Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

<p>Abstract</p> <p>Background</p> <p>Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)_nrepeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated.</p> <p>Methods</p> <p>Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated <it>Plasmodium falciparum </it>malaria (UM) and 80 cases with <it>Plasmodium vivax </it>malaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand.</p> <p>Results</p> <p>The number of (GT)_nrepeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GT_nrepeats. The genotype of (GT)_nrepeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed.</p> <p>Conclusions</p> <p>Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With this limited sample size, the finding of the lack of association between malaria disease pathogenicity/severity genetic polymorphisms of HO-1 (GT)_nrepeat as well as TNF observed in this study may not entirely exclude their possible link with malaria disease pathogenicity/severity. Further study in larger sample size is required.</p

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

ABSTRACT: INTRODUCTION: Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. METHODS: Electronic searches in PubMed, Scopus, the MEDION database and Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. RESULTS: Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square p = 0.1009, I2 = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers

Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

<p>Abstract</p> <p>Background</p> <p>Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC) destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied.</p> <p>Methodology</p> <p>To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated.</p> <p>Results</p> <p>Upon challenge with <it>Plasmodium berghei </it>ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb) drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%), which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively). Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6), followed by C57BL/6 (8.6), CBA (6.9) and NZW (4.0), p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p < 0.001.</p> <p>Conclusion</p> <p>The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also influence the outcome of auto-immune mediated destruction of RBC due to the variation in Hb loss per % parasitaemia and differences in antibody titer for each semi-immune mice strain. However, further studies at the molecular level ought to be carried out to confirm this.</p

Leishmania major Strain-Dependent Macrophage Activation Contributes to Pathogenicity in the Absence of Lymphocytes

Infection of C57BL/6 wild-type mice with Leishmania major 5-ASKH or Friedlin strains results in relatively similar pathogenicity with self-healing lesions within weeks. Parasite clearance depends on nitric oxide production by activated macrophages in response to cytokines produced mainly by CD41 Th1 cells. In contrast, C57BL/6 Rag2 knockout mice, which lack T and B lymphocytes, show distinct pathologies during infection with these strains. Despite of the similar parasite number, the 5-ASKH infection induced severe inflammation rather than the Friedlin. To determine the immunological factors behind this phenomenon, we infected C57BL/6 Rag2 knockout mice with these two strains and compared immune cell kinetics and macrophage activation status. Compared with the Friedlin strain, the 5-ASKH strain elicited increased pathology associated with the accumulation of CD11bhigh, Ly6Ghigh neutrophils by week four and increased the expression of macrophage activation markers. We then analyzed the differentially expressed transcripts in infected bone marrow-derived macrophages by RNA sequencing. It showed upregulation of multiple inflammatory transcripts, including Toll-like receptor 1/2 (TLR1/2), CD69, and CARD14, upon 5-ASKH infection. Our findings suggest that different L. major strains can trigger distinct macrophage activation, contributing to the disease outcome observed in the absence of lymphocytes but not in the presence of lymphocytes

Pilot Study on Interferon-γ-producing T Cell Subsets after the Protective Vaccination with Radiation-attenuated Cercaria of Schistosoma japonicum in the Miniature Pig Model

CLAWN miniature pig has been shown to serve as a suitable host for the experimental infection of Schistosoma japonicum. In this study, we found that radiation-attenuated cercaria (RAC) vaccine gave CLAWN miniature pigs protective immunity against subsequent challenge infection with S. japonicum cercaria. To characterize the protective immune response of the pig model vaccinated by attenuated cercaria, flow cytometric analysis of the reactive T cell subsets was performed. The intracellular interferon (IFN)-γ and the cell surface markers revealed the peripheral blood CD3+ T-lymphocytes produced significant amounts of IFN-γ during the immunization period and after the challenge infection. CD4+ αβ-T cells as well as CD4+/CD8αmid double positive and/or CD8αhigh αβ-T cells were the major IFN-γ-producing CD3+ T cells. On the contrary, γδ T cells did not produce intracellular IFN-γ. Our results suggested that RAC-vaccinated miniature pigs showed effective protective immunity through the activation of αβ T cells bearing antigen specific T-cell receptors but not through the activation of γδ T cells

What Does Soil-Transmitted Helminth Elimination Look Like? Results From a Targeted Molecular Detection Survey in Japan

Background: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs. Methods: Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura. Results: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. Conclusions: To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.[Figure not available: see fulltext.

マラリア感染と治療を繰り返すことにより制御性のCD19陽性B細胞が生じ実験的脳マラリアの発症が抑制される

In African endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. Here, we developed an experimental cerebral malaria (ECM) model for semi-immune mice. C57BL/6 (B6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 104 Plasmodium berghei ANKA without treatment. Our results showed that 100% of naive (0-cure), 67% of 1-cure, 37% of 2-cure and none of 3-cure mice succumbed to ECM within 10 days post challenge infection. In the protected 3-cure mice, significantly higher levels of plasma IL-10 and lower levels of IFN-γ than the others on day 7 post challenge infection were observed. Major increased lymphocyte subset of IL-10 positive cells in 3-cure mice was CD5(?)CD19(+) B cells. Passive transfer of splenic CD19(+) cells from 3-cure mice protected naive mice from ECM. Additionally, aged 3-cure mice were also protected from ECM 12 and 20 months after the last challenge infection. In conclusion, mice became completely resistant to ECM after three exposures to malaria. CD19(+) B cells are determinants in protective mechanism of semi-immune mice against ECM possibly via modulatory IL-10 for pathogenic IFN-γ production.長崎大学学位論文 学位記番号:博(医歯薬)甲第611号 学位授与年月日:平成25年8月7日Author： Lam Quoc Bao , Nguyen Tien Huy , Mihoko Kikuchi, Tetsuo Yanagi, Masachika Senba, Mohammed Nasir Shuaibu, Kiri Honma, Katsuyuki Yui, Kenji HirayamaCitation: PLoS ONE, 8(5), e64836; 2013Nagasaki University (長崎大学)課程博

Pengamanan Data Menggunakan Metoda Enkripsi Einstein

Dalam proses demokrasi maka semua orang bebas untuk berbicara mengutarakan pendapat dan pandangannya berdasarkan pribadi dan perasaannya, tentu saja dengan melihat bahwa hak demokrasinya tersebut tidak melanggar hak demokrasi orang lain. Kebebasan berkomunikasi ini juga termasuk kebebasan untuk berbicara dengan orang yang diinginkan. Untuk itu akan sangat mengganggu bila isi pembicaraan terutama yang menggunakan teknologi informasi ternyata bocor kepada orang yang tidak berhak dan secara demokrasi ini melanggar haknya, padahal dalam teknologi informasi yang berkembang secara sangat pesat ini ternyata tidak dibarengi dengan penggunaan alat untuk pengamanan data yang tepat dalam sistem informasi. Salah satu teknik pengamanan data informasi di dunia internet adalah penggunaan teknik algoritma kriptografi. Suatu algoritma kriptografi berisi fungsi-fungsi matematika yang digunakan untuk melakukan proses enkripsi dan dekripsi. Algoritma kriptografi yang digunakan merupakan jenis algoritma kriptografi simetrik yang menggunakan kunci rahasia yang sama untuk proses enkripsi dan dekripsinya. Pada makalah ini dipaparkan penggunaan algoritma kriptografi Einstein sebagai salah satu cara untuk mengamankan data. Pada algoritma Einstein, terdapat proses acak (random) yang menggunakan metoda kongruensial linear. Algoritma Einstein mempunyai kelebihan dalam melakukan proses enkripsi dan dekripsi pada hampir semua jenis file yang umum digunakan. Algoritma Einstein bisa diimplementasikan untuk semua ukuran file