Non-aqueous bonding of leuprorelin to ochratoxin A for peptide-based solid-phase extraction.

The anticancer therapeutic leuprorelin was found to have excellent affinity to the carcinogen ochratoxin A (OTA), with an equilibrium constant of 2.2 × 108 M-1 at 273 K (dissociation constant Kd = 4.5 nM) when functionalized into a mesoporous polymer. Binding between the surface-bound leuprorelin and mycotoxin was corroborated with DFT calculations, and it was extended to the extraction of OTA from the heavily fatty matrices of coffee, achieving 95% recovery with improved cyclability as compared with immunoaffinity. This work presents the potential of peptide-mycotoxin interactions for durable non-aqueous extraction.

Safety and efficacy of minimalist approach in transfemoral transcatheter aortic valve replacement: insights from the Optimized transCathEter vAlvular interventioN-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry.

OBJECTIVES: Favourable results have been reported for monitored anaesthesia care that includes local anaesthesia and conscious sedation [minimalist approach (MA)] for transfemoral transcatheter aortic valve replacement (TAVR). However, the efficacy of MA is still controversial in Japan. We describe our experience from a Japanese multicentre registry. METHODS: Between October 2013 and April 2016, 1215 consecutive Japanese patients with symptomatic, severe aortic stenosis undergoing TAVR with self-expandable or balloon-expandable valves were prospectively included in the Optimized transCathEter vAlvular intervention-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. Of these patients, we retrospectively reviewed 921 consecutive patients who underwent elective transfemoral-TAVR. We evaluated the perioperative results of MA-TAVR and non-minimalist approach (NMA) TAVR using propensity score matching analysis. RESULTS: A total of 118 patients underwent MA-TAVR, and 802 patients underwent NMA-TAVR [median age 84 vs 85 years, P = 0.25; Society of Thoracic Surgeons (STS) score 7.6 vs 6.4, P = 0.01]. One hundred eighteen matched pairs were compared after propensity score matching. In-hospital mortality and stroke/transient ischaemic attack were not significantly different between the MA-TAVR and the NMA-TAVR groups (2.5% vs 0.8%, P = 0.3; 1.7% vs 0.8%, P = 0.6, respectively). Major or life-threatening bleeding and the transfusion rate were significantly lower in the MA-TAVR group (3.4% vs 17%, P = 0.003; 6.8% vs 29%, P = 0.0002, respectively). The total intensive care unit days and length of hospital stay were significantly lower in the MA-TAVR group (P ≤ 0.0002). CONCLUSIONS: MA-TAVR has similar results to NMA-TAVR in terms of mortality and stroke in this Japanese multicentre registry. Shorter procedure time and hospital stays were seen in the MA-TAVR group. MA-TAVR is as safe and effective as NMA-TAVR.

Clinical outcomes and safety of transfemoral aortic valve implantation under general versus local anesthesia: subanalysis of the French Aortic National CoreValve and Edwards 2 registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) performed under local anesthesia (LA) is becoming increasingly common. We aimed to compare the clinical outcomes in patients who underwent transfemoral-TAVI under general anesthesia (GA) and LA. METHODS AND RESULTS: Data from 2326 patients in the French Aortic National CoreValve and Edwards 2 (FRANCE 2) registry who underwent transfemoral-TAVI were analyzed. During the study period, the percentage of LA procedures increased gradually from 14% in January 2010 to 59% in October 2011. The clinical outcomes for GA (n=1377) and LA (n=949) were compared. Numerous baseline characteristics differed between the 2 groups, and the use of transesophageal echocardiographic guidance was more common in GA than in LA (76.3% versus 16.9%; P<0.001). Device success and cumulative 30-day survival rates were similar in the 2 groups (97.6% versus 97.0%; P=0.41 and 91.6% versus 91.3%; P=0.69, respectively), whereas the incidence of postprocedural aortic regurgitation≥mild was significantly lower in GA than in LA (15.0% versus 19.1%; P=0.015). The groups were also analyzed using a propensity-matching model, including transesophageal echocardiographic usage (GA [n=401] versus LA [n=401]). This model indicated that there were no significant differences between the 2 groups in the rates of 30-day survival (GA [91.4%] versus LA [89.3%]; P=0.27] and postprocedural aortic regurgitation≥mild (GA [12.7%] versus LA [16.2%]; P=0.19). CONCLUSIONS: The less invasive transfemoral-TAVI under LA is preferred in clinical settings and seems to be acceptable; however, the higher incidence of postprocedural aortic regurgitation is emphasized. Therapeutic efforts should be made to reduce such complications during transfemoral-TAVI under LA.

Effect of local anesthetic management with conscious sedation in patients undergoing transcatheter aortic valve implantation.

The present study sought to assess the effectiveness of local anesthesia with conscious sedation (LACS) during transcatheter aortic valve implantation (TAVI). On its introduction, TAVI was mostly performed with the patient under general anesthesia (GA); however, evidence supporting the use of less-invasive LACS has been increasing. The data from 174 consecutive patients who underwent TAVI by way of the femoral artery from December 2007 to December 2011 were analyzed. GA was mainly used in early phase of the study (n = 44); this was gradually shifted to LACS in the late phase (n = 130). The clinical outcomes were compared for those patients who received GA versus LACS. The incidence and causes of "LACS failure," defined as conversion to GA from LACS during TAVI, were also assessed. The rates of procedural success and 30-day mortality were not different between the 2 groups (93.3% vs 95.3%, p = 0.60; 6.7% vs 7.8%, p = 0.55, respectively). Although the clinical backgrounds of the patients showed differences, these results were not significant after adjusting for other influential confounders. The intensive care unit stay and hospital stay were longer in the GA group than in the LACS group (3.9 ± 2.2 vs 3.3 ± 1.5 days, p = 0.044; and 12.2 ± 8.3 vs 8.1 ± 6.5 days, p = 0.001, respectively). LACS failure occurred in 6 patients (4.6%), and the causes were multifactorial, as follows: cardiac tamponade in 2, cardiac arrest in 2, myocardial infarction in 1, and stroke in 1. In conclusion, transfemoral TAVI with the patient under LACS could be successfully performed in most patients, with the advantage of early recovery, although the perioperative risks involved in the TAVI procedure should be considered.

Tea catechin consumption reduces circulating oxidized low-density lipoprotein.

It has been reported that green tea consumption reduces the risk of coronary artery disease and cardiac events. Catechin is a major constituent of Japanese green tea and an antioxidant. Lipids and oxidization of low-density lipoprotein cholesterol (LDL-C) play important roles in atherosclerosis. Therefore, we evaluated the effect of catechin intake on the lipid profile and plasma oxidized LDL. The study population consisted of 40 healthy adult volunteers (10 men, 30 women). Catechin was extracted from green tea leaves. The subjects were randomly divided into two groups, a catechin group (n = 29) and a control group (n = 11). In the catechin group, catechin (500 mg: equivalent to 6 or 7 cups of green tea) was administered orally. Venous blood samples were obtained before eating a meal at the start and after 4 weeks without any lifestyle modification. Plasma oxidized LDL assay was performed with a sandwich-type enzyme immunoassay using anti-oxidized phosphatidylcholine monoclonal antibody. The baseline lipid profiles and tea consumptions were similar between the two groups. Plasma oxidized LDL was significantly decreased after catechin administration (from 9.56 +/- 9.2 to 7.76 +/- 7.7 U/mL, P = 0.005), while plasma LDL-C, triglyceride, and HDL-C concentrations did not change. Catechin decreased the plasma oxidized LDL concentration without significant change in plasma LDL concentration. The mechanism of the beneficial effects of green tea on coronary artery disease might result from a decrease in plasma oxidized LDL.

Identification of nesfatin-1 as a satiety molecule in the hypothalamus.

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.