DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson's disease.

DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.

Propofol-remifentanil intravenous anesthesia and spontaneous ventilation for airway foreign body removal in children with preoperative respiratory impairment.

PURPOSE: To investigate the efficacy and safety of propofol-remifentanil total intravenous anesthesia (TIVA) and spontaneous ventilation for foreign body (FB) removal in pediatric patients with preoperative respiratory impairment. METHODS: We carried out a prospective observational clinical study of FB removal using a rigid bronchoscope under propofol-remifentanil TIVA and spontaneous ventilation in 65 pediatric patients who presented with preoperative respiratory impairment. Heart rate, blood pressure, pulse oxygen saturation (SpO(2)), respiratory rate, endtidal CO(2) (ETCO(2))(ETCO2), induction time, and remifentanil rate were recorded. Adverse events, the intervention for these events, and the duration of postoperative care were also of interest. RESULTS: Sixty children completed the study. The mean induction time was 12.3 min. During the procedure, the maximum remifentanil rate was 0.14 µg · kg(-1) · min(-1). Light breath holding occurred in 16 (26.7%) patients. No severe breath holding or body movements were observed. An SpO(2) below 90% occurred in 10 (16.7%) cases. No progressive desaturation was observed. The mean ETCO(2) at the end of the procedures was 7.91 KPa and returned to normal 5 min after the procedure. In the postanesthesia care unit (PACU), no hypoxemia was observed and the mean recovery time was 23.4 min. No laryngospasm, pneumothorax, or arrhythmias were observed. CONCLUSION: Propofol-remifentanil TIVA and spontaneous ventilation are effective and safe techniques to manage anesthesia during airway FB removal in children with preoperative respiratory impairment.

A second expressed kininogen gene in mice.

We isolated PCR, RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE-PCR)-, and RT-PCR-generated clones from mouse kininogen family transcripts. DNA sequencing indicated that the clones were from two distinct genes. One set (K1) is from the previously reported mouse kininogen gene. The second set (K2) has an open reading frame, is 93% identical to K1 in the overlapping nucleotide sequence, and, unlike T-kininogens in the rat, encodes a bradykinin motif identical to K1. We discovered that K2 exists with two different 5' ends. We used RT-PCR to determine the distribution and relative abundance of K1 and K2 mRNA in mouse tissues. K2 is transcribed and K1 and K2 are generally both expressed in the same tissues; however, they differ in their regulation of the alternative splicing event that yields either low-molecular-weight kininogen (LMWK) or high-molecular-weight kininogen (HMWK). For example, in the liver K1 is expressed as both HMWK and LMWK, whereas K2 is only expressed as LMWK. Conversely, in the kidney K2 is strongly expressed as both HMWK and LMWK, whereas K1 is not expressed as HMWK and expressed only very weakly as LMWK.