The effect of stimulus probability on the somatosensory mismatch field

We investigated the effect of deviant stimulus probability on the somatosensory magnetic mismatch negativity (MMNm) using an electrical two-point stimulation. First, we determined the discrimination threshold (DT) of the two-point distance. We applied standard stimuli at a distance that subjects felt as one point and deviant stimuli at a distance that subjects definitely felt as two points. We used three deviant stimulus probabilities, 10, 30, and 50%. The components peaking around 30–70 ms (first component) and 150–250 ms (fourth component) following deviant stimuli were significantly larger than those following standard stimuli in 10% condition, but not in 30 or 50% condition. The equivalent current dipole (ECD) was located in the contralateral primary somatosensory cortex (cSI) for the first component, and in the cSI and in the contralateral secondary somatosensory cortex (cSII) for the fourth component. The peak amplitude of the MMNm decreased as the probability of the deviant stimulus increased. The Somatosensory MMNm was affected by deviant stimulus probability similar to an auditory mismatch negativity (MMN).     

In vitro metabolism of alectinib,a novel potent ALK inhibitor,in human: contribution of CYP3A enzymes

1.?The in vitro metabolism of alectinib, a potent and highly selective oral anaplastic lymphoma kinase inhibitor, was investigated.

2.?The main metabolite (M4) in primary human hepatocytes was identified, which is produced by deethylation at the morpholine ring. Three minor metabolites (M6, M1a, and M1b) were also identified, and a minor peak of hydroxylated alectinib (M5) was detected as a possible precursor of M4, M1a, and M1b.

3.?M4, an important active major metabolite, was produced and further metabolized to M6 by CYP3A, indicating that CYP3A enzymes were the principal contributors to this route. M5 is possibly produced by CYP3A and other isoforms as the primary step in metabolism, followed by oxidation to M4 mainly by CYP3A. Alternatively, M5 could be oxidized to M1a and M1b via an NAD-dependent process. None of the non-CYP3A-mediated metabolism appeared to be major.

4.?In conclusion, this study suggests that involvement of multiple enzymes in the metabolism of alectinib reduces its potential for drug–drug interactions.     

Effects of Various Pharmaceutical Excipients on the Intestinal Transport and Absorption of Sulfasalazine,a Typical Substrate of Breast Cancer Resistance Protein Transporter

Breast cancer resistance protein (BCRP) transporter is an efflux transporter that utilizes energy from adenosine triphosphate hydrolysis to push its substrates, regardless of the concentration gradient. Its presence on the apical membrane of the intestinal mucosa is a major obstacle for the intestinal absorption of its substrates. In this study, we examined the effects of various pharmaceutical excipients on the intestinal transport and absorption of sulfasalazine, a BCRP substrate. Four excipients, including 0.05% and 0.075% BL-9EX, 0.01% and 0.05% Brij 97, 0.075% Labrasol, and 0.05% and 0.1% Tween 20 decreased the secretory transport of sulfasalazine in an in vitro diffusion chamber. Further investigation in an in situ closed loop experiment in rats showed that 0.05% and 0.1% BL-9EX and 0.1% Brij 97 effectively enhanced the intestinal absorption of sulfasalazine while maintaining minimal toxicity to the intestinal mucosa. However, 0.1% Brij 97 also increased the intestinal absorption of 5(6)-carboxyfluorescein, a paracellular marker compound. These findings suggest that BL-9EX might effectively inhibit the BCRP-mediated efflux of sulfasalazine in vivo, indicating that BL-9EX could improve the intestinal absorption of sulfasalazine and other BCRP substrates.     

Left ventricular apical pseudoaneurysm with aortic prosthetic valve endocarditis

We report an 83-year-old man with a mycotic left ventricular apical pseudoaneurysm and aortic prosthetic valve endocarditis caused by Enterococcus spp. Mycotic left ventricular pseudoaneurysm is very rare and is associated with a high risk of rupture. Here, we report the clinical presentation, diagnosis, prognosis, and treatment of a case of mycotic left ventricular pseudoaneurysm to raise awareness regarding this unusual and potentially fatal complication.     

Distinct intraspecific variations of garlic (Allium sativum L.) revealed by the exon–intron sequences of the alliinase gene

Garlic (Allium sativum L.) has been used worldwide as a food and for medicinal purposes since early times. Garlic cultivars exhibit considerable morphological diversity despite the fact that they are mostly sterile and are grown only by vegetative propagation of cloves. Considerable recombination occurs in garlic genomes, including the genes involved in secondary metabolites. We examined the genomic DNAs (gDNAs) from garlic, encoding alliinase, a key enzyme involved in organosulfur metabolism in Allium plants. The 1.7-kb gDNA fragments, covering three exons (2, 3, and 4) and all four introns, were amplified from total DNAs prepared from garlic samples produced in Asia and Europe, leading to 73 sequences in total: Japan (JPN), China (CHN), India (IND), Spain (ESP), and France (FRA). The exon sequences were highly conserved among all the sequences, probably reflecting the fully functional alliinase associated with the flavor quality. Distinct intraspecific variations were detected for all four intron sequences, leading to the haplotype classifications. A close relationship between JPN and CHN was observed for all four introns, whereas IND showed a more divergent distribution. ESP and FRA afforded clearly different variants compared with those from Asian sequences. The present study provides information that could be useful in the development of an additional molecular marker for garlic authentication and quality control.     

Impact of preoperative uncontrollable hepatic hydrothorax and massive ascites in adult liver transplantation

Purpose

Uncontrollable hepatic hydrothorax and massive ascites (H&MA) requiring preoperative drainage are sometimes encountered in liver transplantation (LT). We retrospectively analyzed the characteristics of such patients and the impact of H&MA on the postoperative course.

Methods

We evaluated 237 adult patients who underwent LT in our institute between April 2006 and October 2010.

Results

Recipients with uncontrollable H&MA (group HA: n = 36) had more intraoperative bleeding, higher Child–Pugh scores, lower serum albumin concentrations and higher blood urea nitrogen concentrations than those without uncontrollable H&MA (group C: n = 201). They were also more likely to have preoperative hepatorenal syndrome and infections. The incidence of postoperative bacteremia was higher (55.6 vs. 46.7 %, P = 0.008) and the 1- and 3-year survival rates were lower (1 year: 58.9 vs. 82.9 %; 3 years: 58.9 vs. 77.7 %; P = 0.003) in group HA than in group C. The multivariate proportional regression analyses revealed that uncontrollable H&MA and the Child–Pugh score were independent risk factors for the postoperative prognosis.

Conclusions

Postoperative infection control may be an important means of improving the outcome for patients with uncontrollable H&MA undergoing LT, and clinicians should strive to perform surgery before H&MA becomes uncontrollable.     

How to successfully resect 70 % of the liver in pigs to model an extended hepatectomy with an insufficient remnant or liver transplantation with a small-for-size graft

An insufficient remnant in extended hepatectomy and small-for-size graft in liver transplantation are critical matters in the field of liver surgery, and reliable and reproducible animal models that can provide clinically relevant and reliable data are needed. We herein describe our detailed surgical procedures for performing 70 % hepatectomy in pigs, and discuss the critical anatomical features, key techniques and pitfalls based on our experience. The porcine liver is divided into four lobes. The right lateral lobe (RLL) accounts for 30 % of the liver volume. Important points, such as selective temporal clamping of the arterial branch, confirmation of a related demarcation line, a two-step process to skeletonize Glisson’s capsules during liver resection and selective ligation of the portal venous branch to the right medial lobe without inducing any subtle injuries to Glisson’s capsules from the RLL to common bile duct, are discussed.     

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review

Esophagus - Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging...