Dose-related effects of olprinone on hypercapnia-Induced impairment of diaphragmatic contractility in pentobarbital-anesthetized dogs

AbstractBackground: In a previous study, olprinone was found to be more effective than milrinone in improving hypercapnic depression of diaphragmatic contractility in dogs.Objective: The purpose of this experimental study was to assess the doserelated effects of olprinone on hypercapnia-induced impairment of diaphragmatic contractility.Methods: This study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Hypercapnia (partial pressure of carbon dioxide [C02] in arterial blood 80-90 mm Hg) was induced in pentobarbital-anesthetized dogs by adding 10% C02 to their inspired gas. When hypercapnia was established, the dogs were randomly assigned to 1 of 4 groups: (all dogs were administered a bolus dose of olprinone 10 mg/kg) group 1 was maintained with olprinone 0.1 μg/kg · min-1; group 2 was maintained with olprinone 0.3 μg/kg · min-1; group 3 was maintained with olprinone 0.5 μg/kg min-1; and group 4 received no study drug. The study drug was administered IV for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). The study investigator was not blinded to treatment assignment.Results: Twenty-four healthy adult mongrel dogs were used in the study; 6 dogs were assigned to each treatment group. In the presence of hypercapnia in each group, Pdi (mean [SD], cm H2O) at low-frequency (20-Hz) and high-frequency (100-Hz) stimulation significantly decreased from baseline (all, P = 0.001). During study drug administration in groups 1, 2, and 3, Pdi at both stimuli levels increased significantly from hypercapnia-induced values (all, P = 0.001); in group 4, Pdi to each stimulus did not change significantly from hypercapnia-induced values. There was a significant correlation between olprinone dose and Pdi at both stimuli (all, P = 0.001). The regression equations were: Pdi at 20-Hz stimulation (cm H2O) = 24.97 × olprinone dose (μg/kg · min-1) + 13.54 (r = 0.887; n = 24) and Pdi at 100-Hz stimulation (cm H2O) = 29.18 × olprinone dose (μg/kg · min-1) + 20.55 (r = 0.911; n = 24).Conclusion: Olprinone was associated with a dose-dependent improvement of hypercapnia-induced impairment of diaphragmatic contractility in these pentobarbital-anesthetized dogs

Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD

Difference in NaCl tolerance of membrane-bound 5′-nucleotidases purified from deep-sea and brackish water Shewanella species

Shewanella species are widely distributed in sea, brackish, and fresh water areas, growing psychrophilically or mesophilically, and piezophilically or piezo-sensitively. Here, membrane-bound 5′-nucleotidases (NTases) from deep-sea Shewanella violacea and brackish water Shewanella amazonensis were examined from the aspect of NaCl tolerance in order to gain an insight into protein stability against salt. Both NTases were single polypeptides with molecular masses of ~59 kDa, as determined on mass spectroscopy. They similarly required 10 mM MgCl2 for their activities, and they exhibited the same pH dependency and substrate specificity for 5′-nucleotides. However, S. violacea 5′-nucleotidase (SVNTase) was active enough in the presence of 2.5 M NaCl, whereas S. amazonensis 5′-nucleotidase (SANTase) exhibited significantly reduced activity with the same concentration of the salt. Although SVNTase and SANTase exhibited high sequence identity (69.7%), differences in the ratio of acidic to basic amino acid residues and the number of potential salt bridges maybe being responsible for the difference in the protein stability against salt. 5′-Nucleotidases from these Shewanella species will provide useful information regarding NaCl tolerance, which may be fundamental for understanding bacterial adaptation to growth environments.This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan [No. 26240045], a grant from the Japan Society for the Promotion of Science [No. 25-1446], and The Salt Science Research Foundation [No. 1655]

Exfoliated graphene sheets decorated with metal / metal oxide nanoparticles: simple preparation from cation exchanged graphite oxide

We produced carbon hybrid materials of graphene sheets decorated with metal or metal oxide nanoparticles of gold, silver, copper, cobalt, or nickel from cation exchanged graphite oxide. Measurements using powder X-ray diffraction, transmission electron microscopy, and X-ray absorption spectra revealed that the Au and Ag in the materials (Au-Gr and Ag-Gr) existed on graphene sheets as metal nanoparticles, whereas Cu and Co in the materials (Cu-Gr and Co-Gr) existed as a metal oxide. Most Ni particles in Ni-Gr were metal, but the surfaces of large particles were partly oxidized, producing a core-shell structure. The Ag-Gr sample showed a catalytic activity for the oxygen reduction reaction in 1.0 M KOH aq. under an oxygen atmosphere. Ag-Gr is superior as a cathode in alkaline fuel cells, which should not be disturbed by the methanol cross-over problem from the anode. We established an effective approach to prepare a series of graphene-nanoparticle composite materials using heat treatment

Probing non-tensorial polarizations of stochastic gravitational-wave backgrounds with ground-based laser interferometers

In a general metric theory of gravitation in four dimensions, six polarizations of a gravitational wave are allowed: two scalar and two vector modes, in addition to two tensor modes in general relativity. Such additional polarization modes appear due to additional degrees of freedom in modified theories of gravitation or theories with extra dimensions. Thus, observations of gravitational waves can be utilized to constrain the extended models of gravitation. In this paper, we investigate detectability of additional polarization modes of gravitational waves, particularly focusing on a stochastic gravitational-wave background, with laser-interferometric detectors on the Earth. We found that multiple detectors can separate the mixture of polarization modes in detector outputs, and that they have almost the same sensitivity to each polarization mode of stochastic gravitational-wave background.Comment: 18 pages, 13 figure

Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels

Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identified ERBB4 at 2q34 as a genetic locus associated with sperm motility. However, GWASs for human semen volume and sperm concentration have not been conducted. In addition, testis size also reportedly correlates with semen quality, and it is important to identify genes that affect testis size. Reproductive hormones also play an important role in spermatogenesis. To date, genetic loci associated with plasma testosterone, sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels have been identified using GWASs. However, GWASs have not identified any relevant loci for plasma inhibin B levels. We conducted a two-stage GWAS using 811 Japanese men in a discovery stage followed by a replication stage using an additional 721 Japanese men. The results of the discovery and replication stages were combined into a meta-analysis. After setting a suggestive significance threshold for P values < 5 × 10-6　in the discovery stage, we identified ten regions with SNPs (semen volume: one, sperm concentration: three, testes size: two, and inhibin B: four). We selected only the most significant SNP in each region for replication genotyping. Combined discovery and replication results in the meta-analysis showed that the locus 12q21.31 associated with plasma inhibin B levels (rs11116724) had the most significant association (P = 5.7 × 10-8). The LRRIQ1 and TSPAN19 genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels

Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin

Fujii K., Fujishima Y., Kita S., et al. Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin. Scientific Reports 14, 3620 (2024); https://doi.org/10.1038/s41598-024-51935-6.Pharmacological activation of hypoxia-inducible factor 1 (HIF-1), a hypoxia-responsive transcription factor, has attracted increasing attention due to its efficacy not only in renal anemia but also in various disease models. Our study demonstrated that a HIF-1 activator enhanced extracellular vesicle (EV) production from cultured endothelial cells synergistically with adiponectin, an adipocyte-derived factor, through both transcriptional induction and posttranscriptional stabilization of an adiponectin binding partner, T-cadherin. Increased EV levels were observed in wild-type mice but not in T-cadherin null mice after consecutive administration of roxadustat. Adiponectin- and T-cadherin-dependent increased EV production may be involved in the pleiotropic effects of HIF-1 activators

Omega-3 Polyunsaturated Fatty Acids Suppress the Cystic Lesion Formation of Peritoneal Endometriosis in Transgenic Mouse Models

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis