Neuroprotective effects of activated fibroblast growth factor receptor 1 via the suppression of p53 accumulation against poly-PR-mediated toxicity.

A GGGGCC hexanucleotide repeat expansion (HRE) within the C9orf72 gene is a major causative factor in amyotrophic lateral sclerosis (ALS). This aberrant HRE results in the generation of five distinct dipeptide repeat proteins (DPRs). Among the DPRs, poly-PR accumulates in the nucleus and exhibits particularly strong toxicity to motor and cortical neurons.

Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management.

Background: Fentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl.

[Questionnaire survey of municipalities on policies to promote physical activity among residents: An examination by administrative sector and population size].

Objectives　National policies to promote physical activity and exercise have been formulated by several ministries and agencies in Japan. This study aimed to examine the formulation and implementation of such policies in municipalities by administrative sector and population size.Methods　After stratifying all municipalities in Japan at the population level, we randomly selected 272 municipalities.

Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report.

Background: Metformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis.

Case Presentation: A 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria.

Establishment to measure oxycodone in plasma with liquid chromatography-tandem mass spectrometry.

Oxycodone (OXY) is classified as a "strong opioid" in the World Health Organization system of cancer pain treatment. However, OXY also causes severe adverse reactions, such as respiratory depression. Thus, in order to adjust the dosage of OXY for well-managed pain relief with less toxicity, we tried establishing and validating a system for measuring plasma concentrations of OXY using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Simplified daptomycin dosing regimen for adult patients with methicillin-resistant Staphylococcus aureus infections based on population pharmacokinetic analysis.

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8-10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach.

Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients.

Background/aim: The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs.

Patients And Methods: We enrolled Japanese patients prescribed OPR for HCV infection.

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo.

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of , , and in hBMSCs.

Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment.

Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients.

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model.

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model.

Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in β-tricalcium phosphate.

Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in β-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model.

Giant left-sided inguinoscrotal hernia containing the cecum and appendix (giant left-sided Amyand's hernia).

The present case involved a 62-year-old male with a large left-sided inguinoscrotal hernia. A CT scan and a clinical examination led to a diagnosis of a giant left-sided Amyand's hernia. The hernia was repaired using the ULTRAPRO Hernia System (UHS), and the patient exhibited an uneventful postoperative course.

The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism.

Bone morphogenetic protein 2 (BMP2) is a potent osteoinductive cytokine that plays crucial roles in bone repair. However, large amounts of BMP2 are required to induce sufficient bone formation in humans possibly due to a feedback response of BMP antagonists. The engineered BMP2 variant L51P is deficient in BMP receptor type I activation but maintains affinity for BMP antagonists and can allow for the inactivation of BMP antagonists, and eventually enhance BMP2 action.

Mesenchymal stem/progenitor cell isolation from tooth extraction sockets.

Bone marrow-derived mesenchymal stem/progenitor cells (BMSCs) are commonly used in regeneration therapy. The current primary source of BMSCs is the iliac crest; however, the procedure is associated with various burdens on the patient, including the risk of pain and infection. Hence, the possibility to collect BMSCs from other, more accessible, sources would be an attractive approach.

Delirium and coma evaluated in mechanically ventilated patients in the intensive care unit in Japan: a multi-institutional prospective observational study.

Purpose: The object of this study is to evaluate the prevalence and effects of delirium on 28-day mortality in critically ill patients on mechanical ventilation in Japan.

Materials And Methods: Prospective cohort study was conducted in medical and surgical intensive care units (ICUs) of 24 medical centers. Patients were followed up daily for delirium during ICU stay after enrollment.

Regeneration of calvarial defects with Escherichia coli -derived rhBMP-2 adsorbed in PLGA membrane.

Objective: Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria.

Novel chondrogenic and chondroprotective effects of the natural compound harmine.

A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee.

Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of epidermal growth factor (EGF) family, is a potent mitogenic peptide for various types of cells. HB-EGF is widely expressed in central nervous system, including hippocampus and cerebral cortex, and is considered to play pivotal roles in the developing and adult nervous system. In this study, we assessed the role of HB-EGF in learning and memory by testing HB-EGF conditional knock-out mice (KO) in two different learning tasks, and evaluated the long-term potentiation (LTP) in hippocampus slices from these mice.

[Treatment indications for sarcopenia: a systematic review of exercise intervention effect].

Objective: To evaluate exercise intervention efficacy for the prevention and treatment of sarcopenia in the elderly.

Methods: We conducted a systematic literature search of randomized controlled trials in the Physical Activity Guidelines Advisory Committee Report (before 2007), Pubmed, the Cochrane database, and Igaku Chuo Zasshi (January 2006 to August 2009).

Data Extraction: Two authors independently extracted relevant data.

Post-treatment of a BiP inducer prevents cell death after middle cerebral artery occlusion in mice.

We previously reported the effect of a selective inducer of BiP (a BiP inducer X; BIX) after permanent middle cerebral artery occlusion (MCAO) in mice. However, in acute stroke, almost all drugs have been used clinically after the onset of events. We evaluated the effect of post-treatment of BIX after permanent MCAO in mice, and examined its neuroprotective properties in in vivo mechanism.

Effects of wind and rain on thermal responses of humans in a mildly cold environment.

The purpose of the present study was to clarify the effects of wind and rain on peripheral heat loss by non-exercising minimally clothed humans in a mildly cold environment. Seven healthy young male subjects wearing only shorts rested in a standing position for 20 min at an ambient temperature of 15 degrees C under three conditions: without exposure to wind or rain (CON), with exposure to wind (3 m/s) (WIND) and with exposure to wind (3 m/s) and rain (40 mm/h) (WIND + RAIN). Mean heat loss measured using a heat flux transducer was significantly greater in the subjects exposed to WIND + RAIN compared to those exposed to CON and WIND conditions (p < 0.

Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice.

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain.

Wall-invasion pattern correlates with survival of patients with gallbladder adenocarcinoma.

Gallbladder carcinomas (GBC) frequently show vascular invasion and metastasis when the carcinoma cells invade the perimuscular connective tissue (pT2 according to the TNM classification) through the muscular layer. In this study, two intramural invasion patterns were defined as (i) infiltrative growth (IG) type, infiltrative growth in the muscle layer without destruction and (ii) destructive growth (DG) type, massive growth with destruction of the muscle layer. Sixty-six surgically resected gallbladder adenocarcinomas invading the perimuscular connective tissue (pT2) and beyond the gallbladder wall, including the visceral serosa, (pT3/pT4) were examined.

Stromal laminin-5gamma2 chain expression is associated with the wall-invasion pattern of gallbladder adenocarcinoma.

Our previous study demonstrated that the pT2 and pT3-4 gallbladder carcinomas can be classified into two groups, i.e. infiltrative growth type (IG type) and destructive growth type (DG type) and that the DG type is associated with poor differentiation, aggressive infiltration, and decreased postoperative survival.

Comparison between intravenous and oral postoperative adjuvant immunochemotherapy in patients with stage II colorectal cancer.

The present study was designed to retrospectively examine the efficacy of postoperative adjuvant chemotherapy in 107 patients with stage II primary colorectal cancer who underwent curative resection. The chemotherapy regimen was intravenous 5FU/LV in 30 patients (FL-IV group) and oral UFT/PSK in 77 patients (oral group). There were no significant differences between the FL-IV and the oral group with respect to the 3-year relapse-free survival rate, 5-year relapse-free survival rate, and 5-year overall survival rate, which were 82.