[Emergent Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Under Local Anesthesia:Report of a Case].

An 89-year-old man who had undergone aortic valve replacement with a 21 mm Mosaic bioprosthetic valve at another hospital 14 years ago was admitted to the emergency room for a sudden respiratory distress two days prior and was diagnosed with severe aortic regurgitation( AR) caused by valve insufficiency and acute heart failure secondary to low cardiac function. Upon admission, he was found to have severe hypoxia with PaO2 of 40 mmHg range, and transcatheter aortic valve replacement (TAVI, TAV in SAV) with a 20 mm SAPIEN3 was performed under local anesthesia for fear of hypotension while under general anesthesia. After confirming that AR had completely disappeared, the patient was intubated and discharged from the operating room on a mechanical ventilator. The patient was weaned from the ventilator on the second postoperative day and was transferred to the other hospital for rehabilitation, 48 days postoperatively. Although there is no report on the comparative study of anesthesia methods for emergency transcatheter aortic valve implantation( TAVI), TAVI under regional anesthesia is minimally invasive with a lower risk for hypotension than general anesthesia. Therefore, we believe it is useful for patients with acute heart failure and hypotension. In addition, it is important to use a balloon expandable valve with excellent implantability to complete the procedure in a short time.

Novel hydrogen-producing Si-based agent reduces oxidative stress, and improves sperm motility and in vitro fertilization rate in varicocoele.

BACKGROUND: Varicocoele-induced male infertility potentially involves oxidative stress. Although varicocoelectomy is recommended for varicocoele patients presenting abnormal semen findings, no pharmacotherapeutic methods currently exist. We have recently developed a silicon-based agent that produces hydrogen by the reaction with water. OBJECTIVES: This study aimed to investigate the therapeutic effects of oral administration of a Si-based agent on varicocoele rat. MATERIALS AND METHODS: Twenty-one rats were divided into four groups: varicocoele + normal diet (n = 5), varicocoele + Si-based agent-supplemented diet (n = 6), sham + normal diet (n = 5), and sham + Si-based agent-supplemented diet (n = 5). All rats were euthanized four weeks after surgery. RESULTS: The mean left epididymal sperm motility was 74.4% in the sham group, 72.3% in the sham + Si group, 57.6% in the varicocoele group, and 66.9% in the varicocoele + Si group. Epididymal sperm motility was significantly lower in the varicocoele group, but was significantly higher upon Si-based agent ingestion (P < .01). The mean left testicular weight, Johnsen's score, and left epididymal sperm concentration did not differ significantly between groups. The 8-OHdG concentration and DNA fragmentation rate were significantly increased in the varicocoele group, but were significantly decreased in the Si-based agent intake group (P < .01). Additionally, the IVF rate was significantly lower in the varicocoele group (26.3%) compared with the sham group (73.4%; P < .01), and was significantly higher in the varicocoele + Si group (51.8%) compared with the varicocoele group (P < .05), indicating that the Si-based agent improves IVF rates. DISCUSSION AND CONCLUSION: Oral intake of the silicon-based agent improves epididymal sperm motility and in vitro fertilization rates through hydrogen production and subsequent reduction of oxidative stress. Considering the lack of effective noninvasive methods, this Si-based agent is potentially applicable for treating varicocoele-induced abnormal semen parameters.

Discovery and structure-activity relationships study of positive allosteric modulators of the M3 muscarinic acetylcholine receptor.

The M3 muscarinic acetylcholine receptor (mAChR) is a member of the family of mAChRs, which are associated with a variety of physiological functions including the contraction of various smooth muscle tissues, stimulation of glandular secretion, and regulation of a range of cholinergic processes in the central nerve system. We report here the discovery and a comprehensive structure--activity relationships (SARs) study of novel positive allosteric modulators (PAMs) of the M3 mAChR through a high throughput screening (HTS) campaign. Compound 9 exhibited potent in vitro PAM activity towards the M3 mAChR and significant enhancement of muscle contraction in a concentration-dependent manner when applied to isolated smooth muscle strips of rat bladder. Compound 9 also showed excellent subtype selectivity over other subtypes of mAChRs including M1, M2, and M4 mAChRs, and moderate selectivity over the M5 mAChR, indicating that compound 9 is an M3-preferring M3/M5 dual PAM. Moreover, compound 9 displayed acceptable pharmacokinetics profiles after oral dosing to rats. These results suggest that compound 9 may be a promising chemical probe for the M3 mAChR for further investigation of its pharmacological function both in vitro and in vivo.

First synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA based on the mechanistic considerations of an unexpected strand break.

This study investigated oligonucleotide (ON) synthesis containing 4'-selenoribonucleoside(s) under standard phosphoramidite conditions. Careful operation using a manual ON synthetic system revealed that an unexpected strand break occurred to afford a C2-symmetric homodimer as a byproduct. In addition, this side reaction occurred during I2 oxidation. On the basis of these findings, the first synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA was achieved using tert-butyl hydroperoxide (TBHP) as the alternative oxidant.