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Sample records for attenuated human rotavirus

  1. Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.

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    Kuldeep S Chattha

    Full Text Available Rotaviruses (RV are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12 and 2-3 fold lower anti-inflammatory (IL10 cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented pigs had significantly higher serum IL12 (PID2 and IFNγ (PID6 compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more

  2. Rotavirus.

    Science.gov (United States)

    Esona, Mathew D; Gautam, Rashi

    2015-06-01

    Group A rotavirus (RVA) is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live, attenuated rotavirus vaccines, Rotarix® and RotaTeq®, has dramatically reduced RVA-associated AGE and mortality. High-throughput, sensitive and specific techniques are required to rapidly diagnose and characterize rotavirus strains in stool samples for proper patient treatment and to monitor circulating vaccine and wild-type rotavirus strains. New molecular assays are rapidly developed that are more sensitive and specific than the conventional assays for detection, genotyping and full genome characterization of circulating rotavirus wild-type and vaccine (Rotarix® and RotaTeq®) strains causing AGE.

  3. Similarity of Bovine Rotavirus Receptor and Human Rotavirus Receptor

    Institute of Scientific and Technical Information of China (English)

    苏琦华; 訾自强; 潘菊芬; 徐燕

    2004-01-01

    The monoclonal antibody against bovine rotavirus (BRV) receptor (BRV-R-mAb) was used to explore the similarity between the receptors of BRV and human rotavirus (HRV). ELISA, dot immunobinding assay, cell protection assay, solid-phase assay and immunohistochemistry method were applied. BRV-R-mAb bound both anti-BRV IgG and anti-HRV IgG respectively and could protect MA 104 cells against BRV and HRV challenges. Immunohistochemistry test showed that there were rotavirus receptors on the surfaces of foetal intestinal, tracheal mucosa and MA 104 cells membrane. We purified the rotavirus receptors on MA 104 ceils, which could bind both BRV and HRV in vitro. It is concluded that BRV receptor and HRV receptor are homogenous proteins and can be recognized by both BRV and HRV.

  4. Unusual assortment of segments in 2 rare human rotavirus genomes.

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    De Grazia, Simona; Giammanco, Giovanni M; Potgieter, Christiaan A; Matthijnssens, Jelle; Banyai, Krisztian; Platia, Maria A; Colomba, Claudia; Martella, Vito

    2010-05-01

    Using full-length genome sequence analysis, we investigated 2 rare G3P[9] human rotavirus strains isolated from children with diarrhea. The genomes were recognized as assortments of genes closely related to rotaviruses originating from cats, ruminants, and humans. Results suggest multiple transmissions of genes from animal to human strains of rotaviruses.

  5. 口服轮状病毒疫苗及其保护效果%Oral live attenuated rotavirus vaccines and their protective efficacy

    Institute of Scientific and Technical Information of China (English)

    何泗涛

    2011-01-01

    Human rotavirus is the most common pathogen of childhood diarrhea,and vaccination is an effective way to reduce the morbidity of rotavirus diseases.This review briefly introduces the epidemiological and clinical characteristics of rotavirus diseases,and summarizes the protection efficacy of oral live attenuated rotavirus vaccines.%人轮状病毒是引起婴幼儿腹泻最常见的病原体,疫苗接种是降低轮状病毒疾病发病率的有效方法.此文简要介绍了轮状病毒疾病的流行病学和临床特征,并对口服轮状病毒减毒活疫苗的保护效果做一综述.

  6. Inactivation of human and simian rotaviruses by ozone

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    Vaughn, J.M.; Chen, Y.S.; Lindburg, K.; Morales, D.

    1987-09-01

    The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

  7. Rotaviruses

    Centers for Disease Control (CDC) Podcasts

    2009-01-06

    CDC's Dr. Jon Gentsch discusses rotaviruses, the most important cause of severe gastroenteritis in children less than five years of age. Essentially, all children around the world get the disease during the first few years of life.  Created: 1/6/2009 by Emerging Infectious Diseases.   Date Released: 1/6/2009.

  8. Dietary rice bran protects against rotavirus diarrhea and promotes Th1-type immune responses to human rotavirus vaccine in gnotobiotic pigs.

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    Yang, Xingdong; Wen, Ke; Tin, Christine; Li, Guohua; Wang, Haifeng; Kocher, Jacob; Pelzer, Kevin; Ryan, Elizabeth; Yuan, Lijuan

    2014-10-01

    Rice bran (RB) contains a distinct stoichiometry of phytochemicals that can promote gut mucosal immune responses against enteric pathogens. The effects of RB on rotavirus diarrhea and immunogenicity of an attenuated human rotavirus (HRV) vaccine were evaluated in gnotobiotic pigs. The four treatment groups studied were RB plus vaccine, vaccine only, RB only, and mock control. Pigs in the RB groups were fed the amount of RB that replaced 10% of the pigs' total daily calorie intake from milk starting from 5 days of age until they were euthanized. Pigs in the vaccine groups were orally inoculated with two doses of the attenuated HRV vaccine. A subset of pigs from each group was orally challenged with the homologous virulent HRV on postinoculation day 28. Diarrhea and virus shedding were monitored daily from postchallenge day 0 to day 7. RB feeding significantly protected against diarrhea upon virulent HRV challenge and enhanced the protective rate of the vaccine against rotavirus diarrhea. Consistent with protection, RB significantly increased gamma interferon (IFN-γ)-producing CD4(+) and CD8(+) T cell responses in intestinal and systemic lymphoid tissues. Furthermore, RB also increased the number of total IgM- and IgA-secreting cells, total serum IgM, IgG, and IgA titers, and HRV-specific IgA titers in intestinal contents. RB reduced the numbers of intestinal and systemic HRV-specific IgA and IgG antibody-secreting cells and reduced serum HRV-specific IgA and IgG antibody titers before the challenge. These results demonstrate clear beneficial effects of RB in protection against rotavirus diarrhea and stimulation of nonspecific and HRV-specific immune responses, as well as its biased Th1-type adjuvant effect for the vaccine.

  9. Sequence Diversity of VP4 and VP7 Genes of Human Rotavirus Strains in Saudi Arabia.

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    Abdel-Moneim, Ahmed S; Al-Malky, Mater I R; Alsulaimani, Adnan A A; Abuelsaad, Abdelaziz S A; Mohamed, Imad; Ismail, Ayman K

    2015-12-01

    Group A rotavirus is responsible for inducing severe diarrhea in young children worldwide. Rotavirus vaccines are used to control the disease in many countries. In the current study, the sequences of human rotavirus G and P types in Saudi Arabia are reported and compared to different relevant published sequences. In addition, the VP4 and VP7 genes of the G1P[8] strains are compared to different antigenic epitopes of the rotavirus vaccines. Stool samples were collected from children under 2 years suffering from severe diarrhea. Screening of the rotavirus-positive samples was performed with rapid antigen detection kit. RNA was amplified from rotavirus-positive samples by reverse transcriptase polymerase chain reaction assay for both VP4 and VP7 genes. Direct sequencing of the VP4 and VP7 genes was conducted and the obtained sequences were compared to each other and to the rotavirus vaccines. Both G1P[8] G1P[4] genotypes were detected. Phylogenetic analysis revealed that the detected strains belong to G1 lineage 1 and 2, P[8] lineage 3, and to P[4] lineage 5. Multiple amino acid substitutions were detected between the Saudi RVA strains and the commonly used vaccines. The current findings emphasize the importance of the continuous surveillance of the circulating rotavirus strains, which is crucial for monitoring virus evolution and helping in predicting the protection level afforded by rotavirus vaccines.

  10. Clinical Symptoms of Human Rotavirus Infection Observed in Children in Sokoto, Nigeria

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    B. R. Alkali

    2015-01-01

    Full Text Available Rotavirus has been identified among the most important causes of infantile diarrhoea, especially in developing countries. The present study was undertaken to determine the occurrence and clinical symptoms of human rotavirus disease among children presenting with varying degree of diarrhoea in selected urban hospitals in Sokoto metropolis, Nigeria. Diarrhoea samples were collected from 200 diarrheic children younger than 5 years of age and tested using a commercially available DAKO Rotavirus ELISA kit which detects the presence of human group A rotaviruses. A questionnaire, based on WHO generic protocol, was completed for each child to generate the primary data. Of the total number of samples collected, 51 were found to be positive for human group A rotavirus indicating 25.5% prevalence of the disease in Sokoto state. The symptoms associated with the disease were analyzed and discussed.

  11. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  12. Human group C rotavirus in children with diarrhea in the Federal District, Brazil

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    Teixeira J.M.S.

    1998-01-01

    Full Text Available Group C rotaviruses are fastidious in their in vitro cell culture requirements. Recent serosurveys indicate that antibody to group C rotavirus is present in 3-45% of the human population in certain geographic locations, suggesting that rotavirus group C infection is more prevalent than previously believed and that the low rate of detection of these agents is probably due to the lack of sensitive diagnostic assays. From March to December 1994, 406 fecal specimens were collected from children under five years of age who were outpatients at the emergency services of nine public hospitals in Brasília, Federal District, Brazil. In addition to the samples from children, one public outpatient unit requested virological investigation of a stool sample from an HIV-seropositive adult male with diarrhea of sudden onset. All samples were analyzed by enzyme immunoassay for group A rotavirus and adenovirus (EIARA and by polyacrylamide gel electrophoresis (PAGE. One hundred and seven (26% were positive for group A rotavirus. Four samples from children and the sample from the HIV-seropositive patient, although negative by EIARA, showed a group C rotavirus profile by PAGE and were positive for rotavirus by electron microscopy. Using specific VP6 and VP7 primers for group C rotavirus, a reverse transcriptase-polymerase chain reaction (RT-PCR was performed and products were detected by agarose gel electrophoresis and ethidium bromide staining. These products were confirmed to be specific for group C rotavirus by using digoxigenin-oligonucleotide probes, Southern hybridization and chemiluminescent detection. The five positive group C rotavirus samples were detected in August (3 samples and September (2 samples. To the best of our knowledge, this is the first report of group C rotavirus detected in the Federal District, Brazil and in an HIV-seropositive patient with acute gastroenteritis.

  13. Inactivation of human and simian rotaviruses by chlorine dioxide

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    Chen, Yu-Shiaw (Brookhaven National Lab., Upton, NY (USA)); Vaughn, J.M. (Univ. of New England College of Medicine, Biddeford, ME (USA))

    1990-05-01

    The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4{degree}C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10{sup 5}-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate a neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants.

  14. Inactivation of human and simian rotaviruses by chlorine dioxide.

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    Chen, Y S; Vaughn, J M

    1990-01-01

    The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4 degrees C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10(5)-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate at neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants. PMID:2160222

  15. Whole genotype constellation of prototype feline rotavirus strains FRV-1 and FRV64 and their phylogenetic relationships with feline-like human rotavirus strains.

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    Gauchan, Punita; Sasaki, Eriko; Nakagomi, Toyoko; Do, Loan Phuong; Doan, Yen Hai; Mochizuki, Masami; Nakagomi, Osamu

    2015-02-01

    Feline rotaviruses, members of the species Rotavirus A, are an infrequent source of zoonotic infections, and were previously shown by RNA-RNA hybridization assays to possess two distinct genomic RNA constellations, represented by strains FRV-1 and FRV64. Due to the lack of whole genome sequence information for FRV-1, human rotavirus strain AU-1 has been used as a surrogate for the genotype constellation of feline rotaviruses. The aim of this study was to determine the whole genome sequence of FRV-1 and FRV64 to help understand the genetic relationships among existing feline rotaviruses from the evolutionary perspective. The genotype constellations of FRV-1 and FRV64 were G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H3 and G3-P[3]-I3-R3-C2-M3-A9-N2-T3-E3-H6, respectively. FRV-1 has a genotype constellation identical to that of the AU-1 strain. Although for individual genes they shared lineages, with the exception of genes encoding VP2, VP6 and VP7, the sequence identity between FRV-1 and AU-1 was considered to be sufficiently high for the AU-1 to be regarded as an example of the direct transmission of a feline rotavirus to a child. On the other hand, the FRV64 strain was not only similar in all the 11 genome segments to another feline rotavirus strain, Cat97, but also to canine rotavirus strains (K9 and CU-1) and feline/canine-like human rotavirus strains (Ro1845 and HCR3A). In conclusion, this study revealed intermingled sharing of genotypes and lineages among feline rotaviruses, suggesting the occurrence of frequent reassortment events over the course of evolution to emerge in four genotype constellations represented by FRV-1, FRV64/Cat97, Cat2 and BA222 strains.

  16. Distinguishing the genotype 1 genes and proteins of human Wa-like rotaviruses vs. porcine rotaviruses.

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    Silva, Fernanda D F; Gregori, F; McDonald, Sarah M

    2016-09-01

    Group A rotaviruses (RVAs) are 11-segmented, double-stranded RNA viruses and important causes of gastroenteritis in the young of many animal species. Previous studies have suggested that human Wa-like RVAs share a close evolutionary relationship with porcine RVAs. Specifically, the VP1-VP3 and NSP2-5/6 genes of these viruses are usually classified as genotype 1 with >81% nucleotide sequence identity. Yet, it remains unknown whether the genotype 1 genes and proteins of human Wa-like strains are distinguishable from those of porcine strains. To investigate this, we performed comprehensive bioinformatic analyses using all known genotype 1 gene sequences. The RVAs analyzed represent wildtype strains isolated from humans or pigs at various geographical locations during the years of 2004-2013, including 11 newly-sequenced porcine RVAs from Brazil. We also analyzed archival strains that were isolated during the years of 1977-1992 as well as atypical strains involved in inter-species transmission between humans and pigs. We found that, in general, the genotype 1 genes of typical modern human Wa-like RVAs clustered together in phylogenetic trees and were separate from those of typical modern porcine RVAs. The only exception was for the NSP5/6 gene, which showed no host-specific phylogenetic clustering. Using amino acid sequence alignments, we identified 34 positions that differentiated the VP1-VP3, NSP2, and NSP3 genotype 1 proteins of typical modern human Wa-like RVAs versus typical modern porcine RVAs and documented how these positions vary in the archival/unusual isolates. No host-specific amino acid positions were identified for NSP4, NSP5, or NSP6. Altogether, the results of this study support the notion that human Wa-like RVAs and porcine RVAs are evolutionarily related, but indicate that some of their genotype 1 genes and proteins have diverged over time possibly as a reflection of sequestered replication and protein co-adaptation in their respective hosts.

  17. Sunlight-induced inactivation of human Wa and porcine OSU rotaviruses in the presence of exogenous photosensitizers

    KAUST Repository

    Romero-Maraccini, Ofelia C.

    2013-10-01

    Human rotavirus Wa and porcine rotavirus OSU solutions were irradiated with simulated solar UV and visible light in the presence of different photosensitizers dissolved in buffered solutions. For human rotavirus, the exogenous effects were greater than the endogenous effects under irradiation with full spectrum and UVA and visible light at 25 C. For porcine rotavirus, the exogenous effects with UVA and visible light irradiation were only observed at high temperatures, >40 C. The results from dark experiments conducted at different temperatures suggest that porcine rotavirus has higher thermostability than human rotavirus. Concentrations of 3′-MAP excited triplet states of 1.8 fM and above resulted in significant human rotavirus inactivation. The measured excited triplet state concentrations of ≤0.45 fM produced by UVA and visible light irradiation of natural dissolved organic matter solutions were likely not directly responsible for rotavirus inactivation. Instead, the linear correlation for human rotavirus inactivation rate constant (kobs) with the phenol degradation rate constant (kexp) found in both 1 mM NaHCO3 and 1 mM phosphate-buffered solutions suggested that OH radical was a major reactive species for the exogenous inactivation of rotaviruses. Linear correlations between rotavirus kobs and specific UV254 nm absorbance of two river-dissolved organic matter and two effluent organic matter isolates indicated that organic matter aromaticity may help predict formation of radicals responsible for rotavirus inactivation. The results from this study also suggested that the differences in rotavirus strains should be considered when predicting solar inactivation of rotavirus in sunlit surface waters. © 2013 American Chemical Society.

  18. Evidence of multiple reassortment events of feline-to-human rotaviruses based on a rare human G3P[9] rotavirus isolated from a patient with acute gastroenteritis.

    Science.gov (United States)

    Nguyen, Tinh Huu; Than, Van Thai; Thanh, Hien Dang; Kim, Wonyong

    2016-06-01

    A rare human/feline-like rotavirus G3P[9] strain, CAU14-1-262, from a 2-year-old girl with severe gastroenteritis was isolated and sequenced. The 11 gene segments of the CAU14-1-262 strain possessed a novel genotype constellation, G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6, which was identified for the first time. Phylogenetic analysis of this strain identified the following genome origins: VP7, VP4, VP6, VP1-VP3, NSP1, NSP2, and NSP4 genes possessed an AU-1-like genotype 3 constellation with high sequence identity to those of the feline and human/feline-like rotaviruses; NSP5 possessed a H6 lineage, with highest sequence identity to the human/feline-like E2541 strain; and the NSP3 gene possessed a Wa-like genotype 1 constellation with high sequence identity to those of the of human rotaviruses. These results provided evidence of multiple reassortment events in G3P[9] rotavirus CAU14-1-262 and possibility of feline-to-human interspecies transmission.

  19. Recombinant monovalent llama-derived antibody fragments (VHH) to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

    Science.gov (United States)

    Vega, Celina G; Bok, Marina; Vlasova, Anastasia N; Chattha, Kuldeep S; Gómez-Sebastián, Silvia; Nuñez, Carmen; Alvarado, Carmen; Lasa, Rodrigo; Escribano, José M; Garaicoechea, Lorena L; Fernandez, Fernando; Bok, Karin; Wigdorovitz, Andrés; Saif, Linda J; Parreño, Viviana

    2013-01-01

    Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

  20. Recombinant Monovalent Llama-Derived Antibody Fragments (VHH) to Rotavirus VP6 Protect Neonatal Gnotobiotic Piglets against Human Rotavirus-Induced Diarrhea

    Science.gov (United States)

    Vlasova, Anastasia N.; Chattha, Kuldeep S.; Gómez-Sebastián, Silvia; Nuñez, Carmen; Alvarado, Carmen; Lasa, Rodrigo; Escribano, José M.; Garaicoechea, Lorena L.; Fernandez, Fernando; Bok, Karin; Wigdorovitz, Andrés; Saif, Linda J.; Parreño, Viviana

    2013-01-01

    Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea. PMID:23658521

  1. Recombinant monovalent llama-derived antibody fragments (VHH to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

    Directory of Open Access Journals (Sweden)

    Celina G Vega

    Full Text Available Group A Rotavirus (RVA is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH to protect against human rotavirus in gnotobiotic (Gn piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256 for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

  2. Physicochemical stability and inactivation of human and simian rotaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  3. Physicochemical stability and inactivation of human and simian rotaviruses.

    Science.gov (United States)

    Meng, Z D; Birch, C; Heath, R; Gust, I

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H2O2 for 1 h each.

  4. The Meta-Analysis of Vaccine Protective Efficacy of Oral Rotavirus Attenuated Live Vaccine%口服轮状病毒减毒活疫苗保护效果研究Meta分析

    Institute of Scientific and Technical Information of China (English)

    胡昱; 李倩; 陈恩富; 戚小华; 陈雅萍

    2012-01-01

    目的 评价口服轮状病毒减毒活疫苗(Oral Rotavirus Attenuated Live Vaccine,ORV)的流行病学保护效果.方法 电子检索《中国生物医学文献数据库》、《中国期刊全文数据库》、《万方全文数据库》、National Center for Biotechnology Information (NCBI)(《美国国家医学图书馆数据库》)、《Cochrane(考柯兰)协作网图书馆》等数据库,将有关接种ORV流行病学保护效果的研究纳入分析.使用Rev Man4.2.10软件进行统计分析.结果 共纳入14篇文献,有6项为随机对照试验研究,8项为队列研究.单价兰州羊(Monovalent Lanzhou Lamb) ORV (ORV-L)对轮状病毒胃肠炎( Rotavirus Gastroenteritis,RVGE)的保护率为76% [95%可信区间(Confidence Interval,CI):67%~83%];单价人(Monovalent Human)ORV (ORV-H)和五价人-牛重配(Pentavalent Human-Bovine Reassortant)ORV(ORV-HB)对RVGE、严重(Severe) RVGE (SRVGE)和住院率(Hospitalized rate)的合并保护率分别为61% (95%CI:28%~79%)、71% (95%CI:44%~85%)和88% (95%CI:67%~96%).7篇文献报道了ORV的安全性,无严重不良反应和死亡报告.结论 接种不同种类的ORV可以不同程度地降低RVGE的发病,减少SRVGE和降低AR,具有良好的保护效果.%Objective To evaluate vaccine protective efficacy (VE) of oral rotavirus attenuated live vaccine(ORV) used in China. Methods Searching "China Biology Medicine disc,CBMd", "China National Knowledge Infrastructure, CNKI", "Wanfang Database, WF" database, "National Center for Biotechnology Information, NCBI"," Cochrane Library,CL", the studies of VE for ORV were included, and meta analysis were made by RevMan4.2.10 software. Results A total of 14 studies were included, 6 studies were random clinic trial (RCT), 8 studies were cohort studies. The VE of monovalent Lanzhou lamb rotavirus vaccine(ORV-L) against rotavirus gastroenteritis(RVGE) was 76% [95% (confidence interval, C/) :61% ~83% ]. The combined VE of monovalent

  5. Rotavirus vaccination: a concise review.

    Science.gov (United States)

    Vesikari, T

    2012-10-01

    Live attenuated oral rotavirus vaccines were tested for proof-of-concept in the early 1980s, the first vaccine (RotaShield, Wyeth) was introduced in 1998 but was subsequently withdrawn because of association with intussusception, and the two currently licensed vaccine (Rotarix, GlaxoSmithKline, and RotaTeq, Merck) were introduced in 2006. Before licensure both vaccines were extensively tested for safety (for intussusception) and efficacy in trials comprising in over 60,000 infants each. Rotarix is a single-strain human rotavirus vaccine (RV1) and RotaTeq is a combination of five bovine-human reassortant rotaviruses (RV5). Although the composition of the two vaccines is different, their field effectiveness and, largely, mechanism of action are similar. Both prevent effectively severe rotavirus gastroenteritis (RVGE) but are less efficacious against mild RVGE or rotavirus infection. Field effectiveness of these vaccines in Europe and the USA against severe RVGE has been above 90% and in Latin America around 80%. Trials in Africa have yielded efficacy rates between 50 and 80%. Rotavirus vaccination has been introduced into the national immunization programmes of about 20 countries in Latin America, with Brazil and Mexico as leading countries, as well as in the USA, Australia and South Africa. Introduction into other African countries will start in 2012. In Europe, Belgium, Luxembourg, Austria and Finland and five federal states of Germany have introduced universal rotavirus vaccination. The reasons for the slow progress in Europe include low mortality from RVGE, unfavourable cost-benefit calculations in some countries, and concerns that still exist over intussusception.

  6. Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

    Directory of Open Access Journals (Sweden)

    Aruna Chandran

    2010-07-01

    Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

  7. Discovery of rotavirus: Implications for child health.

    Science.gov (United States)

    Bishop, Ruth

    2009-10-01

    For centuries, acute diarrhea has been a major worldwide cause of death in young children, and until 1973, no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. In 1973 Ruth Bishop, Geoffrey Davidson, Ian Holmes, and Brian Ruck identified abundant particles of a 'new' virus (rotavirus) in the cytoplasm of mature epithelial cells lining duodenal villi and in feces, from such children admitted to the Royal Children's Hospital, Melbourne. Rotaviruses have now been shown to cause 40-50% of severe acute diarrhea in young children worldwide in both developing and developed countries, and > 600 000 young children die annually from rotavirus disease, predominantly in South-East Asia and sub-Saharan Africa. Longitudinal surveillance studies following primary infection in young children have shown that rotavirus reinfections are common. However the immune response that develops after primary infection is protective against severe symptoms on reinfection. This observation became the basis for development of live oral rotavirus vaccines. Two safe and effective vaccines are now licensed in 100 countries and in use in 17 countries (including Australia). Rotarix (GSK) is a single attenuated human rotavirus, representative of the most common serotype identified worldwide (G1P[8]). RotaTeq (Merck) is a pentavalent mixture of naturally attenuated bovine/human rotavirus reassortants representing G1, G2, G3, G4, and P(8) serotypes. Preliminary surveillance of the numbers of children requiring hospitalization for severe diarrhea, in USA, Brazil, and Australia, after introduction of these vaccines, encourages the hope that rotavirus infection need no longer be a threat to young children worldwide.

  8. Rotavirus vaccines: viral shedding and risk of transmission.

    Science.gov (United States)

    Anderson, Evan J

    2008-10-01

    Rotavirus causes gastroenteritis in almost all children by 5 years of age. Immunity to rotavirus is incomplete, with potential for recurrent infections occurring throughout life. Live rotavirus vaccines have been developed for the protection of children from severe wildtype rotavirus infections. Transmission of vaccine virus strains from vaccinated children to unvaccinated contacts harbours the potential for herd immunity, but also the risk of vaccine-derived disease in immunocompromised contacts. A review of rotavirus vaccine prelicensure studies shows that viral shedding and transmission were higher with the old tetravalent rhesus rotavirus vaccine than with the current human attenuated monovalent rotavirus vaccine and the pentavalent bovine-human reassortant vaccine. Immunocompromised contacts should be advised to avoid contact with stool from the immunised child if possible, particularly after the first vaccine dose for at least 14 days. Since the risk of vaccine transmission and subsequent vaccine-derived disease with the current vaccines is much less than the risk of wildtype rotavirus disease in immunocompromised contacts, vaccination should be encouraged.

  9. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

    Science.gov (United States)

    Nyaga, Martin M; Jere, Khuzwayo C; Esona, Mathew D; Seheri, Mapaseka L; Stucker, Karla M; Halpin, Rebecca A; Akopov, Asmik; Stockwell, Timothy B; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M; Steele, A Duncan; Wentworth, David E; Mphahlele, M Jeffrey

    2015-04-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  10. Analysis of gene selection in reassortant formation between canine rotavirus K9 and human rotaviruses with different antigenic specificities.

    Science.gov (United States)

    Kobayashi, N; Taniguchi, K; Urasawa, T; Urasawa, S

    1993-01-01

    A number of antigenic mosaic reassortants which have neutralization proteins VP4 and VP7 derived from different parental strains were analysed in order to study gene selection in reassortant formation between animal and human rotaviruses (HRV). These reassortants were isolated from mixed infection of MA-104 cells with canine rotavirus strain K9 (subgroup I and G serotype 3) and HRV strains (with subgroup I or II antigen and G serotype 1-4, 9 or 12 antigen), through repeated selections with anti-VP4 and anti-VP7 neutralizing monoclonal antibodies directed specifically at HRV and K9, respectively. By serological and genomic analyses, all the isolated clones were found to be antigenic mosaic reassortants possessing VP4 of K9 and VP7 of HRV. In the reassortants between strain K9 and one of the six strains of subgroup II HRV, a single or a few genotypes with particular constellations of RNA segments were predominant, with only a few RNA segments including gene 4 (encoding VP4) being derived from K9. In contrast, in the reassortants between strain K9 and any one of the subgroup I HRV, more than nine different genotypes were identified and various RNA segments, except for segments 8 and 10, were derived from K9. These findings indicated that the RNA segments of K9 might be reassorted more readily with those of subgroup I HRV than with those of subgroup II HRV, suggesting the possible existence of functional mechanisms which determine the extent of diversity of genome selection depending on the pairs of parent strains in the reassortant formation.

  11. Prevention of surface-to-human transmission of rotaviruses by treatment with disinfectant spray.

    Science.gov (United States)

    Ward, R L; Bernstein, D I; Knowlton, D R; Sherwood, J R; Young, E C; Cusack, T M; Rubino, J R; Schiff, G M

    1991-09-01

    A model was developed to examine the effects of disinfectants on the transmission of infectious rotavirus from a dried surface to humans. The initial experiments were designed to find a method of preserving rotavirus infectivity during drying. Culture-adapted human rotavirus (CJN strain) was dried at room temperature in different organic suspensions, including fecal matter, several laboratory media, and nonfat dry milk (NDM). Recoveries of infectious virus were then compared. Fecal matter provided little protection in this study relative to distilled water, but the other suspensions were quite protective, especially NDM, which consistently allowed recoveries of greater than 50%. When 10(3) focus-forming units of unpassaged CJN virus were dried in NDM and administered to subjects who licked the dried material, 100% (8 of 8) became infected. The effect of Lysol brand disinfectant spray (LDS) was next examined. Although NDM provided some protection against inactivation by LDS, spraying under conditions recommended by the manufacturer consistently caused the CJN virus titer to decrease greater than 5 log10. Consumption of CJN virus (10(3) focus-forming units) sprayed with LDS caused no infection in 14 subjects, whereas 13 of 14 subjects who consumed the unsprayed virus became infected (P less than 0.00001). The methods developed in this study could be used to test the effects of other disinfectants on the spread of infectious rotavirus from inanimate surfaces to humans.

  12. High Titers of Circulating Maternal Antibodies Suppress Effector and Memory B-Cell Responses Induced by an Attenuated Rotavirus Priming and Rotavirus-Like Particle-Immunostimulating Complex Boosting Vaccine Regimen

    Science.gov (United States)

    Nguyen, Trang V.; Yuan, Lijuan; Azevedo, Marli S. P.; Jeong, Kwang-il; Gonzalez, Ana M.; Iosef, Cristiana; Lovgren-Bengtsson, Karin; Morein, Bror; Lewis, Peggy; Saif, Linda J.

    2006-01-01

    We investigated maternal antibody (MatAb) effects on protection and immune responses to rotavirus vaccines. Gnotobiotic pigs were injected intraperitoneally at birth with pooled serum from sows hyperimmunized with human rotavirus (HRV); control pigs received no sow serum. Pigs with or without MatAbs received either sequential attenuated HRV (AttHRV) oral priming and intranasal boosting with VP2/VP6 virus-like particle (VLP)-immunostimulating complex (ISCOM) (AttHRV/VLP) or intranasal VLP-ISCOM prime/boost (VLP) vaccines at 3 to 5 days of age. Subsets of pigs were challenged at 28 or 42 days postinoculation with virulent Wa HRV to assess protection. Isotype-specific antibody-secreting cell (ASC) responses to HRV were quantitated by enzyme-linked immunospot assay to measure effector and memory B-cell responses in intestinal and systemic lymphoid tissues pre- and/or postchallenge. Protection rates against HRV challenge (contributed by active immunity and passive circulating MatAbs) were consistently (but not significantly) lower in the MatAb-AttHRV/VLP groups than in the corresponding groups without MatAbs. Intestinal B-cell responses in the MatAb-AttHRV/VLP group were most suppressed with significantly reduced or no intestinal immunoglobulin A (IgA) and IgG effector and memory B-cell responses or antibody titers pre- and postchallenge. This suppression was not alleviated but was enhanced after extending vaccination/challenge from 28 to 42 days. In pigs vaccinated with nonreplicating VLP alone that failed to induce protection, MatAb effects differed, with intestinal and systemic IgG ASCs and prechallenge memory B cells suppressed but the low intestinal IgA and IgM ASC responses unaffected. Thus, we demonstrate that MatAbs differentially affect both replicating and nonreplicating HRV vaccines and suggest mechanisms of MatAb interference. This information should facilitate vaccine design to overcome MatAb suppression. PMID:16603615

  13. Vacinas contra rotavírus e papilomavírus humano (HPV Vaccines against rotavirus and human papillomavirus (HPV

    Directory of Open Access Journals (Sweden)

    Alexandre C. Linhares

    2006-07-01

    -se que a implementação de vacinas de elevada eficácia na prevenção de tumores benignos e malignos causados por alguns tipos de HPV leve a uma queda acentuada das taxas desses tumores, os quais afetam milhões de pessoas em todo o mundo.OBJECTIVE: To briefly review strategies aimed at the development of rotavirus and HPV vaccines, with emphasis on the current status of studies assessing the safety, reactogenicity, immunogenicity and efficacy of recently developed vaccines. SOURCES OF DATA: This review focuses on articles published from 1996 to 2006, mainly those from the last five years, with special emphasis on data obtained from recently completed studies involving a new live attenuated human rotavirus vaccine and a virus-like particle (HPV vaccine. SUMMARY OF THE FINDINGS: Strategies for developing rotavirus vaccines ranged from Jennerian approaches to the new human-derived rotavirus vaccine. Currently, two rotavirus vaccines are recognized as both efficacious and safe: a pentavalent human-bovine reassortant vaccine and a vaccine derived from an attenuated rotavirus of human origin. The second of these has been evaluated in more than 70,000 infants all over the world. Prophylactic vaccines against HPV have been tested in more than 25,000 young individuals around the world. Results from phase II and III clinical studies indicate that such vaccines against the most common types of HPV, those linked to both genital warts and 70% of cervical cancers, are safe and highly efficacious. CONCLUSIONS: A future rotavirus immunization program covering 60 to 80% of infants worldwide is likely to reduce by at least 50% the number of rotavirus-associated hospitalizations and deaths. It is also reasonable to expect that implementation of HPV prophylactic vaccines will reduce the burden of the HPV-related diseases that presently impact millions of people around the world.

  14. Human rotavirus vaccine (Rotarix): focus on effectiveness and impact 6 years after first introduction in Africa.

    Science.gov (United States)

    O'Ryan, Miguel; Giaquinto, Carlo; Benninghoff, Bernd

    2015-01-01

    A decade after licensure of the human rotavirus vaccine (HRV), a wealth of evidence supports a reduction of rotavirus (RV) gastroenteritis-associated mortality and hospitalizations following HRV inclusion in national immunization programs. Nevertheless, the majority of real-world data has been generated in high- or middle-income settings. Clinical efficacy trials previously indicated RV vaccine performance may be lower in less-developed countries compared with wealthier counterparts. Using recently published data from Africa, we examine the effectiveness and impact of HRV in resource-deprived areas, exploring whether vaccine performance differs by socioeconomic setting and the potential underlying factors. HRV vaccine effectiveness in early adopting African countries has proven to be similar or even superior to the efficacy results observed in pre-licensure studies.

  15. Hypertrophy, hyperplasia, and infectious virus in gut-associated lymphoid tissue of mice after oral inoculation with simian-human or bovine-human reassortant rotaviruses.

    Science.gov (United States)

    Moser, C A; Dolfi, D V; Di Vietro, M L; Heaton, P A; Offit, P A; Clark, H F

    2001-04-01

    Oral inoculation of infants with a vaccine that contains simian-human reassortant rotaviruses has been found to be a rare cause of intussusception. Because intussusception can be associated with enlargement of gut-associated lymphoid tissue, we studied the capacity of simian-human and bovine-human reassortant rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP) of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP after oral inoculation with simian-human or bovine-human reassortant rotaviruses. However, infectious virus was detected in PP and mesenteric lymph nodes after oral inoculation with simian, but not bovine, reassortant rotaviruses. Implications of these findings on the pathogenesis of intussusception are discussed.

  16. Sequence and phylogenetic analysis of the VP4 gene of human rotaviruses isolated in Paraguay.

    Science.gov (United States)

    Espínola, E E; Amarilla, A; Arbiza, J; Parra, G I

    2008-01-01

    Nucleotide and amino acid analyzes of the VP4 gene of human rotaviruses isolated both in Paraguay and worldwide were carried out in order to increase our knowledge about the complex pattern of evolution of this virus in nature. Paraguayan strains bearing the P[8] genotype were grouped in the lineages P[8]-1, P[8]-2, and P[8]-3. Regardless of the year of detection, all of the G4 and G9 strains were related to lineage P[8]-3, whereas the G1 strains were related to the three lineages detected in Paraguay; this fact reinforces the notion of the existence of constraints within specific populations of rotavirus strains except for the G1 strains. In addition, we propose a phylogenetic classification for the P[4] strains in five different lineages (i.e. P[4]-1 to P[4]-5). The findings presented in this paper reinforce the importance of a continuous surveillance of rotavirus strains in order to predict the possible variants that will circulate in a country, and ultimately improve current vaccination programs.

  17. Identification of human rotavirus serotype by hybridization to polymerase chain reaction-generated probes derived from a hyperdivergent region of the gene encoding outer capsid protein VP7

    Energy Technology Data Exchange (ETDEWEB)

    Flores, J.; Sears, J.; Schael, I.P.; White, L.; Garcia, D.; Lanata, C.; Kapikian, A.Z. (National Institutes of Health, Bethesda, MD (USA))

    1990-08-01

    We have synthesized {sup 32}P-labeled hybridization probes from a hyperdivergent region (nucleotides 51 to 392) of the rotavirus gene encoding the VP7 glycoprotein by using the polymerase chain reaction method. Both RNA (after an initial reverse transcription step) and cloned cDNA from human rotavirus serotypes 1 through 4 could be used as templates to amplify this region. High-stringency hybridization of each of the four probes to rotavirus RNAs dotted on nylon membranes allowed the specific detection of corresponding sequences and thus permitted identification of the serotype of the strains dotted. The procedure was useful when applied to rotaviruses isolated from field studies.

  18. Analysis of complete genome sequences of G9P[19] rotavirus strains from human and piglet with diarrhea provides evidence for whole-genome interspecies transmission of nonreassorted porcine rotavirus.

    Science.gov (United States)

    Yodmeeklin, Arpaporn; Khamrin, Pattara; Chuchaona, Watchaporn; Kumthip, Kattareeya; Kongkaew, Aphisek; Vachirachewin, Ratchaya; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat

    2017-01-01

    Whole genomes of G9P[19] human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19]) and porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19]) rotaviruses concurrently detected in the same geographical area in northern Thailand were sequenced and analyzed for their genetic relationships using bioinformatic tools. The complete genome sequence of human rotavirus RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] was most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19] and to those of porcine-like human and porcine rotaviruses reference strains than to those of human rotavirus reference strains. The genotype constellation of G9P[19] detected in human and piglet were identical and displayed as the G9-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes with the nucleotide sequence identities of VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4, and NSP5 at 99.0%, 99.5%, 93.2%, 97.7%, 97.7%, 85.6%, 89.5%, 93.2%, 92.9%, 94.0%, and 98.1%, respectively. The findings indicate that human rotavirus strain RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] containing the genome segments of porcine genetic backbone is most likely a human rotavirus of porcine origin. Our data provide an evidence of interspecies transmission and whole-genome transmission of nonreassorted G9P[19] porcine RVA to human occurring in nature in northern Thailand.

  19. Sequence analysis of VP4 genes of wild type and culture adapted human rotavirus G1P[8] strains

    Institute of Scientific and Technical Information of China (English)

    Ritu Arora; Ganesh S Dhale; Pooja R Patil; Shobha D Chitambar

    2011-01-01

    Objective:To conduct a comparative analysis of the VP4gene sequences of Indian wild type (06361,0613158, 061060and0715880) and cell culture adapted (06361-CA, 0613158-CA, 061060-CAand0715880-CA) G1P[8] rotavirus strains.Methods: Full-length VP4 genes of each of the four wild type G1P[8] rotavirus strains and their cell culture adapted counterparts displaying consistent cytopathic effect were subjected toRT-PCRamplification and nucleotide sequencing. Results: All four cell culture adaptedG1P[8]rotavirus strains showed nucleotide and amino acid substitutions in theVP4 gene as compared to their wild type strains. The number of substitutions however, varied from1-64and 1-13 respectively. The substitutions were distributed in both VP5*andVP8* subunits ofVP4gene respectively of permeabilization and hemagglutinating activity. The presence of unique amino acid substitutions was identified in two of the four wild type (V377G, S387N in 061060and I644Lin0715880) and all four cell culture adapted (A46Vin0613158-CA, T60R in06361-CA, L237V, G389V andQ480H in061060-CA andS615G andT625Pin0715880-CA) strains for the first time in theVP4 gene ofP[8]specificity. Amino acid substitutions generated increase in the hydrophilicity in the cell culture adapted rotavirus strains as compared to their corresponding wild type strains.Conclusions: Amino acid substitutions detected in the VP4 genes ofG1P[8]rotavirus strains from this study together with those from other studies highlight occurrence of only strain and/or host specific substitutions during cell culture adaptation. Further evaluation of such substitutions for their role in attenuation, immunogenicity and conformation is needed for the development of newer rotavirus vaccines.

  20. Rotavirus structural proteins and dsRNA are required for the human primary plasmacytoid dendritic cell IFNalpha response.

    Directory of Open Access Journals (Sweden)

    Emily M Deal

    Full Text Available Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNalpha and beta correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV, have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs with either live or inactivated RRV induces substantial IFNalpha production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNalpha production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNalpha by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNalpha induction in primary

  1. Rotavirus Infections

    Science.gov (United States)

    Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all ... the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

  2. Analysis of the full genome of human group C rotaviruses reveals lineage diversification and reassortment.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Fehér, Enikő; Marton, Szilvia; Calderaro, Adriana; Bányai, Krisztián

    2016-08-01

    Group C rotaviruses (RVC) are enteric pathogens of humans and animals. Whole-genome sequences are available only for few RVCs, leaving gaps in our knowledge about their genetic diversity. We determined the full-length genome sequence of two human RVCs (PR2593/2004 and PR713/2012), detected in Italy from hospital-based surveillance for rotavirus infection in 2004 and 2012. In the 11 RNA genomic segments, the two Italian RVCs segregated within separate intra-genotypic lineages showed variation ranging from 1.9 % (VP6) to 15.9 % (VP3) at the nucleotide level. Comprehensive analysis of human RVC sequences available in the databases allowed us to reveal the existence of at least two major genome configurations, defined as type I and type II. Human RVCs of type I were all associated with the M3 VP3 genotype, including the Italian strain PR2593/2004. Conversely, human RVCs of type II were all associated with the M2 VP3 genotype, including the Italian strain PR713/2012. Reassortant RVC strains between these major genome configurations were identified. Although only a few full-genome sequences of human RVCs, mostly of Asian origin, are available, the analysis of human RVC sequences retrieved from the databases indicates that at least two intra-genotypic RVC lineages circulate in European countries. Gathering more sequence data is necessary to develop a standardized genotype and intra-genotypic lineage classification system useful for epidemiological investigations and avoiding confusion in the literature.

  3. Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review

    Science.gov (United States)

    Thu, Hlaing Myat; Myat, Theingi Win; Win, Mo Mo; Thant, Kyaw Zin; Rahman, Shofiqur; Umeda, Kouji; Nguyen, Sa Van; Icatlo, Faustino C.; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Tsuji, Takao; Oguma, Keiji; Kim, Sang Jong; Bae, Hyun Suk

    2017-01-01

    The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.

  4. Genomic characterization of a rotavirus G8P[1] detected in a child with diarrhea reveal direct animal-to-human transmission.

    Science.gov (United States)

    Martinez, Magaly; Phan, Tung Gia; Galeano, Maria Eugenia; Russomando, Graciela; Parreno, Viviana; Delwart, Eric; Parra, Gabriel I

    2014-10-01

    Group A rotavirus is a major cause of severe gastroenteritis in children and young animals. During a retrospective analysis of samples collected from Paraguayan children under 5 years old with diarrhea, and previously negative for rotavirus and norovirus, we detected the presence of bovine rotavirus sequences by viral metagenomics. Nucleic acid was extracted direct from stool sample and determined to be G8P[1]. The genomic analyzes revealed that the strain presents an Artiodactyl-like genome (G8-P[1]-I2-R2-C2-M1-Ax-N2-T6-E12-H3) suggesting a direct animal-to-human transmission.

  5. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota.

    Science.gov (United States)

    Li, Min; Monaco, Marcia H; Wang, Mei; Comstock, Sarah S; Kuhlenschmidt, Theresa B; Fahey, George C; Miller, Michael J; Kuhlenschmidt, Mark S; Donovan, Sharon M

    2014-08-01

    The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.4 g l(-1)) (PRE) (n=19-21 per group) for 15 days. Piglets (n=7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO- and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.

  6. Zoonotic Transmission of Rotavirus in Denmark; a Case Report

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane;

    Rotavirus type A infection is a common cause of hospitalisation of children. However, in our laboratory almost 30% of rotavirus positive samples are from adults. Due to this an epidemiological study into the riskfactors for rotavirus infection in adults was set up. All identified rotavirus positive...... adults are sent a questionnaire to identify potential risk factors. Rotavirus type A infection can also occur in a range of animals, including domestic dogs, cats, cattle, horses, and birds. There is some data suggesting direct transmission between animals and humans. Rotavirus typing is carried out...... in Denmark as part of the EuroRotaNet vaccine study. Samples positive for rotavirus are type...

  7. Expression and Immunoreactivity of a Human Group A Rotavirus Vp4

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rotavirus capsid protein Vp4 plays an important role in the virus adhering and entering the cells. In this study, a Vp4 gene cloned from a rotavirus strain TB-Chen was highly expressed in E.coli BL21 (DE3). The results of the Western blot showed that the protein possesses specific immuno-reactivities and can be specifically recognized by guinea pig antibodies against rotavirus strain SA11 or Wa. Some Vp4 dimers were formed during renaturation. These data obtained from this study provide a strong basis for further study on the structure and function of the Vp4.

  8. Evolution of human G4P[8] group A rotavirus strains circulating in Italy in 2013.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-06-02

    Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young (humans worldwide are associated with the five major G/P combinations G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. During RVA gastroenteritis surveillance in Italy, a total of 1112 samples collected from children hospitalized with acute gastroenteritis in 2013 were RVA positive and were genotyped following standardized protocols from the EuroRotaNet. Most strains analyzed belonged to the five major human genotypes. Among these common strains, 22 G4P[8] RVA strains from different Italian regions were subjected to nucleotide sequencing of their VP4, VP6, VP7 and NSP4 genes to investigate their evolution. The phylogenetic analysis showed that the Italian strains belonged to lineage G4-I for VP7 and to lineage P[8]-III for VP4, in line with the modern G4P[8] RVA strains detected in children worldwide. The phylogenetic trees revealed high degrees of nucleotide identity between the RVA strains involved in this study and G4P[8] strains detected previously in Europe, Asia and Africa, but also demonstrated at least three separate evolution clusters within the same lineage. Based on the amino acid sequences deduced for their hypervariable regions, both the VP7 and VP8* proteins of the Italian G4P[8] RVA strains presented amino acid substitutions near known neutralizing epitopes.

  9. Antigenic and genomic diversity of human rotavirus VP4 in two consecutive epidemic seasons in Mexico.

    Science.gov (United States)

    Padilla-Noriega, L; Méndez-Toss, M; Menchaca, G; Contreras, J F; Romero-Guido, P; Puerto, F I; Guiscafré, H; Mota, F; Herrera, I; Cedillo, R; Muñoz, O; Calva, J; Guerrero, M L; Coulson, B S; Greenberg, H B; López, S; Arias, C F

    1998-06-01

    In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P[4] and P[8] there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods.

  10. Therapeutics Insight with Inclusive Immunopharmacology Explication of Human Rotavirus A for the Treatment of Diarrhea

    Science.gov (United States)

    Hossain, Mohammad Uzzal; Hashem, Abu; Keya, Chaman Ara; Salimullah, Md.

    2016-01-01

    Rotavirus is the most common cause of severe infant and childhood diarrhea worldwide, and the morbidity and mortality rate is going to be outnumbered in developing countries like Bangladesh. To mitigate this substantial burden of disease, new therapeutics such as vaccine and drug are swiftly required against rotavirus. The present therapeutics insight study was performed with comprehensive immunoinformatics and pharmacoinformatics approach. T and B-cell epitopes were assessed in the conserved region of outer capsid protein VP4 among the highly reviewed strains from different countries including Bangladesh. The results suggest that epitope SU1 (TLKNLNDNY) could be an ideal candidate among the predicted five epitopes for both T and B-cell epitopes for the development of universal vaccine against rotavirus. This research also suggests five novel drug compounds from medicinal plant Rhizophora mucronata Lamk. for better therapeutics strategies against rotavirus diarrhea based on 3D structure building, pharmacophore, ADMET, and QSAR properties. The exact mode of action between drug compounds and target protein VP4 were revealed by molecular docking analysis. Drug likeness and oral bioavailability further confirmed the effectiveness of the proposed drugs against rotavirus diarrhea. This study might be implemented for experimental validation to facilitate the novel vaccine and drug design. PMID:27445802

  11. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* carbohydrate-binding protein of the human rotavirus strain Wa

    Energy Technology Data Exchange (ETDEWEB)

    Kraschnefski, Mark J.; Scott, Stacy A. [Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726 (Australia); Holloway, Gavan; Coulson, Barbara S.; Itzstein, Mark von [Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010 (Australia); Blanchard, Helen, E-mail: h.blanchard@griffith.edu.au [Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726 (Australia)

    2005-11-01

    The carbohydrate-binding component (VP8*{sub 64–223}) of the human Wa rotavirus spike protein has been overexpressed in E. coli, purified and crystallized in two different crystal forms. X-ray diffraction data have been collected that have enabled determination of the Wa VP8*{sub 64–223} structure by molecular replacement. Rotaviruses exhibit host-specificity and the first crystallographic information on a rotavirus strain that infects humans is reported here. Recognition and attachment to host cells, leading to invasion and infection, is critically linked to the function of the outer capsid spike protein of the rotavirus particle. In some strains the VP8* component of the spike protein is implicated in recognition and binding of sialic-acid-containing cell-surface carbohydrates, thereby enabling infection by the virus. The cloning, expression, purification, crystallization and initial X-ray diffraction analysis of the VP8* core from human Wa rotavirus is reported. Two crystal forms (trigonal P3{sub 2}21 and monoclinic P2{sub 1}) have been obtained and X-ray diffraction data have been collected, enabling determination of the VP8*{sub 64–223} structure by molecular replacement.

  12. Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs.

    Directory of Open Access Journals (Sweden)

    Anastasia N Vlasova

    Full Text Available The effects of co-colonization with Lactobacillus rhamnosus GG (LGG and Bifidobacterium lactis Bb12 (Bb12 on 3-dose vaccination with attenuated HRV and challenge with virulent human rotavirus (VirHRV were assessed in 4 groups of gnotobiotic (Gn pigs: Pro+Vac (probiotic-colonized/vaccinated, Vac (vaccinated, Pro (probiotic-colonized, non-vaccinated and Control (non-colonized, non-vaccinated. Subsets of pigs were euthanized pre- [post-challenge day (PCD 0] and post (PCD7-VirHRV challenge to assess diarrhea, fecal HRV shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and Vac groups were completely protected from diarrhea; protection rates against HRV shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and virus shedding were significantly higher in Controls, compared to all other groups, coincident with significantly higher serum interferon-alpha levels post-challenge. LGG+Bb12 colonization ±vaccine promoted immunomaturation as reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing mononuclear cells (MNCs and conventional dendritic cells in intestinal tissues and blood post-challenge. Colonization decreased frequencies of toll-like receptors (TLR 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac pre-challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post-challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4 down-regulation and antiviral (TLR3 up-regulation by HRV dsRNA actions via TLR signaling. Probiotic colonization alone (Pro increased frequencies of intestinal and systemic apoptotic MNCs pre-challenge, thereby regulating immune hyperreactivity and tolerance. However, these frequencies were decreased in intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis. Additionally, post-challenge, Pro+Vac and Pro groups had

  13. Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

    Directory of Open Access Journals (Sweden)

    Eliete C. Araujo

    2007-06-01

    efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV. This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7 focus forming units - FFU, 196 (10(5.2 FFU, 194 (10(5.8 FFU and 194 (placebo. Anti-rotavirus (anti-RV antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE was 63.5% (95%CI 20.8-84.4 for the highest concentration (10(5.8 FFU. Efficacy was 81.5% (95%CI 44.5-95.4 against severe RVGE. At its highest concentration (10(5.8 FFU, RIX4414 provided 79.8% (95%CI 26.4-96.3 protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  14. IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model.

    Science.gov (United States)

    Vega, Celina G; Bok, Marina; Vlasova, Anastasia N; Chattha, Kuldeep S; Fernández, Fernando M; Wigdorovitz, Andrés; Parreño, Viviana G; Saif, Linda J

    2012-01-01

    Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV) diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization -VN- titer = 256) for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC) responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV-specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV). Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.

  15. LAS PROTEÍNAS β3 Y PDI AISLADAS DE PLAQUETAS HUMANAS SE UNEN CON EL ROTAVIRUS ECwt IN VITRO β3 and PDI proteins isolated from human platelets bind with ECwt rotavirus in vitro

    Directory of Open Access Journals (Sweden)

    Diana Mayorga

    2010-01-01

    policlonal contra β3 y establecer que β3 y PDI se unen in vitro, luego de incubar las proteínas aisladas con el rotavirus ECwt, e in vivo, después de incubar el rotavirus con las vellosidades aisladas del intestino delgado de ratón lactante de la cepa ICR.Background. Commercial integrin β3 is currently not available and commercial PDI is too expensive, which is making access difficult to these proteins needed for conducting experiments aimed at the establishment of possible interactions between integrin β3 and PDI and wild type rotavirus strains. Objective. To explore a methodology allowing isolation of proteins β3 and PDI from human platelets to be used as antigens in the generation of rabbit polyclonal antibodies useful in the assessment of interactions between these proteins and rotavirus ECwt. Materials and methods. Proteins β3 and PDI from human platelet lysates were separated using preparative electrophoresis under reducing conditions and then eluted. Interactions of these proteins with rotavirus ECwt were analyzed using co-immunoprecipitation, Western blotting and capture ELISA. Results. Proteins from human platelet lysates were separated by preparative electrophoresis under reducing conditions. The identification of proteins β3 and PDI present in a gel slice was performed through their reaction with commercial antibodies in a Western blotting analysis. Protein purity was established after electroelution from a gel slice. Polyclonal antibodies against protein β3 were generated in rabbit. Incubation of eluted proteins β3 and PDI with rotavirus ECwt showed in co-immunoprecipitation and ELISA assays that these proteins bound virus in vitro. The same binding was showed to occur when rotavirus was incubated with isolated small intestinal villi from suckling mice. Conclusions. Relatively high amounts of proteins β3 and PDI were partially purified from human platelets by preparative electrophoresis. The isolation of these proteins allowed the generation of

  16. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available BACKGROUND: The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents. RESULTS: All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells. CONCLUSIONS: We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  17. Rotavirus Vaccine

    Science.gov (United States)

    ... including a severe allergy to latex. Babies with "severe combined immunodeficiency" (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called "intussusception" should not get ... with moderate or severe diarrhea or vomiting. Check with your doctor if ...

