Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice

Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders

Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory activity

The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance.This study was partly supported by a Grant-in-Aid for Research Activity Start-up (JSPS KAKENHI Grant Number JP15H06427) (to T.Y.) from the Ministry of Education, Science, Sports and Culture, Japan, and grants from Mitsubishi Tanabe Pharma (to T.Y.), Novartis Pharma (to T.Y.), Takeda Science Foundation (to Y.N.), Asahi Life Foundation (to Y.N.) and The Uehara Memorial Foundation (to Y.N.)

Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation

<p>Abstract</p> <p>Background</p> <p>There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation.</p> <p>Method</p> <p>We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%).</p> <p>Results</p> <p>Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively.</p> <p>Conclusion</p> <p>Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.</p

Heart Rate Variability and Non-Linear Dynamics in Risk Stratification

The time-domain measures and power–spectral analysis of heart rate variability (HRV) are classic conventional methods to assess the complex regulatory system between autonomic nervous system and heart rate and are most widely used. There are abundant scientific data about the prognostic significance of the conventional measurements of HRV in patients with various conditions, particularly with myocardial infarction. Some studies have suggested that some newer measures describing non-linear dynamics of heart rate, such as fractal measures, may reveal prognostic information beyond that obtained by the conventional measures of HRV. An ideal risk indicator could specifically predict sudden arrhythmic death as the implantable cardioverter-defibrillator (ICD) therapy can prevent such events. There are numerically more sudden deaths among post-infarction patients with better preserved left ventricular function than in those with severe left ventricular dysfunction. Recent data support the concept that HRV measurements, when analyzed several weeks after acute myocardial infarction, predict life-threatening ventricular tachyarrhythmias in patients with moderately depressed left ventricular function. However, well-designed prospective randomized studies are needed to evaluate whether the ICD therapy based on the assessment of HRV alone or with other risk indicators improves the patients’ prognosis. Several issues, such as the optimal target population, optimal timing of HRV measurements, optimal methods of HRV analysis, and optimal cutpoints for different HRV parameters, need clarification before the HRV analysis can be a widespread clinical tool in risk stratification

Anesthetic management of the emergency laparotomy for a patient with multiple sclerosis -A case report-

A 33-year-old male patient with multiple sclerosis (MS) received an emergency laparotomy because of perforated appendicitis. He had been suffering from MS for 2 years and the symptoms of MS were paraplegia and urinary incontinence. Anesthesia was induced with propofol and remifentanil and maintained with nitrous oxide, sevoflurane and remifentanil. Rocuronium was used for tracheal intubation. Train of four ratio and bispectral index scale were also monitored for adequate muscle relaxation and anesthetic depth. The patient emerged from general anesthesia smoothly and was extubated without any complication. Postoperative exacerbation of MS symptoms did not appear. However, he was rehospitalized because deep vein thrombosis (DVT) occurred after discharge and he received heparinization immediately. Eventually, he was discharged after a full recovery from DVT. We report a safe anesthetic management of the patient with MS, with the use of sevoflurane and with no the aggravation of MS during postoperative period

Open Access

The development of loop-mediated isothermal amplification targeting alpha-tubulin DNA for the rapid detection of Plasmodium viva

Treatment of high-risk neuroblastoma

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose 131I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB