Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis

The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ(-/-)ApoE(-/-)) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ(+/+) ApoE(-/-) mice, in the absence of an effect of cholesterol levels. Immunohistochemical detection of smooth muscle cells, using a smooth muscle alpha-actin antibody, showed greatly reduced staining for these cells in lesions of APJ(-/-)ApoE(-/-) mice fed a high-cholesterol diet. Vascular production of superoxide radicals and the expression of nicotinamide-adenine dinucleotide phosphate oxidase subunits were decreased in APJ(-/-)ApoE(-/-) mice compared with APJ(+/+)ApoE(-/-) mice fed a standard normal diet. In vascular smooth muscle cells, apelin induced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression. Apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium. The apelin-APJ system is a mediator of oxidative stress in vascular tissue, and thus we propose it to be a critical factor in atherogenesis under high-cholesterol dietary conditions. APJ deficiency is preventative against oxidative stress-linked atherosclerosis.     

Characterization of voltage-gated ionic channels in cholinergic amacrine cells in the mouse retina

Recent studies have shown that cholinergic amacrine cells possess unique membrane properties. However, voltage-gated ionic channels in cholinergic amacrine cells have not been characterized systematically. In this study, using electrophysiological and immunohistochemical techniques, we examined voltage-gated ionic channels in a transgenic mouse line the cholinergic amacrine cells of which were selectively labeled with green fluorescent protein (GFP). Voltage-gated K(+) currents contained a 4-aminopyridine-sensitive current (A current) and a tetraethylammonium-sensitive current (delayed rectifier K(+) current). Voltage-gated Ca(2+) currents contained a omega-conotoxin GVIA-sensitive component (N-type) and a omega-Aga IVA-sensitive component (P/Q-type). Tetrodotoxin-sensitive Na(+) currents and dihydropyridine-sensitive Ca(2+) currents (L-type) were not observed. Immunoreactivity for the Na channel subunit (Pan Nav), the K channel subunits (the A-current subunits [Kv. 3.3 and Kv 3.4]) and the Ca channel subunits (alpha1(A) [P/Q-type], alpha1(B) [N-type] and alpha1(C) [L-type]) was detected in the membrane fraction of the mouse retina by Western blot analysis. Immunoreactivity for the Kv. 3.3, Kv 3.4, alpha1(A) [P/Q-type], and alpha1(B) [N-type] was colocalized with the GFP signals. Immunoreactivity for alpha1(C) [L-type] was not colocalized with the GFP signals. Immunoreactivity for Pan Nav did not exist on the membrane surface of the GFP-positive cells. Our findings indicate that signal propagation in cholinergic amacrine cells is mediated by a combination of two types of voltage-gated K(+) currents (the A current and the delayed rectifier K(+) current) and two types of voltage-gated Ca(2+) currents (the P/Q-type and the N-type) in the mouse retina.     

Anatomical names of skeletal surfaces: analysis and classification of Latin names, and comparison with corresponding Japanese names

For better understanding of the structures comprising the human body and in view of possible need for future revision, Latin anatomical names (Terminologia Anatomica) of the skeletal surfaces were analyzed and classified, and compared with the corresponding Japanese anatomical names. The words following Facies indicated: 1) morphological resemblance of the surface; 2) the structure that articulates with the surface; 3) the structure attached to the surface; 4) the structure in contact with the surface; 5) the way of connection between the surface and the structure that faces it; 6) the structure of which the surface is a component; 7) the structure that the surface faces; 8) the site that the surface faces; 9) the relative position of the surface; 10) the non-relative position of the surface; 11) an articulation of the surface; or 12) both the structure with which the surface articulates and the structure of which the surface is a component. Analysis of Latin names and comparison with Japanese names clarified some characteristics of both names and revealed some problems in them.     

Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin-10 gene-deficient mice with colitis

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10-/-) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10-/- mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10-/- mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN-gamma production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10-/- mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN-gamma production.     

Involvement of an Orphan Transporter,SLC22A18, in Cell Growth and Drug Resistance of Human Breast Cancer MCF7 Cells

The SLC22A18 gene, which encodes an orphan transporter, is located at the 11p15.5 imprinted region, an important tumor suppressor gene region. However, the role of SLC22A18 in tumor suppression remains unclear. Here, we investigated the involvement of SLC22A18 in cell growth, invasion, and drug resistance of MCF7 human breast cancer cell line. Western blot analysis indicated that SLC22A18 is predominantly expressed at intracellular organelle membranes. Quantitative proteomics showed that knockdown of SLC22A18 significantly altered the expression of 578 (31.0%) of 1867 proteins identified, including proteins related to malignancy and poor prognosis of breast cancer. SLC22A18 knockdown (1) increased MCF7 cell growth concomitantly with a >7-fold increase of annexin A8 (involved in cell growth and migration; a predictor of poor prognosis), (2) induced spherical morphology of MCF7 cells concomitantly with a nearly 3-fold increase of CD44 (involved in regulation of malignant phenotypes), and (3) increased chemosensitivity to vinca alkaloids concomitantly with a >80% reduction of doublecortin-like kinase 1 (involved in regulation of microtubule polymerization). Our results suggest that SLC22A18 may act as a tumor suppressor by regulating the expression levels of cell growth–related proteins, and vinca alkaloids might show therapeutic efficacy against low-SLC22A18–expressing breast cancer.     

