without history. Results indicated that certain young adults were unsupportive by being permissive of suicide due to their suicidal ideation or becoming bystanders due to inexperience. For young Japanese adults, enhancing preventive education to alter permissive/bystander attitudes is crucial.

Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein.

A 3(')-terminal fragment of a splice variant of KIAA0641, a human homologue of apoptosis-associated tyrosine kinase (AATYK), was screened from human brain cDNA libraries by a yeast two-hybrid system using a Cdk5 activator p35 as a bait. The cloned cDNA encoded 477 amino acids, composed of internal 458 amino acids of KIAA0641 and 19 amino acids unique to this variant after splicing, then referred to this clone as hAATYKs-p35BP (human AATYK short isoform-p35 binding polypeptide). Using GST-fusion protein, hAATYKs-p35BP was shown to bind to Cdk5/p35 in a rat brain extract. hAATYKs made by fusing the kinase domain of KIAA0641 to the N-terminus of hAATYKs-p35BP was used for binding to Cdk5/p35 in HEK293 cells. Both hAATYKs and KIAA0641 bound to and were phosphorylated by Cdk5/p35. These results suggest that both isoforms of hAATYK are novel Cdk5/p35-binding and substrate proteins.