Furanonyl amino acid derivatives as hemostatic drugs: design, synthesis and hemostasis performance.

Using 3,4-dihalo-2(5H)-furanones and easily available hemostatic drugs, such as tranexamic acid (TA), 4-aminomethylbenzoic acid (ABA), aminocaproic acid (AA) as starting materials, serial multi-functional molecules 2(5H)-furanonyl amino acids are designed by the combination of different pharmacophores, and successfully synthesized by a transition metal-free Michael addition-elimination reaction. The reaction is carried out under mild conditions with ethanol-dichloromethane as solvent and only stirring at room temperature for 24 h, and the yield can be up to 91%. All products are well characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), high-resolution mass spectra (HRMS). Ten typical target compounds among them are selected out for the experiments of hemostasis performance by the evaluation of in vitro clot formation model and liver hemorrhage model. The test results show that, their hemostasis effect is better than the original drugs. Especially the target compound G, a TA derivative from 5-borneoloxy-3,4-dibromo-2(5H)-furanone, has the best hemostasis effect among all the tested compounds. These obtained target molecules are expected to be used as multi-functional hemostatic drugs.

A concise synthesis of benzimidazoles via the microwave-assisted one-pot batch reaction of amino acids up to a 10-g scale.

An efficient method for the synthesis of aminomethyl benzimidazoles is developed by using a one-pot batch reaction between amino acids and o-phenylenediamines. This reaction proceeds smoothly in an unmodified household microwave oven, even though scale-up is to 10 g. A desirable method for the quick synthesis of benzimidazoles, which are used as a kind of important intermediates in drug synthesis, is provided by the scale-up utilization of amino acid resource.

Nightmares Are Associated With Future Suicide Attempt and Non-Suicidal Self-Injury in Adolescents.

OBJECTIVE: To determine which sleep variables, including sleep duration, sleep quality, insomnia symptoms, and nightmares, were significantly and independently associated with subsequent adolescent suicidal behavior and non-suicidal self-injury (NSSI). METHODS: A prospective longitudinal study was conducted in Shandong, China. Participants were 7,072 adolescents initially assessed in November and December in 2015 and reassessed 1 year later in 2016. Self-administered structured questionnaires were used to assess suicidal behavior, NSSI, night sleep duration, insomnia symptoms, sleep quality, nightmares, impulsivity, depression, and family demographics. Logistic regression analyses were performed to examine the associations between sleep variables and suicidal behavior and NSSI. RESULTS: At 1-year follow-up, 190 participants (2.7%) attempted suicide and 621 (8.8%) engaged in NSSI. Insomnia symptoms and frequent nightmares (several times a month) at baseline were significantly associated with subsequent suicide attempt and NSSI 1 year later. After adjustment for covariates including adolescent and family demographics, depression, impulsiveness, and prior suicide attempt/NSSI, frequent nightmares in the past year remained significant for suicide attempt (OR = 1.96; 95% CI, 1.15-3.33) and NSSI (OR = 1.52; 95% CI, 1.10-2.08). With further adjustment for insomnia symptoms, sleep quality, and sleep duration, the associations between frequent nightmares and subsequent suicide attempt and NSSI had almost no change. Insomnia, short sleep duration, and poor sleep quality were not independently associated with subsequent suicide attempt and NSSI. CONCLUSIONS: Frequent nightmares were independently associated with subsequent suicide attempt and NSSI among adolescents. Assessing and intervening for nightmares may have important implications for early identification of adolescents at risk and prevention of adolescent self-harm and suicide.

Psychological and behavioral characteristics of suicide attempts and non-suicidal self-injury in Chinese adolescents.

BACKGROUND: Suicide attempts (SA) and non-suicidal self-injury (NSSI) are prevalent in adolescents and important risk factors of suicide death. Both SA and NSSI are associated with multiple psychosocial, behavioral, biological and genetic factors. This study examined similarities and differences in psychological vulnerability and internalizing and externalizing problems between adolescents with SA and NSSI. METHODS: Participants consisted of 11,831 students and had a mean age of 14.97 (SD = 1.46) years. Students completed a structured questionnaire to report their demographic information, psychological characteristics, internalizing and externalizing problems, SA and NSSI. Based on the history of NSSI and SA in the last year, the sample was divided into four groups: non-self-harm (NSH), NSSI only, SA only, and NSSI+SA. Multivariate analyses of covariance and post-hoc pairwise comparisons were performed for multiple comparisons. RESULTS: Compared with NSH group, adolescents with either NSSI or SA scored significantly higher on trait anger, impulsiveness, hopelessness, internalizing and externalizing problems. NSSI+SA group and SA only group scored significantly higher than NSSI only group but both did not score significantly different on most psychological and behavioral variables. LIMITATIONS: Limitations include reliance on self-reported measures and cross-sectional survey. CONCLUSIONS: Psychological and behavioral profiles between adolescents with SA and NSSI are similar but are more severe in suicide attempters. The findings highlight the necessity of assessing psychological and behavioral problems for prevention and early intervention of adolescent self-harm.