Perfusion with carbon monoxide does not affect extracellular glutamate in dialysates of the hippocampus of freely moving mice

Carbon monoxide (CO) produces several neurological effects, including cognitive, mood, and behavioral disturbance. Glutamate is thought to play a particularly important role in learning and memory. Thus, the present study was aimed at investigating the local effect of CO on the glutamate level in the hippocampus of mice using in vivo reverse microdialysis. Mice were perfused with Ringer’s solution (control) or CO (60–125?μM) in Ringer’s solution into the hippocampus via microdialysis probe. Dialysate samples were collected every 20?min, and then analyzed with high-performance liquid chromatography coupled to an electrochemical detector. The result revealed that the perfusion with CO had no significant effect on glutamate levels (p?=?0.316) as compared to the control group. This finding does not support a local CO rise as the cause of the increased glutamate level in the hippocampus of mice.     

Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge,Clathria prolifera

Marine organisms such as marine sponges and soft corals are valuable sources of pharmacologically active secondary metabolites. In our ongoing research on the discovery of new secondary metabolites from marine organisms, two new pyrrolo-2-aminoimidazoles, clathriroles A (1) and B (2), were isolated from the water-soluble portion prepared from the methanol and acetone (2:1) extract of the marine sponge, Clathria prolifera, collected in Myanmar. The chemical structures of the isolated compounds were determined using extensive spectroscopic techniques, including NMR, HRESIMS, IR, and optical rotation, and comparisons with the reported literature. The spectroscopic analyses of 1 and 2 suggested that 1 is an enantiomer of antifungal N-methylmanzacidin C isolated from the marine sponge Axinella brevistyla, whereas 2 is a diastereomer of manzacidin D at C-11 isolated from the marine sponge Astrosclera willeyana. To the best of our knowledge, this is the first report of the isolation of the pyrrolo-2-aminoimidazole compounds from C. prolifera. Furthermore, in contrast to the potency of N-methylmanzacidin C against Saccharomyces cerevisiae, the antifungal assay revealed that 1 and 2 lack any activity against this strain. Thus, these observations may suggest that the absolute configurations at both C-9 and C-11 play an important role in controlling the antifungal activity of this type of compound.

     

Power Outage Preparedness and Concern among Vulnerable New York City Residents

Power outages can impact health, and certain populations may be more at risk. Personal preparedness may reduce impacts, but information on power outage preparedness and risk perception among vulnerable populations is limited. We examined power outage preparedness and concern among New York City residents, including vulnerable populations defined as older adults (≥?65 years), and respondents with household members who require assistance with daily activities or depend on electric medical devices. A random sample telephone survey was conducted during November–December 2016. Preparedness was defined as having a three-day supply of drinking water, non-perishable food, and a working flashlight. Among all respondents (n?=?887), 58% were prepared and 46% expressed concern about health. Respondents with electric-dependent household members (9% of all respondents) tended to have higher preparedness (70 vs. 56% of respondents without electric-dependent household members). Among this group, only 40% reported being registered with a utility company to receive early notification of outages. While the subgroup sample was small, respondents with registered electric-dependent household members had lower preparedness than those with non-registered users (59 vs. 76%). Respondents with household members who needed assistance had comparable levels of preparedness to respondents without someone who needed assistance (59 vs. 57%). Older adults had greater preparedness than younger adults (65 vs. 56%). Health concerns were greater among all vulnerable groups than the general population. Levels of preparedness varied among vulnerable respondents, and awareness of power outage notification programs was low. Our findings highlight the need to increase awareness and preparedness among at-risk people.     

Plasma Amino Acid Concentrations Are Associated with Muscle Function in Older Japanese Women

Background

Although several previous studies have found benefits for amino acid supplementation in terms of muscle function, the role of plasma amino acid concentrations on sarcopenia are not well addressed yet.

Objective

The aim of this study was to compare the amino acid concentrations at each stage of sarcopenia (normal, pre-sarcopenia, dynapenia, and sarcopenia) in community-dwelling older Japanese adults. Setting and Subjects: Community-dwelling older Japanese women (n=232, 79.4±7.0 years) participated in this study.

Measurements

We measured plasma amino acid concentrations, 5-m walking speed, grip strength, and skeletal muscle mass using a bioelectrical impedance data acquisition system and compared them among participants at each stage of sarcopenia.

Results

The proportions of normal, pre-sarcopenia, dynapenia, and sarcopenia patients were 40.5% (n=94), 12.1% (n=28), 26.3% (n=61), and 21.1% (n=49), respectively. Significant differences were observed for concentrations of leucine, branched-chain amino acid (BCAAs), and essential amino acid (EAAs) among the four groups (p<0.05), and the dynapenia and sarcopenia groups showed significantly lower concentrations of leucine than the normal group (p<0.05).

Conclusions

This study indicated a positive relationship between plasma leucine, BCAA and EAA concentrations and muscle function. A longitudinal study is needed to determine the causal relationship between leucine/BCAA concentrations and muscle function.