  18. Rotavirus P[8] Infections in Persons with Secretor and Nonsecretor Phenotypes, Tunisia.

    Science.gov (United States)

    Ayouni, Siwar; Sdiri-Loulizi, Khira; de Rougemont, Alexis; Estienney, Marie; Ambert-Balay, Katia; Aho, Serge; Hamami, Sabeur; Aouni, Mahjoub; Neji-Guediche, Mohamed; Pothier, Pierre; Belliot, Gaël

    2015-11-01

    To determine whether rotavirus infections are linked to secretor status, we studied samples from children in Tunisia with gastroenteritis. We phenotyped saliva for human blood group antigens and tested feces for rotavirus. Rotavirus was detected in 32/114 patients. Secretor genotyping showed that P[8] rotavirus infected secretors and nonsecretors, and infection correlated with presence of Lewis antigen.

  19. Rotavirus genotype distribution during the pre-vaccine period in Bolivia: 2007–2008

    Science.gov (United States)

    Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A.; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S.; Iñiguez, Volga

    2013-01-01

    Summary Objectives Rotavirus is the most important etiology of severe diarrhea in Bolivia. The monovalent attenuated human oral rotavirus vaccine Rotarix® was introduced in Bolivia in 2008. We describe the molecular epidemiology of circulating rotavirus strains before vaccine introduction. Methods Two thousand one hundred thirty-five diarrheal samples were collected from hospitals in four Bolivian cities during 2007–2008. Forty-three percent (445 of 1030 rotavirus-positive samples) were analyzed for G and P genotypes. Among those, 331 were electropherotyped by polyacrylamide gel electrophoresis. Disease severity was quantified using a modified Vesikari scale. Results Among the 445 samples, five genotypes were found to be prevalent: G9P[8] (33%), G1P[6] (17%), G2P[4] (13%), G9P[6] (12%), and G1P[8] (4%). Co-infections with two or more strains accounted for 14% of samples. The most prevalent strain, G9, showed greater electropherotype diversity compared to other serogroups. Strain G1P[6] generally infected younger children and peaked later in the year than other strains. No particular genotype was associated with a higher severity score, though there was a significant difference in the duration of diarrhea between genotypes. Conclusions During the 2-year pre-vaccine period, substantial diversity of rotavirus co-circulating strains was observed. These data constitute a baseline against which changes in circulating strains post-vaccine introduction can be monitored. PMID:23688547

  20. Development and characterization of candidate rotavirus vaccine strains derived from children with diarrhoea in Vietnam.

    Science.gov (United States)

    Luan, Le T; Trang, Nguyen V; Phuong, Nguyen M; Nguyen, Huong T; Ngo, Huong T; Nguyen, Huong T M; Tran, Hanh B; Dang, Ha N; Dang, Anh D; Gentsch, Jon R; Wang, Yuhuan; Esona, Mathew D; Glass, Roger I; Steele, A Duncan; Kilgore, Paul E; Nguyen, Man V; Jiang, Baoming; Nguyen, Hien D

    2009-11-20

    In Vietnam, rotavirus infection accounts for more than one-half of all hospitalizations for diarrhoea among children less than 5 years of age. While new vaccines to prevent rotavirus diarrhoea have been developed and introduced into some countries by multinational manufacturers, the ability for developing countries such as Vietnam to introduce several new and important vaccines into the routine infant immunization schedule may be challenging. In order to be partially self-sufficient in vaccine production, Vietnam has pursued the development of several rotavirus strains as candidate vaccines using isolates obtained from Vietnamese children with diarrhoea. This paper describes the origin, isolation and characterization of 3 human rotavirus strains being considered for further vaccine development in Vietnam. The goal is to prepare a monovalent G1P [8] rotavirus vaccine using one of these strains obtained in Vietnam and naturally attenuated by multiple passages in cell culture. While this is an ambitious project that will require several years' work, we are using the lessons learned to improve the overall quality of vaccine production including the use of Vero cell techniques for the manufacture of other vaccines in Vietnam.

  1. Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs

    Science.gov (United States)

    Paim, Francine C.; Kandasamy, Sukumar; Alhamo, Moyasar A.; Fischer, David D.; Langel, Stephanie N.; Deblais, Loic; Kumar, Anand; Chepngeno, Juliet; Shao, Lulu; Huang, Huang-Chi; Candelero-Rueda, Rosario A.; Rajashekara, Gireesh

    2017-01-01

    ABSTRACT Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103+ and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing

  2. IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model.

    Directory of Open Access Journals (Sweden)

    Celina G Vega

    Full Text Available Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV. Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization -VN- titer = 256 for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV-specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV. Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.

  3. Differential Effects of Escherichia coli Nissle and Lactobacillus rhamnosus Strain GG on Human Rotavirus Binding, Infection, and B Cell Immunity.

    Science.gov (United States)

    Kandasamy, Sukumar; Vlasova, Anastasia N; Fischer, David; Kumar, Anand; Chattha, Kuldeep S; Rauf, Abdul; Shao, Lulu; Langel, Stephanie N; Rajashekara, Gireesh; Saif, Linda J

    2016-02-15

    Rotavirus (RV) causes significant morbidity and mortality in children worldwide. The intestinal microbiota plays an important role in modulating host-pathogen interactions, but little is known about the impact of commonly used probiotics on human RV (HRV) infection. In this study, we compared the immunomodulatory effects of Gram-positive (Lactobacillus rhamnosus strain GG [LGG]) and Gram-negative (Escherichia coli Nissle [EcN]) probiotic bacteria on virulent human rotavirus (VirHRV) infection and immunity using neonatal gnotobiotic piglets. Gnotobiotic piglets were colonized with EcN, LGG, or EcN+LGG or uncolonized and challenged with VirHRV. Mean peak virus shedding titers and mean cumulative fecal scores were significantly lower in EcN-colonized compared with LGG-colonized or uncolonized piglets. Reduced viral shedding titers were correlated with significantly reduced small intestinal HRV IgA Ab responses in EcN-colonized compared with uncolonized piglets post-VirHRV challenge. However the total IgA levels post-VirHRV challenge in the intestine and pre-VirHRV challenge in serum were significantly higher in EcN-colonized than in LGG-colonized piglets. In vitro treatment of mononuclear cells with these probiotics demonstrated that EcN, but not LGG, induced IL-6, IL-10, and IgA, with the latter partially dependent on IL-10. However, addition of exogenous recombinant porcine IL-10 + IL-6 to mononuclear cells cocultured with LGG significantly enhanced IgA responses. The greater effectiveness of EcN in moderating HRV infection may also be explained by the binding of EcN but not LGG to Wa HRV particles or HRV 2/4/6 virus-like particles but not 2/6 virus-like particles. Results suggest that EcN and LGG differentially modulate RV infection and B cell responses.

  4. Longitudinal analysis of VP7 gene of group A human rotavirus G2P[4] strains circulating in the pre-vaccine era in Sapporo, Japan from 1991 to 2011.

    Science.gov (United States)

    Tatsumi, Masatoshi; Nagaoka, Yoshinobu; Tsugawa, Takeshi; Yoto, Yuko; Hori, Tsukasa; Tsutsumi, Hiroyuki

    2014-09-01

    Sequence analysis of the VP7 gene in 23 group A human rotavirus G2P[4] strains obtained during 1991-2011, that is, the pre-vaccine era, in Sapporo, Japan showed considerable genetic diversity, mainly in variable regions. Recent G2P[4] epidemic strains were located in sublineage IVa with a distinctive substitution of D96N. This study provides background data on the genetic variability of G2P[4] rotavirus-VP7 gene prior to the widespread use of rotavirus vaccines in Japan.

  5. Molecular epidemiology of the human group A rotavirus in the Paraná State, Brazil

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    Jucélia Stadinicki dos Santos

    2008-04-01

    Full Text Available From January/2000 to December/2003, 550 diarrheic fecal samples from the children and adults were collected in several geographical regions of Paraná State, Brazil. The enzyme immunoassay showed 120 (21.8% samples positive for the group A rotaviruses. One hundred and fourteen samples were genotyped by multiplex-nested-PCR assay. The highest frequency (77.5% of the positive samples (n=93 was observed in the children under 5 years old. Rotavirus diarrhea was more frequent in the cold and dry seasons of the four evaluated years. The most frequent genotypes were: G1 (50.9%, G4 (9.6%, G9 (7.0%, G2 (1.7%, G3 (0.9%, P[ 8] (71.9%, and P[ 4] (3.5%. The P[ 8] G1 (46.5% and P[ 8] G4 (9.6% were the main combinations found to P and G genotypes. The mixed infections, characterized by the rotaviruses with more than one genotype G or P, and nontypeable rotavirus were observed in 8.8, 3.5, and 16.7% of the samples, respectively. The identification of the G9 genotype in the rotavirus strains tested along the four years of studies ratifies the emergency of this genotype also in Paraná State, South region of Brazil, as the worldwide.No período de janeiro de 2000 a dezembro de 2003 foram colhidas, em várias regiões geográficas do Estado do Paraná, 550 amostras fecais de crianças e adultos com quadro clínico de diarréia aguda. Por meio de ensaio imunoenzimático comercial, 120 (21,8% amostras foram positivas para o rotavírus grupo A. Dessas, 114 amostras foram genotipadas por meio da multiplex-nested-PCR. A maior freqüência (77,5% de amostras positivas (n=93 foi observada em crianças menores de cinco anos de idade. A maior concentração de casos positivos para o rotavírus ocorreu nos meses frios e secos dos quatro anos avaliados. Os genotipos de maior ocorrência foram: G1 (50,9%, G4 (9,6%, G9 (7,0%, G2 (1,7%, G3 (0,9%, P[ 8] (71,9% e P[ 4] (3,5%. P[ 8] G1 (46,5% e P[ 8] G4 (9,6% foram as associações de genotipos P e G mais encontradas. Infec

  6. Feline Origin of Rotavirus Strain, Tunisia, 2008

    Science.gov (United States)

    Fredj, Mouna Ben Hadj; Heylen, Elisabeth; Zeller, Mark; Fodha, Imene; Benhamida-Rebai, Meriam; Van Ranst, Marc; Matthijnssens, Jelle

    2013-01-01

    In Tunisia in 2008, an unusual G6P[9] rotavirus, RVA/human-wt/TUN/17237/2008/G6P[9], rarely found in humans, was detected in a child. To determine the origin of this strain, we conducted phylogenetic analyses and found a unique genotype constellation resembling rotaviruses belonging to the feline BA222-like genotype constellation. The strain probably resulted from direct cat-to-human transmission. PMID:23631866

  7. Molecular epidemiology and genetic evolution of the whole genome of G3P[8] human rotavirus in Wuhan, China, from 2000 through 2013.

    Directory of Open Access Journals (Sweden)

    Yuan-Hong Wang

    Full Text Available Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as "new variant G3" have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated.The complete genomes of 33 G3P[8] human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences.Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted throughout the study period.Chinese G3P[8] rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P[8] in an Asian country.

  8. Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST evaluating the human-bovine (WC3 reassortant pentavalent rotavirus vaccine (RV5

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    Van Damme Pierre

    2010-06-01

    Full Text Available Abstract Background The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5 including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE. The per-protocol (PP analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. Methods Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. Results In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED visits 88.9% (95% CI: 84.9, 91.9 for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6 reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5 and 95.9% (95% CI: 92.2, 97.8 among parents contacted every 2 weeks (number evaluable = 4,451 and every 6 weeks (number evaluable = 52,683 respectively. Conclusions Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations

  9. New advance of group A human rotavirus epidemiology and vaccine development%A组人轮状病毒流行病学及疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    童志礼; 方肇寅

    2002-01-01

    A组人轮状病毒(group A human rotavirus, HRV)是世界范围内婴幼儿重症腹泻的主要病因.本文在介绍HRV结构和特性的基础上,对世界范围内HRV血清型流行病学特征以及HRV疫苗研究现状和趋势分别作了综述.

  10. Human group A rotavirus infections in children in Denmark; detection of reassortant G9 strains and zoonotic P 14 strains

    DEFF Research Database (Denmark)

    Midgley, S.; Bottiger, B.; Jensen, T. G.;

    2014-01-01

    One of the leading causes of severe childhood gastroenteritis are group A rotaviruses, and they have been found to be associated with similar to 40% of the annual gastroenteritis-associated hospitalizations in young Danish children......One of the leading causes of severe childhood gastroenteritis are group A rotaviruses, and they have been found to be associated with similar to 40% of the annual gastroenteritis-associated hospitalizations in young Danish children...

  11. Suspected zoonotic transmission of rotavirus group A in Danish adults

    DEFF Research Database (Denmark)

    Midgley, S. E.; Hjulsager, Charlotte Kristiane; Larsen, Lars Erik;

    2012-01-01

    Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4...... genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8...

  12. Surveillance of rotavirus diarrhea

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    Titis Widowati

    2012-01-01

    Full Text Available Background Rotavirus is a major cause of severe diarrhea and dehydration in children worldwide. Data on the burden of disease in Indonesia is limited. Objective To provide an epidemiological profile of rotavirus infection among children hospitalized for diarrhea in Mohammad Hoesin Hospital, Palembang. Methods In January - December 2006, a prospective, hospital-based surveillance was carried out in children aged less than five years, presenting with diarrhea. Stool samples were examined for rotavirus using enzyme immunoassay (EIA. G- and P-typing were performed on specimens confirmed to be positive by EIA. Results A total of 513 fecal specimens from 534 children were tested for rotavirus. Rotavirus was detected in 64% of the specimens, mostly of the G9 type (62.5%. Incidence of rotavirus diarrhea was highest in the 6 month to 2 years age group (60.4%. Children with rotavirus diarrhea were more likely to present with dehydration, compared to those with non-rotavirus diarrhea (94% vs 70%, respectively, P=0.03. Conclusion Rotavirus was the most common pathogen found in children with diarrhea. Rotavirus was detected in 64% of pediatric diarrheal specimens tested in our study. This finding warrants the use of a large-scale program to prevent disease, such as vaccination against rotavirus. [Paediatr Indones. 2012;52:22-7].

  13. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity.

    Science.gov (United States)

    Yang, Xingdong; Twitchell, Erica; Li, Guohua; Wen, Ke; Weiss, Mariah; Kocher, Jacob; Lei, Shaohua; Ramesh, Ashwin; Ryan, Elizabeth P; Yuan, Lijuan

    2015-10-13

    Previously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN), and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5, and 7 days of age pigs were inoculated with 2 × 10(4) colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 10(5) focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4-5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width, and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens.

  14. Rotavirus Type A in Danish Cattle and Swine Herds

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, Nina; Hjulsager, Charlotte Kristiane;

    Rotavirus group A infection causes gastroenteritis in both humans and a variety of animal species. Both domestic pet species such as cats and dogs, and commercial species such as pigs and cows can be affected. Zoonotic transmission is a possibility and could lead to the introduction into human...... populations of novel rotavirus strains....

  15. Rotavirus Group A in Danish Cattle and Swine Herds 2006

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, Nina; Hjulsager, Charlotte Kristiane;

    Rotavirus group A infection causes gastroenteritis in both humans and a variety of animal species. Both domestic pet species such as cats and dogs, and commercial species such as pigs and cows can be affected. Zoonotic transmission is a possibility and could lead to the introduction into human...... populations of novel rotavirus strains....

  16. Burden of rotavirus in India - Is rotavirus vaccine an answer to it?

    Directory of Open Access Journals (Sweden)

    Davendra K Taneja

    2012-01-01

    Full Text Available Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries. Worldwide Rotavirus is responsible for 611,000 childhood deaths out of which more than 80% occur in low-income countries. The resistance of rotavirus to commonly used disinfectants and ineffectiveness of oral rehydration therapy due to severe vomiting indicates that if an effective vaccine is the preferred option. WHO has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. Currently two vaccines are available against rotavirus. Rotarix (GlaxoSmithKline is a monovalent vaccine recommended to be orally administered in two doses at 6-12 weeks. Rota Teq (Merck is a pentavalent vaccine recommended to be orally administered in three doses starting at 6-12 weeks of age. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. However, the efficacy of available rotavirus vaccines is less in low-income countries. Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. Indigenous vaccine, 116E (Bharat Biotech based on human rotavirus of serotype G9P [11] is still under Phase 2 trials. Another multivalent vaccine is being developed by Shantha Biotechnics in India. The cost effectiveness of the three dose schedule of the available and the rsults of the field trials of the indigenous vaccines should be assessed before inclusion of rotavirus vaccine in the National Immunization

  17. 人A组轮状病毒疫苗研究进展%Progress of human group A rotavirus vaccine

    Institute of Scientific and Technical Information of China (English)

    段招军

    2012-01-01

    Group A rotavirus( RV) is the leading cause of severe diarrhea disease in infants and young children worldwide, which causes a high desease burden. Studies have indicated that further improvements in hygiene are unlikely to prevent the disease. Rotavirus vaccines are the most effective public health interventions for controlling rotavirus diarrhea. Currently there are 3 different brands of rotavirus vaccines put into use globally in more than 100 countries and regions, and have been included in some countries'childhood vaccination programs. This review briefly introduces the development status of Group A rotavirus vaccines, providing a reference for application and further promotion of rotavirus vaccines in our country.%A组轮状病毒是导致全球婴幼儿重症腹泻的最主要病因,其疾病负担巨大.已有研究证实,卫生状况的改善对轮状病毒腹泻的控制效果甚微,疫苗则是控制轮状病毒腹泻最有效的公共卫生干预措施.目前3种轮状病毒疫苗已在全球100多个国家及地区投入使用,并纳入部分国家的儿童计划免疫程序.本文简要综述人A组轮状病毒疫苗的研究进展,以期对我国轮状病毒疫苗的使用和推广提供借鉴.

  18. Detection of rare reassortant G5P[6] rotavirus, Bulgaria.

    Science.gov (United States)

    Mladenova, Zornitsa; Papp, Hajnalka; Lengyel, György; Kisfali, Péter; Steyer, Andrej; Steyer, Adela F; Esona, Mathew D; Iturriza-Gómara, Miren; Bányai, Krisztián

    2012-12-01

    During the ongoing rotavirus strain surveillance program conducted in Bulgaria, an unusual human rotavirus A (RVA) strain, RVA/Human/BG/BG620/2008/G5P[6], was identified among 2200 genotyped Bulgarian RVAs. This strain showed the following genomic configuration: G5-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analysis of the genes encoding the neutralization proteins and backbone genes identified a probable mixture of RVA genes of human and porcine origin. The VP1, VP6 and NSP2 genes were more closely related to typical human rotavirus strains. The remaining eight genes were either closely related to typical porcine and unusual human-porcine reassortant rotavirus strains or were equally distant from reference human and porcine strains. This study is the first to report an unusual rotavirus isolate with G5P[6] genotype in Europe which has most likely emerged from zoonotic transmission. The absence of porcine rotavirus sequence data from this area did not permit to assess if the suspected ancestral zoonotic porcine strain already had human rotavirus genes in its genome when transmitted from pig to human, or, the transmission was coupled or followed by gene reassortment event(s). Because our strain shared no neutralization antigens with rotavirus vaccines used for routine immunization in children, attention is needed to monitor if this G-P combination will be able to emerge in human populations. A better understanding of the ecology of rotavirus zoonoses requires simultaneous monitoring of rotavirus strains in humans and animals.

  19. Rotavirus and Serotonin Cross-Talk in Diarrhoea.

    Directory of Open Access Journals (Sweden)

    Sonja Bialowas

    Full Text Available Rotavirus (RV has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4 significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10 infants, but no (0/8 adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM diarrhoea in infant mice (2.9 vs 4.5 days. Ondansetron-treated mice (n = 11 had significantly (p < 0.05 less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9. Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05. A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05 also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron.

  20. Whole Genomic Analysis of an Unusual Human G6P[14] Rotavirus Strain Isolated from a Child with Diarrhea in Thailand: Evidence for Bovine-To-Human Interspecies Transmission and Reassortment Events.

    Science.gov (United States)

    Tacharoenmuang, Ratana; Komoto, Satoshi; Guntapong, Ratigorn; Ide, Tomihiko; Haga, Kei; Katayama, Kazuhiko; Kato, Takema; Ouchi, Yuya; Kurahashi, Hiroki; Tsuji, Takao; Sangkitporn, Somchai; Taniguchi, Koki

    2015-01-01

    An unusual rotavirus strain, SKT-27, with the G6P[14] genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P[14]), was identified in a stool specimen from a hospitalized child aged eight months with severe diarrhea. In this study, we sequenced and characterized the complete genome of strain SKT-27. On whole genomic analysis, strain SKT-27 was found to have a unique genotype constellation: G6-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. The non-G/P genotype constellation of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3) is commonly shared with rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis indicated that nine of the 11 genes of strain SKT-27 (VP7, VP4, VP6, VP2-3, NSP1, NSP3-5) appeared to be of artiodactyl (likely bovine) origin, while the remaining VP1 and NSP2 genes were assumed to be of human origin. Thus, strain SKT-27 was found to have a bovine rotavirus genetic backbone, and thus is likely to be of bovine origin. Furthermore, strain SKT-27 appeared to be derived through interspecies transmission and reassortment events involving bovine and human rotavirus strains. Of note is that the VP7 gene of strain SKT-27 was located in G6 lineage-5 together with those of bovine rotavirus strains, away from the clusters comprising other G6P[14] strains in G6 lineages-2/6, suggesting the occurrence of independent bovine-to-human interspecies transmission events. To our knowledge, this is the first report on full genome-based characterization of human G6P[14] strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P[14] strains, and into dynamic interactions between human and bovine rotavirus strains.

  1. Multi-reassortant G3P[3] group A rotavirus in a horseshoe bat in Zambia.

    Science.gov (United States)

    Sasaki, Michihito; Orba, Yasuko; Sasaki, Satoko; Gonzalez, Gabriel; Ishii, Akihiro; Hang'ombe, Bernard M; Mweene, Aaron S; Ito, Kimihito; Sawa, Hirofumi

    2016-10-01

    Group A rotavirus is a major cause of diarrhoea in humans, especially in young children. Bats also harbour group A rotaviruses, but the genetic backgrounds of bat rotavirus strains are usually distinct from those of human rotavirus strains. We identified a new strain of group A rotavirus in the intestinal contents of a horseshoe bat in Zambia. Whole genome sequencing revealed that the identified virus, named RVA/Bat-wt/ZMB/LUS12-14/2012/G3P[3], possessed the genotype constellation G3-P[3]-I3-R2-C2-M3-A9-N2-T3-E2-H3. Several genome segments of LUS12-14 were highly similar to those of group A rotaviruses identified from humans, cows and antelopes, indicating interspecies transmission of rotaviruses between bats and other mammals with possible multiple genomic reassortment events.

  2. Pathogenesis of Rotavirus Infection

    NARCIS (Netherlands)

    J.A. Boshuizen

    2005-01-01

    textabstractRotaviruses comprise a genus within the family of the Reoviridae and are recognized as the single most significant cause of severe gastroenteritis, malnutrition and diarrhea in young children. Each year rotavirus causes the death of about 440.000 children <5 years of age (313). The resea

  3. VP4 and VP7 genotyping by reverse transcription-PCR of human rotavirus in mexican children with acute diarrhea.

    Science.gov (United States)

    Rodríguez Castillo, A; Villa, A V; Ramírez González, J E; Mayén Pimentel, E; Melo Munguía, M; Díaz De Jesús, B; Olivera Díaz, H; García Lozano, H

    2000-10-01

    Dual typing (VP4 and VP7) of rotavirus obtained from 257 Mexican children during three epidemiological seasons was performed by reverse transcription-PCR. The P1G1 genotype was the most prevalent (40%), followed by P1G3 (19%) and P2G2 (16%). Thirty-one specimens (12%) presented mixed infections, while some genotypes were not found. This is the first dual typing of isolates from diarrhea cases in Mexico.

  4. Detection of two atypical rotaviruses in the province of Misiones, Argentina.

    Science.gov (United States)

    Basnec, S N; Giordano, M O; Bennun, F R; Nates, S V; Vergara, M; Depetris, A R

    1991-09-01

    Out of 317 human gastroenteritis cases studied between August 1988-August 1989, two atypical antigenically distinct rotaviruses (pararotaviruses) were detected in faecal samples among 19 rotaviruses shedding children from Misiones province, North-Eastern Argentina. A 1 3/4 year old girl a 3 years old boy, both with vomiting and normal temperature, shed these atypical rotaviruses. Their morphology by electron microscopy was identical to other rotaviruses; they contained 11 double-stranded RNA segments detected by polyacrylamide gel electrophoresis and failed to react with the antibody directed against the rotavirus group specific antigen (Rotazyme II ELISA). The electrophoretic migration of these RNAs (electropherotype) in polyacrylamide gels did not coincide with the typical pattern of distinct size classes observed in most human rotaviruses reported, instead, they appeared to be related to patterns of rotaviruses group C.

  5. Characterization of human rotaviruses circulating in Iraq in 2008: atypical G8 and high prevalence of P[6] strains.

    Science.gov (United States)

    Ahmed, Salwa; Klena, John; Albana, Antun; Alhamdani, Faisal; Oskoff, John; Soliman, Mireille; Heylen, Elisabeth; Teleb, Nadia; Husain, Tupur; Matthijnssens, Jelle

    2013-06-01

    Fecal samples from 976 children with gastroenteritis were collected and analyzed for group A rotavirus (RVA), in three different cities in Iraq between January 2008 and December 2008. RVA antigen was detected in 394 (40%) of the samples, and 98 samples were available for further genotype analyses using multiplex RT-PCR and sequence analyses for untypeable strains. The G/P-genotype combination was determined for 69 samples, and 19, 2 and 8 samples remained P-untypeable, G-untypeable and G/P-untypeable (UT), respectively. The most prevalent genotype was G2 (40%, 39/98) most often associated with P[6]. G1 was the second most common genotype (16%, 16/98) mainly associated with P[8] and P[UT]. G3, G4 and G9 were detected at a lower prevalence (3%, 11%, 3%, respectively), mainly associated with P[6]. Surprisingly, five G8P[6], and seven G12 RVA strains in combination with P[6] and P[8] were also detected for the first time in Iraq. Overall, a striking high prevalence of 47% of the analyzed samples possessed the P[6] genotype (65% of the P-typed RVA strains). Atypical genotype combinations such as G1P[4], G1P[6], G2P[8] or strains with mixed G-types were detected sporadically. The detection of unusual G8P[6] RVA strains prompted us to further analyze the NSP2, NSP3, NSP4 and NSP5 gene segments of three selected G8P[6] strains, resulting in their designation to the N2, T2, E2 and H2 genotypes, respectively. The VP7, VP4, NSP2, NSP3 and NSP5 gene segments clustered closely with common human RVA strains, whereas the NSP4 gene sequences were found to cluster with animal derived RVA strains, suggesting a potential reassortment event. The high prevalence of RVA strains with the G8, G12 and P[6] genotypes in combination with a DS-1-like genotype constellation in Iraq, needs to be monitored closely as these RVA strains might challenge the effectiveness of current RVA vaccines.

  6. Restriction fragment length polymorphism analysis of rotavirus VP7-encoding gene from humans and animals of Northeast India: a relative study of Indian and global isolates.

    Science.gov (United States)

    Chakraborty, P; Barman, N N; Sharma, I

    2015-09-01

    A restriction fragment length polymorphism (RFLP) assay was developed to examine the genetic relationship between 67 (29 Indian, 38 global) rotavirus isolates of human, bovine and porcine neonates. The assay involved direct digestion of RT-PCR amplified VP7 cDNAs with three restriction enzymes (VspI, HaeIII, NlaIV) independently. Forty-eight RFLP patterns were identified for all 67 strains, and of these 20 patterns were associated with Indian isolates. A correlation between the restriction patterns and G type was apparent through deduction of enzyme restriction sites from known sequences. Major G serotypes (G1, G2, G6, G8) with a few mixed types could be differentiated where there was a positive assortment of intrinsic serotypes from multiple host origin, and certain single or combined enzyme profiles were highly dominant in the population. Significant genetic variations were established between global and Indian isolates and none of the RFLP patterns were shared between them. These data suggest that the Indian wild-type rotavirus population is distinguishable based on the VP7 gene, and co-circulation of distinct strains in different hosts is foremost, indicating the possible likelihood of inter-species transmission.

  7. Current status of rotavirus vaccines

    Institute of Scientific and Technical Information of China (English)

    Ching-Min Wang; Shou-Chien Chen; Kow-Tong Chen

    2015-01-01

    Background: Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Data sources: Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. Results: In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Conclusions: Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

  8. [Rotavirus infection in Brazil: epidemiology and challenges for its control].

    Science.gov (United States)

    Linhares, A C

    2000-01-01

    Worldwide, rotaviruses account for 600,000 to 870,000 deaths per year among infants and young children. In Brazil, rotaviruses were first seen in 1976 by scanning electron microscopy of stool samples from diarrheic infants in Belém, Pará. Hospital-based studies have shown that rotaviruses are associated with 12-42% of cases of acute diarrhea. In addition, community-based studies yielded an average of 0.25 rotavirus-related diarrheal episodes per child per year. G types 1 to 4 account for about two-thirds of circulating strains, but the (unusual) P[8],G5 genotype has been claimed to cause over 10% of rotavirus diarrheal episodes. It has been shown that over 70% of children develop rotavirus antibodies by the age of 4-5 years. The tetravalent rhesus-human rotavirus vaccine (RRV-TV) conferred 35% protection according to a two-year follow-up study in Belém, Pará, Brazil, but reached an efficacy of 60% during the first year of life. RRV-TV was also shown to be 75% protective against very severe gastroenteritis in northern Brazil. Vaccination with RRV-TV has been suspended recently in the United States because of the detection of intussusception as a side effect. Therefore, further vaccine trials in Brazil will probably involve rotavirus candidate vaccines other than RRV-TV.

  9. P[8] and P[4] Rotavirus Infection Associated with Secretor Phenotypes Among Children in South China

    Science.gov (United States)

    Zhang, Xu-Fu; Long, Yan; Tan, Ming; Zhang, Ting; Huang, Qiong; Jiang, Xi; Tan, Wen-Fang; Li, Jian-Dong; Hu, Gui-Fang; Tang, Shixing; Dai, Ying-Chun

    2016-01-01

    Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a host ligand that is believed to play an important role in rotavirus host susceptibility and host range. In this study, paired fecal and saliva samples collected from children with viral gastroenteritis, as well as paired serum and saliva samples collected from the general population in south China were studied to evaluate potential association between rotavirus infections and human HBGA phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8] rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the rotavirus-infected children were determined through their saliva samples. Secretor statuses were found to correlate with the risk of rotavirus infection and all P[8]/P[4] rotavirus infected children were secretors. Accordingly, recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific IgG and host Lewis and secretor phenotypes has been found among 206 studied serum samples. Our study supported the association between rotavirus infection and the host HBGA phenotypes, which would help further understanding of rotavirus host range and epidemiology. PMID:27708367

  10. [Rotavirus and other viruses of diarrhea].

    Science.gov (United States)

    Bajolet, O; Chippaux-Hyppolite, C

    1998-01-01

    Rotaviruses represent 80% of recognized viral etiologies and 140 million cases of diarrhea per year. They strike young children with similar frequency throughout the world, but the mortality rate is high in developing countries only, with some 870,000 deaths per year (WHO, 1997). Rotaviruses belong to the family of Reoviridae; they are segmented bicatenary RNA viruses, which explains their genetic variability, the presence of mixed infections, the establishment for some time already of a molecular epidemiology by electrophore types. The viruses are "naked" and thus resistant to the outside environment; their massive elimination, 10(8) to 10(10)viral particles per gram of faeces, begins with the first day of diarrhea. They are found in used water and can also be concentrated by shellfish; the environment thus constitutes a notable reservoir for the virus. Oral-faecal transmission is facilitated by deficient sanitary conditions. The 11 fragments of the genome each codify for 1 viral protein; 2 surface proteins, VP4 and VP7, bring about the formation of neutralizing antibodies, which are important for the protection and determination of different serotypes. A non structural protein--NSP4--would seem to intervene in the cytopathogenic effect and may act as a veritable viral enterotoxine. Numerous animal species are infected by rotaviruses which are district from the human ones. The pathology as it affects animals is of economic importance and of interest as an experimental and vaccinal model. Between human and animal rotaviruses there can be genetic rematchings and the VP6 protein is an antigen common to the group. The description of the other viruses responsible for diarrhea has benefited from widespread use of electronic microscopes from the very first years of study of rotaviruses. These other viruses belong to 6 different types: adenovirus, calcivirus, astrovirus, Norwalk agent and related viruses, coronavirus, enterovirus. They therefore have a structural and

  11. Zoonotic transmission of rotavirus in Denmark; a case report

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, N.; Hjulsager, Charlotte Kristiane;

    Rotavirus type A infection is a common cause of hospitalisation of children. In addition, almost 30% of diagnosed persons in Denmark are adults. Rotavirus type A infection can also occur in a range of animals, including domestic dogs, cats, cattle, horses, and birds. There is some data suggesting...... direct transmission between animals and humans. Rotavirus genotyping is carried out in Denmark as part of the EUROTAnet vaccine study. In 2006 a total of 180 samples were successfully typed, and to date 85 samples from 2007 have been typed. 19 samples from pigs and 31 samples from cattle (from 2006...... and 2007) have also been typed. For the human samples all common human G types (1-4 and 9), as well the emerging G12 were identified, and were found in combination with the common P types ([4], [6], and [8]). Two samples contained a G8 P[goat] rotavirus (G8 98% identical to bovine G8, 96% identical to goat...

  12. Non-neutralizing monoclonal antibodies to a trypsin-sensitive site on the major glycoprotein of rotavirus which discriminate between virus serotypes.

    Science.gov (United States)

    Coulson, B S; Fowler, K J; White, J R; Cotton, R G

    1987-01-01

    Monoclonal antibodies were derived to a human rotavirus purified from stools. Three of the antibodies immunoprecipitated the rotavirus outer capsid glycoprotein gp 34 and were non-neutralizing. These antibodies reacted by enzyme immunoassay with cultivable rotaviruses showing the "long" RNA electropherotype but were inefficient as detectors of "long" RNA pattern rotaviruses in stools. Treatment of SA 11 rotavirus with 7.5 micrograms/ml porcine trypsin for 30 minutes at 37 degrees C irreversibly reduced binding of the antibodies to SA 11 rotavirus in enzyme immunoassays by 50 per cent. Binding was abolished in the presence of rotavirus-negative faecal extracts. These results indicate that non-neutralizing sites on gp 34 of rotaviruses can vary with RNA electropherotype and serotype, and that levels of trypsin currently in use to assist growth of rotaviruses in cell culture may alter the serological profile of the viruses.

  13. New approaches in oral rotavirus vaccines.

    Science.gov (United States)

    Kuate Defo, Zenas; Lee, Byong

    2016-05-01

    Rotavirus is the leading cause of severe dehydrating diarrhea worldwide, and affects primarily developing nations, in large part because of the inaccessibility of vaccines and high rates of mortality present therein. At present, there exist two oral rotaviral vaccines, Rotarix™ and RotaTeq™. These vaccines are generally effective in their actions: however, associated costs often stymie their effectiveness, and they continue to be associated with a slight risk of intussusception. While different programs are being implemented worldwide to enhance vaccine distribution and monitor vaccine administration for possible intussusception in light of recent WHO recommendation, another major problem persists: that of the reduced efficacy of the existing rotaviral vaccines in developing countries over time. The development of new oral rotavirus vaccine classes - live-attenuated vaccines, virus-like particles, lactic acid bacteria-containing vaccines, combination therapy with immunoglobulins, and biodegradable polymer-encapsulated vaccines - could potentially circumvent these problems.

  14. Phylogenetic analysis of human group C rotavirus in hospitalized children with gastroenteritis in Belém, Brazil.

    Science.gov (United States)

    Lobo, Patrícia dos Santos; Guerra, Sylvia de Fátima dos Santos; Siqueira, Jones Anderson Monteiro; Soares, Luana da Silva; Gabbay, Yvone Benchimol; Linhares, Alexandre C; Mascarenhas, Joana D'Arc Pereira

    2016-04-01

    Group C rotavirus (RVC) is potentially an important pathogen associated with acute gastroenteritis (AG), especially in outbreaks. This study aims to detect and molecularly characterize RVC in hospitalized children with AG in Belém, Brazil. From May 2008 to April 2011, 279 stools were subjected to reverse-transcription polymerase chain reaction targeting VP7, VP6, VP4, and NSP4 genes. RVC positivity rate was 2.1% (6/279) and phylogenetic analysis of positive samples yields genotype G4-P[2]-I2-E2. No evidence of zoonotic transmission and VP7 gene demonstrated close relationship with Asian strains. RVC surveillance is worth to expand information on evolutionary and epidemiological features of this virus.

  15. Mechanical compression attenuates normal human bronchial epithelial wound healing

    Directory of Open Access Journals (Sweden)

    Malavia Nikita

    2009-02-01

    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  16. Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe

    DEFF Research Database (Denmark)

    Midgley, Sofie E.; Bányai, Krisztián; Buesa, Javier;

    2012-01-01

    Group A rotaviruses can infect both humans and animals. Individual rotavirus strains can occasionally cross species barriers and might hereby contribute to the emergence of new genotypes in heterologous hosts. The incidence and impact of zoonotic rotavirus are not well defined, and one reason...... for this is a lack of data about strains circulating in suspected reservoir animal hosts. In this study we report the incidence, genetic diversity, and molecular epidemiology of rotaviruses detected in domestic cattle and swine in 6 European countries. From 2003 to 2007, 1101 and more than 2000 faecal specimens were...... collected from swine and cattle, both healthy and diarrhoeic, and tested for rotaviruses. Viruses from positive stools were genotyped and a subset of strains was characterized by nucleotide sequencing and phylogenetic analysis of the VP7 (G) and VP4 (P) genes. Rotaviruses were detected in 43% of bovine...

  17. Introduktion. Om rotavirus. Teknologi

    DEFF Research Database (Denmark)

    2012-01-01

    vil skyldes rotavirus. Typisk vil børnene få feber, opkastninger og/eller diarré. Sygdommen går sædvanligvis over af sig selv i løbet af 3 til 7 dage. Nogle børn får dog væske- og saltmangel i en sådan grad, at de må indlægges på hospital til behandling med drop og væske direkte ind i årerne. 85 – 90...... % af danske børn følger det danske børnevaccinationsprogram og bliver vaccineret mod en række infektioner. Der findes i Danmark to velafprøvede og godkendte vacciner mod rotavirus. Begge vacciner gives gennem munden og ikke gennem indsprøjtning i huden, som de øvrige vacciner i det danske...... børnevaccinationsprogram. Verdenssundhedsorganisation (WHO=World Health Organisation) samt nationale og europæiske faglige selskaber har anbefalet at vaccinere mod rotavirus. I en række europæiske lande er vaccination mod rotavirus indført i det nationale børnevaccinationsprogram. Andre europæiske lande har fravalgt...

  18. Glutamine attenuates post-traumatic glutathione depletion in human muscle.

    Science.gov (United States)

    Fläring, U B; Rooyackers, O E; Wernerman, J; Hammarqvist, F

    2003-03-01

    Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56 g x day(-1) x kg(-1)) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72 h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47+/-8% and 37+/-11% and reduced glutathione had decreased by 53+/-10% and 45+/-16% respectively at 24 and 72 h after surgery (P glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.

  19. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices.

  20. Characterization of the NSP4 gene of group A human rotavirus G1P[8] strains circulating in Sapporo, Japan from 1987 to 2000.

    Science.gov (United States)

    Tatsumi, Masatoshi; Nagaoka, Yoshinobu; Tsugawa, Takeshi; Yoto, Yuko; Hori, Tsukasa; Tsutsumi, Hiroyuki

    2014-02-01

    The genetic diversity of the NSP4 gene of rotavirus G1P[8] strains obtained in Sapporo was analyzed, Japan from 1987 to 2000. Sixty-four strains, which were distributed across the whole study period, were included. All G1P[8] NSP4 genes detected in this study belonged to genotype E1, which divided into at least three lineages. The Sapporo rotavirus G1P[8] isolates were found in each lineage. The mean estimated substitution rate was 1.40 × 10(-3) nucleotide substitutions per site per year, which was comparable to that of the G1P[8] VP7 gene. Comparison of the deduced NSP4 amino acid sequences showed genetic diversity at the center of antigenic site II, but not in the enterotoxic domain. This report represents the first investigation of the genetic diversity and evolution of group A rotavirus NSP4 genes in Asia.

  1. Detection of Common, Emerging and Uncommon VP4, and VP7 Human Group A Rotavirus Genotypes from Urban Sewage Samples in Uruguay.

    Science.gov (United States)

    Tort, Luis Fernando Lopez; Victoria, Matías; Lizasoain, Andrés; García, Mariana; Berois, Mabel; Cristina, Juan; Leite, José Paulo Gagliardi; Gómez, Mariela Martínez; Miagostovich, Marize Pereira; Colina, Rodney

    2015-12-01

    Environmental approach has proven to be a useful tool for epidemiological studies demonstrating through environmental studies the diversity of viruses circulating in a given population. The aim of this study was to perform a phylogenetic characterization of the group A rotavirus (RVA) glycoprotein (G)- and protease-sensitive (P)-genotypes obtained from sewage samples (n = 116) collected in six cities of Uruguay during March 2011 to April 2013. A worldwide standardized semi-nested multiplex RT-PCR (SNM RT-PCR) protocol directed against VP4 and VP7 genes were conducted for RVA detection and consensual DNA fragments were submitted to nucleotide sequencing. P and/or G genotype was successfully determined by phylogenetic analysis in 61% (n = 37) of the positive samples obtained by SNM RT-PCR (n = 61). The RVA genotypes were as follow: G1 (n = 2), G2 (n = 14), G3 (n = 5), G12 (n = 2), P[4] (n = 4), P[8] (n = 16), and P[3] (n = 2). Interestingly, through phylogenetic analysis, emerging, and uncommon human genotypes could be detected. Results obtained from the comparison of RVA genotypes detected in the current study and Uruguayan RVA strains previously described for contemporary clinical pediatric cases showed that monitoring sewage may be a good screening option for a rapid and economical overview of the circulating genotypes in the surrounding human population and a useful approximation to study RVA epidemiology in a future vaccine monitoring program. The present study represents the first report in Uruguay that describes the phylogenetic diversity of RVA from urban sewage samples.

  2. Caffeine attenuates scopolamine-induced memory impairment in humans.

    Science.gov (United States)

    Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

    1995-11-01

    Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

  3. 口服轮状病毒减毒活疫苗Rotarix的现状及研究进展%Progress in Research on Oral Live Attenuated Rotavirus Vaccine Rotarix

    Institute of Scientific and Technical Information of China (English)

    李肖锋

    2011-01-01

    轮状病毒(Rotavirus,RV)是全世界范围内导致婴幼儿重症腹泻的重要病原.由于当前尚无治疗RV感染的特效药物,因此,开发安全、有效的疫苗具有重要意义.G1型RV流行范围较广,本文主要对目前国内外上市的3种RV疫苗中的GIP[8]型Rotarix疫苗的情况作一综述.%Rotavirus (RV) is an important pathogen of severe diarrhea in infants worldwide.Since there is no specific drug for RV infection, the development of safe and effective vaccine is of important significance.In the three kinds of domestic and imported commercial RV vaccines, Rotarix is of type G1P [8].Since RV type G1 is epidemic widely, this paper reviews the status of Rotarix.

  4. Modeling of the rotavirus group C capsid predicts a surface topology distinct from other rotavirus species.

    Science.gov (United States)

    Eren, Elif; Zamuda, Kimberly; Patton, John T

    2016-01-01

    Rotavirus C (RVC) causes sporadic gastroenteritis in adults and is an established enteric pathogen of swine. Because RVC strains grow poorly in cell culture, which hinders generation of virion-derived RVC triple-layered-particle (TLP) structures, we used the known Rotavirus A (RVA) capsid structure to model the human RVC (Bristol) capsid. Comparative analysis of RVA and RVC capsid proteins showed major differences at the VP7 layer, an important target region for vaccine development due to its antigenic properties. Our model predicted the presence of a surface extended loop in RVC, which could form a major antigenic site on the capsid. We analyzed variations in the glycosylation patterns among RV capsids and identified group specific conserved sites. In addition, our results showed a smaller RVC VP4 foot, which protrudes toward the intermediate VP6 layer, in comparison to that of RVA. Finally, our results showed major structural differences at the VP8* glycan recognition sites.

  5. Protect Your Child from Rotavirus Disease

    Science.gov (United States)

    ... will be protected from severe rotavirus disease. Most vaccinated children will not get sick from rotavirus at all. ... does not cover vaccines for your child, the Vaccines for Children (VFC) Program may be able to help. This ...

  6. Rotavirus Infections - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Rotavirus Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Rotavirus Infections - Multiple Languages To use the sharing features ...

  7. Phylogenetic and computational structural analysis of VP7 gene of group a human rotavirus G1P[8] strains obtained in Sapporo, Japan from 1987 to 2000.

    Science.gov (United States)

    Nagaoka, Yoshinobu; Tatsumi, Masatoshi; Tsugawa, Takeshi; Yoto, Yuko; Tsutsumi, Hiroyuki

    2012-05-01

    Many studies indicate that G1P[8] genotypes are the most prevalent rotavirus strains worldwide. Although two vaccines have been licensed and their value proven in many countries, continuous surveillance for genetic evolution of circulating rotavirus strains before and after the introduction of the vaccines is desirable. G and P typing were carried out on all field strains isolated during 1987-2000 in Sapporo, Japan. Phylogenetic analysis for the VP7 gene of rotavirus G1P[8] strains was performed. Amino acid substitutions were mapped on the predicted three-dimensional VP7 protein image. G1P[8] genotype predominated. One hundred thirteen strains with G1P[8] genotype were analyzed. Phylogenetic studies of the VP7 gene classified these strains into three lineages. The mean estimated substitution rate was 7.25 × 10(-4) nucleotide substitutions per site per year. One predominant lineage contained the mutant strains which had VP7 amino acid substitutions at residue 91 and 212 that is in the neutralization domains. They were estimated to locate in or near intersubunit boundary of VP7 trimer. It is suggested that the most prevalent G1P[8] lineage strains in Sapporo obtained some survival advantages by changing the neutralization domains of VP7.

  8. Monitoring impact and effectiveness of rotavirus vaccination.

    Science.gov (United States)

    Tate, Jacqueline E; Parashar, Umesh D

    2011-08-01

    Rotavirus infection is the most common cause of severe gastroenteritis in children IVANHOE study was initiated to determine the real-world impact and effectiveness of rotavirus vaccine following introduction in a limited geographic area. This study found a twofold reduction in rotavirus hospitalizations among children <2 years of age who were age-eligible to receive rotavirus vaccine and a 98% vaccine effectiveness, highlighting the health benefits of a vaccination program.

  9. Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

    DEFF Research Database (Denmark)

    Rasmussen, V M; Borgen, A E; Jansen, E C

    2015-01-01

    BACKGROUND: Hyperbaric oxygen (HBO2 ) treatment has in animal experiments demonstrated antinociceptive effects. It was hypothesized that these effects would attenuate secondary hyperalgesia areas (SHAs), an expression of central sensitization, after a first-degree thermal injury in humans. METHODS......, compared with control. These new and original findings in humans corroborate animal experimental data. The thermal injury model may give impetus to future human neurophysiological studies exploring the central effects of hyperbaric oxygen treatment....

  10. Candidate new rotavirus species in sheltered dogs, Hungary.

    Science.gov (United States)

    Mihalov-Kovács, Eszter; Gellért, Ákos; Marton, Szilvia; Farkas, Szilvia L; Fehér, Enikő; Oldal, Miklós; Jakab, Ferenc; Martella, Vito; Bányai, Krisztián

    2015-04-01

    We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A-H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I.

  11. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.

    Science.gov (United States)

    Yamshchikov, Vladimir; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-01

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use.

  12. An atypical rotavirus detected in a child with gastroenteritis in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    H. G. Pereira

    1983-09-01

    Full Text Available Particles morphologically identical to rotaviruses were found in the faeces of a nine week-old child with gastroenteritis. Analysis of the viral RNA genome by polyacrylamine gel electrophoresis revealed 10 bands (probably 11 segments some of wich differed in migration rate from those of the great majority of rotaviruses infecting man and other animal hosts. The virus was not detected by a highly sensitive enzyme immunoassay (ELISA and therefore probably lacked the crossreactive antigen(s shared by the majority rotaviruses. This was the only strain with such behaviour among 230 rotaviruses of human origin examined in this laboratory since 1979. The implications of the existence of non-crossreactive rotaviruses are discussed.Partículas morfologicamente idênticas a rotavirus foram encontradas nas fezes de uma criança de dois meses com gastroenterite. Análise do genoma viral por eletroforese em gel de poliacrilamida revelou 10 faixas (provavelmente 11 segmentos de RNA, algumas das quais diferem em velocidade de migração das observadas na grande maioria de rotavirus de hospedeiros humanos e de diversas espécies de animais. O vírus não foi revelado por um ensaio imuno-enzimático de alta sensibilidade, o que sugere a ausência do antígeno de grupo que da reações cruzadas entre a maioria dos rotavirus. O vírus descrito no presente trabalho foi o único com tal comportamento entre 230 amostras analisadas por nós desde 1979. A relevância de existência de rotavirus não relacionados antigenicamente a outros membros do grupo é discutida.

  13. Rotavirus y campylobacter fetus jejuni asociados a un brote de diarrea en terneros

    OpenAIRE

    1984-01-01

    artículo -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1984 Rotaviruses and Campylobacter fetus jejuni are ubiquitous agents of diarrheal disease in animals and humans. Under natural conditions they do not seem to cross inter-species barriers; a zoonosis has not been documented for man. However, animal rotaviruses might contribute to the emergence of new reassortment strains in view of their segmented genome, and thus, produce new antigenic variants. On the contrary,...

  14. A reação de fixação do complemento na identificação de rotavírus humano The complement fixation test in the identification of human rotavirus

    Directory of Open Access Journals (Sweden)

    J. A. N. Candeias

    1980-09-01

    Full Text Available Após a eliminação da anticomplementaridade, foi utilizada a reação de fixação do complemento na identificação de rotavírus em 134 amostras de fezes de crianças até um ano de idade, com quadros diarréicos agudos. A percentagem total de positividade foi de 28,7% com percentagens mais elevadas de casos positivos nos grupos etários de 6 meses a 1 ano de idade.After eliminating the anticomplementarity of the fecal extracts, complement fixation was used to detect human rotavirus in the stools of 35 (28.7% out of 122 one-to twelve-month-old children with acute gastroenteritis. Infection was nigher in the 6-to 12-month-old children.

  15. Serial observations of chronic rotavirus infection in an immunodeficient child.

    Science.gov (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H

    1991-01-01

    Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host.

  16. Nordihydroguaiaretic Acid Attenuates the Oxidative Stress-Induced Decrease of CD33 Expression in Human Monocytes

    Directory of Open Access Journals (Sweden)

    Silvia Guzmán-Beltrán

    2013-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs. Oxidative stress was induced by iodoacetate (IAA or hydrogen peroxide (H2O2 and was evaluated using reactive oxygen species (ROS production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H2O2 in human MNs. It was also shown that NDGA (20 μM attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H2O2. These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  17. Nordihydroguaiaretic acid attenuates the oxidative stress-induced decrease of CD33 expression in human monocytes.

    Science.gov (United States)

    Guzmán-Beltrán, Silvia; Pedraza-Chaverri, José; Gonzalez-Reyes, Susana; Hernández-Sánchez, Fernando; Juarez-Figueroa, Ulises E; Gonzalez, Yolanda; Bobadilla, Karen; Torres, Martha

    2013-01-01

    Nordihydroguaiaretic acid (NDGA) is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs). Oxidative stress was induced by iodoacetate (IAA) or hydrogen peroxide (H(2)O(2)) and was evaluated using reactive oxygen species (ROS) production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H(2)O(2) in human MNs. It was also shown that NDGA (20  μ M) attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H(2)O(2). These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  18. Molecular characterization of group A rotaviruses detected in children with gastroenteritis in Ireland in 2006-2009.

    LENUS (Irish Health Repository)

    Cashman, O

    2012-02-01

    SUMMARYCommunity and hospital-acquired cases of human rotavirus are responsible for millions of gastroenteritis cases in children worldwide, chiefly in developing countries, and vaccines are now available. During surveillance activity for human rotavirus infections in Ireland, between 2006 and 2009, a total of 420 rotavirus strains were collected and analysed. Upon either PCR genotyping and sequence analysis, a variety of VP7 (G1-G4 and G9) and VP4 (P[4], P[6], P[8] and P[9]) genotypes were detected. Strains G1P[8] were found to be predominant throughout the period 2006-2008, with slight fluctuations seen in the very limited samples available in 2008-2009. Upon either PCR genotyping and sequence analysis of selected strains, the G1, G3 and G9 viruses were found to contain E1 (Wa-like) NSP4 and I1 VP6 genotypes, while the analysed G2 strains possessed E2 NSP4 and I2 VP6 genotypes, a genetic make-up which is highly conserved in the major human rotavirus genogroups Wa- and Kun-like, respectively. Upon sequence analysis of the most common VP4 genotype, P[8], at least two distinct lineages were identified, both unrelated to P[8] Irish rotaviruses circulating in previous years, and more closely related to recent European humans rotaviruses. Moreover, sequence analysis of the VP7 of G1 rotaviruses revealed the onset of a G1 variant, previously unseen in the Irish population.

  19. Attenuated noradrenergic sensitivity during local cooling in aged human skin

    Science.gov (United States)

    Thompson, Caitlin S; Holowatz, Lacy A; Kenney, W. Larry

    2005-01-01

    Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus −56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose-dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or α2C-adrenoceptor function. PMID:15705648

  20. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  1. Respuesta inmune adaptativa al rotavirus

    Directory of Open Access Journals (Sweden)

    Manuel A. Franco

    2004-03-01

    . In Clinical virology. D. D. Richman, F. G. Hayden and R. J. Whitley (Ed., pp. 743-762. Washington DC, ASM Press.

    2. JAIMES, M. C., O. L. ROJAS, A. M. GONZALEZ, I. CAJIAO, A. CHARPILIENNE, P. POTHIER, E. KHOLI, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Frequencies of virus specific cd4+ and cd8+ t lymphocytes secreting interferon gamma after acute natural rotavirus infection in children and adults. J Virology 2002; 76: 4741–4749.

    3. ROJAS, O. L., A. M. GONZÁLEZ, R. GONZÁLEZ, I. PÉREZSCHAEL, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Human rotavirus specific t cells: Quantification by elispot and expression of homing receptors on cd4+ t cells. Virology 2003; 314: 671–679.

    4. GONZALEZ, A. M., M. C. JAIMES, I. CAJIAO, O. L. ROJAS, J. COHEN, P. POTHIER, E. KOHLI, E. C. BUTCHER, H. B. GREENBERG, J. ANGEL AND M. A. FRANCO. Rotavirusspecific B cells induced by recent infection in adults and children predominantly express the intestinal homing receptor alpha4beta7. Virology 2003; 305: 93-105.

  2. Evaluation of the infectivity, gene and antigenicity persistence of rotaviruses by free chlorine disinfection

    Institute of Scientific and Technical Information of China (English)

    Dan Li; April Z.Gu; Siyu Zeng; Wan Yang; Miao He; Hanchang Shi

    2011-01-01

    The effects of free chlorine disinfection of tap water and wastewater effluents on the infectivity,gene integrity and surface antigens of rotaviruses were evaluated by a bench-scale chlorine disinfection experiments.Plaque assays,integrated cell culture-quantitative RTPCR (ICC-RT-qPCR),RT-qPCR,and enzyme-linked immunosorbent assays (ELISA),respectively,were used to assess the influence of the disinfectant on virus infectivity as well as genetic and antigenic integrity of simian rotavirus SA11 as a surrogate for human rotaviruses.The ICC-RT-qPCR was able to detect rotaviruses survival from chlorine disinfection at chlorine dose up to 20 mg/L (60 min contact),which suggested a required chlorine dose of 5 folds (from 1 to 5 mg/L) higher than that indicated by the plaque assay to achieve 1.8 log10 reductions in tap water with 60 min exposing.The VP7 gene was more resistant than the infectivity and existed at chlorine dose up to 20 mg/L (60 min contact),while the antigencity was undetectable with chlorine dose more than 5 mg/L (60 ain contact).The water quality also impacted the inactivation efficiencies,and rotaviruses have a relatively higher resistant in secondary effluents than in the tap water under the same chlorine disinfection treatments.This study indicated that rotaviruses have a higher infectivity,gene and antigencity resistance to chlorine than that previously indicated by plaque assay only,which seemed to underestimate the resistance of rotaviruses to chlorine and the risk of rotaviruses in environments.Present results also suggested that re-evaluation of resistance of other waterborne viruses after disinfections by more sensitive infectivity detection method (such as ICC-RT-qPCR) may be necessary,to determine the adequate disinfectant doses required for the inactivation of waterborne viruses.

  3. Measurement and analysis of channel attenuation characteristics for an implantable galvanic coupling human-body communication.

    Science.gov (United States)

    Zhang, Shuang; Pun, Sio Hang; Mak, Peng Un; Qin, Yu-Ping; Liu, Yi-He; Vai, Mang I

    2016-11-14

    In this study, an experiment was designed to verify the low power consumption of galvanic coupling human-body communication. A silver electrode (silver content: 99%) is placed in a pig leg and a sine wave signal with the power of 0 dBm is input. Compared with radio frequency communication and antenna transmission communication, attenuation is reduced by approximately 10 to 15 dB, so channel characteristics are highly improved.

  4. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide

    OpenAIRE

    2010-01-01

    Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream op...

  5. Molecular characterization of rotavirus isolated from alpaca (Vicugna pacos) crias with diarrhea in the Andean Region of Cusco, Peru.

    Science.gov (United States)

    Garmendia, Antonio E; Lopez, Wellington; Ortega, Nastassja; Chamorro, Marycris J

    2015-10-22

    Alpacas (Vicugna pacos), a species of South American camelids (SAC), suffer high morbidity and mortality from infectious diseases. Diarrhea is one of the leading causes of alpaca cria mortality in Peru and elsewhere. In order to develop appropriate control and/or treatment, it is necessary to identify infectious pathogens that cause diarrhea in crias. Rotavirus was isolated in cell culture from feces collected from crias with acute diarrhea that tested positive to rotaviral antigen by rapid immunochromatographic methods in an earlier study. The isolates were identified as rotaviruses by RT-PCR run with specific primers for human rotavirus VP7 coding sequences using total RNA extracted from cells displaying cytopathic effects as template. These alpaca isolates were further identified as group A rotaviruses by means of a VP6-specific PCR and were designated as ALRVA-K'ayra/Perú/3368-10 and ALRVA-K'ayra/Perú/3386-10. Molecular G and P typing, placed the former as G3/P11 and the latter as G3/P?. Sequence analysis of two genome segments (coding for VP4 and VP7) from the alpaca isolates revealed partial homologies to swine and human rotaviruses, respectively. These results demonstrate that rotaviruses are associated with a proportion of cases of diarrhea in crias, although prevalence and impact remain to be determined. The isolation of rotaviruses from alpaca crias with diarrhea will contribute positively to further understand the pathogen and its role in the diarrhea complex.

  6. Severe Rotavirus gastroenteritis in a patient with infant leukemia

    Directory of Open Access Journals (Sweden)

    Hatice Uygun

    2011-03-01

    Full Text Available Rotavirus is the most common cause of severe gastroenteritis in infants and young children. Reports about the clinical relevance of rotavirus in immunocompromised children are rare. We herein presented a case of life-threatening Rotavirus gastroenteritis in an infant with acute myeloblastic leukemia which could be prevented by recently recommended Rotavirus vaccination.

  7. Development of primers for sequencing the NSP1, NSP3, and VP6 genes of the group A porcine rotavirus

    Directory of Open Access Journals (Sweden)

    Fernanda Dornelas Florentino Silva

    2014-02-01

    Full Text Available Rotavirus is the causative pathogen of diarrhea in humans and in several animal species. Eight pairs of primers were developed and used for Sanger sequencing of the coding region of the NSP1, NSP3, and VP6 genes based on the conserved regions of the genome of the group A porcine rotavirus. Three samples previously screened as positive for group A rotaviruses were subjected to gene amplification and sequencing to characterize the pathogen. The information generated from this study is crucial for the understanding of the epidemiology of the disease.

  8. NF-kB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses

    DEFF Research Database (Denmark)

    Byg, Luise M; Stensson, Jessica; Vasiljevic, Natasa;

    2012-01-01

    -¿B pathway leading to an attenuation of the activity. There is a possible link between development of non melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-¿B pathway is unclear. Seven different E7 proteins, representing four out of the five different species....... In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKa but not with IKKß. The deregulation of the NF-¿B pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors.......The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKKa and IKKß of the IKK complex in the NF...

  9. Establishment of indirect immunofluorescence assay for rotavirus.

    Science.gov (United States)

    Tao, J; Zhang, J; Liu, X; Jin, H; Jiang, C; Yin, Y

    2016-03-01

    Rotavirus infection is the most frequent cause of infantile gastroenteritis worldwide and a significant cause of death in infants and young children, following severe diarrhea and dehydration. Rotavirus vaccines are considered the most effective way to prevent rotavirus infections. In the process of developing rotavirus vaccines, it is crucial to establish a reliable and standardized method to determine vaccine titer. In this study, we developed an indirect immunofluorescence assay (IFA) to determine the infectious titer of Lanzhou lamb rotavirus (LLR) vaccine grown in MA104 cells. The activating concentration of trypsin was 1 µg/ml for healthy monolayers of MA104 cells at 100% confluence. After incubation for 18 hr, a rabbit anti-SA11 polyclonal antibody, diluted at 1:800 in PBS, was added to all wells, followed by an Alexa-488-conjugated secondary antibody diluted at 1:500 in PBS. Cells were examined with a fluorescence microscope. Our results show that IFA was more reproducible, more sensitive, simpler, and more rapid than the log 50% cell culture infectious dose-ELISA (lgCCID50-ELISA) in measuring the rotavirus vaccines. IFA provided a reliable basis for the qualitative and quantitative analysis of rotavirus, and the certification of rotavirus vaccine production.

  10. Rotavirus disrupts cytoplasmic P bodies during infection.

    Science.gov (United States)

    Bhowmick, Rahul; Mukherjee, Arpita; Patra, Upayan; Chawla-Sarkar, Mamta

    2015-12-02

    Cytoplasmic Processing bodies (P bodies), the RNA-protein aggregation foci of translationally stalled and potentially decaying mRNA, have been reported to be differentially modulated by viruses. Rotavirus, the causative agent of acute infantile gastroenteritis is a double stranded RNA virus which completes its entire life-cycle exclusively in host cell cytoplasm. In this study, the fate of P bodies was investigated upon rotavirus infection. It was found that P bodies get disrupted during rotavirus infection. The disruption occurred by more than one different mechanism where deadenylating P body component Pan3 was degraded by rotavirus NSP1 and exonuclease XRN1 along with the decapping enzyme hDCP1a were relocalized from cytoplasm to nucleus. Overall the study highlights decay and subcellular relocalization of P body components as novel mechanisms by which rotavirus subverts cellular antiviral responses.

  11. Unexpected detection of animal VP7 genes among common rotavirus strains isolated from children in Mexico.

    Science.gov (United States)

    Laird, A R; Ibarra, V; Ruiz-Palacios, G; Guerrero, M L; Glass, R I; Gentsch, J R

    2003-09-01

    In the course of characterizing 103 rotaviruses from children in Mexico, we found that the majority of strains were globally common types (55.4% of total), while uncommon types represented 5.7%, mixed infections with common types represented 14.8%, and partially or fully nontypeable isolates represented about 24%. Serotype G9 was detected for the first time in Mexico. We sequenced a subset of strains that were G nontypeable by reverse transcriptase PCR and found surprisingly that two strains having common human rotavirus P genotypes (8 and 6) had serotype G3 and G4 VP7 gene sequences that shared closer homology with canine and porcine strains, respectively, than with human strains, suggesting that these isolates represented reassortants between human and animal rotaviruses.

  12. Burden of Norovirus and Rotavirus in Children After Rotavirus Vaccine Introduction, Cochabamba, Bolivia.

    Science.gov (United States)

    McAtee, Casey L; Webman, Rachel; Gilman, Robert H; Mejia, Carolina; Bern, Caryn; Apaza, Sonia; Espetia, Susan; Pajuelo, Mónica; Saito, Mayuko; Challappa, Roxanna; Soria, Richard; Ribera, Jose P; Lozano, Daniel; Torrico, Faustino

    2016-01-01

    The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5-24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.

  13. Lactodifucotetraose, a human milk oligosaccharide, attenuates platelet function and inflammatory cytokine release.

    Science.gov (United States)

    Newburg, David S; Tanritanir, Ayse C; Chakrabarti, Subrata

    2016-07-01

    Human milk strongly quenches inflammatory processes in vitro, and breastfed infants have lower incidence of inflammatory diseases than those fed artificially. Platelets from neonates, in contrast to those from adults, are less responsive to platelet agonists such as collagen, thrombin, ADP, and epinephrine. Breastfed infants absorb oligosaccharides intact from the human milk in their gut to the circulation. This study was to determine whether these oligosaccharides can attenuate platelet function and platelet secretion of pro-inflammatory proteins, and to identify the active component. The natural mixture of oligosaccharides from human milk and pure individual human milk oligosaccharides were tested for their ability to modulate responses of platelets isolated from human blood following exposure to thrombin, ADP, and collagen. Human milk and the natural mixture of human milk oligosaccharides inhibited platelet release of inflammatory proteins. Of the purified human milk oligosaccharides tested, only lactodifucotetraose (LDFT) significantly inhibited thrombin induced release of the pro-inflammatory proteins RANTES and sCD40L. LDFT also inhibited platelet adhesion to a collagen-coated surface, as well as platelet aggregation induced by ADP or collagen. These data indicate that LDFT may help modulate hemostasis by suppressing platelet-induced inflammatory processes in breastfed infants. This activity suggests further study of LDFT for its potential as a therapeutic agent in infants and adults.

  14. First Molecular Detection of Group A Rotavirus in Urban and Hospital Sewage systems by Nested-RT PCR in Shiraz, Iran

    Directory of Open Access Journals (Sweden)

    Yahya Tahamtan

    2013-05-01

    Full Text Available Group A rotaviruses are the most significant cause of acute gastroenteritis in children worldwide. Rotaviruses are shed in high numbers and dispersed widely throughout bodies of water in the environment. This represents a significant health hazard for humans, mainly due to the stability of the viruses during wastewater treatment processes. This study was conducted to evaluate the prevalence of rotaviruses, to determine G genotypes of circulating rotaviruses and to assess the efficiency of rotavirus removal in urban and hospital sewage treatment plants in Shiraz, Iran.Materials and methods: During the period from October 2010 to June 2011, a total of sixty sewage samples from urban and hospital sewage disposal systems were collected by Grab Sampling in Shiraz, Iran. All the samples were concentrated in pellet form and two-phase methods and then group A rotaviruses were investigated with enzyme immunoassays (EIA. Rotavirus-positive specimens were genotyped by the nested RT-PCR and by using different types of specific primers.Results:In total, rotaviruses were identified in 25% (15 cases of sewage samples, representing 73.33% (11 cases of influent and 26.67% (4 cases of effluent systems. The frequency of rotavirus detection in autumn, winter and spring was 46.67%, 33.33% and 20%, respectively (P= 0.004. The most common circulating genotype was G1 (73.33%, followed by G1G4 (20% and non-typeable (6.67%, respectively.Conclusions:The high prevalence of rotaviruses in urban and hospital sewage systems highlights the importance of environmental surveillance as a tool to detect new genotypes and to investigate the epidemiology of rotaviruses circulating in the community.

  15. 牛轮状病毒基因重配二价减毒疫苗接种怀孕母牛的免疫原性评价%Evaluating the immunogenicity of bovine rotavirus reassortant bivalent attenuated vaccine in pregnant cows

    Institute of Scientific and Technical Information of China (English)

    常继涛; 于力

    2013-01-01

    In order to evaluate the immunogenicity of a candidate reassortant bivalent attenuated bovine rotavirus (BRV)vaccine (strains LLR-85 and R191),the cows pregnant for 7 to 8 months were immunized with the bivalent attenuated vaccine which was combined with LLR-85 (G10) and R191 (G6) strains in equal proportions and emulsified with adjuvant.The IgG,IgA and viral neutralizing (VN) antibodies against BRV in bovine serum were detected by using indirect ELISA and VN test.The results showed that the highest titers of the serum antibodies were induced in all inoculated cows at 2 weeks post immunization,and the antibody titers were up to 4 to 32 times of the original antibody titer,which lasted about 2 months.In addition,the vaccine had no side effects on the pregnant cows,such as abortion and other clinical reactions.Moreover,calves acquired the highest levels of serum and intestinal mucosal antibodies after birth by feeding the colostrum.The results suggested that the bivalent attenuated vaccine was safe for the pregnant cows and able to efficiently induce specific antibodies for protecting of calf through the colostrum.These results provided experimental basis for the clinical application of the bivalent attenuated reassortant BRV vaccine (LLR-85 and R191).%为评价牛轮状病毒(BRV)基因重组二价减毒疫苗(LLR-85和R191株)对怀孕母牛的免疫反应,本研究将RV LLR-85(G10)和R191(G6)株等比例混合后进行乳化,肌肉途径接种怀孕7个~8个月的母牛.采用间接ELISA和病毒中和(VN)试验对接种牛血清抗BRV的IgG、IgA以及VN抗体进行检测.结果显示,接种2周后抗体水平达到峰值,可以使原有的抗体滴度升高4倍~32倍,高滴度抗体可持续约2个月,接种母牛均未发生流产等副反应.犊牛通过饲喂初乳,可以在出生后1d内获得最高水平的血清和肠道粘膜抗体.结果表明,BRV基因重组二价减毒疫苗对孕牛不但具有良好的安全性、而且其高滴度抗体可以

  16. Transgenic Tobacco Expressing a Modified VP6 Gene Protects Mice Against Rotavirus Infection

    Institute of Scientific and Technical Information of China (English)

    Jiang-Li DONG; Bo ZHOU; Gang SHENG; Tao WANG

    2005-01-01

    Elevated expression of the rotavirus VP6 antigen in transgenic plants is a critical factor in the development of a safe and effective rotavirus vaccine. Using codon optimization, a gene that encodes the inner capsid protein VP6 of the human group A rotavirus was synthesized (sVP6). The VP6 and sVp6genes were transformed into tobacco (Nicotiana tabacum L.) plants using Agrobacterium tumefaciens. The expression level of the sVP6 gene in transgenic plants was 3.8-34-fold higher than that of controls containing the non-modified VP6 gene, accounting for up to 0.34% of the total soluble protein (TSP). Then, BALB/c female mice that had been gavaged weekly with 10 mg TSP containing 34 μg VP6 protein, in which VP6-specific serum IgG and mucosal IgA antibodies were investigated. The severity and duration of diarrhea caused by simian rotavirus SA-11 challenge were reduced significantly in passively immunized pups, which indicates that anti-VP6 antibodies generated in orally immunized female mice can be passed onto pups and provide heterotypic protection. An edible vaccine based on the VP6 of human rotavirus group A could provide a means to protect children and young animals from severe acute diarrhea.

  17. Simvastatin Attenuates TGF-β1-Induced Epithelial-Mesenchymal Transition in Human Alveolar Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Tuo Yang

    2013-06-01

    Full Text Available Background: Transforming growth factor-β1 (TGF-β1-induced epithelial-mesenchymal transition (EMT of alveolar epithelial cells (AEC may contribute to idiopathic pulmonary fibrosis (IPF. TGF-β1-induced EMT in A549 cells (a human AEC cell line resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1-Smad2/3 signaling pathway. Simvastatin (Sim, a 3-hydroxy-3-methylglutaryl CoA (HMG-CoA reductase inhibitor, has been previously reported to inhibit EMT in human proximal tubular epithelial cells and porcine lens epithelial cells and to suppress Smad2/3 phosphorylation in animal models. However, whether Sim can attenuate TGF-β1-induced EMT in A549 cells and its underlying mechanisms remains unknown. Methods: Cells were incubated with TGF-β1 in the presence or absence of Sim. The epithelial marker E-cadherin (E-Cad and the mesenchymal markers, α-smooth muscle actin (α-SMA, vimentin (Vi and fibronectin (FN, were detected using western blotting analyses and immunofluorescence. Phosphorylated Smad2 and Smad3 levels and connective tissue growth factor (CTGF were analyzed using western blotting. In addition, a cell migration assay was performed. Moreover, the levels of matrix metalloproteinase (MMP-2 and -9 in the culture medium were examined using ELISA. Results: Sim significantly attenuated the TGF-β1-induced decrease in E-Cad levels and elevated the levels of α-SMA, Vi and FN via the suppression of Smad2 and Smad3 phosphorylation. Furthermore, Sim inhibited the mesenchymal-like responses in A549 cells, including cell migration, CTGF expression and secretion of MMP-2 and -9. However, Sim failed to reverse the cell morphologial changes induced by TGF-β1 in A549 cells. Conclusion: Sim attenuated TGF-β1-induced EMT in A549 cells and might be a promising therapeutic agent for treating IPF.

  18. Live Attenuated Human Salmonella Vaccine Candidates: tracking the pathogen in natural infection and stimulation of host immunity

    Science.gov (United States)

    Galen, James E.; Buskirk, Amanda D.; Tennant, Sharon M.; Pasetti, Marcela F.

    2016-01-01

    Salmonellosis, caused by members of the genus Salmonella, is responsible for considerable global morbidity and mortality, in both animals and humans. In this review, we will discuss the pathogenesis of S. Typhi and S. Typhimurium, focusing on human Salmonella infections. We will trace the path of Salmonella through the body, including host entry sites, tissues and organs affected, and mechanisms involved in both pathogenesis and stimulation of host immunity. Careful consideration of the natural progression of disease provides an important context in which attenuated live oral vaccines can be rationally designed and developed. With this in mind, we will describe a series of attenuated live oral vaccines that have been successfully tested in clinical trials and demonstrated to be both safe and highly immunogenic. The attenuation strategies summarized in this review offer important insights into further development of attenuated vaccines against other Salmonella for which live oral candidates are currently unavailable. PMID:27809955

  19. Live Attenuated Human Salmonella Vaccine Candidates: Tracking the Pathogen in Natural Infection and Stimulation of Host Immunity.

    Science.gov (United States)

    Galen, James E; Buskirk, Amanda D; Tennant, Sharon M; Pasetti, Marcela F

    2016-11-01

    Salmonellosis, caused by members of the genus Salmonella, is responsible for considerable global morbidity and mortality in both animals and humans. In this review, we will discuss the pathogenesis of Salmonella enterica serovar Typhi and Salmonella enterica serovar Typhimurium, focusing on human Salmonella infections. We will trace the path of Salmonella through the body, including host entry sites, tissues and organs affected, and mechanisms involved in both pathogenesis and stimulation of host immunity. Careful consideration of the natural progression of disease provides an important context in which attenuated live oral vaccines can be rationally designed and developed. With this in mind, we will describe a series of attenuated live oral vaccines that have been successfully tested in clinical trials and demonstrated to be both safe and highly immunogenic. The attenuation strategies summarized in this review offer important insights into further development of attenuated vaccines against other Salmonella for which live oral candidates are currently unavailable.

  20. Presencia de rotavirus durante un proceso de compostaje. Abonos como vectores de contaminación viral

    Directory of Open Access Journals (Sweden)

    María Mercedes Martínez

    2009-12-01

    Full Text Available Rotavirus presence in a waste composting process. Organic fertilizers as vehicles for viral contamination. Objective. To show thepresence of rotavirus in different stages of a composting process: matrices used as raw material, mixture to be composted and the finalproduct. Materials and methods. Immunochromatography, ELISA and RT-PCR were used for viral detection. Results. Rotavirus wasfound in the first composting step, no virus was found in the second step, and some inhibitory substances were found in the third step thatposed difficulties in interpreting the PCR results and therefore providing a concluding result on rotavirus presence in the final product.Conclusions. Organic fertilizers can be vectors of human pathogenic viruses; therefore quality control tests must be implemented to avoidfurther viral dissemination. There are inhibitory substances present in organic fertilizers capable of interfering with the detection tests.

  1. [Universal vaccination for Rotavirus infection control].

    Science.gov (United States)

    Mita, Valentin; Capanna, Alessandra; Gervasi, Giuseppe; Zaratti, Laura; Franco, Elisabetta

    2015-01-01

    Rotaviruses are the most common etiological cause for pediatric acute gastroenteritis, particularly in children under 5 years of age or immunocompromised. Since 2008, vaccination program has determined a decrease in Rotavirus-related hospitalization, outpatient's visits, emergency department visits and mortality. These indicators of illness for Rotaviruses diseases remain high in those countries where there is no access to rehydrating therapies. In Italy vaccine coverage is very low, even if the burden of RV disease is well known, and at present vaccination is offered free of charge in a single region.

  2. Effect of monovalent rotavirus vaccine on rotavirus disease burden and circulating rotavirus strains among children in Morocco.

    Science.gov (United States)

    Benhafid, Mohammed; Elomari, Nezha; Azzouzi Idrissi, Meryem; Rguig, Ahmed; Gentsch, Jon R; Parashar, Umesh; Elaouad, Rajae

    2015-06-01

    Rotarix(TM) vaccine was introduced into the National Program of Immunization of Morocco in October 2010, reaching quickly 87% of the target population of children nationally. The incidence of rotavirus gastroenteritis and the prevalence of circulating rotavirus strains has been monitored in three sentinel hospitals since June 2006. The average percentage of rotavirus positive cases among all children under 5 years old hospitalized for gastroenteritis during the pre-vaccine period (2006-2010) was 44%. This percentage dropped to 29%, 15% and 24% in the 3 years post vaccine introduction (2011, 2012 and 2013), which is a decline of 34%, 66%, and 45%, respectively. Declines in prevalence were greatest among children 0-1 years of age (53%) and were most prominent during the winter and autumn rotavirus season. The prevalence of the G2P[4] and G9P[8] genotype sharply increased in the post vaccine period (2011-2013) compared to the previous seasons (2006-2010). Rotavirus vaccines have reduced greatly the number of children hospitalized due to rotavirus infection at the three sentinel hospitals; it is however unclear if the predominance of G2P[4] and G9P[8] genotypes is related to the vaccine introduction, or if this is attributable to normal genotype fluctuations. Continued surveillance will be pivotal to answer this question in the future.

  3. A Systems Survey of Progressive Host-Cell Reorganization during Rotavirus Infection.

    Science.gov (United States)

    Green, Victoria A; Pelkmans, Lucas

    2016-07-13

    Pathogen invasion is often accompanied by widespread alterations in cellular physiology, which reflects the hijacking of host factors and processes for pathogen entry and replication. Although genetic perturbation screens have revealed the complexity of host factors involved for numerous pathogens, it has remained challenging to temporally define the progression of events in host cell reorganization during infection. We combine high-confidence genome-scale RNAi screening of host factors required for rotavirus infection in human intestinal cells with an innovative approach to infer the trajectory of virus infection from fixed cell populations. This approach reveals a comprehensive network of host cellular processes involved in rotavirus infection and implicates AMPK in initiating the development of a rotavirus-permissive environment. Our work provides a powerful approach that can be generalized to order complex host cellular requirements along a trajectory of cellular reorganization during pathogen invasion.

  4. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  5. Impact of rotavirus vaccine on premature infants.

    Science.gov (United States)

    Roué, Jean-Michel; Nowak, Emmanuel; Le Gal, Grégoire; Lemaitre, Thomas; Oger, Emmanuel; Poulhazan, Elise; Giroux, Jean-Dominique; Garenne, Armelle; Gagneur, Arnaud

    2014-10-01

    Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. NCT00740935.).

  6. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  7. Intranasal oxytocin attenuates the human acoustic startle response independent of emotional modulation.

    Science.gov (United States)

    Ellenbogen, Mark A; Linnen, Anne-Marie; Cardoso, Christopher; Joober, Ridha

    2014-11-01

    Oxytocin promotes social affiliation in humans. However, the mechanisms underlying this phenomenon require further elucidation. The present study investigated the influence of intranasal oxytocin on basic emotional processing in men and women, using an emotion-modulated startle response paradigm. Eighty-four participants self-administered 24 IU of intranasal oxytocin or saline and completed an assessment of the acoustic startle reflex, using electromyography (EMG), with varying emotional foregrounds. Oxytocin had no impact on the affective modulation of the startle eye blink response, but significantly diminished the acoustic startle reflex irrespective of the emotional foreground. The results suggest that oxytocin facilitates prosocial behavior, in part, by attenuating basic physiological arousal. The dampening effect of oxytocin on EMG startle could possibly be used as an inexpensive marker of oxytocin's effect on limbic brain circuits.

  8. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  9. A组人轮状病毒VP3基因的原核表达及鉴定%Prokaryotic expression and identification of VP3 gene of group A human rotavirus

    Institute of Scientific and Technical Information of China (English)

    张顺; 潘小霞; 袁静; 文喻玲; 陈元鼎

    2012-01-01

    Objective To clone the gene encoding structural protein VP3 of group A human rotavirus (RV) TB-Chen strain, express in prokaryotic cells and investigate its molecular phylogenesis and genotype. Methods The gene encoding VP3 of TB-Chen strain was amplified by PCR and cloned into pETL vactor. The constructed recombinant plasmid pET-VP3 was transformed to E. Coli BL21 (DE3). The expressed recombinant protein was identified by SDS-PAGE and Western blot, based on which the cloned VP3 gene was analyzed for molecular phylogenesis and genotype. Results Restriction analysis and sequencing proved that recombinant plasmid pET-VP3 was constructed correctly. The expressed recombinant protein, with a relative molecular mass of about 98 000, existed in a form of inclusion body and was recognized by the guinea pig sera against whole virus of SA11 strain. By the so far, the discovered RV VP3 was of seven genotypes, of which those from TB-Chen and SA11 strains were belonged to genotypes M2 and M5 respectively. Conclusion The VP3 protein of group A human RV TB-Chen strain was successfully expressed in prokaryotic cells, which laid a foundation of further study on structure and function as well as development of VP3.%目的 克隆并原核表达A组人轮状病毒( Rotavirus,RV)TB-Chen株结构蛋白VP3基因,并进行分子系统进化和基因分型.方法 采用PCR法扩增A组人轮状病毒TB-Chen株VP3编码基因,克隆至pETL载体上,构建重组原核表达质粒pET-VP3,转化大肠杆菌BL21(DE3),并进行表达.表达的重组蛋白经SDS-PAGE及Western blot鉴定后,对VP3基因进行分子 系统进化及基因型分析.结果 重组表达质粒pET-VP3经双酶切及测序证实构建正确;表达的重组蛋白相对分子质量约为98 000,以包涵体形式存在;重组VP3蛋白可被抗SA11株全病毒豚鼠免疫血清识别;迄今发现的A组RV VP3可分为7个基因型,TB-Chen株和SA11株VP3基因分别属于M2型和M5型.结论

  10. Rotavirus and the Vaccine (Drops) to Prevent It

    Science.gov (United States)

    ... Immunizations Rotavirus and the Vaccine (Drops) to Prevent It Language: English Español (Spanish) Format: Select one PDF [ ... eating and drinking while they are sick. Is it serious? Rotavirus can be very harmful. Diarrhea, vomiting, ...

  11. Amino Acid sequence analysis of the two major outer Capsid Proteins (VP7 and VP4 from human-derived canine G3P[3] Rotavirus Strain Detected in Brazil

    Directory of Open Access Journals (Sweden)

    Adriana Luchs

    2013-12-01

    Full Text Available Introduction: A close look at the rotavirus group A (RVA genotypes in Brazil revealed the detection of a rare G3P[3] strain close related to canine strains. The aim of this study was to add to the already known genetic analysis by the description of the G3P[3] (IAL-R2638 strain amino acid characteristics. Methods: Amino acid sequence analysis and protein based trees were conducted using BioEdit and MEGA 4.0. Results: The VP7 and VP4 protein of the IAL-R2638 strain displayed the highest amino acid identity to the canine-derived human strain HCR3A (99.2%, and to the canine strain RV52/96 (96.4%, respectively. IAL-R2638 strain did not possess an extra VP7 N-linked glycosylation site at amino acid 238 recently described for some G3 strains, as well as RotaTeqTM G3 vaccine strain. The topology exhibited by phylogenetic trees in previous analysis were maintained in the present amino acid-based trees, reinforcing a stable relationship between G3P[3] strains. Conclusions: Amino acid analysis data were consistent with the previous sequence of data obtained for the IAL-R2638 strain, supporting its possible canine origin. Theoretically, RotaTeqTM vaccine could efficiently protect against G3P[3] infections based on the lack of the extra VP7 N-linked glycosylation site at amino acid 238. Phylogenetic analysis hypothesizes that all features undergo evolution independently of each other; however, unfavorable effects of nucleotide substitutions may be compensated by substitutions in other positions. The present study raises the question as to whether the amino acid-based trees could be applied as an approach to the study of RVA evolution, avoiding incorrect phylogenetic reconstructions.

  12. Whole-genome analyses reveals the animal origin of a rotavirus G4P[6] detected in a child with severe diarrhea.

    Science.gov (United States)

    Martinez, Magaly; Galeano, Maria E; Akopov, Asmik; Palacios, Ruth; Russomando, Graciela; Kirkness, Ewen F; Parra, Gabriel I

    2014-10-01

    Group A rotaviruses are a major cause of severe gastroenteritis in children worldwide. Currently, two rotavirus vaccines are being used in vaccination programs, and one of the factors involved in lower vaccine efficacy is the mismatch among the circulating strains and the vaccine strains. Thus, the emergence of animal strains in the human population could affect the efficacy of vaccination programs. Here we report the presence of a G4P[6] strain in a Paraguayan child presenting acute gastroenteritis in 2009. Genomic analyses revealed that the strain presents a porcine-like genome (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1), suggesting a direct animal-to-human transmission. Continuous surveillance of rotaviruses in humans and animals will help us to better understand rotavirus epidemiology and evolution.

  13. Australian Rotavirus Surveillance Program annual report, 2014.

    Science.gov (United States)

    Kirkwood, Carl D; Roczo-Farkas, Suzie

    2015-09-30

    The Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, reports the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis. During the survey period of 1 January to 31 December 2014, 1,022 faecal samples were referred for rotavirus G and P genotype analysis, and of these 733 were confirmed as rotavirus positive. A total of 480 specimens were collected from children under 5 years of age, while 253 were from older children and adults. Genotype analysis of the 733 rotavirus samples collected from both children and adults revealed that G12P[8] was the dominant genotype in this reporting period, identified in 29.6% of strains nationally. Genotype G1P[8] was the 2nd most common strain nationally, representing 22.9% of samples, followed by genotype G3P[8] (14.9%). This report highlights the continued significance of G12P[8] strains as the major cause of disease in this population. The genotype distribution was slightly altered when the analysis was restricted to samples collected from children under 5 years of age, with G1P[8] being the dominant genotype (29%) followed by G12P[8] as the 2nd most common genotype (26%). Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G12P[8] was more common in states and territories using RotaTeq, while G1P[8] was more common in the locations using Rotarix. This survey highlights the yearly fluctuations in rotavirus genotypes observed since vaccine introduction. The continuation of G12P[8] as the dominant genotype further illustrates the dynamic and diversity present in the wild-type rotavirus population evident in the Australian population since vaccine introduction.

  14. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Ben C L van Schaijk

    Full Text Available Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.

  15. Increasing cognitive load attenuates right arm swing in healthy human walking

    Science.gov (United States)

    Killeen, Tim; Easthope, Christopher S.; Filli, Linard; Lőrincz, Lilla; Schrafl-Altermatt, Miriam; Brugger, Peter; Linnebank, Michael; Curt, Armin; Zörner, Björn; Bolliger, Marc

    2017-01-01

    Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

  16. Rutin inhibits proliferation, attenuates superoxide production and decreases adhesion and migration of human cancerous cells.

    Science.gov (United States)

    Ben Sghaier, Mohamed; Pagano, Alessandra; Mousslim, Mohamed; Ammari, Youssef; Kovacic, Hervé; Luis, José

    2016-12-01

    Lung and colorectal cancer are the principal causes of death in the world. Rutin, an active flavonoid compound, is known for possessing a wide range of biological activities. In this study, we examined the effect of rutin on the viability, superoxide anion production, adhesion and migration of human lung (A549) and colon (HT29 and Caco-2) cancer cell lines. In order to control the harmlessness of the tested concentrations of rutin, the viability of cancer cell lines was assessed using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. ROS generation was measured by lucigenin chemiluminescence detecting superoxide ions. To investigate the effect of rutin on the behavior of human lung and colon cancer cell lines, we performed adhesion assays, using various purified extracellular matrix (ECM) proteins. Finally, in vitro cell migration assays were explored using modified Boyden chambers. The viability of cancerous cells was inhibited by rutin. It also significantly attenuated the superoxide production in HT29 cells. In addition, rutin affected adhesion and migration of A549 and HT29 cell. These findings indicate that rutin, a natural molecule, might have potential as anticancer agent against lung and colorectal carcinogenesis.

  17. Identification of the two rotavirus genes determining neutralization specificities

    Energy Technology Data Exchange (ETDEWEB)

    Offit, P.A.; Blavat, G.

    1986-01-01

    Bovine rotavirus NCDV and simian rotavirus SA-11 represent two distinct rotavirus serotypes. A genetic approach was used to determine which viral gene segments segregated with serotype-specific viral neutralization. There were 16 reassortant rotarviruses derived by coinfection of MA-104 cells in vitro with the SA-11 and NCDV strains. The parental origin of reassortant rotavirus double-stranded RNA segments was determined by gene segment mobility in polyacrylamide gels and by hybridization with radioactively labeled parental viral transcripts. The authors found that two rotavirus gene segments found previously to code for outer capsid proteins vp3 and vp7 cosegreated with virus neutralization specificities.

  18. Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency

    Science.gov (United States)

    Patel, Niraj C.; Hertel, Paula M.; Estes, Mary K.; de la Morena, Maite; Petru, Ann M.; Noroski, Lenora M.; Revell, Paula A.; Celine Hanson, I.; Paul, Mary E.; Rosenblatt, Howard M.; Abramson, Stuart L.

    2014-01-01

    SUMMARY Live pentavalent human–bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients. PMID:20107217

  19. Rotavirus vaccination within the South African Expanded Programme on Immunisation.

    Science.gov (United States)

    Seheri, L Mapaseka; Page, Nicola A; Mawela, Mothahadini P B; Mphahlele, M Jeffrey; Steele, A Duncan

    2012-09-07

    Diarrhoeal diseases are ranked the third major cause of childhood mortality in South African children less than 5 years, where the majority of deaths are among black children. Acute severe dehydrating rotavirus diarrhoea remains an important contributor towards childhood mortality and morbidity and has been well documented in South Africa. As the preventive strategy to control rotavirus diarrhoea, South Africa became the first country in the WHO African Region to adopt the rotavirus vaccine in the national childhood immunisation programme in August 2009. The rotavirus vaccine in use, Rotarix, GSK Biologicals, is given at 6 and 14 weeks of age, along with other vaccines as part of Expanded Programme on Immunisation (EPI). Studies which facilitated the introduction of rotavirus vaccine in South Africa included the burden of rotavirus disease and strain surveillance, economic burden of rotavirus infection and clinical trials to assess the safety and efficacy of vaccine candidates. This paper reviews the epidemiology of rotavirus in South Africa, outlines some of the steps followed to introduce rotavirus vaccine in the EPI, and highlights the early positive impact of vaccination in reducing the rotavirus burden of disease based on the post-marketing surveillance studies at Dr George Mukhari hospital, a sentinel site at University of Limpopo teaching hospital in Pretoria, South Africa, which has conducted rotavirus surveillance for >20 years.

  20. Rotavirus is frequent among adults hospitalised for acute gastroenteritis

    DEFF Research Database (Denmark)

    Lausch, Karen Rokkedal; Westh, Lena; Kristensen, Lena Hagelskjær;

    2017-01-01

    INTRODUCTION: Rotavirus infection is the most common aetiology of acute gastroenteritis (AGE) among young children. In adults, diagnostics focus mainly on bacterial causes, though recent studies suggest that rotavirus is a frequent agent. The aim of this study was to examine the proportion...... culture for bacterial pathogens. RESULTS: A total of 265 adult patients were included. 9.4% tested positive for rotavirus. Enteropathogenic bacteria were found in 24.5% of the cases. In the majority of cases (62.3%), no pathogen was found. Overall, rotavirus was the second-most frequent pathogen, exceeded...... only by Campylobacter spp. Immunosuppression and a C-reactive protein (CRP) below 50 mg/l (0-8 mg/l) were associated with rotavirus. The seasonality of rotavirus differed markedly from that of bacterial gastroenteritis. CONCLUSION: Rotavirus is the second-most frequently identified pathogen in adults...

  1. Rotavirus Antagonism of the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Michelle M. Arnold

    2009-11-01

    Full Text Available Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1 that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-κB. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis.

  2. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

    Science.gov (United States)

    Kamiya, Atsunori; Michikami, Daisaku; Shiozawa, Tomoki; Iwase, Satoshi; Hayano, Junichiro; Kawada, Toru; Sunagawa, Kenji; Mano, Tadaaki

    2004-05-01

    Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P antigravity leg muscles.

  3. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide.

    Science.gov (United States)

    Bhushan, Shashi; Meyer, Helge; Starosta, Agata L; Becker, Thomas; Mielke, Thorsten; Berninghausen, Otto; Sattler, Michael; Wilson, Daniel N; Beckmann, Roland

    2010-10-08

    Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream open reading frame 2 (uORF2). The C terminus of the AAP appears to be compacted adjacent to the peptidyl transferase center (PTC). Both nascent chains interact with ribosomal proteins L4 and L17 at tunnel constriction in a distinct fashion. Significant changes at the PTC were observed: the eukaryotic-specific loop of ribosomal protein L10e establishes direct contact with the CCA end of the peptidyl-tRNA (P-tRNA), which may be critical for silencing of the PTC during translational stalling. Our findings provide direct structural insight into two distinct eukaryotic stalling processes.

  4. IL-17 attenuates the anti-apoptotic effects of GM-CSF in human neutrophils.

    Science.gov (United States)

    Dragon, Stéphane; Saffar, Arash Shoja; Shan, Lianyu; Gounni, Abdelilah Soussi

    2008-01-01

    Interleukin (IL)-17A is a pleiotropic, pro-inflammatory cytokine that is implicated in chronic inflammatory and degenerative disorders. IL-17 has been demonstrated to link activated T-lymphocyte with the recruitment of neutrophils at sites of inflammation, however whether IL-17 can mediate neutrophil survival and subsequently affect inflammatory responses has not fully been elucidated. In our study, we demonstrate that human peripheral blood and HL-60 differentiated neutrophils express mRNA and cell surface IL-17A receptor. IL-17A does not affect the rate of spontaneous neutrophil apoptosis, however significantly decreased granulocyte macrophage-colony stimulating factor (GM-CSF)-mediated survival by antagonizing the signal transduction pathways of p38, Erk1/2 and signal transducer and activator of transcription (STAT) 5B. These events were associated with reduced myeloid cell lymphoma-1 (Mcl-1) protein levels, increased translocation and aggregation of Bax to mitochondria, decreased mitochondrial transmembrane potential and in an increase in caspase-3/7 activity. These events were independent of increased Fas or soluble Fas ligand expression levels. Taken together, our findings suggest that IL-17 may regulate neutrophil homeostasis and favor the resolution of inflamed tissues by attenuating the delay in neutrophil apoptosis induced by inflammatory cytokines.

  5. Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Gorissen, Marnix; Bernier, Nicholas J; Manuel, Remy; de Gelder, Stefan; Metz, Juriaan R; Huising, Mark O; Flik, Gert

    2012-08-01

    Proper functioning of the endocrine stress axis requires communication between the stress axis and other regulatory mechanisms. We here describe an intimate interplay between the stress axis and recombinant human leptin (rhLeptin) in a teleostean fish, the common carp Cyprinus carpio. Restraint stress (by netting up to 96h) increased plasma cortisol but did not affect hepatic leptin expression. Perifusion of pituitary glands or head kidneys with rhLeptin revealed direct effects of rhLeptin on both tissues. RhLeptin suppresses basal and CRF-induced ACTH-secretion in a rapid and concentration-dependent manner. The rhLeptin effect persisted for over an hour after administration had been terminated. RhLeptin decreases basal interrenal cortisol secretion in vitro, and by doing so attenuates ACTH-stimulated cortisol production; rhLeptin does not affect interrenal ACTH-sensitivity. Our findings show that the endocrine stress axis activity and leptin are inseparably linked in a teleostean fish, a notion relevant to further our insights in the evolution of leptin physiology in vertebrates.

  6. Australian Rotavirus Surveillance Program annual report, 2015.

    Science.gov (United States)

    Roczo-Farkas, Susie; Kirkwood, Carl D; Bines, Julie E

    2016-12-24

    The Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, reports the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2015. During the survey period, 1,383 faecal samples were referred for rotavirus G and P genotype analysis, and of these, 1,031 were confirmed as rotavirus positive. A total of 634 specimens had been collected from children under 5 years of age, while 397 were from older children and adults. Genotype analysis of samples from both children and adults revealed that G12P[8] was the dominant genotype in this reporting period, identified in 48.2% of strains nationally. Genotype G3P[8] was the second most common strain nationally, representing 22.8% of samples, followed by G2P[4] and G1P[8] (9% and 8% respectively). G3P[8] was further divided as equine-like G3P[8] (13.2% of all strains) and other wild-type G3P[8] (9.6%). This report highlights the continued predominance of G12P[8] strains as the major cause of disease in this population. Genotype distribution was distinct between jurisdictions using RotaTeq and Rotarix vaccines. Genotype G12P[8] was more common in states using RotaTeq, while equine-like G3P[8] and G2P[4] were more common in the states and territories using Rotarix. This survey highlights the dynamic change in rotavirus genotypes observed since vaccine introduction, including the emergence of a novel equine-like G3P[8] as a major strain. The prolonged dominance of G12P[8] for a 4th consecutive year further illustrates the unexpected trends in the wild type rotaviruses circulating in the Australian population since vaccine introduction.

  7. Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination

    Science.gov (United States)

    Steele, A. Duncan; Madhi, Shabir A.; Cunliffe, Nigel A.; Vesikari, Timo; Phua, Kong Boo; Lim, Fong Seng; Nelson, E. Anthony S.; Lau, Yu-Lung; Huang, Li-Min; Karkada, Naveen; Debrus, Serge; Han, Htay Htay; Benninghoff, Bernd

    2016-01-01

    ABSTRACT Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings. PMID:27260009

  8. Reduction in Rotavirus Disease and Sustained Predominance of G2P[4] Rotavirus Strain following Introduction of Rotavirus Vaccine in Recife, Brazil.

    Science.gov (United States)

    Montenegro, Fernanda Maria Ulisses; Falbo, Ana Rodrigues; Germano, Eliane Mendes; Correia, Nancy Barros; Souza, Edvaldo da Silva; Nakagomi, Osamu; Nakagomi, Toyoko; Cuevas, Luis E; Cunliffe, Nigel A; Correia, Jailson B

    2015-06-01

    Rotavirus vaccination was introduced in Brazil in March 2006. We describe the distribution of rotavirus genotypes in children with acute gastroenteritis in a hospital in Recife, Brazil, during pre- and post-vaccination periods. There was a 43.8% reduction in the proportion of diarrhea episodes due to rotavirus. Nevertheless, we observed a sustained predominance of G2P[4] as the main genotype identified in the post-vaccination period.

  9. Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse

    Directory of Open Access Journals (Sweden)

    Michele Salanova

    2013-01-01

    Full Text Available Activity-induced nitric oxide (NO imbalance and “nitrosative stress” are proposed mechanisms of disrupted Ca2+ homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study without and with exercise as countermeasure in order to assess (i the negative effects of chronic muscle disuse by nitrosative stress, (ii to test for possible attenuation by exercise countermeasure in bed rest and (iii to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre and at end (End from a bed rest disuse control group (CTR, n=9 and two bed rest resistive exercise groups either without (RE, n=7 or with superimposed vibration stimuli (RVE, n=7. At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, –SERCA1 and –PMCA and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.

  10. Rotavirus vaccines: targeting the developing world.

    Science.gov (United States)

    Glass, Roger I; Bresee, Joseph S; Turcios, Reina; Fischer, Thea K; Parashar, Umesh D; Steele, A Duncan

    2005-09-01

    For the past 2 decades, rotavirus infection, the most common cause of severe diarrhea in children, has been a priority target for vaccine development. This decision to develop rotavirus vaccines is predicated on the great burden associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm scientific basis for developing live oral vaccines, the belief that increased investment in development at this time could speed the introduction of vaccines in developing countries, and the appreciation that implementation of a vaccine program should result in a measurable decrease in the number of hospitalizations and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth-Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn after 9 months because of a rare association of the vaccine with the development of intussusception. In the developing world, this vaccine could still have had a measurable effect, because the benefits of preventing deaths due to rotavirus disease would have been substantially greater than the rare risk of intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has been licensed in Mexico and the Dominican Republic, and the Merck vaccine could be licensed in the United States within 1 year; several other candidate vaccines are in earlier stages of testing. However, many challenges remain before any of these vaccines can be incorporated into childhood immunization programs in the developing world. First, vaccine efficacy, which has already been demonstrated in children in industrialized and middle-income countries, needs to be proven in poor developing countries in Africa and Asia. The safety of vaccines with regard to the associated risk of intussusception must be demonstrated as well. Novel financing strategies will be needed to ensure that new vaccines are affordable and available in the

  11. An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

    NARCIS (Netherlands)

    Knipping, Karen; Garssen, Johan; van't Land, Belinda

    2012-01-01

    Background: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. Methods: 150 plant extracts with nutri

  12. Mutation distribution in the NSP4 protein in rotaviruses isolated from Mexican children with moderate to severe gastroenteritis.

    Science.gov (United States)

    González-Ochoa, Guadalupe; Menchaca, Griselda E; Hernández, Carlos E; Rodríguez, Cristina; Tamez, Reyes S; Contreras, Juan F

    2013-03-11

    The NSP4 protein is a multifunctional protein that plays a role in the morphogenesis and pathogenesis of the rotavirus. Although NSP4 is considered an enterotoxin, the relationship between gastroenteritis severity and amino acid variations in NSP4 of the human rotavirus remains unclear. In this study, we analyzed the sequence diversity of NSP4 and the severity of gastroenteritis of children with moderate to severe gastroenteritis. The rotavirus-infected children were hospitalized before the rotavirus vaccine program in Mexico. All children had diarrhea within 1-4 days, 44 (88%) were vomiting and 35 (70%) had fevers. The severity analysis showed that 13 (26%) cases had mild gastroenteritis, 23 (46%) moderate gastroenteritis and 14 (28%) severe. NSP4 phylogenetic analysis showed three clusters within the genotype E1. Sequence analysis revealed similar mutations inside each cluster, and an uncommon variation in residue 144 was found in five of the Mexican NSP4 sequences. Most of the amino acid variations were located in the VP4 and VP6 binding site domains, with no relationship to different grades of gastroenteritis. This finding indicates that severe gastroenteritis caused by the rotavirus appears to be related to diverse viral or cellular factors instead of NSP4 activity as a unique pathogenic factor.

  13. Mutation Distribution in the NSP4 Protein in Rotaviruses Isolated from Mexican Children with Moderate to Severe Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Juan F. Contreras

    2013-03-01

    Full Text Available The NSP4 protein is a multifunctional protein that plays a role in the morphogenesis and pathogenesis of the rotavirus. Although NSP4 is considered an enterotoxin, the relationship between gastroenteritis severity and amino acid variations in NSP4 of the human rotavirus remains unclear. In this study, we analyzed the sequence diversity of NSP4 and the severity of gastroenteritis of children with moderate to severe gastroenteritis. The rotavirus-infected children were hospitalized before the rotavirus vaccine program in Mexico. All children had diarrhea within 1-4 days, 44 (88% were vomiting and 35 (70% had fevers. The severity analysis showed that 13 (26% cases had mild gastroenteritis, 23 (46% moderate gastroenteritis and 14 (28% severe. NSP4 phylogenetic analysis showed three clusters within the genotype E1. Sequence analysis revealed similar mutations inside each cluster, and an uncommon variation in residue 144 was found in five of the Mexican NSP4 sequences. Most of the amino acid variations were located in the VP4 and VP6 binding site domains, with no relationship to different grades of gastroenteritis. This finding indicates that severe gastroenteritis caused by the rotavirus appears to be related to diverse viral or cellular factors instead of NSP4 activity as a unique pathogenic factor.

  14. Rotavirus Vaccine: What You Need to Know

    Science.gov (United States)

    ... including a severe allergy to latex. Babies with “severe combined immunodeficiency” (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called “intussusception” should not get ... moderate or severe diarrhea or vomiting. Check with your doctor if ...

  15. Celecoxib attenuates 5-fluorouracil-induced apoptosis in HCT-15 and HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yun Jeong Lim; Jong Chul Rhee; Young Mee Bae; Wan Joo Chun

    2007-01-01

    AIM: To investigate the combined chemotherapeutic effects of celecoxib when used with 5-FU in vitro.METHODS: Two human colon cancer cell lines (HCT-15and HT-29) were treated with 5-FU and celecoxib, alone and in combination. The effects of each drug were evaluated using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry,and western blotting.RESULTS: 5-FU and celecoxib showed a dosedependent cytotoxic effect. When treated with 10-3mol/L 5-FU (IC50) and celecoxib with its concentration ranging from 10-8 mol/L to 10-4 mol/L of celecoxib,cells showed reduced cytotoxic effect than 5-FU(10-3 mol/L) alone. Flow cytometry showed that celecoxib attenuated 5-FU induced accumulation of cells at subG1 phase. Western blot analyses for caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage showed that celecoxib attenuated 5-FU induced apoptosis. Western blot analyses for cell cycle molecules showed that G2/M arrest might be possible cause of 5-FU induced apoptosis and celecoxib attenuated 5-FU induced apoptosis via blocking of cell cycle progression to the G2/M phase,causing an accumulation of cells at the G1/S phase.CONCLUSION: We found that celecoxib attenuated cytotoxic effect of 5-FU. Celecoxib might act via inhibition of cell cycle progression, thus preventing apoptosis induced by 5-FU.

  16. HUMAN PAPILLOMAVIRUS TYPE 16 L1 PROTEIN CAN BE EXPRESSED IN LIVE ATTENUATED SHIGELLA FLEXNERI 5A STRAIN SH42

    Institute of Scientific and Technical Information of China (English)

    Qu Xinzhong; Yang Xiaofeng; Zheng Jin; Wang Kai; Si Lüsheng; Wang Yili

    2005-01-01

    Objective Attenuated strains of Shigella are attractive live vaccine candidates for eliciting mucosal immune responses which is a suitable carrier for the prophylactic human papillomaviruses (HPV) vaccine development, To examine the potential of a live Shigella based prophylactic HPV vaccine, HPV16L1should be expressed in attenuated shigella strain. Methods A Shigella large invasive plasmid (icsA/virG) based prokaryotic expression plasmid pHS3199 was constructed. HPV16L1 gene was inserted into plasmid pHS3199 to form pHS3199-HPV16 L1 construct, and pHS3199-hpv16L1 was electroporated into a live attenuated shigella strain sh42. The expression of HPV16L1 protein was demonstrated by Western blotting with monoclonal antibody to HPV16L1, The genetic stability of recombinant strain sh42-HPV16 L1 was monitored by consecutive passage culture. Invasive ability of sh42-HPV16L1 was evaluated by Hela cell infection assay. Results HPV16 L1 protein can be expressed in recombinant strain sh42-HPV16 L1, and the protein stably expressed over 140 generations. The invasive ability of sh42-HPV16L1 was diminished dramatically compared to its parent strain, but not abolished completely. Conclusion HPV16L1 protein was constitutively expressed in the attenuated strain of shigella flexneri sh42, and maintained partial invasive ability. Our strategy may represent a promising vaccine candidate against genital HPV16 infection.

  17. Pronóstico de la diarrea por rotavirus Prognosis of rotavirus diarrhea

    Directory of Open Access Journals (Sweden)

    Felipe Mota-Hernández

    2001-12-01

    Full Text Available Objetivo. Comparar la gravedad de la diarrea por rotavirus (RV y por no rotavirus. Material y métodos. Estudio transversal en 520 lactantes con diarrea aguda, efectuado entre octubre de 1994 y marzo de 1995 en siete centros del primer nivel de atención en cinco estados de México. El diagnóstico de RV se realizó con ensayo inmunoenzimático o por electroforesis. El análisis se hizo a través de medidas de tendencia central. Los resultados se presentan como promedio y desviación estándar o mediana o variación. Resultados. Se aisló RV en 264 lactantes (50.7% con predominio en varones de 6 meses a un año. Las manifestaciones clínicas fueron significativamente diferentes entre el grupo rotavirus positivo y el grupo rotavirus negativo en mediana de evacuaciones por 24 horas, frecuencia de vómitos, temperatura > 38° C, deshidratación y calificación de gravedad, respectivamente. Conclusiones. Estos resultados mostraron peor pronóstico por mayor gravedad de la diarrea por RV en lactantes, con relación a otra etiología. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjective. To compare the severity of rotavirus diarrhea (RV and non-rotavirus diarrhea. Material and Methods. Between October 1994 and March 1995, a cross-sectional study was performed in 520 infants with acute diarrhea, at seven primary care level centers in five states of Mexico. Diagnosis of RV was done through immunoenzymatic assay or electrophoresis. Central tendency measures were used for data analysis. Results were presented as means and standard deviations, or median and variation. Results. RV was isolated from 264 children; most of them were males aged 6 months to 1 year. Differences in clinical manifestations were statistically significant between the rotavirus-positive group and the rotavirus-negative group, in the following variables: median number of stools/24 hours; frequency of vomiting; temperature > 38

  18. Options for improving effectiveness of rotavirus vaccines in developing countries.

    Science.gov (United States)

    Tissera, Marion S; Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L; Lyras, Dena; Kirkwood, Carl D; Buttery, Jim P

    2016-11-11

    Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.

  19. Incidence and cost of rotavirus hospitalizations in Denmark

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Nielsen, Nete Munk; Wohlfahrt, Jan

    2007-01-01

    In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea-associated hospitalizat......In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea......-associated hospitalizations coded as nonspecified viral or presumed infectious have demonstrated a marked winter peak similar to that of rotavirus-associated hospitalizations, which suggests that the registered rotavirus-coded admissions are grossly underestimated. We therefore obtained more realistic estimates by 2...

  20. Genotypification of bovine group A rotavirus in México.

    Science.gov (United States)

    Rodríguez-Limas, William A; Flores-Samaniego, Beatriz; de la Mora, Germán; Ramírez, Octavio T; Palomares, Laura A

    2009-10-30

    Bovine scours, frequently provoked by rotavirus infection, causes significant economic losses. Nevertheless, no information exists about the bovine rotavirus genotypes present in Mexico. This information is necessary for designing efficient vaccines. In this work, 128 samples from diarrheic calves were collected between 2005 and 2006 in 26 dairy and/or beef cattle herds located in 10 regions of Mexico, and analyzed for the presence of group A rotavirus. G and P genotypes were determined by PCR in rotavirus-positive samples (12/128). Three different genotype combinations were found, G10, P[11]; G6, P[5]; and G10, P[5]; in 67, 25 and 8% of the positive samples, respectively. Some rotavirus-positive animals had been vaccinated with an inactivated rotavirus strain of a different genotype.

  1. Rational Design of Human Metapneumovirus Live Attenuated Vaccine Candidates by Inhibiting Viral mRNA Cap Methyltransferase

    Science.gov (United States)

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan

    2014-01-01

    ABSTRACT The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2′-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2′-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. IMPORTANCE Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine

  2. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  3. Activation and Genetic Modification of Human Monocyte-Derived Dendritic Cells using Attenuated Salmonella typhimurium

    Directory of Open Access Journals (Sweden)

    Agnieszka Michael

    2010-01-01

    Full Text Available Live attenuated bacterial vectors, such as Salmonella typhimurium, have shown promise as delivery vehicles for DNA. We have examined two new strains of S. typhimurium and their impact on dendritic cell maturation (CD12-sifA/aroC mutant and WT05-ssaV/aroC, both in TML background. Strain WT05 matured dendritic cells in a more efficient way; caused higher release of cytokines TNF-α, IL-12, IL-1β; and was efficient for gene transfer. These findings suggest that the genetic background of the attenuation can influence the pattern of inflammatory immune response to Salmonella infection.

  4. Respuesta inmune innata humana al rotavirus

    Directory of Open Access Journals (Sweden)

    Juanita Angel

    2004-03-01

    lymphocytes secreting interferon gamma after acute natural rotavirus infection in children and adults. J Virology 2002; 76: 4741–4749.

    5. ROJAS, O. L., A. M. GONZÁLEZ, R. GONZÁLEZ, I. PÉREZSCHAEL, H. B. GREENBERG, M. A. FRANCO AND J. ANGEL. Human rotavirus specific t cells: Quantification by elispot and expression of homing receptors on cd4+ t cells. Virology 2003; 314: 671–679.

  5. Analysis of human rotavirus G1P[8] strains by RFLP reveals higher genetic drift in the VP7 than the VP4 gene during a 4-year period in Mexico.

    Science.gov (United States)

    Rodríguez-Castillo, Araceli; Ramírez-González, José Ernesto; Padilla-Noriega, Luis; Barrón, Blanca Lilia

    2006-12-01

    Several studies have demonstrated that rotaviruses of the G1P[8] genotype are among the most important worldwide. Sequence analysis of G1P[8] strains has revealed high genetic variability of VP4 and VP7 genes. The aim of this study was to investigate by restriction fragment length polymorphism (RFLP) analysis the genetic variability of the VP7 and VP4 genes within rotaviruses of the G1P[8] genotype. A total of 60 rotavirus-positive fecal samples genotyped as G1P[8], were collected from children with acute diarrhea under 5 years of age, between October 1995 and October 1998. The VP7 and VP4 genes were amplified by RT/PCR, using the Beg9/End9 primer pair and the Con3 and Con2 primers, respectively. VP7 amplicons were digested with three restriction enzymes Hae III, Taq I and Rsa I in separate reactions and VP4 amplicons were digested similarly with endonucleases Hinf I, Sau96 I and Rsa I. Analysis of the digested VP7 and VP4 amplicons showed a higher genetic drift for the VP7 gene (18 RFLPs) compared to the VP4 gene (9 RFLPs). The combination of profiles for both VP7 and VP4 amplicons, showed 27 different patterns, none of them similar to the Wa-1 strain. Furthermore, RFLP analysis of these G1P[8] strains, clearly differentiated the viruses into two main clusters, both of them sharing the same restriction pattern for the VP4 gene, and a different one for the VP7 gene.

  6. Three infants with rotavirus gastroenteritis complicated by severe gastrointestinal bleeding.

    Science.gov (United States)

    Kawamura, Yoshiki; Miura, Hiroki; Mori, Yuji; Sugata, Ken; Nakajima, Yoichi; Yamamoto, Yasuto; Morooka, Masashi; Tsuge, Ikuya; Yoshikawa, Akiko; Taniguchi, Koki; Yoshikawa, Tetsushi

    2016-01-01

    Rotavirus gastroenteritis causes substantial morbidity and mortality worldwide in children. We report three infants with rotavirus gastroenteritis complicated by various severity of gastrointestinal bleeding. Two patients (cases 1 and 2) recovered completely without any specific treatments. One patient (case 3) died despite extensive treatments including a red blood cell transfusion and endoscopic hemostatic therapy. Rotavirus genotypes G1P[8] and G9P[8] were detected in cases 2 and 3, respectively. Rotavirus antigenemia levels were not high at the onset of melena, suggesting that systemic rotaviral infection does not play an important role in causing melena.

  7. [A rare cause of afebrile convulsion: rotavirus gastroenteritis].

    Science.gov (United States)

    Karabel, Müsemma; Karabel, Duran; Kara, Semra; Halıcı Taş, Tuğba; Türkay, Sadi

    2013-04-01

    Rotavirus is the most common infectious diarrhea that causes important mortality and morbidities in small children, severe dehydration and electrolyte imbalance. Extraintestinal signs are rare in rotavirus infections. Recently, afebrile seizures associated with rotavirus gastroenteritis but without encephalopathy, dehydration, electrolyte imbalance or hypoglycemia have being reported. In this article, the fact that rotavirus, which is seen commonly in our country, can be confronted with various clinical manifestations was emphasized by reminding that it can be seen not only in infants with neurologic and systemic disease but also in healthy infants.

  8. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice

    Science.gov (United States)

    Lee, Craig R.; Imig, John D.; Edin, Matthew L.; Foley, Julie; DeGraff, Laura M.; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; Clark, James; Myers, Page; Perrow, A. Ligon; Lepp, Adrienne N.; Kannon, M. Alison; Ronnekleiv, Oline K.; Alkayed, Nabil J.; Falck, John R.; Tomer, Kenneth B.; Zeldin, Darryl C.

    2010-01-01

    Renal cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) regulate sodium transport and blood pressure. Although endothelial CYP-derived EETs are potent vasodilators, their contribution to the regulation of blood pressure remains unclear. Consequently, we developed transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases to increase endothelial EET biosynthesis. Compared to wild-type littermate controls, an attenuated afferent arteriole constrictor response to endothelin-1 and enhanced dilator response to acetylcholine was observed in CYP2J2 and CYP2C8 transgenic mice. CYP2J2 and CYP2C8 transgenic mice demonstrated modestly, but not significantly, lower mean arterial pressure under basal conditions compared to wild-type controls. However, mean arterial pressure was significantly lower in both CYP2J2 and CYP2C8 transgenic mice during coadministration of N-nitro-l-arginine methyl ester and indomethacin. In a separate experiment, a high-salt diet and subcutaneous angiotensin II was administered over 4 wk. The angiotensin/high-salt-induced increase in systolic blood pressure, proteinuria, and glomerular injury was significantly attenuated in CYP2J2 and CYP2C8 transgenic mice compared to wild-type controls. Collectively, these data demonstrate that increased endothelial CYP epoxygenase expression attenuates afferent arteriolar constrictor reactivity and hypertension-induced increases in blood pressure and renal injury in mice. We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure.—Lee, C. R., Imig, J. D., Edin, M. E., Foley, J., DeGraff, L. M., Bradbury, J. A., Graves, J. P., Lih, F. B., Clark, J., Myers, P., Perrow, A. L., Lepp, A. N., Kannon, M. A., Ronnekleiv, O. K., Alkayed, N. J., Falck, J. R., Tomer, K. B., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. PMID:20495177

  9. [原著]Comparison of Rotavirus Immunoglobulin G Titers in Sera Collected in Japan and Kenya

    OpenAIRE

    Makino, Yoshihiro; Iwanaga, Tatsue; Maedar, Yukiko; Igarashi, Akira; Fukunaga, Toshihiko; Department of Virology, School of Medicine, University of the Ryukyus; Department of Virology, Institute for Tropical Medicine, Nagasaki University; Participant m the Oversea Training Project sponsored by Nagasaki Prefectural Government

    1984-01-01

    ELISA for detecting IgG antibody against human rotavirus was carried out on the sera collected in Kumamoto and Nyeri, Kenya. In both areas, most of the infants acquired antibody by 3 years of age and kept high level thereafter. The antibody prevalence among age groups in the two areas showed almost same patterns. Correlation was seen between ELISA titers and neutralization titers.

  10. Novel Rotavirus VP7 Typing Assay Using a One-Step Reverse Transcriptase PCR Protocol and Product Sequencing and Utility of the Assay for Epidemiological Studies and Strain Characterization, Including Serotype Subgroup Analysis

    Science.gov (United States)

    DiStefano, Daniel J.; Kraiouchkine, Nikolai; Mallette, Laura; Maliga, Marianne; Kulnis, Gregory; Keller, Paul M.; Clark, H. Fred; Shaw, Alan R.

    2005-01-01

    Rotavirus is the most common cause of severe dehydrating gastroenteritis in infants. To date, 10 different serotypes of rotavirus have been identified in human stools. While four or five serotypes dominate, serotype circulation varies with season and geography. Since our laboratory has been involved in the development of a multivalent rotavirus vaccine, it is important to identify the serotypes of rotavirus encountered during our clinical trials. We have developed methodologies for the molecular identification of rotavirus strains based on VP7 gene segment sequence. A 365-bp reverse transcriptase PCR product was generated from the VP7 gene segment using a pair of novel degenerate primers. All serotypes tested (both animal and human) yielded an identically sized product after amplification. Sequencing of these products is performed using truncated versions of the original primers. The sequence generated is compared against a database of rotavirus VP7 sequences, with the G type determined, based on the sequence homology. Using this assay, we have correctly identified human VP7 strains from a panel of available serotypes, as well as numerous animal strains. The assay was qualified using rotavirus positive stool samples, negative stool samples, and rotavirus-spiked stool samples. In addition, samples from cases of acute gastroenteritis collected at Children's Hospital of Philadelphia have been evaluated and indicate that the assay is able to discriminate subtle differences within serotypes. The assay has been utilized in the testing of >3,000 antigen-positive (enzyme immunoassay) samples collected during clinical trials of a rotavirus vaccine (RotaTeq) and identified a serotype in ∼92% of samples (3, 17, 19). PMID:16333070

  11. Tylosema esculentum (Marama) Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection

    OpenAIRE

    Walter Chingwaru; Runner T. Majinda; Sam O. Yeboah; Jackson, Jose C.; Petrina T. Kapewangolo; Martha Kandawa-Schulz; Avrelija Cencic

    2011-01-01

    Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin. Marama cotyledon ethan...

  12. A Multi-Center, Qualitative Assessment of Pediatrician and Maternal Perspectives on Rotavirus Vaccines and the Detection of Porcine circovirus

    Directory of Open Access Journals (Sweden)

    Locke David

    2011-09-01

    Full Text Available Abstract Background In 2010, researchers using novel laboratory techniques found that US-licensed rotavirus vaccines contain DNA or DNA fragments from Porcine circovirus (PCV, a virus common among pigs but not believed to cause illness in humans. We sought to understand pediatricians' and mothers' perspectives on this finding. Methods We conducted three iterations of focus groups for pediatricians and non-vaccine hesitant mothers in Seattle, WA, Cincinnati, OH, and Rochester, NY. Focus groups explored perceptions of rotavirus disease, rotavirus vaccination, and attitudes about the detection of PCV material in rotavirus vaccines. Results Pediatricians understood firsthand the success of rotavirus vaccines in preventing severe acute gastroenteritis among infants and young children. They measured this benefit against the theoretical risk of DNA material from PCV in rotavirus vaccines, determining overall that the PCV finding was of no clinical significance. Particularly influential was the realization that the large, randomized clinical trials that found both vaccines to be highly effective and safe were conducted with DNA material from PCV already in the vaccines. Most mothers supported the ideal of full disclosure regarding vaccination risks and benefits. However, with a scientific topic of this complexity, simplified information regarding PCV material in rotavirus vaccines seemed frightening and suspicious, and detailed information was frequently overwhelming. Mothers often remarked that if they did not understand a medical or technical topic regarding their child's health, they relied on their pediatrician's guidance. Many mothers and pediatricians were also concerned that persons who abstain from pork consumption for religious or personal reasons may have unsubstantiated fears of the PCV finding. Conclusions Pediatricians considered the detection of DNA material from PCV in rotavirus vaccines a "non-issue" and reported little hesitation in

  13. Field of view extension and truncation correction for MR-based human attenuation correction in simultaneous MR/PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Blumhagen, Jan O., E-mail: janole.blumhagen@siemens.com; Ladebeck, Ralf; Fenchel, Matthias [Magnetic Resonance, Siemens AG Healthcare Sector, Erlangen 91052 (Germany); Braun, Harald; Quick, Harald H. [Institute of Medical Physics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen 91052 (Germany); Faul, David [Siemens Medical Solutions, New York, New York 10015 (United States); Scheffler, Klaus [MRC Department, Max Planck Institute for Biological Cybernetics, Tübingen 72076, Germany and Department of Biomedical Magnetic Resonance, University Hospital Tübingen, Tübingen 72076 (Germany)

    2014-02-15

    Purpose: In quantitative PET imaging, it is critical to accurately measure and compensate for the attenuation of the photons absorbed in the tissue. While in PET/CT the linear attenuation coefficients can be easily determined from a low-dose CT-based transmission scan, in whole-body MR/PET the computation of the linear attenuation coefficients is based on the MR data. However, a constraint of the MR-based attenuation correction (AC) is the MR-inherent field-of-view (FoV) limitation due to static magnetic field (B{sub 0}) inhomogeneities and gradient nonlinearities. Therefore, the MR-based human AC map may be truncated or geometrically distorted toward the edges of the FoV and, consequently, the PET reconstruction with MR-based AC may be biased. This is especially of impact laterally where the patient arms rest beside the body and are not fully considered. Methods: A method is proposed to extend the MR FoV by determining an optimal readout gradient field which locally compensates B{sub 0} inhomogeneities and gradient nonlinearities. This technique was used to reduce truncation in AC maps of 12 patients, and the impact on the PET quantification was analyzed and compared to truncated data without applying the FoV extension and additionally to an established approach of PET-based FoV extension. Results: The truncation artifacts in the MR-based AC maps were successfully reduced in all patients, and the mean body volume was thereby increased by 5.4%. In some cases large patient-dependent changes in SUV of up to 30% were observed in individual lesions when compared to the standard truncated attenuation map. Conclusions: The proposed technique successfully extends the MR FoV in MR-based attenuation correction and shows an improvement of PET quantification in whole-body MR/PET hybrid imaging. In comparison to the PET-based completion of the truncated body contour, the proposed method is also applicable to specialized PET tracers with little uptake in the arms and might

  14. Impact of rotavirus vaccination on hospitalizations for rotavirus diarrhea: the IVANHOE study.

    Science.gov (United States)

    Gagneur, Arnaud; Nowak, Emmanuel; Lemaitre, Thomas; Segura, Jean-Francois; Delaperrière, Nadège; Abalea, Lydie; Poulhazan, Elise; Jossens, Anne; Auzanneau, Lucie; Tran, Adissa; Payan, Christopher; Jay, Nadine; de Parscau, Loic; Oger, Emmanuel

    2011-05-12

    The aim of the IVANHOE study was to determine the real-world impact of the rotavirus vaccine, controlling for epidemic-to-epidemic variation in disease burden. A population-based prospective cohort study was conducted in Brest City and 7 suburban districts (CUB area), North-western Brittany, France (210,000 inhabitants; 5500 births per year). The vaccination program started in May 2007 for a 2-year period for all infants born in the Brest birth zone through pediatricians, public outpatient clinics and general practitioners. To determine vaccine impact we monitored trends in hospitalizations for rotavirus-specific diarrhea using an active hospital-based surveillance system initiated 5 years before vaccine introduction. The number of hospitalizations for rotavirus-specific diarrhea during the 2008/2009 epidemic in infants less than 2 years of age whose parents lived within the CUB area was modelled as a function of (1) the number of hospitalizations in infants 2-5 years of age to control for epidemic-to-epidemic variation and (2) vaccine introduction. A total of 4684 infants received at least one dose. Of these, 2635 lived within the CUB area. Vaccine coverage for a complete schedule in the CUB area was 47.1%. Poisson modelling revealed a reduction by a factor of 2.04 (1.56-2.66) in the number of hospitalizations during the last epidemic season (2008/2009), the number of observed cases being equal to 30, against an expected number of 61. Relative risk reduction for hospitalizations for rotavirus diarrhea was 98% (95% CI: 83-100%). We observed a noticeable impact of vaccination on rotavirus diarrhea hospitalizations within 2 years of vaccine introduction integrating for the first time rotavirus epidemics variation. The trial is registered with ClinicalTrials.gov, number, NCT00740935.

  15. A new technique to characterize CT scanner bow-tie filter attenuation and applications in human cadaver dosimetry simulations

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xinhua; Shi, Jim Q.; Zhang, Da; Singh, Sarabjeet; Padole, Atul; Otrakji, Alexi; Kalra, Mannudeep K.; Liu, Bob, E-mail: bliu7@mgh.harvard.edu [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Xu, X. George [Nuclear Engineering Program, Rensselaer Polytechnic Institute, Troy, New York 12180 (United States)

    2015-11-15

    Purpose: To present a noninvasive technique for directly measuring the CT bow-tie filter attenuation with a linear array x-ray detector. Methods: A scintillator based x-ray detector of 384 pixels, 307 mm active length, and fast data acquisition (model X-Scan 0.8c4-307, Detection Technology, FI-91100 Ii, Finland) was used to simultaneously detect radiation levels across a scan field-of-view. The sampling time was as short as 0.24 ms. To measure the body bow-tie attenuation on a GE Lightspeed Pro 16 CT scanner, the x-ray tube was parked at the 12 o’clock position, and the detector was centered in the scan field at the isocenter height. Two radiation exposures were made with and without the bow-tie in the beam path. Each readout signal was corrected for the detector background offset and signal-level related nonlinear gain, and the ratio of the two exposures gave the bow-tie attenuation. The results were used in the GEANT4 based simulations of the point doses measured using six thimble chambers placed in a human cadaver with abdomen/pelvis CT scans at 100 or 120 kV, helical pitch at 1.375, constant or variable tube current, and distinct x-ray tube starting angles. Results: Absolute attenuation was measured with the body bow-tie scanned at 80–140 kV. For 24 doses measured in six organs of the cadaver, the median or maximum difference between the simulation results and the measurements on the CT scanner was 8.9% or 25.9%, respectively. Conclusions: The described method allows fast and accurate bow-tie filter characterization.

  16. Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.

    Science.gov (United States)

    Wells, Adam J; Hoffman, Jay R; Gonzalez, Adam M; Stout, Jeffrey R; Fragala, Maren S; Mangine, Gerald T; McCormack, William P; Jajtner, Adam R; Townsend, Jeremy R; Robinson, Edward H

    2013-06-01

    Phosphatidylserine (PS) may attenuate the adverse effects of physical fatigue. Therefore, we investigated the effects of a multi-ingredient supplement containing 400 mg/d PS and 100 mg/d caffeine (supplement [SUP]) for 2 weeks on measures of cognitive function (CF), reaction time (RT), and mood (MD) following an acute exercise stress. It is hypothesized that PS will maintain preexercise CF and RT scores, while attenuating postexercise fatigue. Participants completed 2 acute bouts of resistance exercise (T1 and T2) separated by 2-week ingestion of SUP or control (CON). Outcome measures were assessed pre- and postexercise. When collapsed across groups, a significant decrease in RT performance was seen in the 60-second reaction drill from pre- to postexercise at T1. All other RT tests were similar from pre- to postexercise at T1. Reaction time was not significantly changed by PS. When collapsed across groups, a significant increase in performance of the serial subtraction test was seen. A significant increase (8.9% and 7.1%) in the number of correct answers and a significant decrease (8.0% and 7.5%) in time to answer were seen from pre- to postworkout at T1 and T2, respectively. A significant increase in total MD score from pre- to postworkout was observed for CON but not for PS at T2. Phosphatidylserine significantly attenuated pre- to postexercise perception of fatigue compared to CON. Ingestion of SUP for 14 days appears to attenuate postexercise MD scores and perception of fatigue, but does not affect CF or RT, in recreationally trained individuals.

  17. Development of improved vaccine cell lines against rotavirus

    Science.gov (United States)

    Wu, Weilin; Orr-Burks, Nichole; Karpilow, Jon; Tripp, Ralph A.

    2017-01-01

    Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine. PMID:28248921

  18. Rotavirus epidemiology in San Luis Potosí, Mexico.

    Science.gov (United States)

    Noyola, Daniel E; Herrera, Ismael F

    2005-07-01

    The epidemiology of rotavirus infections was investigated in San Luis Potosí, Mexico during a 6-year period. In each of the study years, the epidemic period started in October or November; peak activity was detected between December and February, and the end of the epidemic occurred in March or April. Rotavirus infections show a consistent temporal pattern in our community.

  19. Cost Effectiveness of Infant Vaccination for Rotavirus in Canada

    Directory of Open Access Journals (Sweden)

    Doug Coyle

    2012-01-01

    Full Text Available INTRODUCTION: Rotavirus is the main cause of gastroenteritis in Canadian children younger than five years of age, resulting in significant morbidity and cost. The present study provides evidence on the cost effectiveness of two alternative rotavirus vaccinations (RotaTeq [Merck Frosst Canada Ltd, Canada] and Rotarix [GlaxoSmithKline, Canada] available in Canada.

  20. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study

    OpenAIRE

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-01-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequen...

  1. A (p)ppGpp-null mutant of Haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes.

    Science.gov (United States)

    Holley, Concerta; Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2014-08-01

    (p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species. Haemophilus ducreyi, the causative agent of chancroid, has homologs of both relA and spoT, which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We constructed relA and relA spoT deletion mutants to assess the contribution of (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in trans. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of lspB, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In E. coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi double mutant expressed higher transcript levels of dksA than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.

  2. An update of "Cost-effectiveness of rotavirus vaccination in the Netherlands : the results of a Consensus Rotavirus Vaccine model"

    NARCIS (Netherlands)

    Tu, Hong Anh T.; Rozenbaum, Mark H.; de Boer, Pieter T.; Noort, Albert C.; Postma, Maarten J.

    2013-01-01

    Background: To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011.Methods: The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated.Results: When updated data was used, rou

  3. A gastrointestinal rotavirus infection mouse model for immune modulation studies

    Directory of Open Access Journals (Sweden)

    van Amerongen Geert

    2011-03-01

    Full Text Available Abstract Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R® could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection. Methods BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH responses were also measured. Results Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected. Conclusions Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.

  4. Diarrheal Diseases Hospitalization in Yemen before and after Rotavirus Vaccination

    Directory of Open Access Journals (Sweden)

    Mohammed Amood AL-Kamarany

    2016-01-01

    Full Text Available The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™ ® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA. The incidence of rotavirus hospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P[4] (55.0%, followed by G1P[8] (15.0%, while in postvaccination period G1P[8] (31% was the predominant genotype, followed by G9P[8] (27.5%. In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains.

  5. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes.

    Science.gov (United States)

    Song, Xiuzu; Xu, Aie; Pan, Wei; Wallin, Brittany; Kivlin, Rebecca; Lu, Shan; Cao, Cong; Bi, Zhigang; Wan, Yinsheng

    2008-08-01

    The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

  6. Household transmission of rotavirus in a community with rotavirus vaccination in Quininde, Ecuador.

    Directory of Open Access Journals (Sweden)

    Ben Lopman

    Full Text Available We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era.Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics and susceptibility (household-contact characteristics.Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR were 55%, 8% and 2%, (n = 137, 130, 137 respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was <18 months and had vomiting, with household contact <10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission.Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case and susceptibility (young age/sharing a room/being a sibling of the index case. Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees.

  7. [Seasonality of rotavirus infection in Venezuela: relationship between monthly rotavirus incidence and rainfall rates].

    Science.gov (United States)

    González Chávez, Rosabel

    2015-09-01

    In general, it has been reported that rotavirus infection was detected year round in tropical countries. However, studies in Venezuela and Brazil suggest a seasonal behavior of the infection. On the other hand, some studies link infection with climatic variables such as rainfall. This study analyzes the pattern of behavior of the rotavirus infection in Carabobo-Venezuela (2001-2005), associates the seasonality of the infection with rainfall, and according to the seasonal pattern, estimates the age of greatest risk for infection. The analysis of the rotavirus temporal series and accumulated precipitation was performed with the software SPSS. The infection showed two periods: high incidence (November-April) and low incidence (May-October). Accumulated precipitation presents an opposite behavior. The highest frequency of events (73.8% 573/779) for those born in the period with a low incidence of the virus was recorded at an earlier age (mean age 6.5 +/- 2.0 months) when compared with those born in the station of high incidence (63.5% 568/870, mean age 11.7 +/- 2.2 months). Seasonality of the infection and the inverse relationship between virus incidence and rainfall was demonstrated. In addition, it was found that the period of birth determines the age and risk of infection. This information generated during the preaccine period will be helpful to measure the impact of the vaccine against the rotavirus.

  8. Co-expression of anti-rotavirus proteins (llama VHH antibody fragments in Lactobacillus: development and functionality of vectors containing two expression cassettes in tandem.

    Directory of Open Access Journals (Sweden)

    Gökçe Günaydın

    Full Text Available Rotavirus is an important pediatric pathogen, causing severe diarrhea and being associated with a high mortality rate causing approximately 500 000 deaths annually worldwide. Even though some vaccines are currently available, their efficacy is lower in the developing world, as compared to developed countries. Therefore, alternative or complementary treatment options are needed in the developing countries where the disease burden is the largest. The effect of Lactobacillus in promoting health and its use as a vehicle for delivery of protein and antibody fragments was previously shown. In this study, we have developed co-expression vectors enabling Lactobacillus paracasei BL23 to produce two VHH fragments against rotavirus (referred to as anti-rotavirus proteins 1 and 3, ARP1 and ARP3 as secreted and/or surface displayed products. ARP1 and ARP3 fragments were successfully co-expressed as shown by Western blot and flow cytometry. In addition, engineered Lactobacillus produced VHH antibody fragments were shown to bind to a broad range of rotavirus serotypes (including the human rotavirus strains 69M, Va70, F45, DS1, Wa and ST3 and simian rotavirus strains including RRV and SA11, by flow cytometry and ELISA. Hereby, we have demonstrated for the first time that when RRV was captured by one VHH displayed on the surface of co-expressor Lactobacillus, targeting other epitope was possible with another VHH secreted from the same bacterium. Therefore, Lactobacillus producing two VHH antibody fragments may potentially serve as treatment against rotavirus with a reduced risk of development of escape mutants. This co-expression and delivery platform can also be used for delivery of VHH fragments against a variety of mucosal pathogens or production of other therapeutic molecules.

  9. A DltA mutant of Haemophilus ducreyi Is partially attenuated in its ability to cause pustules in human volunteers.

    Science.gov (United States)

    Janowicz, Diane; Leduc, Isabelle; Fortney, Kate R; Katz, Barry P; Elkins, Christopher; Spinola, Stanley M

    2006-02-01

    Haemophilus ducreyi produces two outer membrane proteins, called DltA (H. ducreyi lectin A) and DsrA (H. ducreyi serum resistance A), that contribute to the ability of the organism to evade complement-mediated serum killing. In contrast to their isogenic parent strain, 35000HP, the DsrA mutant FX517 exhibits 0% survival in 50% normal human serum and the DltA mutant FX533 exhibits 23% survival. Compared to 35000HP, FX517 does not cause pustule formation in human volunteers. To test whether DltA was required for virulence in humans, seven volunteers were experimentally infected with 35000HP and FX533. Four subjects were inoculated with fixed doses of 35000HP (101 CFU or 130 CFU) at three sites on one arm and escalating doses of FX533 (range, 46 CFU to 915 CFU) at three sites on the other arm. Pustules only developed at mutant-injected sites at doses nearly twofold higher than that of the parent, suggesting that FX533 was partially attenuated. Three subjects were inoculated with similar doses of the parent (67 CFU) and mutant (104 CFU) at three sites. Pustules formed at five of nine parent sites and one of nine mutant sites. Overall, the papule and pustule formation rates for 35000HP and FX533 were similar for the trial. However, for the five subjects who received similar doses of the parent and mutant, pustules developed at 7 of 15 sites (46.7%; 95% confidence interval [CI], 16.9% to 76.5%) inoculated with the parent and at 1 of 15 (6.7%; 95% CI, 0.1% to 18.4%) sites inoculated with the mutant (P = 0.043). We concluded that the DltA mutant was attenuated in its ability to cause disease at doses similar to that of the parent.

  10. Incidence and cost of rotavirus hospitalizations in Denmark

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Nielsen, Nete Munk; Wohlfahrt, Jan;

    2007-01-01

    In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea-associated hospitalizat......In anticipation of licensure and introduction of rotavirus vaccine into the western market, we used modeling of national hospital registry data to determine the incidence and direct medical costs of annual rotavirus-associated admissions over >11 years in Denmark. Diarrhea......-associated hospitalizations coded as nonspecified viral or presumed infectious have demonstrated a marked winter peak similar to that of rotavirus-associated hospitalizations, which suggests that the registered rotavirus-coded admissions are grossly underestimated. We therefore obtained more realistic estimates by 2...... different models, which indicated 2.4 and 2.5 (for children rotavirus-associated admissions per 1,000 children per year, respectively. These admissions amount to associated direct medical costs of US $1.7-1.8 million per year. Using 2 simple...

  11. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    Science.gov (United States)

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.

  12. Lycopene attenuates Aβ1-42 secretion and its toxicity in human cell and Caenorhabditis elegans models of Alzheimer disease.

    Science.gov (United States)

    Chen, Wei; Mao, Liuqun; Xing, Huanhuan; Xu, Lei; Fu, Xiang; Huang, Liyingzi; Huang, Dongling; Pu, Zhijun; Li, Qinghua

    2015-11-03

    Growing evidence suggests concentration of lycopene was reduced in plasma of patients with Alzheimer disease (AD). Lycopene, a member of the carotenoid family, has been identified as an antioxidant to attenuate oxidative damage and has neuroprotective role in several AD models. However, whether lycopene is involved in the pathogenesis of AD and molecular underpinnings are elusive. In this study, we found that lycopene can significantly delay paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101. Lycopene treatment reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found lycopene can down-regulate expression level of β-amyloid precursor protein(APP) in APPsw cells. Moreover, lycopene treatment can not change endogenous reactive oxygen species level and apoptosis in APPsw cells. However, lycopene treatment protected against H2O2-induced oxidative stress and copper-induced damage in APPsw cells. Collectively, our data support that elevated lycopene contributes to the lower pathogenesis of AD. Our findings suggest that increasing lycopene in neurons may be a novel approach to attenuate onset and development of AD.

  13. The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends.

    Science.gov (United States)

    Polheber, John P; Matchock, Robert L

    2014-10-01

    Limited research has addressed how social support in the form of a pet can affect both sympathetic and hypothalamic-pituitary-adrenal reactivity in response to a psychological challenge. The present study examined the effects of social support on salivary cortisol and heart rate (HR). Forty-eight participants were randomly assigned to three different conditions (human friend, novel dog, or control). All participants completed the Trier Social Stress Test and provided cortisol, HR, and State-Trait Anxiety Inventory measures. For participants paired with a dog, overall cortisol levels were attenuated throughout the experimental procedure, and HR was attenuated during the Trier Social Stress Test. For all groups, state anxiety increased after the Trier Social Stress Test, and HR during the Trier Social Stress Test was a predictor of cortisol. These results suggest that short-term exposure to a novel dog in an unfamiliar setting can be beneficial. They also suggest a possible mechanism for the beneficial effect associated with affiliation with pets.

  14. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study.

    Science.gov (United States)

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-10-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

  15. Avian rotavirus enteritis - an updated review.

    Science.gov (United States)

    Dhama, Kuldeep; Saminathan, Mani; Karthik, Kumaragurubaran; Tiwari, Ruchi; Shabbir, Muhammad Zubair; Kumar, Naveen; Malik, Yashpal Singh; Singh, Raj Kumar

    2015-01-01

    Rotaviruses (RVs) are among the leading causes of enteritis and diarrhea in a number of mammalian and avian species, and impose colossal loss to livestock and poultry industry globally. Subsequent to detection of rotavirus in mammalian hosts in 1973, avian rotavirus (AvRV) was first reported in turkey poults in USA during 1977 and since then RVs of group A (RVA), D (RVD), F (RVF) and G (RVG) have been identified around the globe. Besides RVA, other AvRV groups (RVD, RVF and RVG) may also contribute to disease. However, their significance has yet to be unraveled. Under field conditions, co-infection of AvRVs occurs with other infectious agents such as astroviruses, enteroviruses, reoviruses, paramyxovirus, adenovirus, Salmonella, Escherichia coli, cryptosporidium and Eimeria species prospering severity of disease outcome. Birds surviving to RV disease predominantly succumb to secondary bacterial infections, mostly E. coli and Salmonella spp. Recent developments in molecular tools including state-of-the-art diagnostics and vaccine development have led to advances in our understanding towards AvRVs. Development of new generation vaccines using immunogenic antigens of AvRV has to be explored and given due importance. Till now, no effective vaccines are available. Although specific as well as sensitive approaches are available to identify and characterize AvRVs, there is still need to have point-of-care detection assays to review disease burden, contemplate new directions for adopting vaccination and follow improvements in public health measures. This review discusses AvRVs, their epidemiology, pathology and pathogenesis, immunity, recent trends in diagnostics, vaccines, therapeutics as well as appropriate prevention and control strategies.

  16. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  17. Multi-frequency characterization of the speed of sound and attenuation coefficient for longitudinal transmission of freshly excised human skulls

    Science.gov (United States)

    Pichardo, Samuel; Sin, Vivian W.; Hynynen, Kullervo

    2011-01-01

    For medical applications of ultrasound inside the brain, it is necessary to understand the relationship between the apparent density of skull bone and its corresponding speed of sound and attenuation coefficient. Although there have been previous studies exploring this phenomenon, there is still a need to extend the measurements to cover more of the clinically relevant frequency range. The results of measurements of the longitudinal speed of sound and attenuation coefficient are presented for specimens of human calvaria. The study was performed for the frequencies of 0.27, 0.836, 1.402, 1.965 and 2.525 MHz. Specimens were obtained from fresh cadavers through a protocol with the Division of Anatomy of the University of Toronto. The protocol was approved by the Research Ethics Board of Sunnybrook Health Sciences Centre. The specimens were mounted in polycarbonate supports that were marked for stereoscopic positioning. Computer tomography (CT) scans of the skulls mounted on their supports were performed, and a three-dimensional skull surface was reconstructed. This surface was used to guide a positioning system to ensure the normal sound incidence of an acoustic signal. This signal was produced by a focused device with a diameter of 5 cm and a focal length of 10 cm. Measurements of delay in time of flight were carried out using a needle hydrophone. Measurements of effective transmitted energy were carried out using a radiation force method with a 10 µg resolution scale. Preliminary functions of speed of sound and attenuation coefficient, both of which are related to apparent density, were established using a multi-layer propagation model that takes into account speed of sound, density and thickness of the layer. An optimization process was executed from a large set of random functions and the best functions were chosen for those ones that closest reproduced the experimental observations. The final functions were obtained after a second pass of the optimization

  18. Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

    Science.gov (United States)

    Freiesleben de Blasio, Birgitte; Flem, Elmira; Latipov, Renat; Kuatbaeva, Ajnagul; Kristiansen, Ivar Sønbø

    2014-01-01

    The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children vaccine cost at vaccination program costs would be entirely offset. To further evaluate efficacy of a vaccine program, benefits of indirect protection conferred by vaccination warrant further study.

  19. Gracilaria bursa-pastoris (Gmelin) Silva extract attenuates ultraviolet B radiation-induced oxidative stress in human keratinocytes.

    Science.gov (United States)

    Piao, M J; Kim, K C; Zheng, J; Yao, C W; Cha, J W; Kang, H K; Yoo, E S; Koh, Y S; Ko, M H; Lee, N H; Hyun, Jin Won

    2014-01-01

    The purpose of this study was to assess the protective effects of an ethanol extract derived from the red alga Gracilaria bursa-pastoris (Gmelin) Silva (GBE) on ultraviolet B (UVB)-irradiated human HaCaT keratinocytes. GBE exhibited scavenging activity against intracellular reactive oxygen species that were induced by either hydrogen peroxide or UVB radiation. In addition, both the superoxide anion and the hydroxyl radical were scavenged by GBE in cell-free systems. GBE absorbed light in the UVB range (280-320 nm) of the electromagnetic spectrum and lessened the extent of UVB-induced oxidative damage to cellular lipids, proteins, and DNA. Finally, GBE-treated keratinocytes showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies. These results suggest that GBE exerts cytoprotective actions against UVB-stimulated oxidative stress by scavenging ROS and absorbing UVB rays, thereby attenuating injury to cellular constituents and preventing cell death.

  20. Development of a human live attenuated West Nile infectious DNA vaccine: conceptual design of the vaccine candidate.

    Science.gov (United States)

    Yamshchikov, Vladimir

    2015-10-01

    West Nile virus has become an important epidemiological problem attracting significant attention of health authorities, mass media, and the public. Although there are promising advancements toward addressing the vaccine need, the perspectives of the commercial availability of the vaccine remain uncertain. To a large extent this is due to lack of a sustained interest for further commercial development of the vaccines already undergoing the preclinical and clinical development, and a predicted insignificant cost effectiveness of mass vaccination. There is a need for a safe, efficacious and cost effective vaccine, which can improve the feasibility of a targeted vaccination program. In the present report, we summarize the background, the rationale, and the choice of the development pathway that we selected for the design of a live attenuated human West Nile vaccine in a novel infectious DNA format.

  1. Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Birk, Jesper Bratz; Klein, Ditte Kjærsgaard

    2006-01-01

    5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK...... activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo...... drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P

  2. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-02-01

    The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

  3. Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

    Science.gov (United States)

    Bart, Nicole K; Curtis, M Kate; Cheng, Hung-Yuan; Hungerford, Sara L; McLaren, Ross; Petousi, Nayia; Dorrington, Keith L; Robbins, Peter A

    2016-08-01

    Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.

  4. Structural correlates of rotavirus cell entry.

    Directory of Open Access Journals (Sweden)

    Aliaa H Abdelhakim

    2014-09-01

    Full Text Available Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex--for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼ 700 Å inner capsid particle ("double-layered particle", DLP. We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼ 10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.

  5. The rotavirus experience in Mexico: discovery to control.

    Science.gov (United States)

    Patel, Manish M; Parashar, Umesh D; Santosham, Mathuram; Richardson, Vesta

    2013-02-01

    The recent introduction of a rotavirus vaccine program in Mexico to control rotavirus disease, a common killer of children worldwide, has dramatically reduced the number of Mexican children dying and being hospitalized because of diarrhea. The successful introduction of a rotavirus vaccine program was preceded by several decades of focused research efforts to document the burden of disease and to generate the knowledge base to develop and deploy a vaccine. The postlicensure experience from Mexico demonstrates that evaluating the impact and safety of the vaccination program is vitally necessary for sustaining it. All in all, the immensely successful Mexico experience with control of rotavirus disease, if copied, could yield tremendously favorable results for children and parents worldwide.

  6. Human thioredoxin exerts cardioprotective effect and attenuates reperfusion injury in rats partially via inhibiting apoptosis

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-wei; TENG Zong-yan; JIANG Li-hong; FAN Ying; ZHANG Yu-hua; LI Xiu-rong; ZHANG Yi-na

    2008-01-01

    Background Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.Methods Purified human thioredoxin was injected into adult Wister rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondia by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling ('rUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.Results Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P<0.01), notable reduction of myocyte apoptosis (P <0.01), lower systemic oxidative stress level (P <0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P<0.05),and inhibited the activity of caspase-9 (P <0.05) and caspase-3 (P <0.01 in mRNA and P <0.05 at protein level).Meanwhile, human thioredoxin markedly increased bcl-2 expression (P <0.05).Conclusions These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.

  7. Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation.

    Science.gov (United States)

    Newburg, David S; He, Yingying

    2015-12-01

    Glycans of the intestinal mucosa and oligosaccharides of human milk influence the early colonization of the infant gut and establishment of mucosal homeostasis, and differences in colonization of the gut influence the ontogeny of glycans on the surface of the intestinal mucosa, proinflammatory signaling, homeostasis, and resilience to insult. This interkingdom reciprocal interaction is typical of a mutualistic symbiotic relationship. The period in which the infant gut most needs protection from hypersensitive inflammation overlaps with the recommended period of exclusive nursing; electively substituting artificial formula that lacks human milk protective glycans seems ill advised, especially for premature infants.

  8. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M;

    2015-01-01

    CA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline...... neuroprotective effect by enhancing dCA in patients with early sepsis....

  9. THE IMPROVEMENT OF RT-PCR TECHNIQUE ON DETECTING ROTAVIRUS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To establish a speed and effective method to detect rotavirus. Methods Using ELISA and one step RT-PCR to detect 196 clinic samples from Xi'an area. Results Compared with ELISA method, one step RT PCR was more sensitive and specific (P <0.05). Conclusion One step RT-PCR is a simple, speed, sensitive and spe cific method for clinic and epidemic studies of rotavirus.

  10. Unexpectedly high burden of rotavirus gastroenteritis in very young infants

    Directory of Open Access Journals (Sweden)

    Reilly Megan

    2010-06-01

    Full Text Available Abstract Background The highest incidence of rotavirus gastroenteritis has generally been reported in children 6-24 months of age. Young infants are thought to be partially protected by maternal antibodies acquired transplacentally or via breast milk. The purpose of our study was to assess the age distribution of children with confirmed community-acquired rotavirus gastroenteritis presenting to an urban referral hospital. Methods Children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by ELISA (followed by genotyping if ELISA-positive since the 1994-95 epidemic season. Results Over the last 12 rotavirus seasons prior to the introduction of the pentavalent rotavirus vaccine in 2006, stool specimens from 1646 patients tested positive for community-acquired rotavirus infection. Gender or age was not recorded in 6 and 5 cases, respectively. Overall, 58% of the cases occurred in boys. G1 was the predominant VP7 serotype, accounting for 72% of cases. The median (IQR age was 11 (5-21 months. A total of 790 (48% cases occurred in children outside the commonly quoted peak age range, with 27% in infants 24 months of age. A total of 220 (13% cases occurred during the first 3 months of life, and the highest number of episodes per month of age [97 (6%] was observed during the second month of life. Conclusions The incidence of community-acquired rotavirus gastroenteritis monitored over 12 seasons in the prevaccine era at a major university hospital was nearly constant for each month of age during the first year of life, revealing an unexpectedly high incidence of symptomatic rotavirus disease in infants

  11. Haze is an important medium for the spread of rotavirus.

    Science.gov (United States)

    Ye, Qing; Fu, Jun-Feng; Mao, Jian-Hua; Shen, Hong-Qiang; Chen, Xue-Jun; Shao, Wen-Xia; Shang, Shi-Qiang; Wu, Yi-Feng

    2016-09-01

    This study investigated whether the rotavirus infection rate in children is associated with temperature and air pollutants in Hangzhou, China. This study applied a distributed lag non-linear model (DLNM) to assess the effects of daily meteorological data and air pollutants on the rotavirus positive rate among outpatient children. There was a negative correlation between temperature and the rotavirus infection rate. The impact of temperature on the detection rate of rotavirus presented an evident lag effect, the temperature change shows the greatest impact on the detection rate of rotavirus approximate at lag one day, and the maximum relative risk (RR) was approximately 1.3. In 2015, the maximum cumulative RR due to the cumulative effect caused by the temperature drop was 2.5. Particulate matter (PM) 2.5 and PM10 were the primary air pollutants in Hangzhou. The highest RR of rotavirus infection occurred at lag 1-1.5 days after the increase in the concentration of these pollutants, and the RR increased gradually with the increase in concentration. Based on the average concentrations of PM2.5 of 53.9 μg/m(3) and PM10 of 80.6 μg/m(3) in Hangzhou in 2015, the cumulative RR caused by the cumulative effect was 2.5 and 2.2, respectively. The current study suggests that temperature is an important factor impacting the rotavirus infection rate of children in Hangzhou. Air pollutants significantly increased the risk of rotavirus infection, and dosage, lag and cumulative effects were observed.

  12. Change in incidence of clinic visits for all-cause and rotavirus gastroenteritis in young children following the introduction of universal rotavirus vaccination in Israel.

    Science.gov (United States)

    Muhsen, Khitam; Chodick, Gabriel; Goren, Sophy; Anis, Emilia; Ziv-Baran, Tomer; Shalev, Varda; Cohen, Dani

    2015-01-01

    Both rotavirus vaccines RotaTeq and Rotarix were efficacious against severe rotavirus gastroenteritis in clinical trials; yet real-world data on the effect of rotavirus vaccines on mild to moderate disease are limited. We used a large computerised database of Maccabi Health Services Health Maintenance Organisation (HMO), the second largest HMO in Israel covering 25% of the Israeli population, to compare the incidence of acute gastroenteritis (AGE) clinic visits in community settings (n=302,445) before (2005-10) and after (2011-13) the introduction of universal rotavirus immunisation in Israel. We retrieved laboratory results of rotavirus antigen tests (n=18,133) and using a weighted analysis, we estimated the impact of rotavirus immunisation on the disease burden of rotavirus AGE clinic visits. Following the introduction of universal rotavirus immunisation, the typical winter peaks of rotavirus AGE were substantially lower and significant reductions of 14.8% (95% confidence interval (CI): 13.5-16.1) in all-cause AGE clinic visits and of 59.7% (95% CI: 59.8-62.6) in rotavirus AGE clinic visits were observed. The decrease was observed in all age groups, but it was greater in children aged 0 to 23 months than those aged 24 to 59 months. Continued rotavirus laboratory surveillance is warranted to monitor the sustainability of these changes.

  13. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hong [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China); Wu, Xinyi, E-mail: xywu8868@163.com [Department of Ophthalmology, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-{beta}. Black-Right-Pointing-Pointer Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. Black-Right-Pointing-Pointer Hypoxia inhibits Acanthamoeba-induced the activation of NF-{kappa}B and ERK1/2 in HCECs. Black-Right-Pointing-Pointer Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. Black-Right-Pointing-Pointer LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cells has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-{beta} (IFN-{beta}) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-{beta}. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-{kappa}B and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response gene (88

  14. Tamarind seed coat extract restores reactive oxygen species through attenuation of glutathione level and antioxidant enzyme expression in human skin fibroblasts in response to oxidative stress

    Directory of Open Access Journals (Sweden)

    Oranuch Nakchat

    2014-05-01

    Conclusions: TSCE exhibited antioxidant activities by scavenging ROS, attenuating GSH level that could protect human skin fibroblast cells from oxidative stress. Our results highlight the antioxidant mechanism of tamarind seed coat through an antioxidant enzyme system, the extract potentially benefits for health food and cosmeceutical application of tamarind seed coat.

  15. Scope for rotavirus vaccination in India: revisiting the scientific evidence.

    Science.gov (United States)

    Neogi, Sutapa Bandyopadhyay; Hasan, Habib; Sheikh, Kabir; Zodpey, Sanjay

    2011-10-01

    Rotavirus vaccines have been developed to prevent deaths resulting from severe diarrhea of rotavirus origin. The use of vaccines as an intervention at scale to prevent and control the burden of rotavirus diarrhea is supported by the argument that prevailing public health measures such as hygiene and sanitation, breast feeding and use of ORS have failed to prevent severe dehydration resulting from diarrhea. The article reviews the existing evidence on the rationale of using rotavirus vaccine as against the feasibility of scaling it up in developing countries like India. The vaccines currently available may not cover the strains circulating in Indian population. The diversity of Rotavirus infection in the country is tremendous and since the safety, immunogenicity and efficacy data has not been collected for India, there is first a need to conduct studies to measure the extent of protection and cross-protection provided by the available vaccines for local strains, before venturing into Rotavirus vaccination program. The potential benefits of immunization have to be first vetted against the risks involved by the policymakers and other stakeholders.

  16. Genotyping of Rotavirus by Using RT-PCR Methods

    Directory of Open Access Journals (Sweden)

    Hera Nirwati

    2015-11-01

    Full Text Available There is a great diversity of rotavirus genotypes circulating worldwide, with dominant genotypes changing from year to year. Rotavirus genotyping was performed by using reverse transcription PCR with type-specifi c-primers. Since rotavirus is a RNA virus that has high mutation rate, there was a possibility of technical diffi culty in genotyping due to mutation in the primer binding sites. During Indonesian rotavirus surveillance study 2006-2009, it was reported that 17% of samples subjected for G type and 21% of samplessubjected for P type were untypeable. The objective of this study was to identify genotypes of the samples that were untypeable previously using RT-PCR based on the method described by Das et al. (1994 and Gentsch et al. (1992. There were 30 samples subjected to G type and 61 samples subjected to P type to be re-typed using method described by Gouvea et al. (1990 and Simmond et al. (2008 for G and P typing, respectively. By using another set of primer, the genotype of all samples was identifi ed. This study highlights the importance of a constant reconsideration of primer sequences employed for the molecular typing of rotaviruses.Key words: rotavirus, G typing, P typing

  17. An improved method for concentrating rotavirus from water samples

    Directory of Open Access Journals (Sweden)

    Kittigul Leera

    2001-01-01

    Full Text Available A modified adsorption-elution method for the concentration of seeded rotavirus from water samples was used to determine various factors which affected the virus recovery. An enzyme-linked immunosorbent assay was used to detect the rotavirus antigen after concentration. Of the various eluents compared, 0.05M glycine, pH 11.5 gave the highest rotavirus antigen recovery using negatively charged membrane filtration whereas 2.9% tryptose phosphate broth containing 6% glycine; pH 9.0 was found to give the greatest elution efficiency when a positively charged membrane was used. Reconcentration of water samples by a speedVac concentrator showed significantly higher rotavirus recovery than polyethylene glycol precipitation through both negatively and positively charged filters (p-value 1,800 MPN/100 ml were observed but rotavirus was not detected in any sample. This study suggests that the speedVac reconcentration method gives the most efficient rotavirus recovery from water samples.

  18. Rotavirus activates lymphocytes from non-obese diabetic mice by triggering toll-like receptor 7 signaling and interferon production in plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Jessica A Pane

    2014-03-01

    Full Text Available It has been proposed that rotavirus infection promotes the progression of genetically-predisposed children to type 1 diabetes, a chronic autoimmune disease marked by infiltration of activated lymphocytes into pancreatic islets. Non-obese diabetic (NOD mice provide a model for the human disease. Infection of adult NOD mice with rhesus monkey rotavirus (RRV accelerates diabetes onset, without evidence of pancreatic infection. Rather, RRV spreads to the pancreatic and mesenteric lymph nodes where its association with antigen-presenting cells, including dendritic cells, induces cellular maturation. RRV infection increases levels of the class I major histocompatibility complex on B cells and proinflammatory cytokine expression by T cells at these sites. In autoimmunity-resistant mice and human mononuclear cells from blood, rotavirus-exposed plasmacytoid dendritic cells contribute to bystander polyclonal B cell activation through type I interferon expression. Here we tested the hypothesis that rotavirus induces bystander activation of lymphocytes from NOD mice by provoking dendritic cell activation and proinflammatory cytokine secretion. NOD mouse splenocytes were stimulated with rotavirus and assessed for activation by flow cytometry. This stimulation activated antigen-presenting cells and B cells independently of virus strain and replicative ability. Instead, activation depended on virus dose and was prevented by blockade of virus decapsidation, inhibition of endosomal acidification and interference with signaling through Toll-like receptor 7 and the type I interferon receptor. Plasmacytoid dendritic cells were more efficiently activated than conventional dendritic cells by RRV, and contributed to the activation of B and T cells, including islet-autoreactive CD8+ T cells. Thus, a double-stranded RNA virus can induce Toll-like receptor 7 signaling, resulting in lymphocyte activation. Our findings suggest that bystander activation mediated by type I

  19. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V.; Negi, Narender Singh; Dubey, Uma S.; Nakhasi, Hira L.; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  20. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P[4] rotavirus strain in Mexico.

    Science.gov (United States)

    Yen, Catherine; Figueroa, Jesùs Reyna; Uribe, Edgar Sánchez; Carmen-Hernández, Luz Del; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M; Richardson López-Collado, Vesta

    2011-09-01

    After the introduction of monovalent rotavirus vaccine (RV1) in Mexico in 2006-2007, diarrhea mortality and morbidity declined substantially among Mexican children under 5 years of age. In January 2010, surveillance identified the emergence of a novel G9P[4] rotavirus strain nationwide. We conducted a case-control study to assess the field effectiveness of RV1 against severe rotavirus gastroenteritis caused by this unusual strain and to determine whether the G9P[4] emergence was related to vaccine failure or failure to vaccinate. RV1 was 94% effective (95% confidence interval, 16%-100%) against G9P[4] rotavirus-related hospitalization, indicating that its emergence was likely unrelated to vaccine pressure.

  1. Rotavirus landscape in Africa-Towards prevention and control: A report of the 8th African rotavirus symposium, Livingstone, Zambia.

    Science.gov (United States)

    Rudd, Cheryl; Mwenda, Jason; Chilengi, Roma

    2015-06-26

    The 8th African Rotavirus Symposium was held in Livingstone, Zambia from the 12-13 June 2014. Over 130 delegates from 35 countries - 28 from African nations - participated in this symposium, which included scientists, clinicians, immunisation managers, public health officials, policymakers and vaccine manufacturers. The theme for the symposium was Rotavirus Landscape in Africa-Towards Prevention and Control. At the time of the symposium, a total of 21 African countries had introduced the rotavirus vaccine into their national immunisation schedules. This meeting was particularly timely and relevant to review early data on vaccine adoption and impact from these countries. The concluding panel discussion proposed several recommendations for areas of focus moving forward in rotavirus advocacy and research.

  2. Determination of cholesterol concentration in human milk samples using attenuated total reflectance Fourier transform infrared spectroscopy

    Science.gov (United States)

    Kamelska, A. M.; Pietrzak-Fiećko, R.; Bryl, K.

    2013-03-01

    Results of an inexpensive and rapid evaluation of the cholesterol concentration in human milk using ATR-FTIR techniques are presented. The FTIR spectrum of pure cholesterol was characterized and quantitatively estimated in the region between 2800 and 3200 cm-1. 125 samples at different stages of lactation were analyzed. There were no differences between the cholesterol concentrations in the samples of early (1-3 months), medium (4-6 months), and late (> 6 months) lactation stages ( p = 0.096968). The cholesterol concentration ranged from 4.30 to 21.77 mg/100 cm3. Such a broad range was due to the differences between the samples from different women ( p = 0.000184). The results indicate that ATR-FTIR has potential for rapid estimation of cholesterol concentration in human milk.

  3. Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts

    DEFF Research Database (Denmark)

    Sørensen, M G; Henriksen, K; Dziegiel, Morten Hanefeld;

    2006-01-01

    Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen......-receptor mediated effects on the bone-resorbing osteoclasts have also been proposed. Little information is available on whether estrogens modulate human osteoclastogenesis or merely inhibit the functional activity of osteoclasts. To clarify whether estrogens directly modulate osteoclastic activities human CD14...... not affect bone resorption or TRACP activity. We investigated expression of the estrogen receptors, using immunocytochemistry and Western blotting. We found that ER-alpha is expressed in osteoclast precursors, whereas ER- beta is expressed at all stages, indicating that the inhibitory effect of estrogen...

  4. How can a multilevel promotion of breastfeeding reduce the required budget for rotavirus vaccination in Indonesia?

    NARCIS (Netherlands)

    Zakiyah, N.; Suwantika, A.A.; Postma, M.J.

    2014-01-01

    Objectives: Breast milk is considered to give protection against rotavirus infection since it contains anti-rotavirus maternal antibodies and other nonspecific inhibitors. Multilevel promotion of breastfeeding is a complex intervention that modifies behavioral determinants through multiple levels of

  5. Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

    NARCIS (Netherlands)

    Rozenbaum, M.H.; Mangen, M.J.J.; Giaquinto, C.; Wilschut, J.C.; Hak, E.; Postma, M.J.

    2011-01-01

    Background: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showe

  6. Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

    NARCIS (Netherlands)

    Rozenbaum, M.H.; Mangen, M.J.; Giaquinto, C.; Wilschut, J.C.; Hak, E.; Postma, M.J.; Groot, R. de

    2011-01-01

    BACKGROUND: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showe

  7. Report of the 7th African Rotavirus Symposium, Cape Town, South Africa, 8th November 2012.

    Science.gov (United States)

    Seheri, L M; Mwenda, J M; Page, N

    2014-11-12

    The 7th African Rotavirus Symposium was held in Cape Town, South Africa, on the 8th November 2012 as a Satellite Symposium at the First International African Vaccinology Conference. Over 150 delegates participated in this symposium including scientists, clinicians, health officials, policymakers and vaccine manufacturers from across Africa. Key topics discussed included rotavirus surveillance, rotavirus vaccine introduction, post rotavirus vaccine impact analysis and intussusception data and surveillance in Africa. The symposium provided early rotavirus vaccine adopter countries in Africa (South Africa, Ghana and Botswana) an opportunity to share up-to-date information on vaccine introduction, and allowed colleagues to share experiences in establishing routine rotavirus surveillance (Tanzania, Niger and Rwanda). Overall, the symposium highlighted the high burden of rotavirus in Africa, and the need to continue to strengthen efforts in preventing rotavirus diarrhoea in Africa.

  8. Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function

    Institute of Scientific and Technical Information of China (English)

    Run-Ping Gao; David R Brigstock

    2009-01-01

    AIM: To determine the effect of hammerhead ribozyme targeting connective tissue growth factor (CCN2) on human hepatic stellate cell (HSC) function. METHODS: CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor (TGF)-b1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen Ⅰ, while protein levels of each molecule in cell lysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry. RESULTS: In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen Ⅰ, and an increase in produced and secreted CCN2 or extracellular collagen Ⅰ protein levels. pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen Ⅰ protein. Furthermore, the TGF-b1-induced increase in mRNA or protein for CCN2 or collagen Ⅰ was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase. CONCLUSION: Endogenous CCN2 is a mediator of basal or TGF-b1-induced collagen Ⅰ production in human HSCs and regulates entry of the cells into Sphase.

  9. Targeting of rotavirus VP6 to DEC-205 induces protection against the infection in mice.

    Science.gov (United States)

    Badillo-Godinez, O; Gutierrez-Xicotencatl, L; Plett-Torres, T; Pedroza-Saavedra, A; Gonzalez-Jaimes, A; Chihu-Amparan, L; Maldonado-Gama, M; Espino-Solis, G; Bonifaz, L C; Esquivel-Guadarrama, F

    2015-08-20

    Rotavirus (RV) is the primary etiologic agent of severe gastroenteritis in human infants. Although two attenuated RV-based vaccines have been licensed to be applied worldwide, they are not so effective in low-income countries, and the induced protection mechanisms have not been clearly established. Thus, it is important to develop new generation vaccines that induce long lasting heterotypic immunity. VP6 constitutes the middle layer protein of the RV virion. It is the most conserved protein and it is the target of protective T-cells; therefore, it is a potential candidate antigen for a new generation vaccine against the RV infection. We determined whether targeting the DEC-205 present in dendritic cells (DCs) with RV VP6 could induce protection at the intestinal level. VP6 was cross-linked to a monoclonal antibody (mAb) against murine DEC-205 (αDEC-205:VP6), and BALB/c mice were inoculated subcutaneously (s.c.) twice with the conjugated containing 1.5 μg of VP6 in the presence of polyinosinic-polycytidylic acid (Poly I:C) as adjuvant. As controls and following the same protocol, mice were immunized with ovalbumin (OVA) cross-linked to the mAb anti-DEC-205 (αDEC-205:OVA), VP6 cross-linked to a control isotype mAb (Isotype:VP6), 3 μg of VP6 alone, Poly I:C or PBS. Two weeks after the last inoculation, mice were orally challenged with a murine RV. Mice immunized with α-DEC-205:VP6 and VP6 alone presented similar levels of serum Abs to VP6 previous to the virus challenge. However, after the virus challenge, only α-DEC-205:VP6 induced up to a 45% IgA-independent protection. Memory T-helper (Th) cells from the spleen and the mesenteric lymph node (MLN) showed a Th1-type response upon antigen stimulation in vitro. These results show that when VP6 is administered parenterally targeting DEC-205, it can induce protection at the intestinal level at a very low dose, and this protection may be Th1-type cell dependent.

  10. Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport.

    Science.gov (United States)

    Mukherjee, Subhas; Tucker-Burden, Carol; Zhang, Changming; Moberg, Kenneth; Read, Renee; Hadjipanayis, Costas; Brat, Daniel J

    2016-04-15

    Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443-52. ©2016 AACR.

  11. Rotavirus genotypes in Belarus, 2008-2012.

    Science.gov (United States)

    Semeiko, Galina V; Yermalovich, Marina A; Poliakova, Nadezhda; Mijatovic-Rustempasic, Slavica; Kerin, Tara K; Wasley, Annemarie; Videbaek, Dovile; Gentsch, Jon R; Bowen, Michael D; Samoilovich, Elena O

    2014-12-01

    This study describes group A rotavirus (RVA) genotype prevalence in Belarus from 2008 to 2012. In 2008, data from 3 sites in Belarus (Brest, Mogilev, Minsk) indicated that G4P[8] was the predominant genotype. Data from Minsk (2008-2012) showed that G4P[8] was the predominant RVA genotype in all years except in 2011 when G3P[8] was most frequently detected. Other RVA genotypes common in Europe (G1P[8], G2P[4]) were detected each year of the study. This study reveals the dominance of genotype G4P[8] in Belarus and helps to establish the baseline genotype prevalence prior to RVA vaccine introduction in the country.

  12. E durans strain M4-5 isolated from human colonic flora attenuates intestinal inflammation

    DEFF Research Database (Denmark)

    Avram-Hananel, Liraz; Stock, Julia; Parlesak, Alexandr;

    2010-01-01

    effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.......PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model...... was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli-stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-α) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used...

  13. Antibodies against human BLyS and APRIL attenuate EAE development in marmoset monkeys.

    Science.gov (United States)

    Jagessar, S Anwar; Heijmans, Nicole; Oh, Luke; Bauer, Jan; Blezer, Erwin L A; Laman, Jon D; Migone, Thi-Sau; Devalaraja, Matt N; 't Hart, Bert A

    2012-09-01

    B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a common marmoset (Callithrix jacchus) model of experimental autoimmune encephalomyelitis (EAE). A MS-like disease was induced by immunization with recombinant human myelin/oligodendrocyte glycoprotein (rhMOG) in complete Freund's adjuvant. The results show that the anti-BLyS and anti-APRIL antibody cause significant depletion of circulating CD20+ B cells, but a small subset of CD20 + CD40(high) B cells was not depleted. Induction of CD20+ B cell depletion from lymph nodes was only observed in the anti-BLyS treated monkeys. Both antibodies had a significant inhibitory effect on disease development, but all monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were sacrificed with the same clinical signs as saline-treated monkeys, but nevertheless displayed significantly reduced spinal cord demyelination. This effect was not observed in the anti-APRIL treated monkeys. The two antibodies had a different effect on T cell subset activation and the profiles of ex vivo released cytokines. In conclusion, treatment with anti-BLyS and anti-APRIL delays the development of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms.

  14. Serological and molecular diversity of human rotavirus in São Paulo, Brazil Diversidade sorológica e molecular de rotavírus identificados em crianças em São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Veridiana Munford

    2007-09-01

    Full Text Available From a total of 187 fecal samples from children with ages between 0 and 5 years, collected in the Hospital Universitário -USP, Brazil, from 1994 to 1996, 54 (28.9% were positive for rotavirus. Positive samples were characterized by electropherotyping, subgrouping, G serotype and genotype and P genotype. Rotavirus electropherotypes were characterized in four different long genome patterns (38.9%, one short genome pattern (34.0% and 18.0% were characterized as an unusual pattern. Subgroup I was found in 38.9% strains, subgroup II in 50.0% and 7.7% was subgroup nonI-nonII. For G serotypes, G2 was found in 59.3%, G1 was identified in 33.3% of strains, two samples showed mixtures of G1+G2 and one sample was G1+G3. Ten samples characterized as serotype G2 showed a long eletropherotype. Genotype G2 was the most frequently and was found in 37 (44.0% samples (23 samples as a single genotype and 14 as mixtures of genotypes. G1 was found in 15 samples. G3 and G4 was detected mainly in mixtures of genotypes and G5, G6 and G9 were identified only in mixtures. A total of 20 (38.5% samples were characterized as G genotype mixtures and P mixtures were found in 16 (29.6% samples. P[4] was found in 55.6% of samples, P[8] in 51.9% and P[6-M37 like] in 22.3% of cases. P[6-Gottfried like] and P[11] were detected only in mixtures. One sample with G6 specificity, mixed with a G2 rotavirus and a P[11] strain, mixed with P[4] and P[8]strain was described for the first time in Latin America.De um total de 187 amostras fecais de crianças com idades entre 0 e 5 anos, coletadas no Hospital Universitário -USP, Brasil, de 1994 a 1996, 54 (28.9% foram positivas para rotavírus. As amostras positivas foram caracterizadas quanto ao eletroferótipo, subgrupo, sorotipo G e genotipo G e P. Foram identificados quatro diferentes eletroferótipo longos em 38.9% das amostras, um eletroferótipo curto (34,0% e 18,0% foram caracterizadas como um eletroferótipo não usual. O subgrupo

  15. Health economics of rotavirus immunization in Vietnam : Potentials for favorable cost-effectiveness in developing countries

    NARCIS (Netherlands)

    Tu, Hong-Anh T.; Rozenbaum, Mark H.; Coyte, Peter C.; Li, Shu Chuen; Woerdenbag, Herman J.; Postma, Maarten J.

    2012-01-01

    Introduction: Rotavirus is the most common cause of severe diarrhoea worldwide. Vietnam is situated in the region of high rotavirus infection incidence and eligible for financial support to introduce rotavirus vaccines into the Expanded Program of Immunization (EPI) from the GAVI. This study was des

  16. Rotavirus enterotoxin NSP4 binds to the extracellular matrix proteins laminin-beta3 and fibronectin.

    NARCIS (Netherlands)

    J.A. Boshuizen; J.W. Rossen (John); C.K. Sitaram; F.F.P. Kimenai; Y. Simons-Oosterhuis (Ytje); C. Laffeber; H.A. Büller (Hans); A.W.C. Einerhand (Sandra)

    2004-01-01

    textabstractRotavirus is the most important cause of viral gastroenteritis and dehydrating diarrhea in young children. Rotavirus nonstructural protein 4 (NSP4) is an enterotoxin that was identified as an important agent in symptomatic rotavirus infection. To identify cellular prote

  17. Rotavirus enterotoxin NSP4 binds to the extracellular matrix proteins laminin-beta3 and fibronectin

    NARCIS (Netherlands)

    Boshuizen, J A; Rossen, J W A; Sitaram, C K; Kimenai, F F P; Simons-Oosterhuis, Y; Laffeber, C; Büller, H A; Einerhand, A W C

    2004-01-01

    Rotavirus is the most important cause of viral gastroenteritis and dehydrating diarrhea in young children. Rotavirus nonstructural protein 4 (NSP4) is an enterotoxin that was identified as an important agent in symptomatic rotavirus infection. To identify cellular proteins that interact with NSP4, a

  18. Determinants of Parents' Decision to Vaccinate Their Children against Rotavirus: Results of a Longitudinal Study

    Science.gov (United States)

    Dube, E.; Bettinger, J. A.; Halperin, B.; Bradet, R.; Lavoie, F.; Sauvageau, C.; Gilca, V.; Boulianne, N.

    2012-01-01

    Rotavirus disease is a common cause of health care utilization and almost all children are affected by the age of 5 years. In Canada, at the time of this survey (2008-09), immunization rates for rotavirus were less than 20%. We assessed the determinants of a parent's acceptance to have their child immunized against rotavirus. The survey…

  19. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts.

    Science.gov (United States)

    Chen, Baosheng; Tuuli, Methodius G; Longtine, Mark S; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D

    2012-05-15

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

  20. Smoking attenuated the association between IκBα rs696 polymorphism and defective spermatogenesis in humans.

    Science.gov (United States)

    Yu, B; Ding, Q; Zheng, T; Jiang, L; Li, Q; Sun, X; Bai, C; Huang, Z

    2015-11-01

    Defective spermatogenesis is prevalent in infertile men, but the molecular mechanisms underlying its aetiology are largely unknown. In this study, a proposed association between IκBα SNPs, smoking-related ROS and sperm quality was investigated. Two polymorphisms in the IκBα gene, rs2233406 and rs696 were genotyped in 342 controls and 338 patients with defective spermatogenesis from a southern Chinese population. The results showed the rs696 AA genotype to be significantly more common (21.60% versus 14.33%, P = 0.013) and the rs696 GG genotype to be significantly rarer (28.99% versus 37.13%, P = 0.024) in the cases than in the controls. After subjects were stratified into smokers and nonsmokers, these differences were only observed in nonsmokers. Further analysis showed the rs696 AA genotype to be significantly closely associated with defective spermatogenesis in all subjects (P = 0.014, OR = 1.647) and in nonsmokers (P = 0.036, OR = 1.889). In a TM3 cell model, exposure to cigarette smoke condensate was found to activate NF-κB luciferase activity and altered transcriptional level of NF-κB pathway genes. In conclusion, this study demonstrates an association between functional polymorphisms of the IκBα rs696 and cigarette smoking with the risk of defective spermatogenesis, suggesting some interaction between the NF-κB signalling pathway and smoking-related ROS in human spermatogenesis.

  1. First Evidence that Ecklonia cava-Derived Dieckol Attenuates MCF-7 Human Breast Carcinoma Cell Migration

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    Eun-Kyung Kim

    2015-03-01

    Full Text Available We investigated the effect of Ecklonia cava (E. cava-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6′-biecko, and 2,7″-phloroglucinol-6,6′-bieckol were purified from E. cava by using centrifugal partition chromatography. Among the phlorotannins, we found that dieckol inhibited breast cancer cell the most and was selected for further study. Radius™-well was used to assess cell migration, and dieckol (1–100 µM was found to suppress breast cancer cell movement. Metastasis-related gene expressions were evaluated by RT-PCR and Western blot analysis. In addition, dieckol inhibited the expression of migration-related genes such as matrix metalloproteinase (MMP-9 and vascular endothelial growth factor (VEGF. On the other hand, it stimulated the expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2. These results suggest that dieckol exerts anti-breast cancer activity via the regulation of the expressions of metastasis-related genes, and this is the first report on the anti-breast cancer effect of dieckol.

  2. Vibration Attenuation of Magnetorheological Landing Gear System with Human Simulated Intelligent Control

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    X. M. Dong

    2013-01-01

    Full Text Available Due to the short duration of impulsive impact of an aircraft during touchdown, a traditional landing gear can only achieve limited performance. In this study, a magnetorheological (MR absorber is incorporated into a landing gear system; an intelligent control algorithm, a human simulated intelligent control (HSIC, is proposed to adaptively tune the MR absorber. First, a two degree-of-freedom (DOF dynamic model of a landing gear system featuring an MR absorber is constructed. The control model of an MR damper is also developed. After analyzing the impact characteristic during touchdown, an HSIC is then formulated. A genetic algorithm is adopted to optimize the control parameters of HSIC. Finally, a numerical simulation is performed to validate the proposed damper and the controller considering the varieties of sink velocities and sprung masses. The simulations under different scenarios show that the landing gear system based on the MR absorber can greatly reduce the peak impact load of sprung mass within the stroke. The biggest improvement of the proposed controller is over 40% compared to that of skyhook controller. Furthermore, HSIC exhibits better adaptive ability and strong robustness than skyhook controller under various payloads and sink velocities.

  3. Porcine Rotaviruses: Epidemiology, Immune Responses and Control Strategies

    Science.gov (United States)

    Vlasova, Anastasia N.; Amimo, Joshua O.; Saif, Linda J.

    2017-01-01

    Rotaviruses (RVs) are a major cause of acute viral gastroenteritis in young animals and children worldwide. Immunocompetent adults of different species become resistant to clinical disease due to post-infection immunity, immune system maturation and gut physiological changes. Of the 9 RV genogroups (A–I), RV A, B, and C (RVA, RVB, and RVC, respectively) are associated with diarrhea in piglets. Although discovered decades ago, porcine genogroup E RVs (RVE) are uncommon and their pathogenesis is not studied well. The presence of porcine RV H (RVH), a newly defined distinct genogroup, was recently confirmed in diarrheic pigs in Japan, Brazil, and the US. The complex epidemiology, pathogenicity and high genetic diversity of porcine RVAs are widely recognized and well-studied. More recent data show a significant genetic diversity based on the VP7 gene analysis of RVB and C strains in pigs. In this review, we will summarize previous and recent research to provide insights on historic and current prevalence and genetic diversity of porcine RVs in different geographic regions and production systems. We will also provide a brief overview of immune responses to porcine RVs, available control strategies and zoonotic potential of different RV genotypes. An improved understanding of the above parameters may lead to the development of more optimal strategies to manage RV diarrheal disease in swine and humans. PMID:28335454

  4. Rotavirus vaccination and herd immunity: an evidence-based review

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    Seybolt LM

    2012-06-01

    Full Text Available Lorna M Seybolt, Rodolfo E BéguéDepartment of Pediatrics, Division of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, USAAbstract: Until recently, rotavirus was the most common cause of diarrhea in infants and young children with over 100 million cases and 400,000 deaths every year worldwide. Yet, its epidemiology is changing rapidly with the introduction of two rotavirus vaccines in the mid 2000s. Both vaccines were shown to be highly efficacious in prelicensure studies to reduce severe rotavirus disease; the efficacy being more pronounced in high- and middle-income countries than in low-income countries. Herd immunity – the indirect protection of unimmunized individuals as a result of others being immunized – was not expected to be a benefit of rotavirus vaccination programs since the vaccines were thought to reduce severe disease but not to decrease virus transmission significantly. Postlicensure studies, however, have suggested that this assumption may need reassessment. Studies in a variety of settings have shown evidence of greater than expected declines in rotavirus disease. While these studies were not designed specifically to detect herd immunity – and few failed to detect this phenomenon – the consistency of the evidence is compelling. These studies are reviewed and described here. While further work is needed, clarifying the presence of herd immunity is not just an academic exercise but an important issue for rotavirus control, especially in lower income countries where the incidence of the disease is highest and the direct protection of the vaccines is lower.Keywords: rotavirus, vaccine, herd immunity, efficacy

  5. Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea

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    Alfajaro Mia Madel

    2012-12-01

    Full Text Available Abstract Background Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea. Methods Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7] strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α, signaling molecules (p38 and JNK, and transcription factor (NFκB in the small intestine and spleen were determined. Results Among the dosages (100-400 mg/ml administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α, signaling molecules (p38 and JNK, and transcription factor (NFκB in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea. Conclusions GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.

  6. Vanillin attenuates negative effects of ultraviolet A on the stemness of human adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Lee, Sang Yeol; Park, See-Hyoung; Kim, Mi Ok; Lim, Inhwan; Kang, Mingyeong; Oh, Sae Woong; Jung, Kwangseon; Jo, Dong Gyu; Cho, Il-Hoon; Lee, Jongsung

    2016-10-01

    Ultraviolet A (UVA) irradiation induces various changes in cell biology. The objective of this study was to determine the effect of vanillin on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). UVA-antagonizing mechanisms of vanillin were also examined. The results revealed that vanillin attenuated UVA-induced reduction of the proliferative potential and stemness of hAMSCs evidenced by increased proliferative activity in BrdU incorporation assay and upregulation of stemness-related genes (OCT4, NANOG and SOX2) in response to vanillin treatment. UVA-induced reduction in mRNA level of hypoxia-inducible factor (HIF)-1α was significantly recovered by vanillin. In addition, the antagonizing effect of vanillin on UVA was found to be mediated by reduced production of PGE2 through inhibiting JNK and p38 MAPK. Taken together, these findings showed that vanillin could improve the reduced stemness of hAMSCs induced by UVA. The effect of vanillin is mediated by upregulating HIF-1α via inhibiting PGE2-cAMP signaling. Therefore, vanillin might be used as an antagonizing agent to mitigate the effects of UVA.

  7. Offset-Control Attenuates Context Conditioning Induced by US-unpredictability in a Human Conditioned Suppression Paradigm

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    Ann Meulders

    2013-03-01

    Full Text Available We investigated whether offset-control of the unconditioned stimulus (US reduces context conditioning induced by US-unpredictability within a human conditioned suppression preparation. We also examined lack of control 'vs'. loss of control. Three groups (No Controllability, NC; Controllability, C; Loss of Controllability, LC received unsignaled USs during two learning phases (ACQ1-2. The NC group, never had offset-control, whereas the C group, always had offset-control. The LC group, had offset-control during ACQ1, but not during ACQ2. Results indicated that US-unpredictability led to contextual conditioned suppression during ACQ1, only when participants did not have offset-control; when they did, no context conditioning was established. From ACQ1 to ACQ2, contextual conditioned suppression increased in the LC group, but it was not more pronounced than in the NC group. These data suggest that offset-control attenuates context conditioning induced by US-unpredictability and – at least in this paradigm – loss of control is not worse than lack of control.

  8. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

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    Yuben Moodley

    2016-07-01

    Full Text Available Acute lung injury/acute respiratory distress syndrome (ALI/ARDS is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n = 6 to intravenous oleic acid (OA injury, ventilation and hMSC infusion, while the controls (n = 5 had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1 h after the administration of OA. The animals were monitored for additional 4 h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB, a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p = 0.04. There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p = 0.063. There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4 h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  9. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model.

    Science.gov (United States)

    Kirkpatrick, Beth D; Whitehead, Stephen S; Pierce, Kristen K; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen A; Larsson, Catherine J; Sabundayo, Beulah P; Talaat, Kawsar R; Janiak, Anna; Carmolli, Marya P; Luke, Catherine J; Diehl, Sean A; Durbin, Anna P

    2016-03-16

    A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials.

  10. Lithocholic acid attenuates cAMP-dependent Cl- secretion in human colonic epithelial T84 cells.

    Science.gov (United States)

    Ao, Mei; Domingue, Jada C; Khan, Nabihah; Javed, Fatima; Osmani, Kashif; Sarathy, Jayashree; Rao, Mrinalini C

    2016-06-01

    Bile acids (BAs) play a complex role in colonic fluid secretion. We showed that dihydroxy BAs, but not the monohydroxy BA lithocholic acid (LCA), stimulate Cl(-) secretion in human colonic T84 cells (Ao M, Sarathy J, Domingue J, Alrefai WA, Rao MC. Am J Physiol Cell Physiol 305: C447-C456, 2013). In this study, we explored the effect of LCA on the action of other secretagogues in T84 cells. While LCA (50 μM, 15 min) drastically (>90%) inhibited FSK-stimulated short-circuit current (Isc), it did not alter carbachol-stimulated Isc LCA did not alter basal Isc, transepithelial resistance, cell viability, or cytotoxicity. LCA's inhibitory effect was dose dependent, acted faster from the apical membrane, rapid, and not immediately reversible. LCA also prevented the Isc stimulated by the cAMP-dependent secretagogues 8-bromo-cAMP, lubiprostone, or chenodeoxycholic acid (CDCA). The LCA inhibitory effect was BA specific, since CDCA, cholic acid, or taurodeoxycholic acid did not alter FSK or carbachol action. While LCA alone had no effect on intracellular cAMP concentration ([cAMP]i), it decreased FSK-stimulated [cAMP]i by 90%. Although LCA caused a small increase in intracellular Ca(2+) concentration ([Ca(2+)]i), chelation by BAPTA-AM did not reverse LCA's effect on Isc LCA action does not appear to involve known BA receptors, farnesoid X receptor, vitamin D receptor, muscarinic acetylcholine receptor M3, or bile acid-specific transmembrane G protein-coupled receptor 5. LCA significantly increased ERK1/2 phosphorylation, which was completely abolished by the MEK inhibitor PD-98059. Surprisingly PD-98059 did not reverse LCA's effect on Isc Finally, although LCA had no effect on basal Isc, nystatin permeabilization studies showed that LCA both stimulates an apical cystic fibrosis transmembrane conductance regulator Cl(-) current and inhibits a basolateral K(+) current. In summary, 50 μM LCA greatly inhibits cAMP-stimulated Cl(-) secretion, making low doses of LCA of

  11. Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin.

    Science.gov (United States)

    Bruning, Rebecca S; Santhanam, Lakshmi; Stanhewicz, Anna E; Smith, Caroline J; Berkowitz, Dan E; Kenney, W Larry; Holowatz, Lacy A

    2012-06-01

    Local skin heating is used to assess microvascular function in clinical populations because NO is required for full expression of the response; however, controversy exists as to the precise NO synthase (NOS) isoform producing NO. Human aging is associated with attenuated cutaneous vasodilation but little is known about the middle aged, an age cohort used for comparison with clinical populations. We hypothesized that endothelial NOS (eNOS) is the primary isoform mediating NO production during local heating, and eNOS-dependent vasodilation would be reduced in middle-aged skin. Vasodilation was induced by local heating (42°C) and during acetylcholine dose-response (ACh-DR: 0.01, 0.1, 1.0, 5.0, 10.0, 50.0, 100.0 mmol/l) protocols. Four microdialysis fibers were placed in the skin of 24 men and women; age cohorts were 12 middle-aged (53 ± 1 yr) and 12 young (23 ± 1 yr). Sites served as control, nonselective NOS inhibited [N(G)-nitro-l-arginine methyl ester (l-NAME)], inducible NOS (iNOS) inhibited (1400W), and neuronal NOS (nNOS) inhibited (N(ω)-propyl-l-arginine). After full expression of the local heating response, l-NAME was perfused at all sites. Cutaneous vascular conductance was measured and normalized to maximum (%CVC(max): Nitropress). l-NAME reduced %CVCmax at baseline, all phases of the local heating response, and at all ACh concentrations compared with all other sites. iNOS inhibition reduced the initial peak (53 ± 2 vs. 60 ± 2%CVC(max); P vasodilation during local heating (52 ± 6 vs. 68 ± 4%CVC(max); P = 0.013) and ACh perfusion (50 mmol/l: 83 ± 3 vs. 93 ± 2%CVC(max); 100 mmol/l: 83 ± 4 vs. 92 ± 3%CVC(max); both P = 0.03) were reduced in middle-aged skin. There were no differences in NOS isoform expression obtained from skin biopsy samples between groups (all P > 0.05). These data suggest that eNOS mediates the production of NO during local heating and that cutaneous vasodilation is attenuated in middle-aged skin.

  12. Expression of NF-kappaB in rotavirus-induced damage to the liver and biliar y tract in neonatal mice

    Institute of Scientific and Technical Information of China (English)

    Lei Huang; Wei-Zhong Gu; Xin-Min Si; Ming-Fa Wei; Jie-Xiong Feng

    2007-01-01

    in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-κB in the liver and biliary tract.

  13. Nursing Care of Patients With Rotavirus Infection%人轮状病毒感染患者的护理

    Institute of Scientific and Technical Information of China (English)

    刘华

    2016-01-01

    Objective To investigate the clinical nursing measures of human rotavirus infection.MethodsFrom March 2013 to June 2014, 30 cases were treated in our hospital for human rotavirus infection, analysised the clinical nursing.ResultsAmong the 30 cases, 13 cases were markedly effective, 11 cases were effective, 6 cases were ineffective, the total effective rate was 75%.Conclusion It is helpful to improve the clinical effcacy of comprehensive nursing intervention for patients with rotavirus infection in the condition of disease monitoring and symptomatic nursing.%目的:探讨人轮状病毒感染患者的临床护理措施。方法选取2013年3月~2014年6月收治的人轮状病毒感染患者30例,分析其临床护理方法。结果30例患者经治疗,显效13例,有效11例,无效6例,总有效率为75.00%。结论对轮状病毒感染患者做好病情监测和对症护理等综合护理干预,有助于提高临床疗效。

  14. Effects of wastewater sludge and its detergents on the stability of rotavirus

    Energy Technology Data Exchange (ETDEWEB)

    Ward, R.L. (Sandia Labs., Albuquerque, NM); Ashley, C.S.

    1980-06-01

    Wastewater sludge reduced the heat required to inactivate rotavirus SA-11, and ionic detergents were identified as the sludge components responsible for this effect. A similar result was found previously with reovirus. The quantitative effects of individual ionic detergents on rotavirus and reovirus were very different, and rotavirus was found to be extremely sensitive to several of these detergents. However, neither virus was destabilized by nonionic detergents. On the contrary, rotavirus was stabilized by a nonionic detergent against the potent destabilizing effects of the ionic detergent sodium dodecyl sulfate. The destabilizing effects of both cationic and anionic detergents on rotavirus were greatly altered by changes in the pH of the medium.

  15. Escherichia coli Meningitis after Rotavirus Gastroenteritis in an Infant

    Science.gov (United States)

    Vermezoglu, Oznur; Ocal Topcu, Didem; Karbuz, Adem; Hacihamdioglu, Bulent

    2016-01-01

    Although rotavirus gastroenteritis is quite common in the pediatric population, secondary bacterial sepsis following rotavirus infection is a rare clinical entity. Gram-negative bacilli are the fifth most common cause of meningitis in infants but this infection rarely occurs after gastroenteritis. Here, we report a 2.5-month-old infant who developed Escherichia coli (E. coli) meningitis after acute rotavirus gastroenteritis. The 2.5-month-old male infant with fever, vomiting, and watery diarrhea that started 1 day earlier was admitted to the hospital. Rotavirus antigen in stool sample was positive. He was hospitalized, and fever was measured at 39.5°C on the second day. Lumbar puncture was done for suspicion of meningitis, and cerebrospinal fluid (CSF) findings suggested meningitis. Intravenous vancomycin and cefotaxime were started empirically. Since E. coli reproduction was seen in blood culture and CSF culture, treatment was continued with cefotaxime. The patient was discharged with minimal midlevel hydrocephalus findings in cranial ultrasonography and magnetic resonance imaging following 21 days of antibiotics treatment. Septicemia development following rotavirus gastroenteritis is an extremely rare clinical condition. It is vital to start prompt antibiotic treatment as soon as the diagnosis of secondary bacterial infection is made because of high mortality and morbidity rates.

  16. Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1 vaccine candidates containing stabilized mutations in the P/C and L genes

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    Skiadopoulos Mario H

    2007-07-01

    Full Text Available Abstract Background Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1 mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non-ts attenuating (att mutations primarily in the P/C gene, namely CR84GHNT553A (two point mutations used together as a set and CΔ170 (a short deletion mutation, and two ts att mutations in the L gene, namely LY942A (a point mutation, and LΔ1710–11 (a short deletion, the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs. Results The rHPIV1 mutant bearing the novel LΔ1710–11 mutation was highly ts and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates were highly ts, with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-CR84G/Δ170HNT553ALY942A protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host. Conclusion The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.

  17. Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.

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    Charlotte J Green

    Full Text Available BACKGROUND: Glucagon like peptide-1 (GLP-1 stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined. METHODS: Skeletal muscle satellite cells isolated from young (22.5 ± 0.97 yr, lean (BMI 22.5 ± 0.6 kg/m(2, healthy males were differentiated in media containing either 22.5 mM (high or 5 mM (normal glucose for 7 days in the absence or presence of insulin and/or various GLP-1 concentrations. Myocellular effects of GLP-1, insulin and glucose were assessed by western-blot, glucose uptake and glycogen synthesis. RESULTS: We firstly show that the GLP-1 receptor protein is expressed in differentiated human muscle satellite cells (myocytes. Secondly, we show that in 5 mM glucose media, exposure of myocytes to GLP-1 results in a dose dependent increase in glucose uptake, GLUT4 amount and subsequently glycogen synthesis in a PI3K dependent manner, independent of the insulin signaling cascade. Importantly, we provide evidence that differentiation of human satellite cells in hyperglycemic (22.5 mM glucose conditions increases GLUT1 expression, and renders the cells insulin resistant and interestingly GLP-1 resistant in terms of glucose uptake and glycogen synthesis. Hyperglycemic conditions did not affect the ability of insulin to phosphorylate downstream targets, PKB or GSK3. Interestingly we show that at 5 mM glucose, GLP-1 increases GLUT4 protein levels and that this effect is abolished by hyperglycemia. CONCLUSIONS: GLP-1 increases glucose uptake and glycogen synthesis into fully-differentiated human satellite cells in a PI3-K dependent mechanism potentially through increased GLUT4 protein levels. The latter occurs independently of the insulin signaling pathway. Attenuation

  18. Hospital-based Surveillance for Rotavirus Gastroenteritis Among Young Children in Bangladesh

    Science.gov (United States)

    Gastanaduy, Paul A.; Islam, Khaleda; Rahman, Mahmudur; Rahman, Mustafizur; Luby, Stephen P.; Heffelfinger, James D.; Parashar, Umesh D.; Gurley, Emily S.

    2017-01-01

    Background: In anticipation of introduction of a rotavirus vaccine into the national immunization program of Bangladesh, active hospital-based surveillance was initiated to provide prevaccine baseline data on rotavirus disease. Methods: Children 5 years of age and younger admitted with acute gastroenteritis (AGE) (≥3 watery or looser-than-normal stools or ≥1 episode of forceful vomiting) at 7 hospitals throughout Bangladesh were identified. Clinical information and stool specimens were collected from every 4th patient. Specimens were tested for rotavirus antigen by enzyme immunoassays; 25% of detected rotaviruses were genotyped. Results: From July 2012 to June 2015, rotavirus was detected in 2432 (64%) of 3783 children hospitalized for AGE. Eight enrolled children died, including 4 (50%) who were rotavirus positive. Rotavirus was detected year-round in Bangladesh with peak detection rates of >80% during November–February. Most (86%) rotavirus AGE cases were 6–23 months of age. Sixty-nine percent of children with rotavirus had severe disease (Vesikari score, ≥11). Among 543 strains genotyped, G1P[8] (31%) and G12P[8] (29%) were the most common. Conclusions: Rotavirus is a major cause of morbidity in Bangladeshi children, accounting for nearly two-thirds of AGE hospitalizations. These data highlight the potential value of rotavirus vaccination in Bangladesh, and will be the key for future measurement of vaccine impact. PMID:27798545

  19. Fulfilling the promise of rotavirus vaccines: how far have we come since licensure?

    Science.gov (United States)

    Patel, Manish M; Glass, Roger; Desai, Rishi; Tate, Jacqueline E; Parashar, Umesh D

    2012-07-01

    Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.

  20. Induction of progesterone receptor A form attenuates the induction of cytosolic phospholipase A2alpha expression by cortisol in human amnion fibroblasts.

    Science.gov (United States)

    Guo, Chunming; Ni, Xiaotian; Zhu, Ping; Li, Wenjiao; Zhu, Xiaoou; Sun, Kang

    2010-05-01

    Cytosolic phospholipase A2alpha (cPLA(2alpha), now known as PLA2G4A) is the enzyme catalyzing the formation of the rate-limiting substrate, arachidonic acid, for prostaglandin (PG) synthesis. The increasing expression of PLA2G4A toward term gestation in human amnion fibroblasts is believed to be the crucial event in parturition. Human amnion fibroblasts produce cortisol, progesterone and express glucocorticoid receptor (GR), progesterone receptor A (PGRA) form at term. The roles of progesterone and PGRA in the induction of PLA2G4A by cortisol via GR in the amnion fibroblasts remain largely unknown. Using cultured human term amnion fibroblasts, we found that cortisol induced the expression of PGRA, which was attenuated by inhibiting PG synthesis with indomethacin. Knockdown of PGRA expression or inhibition of endogenous progesterone production with trilostane significantly enhanced the induction of PLA2G4A by cortisol, whereas overexpression of PGRA attenuated the induction of PLA2G4A by cortisol. Although exogenous progesterone did not alter PLA2G4A expression under basal conditions, it attenuated cortisol-induced PLA2G4A expression at concentrations about tenfold higher, which might be achieved by competition with cortisol for GR. In conclusion, PGRA in the presence of endogenous progesterone is a transdominant repressor of the induction of PLA2G4A by cortisol. High level of progesterone may compete with cortisol for GR, thus further inhibiting the induction of PLA2G4A by cortisol. Moreover, increased PG synthesis by cortisol may feed back on the expression of PGRA leading to attenuation of cortisol-induced PLA2G4A expression. The above findings may be pertinent to the inconsistent effects of glucocorticoids on parturition in humans.

  1. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Yi-Ning Chao

    2016-08-01

    Full Text Available Cyclooxygenase-2 (COX-2 and interleukin-8 (IL-8 are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC activator phorbol 12, 13-didecanoate (PDD and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2. GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2 and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1 reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1 and protein phosphatase 2 (PP2A reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2 in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

  2. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates.

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    Fiona R Strouts

    2016-05-01

    Full Text Available The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection.In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV, suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30.These results suggest that early transcriptional responses may be predictive of development of adaptive immunity to TDV

  3. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

  4. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates

    Science.gov (United States)

    Strouts, Fiona R.; Popper, Stephen J.; Partidos, Charalambos D.; Stinchcomb, Dan T.; Osorio, Jorge E.; Relman, David A.

    2016-01-01

    Background The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection. Methodology/Principal Findings In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV), suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN) response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal) vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30. Conclusions/Significance These results suggest that early transcriptional responses may be

  5. Comparison of fecal indicators with pathogenic bacteria and rotavirus in groundwater

    Science.gov (United States)

    Ferguson, Andrew S.; Layton, Alice C.; Mailloux, Brian J; Culligan, Patricia J.; Williams, Daniel E.; Smartt, Abby E.; Sayler, Gary S.; Feighery, John; McKay, Larry; Knappett, Peter S.K.; Alexandrova, Ekaterina; Arbit, Talia; Emch, Michael; Escamilla, Veronica; Ahmed, Kazi Matin; Alam, Md. Jahangir; Streatfield, P. Kim; Yunus, Mohammad; van Geen, Alexander

    2012-01-01

    Groundwater is routinely analyzed for fecal indicators but direct comparisons of fecal indicators to the presence of bacterial and viral pathogens are rare. This study was conducted in rural Bangladesh where the human population density is high, sanitation is poor, and groundwater pumped from shallow tubewells is often contaminated with fecal bacteria. Five indicator microorganisms (E. coli, total coliform, F+RNA coliphage, Bacteroides and human-associated Bacteroides) and various environmental parameters were compared to the direct detection of waterborne pathogens by quantitative PCR in groundwater pumped from 50 tubewells. Rotavirus was detected in groundwater filtrate from the largest proportion of tubewells (40%), followed by Shigella (10%), Vibrio (10%), and pathogenic E. coli (8%). Spearman rank correlations and sensitivity-specificity calculations indicate that some, but not all, combinations of indicators and environmental parameters can predict the presence of pathogens. Culture-dependent fecal indicator bacteria measured on a single date did not predict total bacterial pathogens, but annually averaged monthly measurements of culturable E. coli did improve prediction for total bacterial pathogens. A qPCR-based E. coli assay was the best indicator for the bacterial pathogens. F+RNA coliphage were neither correlated nor sufficiently sensitive towards rotavirus, but were predictive of bacterial pathogens. Since groundwater cannot be excluded as a significant source of diarrheal disease in Bangladesh and neighboring countries with similar characteristics, the need to develop more effective methods for screening tubewells with respect to microbial contamination is necessary. PMID:22705866

  6. Efficacy of synbiotic treatment in children with acute rotavirus diarrhea

    Directory of Open Access Journals (Sweden)

    Made Ratna Dewi

    2015-03-01

    Full Text Available Background Diarrhea is one of the major causes of morbidity and mortality in children throughout the world, mostly due to rotavirus infection. In daily practice, we routinely use the World Health Organization Five steps for managing acute diarrhea.This practice has shown great success in diarrhea management, but concerns remain on reducing the duration of diarrhea to prevent complications. Synbiotics can reduce the severity of diarrhea. However, there has been limited data on synbiotic therapy for treating acute rotavirus diarrhea in children. Objective To compare the durations of acute rotavirus diarrhea treated with synbiotics vs. placebo. Methods This study was a randomized, double-blind, clinical trial, performed at the Pediatric Gastrohepatology Division, Sanglah and Wangaya Hospitals in Denpasar. Subjects were children aged 6 to 59 months with acute rotavirus diarrhea. Rotavirus was diagnosed by immune chromatography assay. The synbiotic group received probiotic comprised of Lactobacillus sp., Streptococcus sp., Bifidobacterium sp. (total viable count 1.00x109 CFU per dose, and prebiotic consisted of 990.00 mg fructooligosacharide (FOS. The placebo consisted of lactose monohydrate packaged similarly as the synbiotics. Subjects orally ingested 1 pack per day for 5 days. Results Seventy children with acute rotavirus diarrhea was involved in this study. The median duration of diarrhea in the synbiotic group was 50.0 (SE 1.1; 95%CI 47.9 to 52.1 hours, while that of the placebo group was 63.0 (SE 5.9; 95%CI 51.4 to 74.6 hours. Based on Kaplan-Meier survival analysis, the duration of diarrhea in the synbiotic group was significantly shorter than that of the placebo group (log-rank test P <0.0001. Conclusion In children with acute rotaviral diarrhea, synbiotic reduces the duration of diarrhea compared to placebo. [Paediatr Indones. 2015;55:74-8.].

  7. PATHOGENETIC ROLE OF CYTOKINES IN CHILDHOOD ROTAVIRUS INFECTION

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    S. N. Benyova

    2007-01-01

    Full Text Available Abstract. Results of cytokine network studies system in children with rotavirus infection are presented. Concentrations of cytokines were determined at both local and systemic levels. Analysis of cytokine levels was performed at initial terms (day 1 to 3, and in the course of disease (day 7 to 10. It was revealed that mild and mid-severe cases of rotavirus infection in the children are characterized by early increase in proinflammatory cytokines with restricted overshoot of proinflammatory cytokines at early recovery period. Meanwhile, the patients with severe forms of viral gastroenteritis exhibited high levels of proinflammatory cytokines. However, this balance was shifted towards anti-inflammatory cytokines during early reconvalescence.

  8. Detection of porcine rotavirus from tissue and faecal specimens

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    Prabha Suji

    2009-01-01

    Full Text Available Porcine small intestinal sub-mucosa is a cell-free collagen matrix that has demonstrated its ability as a scaffold material. Transplantation poses special hazards because grafted tissues and organs transmit pathogens efficiently, especially viruses. Rotavirus is thought to be confined to the intestine, causing acute diarrhoea. The purpose of this study was to evaluate the porcine intestinal tissue scaffold for Rotavirus and to study the incidence of this virus among pig herds. Only one isolate was successfully adapted to grow in cell line MA 104 from faecal samples. This isolate was further confirmed by reverse transcriptase polymerase chain reaction and sequence analysis.

  9. Rotavirus electropherotypes from the Kuala Lumpur Hospital: a re-examination after an interval of seven years.

    Science.gov (United States)

    Yap, K L; Lim, Y H; Tan, S C

    1998-06-01

    The objective of this study was to ascertain the extent changes have occurred in the epidemiology of human rotavirus electropherotypes from the same location 7 to 8 years after an earlier study. Genomic RNA profiles of rotaviruses from diarrhoeic children admitted to the Kuala Lumpur Hospital from April to December 1996 were determined by polyacrylamide gel electrophoresis and silver staining. A total of 179 group A rotaviruses were detected from 870 children: 175 with legible staining of all RNA segments were classified into 14 distinct electropherotypes (10 and 4 with long and short migration patterns respectively). In addition, the results revealed: high predominance of long pattern electropherotypes (94% of the total electropherotypes); most long electropherotypes with RNA profiles which all 11 RNAs migrated separately (8 of 10 electropherotypes); all short electropherotypes had segments 2 and 3 that co-migrated; presence of a very numerically dominant electropherotype (75% of all electropherotypes); frequent co-circulation of the dominant electropherotype-present throughout the study period--with other electropherotypes present for limited periods; sequential temporal appearances by similar electropherotypes. These observations were similar to that of an earlier study conducted in 1988/89. Nevertheless, the dominant electropherotype in the present study was different and not among the electropherotypes detected in the earlier study.

  10. Development of a Rotavirus-Shedding Model in Rhesus Macaques, Using a Homologous Wild-Type Rotavirus of a New P Genotype

    Science.gov (United States)

    McNeal, Monica M.; Sestak, Karol; Choi, Anthony H.-C.; Basu, Mitali; Cole, Michael J.; Aye, Pyone P.; Bohm, Rudolf P.; Ward, Richard L.

    2005-01-01

    Although there are several reports on rotavirus inoculation of nonhuman primates, no reliable model exists. Therefore, this study was designed to develop a rhesus macaque model for rotavirus studies. The goals were to obtain a wild-type macaque rotavirus and evaluate it as a challenge virus for model studies. Once rotavirus was shown to be endemic within the macaque colony at the Tulane National Primate Research Center, stool specimens were collected from juvenile animals (2.6 to 5.9 months of age) without evidence of previous rotavirus infection and examined for rotavirus antigen. Six of 10 animals shed rotavirus during the 10-week collection period, and the electropherotypes of all isolates were identical to each other but distinct from those of prototype simian rotaviruses. These viruses were characterized as serotype G3 and subgroup 1, properties typical of many animal rotaviruses, including simian strains. Nucleotide sequence analysis of the VP4 gene was performed with a culture-grown isolate from the stool of one animal, designated the TUCH strain. Based on both genotypic and phylogenetic comparisons between TUCH VP4 and cognate proteins of representatives of the reported 22 P genotypes, the TUCH virus belongs to a new genotype, P[23]. A pool of wild-type TUCH was prepared and intragastrically administered to eight cesarean section-derived, specific-pathogen-free macaques 14 to 42 days of age. All animals were kept in a biocontainment level 2 facility. Although no diarrhea was observed and the animals remained clinically normal, all animals shed large quantities of rotavirus antigen in their feces after inoculation, which resolved by the end of the 14-day observation period. Therefore, TUCH infection of macaques provides a useful nonhuman primate model for studies on rotavirus protection. PMID:15613323

  11. Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate

    Science.gov (United States)

    Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L.; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M.; Lukashevich, Igor S.; Salvato, Maria S.

    2013-01-01

    Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease. PMID:24069471

  12. Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29, a vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Zapata

    Full Text Available Lassa virus (LASV is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG, as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

  13. Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29), a vaccine candidate.

    Science.gov (United States)

    Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M; Lukashevich, Igor S; Salvato, Maria S

    2013-01-01

    Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

  14. Immunogenicity and protective efficacy of yeast extracts containing rotavirus-like particles: a potential veterinary vaccine.

    Science.gov (United States)

    Rodríguez-Limas, William A; Pastor, Ana Ruth; Esquivel-Soto, Ernesto; Esquivel-Guadarrama, Fernando; Ramírez, Octavio T; Palomares, Laura A

    2014-05-19

    Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD50) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus.

  15. Progress in the introduction of rotavirus vaccine--Latin America and the Caribbean, 2006-2010.

    Science.gov (United States)

    2011-12-01

    Rotavirus disease is the leading cause of childhood morbidity and mortality related to diarrhea in Latin America and the Caribbean (LAC), where an estimated 8,000 deaths related to rotavirus diarrhea occur annually among children aged rotavirus vaccines became available, the World Health Organization (WHO) in 2007 recommended inclusion of rotavirus vaccine in the immunization programs of Europe and the Americas, and in 2009 expanded the recommendation to all infants aged rotavirus vaccine in LAC, where it was first introduced in 2006 in Brazil, El Salvador, Mexico, Nicaragua, Panama, and Venezuela; by January 2011, it was included in the national immunization schedules of 14 countries in LAC. Estimated national rotavirus vaccine coverage (2 doses of the monovalent vaccine or 3 doses of the pentavalent vaccine) among children aged rotavirus vaccine into their national immunization programs, 13 participate in a hospital-based rotavirus surveillance network. Data from some countries in this network and from other monitoring efforts in LAC countries have shown declines in hospitalizations and deaths related to severe diarrhea after rotavirus vaccine introduction. The rapid introduction of rotavirus vaccine in LAC demonstrates the benefits of the early commitment of national decision makers to introduce these vaccines in low-income and middle-income countries at the same time as in high-income countries.

  16. Detection of emerging rotavirus G12P[8] in Sonora, México.

    Science.gov (United States)

    González-Ochoa, G; J, G de; Calleja-García, P M; Rosas-Rodríguez, J A; Virgen-Ortíz, A; Tamez-Guerra, P

    2016-06-01

    Rotavirus is the most common cause of gastroenteritis in children up to five years of age worldwide. The aim of the present study was to analyze the genotypes of rotavirus strains isolated from children with gastroenteritis, after the introduction of the rotavirus vaccine in México. Rotavirus was detected in 14/100 (14%) fecal samples from children with gastroenteritis, using a commercial test kit. The viral genome was purified from these samples and used as a template in RT-PCR amplification of the VP4 and VP7 genes, followed by gene cloning and sequencing. Among the rotavirus strains, 4/14 (28.5%) were characterized as G12P[8], 2/14 (14.3%), as G12P (not typed), and 3/14 (21.42%) as G (not typed) P[8]. Phylogenetic analysis of the VP7 gene showed that G12 genotypes clustered in lineage III. Phylogenetic analysis revealed that VP4 genotype P[8] sequences clustered in lineage V, whereas other P[8] sequences previously reported in Mexico (2005-2008) clustered in different lineages. Rotavirus genotype G12 is currently recognized as a globally emerging rotavirus. To our knowledge, this is the first report of this emerging rotavirus strain G12P[8] in México. Ongoing surveillance is recommended to monitor the distribution of rotavirus genotypes and to continually reassess the suitability of currently available rotavirus vaccines.

  17. Role of Temperature and Suwannee River Natural Organic Matter on Inactivation Kinetics of Rotavirus and Bacteriophage MS2 by Solar Irradiation

    KAUST Repository

    Romero, Ofelia C.

    2011-12-15

    Although the sunlight-mediated inactivation of viruses has been recognized as an important process that controls surface water quality, the mechanisms of virus inactivation by sunlight are not yet clearly understood. We investigated the synergistic role of temperature and Suwannee River natural organic matter (SRNOM), an exogenous sensitizer, for sunlight-mediated inactivation of porcine rotavirus and MS2 bacteriophage. Upon irradiation by a full spectrum of simulated sunlight in the absence of SRNOM and in the temperature range of 14-42 °C, high inactivation rate constants, kobs, of MS2 (k obs ≤ 3.8 h-1 or 1-log10 over 0.6 h) and rotavirus (kobs ≤ 11.8 h-1 or ∼1-log10 over 0.2 h) were measured. A weak temperature (14-42 °C) dependence of kobs values was observed for both viruses irradiated by the full sunlight spectrum. Under the same irradiation condition, the presence of SRNOM reduced the inactivation of both viruses due to attenuation of lower wavelengths of the simulated sunlight. For rotavirus and MS2 solutions irradiated by only UVA and visible light in the absence of SRNOM, inactivation kinetics were slow (kobs < 0.3 h-1 or <1-log10 unit reduction over 7 h) and temperature-independent for the range considered. Conversely, under UVA and visible light irradiation and in the presence of SRNOM, temperature-dependent inactivation of MS2 was observed. For rotavirus, the SRNOM-mediated exogenous inactivation was only important at temperatures >33 °C, with low rotavirus kobs values (kobs ≈ 0.2 h-1; 1-log10 unit reduction over 12 h) for the temperature range of 14-33 °C. These kobs values increased to 0.5 h-1 at 43 °C and 1.5 h-1 (1-log10 reduction over 1.6 h) at 50 °C. While SRNOM-mediated exogenous inactivation of MS2 was triggered by singlet oxygen, the presence of hydrogen peroxide was important for rotavirus inactivation in the 40-50 °C range. © 2011 American Chemical Society.

  18. Rapid detection of infectious rotavirus group A using a molecular beacon assay.

    Science.gov (United States)

    Bertol, Jéssica Wildgrube; Gatti, Maria Silvia Viccari

    2016-08-01

    Rapid, sensitive and specific methods are necessary to detect and quantify infectious viruses. Cultivating and detecting enteric viruses in cell culture are difficult, thus impairing the advancement of knowledge regarding virus-induced diarrhea. Rotavirus (RV) detection has been conducted by serological or molecular biology methods, which do not provide information regarding viral infectivity. Molecular beacons (MBs) have demonstrated efficacy for viral detection in cell culture. We propose a MB assay to detect human rotavirus group A (HuRVA) in cell culture. MA104 cells were mock-infected or infected with HuRVA strains (RotaTeq(®) vaccine and K8 strains), and a specific MB for the HuRVA VP6 gene was used for virus detection. Mock-infected cells showed basal fluorescence, while infected cells exhibited increased fluorescence emission. MB hybridization to the viral mRNA target of HuRVA was confirmed. Fluorescence increased according to the increase in the number of infectious viral particles per cell (MOI 0.5-MOI 1). This technique provides quick and efficient HuRVA detection in cell culture without a need for viral culture for several days or many times until cytopathic effects are visualized. This methodology could be applied in the selection of samples for developing RV vaccines.

  19. Rotavirus infection in a tertiary hospital: laboratory diagnosis and impact of immunization on pediatric hospitalization

    Directory of Open Access Journals (Sweden)

    Luciane Aparecida Pereira

    2011-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Rotavirus (RV is the main etiological agent of diarrhea in childhood; its laboratory diagnosis is crucial to guide the clinical management and prevention of its spread. RV immunization was introduced in Brazilian 6-month-old children in 2006. The present study was aimed to evaluate three methodologies used for human RV detection in stool samples obtained from patients hospitalized due to gastroenteritis in a teaching hospital and report the impact of RV immunization in hospitalization by diarrhea. METHODS: 293 stool samples collected in the 2001-2008 period were analyzed by enzyme immunoassay (EIA, latex agglutination (LA and polyacrylamide gel electrophoresis (PAGE. RESULTS: Rotavirus was detected in 34.8% of samples by LA assay, 28.3% of samples by EIA assay and in 25.6% of samples by PAGE assay. Considering the PAGE method as gold standard, the sensitivity, specificity and accuracy of EIA were 94.6%, 94.4% and 94.5%, and to LA were 82.6%, 81.6% and 81.9%, respectively. CONCLUSION: These results indicate that antigen detection by EIA is a rapid, sensitive and specific method, and could be used in large-scale applications for screening stool samples suspected of RV infection. This study showed decreased incidence of RV infection in hospitalized children prior to the implementation of the national immunization program against RV.

  20. The burden of rotavirus disease in Denmark 2009-2010

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Rungø, Christine; Jensen, Claus Sixtus

    2011-01-01

    BACKGROUND: This study sought to determine the incidence and the burden of severe diarrheal disease in Denmark with emphasis on rotavirus (RV) disease. METHODS: This study was designed as a national prospective disease surveillance of children <5 years of age hospitalized for acute gastroenteriti...

  1. Rotavirus-Like Particles: A Novel Nanocarrier for the Gut

    Directory of Open Access Journals (Sweden)

    Naima G. Cortes-Perez

    2010-01-01

    Full Text Available The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP, into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells.

  2. Accelerating the introduction of rotavirus immunization in Indonesia

    NARCIS (Netherlands)

    Suwantika, Auliya A.; Zakiyah, Neily; Lestari, Keri; Postma, Maarten J.

    2014-01-01

    The introduction of the rotavirus vaccine in Indonesia is currently in its infancy. Delay in its development might be caused by factors related to the perceived value of the vaccine, health system characteristics and policy considerations. Other factors, which may also interfere with optimizing the

  3. Characterization of a porcine enterocyte receptor for group A rotavirus.

    Science.gov (United States)

    Kuhlenschmidt, M S; Rolsma, M D; Kuhlenschmidt, T B; Gelberg, H B

    1997-01-01

    We have identified, purified to apparent homogeneity and chemically characterized a biologically-relevant porcine enterocyte receptor for group A porcine rotavirus. Ceramide glycanase digestion followed by acid hydrolysis and monosaccharide compositional analyses indicated the receptor is a family of two GM, gangliosides, one containing N-glycolyl-neuraminic acid and the other N-acetylneuraminic acid. Both gangliosides displayed dose-dependent inhibition of rotavirus binding to, and infectivity of, host cells. Inhibition of infectivity in a focus-forming-unit-reduction assay was achieved with as little as 2 nmols of NeuGcGM3 (50% inhibition with 3.97 nmol) or NeuAcGM3 (50% inhibition with 9.84 nmol) per 10(4) FFU of virus. Preliminary data suggest specific porcine GM3 carbohydrate fine structure or spatial orientation of the sialyloligosaccharide epitopes of the holoGM3 gangliosides may be crucial to enterocyte receptor recognition by rotavirus. We have quantified both NeuGcGM3 and NeuAcGM3 in enterocytes of various-aged pigs from newborn through 16 weeks and have found with increasing age the amount of both GM3 derivatives, especially NeuGcGM3 per gram (dry weight) intestinal brush border decreases rapidly from newborn through 4 weeks of age. These results may help explain the age-sensitivity of piglets to severe rotavirus diarrhea.

  4. Pronóstico de la diarrea por rotavirus

    Directory of Open Access Journals (Sweden)

    Mota-Hernández Felipe

    2001-01-01

    Full Text Available Objetivo. Comparar la gravedad de la diarrea por rotavirus (RV y por no rotavirus. Material y métodos. Estudio transversal en 520 lactantes con diarrea aguda, efectuado entre octubre de 1994 y marzo de 1995 en siete centros del primer nivel de atención en cinco estados de México. El diagnóstico de RV se realizó con ensayo inmunoenzimático o por electroforesis. El análisis se hizo a través de medidas de tendencia central. Los resultados se presentan como promedio y desviación estándar o mediana o variación. Resultados. Se aisló RV en 264 lactantes (50.7% con predominio en varones de 6 meses a un año. Las manifestaciones clínicas fueron significativamente diferentes entre el grupo rotavirus positivo y el grupo rotavirus negativo en mediana de evacuaciones por 24 horas, frecuencia de vómitos, temperatura > 38° C, deshidratación y calificación de gravedad, respectivamente. Conclusiones. Estos resultados mostraron peor pronóstico por mayor gravedad de la diarrea por RV en lactantes, con relación a otra etiología. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

  5. Hydrophobic polycationic coatings disinfect poliovirus and rotavirus solutions.

    Science.gov (United States)

    Larson, Alyssa M; Hsu, Bryan B; Rautaray, Debabrata; Haldar, Jayanta; Chen, Jianzhu; Klibanov, Alexander M

    2011-03-01

    Coating surfaces with N-alkylated polyethylenimines (PEIs), namely branched N,N-hexyl,methyl-PEI via covalent attachment to glass or linear N,N-dodecyl,methyl-PEI by physical deposition ("painting") onto polyethylene, enables the resultant materials to quickly and efficiently disinfect aqueous solutions of (non-enveloped) poliovirus and rotavirus.

  6. A significant and consistent reduction in rotavirus gastroenteritis hospitalization of children under 5 years of age, following the introduction of universal rotavirus immunization in Israel.

    Science.gov (United States)

    Muhsen, Khitam; Rubenstein, Uri; Kassem, Eias; Goren, Sophy; Schachter, Yaakov; Kremer, Adi; Shulman, Lester M; Ephros, Moshe; Cohen, Dani

    2015-01-01

    Universal rotavirus vaccination with RotaTeq was introduced in Israel in December 2010. We examined hospitalization rates of children under 5 years of age due to all-cause and rotavirus gastroenteritis, both before and 3 years after universal introduction of the vaccination. An ongoing hospital-based surveillance network that was established in November 2007, accessed information regarding hospitalization of children due to gastroenteritis (n = 6205) in 3 hospitals in northern Israel, with an annual average of about 60,000 children under 5 years of age living in the catchment area of these hospitals. Stool samples were tested for rotavirus by immunochromatography. Compared to the period preceding implementation of the universal rotavirus vaccination (2008-2010), hospitalizations due to rotavirus gastroenteritis in children gastroenteritis was also observed. During the period preceding universal vaccination, rotavirus diarrhea showed typical winter seasonality, with highest incidence in December. However, the winter peak was substantially blunted during the period of universal immunization. Surveillance of rotavirus gastroenteritis should continue to assess the long-term impact of such a program. Our findings are of relevance to high and middle-income countries considering the introduction of a universal rotavirus immunization program.

  7. Rotavirus strain surveillance for three years following the introduction of rotavirus vaccine into Belém, Brazil.

    Science.gov (United States)

    Guerra, Sylvia F S; Linhares, Alexandre C; Mascarenhas, Joana D'Arc P; Oliveira, Alessilva; Justino, Maria Cleonice A; Soares, Luana S; Müller, Elza Caroline; Brasil, Patrícia; Tuboi, Suely; Ortega-Barria, Eduardo; Colindres, Rómulo

    2015-08-01

    The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non-G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV-gastroenteritis (≥3 liquid or semi-liquid motions over a 24-h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV-gastroenteritis was detected by ELISA and the G- and P-types were determined by RT-PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT-PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine-induced selective pressure.

  8. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage.

    Directory of Open Access Journals (Sweden)

    Javier M Rodríguez

    2014-05-01

    Full Text Available The infectivity of rotavirus, the main causative agent of childhood diarrhea, is dependent on activation of the extracellular viral particles by trypsin-like proteases in the host intestinal lumen. This step entails proteolytic cleavage of the VP4 spike protein into its mature products, VP8* and VP5*. Previous cryo-electron microscopy (cryo-EM analysis of trypsin-activated particles showed well-resolved spikes, although no density was identified for the spikes in uncleaved particles; these data suggested that trypsin activation triggers important conformational changes that give rise to the rigid, entry-competent spike. The nature of these structural changes is not well understood, due to lack of data relative to the uncleaved spike structure. Here we used cryo-EM and cryo-electron tomography (cryo-ET to characterize the structure of the uncleaved virion in two model rotavirus strains. Cryo-EM three-dimensional reconstruction of uncleaved virions showed spikes with a structure compatible with the atomic model of the cleaved spike, and indistinguishable from that of digested particles. Cryo-ET and subvolume average, combined with classification methods, resolved the presence of non-icosahedral structures, providing a model for the complete structure of the uncleaved spike. Despite the similar rigid structure observed for uncleaved and cleaved particles, trypsin activation is necessary for successful infection. These observations suggest that the spike precursor protein must be proteolytically processed, not to achieve a rigid conformation, but to allow the conformational changes that drive virus entry.

  9. 口服轮状病毒活疫苗罗特威研究进展%Progress of oral rotavirus (live) vaccine

    Institute of Scientific and Technical Information of China (English)

    谢澎; 李青; 庞兴; 付敏强; 魏至栋

    2012-01-01

    Rotavirus is the most common cause of severe diarrhea disease in infants and young children worldwide, and its infection has a major global impact on childhood morbidity and mortality. Rotavirus can cause an annual morbidity of more than 10 million diarrhea in children under the age of five in China, of which almost 30 000 to 40 000 children die. Safe and effective vaccination is the principal means to prevent diarrhea caused by rotaviruses. Oral rotavirus (live) vaccine has been approved for human use in 2001 and the sale has been accumulated to more than 30 million doses on the market. The result proved that it is safe and effective, and can effectively reduce the incidence of rotavirus diarrhea.%轮状病毒是引起婴幼儿重症腹泻的最主要病原体,是全球范围内导致婴幼儿发病和死亡的主要病因之一.我国5岁以下婴幼儿轮状病毒腹泻发病人数每年超过1 000万,每年导致大约3~4万名婴幼儿死亡.接种安全有效的疫苗是预防轮状病毒腹泻的主要手段.口服轮状病毒活疫苗罗特威于2001年获准上市,累计接种已超过3 000万剂,安全有效,可有效降低轮状病毒腹泻的发病率.

  10. Efficacy of synbiotic treatment in children with acute rotavirus diarrhea

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    Made Ratna Dewi

    2016-06-01

    Full Text Available Background Diarrhea is one of the major causes of morbidityand mortality in children throughout the world, mostly due torotavirus infection. In daily practice, we routinely use the WorldHealth Organization Five steps for managing acute diarrhea.Thispractice has shown great success in diarrhea management, butconcerns remain on reducing the duration of diarrhea to preventcomplications. Synbiotics can reduce the severity of diarrhea.However, there has been limited data on synbiotic therapy fortreating acute rotavirus diarrhea in children.Objective To compare the durations of acute rotavirus diarrheatreated with synbiotics vs. placebo.Methods This study was a randomized, double-blind, clinical trial,performed at the Pediatric Gastrohepatology Division, Sanglahand Wangaya Hospitals in Denpasar. Subjects were children aged6 to 59 months with acute rotavirus diarrhea. Rotavirus wasdiagnosed by immune chromatography assay. The synbiotic groupreceived probiotic comprised of Lactobacillus sp., Streptococcus sp.,Bifidobacterium sp. (total viable count 1.00x109 CFU per dose, andprebiotic consisted of 990.00 mg fructooligosacharide (FOS. Theplacebo consisted of lactose monohydrate packaged similarly as thesynbiotics. Subjects orally ingested 1 pack per day for 5 days.Results Seventy children with acute rotavirus diarrhea wasinvolved in this study. The median duration of diarrhea in thesynbiotic group was 50.0 (SE 1.1; 95%CI 47.9 to 52.1 hours, whilethat of the placebo group was 63.0 (SE 5.9; 95%CI 51.4 to 74.6hours. Based on Kaplan-Meier survival analysis, the duration ofdiarrhea in the synbiotic group was significantly shorter than thatof the placebo group (log-rank test P <0.0001.Conclusion In children with acute rotaviral diarrhea, synbioticreduces the duration of diarrhea compared to placebo.

  11. Incidence of rotavirus infection in children with gastroenteritis attending Jos university teaching hospital, Nigeria

    Directory of Open Access Journals (Sweden)

    Olabode Atanda O

    2011-05-01

    Full Text Available Abstract This study was conducted to determine the incidence of rotavirus infection in children with gastroenteritis attending Jos university teaching hospital, Plateau State. A total of 160 children with acute diarrhea were selected by random sampling. Stool samples were obtained and assayed for rotavirus antigens by enzyme linked immunosorbent assay technique using standard diagnostic BIOLINE Rotavirus kit. Demographic data of parents were also recorded. Rotavirus were detected in faeces of 22(13.8% children with acute diarrhea, 90.9% of positive cases of rotavirus gastroenteritis were under 2 years of age with highest prevalence in children 7-12 months of age. Males excreted rotavirus at a significant higher rate than females (P

  12. Discrepancies between Antigen and Polymerase Chain Reaction Tests for the Detection of Rotavirus and Norovirus.

    Science.gov (United States)

    Kim, Hyun Soo; Kim, Jae-Seok

    2016-05-01

    We compared the results of an antigen test (ELISA) with those of polymerase chain reaction (PCR) for the detection of rotavirus and norovirus in stool specimens. Rotavirus and norovirus antigen-positive stool specimens were collected, and rotavirus and norovirus PCRs were performed on these specimens. Of the 325 rotavirus antigen-positive specimens, 200 were positive for both assays and 125 were PCR negative. Of 286 norovirus antigen-positive specimens, 51 were PCR negative. Comparison of the lower limit of detection showed that rotavirus PCR was 16 times more sensitive and norovirus PCR was over 4,000 times more sensitive than the ELISA. Discrepant results between ELISA and PCR were common, and the possibility of false-positive and false-negative results should be considered with rotavirus and norovirus assays.

  13. Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule

    NARCIS (Netherlands)

    Buttery, Jim P.; Lambert, Stephen B.; Grimwood, Keith; Nissen, Michael D.; Field, Emma J.; Macartney, Kristine K.; Akikusa, Jonathan D.; Kelly, Julian J.; Kirkwood, Carl D.

    2011-01-01

    Introduction: Rotavirus vaccines were introduced into the funded Australian National Immunization Program (NIP) in July 2007. Due to purchasing arrangements, individual states and territories chose either a 2-dose RV1 (Rotarix, GSK) regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed co

  14. Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.

    Science.gov (United States)

    Suarez-Castaneda, Eduardo; Burnett, Eleanor; Elas, Miguel; Baltrons, Rafael; Pezzoli, Lorenzo; Flannery, Brendan; Kleinbaum, David; de Oliveira, Lucia Helena; Danovaro-Holliday, M Carolina

    2015-11-27

    Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP-HepB-Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24-59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1-12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p=0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.

  15. Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

    OpenAIRE

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

    2013-01-01

    Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bac...

  16. Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

    OpenAIRE

    Pant, Neha; Marcotte, Harold; Brüssow, Harald; Svensson, Lennart; Hammarström, Lennart

    2007-01-01

    Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluati...

  17. Impact of the rotavirus vaccine in Valladolid, Spain: An interrupted time series analysis

    OpenAIRE

    Alberto Pérez-Rubio; Francisco Javier Luquero; Maria Rosario Bachiller Luque; Paz de la Torre Pardo; José María Eiros Bouza

    2016-01-01

    Rotavirus vaccines (RV) have decreased the infant morbidity and mortality in countries that included RV in their national schedule. Rotavirus vaccination is recommended by the Spanish Society of Pediatrics; however, Spain, as most countries in Europe, has authorized commercialization but not included RV in its national vaccination program. We assessed the impact of RV on the rotavirus hospitalization rate through an interrupted time series analysis. There was a 46.8% (95% CI: 29.3–60.2) decre...

  18. Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells

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    Madhu C Mohanty

    2013-01-01

    Full Text Available Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV and Sabin attenuated type 1 poliovirus (Sabin PV in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5 m-RNA in neuronal cells at the beginning of infection (up to 4 h as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

  19. Expression of the Surface Glycoproteins of Human Parainfluenza Virus Type 3 by Bovine Parainfluenza Virus Type 3, a Novel Attenuated Virus Vaccine Vector

    OpenAIRE

    Haller, Aurelia A.; Miller, Tessa; Mitiku, Misrach; Coelingh, Kathleen

    2000-01-01

    Bovine parainfluenza virus type 3 (bPIV3) is being evaluated as an intranasal vaccine for protection against human PIV3 (hPIV3). In young infants, the bPIV3 vaccine appears to be infectious, attenuated, immunogenic, and genetically stable, which are desirable characteristics for an RNA virus vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive...

  20. Outstanding challenges for rotavirus vaccine introduction in low-income countries

    DEFF Research Database (Denmark)

    Ustrup, Marte; Madsen, Lizell B; Bygbjerg, Ib C

    2011-01-01

    Rotavirus infections are the most common cause of severe diarrhoea in children worldwide. Two internationally licensed rotavirus vaccines have proven to be efficacious in middle and high-income countries and they could potentially be valuable tools for the prevention of rotavirus-associated diarr......Rotavirus infections are the most common cause of severe diarrhoea in children worldwide. Two internationally licensed rotavirus vaccines have proven to be efficacious in middle and high-income countries and they could potentially be valuable tools for the prevention of rotavirus......-associated diarrhoea in low-income countries where the disease burden is greatest. However, before the vaccines can be introduced into the national immunisation programmes in these countries, many challenges related to the financing of vaccine purchase, the cold chain capacity and vaccine efficacy must be overcome....... There is also a need for political commitment to prevent rotavirus infections as well as a need for an overall strengthening of the health systems in low-income countries. If these challenges were met, rotavirus vaccination could substantially improve child health and survival from rotavirus...

  1. Rotavirus disease in Guinea-Bissau, West Africa: a review of longitudinal community and hospital studies

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Aaby, Peter; Mølbak, Kåre;

    2010-01-01

    Rotavirus is one of the most common causes of childhood diarrheal disease and deaths in sub-Saharan Africa. This article reviews community- and hospital-based surveillance of rotavirus disease in Bissau, Guinea-Bissau, West Africa. Here, rotavirus infections exhibit a seasonal pattern, with annual...... epidemics occurring during the relatively dry and cooler months, from January to April, and few cases registered from May to December. Most children (74%) experience their first infection before the age of 2 years, and rotavirus has been identified as the most pathogenic of all diarrheal agents during 2...

  2. Prospective study of the burden of rotavirus gastroenteritis in Danish children and their families

    DEFF Research Database (Denmark)

    Hoffmann, Thomas; Iturriza, Miren; Faaborg-Andersen, Jens;

    2011-01-01

    This was the first study to characterize the total burden of rotavirus gastroenteritis (RVGE) at both hospital and general physician (GP) clinics in Denmark, and also the first to confirm rotavirus (RV) as the leading cause of acute gastroenteritis (GE) among children......This was the first study to characterize the total burden of rotavirus gastroenteritis (RVGE) at both hospital and general physician (GP) clinics in Denmark, and also the first to confirm rotavirus (RV) as the leading cause of acute gastroenteritis (GE) among children...

  3. Socio-economic modelling of rotavirus vaccination in Castilla y Leon, Spain.

    Science.gov (United States)

    Pérez-Rubio, Alberto; Luquero, Francisco Javier; Eiros Bouza, Jose María; Castrodeza Sanz, Jose Javier; Bachiller Luque, Maria Rosario; de Lejarazu, Raúl Ortiz; Sánchez Porto, Antonio

    2011-09-01

    Rotavirus is one of the main causes of acute gastroenteritis in infants and young children. Furthermore, rotavirus is the leading cause of hospitalization and death from acute gastroenteritis among infants and young children worldwide. Although death due to rotavirus is rare in industrialized regions such as Spain, the rotavirus disease burden and its economic impact is severe. This study aims to assess systematic vaccination against rotavirus economically and socially in a Spanish region. Economic cost-effectiveness and cost-benefit assessment through a choice tree was designed. We estimated health provider costs, economic costs and quality-adjusted life years (QALYs) lost due to rotavirus infections. The study includes a fictitious cohort of 100,000 children from Castilla y Leon who were also administered the rotavirus vaccine together with diphtheria and tetanus toxoids and pertussis (DTP) . The study adopted a society and health care system perspective. A sensitivity analysis was developed to assess the uncertainty of some variables. According to the estimated incidence rate for children in Castilla y Leon, rotavirus immunization is projected to prevent 45% of cases with RotaTeq and 57% with Rotarix. The respective cost per QALY is about Euro 75,000 and 50,000 from the perspective of the health care system. Routine infant vaccination in Castilla y Leon using either rotavirus vaccine is not profitable from the payer's perspective and is not cost-effective under basic case assumptions unless the vaccine is available at a lower cost.

  4. Emergence of a novel equine-like G3P[8] inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children.

    Science.gov (United States)

    Cowley, Daniel; Donato, Celeste M; Roczo-Farkas, Susie; Kirkwood, Carl D

    2016-02-01

    During 2013, a novel equine-like G3P[8] rotavirus emerged as the dominant strain in Australian children with severe rotavirus gastroenteritis. Full genome analysis demonstrated that the strain was an inter-genogroup reassortant, containing an equine-like G3 VP7, a P[8] VP4 and a genogroup 2 backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. The genome constellation of the equine-like G3P[8] was distinct to Australian and global G3P[8] strains. Phylogenetic analysis demonstrated a genetic relationship to multiple gene segments of Japanese strains RVA/JPN/S13-30/2013/G3P[4] and RVA/Human-wt/JPN/HC12016/2012/G1P[8]. The Australian equine-like G3P[8] strain displayed a distinct VP7 antigenic profile when compared with the previously circulating Australian G3P[8] strains. Identification of similar genes in strains from several geographical regions suggested the equine-like G3P[8] strain was derived by multiple reassortment events between globally co-circulating strains from both human and animal sources. This study reinforces the dynamic nature of rotavirus strains and illustrates the potential for novel human/animal reassortant strains to emerge within the human population.

  5. SEASONALITY OF ROTAVIRUS IN SOUTH ASIA: A META-ANALYSIS APPROACH ASSESSING ASSOCIATIONS WITH TEMPERATURE, PRECIPTATION, AND VEGETATION INDEX

    Science.gov (United States)

    Background: Rotavirus infection causes a significant proportion of diarrhea in infants and young children worldwide leading to dehydration, hospitalization, and in some cases death. Rotavirus infection represents a significant burden of disease in developing countries, such as th...

  6. ACUMULACIÓN DE LA PROTEÍNA DE CHOQUE TÉRMICO, HSC70, EN CÉLULAS MA104 DESPUÉS DE LA INFECCIÓN CON ROTAVIRUS Increase of heat shock cognate protein, HSC70, in MA104 cells following rotavirus infection

    Directory of Open Access Journals (Sweden)

    Diana Rocio Pulido Morera

    2007-12-01

    rotavirus particles during the infection of MA104 cells, but changes in the accumulation levels of this protein through the rotavirus infection cycle are unknown. Objetive. To determine if the accumulation levels of HSC70 in MA104 cells change during the infection by rotavirus. Materials and methods. Immunofluorescene microscopy, Western blotting an ELISA were used in order to determine HSC70 accumulation levels in MA104 cells after infection (0 up to 16 h p.i. by rotavirus strains Wa (human, Rf (bovine and RRV (simian. Additionally, a rabbit polyclonal serum against purified rotavirus particles was used for detecting rotavirus antigen in an immunoperoxidase assay. Results. The immunofluorescence staining of cells infected with each of three rotavirus strains showed a direct correlation between the increase of fluorescence in the cytoplasm and the increase of the viral antigen. The intensity of the cytoplasm fluorescence was 1.1 to 2.0 times higher in infected cells than that observed in control cells. On the other hand, the intensity of the fluorescence in the cell membrane was similar to that of the non-infected control cells. The Western blotting assay did not allow to establish measurable differences between infected and non-infected MA104 cells, because the increase of the protein are below the detection limit. According to the results of ELISA, HSC70 level increases 1 to 3 times in MA104 cells after (8 h p.i. the infection with strain RRV, whereas infection with strain RF produced an increase which ranged from 1.3 to 2.5 times after 10 h p.i. Infection by strain Wa was correlated with un increase of HSC70 level between 1.7 and 3.0 times after 2 h p.i. Conclusions. The results suggest that the increase of HSC70 accumulation level possibly corresponds to an increased expression of its gene during the rotavirus infection and probably it is involved in rotavirus multiplication steps additional to those of entry and exit processes.

  7. Rotavirus strain diversity in Blantyre, Malawi, from 1997 to 1999.

    Science.gov (United States)

    Cunliffe, N A; Gondwe, J S; Graham, S M; Thindwa, B D; Dove, W; Broadhead, R L; Molyneux, M E; Hart, C A

    2001-03-01

    In a 2-year study of viral gastroenteritis in children in Blantyre, Malawi, the diversity of rotavirus strains was investigated by using electropherotyping, reverse transcription-PCR amplification of the VP7 and VP4 genes (G and P genotyping), and nucleotide sequencing. Of 414 rotavirus strains characterized, the following strain types were identified: P[8], G1 (n = 111; 26.8%); P[6], G8 (n = 110; 26.6%); P[8], G3 (n = 93; 22.5%); P[4], G8 (n = 31; 7.5%); P[8], G4 (n = 21; 5.1%); P[6], G3 (n = 12; 2.9%); P[6], G1 (n = 7; 1.7%); P[6], G9 (n = 3; 0.7%); P[6], G4 (n = 3; 0.7%); P[4], G3 (n = 1; 0.2%); and mixed (n = 15; 3.6%). While all strains could be assigned a G type, seven strains (1.7%) remained P nontypeable. The majority of serotype G8 strains and all serotype G9 strains had short electropherotype profiles. All remaining typeable strains had long electropherotypes. Divergent serotype G1 rotaviruses, which contained multiple base substitutions in the 9T-1 primer binding site, were commonly identified in the second year of surveillance. Serotype G2 was not identified. Overall, G8 was the most frequently identified VP7 serotype (n = 144; 34.8%) and P[8] was the most frequently detected VP4 genotype (n = 227; 54.8%). Partial sequence analysis of the VP4 gene of genotype P[8] rotaviruses identified three distinct clusters, which predominantly (but not exclusively) comprised strains belonging to a distinct VP7 serotype (G1, G3, or G4). As a result of mutations in the 1T-1 primer binding site, strains belonging to each cluster required a separate primer for efficient typing. One cluster, represented by P[8], G4 strain OP354, was highly divergent from the established Wa and F45 VP4 P[8] lineages. As is the case for some other countries, the diversity of rotaviruses in Malawi implies that rotavirus vaccines in development will need to protect against a wider panel of serotypes than originally envisioned.

  8. Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice.

    Science.gov (United States)

    Wu, Wen-Huey; Wang, Shu-Huei; Kuan, I-I; Kao, Ya-Shi; Wu, Pei-Jhen; Liang, Chan-Jung; Chien, Hsiung-Fei; Kao, Chiu-Hua; Huang, Ching-Jang; Chen, Yuh-Lien

    2010-09-01

    Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

  9. Tamarind seed coat extract restores reactive oxygen species through attenuation of glutathione level and antioxidant enzyme expression in human skin fibroblasts in response to oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Oranuch Nakchat; Nonthaneth Nalinratana; Duangdeun Meksuriyen; Sunanta Pongsamart

    2014-01-01

    Objective:To investigate the role and mechanism of tamarind seed coat extract (TSCE) on normal human skin fibroblast CCD-1064Sk cells under normal and oxidative stress conditions induced by hydrogen peroxide (H2O2). Methods:Tamarind seed coats were extracted with boiling water and then partitioned with ethyl acetate before the cell analysis. Effect of TSCE on intracellular reactive oxygen species (ROS), glutathione (GSH) level, antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activity including antioxidant protein expression was investigated. Results: TSCE significantly attenuated intracellular ROS in the absence and presence of H2O2 by increasing GSH level. In the absence of H2O2, TSCE significantly enhanced SOD and catalase activity but did not affected on GPx. Meanwhile, TSCE significantly increased the protein expression of SOD and GPx in H2O2-treated cells. Conclusions: TSCE exhibited antioxidant activities by scavenging ROS, attenuating GSH level that could protect human skin fibroblast cells from oxidative stress. Our results highlight the antioxidant mechanism of tamarind seed coat through an antioxidant enzyme system, the extract potentially benefits for health food and cosmeceutical application of tamarind seed coat.

  10. Cost-effectiveness of rotavirus immunization in vietnam: Exploring impacts of herd immunity and patterns of breastfeedingof

    NARCIS (Netherlands)

    Tu, H.A.T.; Coyte, P.; Li, S.C.; Postma, M.J.

    2012-01-01

    OBJECTIVES: : Rotavirus is the most common cause of severe diarrhoea worldwide. This study was designed to evaluate the cost-effectiveness of rotavirus immunization in Vietnam taking into account herd immunity and patterns of breastfeeding. The affordability of implementing universal rotavirus immun

  11. Human Transcriptome Response to Immunization with Live- Attenuated Venezuelan equine encephalitis Virus Vaccine (TC 83): Analysis of Whole Blood

    Science.gov (United States)

    2016-11-21

    Cynomolgus macaques (Macaca 519 fascicularis). Virology J 2007; 4: 82. DOI: 10.1186/1743-422X-4-82. 520 13. Koterski J, Twenhafel N, Porter A, Reed DS...UNCLASSIFIED Page 26 of 39 18. Erwin-Cohen RA, Porter A, Pittman PR, Rossi CA, DaSilva L. (2012). Host responses to 537 live-attenuated...T, Stohlman SA, Bergmann CC, Diamond 551 MS, Virgin HW, Sen GC. Interferon-induced Ifit2/ISG54 protects mice from lethal VSV 552 neuropathogenesis

  12. The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales.

    Science.gov (United States)

    Atkins, Katherine E; Shim, Eunha; Carroll, Stuart; Quilici, Sibilia; Galvani, Alison P

    2012-11-01

    Rotavirus vaccines have shown great potential for reducing the disease burden of the major cause of severe childhood gastroenteritis. The decision regarding whether rotavirus vaccination will be introduced into the national immunization program is currently being reviewed. The conclusions of previous evaluations of rotavirus vaccination cost-effectiveness contradict each other. This is the first analysis to incorporate a dynamic transmission model to assess the cost-effectiveness of rotavirus vaccination in England and Wales. Most previously reported models do not include herd protection, and thus may underestimate the cost-effectiveness of vaccination against rotavirus. We incorporate a dynamic model of rotavirus transmission in England and Wales into a cost-effectiveness analysis to determine the probability that the pentavalent rotavirus vaccination will be cost-effective over a range of full-course vaccine prices. This novel approach allows the cost-effectiveness analysis to include a feasible level of herd protection provided by a vaccination program. Our base case model predicts that pentavalent rotavirus vaccination is likely to be cost-effective in England and Wales at £ 60 per course. In some scenarios the vaccination is predicted to be not only cost-effective but also cost-saving. These savings could be generated within ten years after vaccine introduction. Our budget impact analysis demonstrates that for the realistic base case scenarios, 58-96% of the cost outlay for vaccination will be recouped within the first four years of a program. Our results indicate that rotavirus vaccination would be beneficial to public health and could be economically sound. Since rotavirus vaccination is not presently on the immunization schedule for England and Wales but is currently under review, this study can inform policymakers of the cost-effectiveness and budget impact of implementing a mass rotavirus vaccine strategy.

  13. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons

    Science.gov (United States)

    Ramsden, Nigel; Perrin, Jessica; Ren, Zhao; Lee, Byoung Dae; Zinn, Nico; Dawson, Valina L.; Tam, Danny; Bova, Michael; Delling, Manja; Drewes, Gerard; Bantscheff, Marcus; Bard, Frederique; Dawson, Ted M.; Hopf, Carsten

    2013-01-01

    Leucine-rich repeat kinase-2 (LRRK2) mutations are the most important cause of familial Parkinson's disease and non-selective inhibitors are protective in rodent disease models. Due to their poor potency and selectivity, the neuroprotective mechanism of these tool compounds has remained elusive so far and it is still unknown whether selective LRRK2 inhibition can attenuate mutant LRRK2-dependent toxicity in human neurons. Here, we employ a chemoproteomics strategy to identify potent, selective and metabolically stable LRRK2 inhibitors. We demonstrate that CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency. These precise chemical probes further validate this emerging therapeutic strategy. They will enable more detailed studies of LRRK2-dependent signaling and pathogenesis and accelerate drug discovery. PMID:21812418

  14. Development of a Real-time PCR test for porcine group A rotavirus diagnosis

    Directory of Open Access Journals (Sweden)

    Elizabeth C.M. Marconi

    2015-01-01

    Full Text Available Group A Rotavirus (RVA is one of the most common causes of diarrhea in humans and several animal species. A SYBR-Green Real-Time polymerase chain reaction (PCR was developed to diagnose RVA from porcine fecal samples, targeting amplification of a 137-bp fragment of nonstructural protein 5 (NSP5 gene using mRNA of bovine NADH-desidrogenase-5 as exogenous internal control. Sixty-five samples were tested (25 tested positive for conventional PCR and genetic sequencing. The overall agreement (kappa was 0.843, indicating 'very good' concordance between tests, presenting 100% of relative sensitivity (25+ Real Time PCR/25+ Conventional PCR and 87.5% of relative sensitivity (35- Real Time PCR/40- Conventional PCR. The results also demonstrated high intra- and inter-assay reproducibility (coefficient of variation ≤1.42%; thus, this method proved to be a fast and sensitive approach for the diagnosis of RVA in pigs.

  15. Diversity of VP7 genes of G1 rotaviruses isolated in Iran, 2009-2013.

    Science.gov (United States)

    Jalilvand, Somayeh; Afchangi, Atefeh; Mohajel, Nasir; Roohvand, Farzin; Shoja, Zabihollah

    2016-01-01

    Genotype G1 of rotaviruses (RVs) is the most prevalent strain in human RV infections around the world. The present study evaluated genetic variations in the VP7 gene of RV G1 genotype isolates from Iran. Genetic and phylogenetic analyses indicated that RV strains from Iran clustered with G1 lineages IA, IC, and IIC, showing highest average of similarity versus reference sequences of the G1 lineages I and II. This study highlights the genetic pattern of G1 RV on the basis of distinct lineages and sublineages and indicates the importance of continuous monitoring on genetic variation and evolution pattern of G1 RV strains across the Iranian population for the final aim of RV vaccine introduction.

  16. Perspectivas de la diarrea por rotavirus en El Salvador.

    Directory of Open Access Journals (Sweden)

    Roberto Arturo Zablah

    2009-11-01

    Full Text Available Materiales y métodos: En diciembre del año 2000, un brote epidémico de gastroenteritis ocurrió en El Salvador que se asoció con numerosas hospitalizaciones y muertes de niños en todo el país. El Ministerio de Salud Pública se mostró preocupado, pues se ignoraba su etiología y las medidas de control usuales fueron ineficaces. El brote lo produjo un rotavirus, y las medidas de control fueron rediseñadas para mejorar el tratamiento con rehidratación oral e iniciar un sistema de vigilancia para conocer los agentes etiológicos de la gastroenteritis. Se colectaron datos clínicos, demográficos y también muestras de heces en niños menores de 5 años que presentaron gastroenteritis aguda. A las muestras de heces se les realizó exámenes para determinar la presencia de rotavirus, parásitos y bacterias. El sistema revigilancia se extrapoló con los datos nacionales para estimar el impacto nacional de la enfermedad por rotavirus. Resultados: La vigilancia epidemiológica entre mayo 2001 y abril 2002 demostró que el rotavirus tuvo predominio en la estación de invierno, y se asoció con la presencia de vómitos que se informaron en 27% de 12,083 consultas por diarrea. Los niños con gastroenteritis por rotavirus eran lactantes con un promedio de edad de 9 meses en comparación con las diarreas causadas por otros agentes (13 meses para bacterias y 16 meses para parásitos. Al extrapolar los datos nacionales, se estimó que el riesgo de un niño que consultaba por diarrea por rotavirus, que se hospitalizaba, y riesgo de muerte antes de los 5 años fue 1:7, 1:56, y 1:531, respectivamente. Conclusiones: El brote de gastroenteritis en niños menores de 5 años entre diciembre 2000 y febrero 2001 representó un exagerado predominio estacional de la infección por rotavirus. La actividad de vigilancia epidemiológica después del brote sugiere que el rotavirus es la causa mas frecuente de diarrea en El Salvador. Un seguimiento en la vigilancia

  17. Dielectrophoresis and dielectrophoretic impedance detection of adenovirus and rotavirus

    Science.gov (United States)

    Nakano, Michihiko; Ding, Zhenhao; Suehiro, Junya

    2016-01-01

    The aim of this study is the electrical detection of pathogenic viruses, namely, adenovirus and rotavirus, using dielectrophoretic impedance measurement (DEPIM). DEPIM consists of two simultaneous processes: dielectrophoretic trapping of the target and measurement of the impedance change and increase in conductance with the number of trapped targets. This is the first study of applying DEPIM, which was originally developed to detect bacteria suspended in aqueous solutions, to virus detection. The dielectric properties of the viruses were also investigated in terms of their dielectrophoretic behavior. Although their estimated dielectric properties were different from those of bacteria, the trapped viruses increased the conductance of the microelectrode in a manner similar to that in bacteria detection. We demonstrated the electrical detection of viruses within 60 s at concentrations as low as 70 ng/ml for adenovirus and 50 ng/ml for rotavirus.

  18. Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells.

    Science.gov (United States)

    Ferrand, Nathalie; Stragier, Emilien; Redeuilh, Gérard; Sabbah, Michèle

    2012-10-01

    CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

  19. Efficacy of synbiotic treatment in children with acute rotavirus diarrhea

    OpenAIRE

    Made Ratna Dewi; Yati Soenarto; I Putu Gede Karyana

    2015-01-01

    Background Diarrhea is one of the major causes of morbidity and mortality in children throughout the world, mostly due to rotavirus infection. In daily practice, we routinely use the World Health Organization Five steps for managing acute diarrhea.This practice has shown great success in diarrhea management, but concerns remain on reducing the duration of diarrhea to prevent complications. Synbiotics can reduce the severity of diarrhea. However, there has been limited data on synbiotic therap...

  20. Sequence analysis and structural implications of rotavirus capsid proteins.

    Science.gov (United States)

    Parbhoo, N; Dewar, J B; Gildenhuys, S

    Rotavirus is the major cause of severe virus-associated gastroenteritis worldwide in children aged 5 and younger. Many children lose their lives annually due to this infection and the impact is particularly pronounced in developing countries. The mature rotavirus is a non-enveloped triple-layered nucleocapsid containing 11 double stranded RNA segments. Here a global view on the sequence and structure of the three main capsid proteins, VP2, VP6 and VP7 is shown by generating a consensus sequence for each of these rotavirus proteins, for each species obtained from published data of representative rotavirus genotypes from across the world and across species. Degree of conservation between species was represented on homology models for each of the proteins. VP7 shows the highest level of variation with 14-45 amino acids showing conservation of less than 60%. These changes are localised to the outer surface alluding to a possible mechanism in evading the immune system. The middle layer, VP6 shows lower variability with only 14-32 sites having lower than 70% conservation. The inner structural layer made up of VP2 showed the lowest variability with only 1-16 sites having less than 70% conservation across species. The results correlate with each protein's multiple structural roles in the infection cycle. Thus, although the nucleotide sequences vary due to the error-prone nature of replication and lack of proof reading, the corresponding amino acid sequence of VP2, 6 and 7 remain relatively conserved. Benefits of this knowledge about the conservation include the ability to target proteins at sites that cannot undergo mutational changes without influencing viral fitness; as well as possibility to study systems that are highly evolved for structure and function in order to determine how to generate and manipulate such systems for use in various biotechnological applications.

  1. Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

    Directory of Open Access Journals (Sweden)

    Wing-Hon Lai

    Full Text Available Functional endothelial-like cells (EC have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC, human embryonic stem cells (hESC-EC and human induced pluripotent stem cells (hiPSC-EC, and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC and BM-EC (P>0.05. While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05, the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05. Compared with medium, transplanting BM-EC (n = 6, HUVEC (n = 6, hESC-EC (n = 8 or hiPSC-EC (n = 8 significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment

  2. Application of Xiyanping in treatment of infantile rotavirus diarrhea

    Institute of Scientific and Technical Information of China (English)

    Tian-Xiong Tang

    2016-01-01

    Objective: To observe the application effect of Xiyanping in the treatment of infantile rotavirus diarrhea.Methods:A total of 80 children with rotavirus diarrhea who were admitted in our hospital from January, 2014 to April, 2015 were included in the study and randomized into the treatment group and the control group with 40 cases in each group. The patients in the two groups were given ribavirin 10 mg/kg.d, iv drip, qd. On this basis, the patients in the treatment group were given additional Xiyanping injection 7.5 mg/kg, iv drip, qd. The symptom and sign relieving time and temperature reduced degree after treatment in the two groups were compared. The serum BDNF, NGF, and NTF levels in the two groups were detected.Results:The treatment total effective rate in the treatment group was significantly higher than that in the control group (P<0.05). The symptom and sign relieving time in the treatment group was significantly shorter than that in the control group (P<0.05), and the temperature recovering degree was significantly superior to that in the control group (P<0.05). The serum BDNF, NGF, and NTF levels after treatment in the treatment group were significantly higher than those in the control group (P<0.05).Conclusions: Xiyanping in combined with ribavirin in the treatment of infantile rotavirus diarrhea can effectively relieve the symptoms and signs, and protect the neurological function, with efficacy superior to that by pure ribavirin treatment.

  3. [Epidemic of nosocomial infection by rotavirus in a neonatology service].

    Science.gov (United States)

    Bentama, I; Soussi, I; Ghanimi, Z; Riane, S; Tligui, H; Mdaghri Alaoui, A; Thimou Izgua, A

    2012-01-01

    The goal of work is to establish a clinical descriptive analysis of the epidemic of nosocomial rotavirus occurred in the Neonatal Unit of the Hospital's Child Rabat for a winter period. We systematically collected all the patients of the service right from the first case of rotavirus nosocomial infection. Patients with a stay of less than 48 hours of hospitalization were excluded. We have established operating sheets for all positive cases, with the term, birth weight, postnatal age and weight during the sampling, clinical symptoms, treatment, and the evolution. Out of the 36 cases analyzed (where 26 preterm and 10 term neonates), 12 samples were positive for rotavirus, so one third of patients. The patients with positive samples were in 75% symptomatic cases. The clinical signs were represented in term newborns with stool weight with stagnant fluid in 2 cases and weight loss in one case and in premature infants with mucous stools with abdominal distension in 2/3 of cases, and fluid and stool dehydration in 1/3 of cases. A very low rate of breastfeeding (17%) was noted among all newborns service in this epidemic. We performed the isolation of positive patients, with a strengthening of hygiene measures. In addition, infants were started on symptomatic treatment with careful clinical monitoring. Evolution was complicated by necrotizing enterocolitis in 3 cases of preterm infants.

  4. Electron microscopic analysis of rotavirus assembly-replication intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Boudreaux, Crystal E.; Kelly, Deborah F. [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); McDonald, Sarah M., E-mail: mcdonaldsa@vtc.vt.edu [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); Department of Biomedical Sciences and Pathobiology, Virginia—Maryland Regional College of Veterinary Medicine, Blacksburg, VA (United States)

    2015-03-15

    Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy.

  5. 鼠李糖乳杆菌对感染人轮状病毒乳鼠空肠黏膜上皮细胞的保护作用%Protective Effect of Lactobacillus Rhamnosus GG on Jejunum Mucosal EpithelialCells of Human Rotavirus-infected Neonatal Mice

    Institute of Scientific and Technical Information of China (English)

    张振; 王晓梅; 汤建桥; 高源; 王宝香; 郑义

    2012-01-01

    目的 观察鼠李糖乳杆菌(Lactobacillus rhamnosus GG,LGG)对感染人轮状病毒(human rotavirus,HRV)乳鼠空肠黏膜上皮细胞的保护作用.方法 将60只昆明种乳鼠均分为4组:灌服HRV作为感染组;灌服HRV前和后灌服LGG作为预处理组和治疗组;正常对照组灌服细胞培养液.从第4天开始,连续5 d观察各组乳鼠的临床症状,每天2次检测乳鼠大便HRV抗原.在实验的第9天随机处死每组中的8只乳鼠,取出空肠段苏木精-伊红染色,利用Image-Pro Plus 5.1图像软件分析各组乳鼠空肠黏膜厚度、绒毛高度和隐窝深度.利用光学显微镜和透射电子显微镜观察乳鼠空肠黏膜上皮细胞的病理变化.结果 至第9天,对照组乳鼠无腹泻、无死亡.HRV感染组、预处理组、治疗组乳鼠腹泻率和死亡率分别为100.00%、46.67%,13.33%、0%,26.66%、6.67%.对照组、HRV感染组、预处理组、治疗组乳鼠空肠黏膜隐窝深度分别为(35.2±2.4)、(45.9±3.6)、(35.8±5.6)和(38.9±2.9)μm,HRV感染组明显高于其它3组(均P<0.01).病理检测发现HRV感染组乳鼠空肠黏膜上皮细胞出现广泛的空泡样变性,而预处理组和治疗组乳鼠空肠黏膜上皮细胞空泡样变性的情况均有减少.预处理组与治疗组相比,前者对乳鼠空肠黏膜上皮细胞的保护效果更好.结论 LGG对感染HRV的乳鼠空肠黏膜上皮细胞有一定的保护作用,感染前灌服LGG的保护效果好于感染后灌服.%Objective To investigate the possible protective effect of Laclobacillus rhamnosus GG(LGG)on jejunum muco-sal epithelial cells of human rotavirus(HRV)-infected neonatal mice. Methods Sixty 4-day-old Kunming mice were randomly divided into control group, HRV infected group, LGG pretreated group (treated before HRV infection) and LGG treated group (treated after HRV infection). From 4th to 9th day,the clinical manifestation of neonatal mice was observed,and stool HRV antigen was examined. On the 9th day,8

  6. Effect of breastfeeding promotion interventions on cost-effectiveness of rotavirus immunization in Indonesia

    NARCIS (Netherlands)

    Suwantika, Auliya A.; Postma, Maarten J.

    2013-01-01

    BACKGROUND: Rotavirus infection has been reported to be responsible for the majority of severe diarrhea in children under-5-years-old in Indonesia. Breast milk is considered to give protection against rotavirus infection. Increasing breastfeeding promotion programs could be an alternative target to

  7. Inhibition of cyclooxygenase activity reduces rotavirus infection at a postbinding step.

    NARCIS (Netherlands)

    J.W. Rossen (John); J. Bouma (Janneke); R.H. Raatgeep (Rolien); H.A. Büller (Hans); A.W.C. Einerhand (Sandra)

    2004-01-01

    textabstractElevated levels of prostaglandins (PGs), products of cyclooxygenases (COXs), are found in the plasma and stool of rotavirus-infected children. We sought to determine the role of COXs, PGs, and the signal transduction pathways involved in rotavirus infection to elucidate

  8. Cost-effectiveness of rotavirus immunization in Vietnam: Results and challenges

    NARCIS (Netherlands)

    Tu, H.A.T.; Rozenbaum, M.; Coyte, P.C.; Li, S.C.; Postma, M.J.

    2011-01-01

    OBJECTIVES: To assess the cost-effectiveness of universal rotavirus immunization, explicitly the use of Rotateq® and affordability of implementing rotavirus immunization based on the Global Alliance for Vaccines and Immunization (GAVI)-subsidized vaccine price in the context of Vietnamese health car

  9. Inhibition of cyclooxygenase activity reduces rotavirus infection at a postbinding step

    NARCIS (Netherlands)

    Rossen, John W A; Bouma, Janneke; Raatgeep, Rolien H C; Büller, Hans A; Einerhand, Alexandra W C

    2004-01-01

    Elevated levels of prostaglandins (PGs), products of cyclooxygenases (COXs), are found in the plasma and stool of rotavirus-infected children. We sought to determine the role of COXs, PGs, and the signal transduction pathways involved in rotavirus infection to elucidate possible new targets for anti

  10. Detection and distribution of rotavirus in raw sewage and creeks in Sao Paulo, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mehnert, D.U.; Stewien, K.E. (Univ. of Sao Paulo (Brazil))

    1993-01-01

    Rotavirus invection is an important cause of hospitalization and mortality of infants and children in developing countries, especially where the water supply and sewage disposal systems are in precarious conditions. This report describes the detection, quantitation, and distribution of rotaviruses in domestic sewage and sewage polluted creeks in the city of San Paulo. 22 refs., 1 fig., 3 tabs.

  11. Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice

    NARCIS (Netherlands)

    J.A. Boshuizen; J.H. Reimerink; A.M. Korteland-van Male (Anita); V.J. van Ham; H.A. Büller (Hans); J. Dekker (Jan); A.W.C. Einerhand (Sandra); M.P.G. Koopmans D.V.M. (Marion)

    2003-01-01

    textabstractRotavirus is the most important cause of infantile gastroenteritis. Since in vivo mucosal responses to a rotavirus infection thus far have not been extensively studied, we related viral replication in the murine small intestine to alterations in mucosal structure, epith

  12. Economic evaluations of rotavirus immunization for developing countries : a review of the literature

    NARCIS (Netherlands)

    Tu, H.A.T.; Woerdenbag, H.J.; Kane, S.; Rozenbaum, M.H.; Li, S.C.; Postma, M.J.

    2011-01-01

    Diarrhea is a leading cause of mortality for children under 5 years of age, and rotavirus is identified as the main cause of severe diarrhea worldwide. Since 2006, two rotavirus vaccines, Rotarix and Rotateq, have been available in the market. These vaccines have proved to have high efficacy in deve

  13. Estimating the costs of implementing the rotavirus vaccine in the national immunisation programme

    DEFF Research Database (Denmark)

    Madsen, Lizell B; Ustrup, Marte; Hansen, Kristian S;

    2014-01-01

    OBJECTIVES: Worldwide, rotavirus infections cause approximately 453,000 child deaths annually. Two licensed vaccines could be life- and cost-saving in low-income countries where the disease burden is highest. The aim of our study was to estimate the total cost of implementing the rotavirus vaccine...

  14. Rotavirus in Ireland: national estimates of disease burden, 1997 to 1998.

    LENUS (Irish Health Repository)

    Lynch, M

    2012-02-03

    BACKGROUND: We estimated the disease burden caused by rotavirus hospitalizations in the Republic of Ireland by using national data on the number of hospitalizations for diarrhea in children and laboratory surveillance of confirmed rotavirus detections. METHODS: We examined trends in diarrheal hospitalizations among children <5 years old as coded by ICD-9-CM for the period January, 1997, to December, 1998. We collated data on laboratory-confirmed rotavirus detections nationally for the same period among children <2 years old. We calculated the overall contribution of rotavirus to laboratory-confirmed intestinal disease in children <5 years old from INFOSCAN, a disease bulletin for one-third of the population. We compared data from all sources and estimated the proportion of diarrheal hospitalizations that are likely the result of rotavirus in children <5 years old. RESULTS: In children <5 years old, 9% of all hospitalizations are for diarrheal illness. In this age group 1 in 8 are hospitalized for a diarrheal illness, and 1 in 17 are hospitalized for rotavirus by 5 years of age. In hospitalized children <2 years old, 1 in 38 have a laboratory confirmed rotavirus infection. CONCLUSIONS: The disease burden of rotavirus hospitalizations is higher than in other industrialized countries. Access to comprehensive national databases may have contributed to the high hospitalization rates, as well as a greater tendency to hospitalize children with diarrhea in Ireland.

  15. Increased Rotavirus Prevalence in Diarrheal Outbreak Precipitated by Localized Flooding, Solomon Islands, 2014.

    Science.gov (United States)

    Jones, Forrest K; Ko, Albert I; Becha, Chris; Joshua, Cynthia; Musto, Jennie; Thomas, Sarah; Ronsse, Axelle; Kirkwood, Carl D; Sio, Alison; Aumua, Audrey; Nilles, Eric J

    2016-05-01

    Flooding on 1 of the Solomon Islands precipitated a nationwide epidemic of diarrhea that spread to regions unaffected by flooding and caused >6,000 cases and 27 deaths. Rotavirus was identified in 38% of case-patients tested in the city with the most flooding. Outbreak potential related to weather reinforces the need for global rotavirus vaccination.

  16. Construction of Prophylactic Human Papillomavirus Type 16 L1 Capsid Protein Vaccine Delivered by Live Attenuated Shigella flexneri Strain sh42

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng YANG; Xin-Zhong QU; Kai WANG; Jin ZHENG; Lü-Sheng SI; Xiao-Ping DONG; Yi-Li WANG

    2005-01-01

    To express human papillomavirus (HPV) L1 capsid protein in the recombinant strain of Shigella and study the potential of a live attenuated Shigella-based HPV prophylactic vaccine in preventing HPV infection, the icsA/virG fragment of Shigella-based prokaryotic expression plasmid pHS3199 was constructed.HPV type 16 L 1 (HPV 16L 1) gene was inserted into plasmid pHS 3199 to form the pHS3199-HPV 16L1construct, and pHS3199-HPV16L1 was electroporated into a live attenuated Shigella strain sh42. Western blotting analysis showed that HPV 16L1 could be expressed stably in the recombinant strain sh42-HPV 16L1.Sereny test results were negative, which showed that the sh42-HPV16L1 lost virulence. However, the attenuated recombinant strain partially maintained the invasive property as indicated by the HeLa cell infection assay. Specific IgG, IgA antibody against HPV16L1 virus-like particles (VLPs) were detected in the sera,intestinal lavage and vaginal lavage from animals immunized by sh42-HPV 16L 1. The number of antibodysecreting cells in the spleen and draining lymph nodes were increased significantly compared with the control group. Sera from immunized animals inhibited murine hemagglutination induced by HPV16L1 VLPs, which indicated that the candidate vaccine could stimulate an efficient immune response in guinea pig's mucosal sites. This may be an effective strategy for the development of an HPV prophylactic oral vaccine.

  17. Morusin inhibits human cervical cancer stem cell growth and migration through attenuation of NF-κB activity and apoptosis induction.

    Science.gov (United States)

    Wang, Li; Guo, Huijie; Yang, Liuqi; Dong, Lihua; Lin, Caiyu; Zhang, Jie; Lin, Ping; Wang, Xiujie

    2013-07-01

    Cancer stem cells (CSCs) are believed to be responsible for tumor metastasis, recurrence, and high mortality of cancer patients due to their high tumorigenicity resistance to chemo-radiotherapy. Morusin possesses anti-cancer activity through attenuation of NF-κB activity, which is up-regulated in cancer stem cells. The purpose of this study is to confirm the growth and migration inhibition effect of morusin on human cervical CSCs, and to clarify its partial mechanism of activity. Human cervical CSCs were enriched using non-adhesive culture system. Their stemness characteristics were identified with tumor sphere formation, self-renewal, toluidine blue staining, migration assays, RT-PCR analysis, and immunofluorescence staining of putative stem cell markers, Oct4, SOX2, and ALDH1; the epithelial-to-mesenchymal (EMT) transition markers and relevant transcription factors were evaluated with Western blotting. The growth and migration inhibition effects of morusin on human cervical CSCs were tested by cell proliferation, tumor sphere formation, and transwell assay; apoptotic death of human cervical CSCs in response to morusin was measured with DAPI staining, apoptotic DNA fragmentation; NF-κBp65, Bcl-2, Bax, and caspase-3 protein expressions were detected through Western blotting. Under this non-adhesive culture system, typical tumor spheres appeared within 5-7 days, the tumor sphere formation, self-renewal, and cell migration, expressions of putative stem cell markers, EMT markers, and relevant transcription factors of the tumor sphere cells were increased significantly. After morusin treatment, the proliferation, tumor sphere formation, and migration of human cervical CSCs were decreased significantly, DAPI-stained apoptotic cells increased, apoptotic DNA fragmentations formed evidently; the expression levels of NF-κBp65 and Bcl-2 decreased significantly, Bax, and caspase-3 increased significantly in a dose-dependent manner. Using the non-adhesive culture system

  18. The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23

    Science.gov (United States)

    Weinhold, Mario; Eisenblätter, Martin; Jasny, Edith; Fehlings, Michael; Finke, Antje; Gayum, Hermine; Rüschendorf, Ursula; Renner Viveros, Pablo; Moos, Verena; Allers, Kristina; Schneider, Thomas; Schaible, Ulrich E.; Schumann, Ralf R.; Mielke, Martin E.; Ignatius, Ralf

    2013-01-01

    Background Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4+ and CD8+ T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs), which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S) 19, which has previously been employed successfully to vaccinate cattle. Methodology/Principal findings We first looked into the potential of S19 to hamper the cytokine-induced maturation of DCs; however, infected cells expressed CD25, CD40, CD80, and CD86 to a comparable extent as uninfected, cytokine-matured DCs. Furthermore, S19 activated DCs in the absence of exogeneous stimuli, enhanced the expression of HLA-ABC and HLA-DR, and was able to persist intracellularly without causing cytotoxicity. Thus, DCs provide a cellular niche for persisting brucellae in vivo as a permanent source of antigen. S19-infected DCs produced IL-12/23p40, IL-12p70, and IL-10, but not IL-23. While heat-killed bacteria also activated DCs, soluble mediators were not involved in S19-induced activation of human DCs. HEK 293 transfectants revealed cellular activation by S19 primarily through engagement of Toll-like receptor (TLR)2. Conclusions/Significance Thus, as an immunological prerequisite for vaccine efficacy, B. abortus S19 potently infects and potently activates (most likely via TLR2) human DCs to produce Th1-promoting cytokines. PMID:23805193

  19. Angiotensin-(1-7)-induced renal vasodilation in hypertensive humans is attenuated by low sodium intake and angiotensin II co-infusion.

    Science.gov (United States)

    van Twist, Daan J L; Houben, Alfons J H M; de Haan, Michiel W; Mostard, Guy J M; Kroon, Abraham A; de Leeuw, Peter W

    2013-10-01

    Current evidence suggests that angiotensin-(1-7) plays an important role in the regulation of tissue blood flow. This evidence, however, is restricted to studies in animals and human forearm. Therefore, we studied the effects of intrarenal angiotensin-(1-7) infusion on renal blood flow in hypertensive humans. To assess the influence of renin-angiotensin system activity, sodium intake was varied and co-infusion with angiotensin II was performed in a subgroup. In 57 hypertensive patients who were scheduled for renal angiography, renal blood flow was measured ((133)Xenon washout method) before and during intrarenal infusion of angiotensin-(1-7) (3 incremental doses: 0.27, 0.9, and 2.7 ng/kg per minute). Patients were randomized into low or high sodium intake. These 2 groups of patients received angiotensin-(1-7), with or without intrarenal co-infusion of angiotensin II (0.3 ng/kg per minute). Angiotensin-(1-7) infusion resulted in intrarenal vasodilation in patients adhering to a sodium-rich diet. This vasodilatory effect of angiotensin-(1-7) was clearly attenuated by low sodium intake, angiotensin II co-infusion, or both. Regression analyses showed that the prevailing renin concentration was the only independent predictor of angiotensin-(1-7)-induced renal vasodilation. In conclusion, angiotensin-(1-7) induces renal vasodilation in hypertensive humans, but the effect of angiotensin-(1-7) is clearly attenuated by low sodium intake and co-infusion of angiotensin II. This supports the hypothesis that angiotensin-(1-7) induced renal vasodilation depends on the degree of renin-angiotensin-system activation.

  20. The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23.

    Directory of Open Access Journals (Sweden)

    Mario Weinhold

    Full Text Available Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4(+ and CD8(+ T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs, which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S 19, which has previously been employed successfully to vaccinate cattle.We first looked into the potential of S19 to hamper the cytokine-induced maturation of DCs; however, infected cells expressed CD25, CD40, CD80, and CD86 to a comparable extent as uninfected, cytokine-matured DCs. Furthermore, S19 activated DCs in the absence of exogeneous stimuli, enhanced the expression of HLA-ABC and HLA-DR, and was able to persist intracellularly without causing cytotoxicity. Thus, DCs provide a cellular niche for persisting brucellae in vivo as a permanent source of antigen. S19-infected DCs produced IL-12/23p40, IL-12p70, and IL-10, but not IL-23. While heat-killed bacteria also activated DCs, soluble mediators were not involved in S19-induced activation of human DCs. HEK 293 transfectants revealed cellular activation by S19 primarily through engagement of Toll-like receptor (TLR2.Thus, as an immunological prerequisite for vaccine efficacy, B. abortus S19 potently infects and potently activates (most likely via TLR2 human DCs to produce Th1-promoting cytokines.

  1. Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

    Science.gov (United States)

    Meier, Anita F.; Suter, Mark; Schraner, Elisabeth M.; Humbel, Bruno M.; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S.

    2017-01-01

    Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species. PMID:28212334

  2. The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells.

    Science.gov (United States)

    Torres-Flores, Jesús M; Silva-Ayala, Daniela; Espinoza, Marco A; López, Susana; Arias, Carlos F

    2015-01-15

    Several molecules have been identified as receptors or coreceptors for rotavirus infection, including glycans, integrins, and hsc70. In this work we report that the tight junction proteins JAM-A, occludin, and ZO-1 play an important role during rotavirus entry into MA104 cells. JAM-A was found to function as coreceptor for rotavirus strains RRV, Wa, and UK, but not for rotavirus YM. Reassortant viruses derived from rotaviruses RRV and YM showed that the virus spike protein VP4 determines the use of JAM-A as coreceptor.

  3. Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

    Science.gov (United States)

    Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

    2014-12-01

    While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines.

  4. One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.

    Science.gov (United States)

    Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D

    2016-01-01

    Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98

  5. Changes in epidemiology of rotavirus in the Triângulo Mineiro region of Brazil: lack of two consecutive rotavirus seasons.

    Science.gov (United States)

    Dulgheroff, A C B; Figueiredo, E F; Gouvêa, V S; Domingues, A L S

    2014-12-01

    Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.

  6. Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps.

    Science.gov (United States)

    Basu, Reetobrata; Baumgaertel, Nicholas; Wu, Shiyong; Kopchick, John J

    2017-03-14

    Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We found that GH treatment of human melanoma cells upregulates expression of multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted in significantly increased drug retention, decreased cell proliferation and increased drug efficacy, compared to mock-transfected controls. Our set of findings identify an unknown mechanism of GH regulation in mediating melanoma drug resistance and validates GHR as a unique therapeutic target for sensitizing highly therapy-resistant human melanoma cells to lower doses of anti-cancer drugs.

  7. Cost-effectiveness of universal rotavirus vaccination in reducing rotavirus gastroenteritis in Ireland.

    LENUS (Irish Health Repository)

    Tilson, L

    2011-10-06

    We evaluated the cost-effectiveness of universal infant rotavirus (RV) vaccination compared to current standard of care of "no vaccination". Two RV vaccines are currently licensed in Ireland: Rotarix and RotaTeq. A cohort model used in several European countries was adapted using Irish epidemiological, resource utilisation and cost data. The base case model considers the impact of Rotarix vaccination on health-related quality of life of children under five years old from a healthcare payer perspective. Other scenarios explored the use of RotaTeq, impact on one caregiver, on societal costs and on cases that do not seek medical attention. Cost was varied between the vaccine list price (€100\\/course) in the base case and an assumed tender price (€70\\/course). One-way and probabilistic sensitivity analyses were conducted. Implementing universal RV vaccination may prevent around 1970 GP visits, 3280 A&E attendances and 2490 hospitalisations. A vaccination programme was estimated to cost approximately €6.54 million per year but €4.65 million of this would be offset by reducing healthcare resource use. The baseline ICER was €112,048\\/QALY and €72,736\\/QALY from the healthcare payer and societal perspective, respectively, falling to €68,896 and €43,916\\/QALY, respectively, if the impact on one caregiver was considered. If the price fell to €70 per course, universal RV vaccination would be cost saving under all scenarios. Results were sensitive to vaccination costs, incidence of RV infection and direct medical costs. Universal RV vaccination would not be cost-effective under base case assumptions. However, it could be cost-effective at a lower vaccine price or from a wider societal perspective.

  8. Detection of Rotavirus Genotypes in Korea 5 Years after the Introduction of Rotavirus Vaccines.

    Science.gov (United States)

    Chung, Ju-Young; Kim, Min-Sung; Jung, Tae Woong; Kim, Seong Joon; Kang, Jin-Han; Han, Seung Beom; Kim, Sang Yong; Rhim, Jung Woo; Kim, Hwang-Min; Park, Jae Hong; Jo, Dae Sun; Ma, Sang Hyuk; Jeong, Hye-Sook; Cheon, Doo-Sung; Kim, Jong-Hyun

    2015-10-01

    Rotavirus (RV) is one of the most important viral etiologic agents of acute gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now used worldwide, novel genotypes and outbreaks resulting from rare genotype combinations have emerged. This study documented RV genotypes in a Korean population of children with AGE 5 yr after the introduction of RVV and assessed potential genotype differences based on vaccination status or vaccine type. Children less than 5-yr-old diagnosed with AGE between October 2012 and September 2013 admitted to 9 medical institutions from 8 provinces in Korea were prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay and genotyped by multiplex reverse-transcription polymerase chain reaction. In 346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were infected with RV alone. Eighty-six of 114 RV-positive stool samples were successfully genotyped, and their combinations of genotypes were G1P[8] (36, 41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035). Vaccination history was available for 67 of 86 cases with successfully genotyped RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated (40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared to the unvaccinated group with no evidence of substitution with unusual genotype combinations.

  9. DETECCIÓN DE ROTAVIRUS BOVINO DEL GRUPO A. ANÁLISIS FILOGENÉTICO DEL GEN QUE CODIFICA PARA LA PROTEÍNA VP7 DE SU CÁPSIDE EXTERNA

    Directory of Open Access Journals (Sweden)

    M.E. Guriérrez

    2007-12-01

    Full Text Available Rotaviruses of group A are the major cause of diarrhea in young calves. To investigate the percentage ofgroup A rotaviruses in newborn calves and examine their evolutionary relationship with those from otheranimals and humans, we collected 74 fecal specimens from calves of 0-1 month of age with acute diarrheain towns of Colombia. Using an enzyme-linked immunosorbent assay was found that 7% of specimenswere positive for rotaviruses of group A. A representative strain (UJ was chosen to determine its nucleotide and to deduce amino acid sequences of VP7 gene. Nucleotide sequence of UJ VP7 gene was aligned withcorresponding sequences from 15 other strains, including 2 from cattle, 4 from swine, 6 from humans,and 1 each from chickens, dogs, and rabbits, by using Clustal W. Phylogenetic analysis was performedwith the MEGA analytical package. UJ strain clusters with a group A rotavirus strain (SI-B8 recentlyisolated from a calf in Slovenia in the neighbor-joining tree. UJ VP7 gene shares 84% and 70% amino acidsequence identity with the corresponding gene of the recently isolated bovine strains SI-B8 in Sloveniaand PP-1 in the United Kingdom. Identities in amino acid sequence between 48-73% were found withrotavirus of group A strains from humans and other animals, including swine, dogs, and rabbits. To ourknowledge, this is the first study to detect and characterize a bovine group A rotavirus in Colombia.Findings may increase our understanding of burden of viral gastroenteritis in calves and allow us todevelop strategies to prevent and control this important livestock disease.

  10. Safety and immunogenicity of a mutagenized, live attenuated Rift Valley fever vaccine, MP-12, in a Phase 1 dose escalation and route comparison study in humans.

    Science.gov (United States)

    Pittman, Phillip R; McClain, David; Quinn, Xiaofei; Coonan, Kevin M; Mangiafico, Joseph; Makuch, Richard S; Morrill, John; Peters, Clarence J

    2016-01-20

    Rift Valley fever (RVF) poses a risk as a potential agent in bioterrorism or agroterrorism. A live attenuated RVF vaccine (RVF MP-12) has been shown to be safe and protective in animals and showed promise in two initial clinical trials. In the present study, healthy adult human volunteers (N=56) received a single injection of (a) RVF MP-12, administered subcutaneously (SQ) at a concentration of 10(4.7) plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 10(3.4)pfu (IM Group 1); (c) RVF MP-12, administered IM at 10(4.4)pfu (IM Group 2); or (d) saline (Placebo Group). The vaccine was well tolerated by volunteers in all dose and route groups. Infrequent and minor adverse events were seen among recipients of both placebo and RVF MP-12. One subject had viremia detectable by direct plaque assay, and six subjects from IM Group 2 had transient low-titer viremia detectable only by nucleic acid amplification. Of the 43 vaccine recipients, 40 (93%) achieved neutralizing antibodies (measured as an 80% plaque reduction neutralization titer [PRNT80]) as well as RVF-specific IgM and IgG. The highest peak geometric mean PRNT80 titers were observed in IM Group 2. Of 34 RVF MP-12 recipients available for testing 1 year following inoculation, 28 (82%) remained seropositive (PRNT80≥1:20); this included 20 of 23 vaccinees (87%) from IM Group 2. The live attenuated RVF MP-12 vaccine was safe and immunogenic at the doses and routes studied. Given the need for an effective vaccine against RVF virus, further evaluation in humans is warranted.

  11. Phylogenetic analysis of porcine rotavirus in Argentina: increasing diversity of G4 strains and evidence of interspecies transmission.

    Science.gov (United States)

    Parra, Gabriel I; Vidales, Graciela; Gomez, Jorge A; Fernandez, Fernando M; Parreño, Viviana; Bok, Karin

    2008-01-01

    Group A rotaviruses are one of the most frequently detected viral agents associated with neonatal diarrhea in piglets. In order to characterize rotavirus (RV) strains circulating in Argentinean swine, four porcine production farms located in Buenos Aires were studied. RV strains genotyped as P[6]G4, P[6]G8 and P[1]G6 were found in piglets under 30 days of age, without diarrhea. Phylogenetic and sequence analysis of the VP7 gene from G4 strains available in databases, reveals five porcine new lineages (III-VII) and three sublineages (VIIa-VIIc). The G4 porcine Argentinean strains were grouped with a porcine RV strain isolated in Brazil and another RV strain isolated from a child with diarrhea in Mexico, constituting an American lineage (VII). On the other hand, porcine G6 and G8 were closely related to RV's circulating in Argentinean cattle and South-American camelids, respectively. The fact that G4 porcine lineages were epidemiologically related to human strains, and G6 and G8 Argentinean porcine strains were found related to bovine and South-American camelids, respectively, suggests that pigs might play a crucial role as reservoir and generator of newly adapted emerging RV strains for human and other species.

  12. Molecular epidemiology of rotavirus and norovirus in Ile-Ife, Nigeria: high prevalence of G12P[8] rotavirus strains and detection of a rare norovirus genotype.

    Science.gov (United States)

    Oluwatoyin Japhet, Margaret; Adeyemi Adesina, Olufisayo; Famurewa, Oladiran; Svensson, Lennart; Nordgren, Johan

    2012-09-01

    Rotavirus (RV) and norovirus (NoV) are considered the most common causes of viral gastroenteritis in children. In this study, the prevalence of RV and NoV infection in 55 children with diarrhea from the rural community Akinlalu in Southwestern Nigeria was investigated using real-time PCR assays. The RV and NoV strains were genotyped by PCR and/or sequencing. RV and NoV infections occurred with a prevalence of 34.5% and 25.5% respectively, with predominance in children 99%) indicating introduction in Nigeria from a single donor. Furthermore, a putative novel genotype within genogroup I NoV was detected, which till date has only been reported once in humans. To conclude, a high prevalence of the emerging G12P[8] RV strain was observed for the first time in Nigeria, as well as a putative novel NoV genotype in humans. These results provide new information which can be important for future vaccine evaluations and possible introduction in Nigeria.

  13. The influence of cortical end-plate on broadband ultrasound attenuation measurements at the human calcaneus using scanning confocal ultrasound

    Science.gov (United States)

    Xia, Yi; Lin, Wei; Qin, Yi-Xian

    2005-09-01

    Quantitative ultrasound (QUS) assessment, including broadband ultrasound attenuation (BUA), is an efficient technique for assessing bone quality in various statuses, e.g., osteoporosis. While assessing trabecular bone loss is essential to bone quality, the existence of cortical bone can substantially reduce the accuracy of BUA measurement. In this study, we developed an approach to quantify the influence of the cortical end-plate in the QUS on 18 cadaver calcanei using both analytical and experimental analyses. A simplified cortical-trabecular-cortical sandwich model has been developed for simulation of wave propagations. Results show that the cortical end-plate has a significant effect on BUA (yielding 8.5+/-3.6 dB/MHz in cortical bone alone), approximately 15% of the BUA value over the whole bone BUA measurement (54.1+/-20.1 dB/MHz). The phenomenon has been predicted by the developed analytical model with a high correlation (r2=0.63,pdiagnosis of bone diseases.

  14. Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity.

    Directory of Open Access Journals (Sweden)

    Wenbo Wang

    Full Text Available The known functions of telomerase in tumor cells include replenishing telomeric DNA and maintaining cell immortality. We have previously shown the existence of a negative correlation between human telomerase reverse transcriptase (hTERT and radiosensitivity in tumor cells. Here we set out to elucidate the molecular mechanisms underlying regulation by telomerase of radiosensitivity in MCF-7 cells. Toward this aim, yeast two-hybrid (Y2H screening of a human laryngeal squamous cell carcinoma radioresistant (Hep2R cDNA library was first performed to search for potential hTERT interacting proteins. We identified ubiquitin-conjugating enzyme E2D3 (UBE2D3 as a principle hTERT-interacting protein and validated this association biochemically. ShRNA-mediated inhibition of UBE2D3 expression attenuated MCF-7 radiosensitivity, and induced the accumulation of hTERT and cyclin D1 in these cells. Moreover, down-regulation of UBE2D3 increased hTERT activity and cell proliferation, accelerating G1 to S phase transition in MCF-7 cells. Collectively these findings suggest that UBE2D3 participates in the process of hTERT-mediated radiosensitivity in human breast cancer MCF-7 cells by regulating hTERT and cyclin D1.

  15. Live Attenuated Influenza Vaccine Strains Elicit a Greater Innate Immune Response than Antigenically-Matched Seasonal Influenza Viruses during Infection of Human Nasal Epithelial Cell Cultures

    Science.gov (United States)

    Fischer, William A.; Brighton, Missy; Jaspers, Ilona

    2014-01-01

    Influenza viruses are global pathogens that infect approximately 10–20% of the world’s population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the

  16. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    Science.gov (United States)

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  17. A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε

    Institute of Scientific and Technical Information of China (English)

    Deguang Liang; Yuan Gao; Xianzhi Lin; Zhiheng He; Qinglan Zhao; Qiang Deng; Ke Lan

    2011-01-01

    Type I interferon(IFN)signaling is the principal response mediating antiviral innate immunity. IFN transcription is dependent upon the activation of transcription factors IRF3/IRF7 and NF-KB. Many viral proteins have been shown as being capable of interfering with IFN signaling to facilitate evasion from the host innate immune response.Here, we report that a viral miRNA, miR-K12-11, encoded by Kaposi's sarcoma-associated herpesvirus(KSHV)is critical for the modulation of IFN signaling and acts through targeting 1-kappa-B kinase epsilon(IKKε). Ectopic expression of miR-K12-11 resulted in decreased IKKε expression, while inhibition of miR-K12-11 was found to restore IKKE expression in KSHV-infected cells. Importantly, expression of milk-K12-I1 attenuated IFN signaling by decreasing IKKε-mediated IRF3/IRF7 phosphorylation and by inhibiting the activation of IKKE-dependent IFN stimulating genes(ISGs), allowing miR-K12-11 suppression of antiviral immunity. Our data suggest that IKKE targeting by miR-K12-11 is an important strategy utilized by KSHV to modulate IFN signaling during the KSHV lifecycle, especially in latency. We also demonstrated that IKKE was able to enhance KSHV reactivation synergistically with the treatment of 12-O-tetradecanoylphorbol 13-acetate. Moreover, inhibition of miR-K12-11enhanced KSHV reactivation induced by vesicular stomatitis virus infection. Taken together, our findings also suggest that miR-K12-11 can contribute to maintenance of KSHV latency by targeting IKKE.

  18. Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward.

    Science.gov (United States)

    Parashar, Umesh D; Johnson, Hope; Steele, A Duncan; Tate, Jacqueline E

    2016-05-01

    Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.

  19. Detection of Rotavirus in children with acute gastroenteritis in Zagazig University Hospitals in Egypt

    Science.gov (United States)

    Ibrahim, Salwa Badrelsabbah; El-Bialy, Abdallah Abdelkader; Mohammed, Mervat Soliman; El-Sheikh, Azza Omar; Elhewala, Ahmed; Bahgat, Shereen

    2015-01-01

    Introduction: Rotavirus is the major cause of acute gastroenteritis (AGE) in infants and young children all over the world. The objective of the study was to compare different methods for detecting rotavirus and to assess the burden of rotavirus as a causative agent for AGE in children younger than five. Methods: This case control study included 65 children with AGE and 35 healthy control children. They were chosen from the Pediatric Department of Zagazig University Hospitals from October 2014 to March 2015. Stool samples were obtained and assayed for rotavirus by the immunochromatography test (ICT), enzyme linked immunosorbent assay (ELISA) and quantitative real time RT-PCR (qr RT-PCR). Results: Fifty out of the 65 patients (76.9%) were positive for qr RT-PCR. Forty-five (69.2%) and 44 (67.7%) were positive for ICT and ELISA, respectively. There was a significant association between the severity of the disease as determined by the Vesikari score and rotavirus infection. Conclusion: This study demonstrated that ICT is a useful method for the rapid screening of group A rotavirus in fecal specimens, because it is rapid, inexpensive, easy to perform, and requires very little equipment. In addition, this study highlights the substantial health burden of rotavirus AGE among children less than five. PMID:26435821

  20. Influence of birth rates and transmission rates on the global seasonality of rotavirus incidence.

    Science.gov (United States)

    Pitzer, Virginia E; Viboud, Cécile; Lopman, Ben A; Patel, Manish M; Parashar, Umesh D; Grenfell, Bryan T

    2011-11-07

    Rotavirus is a major cause of mortality in developing countries, and yet the dynamics of rotavirus in such settings are poorly understood. Rotavirus is typically less seasonal in the tropics, although recent observational studies have challenged the universality of this pattern. While numerous studies have examined the association between environmental factors and rotavirus incidence, here we explore the role of intrinsic factors. By fitting a mathematical model of rotavirus transmission dynamics to published age distributions of cases from 15 countries, we obtain estimates of local transmission rates. Model-predicted patterns of seasonal incidence based solely on differences in birth rates and transmission rates are significantly correlated with those observed (Spearman's ρ = 0.65, p rates and transmission rates and explore how vaccination may impact these patterns. Our results suggest that the relative lack of rotavirus seasonality observed in many tropical countries may be due to the high birth rates and transmission rates typical of developing countries rather than being driven primarily by environmental conditions. While vaccination is expected to decrease the overall burden of disease, it may increase the degree of seasonal variation in the incidence of rotavirus in some settings.

  1. Analysis of factors in response to rotavirus vaccination counselling in a private paediatric clinic.

    Science.gov (United States)

    Kannan Kutty, P; Pathmanathan, G; Salleh, N M

    2010-06-01

    Rotavirus vaccine is available as an optional vaccine in Malaysia. The counselling of optional vaccines is considered an integral part of the health services offered in a private paediatric clinic. While ensuring that all babies are up-todate with their compulsory immunization, counselling of optional vaccines like the rotavirus vaccine could give parents the choice to make an informed decision on the acceptance of this vaccine. Over a period of two years, we counselled the parents regarding diarrhoea caused by rotavirus disease and the rotavirus vaccine. In this study, the factors that were significantly associated with the acceptance of the rotavirus vaccine were the gender of the baby, the mother's age, the mother's occupation, the mode of payment for the vaccine, the number of previous visits to the clinic by the parents, the number of counselling sessions given to the parents and the pre-counselling awareness or knowledge of rotavirus disease and rotavirus vaccine. It is hoped that these findings may assist busy clinicians in their continuous efforts to provide health education and vaccination counselling to the parents of their patients.

  2. Burden of rotavirus infections in Liguria, Northern Italy: hospitalisations and potential savings by vaccination.

    Science.gov (United States)

    Panatto, D; Amicizia, D; Giacchino, R; Tacchella, A; Natalizia, A R; Melioli, G; Bandettini, R; Di Pietro, P; Diana, M C; Gasparini, R

    2011-08-01

    We evaluated the rates of gastroenteritis admissions to the emergency department and of rotavirus-related hospitalisations in children ≤5 years of age in 2006 at an Italian paediatric hospital. We calculated the number of rotavirus cases avoidable through the universal vaccination of children. Epidemiological data were extracted from the Data Elaboration Centre. To calculate the hospitalisation rate due to rotavirus, the virus was sought in the faeces of children hospitalised for acute gastroenteritis by means of rapid immunochromatographic assay. Emergency department admissions due to gastroenteritis numbered 2,396 (11.58% of the total admissions). Of these, 276 children (11.52%) were examined and then sent home, 1,286 (53.67%) were kept in short observation and 776 (32.38%) were hospitalised. In 27.83% of hospitalised cases, the rotavirus test proved positive. The rotavirus hospitalisation rate was 55 per 10,000 children ≤5 years of age in Genoa in 2006. In 85.6% of hospitalised patients with community-acquired rotavirus infection, the disease was severe. The number of avoidable cases confirmed that the vaccination of children ≤1 year of age could reduce the burden of rotavirus infection, especially with regard to hospitalisation (45 per 10,000 children ≤5 years of age) and admissions to short observation (85 per 10,000), generating benefits for the Italian healthcare system.

  3. The cost-effectiveness of rotavirus vaccination in Armenia.

    Science.gov (United States)

    Jit, Mark; Yuzbashyan, Ruzanna; Sahakyan, Gayane; Avagyan, Tigran; Mosina, Liudmila

    2011-11-01

    The cost-effectiveness of introducing infant rotavirus vaccination in Armenia in 2012 using Rotarix(R) was evaluated using a multiple birth cohort model. The model considered the cost and health implications of hospitalisations, primary health care consultations and episodes not leading to medical care in children under five years old. Rotavirus vaccination is expected to cost the Ministry of Health $220,000 in 2012, rising to $830,000 in 2016 following termination of GAVI co-financing, then declining to $260,000 in 2025 due to vaccine price maturity. It may reduce health care costs by $34,000 in the first year, rising to $180,000 by 2019. By 2025, vaccination may be close to cost saving to the Ministry of Health if the vaccine purchase price declines as expected. Once coverage has reached high levels, vaccination may prevent 25,000 cases, 3000 primary care consultations, 1000 hospitalisations and 8 deaths per birth cohort vaccinated. The cost per disability-adjusted life year (DALY) saved is estimated to be about $650 from the perspective of the Ministry of Health, $850 including costs accrued to both the Ministry and to GAVI, $820 from a societal perspective excluding indirect costs and $44 from a societal perspective including indirect costs. Since the gross domestic product per capita of Armenia in 2008 was $3800, rotavirus vaccination is likely to be regarded as "very cost-effective" from a WHO standpoint. Vaccination may still be "very cost-effective" if less favourable assumptions are used regarding vaccine price and disease incidence, as long as DALYs are not age-weighted.

  4. Perspectivas de la diarrea por rotavirus en El Salvador

    OpenAIRE

    Roberto Arturo Zablah

    2005-01-01

    Materiales y métodos: En diciembre del año 2000, un brote epidémico de gastroenteritis ocurrió en El Salvador que se asoció con numerosas hospitalizaciones y muertes de niños en todo el país. El Ministerio de Salud Pública se mostró preocupado, pues se ignoraba su etiología y las medidas de control usuales fueron ineficaces. El brote lo produjo un rotavirus, y las medidas de control fueron rediseñadas para mejorar el tratamiento con rehidratación oral e iniciar un sistema de vigilancia para c...

  5. Field tests on human tolerance to (LNG) fire radiant heat exposure, and attenuation effects of clothing and other objects.

    Science.gov (United States)

    Raj, Phani K

    2008-09-15

    A series of field tests exposing mannequins clothed with civilian clothing to a 3m x 3m square liquefied natural gas (LNG) pool fire was conducted. Both single layer clothing and double layer clothing were used. The radiant heat flux incident outside the clothing and incident on the skin covered by clothing were measured using wide-angle radiometers, for durations of 100-200 s (per test). The levels of heat flux incident on the clothing were close to 5 kW/m(2). The magnitude of the radiant heat attenuation factor (AF) across the thickness was determined. AF varies between 2 and higher for cotton and polyester clothing (thickness 0.286-1.347 mm); AF value of 6 was measured for 1.347 mm thickness. Single sheet newspaper held about 5 cm in front of mannequins and exposed to incident flux of 5 kW/m(2) resulted in AF of 5, and AF of 8 with double sheets. AF decreases linearly with increasing heat flux values and linearly increases with thickness. The author exposed himself, in normal civilian clothing (of full sleeve cotton/polyester shirt and jean pants), to radiant heat from a LNG fire. The exposure was for several tens of seconds to heat flux levels ranging from 3.5 kW/m(2) to 5(+) kW/m(2) (exposure times from 25s to 97 s at average heat flux values in the 4 kW/m(2) and 5 kW/m(2)range). Occasionally, he was exposed to (as high as) 7 kW/m(2) for durations of several seconds. He did not suffer any unbearable or even severe pain nor did he experience blisters or burns or any other injury on the unprotected skin of his body. The incident heat fluxes on the author were measured by a hand-held radiometer (with digital display) as well as by strapped on wide-angle radiometers connected to a computer. He could withstand the US regulatory criterion of 5 kW/m(2) (for 30 s) without suffering any damage or burns. Temperature measured on author's skin covered by clothing did not rise above the normal body temperature even after 200 s of exposure to 4 kW/m(2) average heat flux.

  6. A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates

    Directory of Open Access Journals (Sweden)

    Yuping eAmbuel

    2014-06-01

    Full Text Available Dengue viruses (DENVs cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2 and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0 at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI delivery devices (PharmaJet in non-human primates (NHP. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge. RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.

  7. Human CD4(+) T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity.

    Science.gov (United States)

    Angelo, Michael A; Grifoni, Alba; O'Rourke, Patrick H; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D; Phillips, Elizabeth; Mallal, Simon; Diehl, Sean A; Kirkpatrick, Beth D; Whitehead, Stephen S; Durbin, Anna P; Sette, Alessandro; Weiskopf, Daniela

    2017-03-01

    Dengue virus (DENV) is responsible for growing numbers of infections worldwide and has proven to be a significant challenge for vaccine development. We previously demonstrated that CD8(+) T cell responses elicited by a dengue live attenuated virus (DLAV) vaccine resemble those observed after natural infection. In this study, we screened peripheral blood mononuclear cells (PBMCs) from donors vaccinated with a tetravalent DLAV vaccine (TV005) with pools of dengue virus-derived predicted major histocompatibility complex (MHC) class II binding peptides. The definition of CD4(+) T cell responses after live vaccination is important because CD4(+) T cells are known contributors to host immunity, including cytokine production, help for CD8(+) T and B cells, and direct cytotoxicity against infected cells. While responses to all antigens were observed, DENV-specific CD4(+) T cells were focused predominantly on the capsid and nonstructural NS3 and NS5 antigens. Importantly, CD4(+) T cell responses in vaccinees were similar in magnitude and breadth to those after natural infection, recognized the same antigen hierarchy, and had similar profiles of HLA restriction. We conclude that TV005 vaccination has the capacity to elicit CD4(+) cell responses closely mirroring those observed in a population associated with natural immunity.IMPORTANCE The development of effective vaccination strategies against dengue virus infection is of high global public health interest. Here we study the CD4 T cell responses elicited by a tetravalent live attenuated dengue vaccine and show that they resemble responses seen in humans naturally exposed to dengue virus. This is an important issue, since it is likely that optimal immunity induced by a vaccine requires induction of CD4(+) responses against the same antigens as those recognized as dominant in natural infection. Detailed knowledge of the T cell response may further contribute to the identification of robust correlates of protection against

  8. Attenuation of TGF-β signaling suppresses premature senescence in a p21-dependent manner and promotes oncogenic Ras-mediated metastatic transformation in human mammary epithelial cells.

    Science.gov (United States)

    Lin, Shu; Yang, Junhua; Elkahloun, Abdel G; Bandyopadhyay, Abhik; Wang, Long; Cornell, John E; Yeh, I-Tien; Agyin, Joseph; Tomlinson, Gail; Sun, Lu-Zhe

    2012-04-01

    The molecular mechanisms that drive triple-negative, basal-like breast cancer progression are elusive. Few molecular targets have been identified for the prevention or treatment of this disease. Here we developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered transforming growth factor-β (TGF-β) sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. We found that expression of a dominant-negative type II receptor (DNRII) of TGF-β abrogated autocrine TGF-β signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12-induced senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H-Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison with H-Ras-V12-transformed HMECs that spontaneously escaped H-Ras-V12-induced SLGA. Microarray analysis revealed that p21 was the major player mediating Ras-induced SLGA, and attenuated or loss of p21 expression contributed to the escape from SLGA when autocrine TGF-β signaling was blocked in HMECs. Furthermore, knockdown of p21 also suppressed H-Ras-V12-induced SLGA. Our results identify that autocrine TGF-β signaling is an integral part of the cellular anti-transformation network by suppressing the expression of a host of genes, including p21-regulated genes, that mediate oncogene-induced transformation in basal-like breast cancer.

  9. Whole genome characterization of a G6P[5] rotavirus A strain isolated from a stray cat in Japan.

    Science.gov (United States)

    Kaneko, Miho; Mochizuki, Masami; Nakagomi, Osamu; Nakagomi, Toyoko

    2016-05-30

    The whole genome of an unusual G6P[5] rotavirus A strain named FRV537, which was isolated from a stray cat in Japan, was characterized to determine its species of origin. The genotype constellation of FRV537 was G6-P[5]-I2-R2-C2-M2-A13-N2- T6-E2-H3. No known feline rotavirus has this genotype constellation; the Japanese equine strain OH-4 is the only known strain that does. While FRV537 shares the same genotype with some feline rotaviruses in all genes except those encoding VP4 and NSP1, none of these genes are closely related to those of known feline rotaviruses. By contrast, G6P[5] is almost exclusively present in bovine rotaviruses. The VP7 and VP4 genes of FRV537 formed a lineage with typical bovine rotaviruses with high bootstrap values. As to the internal capsid and nonstructural gene constellation, three bovine rotavirus strains had a constellation identical to that of FRV537. Moreover, each of the genotypes of FRV537 was found to be a common bovine genotype. In addition to the high nucleotide sequence identities between FRV537 and bovine rotaviruses in each genome segment (≥95%), phylogenetic analysis revealed a close relationship to bovine/artiodactyl rotaviruses. Thus, the molecular and phylogenetic evidence suggests that FRV537 isolated from a stray cat was of bovine rotavirus origin.

  10. [Research progress of real-time quantitative PCR method for group A rotavirus detection].

    Science.gov (United States)

    Guo, Yan-Qing; Li, Dan-Di; Duan, Zhao-Jun

    2013-11-01

    Group A rotavirus is one of the most significant etiological agents which causes acute gastroenteritis among infants and young children worldwide. So far, several method which includes electron microscopy (EM), enzyme immunoassay (EIA), reverse transcription-polymerase chain reaction (RT-PCR)and Real-time Quantitative PCR has been established for the detection of rotavirus. Compared with other methods, Real-time quantitative PCR have advantages in specificity, sensitivity, genotyping and quantitative accuracy. This article shows a overview of the application of real-time quantitative PCR technique to detecte group A rotavirus.

  11. THE PREVENTION OF ROTAVIRUS INFECTION: THE MODERN VIEW OF THE POSSIBILITY

    Directory of Open Access Journals (Sweden)

    T. A. Grechukha

    2014-01-01

    Full Text Available Rotavirus is a major public health problem in all countries. The incidence of rotavirus infection is growing steadily in the Russian Federation and over the past 10 years increased by 7 times, amounting to 72 cases per 100,000 in 2010. The rotavirus vaccine was registered in the Russian Federation in 2012 and successfully applied from 2013. The vaccine used for more than 8 years and have enough experience on the efficacy and safety. Different foreign investigations have shown the herd immunity of the vaccine. The authors present data about the effectiveness and safety of vaccines, established during clinical studies of the foreign scientists.

  12. Role of the Enteric Nervous System in the Fluid and Electrolyte Secretion of Rotavirus Diarrhea

    Science.gov (United States)

    Lundgren, Ove; Peregrin, Attila Timar; Persson, Kjell; Kordasti, Shirin; Uhnoo, Ingrid; Svensson, Lennart

    2000-01-01

    The mechanism underlying the intestinal fluid loss in rotavirus diarrhea, which often afflicts children in developing countries, is not known. One hypothesis is that the rotavirus evokes intestinal fluid and electrolyte secretion by activation of the nervous system in the intestinal wall, the enteric nervous system (ENS). Four different drugs that inhibit ENS functions were used to obtain experimental evidence for this hypothesis in mice in vitro and in vivo. The involvement of the ENS in rotavirus diarrhea indicates potential sites of action for drugs in the treatment of the disease.

  13. Vigilancia de diarreas por rotavirus en hospitales centinelas, Chile 2006-2008

    OpenAIRE

    Díaz Tito, Janepsy

    2010-01-01

    La infección por rotavirus es una de las más importantes causas de diarrea moderada a grave en niños menores de cinco años en todo el mundo. En Chile, la enteritis por rotavirus ha ido en aumento con el transcurso de los años. En el periodo de enero a diciembre de 2006-2008, se condujo una investigación operacional, con el propósito de desarrollar una estrategia de vigilancia que permitiera la caracterización integral de las diarreas causadas por rotavirus en niños chilenos menores de cinco a...

  14. Assignment of simian rotavirus SA11 temperature-sensitive mutant groups B and E to genome segments

    Energy Technology Data Exchange (ETDEWEB)

    Gombold, J.L.; Estes, M.K.; Ramig, R.F.

    1985-05-01

    Recombinant (reassortant) viruses were selected from crosses between temperature-sensitive (ts) mutants of simian rotavirus SA11 and wild-type human rotavirus Wa. The double-stranded genome RNAs of the reassortants were examined by electrophoresis in Tris-glycine-buffered polyacrylamide gels and by dot hybridization with a cloned DNA probe for genome segment 2. Analysis of replacements of genome segments in the reassortants allowed construction of a map correlating genome segments providing functions interchangeable between SA11 and Wa. The reassortants revealed a functional correspondence in order of increasing electrophoretic mobility of genome segments. Analysis of the parental origin of genome segments in ts+ SA11/Wa reassortants derived from the crosses SA11 tsB(339) X Wa and SA11 tsE(1400) X Wa revealed that the group B lesion of tsB(339) was located on genome segment 3 and the group E lesion of tsE(1400) was on segment 8.

  15. Complete genomic sequence analyses of the first group A giraffe rotavirus reveals close evolutionary relationship with rotaviruses infecting other members of the Artiodactyla.

    Science.gov (United States)

    O'Shea, Helen; Mulherin, Emily; Matthijnssens, Jelle; McCusker, Matthew P; Collins, P J; Cashman, Olivia; Gunn, Lynda; Beltman, Marijke E; Fanning, Séamus

    2014-05-14

    Group A Rotaviruses (RVA) have been established as significant contributory agents of acute gastroenteritis in young children and many animal species. In 2008, we described the first RVA strain detected in a giraffe calf (RVA/Giraffe-wt/IRL/GirRV/2008/G10P[11]), presenting with acute diarrhoea. Molecular characterisation of the VP7 and VP4 genes revealed the bovine-like genotypes G10 and P[11], respectively. To further investigate the origin of this giraffe RVA strain, the 9 remaining gene segments were sequenced and analysed, revealing the following genotype constellation: G10-P[11]-I2-R2-C2-M2-A3-N2-T6-E2-H3. This genotype constellation is very similar to RVA strains isolated from cattle or other members of the artiodactyls. Phylogenetic analyses confirmed the close relationship between GirRV and RVA strains with a bovine-like genotype constellation detected from several host species, including humans. These results suggest that RVA strain GirRV was the result of an interspecies transmission from a bovine host to the giraffe calf. However, we cannot rule out completely that this bovine-like RVA genotype constellation may be enzootic in giraffes. Future RVA surveillance in giraffes may answer this intriguing question.

  16. An ethanol extract derived from Bonnemaisonia hamifera scavenges ultraviolet B (UVB) radiation-induced reactive oxygen species and attenuates UVB-induced cell damage in human keratinocytes.

    Science.gov (United States)

    Piao, Mei Jing; Hyun, Yu Jae; Cho, Suk Ju; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Lee, Nam Ho; Ko, Mi Hee; Hyun, Jin Won

    2012-12-14

    The present study investigated the photoprotective properties of an ethanol extract derived from the red alga Bonnemaisonia hamifera against ultraviolet B (UVB)-induced cell damage in human HaCaT keratinocytes. The Bonnemaisonia hamifera ethanol extract (BHE) scavenged the superoxide anion generated by the xanthine/xanthine oxidase system and the hydroxyl radical generated by the Fenton reaction (FeSO₄ + H₂O₂), both of which were detected by using electron spin resonance spectrometry. In addition, BHE exhibited scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS) that were induced by either hydrogen peroxide or UVB radiation. BHE reduced UVB-induced apoptosis, as shown by decreased apoptotic body formation and DNA fragmentation. BHE also attenuated DNA damage and the elevated levels of 8-isoprostane and protein carbonyls resulting from UVB-mediated oxidative stress. Furthermore, BHE absorbed electromagnetic radiation in the UVB range (280-320 nm). These results suggest that BHE protects human HaCaT keratinocytes against UVB-induced oxidative damage by scavenging ROS and absorbing UVB photons, thereby reducing injury to cellular components.

  17. An Ethanol Extract Derived from Bonnemaisonia hamifera Scavenges Ultraviolet B (UVB Radiation-Induced Reactive Oxygen Species and Attenuates UVB-Induced Cell Damage in Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Nam Ho Lee

    2012-12-01

    Full Text Available The present study investigated the photoprotective properties of an ethanol extract derived from the red alga Bonnemaisonia hamifera against ultraviolet B (UVB-induced cell damage in human HaCaT keratinocytes. The Bonnemaisonia hamifera ethanol extract (BHE scavenged the superoxide anion generated by the xanthine/xanthine oxidase system and the hydroxyl radical generated by the Fenton reaction (FeSO4 + H2O2, both of which were detected by using electron spin resonance spectrometry. In addition, BHE exhibited scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS that were induced by either hydrogen peroxide or UVB radiation. BHE reduced UVB-induced apoptosis, as shown by decreased apoptotic body formation and DNA fragmentation. BHE also attenuated DNA damage and the elevated levels of 8-isoprostane and protein carbonyls resulting from UVB-mediated oxidative stress. Furthermore, BHE absorbed electromagnetic radiation in the UVB range (280–320 nm. These results suggest that BHE protects human HaCaT keratinocytes against UVB-induced oxidative damage by scavenging ROS and absorbing UVB photons, thereby reducing injury to cellular components.

  18. Innate and adaptive cellular immunity in flavivirus-naïve human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3).

