Weak Glycolipid Binding of a Microdomain-Tracer Peptide Correlates with Aggregation and Slow Diffusion on Cell Membranes

10.1371/journal.pone.0051222PLoS ONE712

Development and Application of Discrimination Method of Substandard and Falsified Medical Products using Quality Test and Non-destructive Spectroscopy

13301甲第4604号博士（創薬科学）金沢大学博士論文要旨Abstract 以下に掲載：American Journal of Tropical Medicine and Hygiene 97(3) pp.684-689 2017. The American Society of Tropical Medicine and Hygiene. 共著者：Tomoko Kakio, Naoko Yoshida, Susan Macha, Kazunobu Moriguchi, Takashi Hiroshima, Yukihiro Ikeda, Hirohito Tsuboi, Kazuko Kimur

Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice

The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis

Pencegahan Stunting di Desa Talaga Melalui Program SANTAP: Solusi Atasi Stunting dengan Biji Pepaya

Stunting merupakan masalah serius yang dihadapi Indonesia pada saat ini, masalah ini mempengaruhi kesehatan dan sosial masyarakat serta keberlangsungan bangsa dimasa yang akan datang, salah satu penyebab stunting adalah terjadinya infeksi yang tidak tertangani pada bayi dan anak-anak. Program ini bertujuan untuk mencegah stunting dengan mengatasi masalah cacingan. Sebagai alternatif mengatasi cacingan tersebut adalah dengan memberikan obat dari bahan dasar alam yaitu biji buah papaya yang diolah dan dijadikan puding. Sasaran utama adalah pada anak-anak di desa Talaga, program dilaksanakan dengan melakukan sosialisasi dan pelatihan pembuatan pudding dari biji papaya kepada masyarakat desa Talaga. Dengan keterlibatan mitra seperti puskesmas setempat, kader Kesehatan dan pemerintah desa, program ini terlaksana dengan baik dan mendapatkan atensi yang baik dari masyarakat. Masyarakat menjadi paham terhadap pentingnya mengatasi terjadi cacingan pada anak yang menjadi salah satu faktor penyebab stunting serta dapat memanfaatkan bahan yang sering tidak digunakan seperti biji pepaya dalam mengatasi masalah kesehatan mereka

Survival simulation of hepatocellular carcinoma derived from follow-up studies of 450 patients.

A simulation model to predict the survival probability of individual patients with hepatocellular carcinoma (HCC) after therapy was derived from the results of various therapies and follow-up studies of 450 HCC patients. Twenty-two prognostically important variables were analyzed by Cox's proportional hazards model. The 9 significant variables that were extracted were used to build the simulation. In this model, S(t), the expected estimated survival rate for individual patient at time t (month), is calculated by the following equation: S(t) = (exp (-0.03655t) (exp [0.9479 ([portal vein invasion]-0.222) + 0.3846 ([tumor number]-2.00) + 0.2578 ([tumor size]-3.231) + 0.0742 ([loge AFP]-5.647) + 0.8184 ([metastasis]-0.036) + 0.2810 ([Child's class]-1.689)-0.7088 ([transcatheter arterial embolization]-0.578)-0.9746 ([percutaneous ethanol injection]-0.153)-0.5377 ([hepatectomy]-0.109)]) The validity of the model was assessed using a split-sample technique. This paper does not discuss the superiority or inferiority of the therapies, because some selection bias for prognostic factors among the therapies can not be completely excluded. But this model is proposed as a practical model to predict the survival of patients with HCC.</p

The Slowly Aggregating Salmon Calcitonin: A Useful Tool for the Study of the Amyloid Oligomers Structure and Activity

Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature). In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. In particular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect

IgA Nephropathy Complicated with X-linked Thrombocytopenia

Renal involvement is occasionally observed in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). It has been reported that galactose-deficient IgA is a closely linked to IgA nephropathy (IgAN), suggesting that patients with XLT/WAS associated with reduced galactosylation on serum IgA are susceptible to IgAN. It is necessary to pay more attention to patients with IgAN due to the potential complication with XLT/WAS. We here present a patient of XLT complicated with mild IgAN who underwent tonsillectomy combined with steroid pulse therapy to achieve complete clinical remission

Hemostasis of Gastric Variceal Hemorrhage by Transileocoecal and Transhepatic Obliteration

Obliteration for gastric or duodenal variceal hemorrhage was performed via transileocoecal or transhepatic portal catheterization in 8 patients with portal hypertension. The patients were 6 men and 2 women, whose average age was 59 years. All of the patients had cirrhosis of the liver. The obliteration was performed as an emergency procedure in 6 cases, and 2 patients were electively treated. Transileocoecal obliteration (TIO) and transhepatic obliteration (PTO) were selected for 6, and 2 patients, respectively. Variceal bleeding was successfully controlled in all patients after completion of the therapy. One patient died after 3 months when duodenal variceal bleeding recurred. Elective surgical operations were performed on 2 patients after the initial therapy, because the vein feeding toward the varices remained. Six of the patients have survived to date without bleeding. Transient oliguria and jaundice after the therapy were noticed in 2 patients. Histological examination revealed cast formation of polymerized cyanoacrylate in the obliterated gastric varices of 2 patients. TIO and PTO seem to be safe, effective procedures to stop bleeding from ectopic varices, gastric or duodenal. This therapy is useful either to obtain accurate information about the varices or to obliterate the collateral veins in patients with ruptured ectopic varices.</p