Impact of vancomycin-induced changes in the intestinal microbiota on the pharmacokinetics of simvastatin

The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, whereas that of proteobacteria increased. In addition, changes in fecal metabolites, including D-glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed whereas that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of PKs of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed

Physical properties and biological effects of mineral trioxide aggregate mixed with methylcellulose and calcium chloride

Objectives: Methylcellulose (MC) is a chemical compound derived from cellulose. MTA mixed with MC reduces setting time and increases plasticity. This study assessed the influence of MC as an anti-washout ingredient and CaCl2 as a setting time accelerator on the physical and biological properties of MTA. Material and Methods: Test materials were divided into 3 groups; Group 1(control): distilled water; Group 2: 1% MC/CaCl2; Group 3: 2% MC/CaCl2. Compressive strength, pH, flowability and cell viability were tested. The gene expression of bone sialoprotein (BSP) was detected by RT-PCR and real­ time PCR. The expression of alkaline phosphatase (ALP) and mineralization behavior were evaluated using an ALP staining and an alizarin red staining. Results: Compressive strength, pH, and cell viability of MTA mixed with MC/CaCl2 were not significantly different compared to the control group. The flowability of MTA with MC/CaCI2 has decreased significantly when compared to the control (

Acute gastritis associated with Epstein-Barr virus infection in a child

Infectious mononucleosis is Epstein-Barr virus (EBV) inducing a self-limiting clinical syndrome characterized by fever, sore throat, hepatosplenomegaly, and generalized lymphadenopathy. Gastrointestinal symptoms of EBV infection are nonspecific and occur rarely. EBV inducing acute gastrointestinal pathology is poorly recognized without suspicion. Careful consideration is needed to diagnose gastric involvement of EBV infection including gastric lymphoma, gastric cancer, and gastritis. A few recent cases of gastritis associated with EBV infection have been reported in adolescents and adults. However, there is no report of EBV-associated gastritis in early childhood. We experienced a rare case of 4-year-old girl with EBV gastritis confirmed by in situ hybridization

Comparative analysis of FBS containing media and serum free chemically defined media, CellCor for adipose derived stem cells production

Background: As a result of the aging society, the average OECD life expectancy has grown to about 80 years, yet the average health life still remains at only 65 years, leaving more than 15 years of life in an uncertain health state. Regenerative medicine is a new concept of medicine that combines cells and biomaterials to restore the functions of aged or damaged tissues or organs. It is also a good treatment for chronic diseases and incurable diseases, receiving attention as a new paradigm for treating diseases. Problems: As the market for regenerative medicine grows, mass production of consistent quality cells is required. Media is the most important thing in mass production of consistent quality cells. However, the fetal bovine serum (FBS) containing media that is currently wide used has many problems, such as unidentified viral infection, immunogenicity, lot variations, unstable supply, and ethical issues. To solve these problems and make rapid progress in regenerative medicine, a high-performance serum free chemically defined media (CDM) is needed. Solution: CellCor is a serum free CDM that provides excellent performance, safety, economy and consistency in stem cell production. CellCor allows higher-speed cell production rate than current FBS containing culture media (Figure 1). Compared to the FBS containing media, CellCor is able to maintain stem cell markers, higher population homogeneity, genetic stability, and excellent differentiation potency even at later passage. Please click Additional Files below to see the full abstract

A remnant choledochal cyst after choledochal cyst excision treated with a lumen-apposing metal stent: a case report

A lumen-apposing metal stent (LAMS) is a saddle-shaped stent with large flanges at both ends, thereby preventing stent migration and helping with approximation of the adjacent structures. We report the case of a 25-year-old female with remnant choledochal cyst which was successfully treated with LAMS after initial treatment failure with a plastic stent. Although complete excision of the cyst is the definite treatment of choledochal cysts, endoscopic ultrasonography-guided cystoduodenostomy can be considered in cases wherein surgery is not feasible and dysplasia is not present. LAMS may be preferred to plastic stents for effective resolution of remnant choledochal cyst and prevention of ascending infection

Design of aqueous redox-enhanced electrochemical capacitors with high specific energies and slow self-discharge

Electrochemical double-layer capacitors exhibit high power and long cycle life but have low specific energy compared with batteries, limiting applications. Redox-enhanced capacitors increase specific energy by using redox-active electrolytes that are oxidized at the positive electrode and reduced at the negative electrode during charging. Here we report characteristics of several redox electrolytes to illustrate operational/self-discharge mechanisms and the design rules for high performance. We discover a methyl viologen (MV)/bromide electrolyte that delivers a high specific energy of ~14 Wh kg⁻¹ based on the mass of electrodes and electrolyte, without the use of an ion-selective membrane separator. Substituting heptyl viologen for MV increases stability, with no degradation over 20,000 cycles. Self-discharge is low, due to adsorption of the redox couples in the charged state to the activated carbon, and comparable to cells with inert electrolyte. An electrochemical model reproduces experiments and predicts that 30–50 Wh kg⁻¹ is possible with optimization.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/ncomms/2015/150804/ncomms8818/full/ncomms8818.htm

Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis

PurposeHypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes.MethodsPrimary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay.ResultsAll MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05).ConclusionPretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways

Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

Background/AimsThe efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps.MethodsAmong patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed.ResultsOverall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period.ConclusionsCautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy

Usefulness of the Cytomegalovirus Antigenemia Assay in Patients With Ulcerative Colitis

Background/AimsPatients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC.MethodsWe retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2×105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration.ResultsA total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025).ConclusionsThe CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia