Conservative Management of Spontaneous Isolated Dissection of the Superior Mesenteric Artery

Purpose. We report the clinical outcomes of patients with spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) who were treated conservatively. Materials and Methods. A retrospective review was performed in 14 patients from 2006 to 2016 with SIDSMA. Their clinical features and computed tomographic angiography (CTA) characteristics, treatment methods, and clinical outcomes were analyzed. The mean age was 53.6 (range, 41–73) years, and the mean follow-up duration was 20.6 (range, 1–54) months. Conservative management was the primary treatment if no bowel ischemia or arterial rupture was noted. Results. The mean initial abdominal visual analog pain score was 7 (range, 5–9) in seven patients. The mean total duration of abdominal pain was 10.2 days (range, 2–42 days) in 10 patients. The mean percentage stenosis of the dissected SMA at the initial presentation was 78.8% in 14 patients. Complete obstruction of the SMA at the initial presentation was evident in 4 of the 14 patients (28.6%). Conservative management was successful in all 14 patients. None of the 14 patients developed bowel ischemia or an infarction. Abdominal pain did not recur in any patient during follow-up (mean, 20.6 months; range, 1–54 months). Conclusion. Conservative management was successful for all SIDSMA patients, even those with severe compression of the true lumen or complete obstruction of the dissected SMA

Recycling Studies for Swine Manure Slurry Using Multi Process of Aerobic Digestion (MPAD)

This study was carried out to investigate the feasibility of Multi Process of Aerobic Digestion (MPAD) for recycling of swine manure slurry as fertilizer. MPAD consisted of three kinds of difference process which are thermophilic aerobic oxidation (TAO) system, lime solidification system, and reverse osmosis (R/O) membrane system. TAO system was studied well previously for decade. The chemical composition of the lime-treated solid fertilizer was as like that organic matter 17.4%, moisture 34.1%, N 0.9%, P 1.7%, K 0.3%, Ca 12.7%, and which was expected to be useful as acid soil amendment material. The concentrated liquid material produced by R/O membrane system was also expected as a good fertilizer for crops production and soil fertility improvement.OtherShinshu University International Symposium 2010 : Sustainable Agriculture and Environment : Asian Networks II 　信州大学国際シンポジウム2010 : 持続的農業と環境 : アジアネットワークII ― アジアネットワークの発展をめざして―. 信州大学農学部, 2010, 71-77conference pape

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes

Type 2 diabetes is caused by chronic insulin resistance and progressive decline in beta-cell function. Optimal beta-cell function and mass is essential for glucose homeostasis and beta-cell impairment leads to the development of diabetes. Elevated levels of circulating fatty acids (FAs) and disturbances in lipid metabolism regulation are associated with obesity, and they are major factors influencing the increase in the incidence of type 2 diabetes. Chronic free FA (FFA) treatment induces insulin resistance and beta-cell dysfunction; therefore, reduction of elevated plasma FFA levels might be an important therapeutic target in obesity and type 2 diabetes. Lipid signals via receptors, and intracellular mechanisms are involved in FFA-induced apoptosis. In this paper, we discuss lipid actions in beta cells, including effects on metabolic pathways and stress responses, to help further understand the molecular mechanisms of lipotoxicity-induced type 2 diabetes

Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

BACKGROUND: Betacellulin (BTC), a member of the epidermal growth factor family, is known to play an important role in regulating growth and differentiation of pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4; however, the exact mechanism for beta cell proliferation has not been elucidated. Therefore, we investigated which ErbBs are involved and some molecular mechanisms by which BTC regulates beta cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS: The expression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 mRNA was detected by RT-PCR in both a beta cell line (MIN-6 cells) and C57BL/6 mouse islets. Immunoprecipitation and western blotting analysis showed that BTC treatment of MIN-6 cells induced phosphorylation of only ErbB-1 and ErbB-2 among the four EGF receptors. BTC treatment resulted in DNA synthetic activity, cell cycle progression, and bromodeoxyuridine (BrdU)-positive staining. The proliferative effect was blocked by treatment with AG1478 or AG825, specific tyrosine kinase inhibitors of ErbB-1 and ErbB-2, respectively. BTC treatment increased mRNA and protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by the ErbB-1 and ErbB-2 inhibitors. Inhibition of IRS-2 by siRNA blocked cell cycle progression induced by BTC treatment. Streptozotocin-induced diabetic mice injected with a recombinant adenovirus expressing BTC and treated with AG1478 or AG825 showed reduced islet size, reduced numbers of BrdU-positive cells in the islets, and did not attain BTC-mediated remission of diabetes. CONCLUSIONS/SIGNIFICANCE: These results suggest that BTC exerts proliferative activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors, which may increase IRS-2 expression, contributing to the regeneration of beta cells

