Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac sympathetic nerve injury.

BACKGROUND: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. METHODS AND RESULTS: Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. CONCLUSION: A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.     

Susceptibility of muridae cell lines to ecotropic murine leukemia virus and the cationic amino acid transporter 1 viral receptor sequences: implications for evolution of the viral receptor

Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection. Comparison of amino acid sequences between the rat and mouse CAT1s shows amino acid insertions in the rat protein near the Eco-MLV-binding motif. In addition to the insertion present in the rat CAT1, the hamster CAT1 has additional amino acid insertions. In contrast, tunicamycin treatment of mink and human cells does not elevate the infection, because their CAT1s do not have the Eco-MLV-binding motif. To define the evolutionary pathway of the Eco-MLV receptor, we analyzed CAT1 sequences and susceptibility to Eco-MLV infection of other several murinae animals, including the southern vole (Microtus rossiaemeridionalis), large Japanese field mouse (Apodemus speciosus), and Eurasian harvest mouse (Micromys minutus). Eco-MLV infection was enhanced by tunicamycin in these cells, and their CAT1 sequences have the insertions like the hamster CAT1. Phylogenetic analysis of mammalian CAT1s suggested that the ancestral CAT1 does not have the Eco-MLV-binding motif, like the human CAT1, and the mouse CAT1 is thought to be generated by the amino acid deletions in the third extracellular loop of CAT1.     

Severe liver injury associated with simeprevir plus pegylated interferon/ribavirin therapy in a patient with treatment-naïve genotype 1b hepatitis C virus: a case report

A second-generation direct-acting antiviral agent, simeprevir, now provides a new treatment option for hepatitis C virus (HCV) infection with good safety profile in combination with pegylated interferon and ribavirin. We herein report a rare case of severe liver injury under simeprevir plus pegylated interferon/ribavirin therapy. We initiated this therapy in a 65-year-old male with treatment-naïve genotype 1b HCV. On day 28, the patient’s HCV-RNA was successfully eliminated, and his liver function was fully restored. However, on day 49, the serum alanine aminotransferase level was elevated at 700 IU/L. The HCV-RNA titer was still undetectable and the involvement of other possible viruses was negligible. A liver biopsy performed on day 60 showed an acute hepatitis pattern. The discontinuation of therapy alone successfully improved his liver damage on day 84. No other treatments such as steroids were required. According to the diagnostic criteria for drug-induced liver injury in Japan (DDW-J2004), the liver injury observed in this case can be associated with the administration of simeprevir plus pegylated interferon/ribavirin therapy. In conclusion, simeprevir plus pegylated interferon/ribavirin should be used with caution, as these agents may cause unreported serious adverse events including severe liver injury, despite their clinical safety profile.     

Development and characterization of new microsatellite loci in the Otton frog (Babina subaspera) and cross-amplification in a congeneric species, Holst’s frog (B. holsti)

The Otton frog (Babina subaspera) and Holst’s frog (Babina holsti) are both endangered sister species belonging to family Ranidae. For extensive genetic and ecological research of these species, we isolated and characterized 8 new microsatellite loci of the Otton frog and validated cross-amplification in Holst’s frog along with 8 previously reported loci. The total number of alleles and the expected heterozygosity of newly isolated loci in the Otton frog population ranged from 5 to 12 and from 0.620 to 0.905, respectively. We also confirmed cross-amplification in 4 of the new loci and in all previously reported loci in Holst’s frog with the same level of polymorphism as the Otton frog. Our findings suggest that these novel loci will be applicable for conservation genetic studies across varying scales.     

Long-term results after 12-year follow-up of patients treated with whole-breast and boost irradiation after breast-conserving surgery

Purpose

The long-term outcomes of whole-breast and boost irradiation after breast-conserving surgery (BCS) for patients with breast cancer were retrospectively analyzed.

Materials and methods

Patients who received whole-breast and boost irradiation after BCS from 1990 to 2002 were included. Boost irradiation was administered to each tumor bed, regardless of the surgical margin status. The median doses of whole-breast and boost irradiation were 45 Gy in 25 fractions (range 36–45 Gy), and 14 Gy in 7 fractions (range 0–14 Gy), respectively.

Results

Data for 306 patients were analyzed. With a median follow-up time of 144 months, the 10-year overall survival, disease-free survival, ipsilateral breast tumor recurrence (IBTR), and metachronous contralateral breast cancer (MCBC) occurrence rates were 93.0, 84.1, 2.1, and 4.1 %, respectively. In the multivariate analysis, pT2 was a significant risk factor for IBTR (p = 0.041), while age ≤ 50 years and pT2 were significant risk factors for MCBC occurrence (p = 0.003 and 0.043, respectively). One patient (0.3 %) developed angiosarcoma in the irradiated region 120 months after the completion of radiation therapy.

Conclusion

The 12-year outcome of breast-conserving therapy using whole-breast and boost irradiation with doses of 45 and 14 Gy, respectively, was favorable.