1. Favipiravir and its potentials in COVID-19 pandemic: An update
Dao TAM ; Ahmad QARAWI ; Mai LUU ; Gehad TAWFIK ; Le MINH ; Dao TAM ; Ahmad QARAWI ; Mai LUU ; Morgan TURNAGE ; Linh TRAN ; Linh TRAN ; Gehad TAWFIK ; Le MINH ; Nguyen HUY ; Kyoshi KITA ; Kenji HIRAYAMA ; Tatsuo IIYAMA
Asian Pacific Journal of Tropical Medicine 2021;14(10):433-439
The COVID-19 pandemic has caused millions of deaths and hundreds of millions of confirmed infections worldwide. This pandemic has prompted researchers to produce medications or vaccines to reduce or stop the progression and spread of this disease. A variety of previously licensed and marketed medications are being tested for the treatment and recurrence of SARS-CoV2, including favipiravir (Avigan). Favipiravir was recognized as an influenza antiviral drug in Japan in 2014, and has been known to have a potential in vitro activity against SARS-CoV-2, in addition to its broad therapeutic safety scope. Favipiravir was recently approved and officially used in many countries worldwide. Our review provides insights and up-to-date knowledge of the current role of favipiravir in the treatment of COVID-19 infection, focusing on preclinical and ongoing clinical trials, evidence of its efficacy against SARS-CoV-2 in COVID-19, side effects, anti-viral mechanism, and the pharmacokinetic properties of the drug in the treatment of COVID-19. Due to its teratogenic effects, favipiravir cannot be offered to expectant or pregnant mothers. The practical efficacy of such an intervention regimen will depend on its dose, treatment duration, and cost as well as difficulties in application.
4.The Association of Cytokines with Severe Dengue in Children
Julia N.A. Mangione ; Nguyen Tien Huy ; Nguyen Thi Phuong Lan ; Evaristus Chibunna Mbanefo ; Tran Thi Ngoc Ha ; Lam Quoc Bao ; Cao Thi Phi Nga ; Vo Van Tuong ; Tran Van Dat ; Tran Thi Thuy ; Ha Manh Tuan ; Vu Thi Que Huong ; Kenji Hirayama
Tropical Medicine and Health 2014;():-
Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex Immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, the multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to further investigate the function of these cytokines in severe dengue.
5.The Association of Cytokines with Severe Dengue in Children
Julia N.A. Mangione ; Nguyen Tien Huy ; Nguyen Thi Phuong Lan ; Evaristus Chibunna Mbanefo ; Tran Thi Ngoc Ha ; Lam Quoc Bao ; Cao Thi Phi Nga ; Vo Van Tuong ; Tran Van Dat ; Tran Thi Thuy ; Ha Manh Tuan ; Vu Thi Que Huong ; Kenji Hirayama
Tropical Medicine and Health 2014;42(4):137-144
Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.
6.Immunoproteomics Identification of Major IgE and IgG4 Reactive Schistosoma japonicum Adult Worm Antigens Using Chronically Infected Human Plasma
Daniel Boamah ; Mihoko Kikuchi ; Nguyen Tien Huy ; Kenta Okamoto ; Honggen Chen ; Irene Ayi ; Daniel Adjei Boakye ; Kwabena Mante Bosompem ; Kenji Hirayama
Tropical Medicine and Health 2012;40(3):89-102
Immunoepidemiological studies from endemic areas have revealed age-dependent resistance correlation with increased level of IgE and decreased level of IgG4 antibodies in responses to schistosomes’ soluble worm antigen. However, there have been limited studies on analyses of major antigens that provoke IgE and IgG4 immune response during chronic stage of schistosomiasis. In this study, for the first time, immunoproteomics approach has been applied to identify S. japonicum worm antigens in liquid fractions that are recognized by IgE and IgG4 antibody using plasma from chronically infected population. ProteomeLabPF 2D fractionated 1-D and 2-D fractions of SWA antigens were screened using pooled high IgE/IgG4 reactive plasma samples by dot-blot technique. In 1-D fractions, IgE isotype was detected by fewer antigenic fractions (43.2%). The most recognized isotype was IgG3 (79.5%) followed by IgG1 (75.0%) and IgG4 (61.4%). Liquid chromatography MS/MS protein sequencing of reactive 2-D fractions revealed 18 proteins that were identified, characterized and gene ontology categories determined. 2-D fractions containing proteins such as zinc finger, RanBP2-type, domain-containing protein were strongly recognized by IgE and moderately by IgG4 whereas fractions containing proteins such as ubiquitin-conjugating enzyme and cytosolic II 5'-nucleotidase strongly recognizing by IgG subclasses (IgG1, IgG3 and IgG4) but not IgE. By this study, a simple and reproducible proteomic method has been established to identify major immunoreactive S. japonicum antigens. It is anticipated that this will stimulate further research on the immunogenicity and protective potential of proteins identified as well as discovery of novel compounds that have therapeutic importance.
7.Suggestions and recommendations from health care professionals involved in regional palliative care program
Tatsuya Morita ; Chizuru Imura ; Yoshiko Nozue ; Satoshi Suzuki ; Mie Shibuya ; Hiroya Kinoshita ; Kumiko Harada ; Yutaka Shirahige ; Mika Hirayama ; Kenji Eguchi
Palliative Care Research 2012;7(1):163-171
The aim of this study is to collect the suggestions and recommendations of health care professionals involved in the regional palliative care program (OPTIM-study). A total of 101 multidisciplinary health care professionals who participated in the intervention program were interviewed, and 107 meaningful units were obtained from 89 valid interviews. The responses were categorized into “suggestions regardless of profession” (n=59), including “Participate in a multi-disciplinary conference to expand the network of people”, “Try to understand the situation of others”, “Seek support from others when you cannot solve the problem by yourself”, “Pursue all possibilities before giving up”, and “Do not try too hard”. As suggestions to those engaged in each profession, “Suggestions to community pharmacies” and “Suggestions to care managers” are frequently described. An examination of suggestions by the participants in the regional palliative care program could provide some insights to improve community palliative care.
8.What is the greatest impact of the regional palliative care program?: the OPTIM-study
Tatsuya Morita ; Chizuru Imura ; Yoshiko Nozue ; Satoshi Suzuki ; Mie Shibuya ; Hiroya Kinoshita ; Kumiko Harada ; Yutaka Shirahige ; Mika Hirayama ; Kenji Eguchi
Palliative Care Research 2012;7(2):209-217
The purpose of this study was to identify the greatest impact of the regional palliative care program on community health care professionals. Interviews were conducted involving 101 people who became involved in the intervention program implemented in 4 areas across Japan, and 96 valid responses were collected. The following were cited as the greatest impact: [I developed a network of people, and realized the importance of collaboration] (n=61; “I was able to develop an interpersonal relationship” and “Now I understand the significance of collaboration”), [My knowledge and skills regarding palliative care were improved] (n=18; “Knowledge and support helped me respond to patients with confidence” and “I have come to think that there is more to palliative care than terminal care”), [I rediscovered my role through a wide variety of experiences] (n=10), [Both collaboration and palliative knowledge/skills meant a lot to me] (n=4), [What I experienced in this program will help me play my role] (n=2), and [Patients and their families became satisfied] (n=1). The community palliative care program was most effective in facilitating collaboration, and helped participants develop knowledge and skills concerning palliative care.
9.CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea
hikota osawa ; marita troye-blomberg ; kenji hirayama ; mihoko kikuchi ; francis hombhanje ; takeo tanihata ; rachanee udomsangpetch ; anders björkman ; takatoshi kobayakawa ; akira kaneko
Tropical Medicine and Health 2008;36(2):93-100
In malaria endemic areas, people naturally acquire an age-related immunity to malaria. Part of this immunity involves anti-malarial specific antibodies. Acquisition of these malaria-specific antibodies depends not only on exposure to malaria parasites but also on the human genetic predisposition. CTLA-4 is a costimulatory molecule that delivers an inhibitory signal to suppress T-cell as well as B-cell responses. We investigated associations between malaria-specific antibody levels and CTLA-4 polymorphisms in 189 subjects living in a hyper-endemic area of Papua New Guinea (PNG), where both P. falciparum and P. vivax are prevalent. We determined P. falciparum⁄ P. vivax specific IgG⁄IgE levels (Pf-IgG, Pv-IgG, Pf-IgE, Pv-IgE) and polymorphisms in the CTLA-4 gene at position -1661 promoter region (A⁄G), the +49 exon 1 non-synonymous mutation (A⁄G), and the +6230 3‘-UTR (A⁄G). All quantified antibody levels were significantly higher in subjects > 5 years (n = 150) than in subjects ≤ 5 years of age (n = 39). In children ≤ 5 years old, significant associations were detected between CTLA-4 +49 (GG⁄AG vs. AA) and Pv-IgG (median 18.7 vs. 13.7 Μg⁄ml, P = 0.017) and Pv-IgE (266.6 vs. 146.5 pg⁄ml, P = 0.046). No significant difference was observed in subjects > 5 years old. These results suggest that the CTLA-4+49 polymorphism influenced Pv-IgG and Pv-IgE levels among children less than five years old in the studied population, which may regulate the age- and species-specific clinical outcomes of malaria infection.
10.Population Polymorphism of Trypanosoma cruzi in Latin America indicated by Proteome analysis and by in vitro amastigote proliferation
JIAN-BING MU ; TOSHIO SONE ; TETSUO YANAGI ; ISAO TADA ; MIHOKO KIKUCHI ; KENJI HIRAYAMA
Tropical Medicine and Health 2006;34(4):167-174
Nineteen stocks of Trypanosoma cruzi originating from several endemic countries for Chagas‘ disease in Central and South America were subjected to two-dimensional protein electrophoresis analysis. The presence or absence of a total of492polypeptide spots among19gel profiles was determined. The stocks were classified into three major distinctive groups derived from (I) Central America and the northern part of South America; (IIa) Central America and the northern part of South America; and (IIb) central and southern parts of South America, which showed perfect concordance with the previously reported classification based on isozyme and DNA sequence analyses. Late log phase of each epimastigote was inoculated to human cell lines WI-38and Hs224.T originating from the lung and muscle, respectively, and the number of trypomastigotes released was counted. The number of trypomastigotes from T. cruzi in group I released from the two cell lines was significantly higher than that in group III (p&It;0.05). The findings suggested that the phenetic distance appearing within the T. cruzi may, to some extent, be associated with the intracellular growth of T. cruzi, one of the characteristic features of growth found in the species.


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