To compare the fundamental structure of the human liver, in relation to that of the rat a comparative study was performed, in which 20 rat livers and 78 human cadaver livers were examined. The rat livers had four lobes (left, middle, right, and caudate). The left and middle lobes formed a single lobe but the middle lobe had a deep notch to which the round ligament attached. The right lobe was split into two sub-lobes and the caudate lobe was divided into the paracaval portion and the Spiegel lobe, which was split into two sub-lobes. The left, right, and caudate lobes had one primary portal branch, whereas the middle lobe had two portal branches. The left and the right sub- and caudate lobes had one large hepatic vein each, whereas three large hepatic veins were observed in the middle lobe. Based on the ramifying patterns of the portal and hepatic veins, the rat middle lobe possessed left and right hepatic components and a main portal fissure. The following rat hepatic lobes were equivalent to the following human liver segments: the left lobe to segment II; the middle lobe to segments III, IV, V, and VIII; and the right lobe to segments VI and VII. The fundamental structures of rat and human livers were similar, and the findings demonstrated a new interpretation of the anatomy of the human liver.

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Background and purposeOxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients.MethodsWe retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016.ResultsThe differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients.ConclusionOur retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

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Skeletal muscle expressing Pro104Leu mutant caveolin 3 (CAV3 P104L ) in mouse becomes atrophied and serves as a model of autosomal dominant limb-girdle muscular dystrophy 1C. We previously found that caveolin 3-deficient muscles showed activated intramuscular transforming growth factor beta (TGF-b) signals. However, the cellular mechanism by which loss of caveolin 3 leads to muscle atrophy is unknown. Recently, several small-molecule inhibitors of TGF-b type I receptor (TbRI) kinase have been developed as molecular-targeting drugs for cancer therapy by suppressing intracellular TGF-b1, -b2, and -b3 signaling. Here, we show that a TbRI kinase inhibitor, Ki26894, restores impaired myoblast differentiation in vitro caused by activin, myostatin, and TGF-b1, as well as CAV3 P104L . Oral administration of Ki26894 increased muscle mass and strength in vivo in wild-type mice, and improved muscle atrophy and weakness in the CAV3 P104L mice. The inhibitor restored the number of satellite cells, the resident stem cells of adult skeletal muscle, with suppression of the increased phosphorylation of Smad2, an effector, and the upregulation of p21 (also known as Cdkn1a), a target gene of the TGF-b family members in muscle. These data indicate that both TGF-b-dependent reduction in satellite cells and impairment of myoblast differentiation contribute to the cellular mechanism underlying caveolin 3-deficient muscle atrophy. TbRI kinase inhibitors could antagonize the activation of intramuscular anti-myogenic TGF-b signals, thereby providing a novel therapeutic rationale for the alternative use of this type of anticancer drug in reversing muscle atrophy in various clinical settings.

Duchenne muscular dystrophy (DMD) is a fatal, progressive, muscle-wasting disease caused by defects in the dystrophin. No viral vector except the helper-dependent adenovirus vector (HDAdv) can package 14-kilobase (kb) full-length dystrophin complementary DNA (cDNA), and HDAdv is considerably safer than old-generation adenovirus vectors because of the large-size deletion in its genome. We have generated HDAdv that carries myc-tagged murine full-length dystrophin cDNA (HDAdv-myc-mFLdys). We injected it into multiple proximal muscles of 7-day-old utrophin/dystrophin double knockout mice (dko mice) (which typically show symptoms quite similar to human DMD) because the proximal muscles are affected in DMD patients. Eight weeks after the injections, the transduced dystrophin was widely expressed, and we found a significant reduction in centrally nucleated myofibers and the restoration of the dystrophin-associated proteins, beta-dystroglycan (beta-DG) and alpha-sarcoglycan (alpha-SG), as well as neuronal nitric oxide synthase (nNOS). The injected dko mice also showed an increase in body weight, an improvement in motor performance, and a prolongation of life span. Using HDAdv, we could treat DMD model mice even by transferring the therapeutic gene into multiple skeletal muscles. Our results suggest that multiple intramuscular administrations of HDAdv carrying full-length dystrophin cDNA may reduce symptoms and compensate for lost functions in DMD patients.

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