Differential Genomic Imprinting and Expression of Imprinted microRNAs in Testes-Derived Male Germ-Line Stem Cells in Mouse

BACKGROUND: Testis-derived male germ-line stem (GS) cells, the in vitro counterpart of spermatogonial stem cells (SSC), can acquire multipotency under appropriate culture conditions to become multipotent adult germ-line stem (maGS) cells, which upon testicular transplantation, produce teratoma instead of initiating spermatogenesis. Consequently, a molecular marker that can distinguish GS cells from maGS cells would be of potential value in both clinical and experimental research settings. METHODS AND FINDINGS: Using mouse as a model system, here we show that, similar to sperm, expression of imprinted and paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) were consistently higher (P<0.001), while those of imprinted and maternally expressed miRNA (miR-127, miR-127-5p) were consistently lower (P<0.001) in GS cells than in control embryonic stem (ES) cells. DNA methylation analyses of imprinting control regions (ICR), that control the expression of all imprinted miRNAs in respective gene clusters (Gnas-Nespas DMR, Igf2-H19 ICR and Dlk1-Dio3 IG-DMR), confirmed that imprinted miRNAs were androgenetic in GS cells. On the other hand, DNA methylation of imprinted miRNA genes in maGS cells resembled those of ES cells but the expression pattern of the imprinted miRNAs was intermediate between those of GS and ES cells. The expression of imprinted miRNAs in GS and maGS cells were also altered during their in vitro differentiation and varied both with the differentiation stage and the miRNA. CONCLUSIONS: Our data suggest that GS cells have androgenetic DNA methylation and expression of imprinted miRNAs which changes to ES cell-like pattern upon their conversion to maGS cells. Differential genomic imprinting of imprinted miRNAs may thus, serve as epigenetic miRNA signature or molecular marker to distinguish GS cells from maGS cells

Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons

<p>Abstract</p> <p>Background</p> <p>Proanthocyanidin is a polyphenolic bioflavonoid with known antioxidant activity. Some flavonoids have a modulatory effect on [Ca²⁺]_i. Although proanthocyanidin extract from blueberries reportedly affects Ca²⁺buffering capacity, there are no reports on the effects of proanthocyanidin on glutamate-induced [Ca²⁺]_ior cell death. In the present study, the effects of grape seed proanthocyanidin extract (GSPE) on glutamate-induced excitotoxicity was investigated through calcium signals and nitric oxide (NO) in cultured rat hippocampal neurons.</p> <p>Results</p> <p>Pretreatment with GSPE (0.3-10 μg/ml) for 5 min inhibited the [Ca²⁺]_iincrease normally induced by treatment with glutamate (100 μM) for 1 min, in a concentration-dependent manner. Pretreatment with GSPE (6 μg/ml) for 5 min significantly decreased the [Ca²⁺]_iincrease normally induced by two ionotropic glutamate receptor agonists, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). GSPE further decreased AMPA-induced response in the presence of 1 μM nimodipine. However, GSPE did not affect the 50 mM K⁺-induced increase in [Ca²⁺]_i. GSPE significantly decreased the metabotropic glutamate receptor agonist (<it>RS</it>)-3,5-Dihydroxyphenylglycine-induced increase in [Ca²⁺]_i, but it did not affect caffeine-induced response. GSPE (0.3-6 μg/ml) significantly inhibited synaptically induced [Ca²⁺]_ispikes by 0.1 mM [Mg²⁺]_o. In addition, pretreatment with GSPE (6 μg/ml) for 5 min inhibited 0.1 mM [Mg²⁺]_o- and glutamate-induced formation of NO. Treatment with GSPE (6 μg/ml) significantly inhibited 0.1 mM [Mg²⁺]_o- and oxygen glucose deprivation-induced neuronal cell death.</p> <p>Conclusions</p> <p>All these data suggest that GSPE inhibits 0.1 mM [Mg²⁺]_o- and oxygen glucose deprivation-induced neurotoxicity through inhibition of calcium signals and NO formation in cultured rat hippocampal neurons.</p