Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.     

Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse

We investigated quantitative changes in spinal cord motoneurons following chronic compression using a mouse model of cervical cord compression. Twenty-five tiptoe-walking Yoshimura (twy) mice with calcified mass lesions compressing the spinal cord posterolaterally at the C1–C2 vertebral levels were compared with five Institute of Cancer Research (ICR) mice that served as controls. Spinal cord motoneurons in the anterior grey horn between the C1 and C3 spinal cord segments were Nissl-stained and counted topographically and then analysed in relation to the extent of spinal cord compression. The number of motoneurons in C1–C3 spinal cord segments decreased significantly with a linear correlation with the transverse area of the spinal cord when the cord was compressed to 50–70% of control values. A significant reduction in the number of motoneurons occurred at the C2–C3 spinal cord segment compressed at the C1–C2 vertebral level. In contrast, at the level rostral to the C1 vertebra, the number of motoneurons increased significantly in proportion to the magnitude of compression. The current study demonstrates that a number of neurons, morphologically consistent with anterior horn cells, were observed at a rostral site absolutely free of external compression where no such cells normally exist.     

Decreased serum levels of epidermal growth factor in adult subjects with high-functioning autism.

BACKGROUND: The neurobiological basis for autism remains poorly understood. Given the role of growth factors in brain development, we hypothesized that epidermal growth factor (EGF) may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of EGF are altered in adult subjects with high-functioning autism. METHODS: We measured serum levels of EGF in the 17 male subjects with high-functioning autism and 18 age-matched healthy male subjects. RESULTS: The serum levels of EGF in the subjects with high-functioning autism (72.4 +/- 102.8 pg/mL [mean +/- SD]) were significantly lower (Mann-Whitney U = 22.0, p < .001) than those of normal control subjects (322.3 +/- 122.0 pg/mL [mean +/- SD]). However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. CONCLUSIONS: This study suggests that decreased levels of EGF might be implicated in the pathophysiology of high-functioning autism.     

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.     

Successful Treatment of Nephrotic Syndrome Due to Collapsing Focal Segmental Glomerulosclerosis Accompanied by Acute Interstitial Nephritis

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

O6-Methylguanine-DNA Methyltransferase (MGMT) as a Determinant of Resistance to Camptothecin Derivatives

The precise mechanisms of resistance to camptothecin (CPT)-derived DNA topoisomerase (topo I) inhibitors and the determinants remain unclear. We found that a DNA repair protein, O⁶-methylguanine-DNA methyltransferase(MGMT), participated in resistance to irinotecan hydrochloride (CPT-11), its active metabolite SN-38, and a novel CPT derivative, DX-8951f. In 17 human cancer cell lines, MGMT gene expression level closely correlated with sensitivity to the CPT derivatives, and inhibition of MGMT activity by nontoxic 5 μM O⁶-benzylguanine augmented the drug activity in relation to the MGMT expression levels in 8 cell lines examined. Transfection of pCR/MGMT-sense into U-251MG and pCR/MGMT-antisense into T98G and HEC-46 cells revealed that increased MGMT expression decreased the sensitivity to CPT-11, SN-38, and DX-8951f, whereas repressed MGMT expression sensitized cells to the drugs. Western analysis revealed that treatment of MGMT -expressing T98G cells with the drugs caused a decrease of both MGMT and topo I in a dose-dependent manner. Although, in the transfectants, MGMT expression did not so closely correlate with the sensitivity to drugs as to nimustine hydrochloride (ACNU), MGMT is probably an important resistance determinant to CPT derivatives, and may play some role in the topo I-mediated DNA damage and/or the repair process.