    Science.gov (United States)

    Sanchez, Violette; Gimenez, Sophie; Tomlinson, Brian; Chan, Paul K S; Thomas, G Neil; Forrat, Remi; Chambonneau, Laurent; Deauvieau, Florence; Lang, Jean; Guy, Bruno

    2006-06-05

    VDV3, a clonal derivative of the Mahidol live-attenuated dengue 3 vaccine was prepared in Vero cells. Despite satisfactory preclinical evaluation, VDV3 was reactogenic in humans. We explored whether immunological mechanisms contributed to this outcome by monitoring innate and adaptive cellular immune responses for 28 days after vaccination. While no variations were seen in serum IL12 or TNFalpha levels, a high IFNgamma secretion was detected from Day 8, concomitant to IFNalpha, followed by IL10. Specific Th1 and CD8 responses were detected on Day 28, with high IFNgamma/TNFalpha ratios. Vaccinees exhibited very homogeneous class I HLA profiles, and a new HLA B60-restricted CD8 epitope was identified in NS3. We propose that, among other factors, adaptive immunity may have contributed to reactogenicity, even after this primary vaccination. In addition, the unexpected discordance observed between preclinical results and clinical outcome in humans led us to reconsider some of our preclinical acceptance criteria. Lessons learned from these results will help us to pursue the development of safe and immunogenic vaccines.

  19. EXPRESSION AND GLYCOSYLATION OF ROTAVIRUS STRAIN SA11 VP4 PROTEIN IN A RECOMBINANT ADENOVIRUS

    Institute of Scientific and Technical Information of China (English)

    孙茂盛; 昝云红; 马雁冰; 张光明; 杜秋江; 戴长柏

    2001-01-01

    Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain.``Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terninal.``The chimera gene was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co-transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation.``Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed product in recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence assay. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosylation of VP4 protein.``Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicity and immunogenicity of expressed protein.``

  20. EXPRESSION AND GLYCOSYLATION OF ROTAVIRUS STRAIN SAIl VP4 PROTEIN IN A RECOMBINANT ADENOVIRUS

    Institute of Scientific and Technical Information of China (English)

    孙茂盛; 昝云红; 马雁冰; 张光明; 杜秋江; 戴长柏

    2001-01-01

    Objective. Using a recombinant human adenovirus to express modified VP4 gene of rotavirus SA11 strain. Methods. A whole VP4 gene was obtained with PCR and induced the signal peptide at the gene N terminal.The chimera gene Was cloned into pCMV plasmid that consists of human cytomegalovirus promoter, and then the gene was cloned to the transfer vector of human adenovirus type 5. Homologous recombination was performed by co-transfection to 293 cell lines with recombinant plasmid and viral genome using CaPO4 precipitation. Results. No mutation was found in the whole VP4 gene sequence of 2362 base pair. The expressed productin recombinant adenovirus was confirmed to be specific and more antigenicity by indirect immunofluorescence as-say. Both the Western blot and immunoprecipitation assay showed that the molecular mass of the expressed protein was higher than the wild type VP4 protein, and that the modified product was corresponding to a glycosyla-tion of VP4 protein. Conclusion. To modify the target gene might be an effective method to enhance the stability, antigenicityand immunogenicity of expressed protein.

  1. KR-31543 reduces the production of proinflammatory molecules in human endothelial cells and monocytes and attenuates atherosclerosis in mouse model.

    Science.gov (United States)

    Choi, Jae-Hoon; Yoo, Ji-Young; Kim, Sun-Ok; Yoo, Sung-Eun; Oh, Goo Taeg

    2012-12-31

    KR-31543, (2S, 3R, 4S)-6-amino-4-[N-(4-chlorophenyl)- N-(2-methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro- 2-dimethyoxymethyl-3-hydroxy-2-methyl-2H-1-benz opyran is a new neuroprotective agent for ischemiareperfusion damage. It has also been reported that KR-31543 has protective effects on lipid peroxidation and H₂O₂-induced reactive oxygen species production. In this study, we investigated the anti-inflammatory and anti-atherogenic properties of KR-31543. We observed that KR-31543 treatment reduced the production of MCP-1, IL-8, and VCAM-1 in HUVECs, and of MCP-1 and IL-6 in THP-1 human monocytes. We also examined the effect of KR-31543 on monocytes migration in vitro. KR-31543 treatment effectively reduced the migration of THP-1 human monocytes to the HUVEC monolayer in a dose-dependent manner. We next examined the effects of this compound on atherogenesis in LDL receptor deficient (Ldlr ⁻/⁻) mice. After 10 weeks of western diet, the formation of atherosclerotic lesion in aorta was reduced in the KR-31543-treated group compared to the control group. The accumulation of macrophages in lesion was also reduced in KR-31543 treated group. However, the plasma levels of total cholesterol, HDL, LDL, and triglyceride were not affected by KR-31543 treatment. Taken together, these results show that KR-31543 has anti-inflammatory properties on human monocytes and endothelial cells, and inhibits fatty streak lesion formation in mouse model of atherosclerosis, suggesting the potential of KR-31543 for the treatment for atherosclerosis.

  2. Full-length genomic analysis of porcine rotavirus strains isolated from pigs with diarrhea in Northern Italy.

    Science.gov (United States)

    Monini, Marina; Zaccaria, Guendalina; Ianiro, Giovanni; Lavazza, Antonio; Vaccari, Gabriele; Ruggeri, Franco M

    2014-07-01

    Group A rotaviruses (RVA) cause acute dehydrating diarrhea in young of man and many animal species, including pigs. Swine RVA has an important economic impact on the farming industry, and pigs represent a potential reservoir for zoonotic transmission of RVA to humans. To investigate the genetic diversity of porcine RVA strains in Italy and identify their possible zoonotic characteristics, 25 RVA-positive feces were collected from diarrheic pigs in Northern Italy, in 2009-2010; all viral strains were characterized by G and P genotyping RT-PCR. Three samples were selected for full genome sequencing. Sequencing of the NSP3 genes of all samples was also performed. Rotavirus diagnosis was carried out by ELISA and electron microscopy. RT-PCR and Sanger sequencing were performed in a one-tube format, using primer sets specific for each of the 11 genome segments. Analysis of the G (VP7) and P (VP4) genotypes showed that all strains identified were typical porcine RVAs (G4, G5, G9; P[6], P[13], P[23]). Full-length genome sequencing was performed on selected G9 isolates. Most segments belonged to the genotype constellation 1 (Wa-like), which is shared by most human RVA strains, but gene types such as I5 (VP6) and A8 (NSP1), which are typical of porcine and rare among human RVAs, were also detected. We identified RVA strains showing the T7 genotype, an NSP3 gene type that was previously reported in unusual strains of possible porcine or bovine origin from children with diarrhea. Recent reports suggested that G9 RVA may have been introduced from swine to human populations involving gene reassortment events. The observation that some of the RVA genotypes from swine in Italy were similar to viruses characterized in children underlines the importance of animal RVA surveillance, to clarify and monitor the role of animals as genetic reservoirs of emerging RVA strains pathogenic for humans.

  3. Genetic analysis of the porcine group B rotavirus NSP2 gene from wild-type Brazilian strains

    Directory of Open Access Journals (Sweden)

    K.C. Médici

    2010-01-01

    Full Text Available Group B rotaviruses (RV-B were first identified in piglet feces, being later associated with diarrhea in humans, cattle, lambs, and rats. In human beings, the virus was only described in China, India, and Bangladesh, especially infecting adults. Only a few studies concerning molecular analysis of the RV-B NSP2 gene have been conducted, and porcine RV-B has not been characterized. In the present study, three porcine wild-type RV-B strains from piglet stool samples collected from Brazilian pig herds were used for analysis. PAGE results were inconclusive for those samples, but specific amplicons of the RV-B NSP2 gene (segment 8 were obtained in a semi-nested PCR assay. The three porcine RV-B strains showed the highest nucleotide identity with the human WH1 strain and the alignments with other published sequences resulted in three groups of strains divided according to host species. The group of human strains showed 92.4 to 99.7% nucleotide identity while the porcine strains of the Brazilian RV-B group showed 90.4 to 91.8% identity to each other. The identity of the Brazilian porcine RV-B strains with outer sequences consisting of group A and C rotaviruses was only 35.3 to 38.8%. A dendrogram was also constructed to group the strains into clusters according to host species: human, rat, and a distinct third cluster consisting exclusively of the Brazilian porcine RV-B strains. This is the first study of the porcine RV-B NSP2 gene that contributes to the partial characterization of this virus and demonstrates the relationship among RV-B strains from different host species.

  4. 上海市闵行区婴幼儿轮状病毒腹泻监测结果分析%Epidemiological characteristics of rotavirus diarrhea in infants and young children in Minhang District, Shanghai

    Institute of Scientific and Technical Information of China (English)

    余峰; 曾玫; 杜艳; 张莉萍; 苏华林; 陆佳; 金宝芳; 王烨; 梅克雯

    2015-01-01

    Objective To analyze the epidemiological characteristics of human rotavirus (HRV) diarrhea in infants and young children in Minhang District and to provide the gudance for the prevention and control of infectious diarrhea in infants.Methods Stool samples were collected from children under 5 years old with diarrhea attending the infants' diarrhea monitoring hospitals in Minhang district from June 1,2013 to June 30,2015 and then tested for etiological analysis.Moreover,a survey was conducted on the parents of these patients by using a face to face questionnaire administration mode.Results A total of 797 stool specimens were collected,15.31% (122/797) of which were positive for HRV.Most of the HRV infections occurred during November to January.The peak of HRV infection reached in December with an infection rate of 46.91%,followed by 40% in November and 25.76% in January.Forty-five out of 185 (24.32%) children at age 12-<18 months were positive for HRV infection,which was the highest HRV infection rate as compared with those of other age groups.There were significant differences in HRV infection rate among children from different age groups (x2 =18.479,P=0.001).Among the 122 children positive for HRV,scattered inhabiting children accounted for 95.08%,kindergarten children accounted for 4.92%,children with the household register accounted for 22.13% and those without the household register accounted for 77.87%.Children with moderate (Vesikari scores of 6 to 10 points),mild (Vesikari scores of 1 to 5 points) and severe (Vesikari scores ≥ 11 points) clinical symptoms accounted for 59.84%,28.69% and 11.48% of the 122 subjects positive for HRV,respectively.The differences in clinical symptoms between children from different age groups were statistically significant (x2=17.367,P=0.002).Among the 122 children with HRV infection,20 (16.39%) cases had the immunization history of oral rotavirus attenuated live vaccine (ORV) with 2 cases immunized

  5. Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model.

    Science.gov (United States)

    Murray, Lynne A; Zhang, Huilan; Oak, Sameer R; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R; Lee, Joyce; Bell, Matt; Knight, Darryl A; Martinez, Fernando J; Sleeman, Matthew A; Herzog, Erica L; Hogaboam, Cory M

    2014-05-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung.

  6. Evaluation of seasonal patterns of Kawasaki Syndrome- and rotavirus-associated hospitalizations in California and New York, 2000-2005

    Directory of Open Access Journals (Sweden)

    Parashar Umesh D

    2009-10-01

    Full Text Available Abstract Background Kawasaki Syndrome (KS is an uncommon childhood disease with unknown etiology. It has been suggested that rotavirus infection may play a causative role in the development of KS. Methods To examine potential temporal associations between KS and rotavirus infection, seasonal patterns of KS- and rotavirus-associated hospitalizations among children in California and New York during 2000-2005 were compared. Results Rotavirus hospital admissions were markedly winter seasonal, with very few summer hospitalizations. KS hospitalizations occurred year-round but also peaked slightly during winter and spring. Conclusion The strong winter seasonal pattern of rotavirus clearly differed from the year-round pattern of KS hospitalizations. While the present study cannot completely rule out rotavirus as having a role in the development of KS, other agents must be involved in the etiology of KS.

  7. Inhibition of connective tissue growth factor attenuates paraquat-induced lung fibrosis in a human MRC-5 cell line.

    Science.gov (United States)

    Huang, Min; Yang, Huifang; Zhu, Lingqin; Li, Honghui; Zhou, Jian; Zhou, Zhijun

    2016-11-01

    Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016.

  8. Histamine H3 receptor antagonist OUP-186 attenuates the proliferation of cultured human breast cancer cell lines.

    Science.gov (United States)

    Tanaka, Satoshi; Sakaguchi, Minoru; Yoneyama, Hiroki; Usami, Yoshihide; Harusawa, Shinya

    2016-11-18

    Histamine is involved in various physiological functions, including its neurotransmitter actions in the central nervous system and its action as a causative agent of inflammation, allergic reactions, and gastric acid secretions. Histamine expression and biosynthesis have been detected in breast cancer cells. It was recently suggested that the histamine H3 receptor (H3R) plays a role in the proliferation of breast cancer cells. We recently developed the non-imidazole H3R antagonist OUP-186 which exhibited a potent and selective human H3R antagonistic activity as well as no activity against the human histamine H4 receptor (H4R). In this study, we compared the effects of OUP-186 on the proliferation of estrogen receptor negative (ER-) breast cancer cells (MDA-MB-231) and ER+ breast cancer cells (MCF7) to the effects of clobenpropit (potent imidazole-containing H3R antagonist). OUP-186 and clobenpropit suppressed the proliferation of breast cancer cells. The IC50 values at 48 h for OUP-186 and clobenpropit were approximately 10 μM and 50 μM, respectively. Furthermore, OUP-186 potently induced cell death by activating caspase-3/7, whereas cell death was only slightly induced by clobenpropit. In addition, OUP-186 treatment blocked the proliferation increase triggered by 100 μM (R)-(-)-α-methylhistamine (H3R agonist). The use of 4-methylhistamine (H4R agonist) and JNJ10191584 (selective H4R antagonist) did not affect breast cancer proliferation. These results indicate that OUP-186 potently suppresses proliferation and induces caspase-dependent apoptotic death in both ER+ and ER-breast cancer cells.

  9. Acquisition and extinction of human avoidance behavior: Attenuating effect of safety signals and associations with anxiety vulnerabilities

    Directory of Open Access Journals (Sweden)

    Jony eSheynin

    2014-09-01

    Full Text Available While avoidance behavior is often an adaptive strategy, exaggerated avoidance can be detrimental and result in the development of psychopathologies, such as anxiety disorders. A large animal literature shows that the acquisition and extinction of avoidance behavior in rodents depends on individual differences (e.g., sex, strain and might be modulated by the presence of environmental cues. However, there is a dearth of such reports in human literature, mainly due to the lack of adequate experimental paradigms. In the current study, we employed a computer-based task, where participants control a spaceship and attempt to gain points by shooting an enemy spaceship that appears on the screen. Warning signals predict on-screen aversive events; the participants can learn a protective response to escape or avoid these events. This task has been recently used to reveal facilitated acquisition of avoidance behavior in individuals with anxiety vulnerability, due to female sex or inhibited personality. Here, we extended the task to include an extinction phase, and tested the effect of signals that appeared during safe periods. Healthy young adults (n=122 were randomly assigned to a testing condition with or without such signals. Results showed that the addition of safety signals during the acquisition phase impaired acquisition (in females and facilitated extinction of the avoidance behavior. We also replicated our recent finding of an association between female sex and longer avoidance duration and further showed that females continued to demonstrate more avoidance behavior even on extinction trials when the aversive events no longer occurred. This study is the first to show sex differences on the acquisition and extinction of human avoidance behavior and to demonstrate the role of safety signals in such behavior, highlighting the potential relevance of safety signals for cognitive therapies that focus on extinction learning to treat anxiety symptoms.

  10. Protection against gastroenteritis in US households with children who received rotavirus vaccine.

    Science.gov (United States)

    Cortese, Margaret M; Dahl, Rebecca Moritz; Curns, Aaron T; Parashar, Umesh D

    2015-02-15

    We used Truven Health Marketscan claims database (2008-2011) to compare gastroenteritis rates during January-June among households whose child had received rotavirus vaccine with those whose child did not receive vaccine. Statistically significantly lower rates of hospitalization with a rotavirus gastroenteritis or unspecified-gastroenteritis discharge code occurred in vaccinated households among persons 20-29 years and females 20-29 years (2008/2009), and males 30-39 years (2009/2010). Lower emergency department gastroenteritis rates occurred in vaccinated households among females 20-29 years (2009/2010) and individuals 5-19 years (2010/2011). These data suggest rotavirus vaccination of infants provides indirect protection against moderate-to-severe rotavirus disease in young parents and older siblings.

  11. [Molecular epidemiology of rotaviruses circulating among residents of St. Petersburg from 1986 through 1991].

    Science.gov (United States)

    Vasil'ev, B Ia; Moskvin, A A; Semenov, N V; Grits'ko, R Iu; Marchenko, L G; Bannikov, A I

    1995-01-01

    The results of screening of 510 patients with acute gastrointestinal diseases over the period of 1986 to 1991 are presented. Rotaviruses were shown to be the infection agents in 112 (60%) children and 76 (40%) adults. The phoretyping of the isolated strains revealed cocirculation of 17 different phoretypes of rotaviruses: 8 "long" and 9 "short" ones. At the same time, two predominant phoretypes were found to alternately circulate in various epidemic seasons. The "long" phoretypes were found to be equally prevalent among adults and children, whereas the "short" phoretype rotaviruses were isolated mainly from children. The cyclic pattern of circulation of rotavirus phoretypes and genetic changeability of these viruses as a factor determining the prevalence of rotaviral infection are discussed.

  12. [Identification of rotavirus associated to serotype G2 in Yucatan, Mexico].

    Science.gov (United States)

    Gonzales-Loza, M del R; Polanco-Marín, G G; Puerto-Solis, M

    2000-01-01

    In the present study, rotavirus G2 serotype was identified from fecal samples of children with gastroenteritis from the city of Merida, Yucatan, Mexico. Virological diagnosis of disease was performed using polycrylamide gel electrophoresis and immunoenzymatic assay. Out of 149 analyzed samples 25 (16.7%) gave positive reaction to rotavirus groups A, of these 23 (92%) were identified as serotype g2, subgroup i and electrophoretic short pattern, whereas 2 (8%) were identified as subgroups II and electrophoretic long pattern, however, the G serotype was not possible to determine. Rotavirus G serotype has not been detected in more than 90% of samples since 1985. This indicates that the number of people susceptible to G2 serotype within the population has increased over recent years, which perhaps indicates that an important outbreak of acute infectious diarrhea caused by the rotavirus G2 serotype may be forthcoming.

  13. Rotavirus vaccine: early introduction in Latin America-risks and benefits.

    Science.gov (United States)

    Pérez-Vargas, Jimena; Isa, Pavel; López, Susana; Arias, Carlos F

    2006-01-01

    Rotavirus infection is the cause of severe gastroenteritis of young children worldwide, leading to an estimate of 600,000 deaths a year. Efforts to develop an effective and safe vaccine resulted in licensing in 1998 of a live oral vaccine (RotaShield) that was withdrawn less than 1 year later when reports of cases of intussusception were linked to its application. This led to development of new rotavirus vaccine candidates that are currently in late phase III clinical trials. One of these vaccines, GlaxoSmithKline's Rotarix, was licensed in July 2004 to be used in Mexico. This review describes the general background for rotavirus vaccine development, the different vaccine candidates that have been tested or are currently being evaluated, the association of rotavirus vaccination with the bowel blockage known as intussuception, and discusses the benefits and risks of the fast-track introduction of Rotarix in Latin America, and particularly in Mexico.

  14. Ninety-Four Cases of Enteritis Caused by Rotavirus with Different RNA Types Treated with Qiuxieling (

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It has been known that Qiuxieling (秋泻灵,QXL) is a safe and effective drug for treating rotaviral enteritis. Some studies showed that rotavirus with different RNA types were different in toxicity and would induce enteritis with different clinical manifestations(1). So the effect of QXL in treating enteritis caused by rotavirus with different RNA types was studied and reported as follows.……

  15. Frequency of Adenoviruses, Rotaviruses and Noroviruses Among Diarrhea Samples Collected From Infants of Zabol, Southeastern Iran

    OpenAIRE

    Sharifi-Rad, Javad; Hoseini Alfatemi, Seyedeh Mahsan; Sharifi-Rad, Mehdi; Miri, Abdolhossein

    2015-01-01

    Background: Viruses are one of the major reasons of gastrointestinal disease worldwide, and commonly infect children less than five years of age in developing countries. Objectives: The current study aimed to determine the frequency of adenoviruses, rotaviruses and noroviruses among diarrhea samples collected from infants of Zabol, south-east of Iran. This study is the first investigation of adenoviruses, rotaviruses and noroviruses among diarrhea samples in Zabol. Patients and Methods: In th...

  16. Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

    OpenAIRE

    Hammarström Lennart; Svensson Lennart; Brüssow Harald; Marcotte Harold; Pant Neha

    2007-01-01

    Abstract Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an...

  17. [Rotavirus Vaccine. Statement of the Consultive Committee of Immunizations on behalf of The Chilean Infectious Diseases Society. March 2006].

    Science.gov (United States)

    Muñoz M, Alma; Abarca V, Katia; Luchsinger F, Vivian; Valenzuela B, M Teresa; Jiménez de la J, Jorge

    2006-06-01

    The article briefly reviews the epidemiology of rotavirus infection and the scientific information of the rotavirus vaccines: Rotashield, withdrawn from the market due to its association with intussusception, Rotateq currently in an advanced phase of development, and Rotarix, recently licensed in Chile. Considering the available information, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases, summarizes its conclusions and makes recommendations for infants vaccination against rotavirus in our country.

  18. Novel group A rotavirus G8 P[1] as primary cause of an ovine diarrheic syndrome outbreak in weaned lambs

    OpenAIRE

    Galindo-Cardiel, I.; Fernández-Jiménez, M.; Luján, L.; Buesa, J.; Espada, J.; Fantova, E.; Blanco, J; Segalés, J.; Badiola, J. J.

    2011-01-01

    Abstract Rotavirus is a worldwide major cause of diarrhea outbreaks in neonatal ruminants. An outbreak of ovine diarrheic syndrome (ODS) in 50-75 days-old lambs (weaned lambs) is described. Fecal immunochromatography and intestinal immunohistochemistry for rotavirus group A were performed. In addition, semi-nested multiplex RT-PCR for G and P rotavirus genotyping in combination with sequencing were performed, to support the diagnosis and identify the viral strain. A novel ovine rot...

  19. Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells

    Directory of Open Access Journals (Sweden)

    Marzena Wojewodzka-Zelezniakowicz

    2017-01-01

    Full Text Available Introduction: The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro. Materials and methods: We examined the effects of propofol (50 μM, quinaprilat and enalaprilat (10−5 M on fibrinolysis (t-PA, PAI-1, TAFI antigen levels, oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA in human umbilical vein endothelial cells (HUVECs. Results: We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is. Conclusions: This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.

  20. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  1. Mastic oil from Pistacia lentiscus var. chia inhibits growth and survival of human K562 leukemia cells and attenuates angiogenesis.

    Science.gov (United States)

    Loutrari, Heleni; Magkouta, Sophia; Pyriochou, Anastasia; Koika, Vasiliki; Kolisis, Fragiskos N; Papapetropoulos, Andreas; Roussos, Charis

    2006-01-01

    Mastic oil from Pistacia lentiscus var. chia, a natural plant extract traditionally used as a food additive, has been extensively studied for its antimicrobial activity attributed to the combination of its bioactive components. One of them, perillyl alcohol (POH), displays tumor chemopreventive, chemotherapeutic, and antiangiogenic properties. We investigated whether mastic oil would also suppress tumor cell growth and angiogenesis. We observed that mastic oil concentration and time dependently exerted an antiproliferative and proapoptotic effect on K562 human leukemia cells and inhibited the release of vascular endothelial growth factor (VEGF) from K562 and B16 mouse melanoma cells. Moreover, mastic oil caused a concentration-dependent inhibition of endothelial cell (EC) proliferation without affecting cell survival and a significant decrease of microvessel formation both in vitro and in vivo. Investigation of underlying mechanism(s) demonstrated that mastic oil reduced 1) in K562 cells the activation of extracellular signal-regulated kinases 1/2 (Erk1/2) known to control leukemia cell proliferation, survival, and VEGF secretion and 2) in EC the activation of RhoA, an essential regulator of neovessel organization. Overall, our results underscore that mastic oil, through its multiple effects on malignant cells and ECs, may be a useful natural dietary supplement for cancer prevention.

  2. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

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    Rushika Conroy

    2014-01-01

    Full Text Available Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily. At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was 53±2.3 months; mean BMI was 34.6±0.2 kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (P<0.05. No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women.

  3. Synthesis and characterization of different immunogenic viral nanoconstructs from rotavirus VP6 inner capsid protein

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    Bugli F

    2014-05-01

    Full Text Available Francesca Bugli,1 Valeria Caprettini,2 Margherita Cacaci,1 Cecilia Martini,1 Francesco Paroni Sterbini,1 Riccardo Torelli,1 Stefano Della Longa,3 Massimiliano Papi,4 Valentina Palmieri,4 Bruno Giardina,5 Brunella Posteraro,1 Maurizio Sanguinetti,1 Alessandro Arcovito5 1Istituto di Microbiologia, Università Cattolica del Sacro Cuore, 2Dipartimento di Fisica, Sapienza Università di Roma, Rome, 3Dipartimento di Medicina Clinica, Sanità Pubblica, Scienze della Vita e dell’Ambiente, Università dell’Aquila, L’Aquila, 4Istituto di Fisica, 5Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy Abstract: In order to deliver low-cost viral capsomeres from a large amount of soluble viral VP6 protein from human rotavirus, we developed and optimized a biotechnological platform in Escherichia coli. Specifically, three different expression protocols were compared, differing in their genetic constructs, ie, a simple native histidine-tagged VP6 sequence, VP6 fused to thioredoxin, and VP6 obtained with the newly described small ubiquitin-like modifier (SUMO fusion system. Our results demonstrate that the histidine-tagged protein does not escape the accumulation in the inclusion bodies, and that SUMO is largely superior to the thioredoxin-fusion tag in enhancing the expression and solubility of VP6 protein. Moreover, the VP6 protein produced according to the SUMO fusion tag displays well-known assembly properties, as observed in both transmission electron microscopy and atomic force microscopy images, giving rise to either VP6 trimers, 60 nm spherical virus-like particles, or nanotubes a few micron long. This different quaternary organization of VP6 shows a higher level of immunogenicity for the elongated structures with respect to the spheres or the protein trimers. Therefore, the expression and purification strategy presented here – providing a large amount of the viral capsid protein in the native

  4. Surfactant protein A (SP-A) and SP-A-derived peptide attenuate chemotaxis of mast cells induced by human β-defensin 3.

    Science.gov (United States)

    Uehara, Yasuaki; Takahashi, Motoko; Murata, Masaki; Saito, Atsushi; Takamiya, Rina; Hasegawa, Yoshihiro; Kuronuma, Koji; Chiba, Hirofumi; Hashimoto, Jiro; Sawada, Norimasa; Takahashi, Hiroki; Kuroki, Yoshio; Ariki, Shigeru

    2017-02-08

    Human β-defensin 3 (hBD3) is known to be involved in mast cell activation. However, molecular mechanisms underlying the regulation of hBD3-induced mast cell activation have been poorly understood. We previously reported that SP-A and SP-A-derived peptide 01 (SAP01) regulate the function of hBD3. In this study, we focused on the effects of SP-A and SAP01 on the activation of mast cells induced by hBD3. SAP01 directly bound to hBD3. Mast cell-mediated vascular permeability and edema in hBD3 administered rat ears were decreased when injected with SP-A or SAP01. Compatible with the results in rat ear model, both SP-A and SAP01 inhibited hBD3-induced chemotaxis of mast cells in vitro. Direct interaction between SP-A or SAP01 and hBD3 seemed to be responsible for the inhibitory effects on chemotaxis. Furthermore, SAP01 attenuated hBD3-induced accumulation of mast cells and eosinophils in tracheas of the OVA-sensitized inflammatory model. SP-A might contribute to the regulation of inflammatory responses mediated by mast cells during infection.

  5. Prevalence of rotavirus in children hospitalized with acute gastroenteritis in Imam Sajjad Hospital of Yasuj, 2011

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    P Khodadadi

    2013-04-01

    Full Text Available Abstract Background & Aim: Rotavirus infection is the most common cause of dehydrating and gastroenteritis among children worldwide. . The aim of this study was to determine the prevalence of rotavirus in children hospitalized with acute gastroenteritis in Imam Sajjad Hospital of Yasuj. Methods: This cross sectional – descriptive study was done on 184 stool samples of children younger than 7 years of age hospitalized at Imam Sajjad hospital of Yasuj in 2011 due to acute gastroenteritis. All samples were routinely analyzed for detection of rotavirus by Enzyme Immunoassay (EIA test. Data was analyzed by SPSS version 16, Chi-square test and Fisher's exact test. Results: Of the 184 samples analyzed, 52(28.26% were positive.The Results showed significant relationship between the seasonal distribution and virus detection (p=0/001. The highest incidence of rotavirus was seen in autumn with frequency of (48.08% and the lowest in spring (5.77%. Conclusions: According to high prevalence of rotavirus infection, continual surveillance is necessary to provide useful data for formulating effective vaccines and perform diarrhea prevention programs. Key words: Rotavirus, Gastroenteritis, Prevalence, Elisa

  6. Interactions between Rotavirus and Suwannee River Organic Matter: Aggregation, Deposition, and Adhesion Force Measurement

    KAUST Repository

    Gutierrez, Leonardo

    2012-08-21

    Interactions between rotavirus and Suwannee River natural organic matter (NOM) were studied by time-resolved dynamic light scattering, quartz crystal microbalance, and atomic force microscopy. In NOM-containing NaCl solutions of up to 600 mM, rotavirus suspension remained stable for over 4 h. Atomic force microscopy (AFM) measurement for interaction force decay length at different ionic strengths showed that nonelectrostatic repulsive forces were mainly responsible for eliminating aggregation in NaCl solutions. Aggregation rates of rotavirus in solutions containing 20 mg C/L increased with divalent cation concentration until reaching a critical coagulation concentration of 30 mM CaCl2 or 70 mM MgCl2. Deposition kinetics of rotavirus on NOM-coated silica surface was studied using quartz crystal microbalance. Experimental attachment efficiencies for rotavirus adsorption to NOM-coated surface in MgCl2 solution were lower than in CaCl2 solution at a given divalent cation concentration. Stronger adhesion force was measured for virus-virus and virus-NOM interactions in CaCl2 solution compared to those in MgCl2 or NaCl solutions at the same ionic strength. This study suggested that divalent cation complexation with carboxylate groups in NOM and on virus surface was an important mechanism in the deposition and aggregation kinetics of rotavirus. © 2012 American Chemical Society.

  7. Economic and psychosocial impact of rotavirus infection in Spain: a literature review.

    Science.gov (United States)

    Álvarez Aldeán, Javier; Aristegui, Javier; López-Belmonte, Juan Luis; Pedrós, Montse; Sicilia, José García

    2014-06-24

    Severe rotavirus gastroenteritis is common in children under 5 years of age. A literature review was performed to investigate the economic and psychosocial impact of rotavirus infection in children in this age group. We retrieved 56 articles on the economic burden of the disease in Europe, 18 of them reported data from Spain; 8 articles were retrieved analysing its psychosocial impact. In Spain, rotavirus is responsible for 14% to 30% of all cases of gastroenteritis, and a quarter of these require hospitalisation. It is also associated with high use of health care resources (emergency and primary care visits). Rotavirus gastroenteritis costs the Spanish national health system EUR 28 million a year and causes productivity loss in two-thirds of parents (mean of 4 days). Taking into account these costs, it was estimated that implementing universal vaccination could prevent 76% to 95% of hospital admissions due to rotavirus gastroenteritis, as well as reduce emergency and paediatric visits, nosocomial infections, and days missed from work (77% reduction). Rotavirus gastroenteritis also has a considerable psychosocial impact on the family, although it is difficult to compare results due to the diversity of study designs and the low specificity of the measurement tools used. It also causes high stress among parents, adding to their workload and adversely affecting their quality of life.

  8. Cost-effectiveness analysis of rotavirus vaccination among Libyan children using a simple economic model

    Science.gov (United States)

    Alkoshi, Salem; Maimaiti, Namaitijiang; Dahlui, Maznah

    2014-01-01

    Background Rotavirus infection is a major cause of childhood diarrhea in Libya. The objective of this study is to evaluate the cost-effectiveness of rotavirus vaccination in that country. Methods We used a published decision tree model that has been adapted to the Libyan situation to analyze a birth cohort of 160,000 children. The evaluation of diarrhea events in three public hospitals helped to estimate the rotavirus burden. The economic analysis was done from two perspectives: health care provider and societal. Univariate sensitivity analyses were conducted to assess uncertainty in some values of the variables selected. Results The three hospitals received 545 diarrhea patients aged≤5 with 311 (57%) rotavirus positive test results during a 9-month period. The societal cost for treatment of a case of rotavirus diarrhea was estimated at US$ 661/event. The incremental cost-effectiveness ratio with a vaccine price of US$ 27 per course was US$ 8,972 per quality-adjusted life year gained from the health care perspective. From a societal perspective, the analysis shows cost savings of around US$ 16 per child. Conclusion The model shows that rotavirus vaccination could be economically a very attractive intervention in Libya. PMID:25499622

  9. Probiotic Lactobacillus rhamnosus GG enhanced Th1 cellular immunity but did not affect antibody responses in a human gut microbiota transplanted neonatal gnotobiotic pig model.

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    Ke Wen

    Full Text Available This study aims to establish a human gut microbiota (HGM transplanted gnotobiotic (Gn pig model of human rotavirus (HRV infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota.

  10. Acute myositis associated with concurrent infection of rotavirus and norovirus in a 2-year-old girl

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    Kei Yamamoto

    2015-09-01

    Full Text Available Rotavirus and norovirus are common pathogens associated with gastroenteritis in children. Although rotavirus occasionally induces central nervous system disease, only 3 cases with rotavirus-induced acute myositis have been reported in the English literature. We recently treated a female patient with acute myositis associated with gastroenteritis induced by concurrent infection with rotavirus and norovirus. Having suffered from gastroenteritis for 3 days, she suddenly developed myositis affecting her lower extremities with concomitant creatine kinase elevation. Herein, we present our patient and review the previous cases including those reported in the Japanese literature.

  11. Progresses of the pathogenesis of rotavirus infection%轮状病毒感染机制新进展

    Institute of Scientific and Technical Information of China (English)

    郑灵玲

    2015-01-01

    轮状病毒(rotavirus,RV)是世界范围内引起婴幼儿重症腹泻的最主要病原,而对于RV腹泻至今尚无特效治疗药物.目前对于RV感染的致病机制有多种说法,但尚无确切结论.在RV感染过程中,RV病原体必须克服宿主抗病毒先天免疫反应才能在宿主细胞中成功复制,而在此过程中RV编码的蛋白起到了重要作用.该文对RV编码蛋白在RV感染机制中的作用的研究进展加以综述.%Rotavirus is the most important pathogen causing severe diarrhea in infants and young children worldwide,and for rotavirus diarrhea there is no specific treatment so far.At present,there are a variety of claims on the pathogenesis of rotavirus infection,but none is conclusive.In the process of infection,rotavirus pathogens must overcome antiviral innate immune response that can replicate in host cell.Rotavirus encoded proteins play an important role in the process of rotavirus infection.This paperreviews the role of rotavirus encoding proteins in the pathogenesis of rotavirus infection.

  12. 轮状病毒疫苗研究进展%Advances in research of rotavirus vaccines

    Institute of Scientific and Technical Information of China (English)

    王奔

    2012-01-01

    轮状病毒是引起婴幼儿严重腹泻的主要原因,疫苗接种是预防轮状病毒感染的有效方法.此文讨论了轮状病毒的生物学和流行病学特征及轮状病毒疫苗的研究进展.%Rotavirus is the leading cause of severe diarrhea among young children,and vaccination is an effective method to prevent rotavirus infection.This review describes biological and epidemiological characteristics of rotavirus and research progress of rotavirus vaccines.

  13. High prevalence of G12P[8] rotavirus strains in Rio Branco, Acre, Western Amazon, in the post-rotavirus vaccine introduction period.

    Science.gov (United States)

    Neves, Mayara A O; Pinheiro, Helder H C; Silva, Rita S U; Linhares, Alexandre C; Silva, Luciana D; Gabbay, Yvone B; Silva, Mônica C M; Loureiro, Edvaldo C B; Soares, Luana S; Mascarenhas, Joana D'Arc P

    2016-05-01

    The present study aimed to provide a molecular characterization of circulating rotavirus (RVA) strains in Rio Branco, Acre, in the post-rotavirus vaccination period, particularly with regard to the emerging, increasingly prevalent G12P[8] genotype. A total of 488 fecal specimens from diarrheic and non-diarrheic children were obtained between January and December 2012. RVA detection was initially performed using enzyme-linked immunosorbent assay (ELISA) method, followed by reverse-transcription polymerase chain reaction (RT-PCR) using specific primers. RVA was detected in 18.3% (44/241) of the children with acute diarrhea and in 1.2% (3/247) of the non-diarrheic children (P rotavirus vaccine introduction in Brazil and elsewhere, since the occurrence of either unusual our emerging genotypes may pose a challenge to vaccination strategies.

  14. Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine.

    Science.gov (United States)

    Cohen, Mitchell B; Giannella, Ralph A; Bean, Judy; Taylor, David N; Parker, Susan; Hoeper, Amy; Wowk, Stephen; Hawkins, Jennifer; Kochi, Sims K; Schiff, Gilbert; Killeen, Kevin P

    2002-04-01

    Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 x 10(8) CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (> or = 3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.

  15. A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

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    Stroh Thorsten

    2011-05-01

    Full Text Available Abstract Background In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC cell lines and the signaling pathways involved. Methods Four human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined. Results L.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase. Conclusions The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary treatment option for HCC.

  16. Recombinant human MFG-E8 attenuates intestinal injury and mortality in severe whole body irradiation in rats.

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    Michael A Ajakaiye

    Full Text Available The gastrointestinal (GI syndrome component of acute radiation syndrome (ARS results from depletion of immature parenchymal stem cells after high dose irradiation and contributes significantly to early mortality. It is associated with severe, irreparable damage in the GI tract and extremely low survival. There is a need for the development of viable mitigators of whole body irradiation (WBI due to the possibility of unexpected high level radiation exposure from nuclear accidents or attacks. We therefore examined the effect of recombinant human milk fat globule-EGF factor 8 (rhMFG-E8 in mitigating damage after WBI. Male Sprague-Dawley rats were exposed to 10 Gy WBI using Cesium-137 as the radiation source. The animals in the treatment group received rhMFG-E8 (166 µg/kg BW subcutaneously once a day with the first dose given 6 h after WBI. Blood and tissue samples from the ileum were collected after 3 days of treatment. A separate cohort of animals was treated for 7 days and the 21 day mortality rate was determined. Treatment with rhMFG-E8 significantly improved the survival from 31% to 75% over 21 days. Furthermore, rhMFG-E8 treatment resulted in a 36% reduction in the radiation injury intestinal mucosal damage score, corresponding to visible histological changes. MFG-E8 gene expression was significantly decreased in WBI-induced animals as compared to sham controls. Treatment with rhMFG-E8 increased p53 and p21 expression by 207% and 84% compared to untreated controls. This was accompanied by an 80% increase in the expression of anti-apoptotic cell regulator Bcl-2. p53 and p21 levels correlate with improved survival after radiation injury. These cell regulators arrest the cell after DNA damage and enable DNA repair as well as optimize cell survival. Taken together, these results indicate that rhMFG-E8 ameliorates the GI syndrome and improves survival after WBI by minimizing intestinal cell damage and optimizing recovery.

  17. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

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    Mühlfeld Christian

    2007-10-01

    Full Text Available Abstract Background Surfactant protein D (SP-D deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. Methods SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. Main Results After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Conclusion Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are

  18. Rotavirus gastroenteritis-associated urinary ammonium acid urate crystals.

    Science.gov (United States)

    Yokoyama, Tadafumi; Sugimoto, Naotoshi; Kato, Eiji; Ohta, Kazuhide; Ishikawa, Sayaka; Ueno, Kazuyuki; Shimizu, Masaki; Yachie, Akihiro

    2015-01-01

    Although ammonium acid urate (AAU) calculi are extremely rare renal stone components, it was recently found that many urinary tract calculi that cause post-renal renal failure in rotavirus (RV) gastroenteritis are AAU calculi. The mechanism of AAU calculi development in RV gastroenteritis has not been fully elucidated. We analyzed data from eight RV gastroenteritis patients who transiently had AAU crystals in their urinary sediment. In these patients, formation of AAU crystals occurred earlier than the formation of AAU calculi. No difference was observed in serum and urine uric acid levels between RV gastroenteritis patients with or without AAU crystals. Interestingly, fractional excretion of sodium was extremely low among patients with AAU crystals. These results suggest that the formation of AAU crystals might not be due to excretion of uric acid, but excretion of sodium.

  19. Assortment and packaging of the segmented rotavirus genome.

    Science.gov (United States)

    McDonald, Sarah M; Patton, John T

    2011-03-01

    The rotavirus (RV) genome comprises 11 segments of double-stranded RNA (dsRNA) and is contained within a non-enveloped, icosahedral particle. During assembly, a highly coordinated selective packaging mechanism ensures that progeny RV virions contain one of each genome segment. Cis-acting signals thought to mediate assortment and packaging are associated with putative panhandle structures formed by base-pairing of the ends of RV plus-strand RNAs (+RNAs). Viral polymerases within assembling core particles convert the 11 distinct +RNAs to dsRNA genome segments. It remains unclear whether RV +RNAs are assorted before or during encapsidation, and the functions of viral proteins during these processes are not resolved. However, as reviewed here, recent insights gained from the study of RV and two other segmented RNA viruses, influenza A virus and bacteriophage Φ6, reveal potential mechanisms of RV assortment and packaging.

  20. Stress Response and Translation Control in Rotavirus Infection

    Directory of Open Access Journals (Sweden)

    Susana López

    2016-06-01

    Full Text Available The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns to prevent viral invasions. In turn, viruses counter attack these cell responses to ensure their replication. The mechanisms by which viruses attempt to control host cell responses are as varied as the number of different virus families. One of the most recurrent strategies used by viruses to control the antiviral response of the cell is to hijack the translation machinery of the host, such that viral proteins are preferentially synthesized, while the expression of the stress and antiviral responses of the cell are blocked at the translation level. Here, we will review how rotaviruses, an important agent of acute severe gastroenteritis in children, overcome the stress responses of the cell to establish a productive infectious cycle.

  1. Stress Response and Translation Control in Rotavirus Infection

    Science.gov (United States)

    López, Susana; Oceguera, Alfonso; Sandoval-Jaime, Carlos

    2016-01-01

    The general stress and innate immune responses are closely linked and overlap at many levels. The outcomes of these responses serve to reprogram host expression patterns to prevent viral invasions. In turn, viruses counter attack these cell responses to ensure their replication. The mechanisms by which viruses attempt to control host cell responses are as varied as the number of different virus families. One of the most recurrent strategies used by viruses to control the antiviral response of the cell is to hijack the translation machinery of the host, such that viral proteins are preferentially synthesized, while the expression of the stress and antiviral responses of the cell are blocked at the translation level. Here, we will review how rotaviruses, an important agent of acute severe gastroenteritis in children, overcome the stress responses of the cell to establish a productive infectious cycle. PMID:27338442

  2. Prevalence of rotavirus, adenovirus, hepatitis A virus and enterovirus in water samples collected from different region of Peshawar, Pakistan.

    Science.gov (United States)

    Ahmad, Tahir; Arshad, Najma; Adnan, Fazal; Sadaf Zaidi, Najam-Us-Sahar; Shahid, Muhammad Talha; Zahoor, Usman; Afzal, Muhammad S; Anjum, Sadia

    2016-12-23

    Viral gastroenteritis and other water-borne diseases are the most neglected areas of research in Pakistan. To determine the quality of water, 4 enteric viruses were studied from different localities of Peshawar, Pakistan. The study validates the viral detection method for Rotavirus (RV), Human adenovirus (HAdV), Enterovirus (EV) and Hepatitis A virus (HAV), directly from water sources of rural areas of Peshawar, KPK, Pakistan. Overall, 95 five water samples were tested; among them, 9.47% were positive for RV, 38.94% for HAdV, 48.42% for EV and 12.63% for HAV. The presence of these viruses in water was directly correlated with meteorological data. High prevalence of EV and HAdV was detected frequently in the wet season from May - September, which can be the potential cause of spreading of gastroenteritis in the population. Environmental surveillance is an additional tool to evaluate the epidemiology of enteric viruses circulating in a given community.

  3. Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K;

    2011-01-01

    To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

  4. Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K

    2011-01-01

    To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes.......To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

  5. Tylosema esculentum (Marama Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection

    Directory of Open Access Journals (Sweden)

    Walter Chingwaru

    2011-01-01

    Full Text Available Tylosema esculentum (marama beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4, adult pig (CLAB and adult bovine (CIEB origin. Marama cotyledon ethanolic extract (MCE and cotyledon water extract (MCW without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity. Marama cotyledon ethanolic and water extracts (MCE and MCW, resp. (≥0.1 mg/mL, seed coat extract (MSCE and seed coat water extract (MSCW (0.01 to 0.001 mg/mL, especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments. All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm2 of enterocyte barriers after coincubation with RV. Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide. Marama extracts are therefore promising microbicides against RV.

  6. Tylosema esculentum (Marama) Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection.

    Science.gov (United States)

    Chingwaru, Walter; Majinda, Runner T; Yeboah, Sam O; Jackson, Jose C; Kapewangolo, Petrina T; Kandawa-Schulz, Martha; Cencic, Avrelija

    2011-01-01

    Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin. Marama cotyledon ethanolic extract (MCE) and cotyledon water extract (MCW) without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity. Marama cotyledon ethanolic and water extracts (MCE and MCW, resp.) (≥0.1 mg/mL), seed coat extract (MSCE) and seed coat water extract (MSCW) (0.01 to 0.001 mg/mL), especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments. All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm(2)) of enterocyte barriers after coincubation with RV. Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide. Marama extracts are therefore promising microbicides against RV.

  7. Removal of Rotavirus and Bacteriophages by Membrane Bioreactor Technology from Sewage.

    Science.gov (United States)

    Hmaied, F; Keskes, S; Jebri, S; Amri, I; Yahya, M; Loisy-Hamon, F; Lebeau, B; Hamdi, M

    2015-11-01

    Human enteric viruses constitute a public health concern due to their low infectious dose and their resistance to environmental factors and to inactivation processes. We aimed at assessing the performance of a laboratory scale Submerged membrane bioreactor (SMBR) treating abattoir wastewaters for Rotavirus (RV) and total coliphages removal. We also aimed at evaluating removal efficiency of enteric viruses through conventional activated sludge treatment by measuring concentrations of total coliphages, considered as fecal and viral contamination indicators, with double-layer agar technique. The Log10 reduction values of bacteriophages ranged from 1.06 to 1.47. Effluents were analyzed to investigate and quantify RV, hepatitis A virus (HAV), Hepatitis E virus (HEV), Noroviruses genogroup I (NoV GI) and genogroup II (NoVGII), and Enterovirus (EV) by real-time PCR, using standardized detection kits (ceeramTools detection kits(®)). All effluent samples were positive for RV; concentrations ranged from 5.2 × 10(5) to 1.3 × 10(7) genome copies/L. These results highlight the inefficiency of conventional biological process for viral removal. A complete removal of RV during Membrane Bioreactor treatment was obtained. To the best of our knowledge, this is the first study providing an evidence of removal of RV simultaneously with total coliphages by SMBR.

  8. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana

    Science.gov (United States)

    Harris, Vanessa C.; Armah, George; Fuentes, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D. C.; de Vos, Willem M.

    2017-01-01

    Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. PMID:27803175

  9. Attenuation of pathogenic immune responses during infection with human and simian immunodeficiency virus (HIV/SIV by the tetracycline derivative minocycline.

    Directory of Open Access Journals (Sweden)

    Julia L Drewes

    Full Text Available HIV immune pathogenesis is postulated to involve two major mechanisms: 1 chronic innate immune responses that drive T cell activation and apoptosis and 2 induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1 and TNF-related apoptosis inducing ligand (TRAIL in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4 in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3 but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo.

  10. Sanguis draconis, a Dragon’s Blood Resin, Attenuates High Glucose-Induced Oxidative Stress and Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Yi Chang

    2014-01-01

    Full Text Available Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by limiting the proliferative potential of these cells. Here we aimed to investigate the effect of an ethanolic extract of Sanguis draconis (SD, a kind of dragon’s blood resin that is obtained from Daemonorops draco (Palmae, on human umbilical vein endothelial cells (HUVEC under high-glucose (HG stimulation and its underlying mechanism. Concentration-dependent (0–50 μg/mL assessment of cell viability showed that SD does not affect cell viability with a similar trend up to 48 h. Remarkably, SD (10–50 μg/mL significantly attenuated the high-glucose (25 and 50 mM induced cell toxicity in a concentration-dependent manner. SD inhibited high glucose-induced nitrite (NO and lipid peroxidation (MDA production and reactive oxygen species (ROS formation in HUVEC. Western blot analysis revealed that SD treatments abolished HG-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2, nuclear transcription factor, κB (NF-κB, VCAM-1, and E-selectin, and it also blocked the breakdown of PARP-116 kDa protein in a dose-dependent manner. Furthermore, we found that SD increased the expression of Bcl-2 and decreased Bax protein expression in HG-stimulated HUVEC. Thus, these results of this study demonstrate for the first time that SD inhibits glucose induced oxidative stress and vascular inflammation in HUVEC by inhibiting the ERK/NF-κB/PARP-1/Bax signaling cascade followed by suppressing the activation of VCAM-1 and E-selectin. These data suggest that SD may have a therapeutic potential in vascular inflammation due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activation.

  11. Microvesicles derived from human umbilical cord Wharton's jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Shuai Wu

    Full Text Available Several studies suggest that mesenchymal stem cells (MSCs possess antitumor properties; however, the exact mechanisms remain unclear. Recently, microvesicles (MVs are considered as a novel avenue intercellular communication, which may be a mediator in MSCs-related antitumor effect. In the present study, we evaluated whether MVs derived from human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs may inhibit bladder tumor T24 cells growth using cell culture and the BALB/c nu/nu mice xenograft model. CCK-8 assay and Ki-67 immunostaining were performed to estimate cell proliferation in vitro and in vivo. Flow cytometry and TUNEL assay were used to assess cell cycle and apoptosis. To study the conceivable mechanism by which hWJMSC-MVs attenuate bladder tumor T24 cells, we estimated the expression of Akt/p-Akt, p-p53, p21 and cleaved Caspase 3 by Western blot technique after exposing T24 cells to hWJMSC-MVs for 24, 48 and 72h. Our data indicated that hWJMSC-MVs can inhibit T24 cells proliferative viability via cell cycle arrest and induce apoptosis in T24 cells in vitro and in vivo. This study showed that hWJMSC-MVs down-regulated phosphorylation of Akt protein kinase and up-regulated cleaved Caspase 3 during the process of anti-proliferation and pro-apoptosis in T24 cells. These results demonstrate that hWJMSC-MVs play a vital role in hWJMSC-induced antitumor effect and may be a novel tool for cancer therapy as a new mechanism of cell-to-cell communication.

  12. Salvianolic acid A inhibits angiotensin II-induced proliferation of human umbilical vein endothelial cells by attenuating the production of ROS

    Science.gov (United States)

    Yang, Luan-luan; Li, Dong-ye; Zhang, Yan-bin; Zhu, Man-yi; Chen, Dan; Xu, Tong-da

    2012-01-01

    Aim: To investigate the action of salvianolic acid A (SalA) on angiotensin II (Ang II)-induced proliferation of human umbilical vein endothelial cells (HUVECs) and the possible signaling pathways mediating this action. Methods: Cell proliferation was examined with MTT assay. The expression levels of Src phosphorylation (phospho-Src), Akt phosphorylation (phospho-Akt), and NADPH oxidase 4 (Nox4) in HUVECs were determined by Western blot. The production of reactive oxygen species (ROS) was estimated using fluorescence-activated cell sorting (FACS). Results: SalA (6.25–50 μmol/L) did not affect the viability of HUVECs. Treatment of HUVECs with Ang II (1 μmol/L) markedly increased the cell viability; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) prevented Ang II-induced increase of the cell viability in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) markedly up-regulated the protein expression levels of phospho-Src, phospho-Akt (473) and Nox4; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked all the effects in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) dramatically increased ROS production in HUVECs; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked the ROS production in a concentration-dependent manner. Conclusion: SalA inhibits Ang II-induced proliferation of HUVECs via reducing the expression levels of phospho-Src and phospho-Akt (473), thereby attenuating the production of ROS. PMID:22101169

  13. Salvianolic acid A reverses paclitaxel resistance in human breast cancer MCF-7 cells via targeting the expression of transgelin 2 and attenuating PI3 K/Akt pathway.

    Science.gov (United States)

    Cai, Jiangxia; Chen, Siying; Zhang, Weipeng; Zheng, Xiaowei; Hu, Sasa; Pang, Chengsen; Lu, Jun; Xing, Jianfeng; Dong, Yalin

    2014-10-15

    Chemotherapy resistance represents a major problem for the treatment of patients with breast cancer and greatly restricts the use of first-line chemotherapeutics paclitaxel. The purpose of this study was to investigate the role of transgelin 2 in human breast cancer paclitaxel resistance cell line (MCF-7/PTX) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) indicated that transgelin 2 may mediate paclitaxel resistance by activating the phosphatidylinositol 3-kinase (PI3 K)/Akt signaling pathway to suppress MCF-7/PTX cells apoptosis. The reversal ability of SAA was confirmed by MTT assay and flow cytometry, with a superior 9.1-fold reversal index and enhancement of the apoptotic cytotoxicity induced by paclitaxel. In addition, SAA effectively prevented transgelin 2 and adenosine-triphosphate binding cassette transporter (ABC transporter) including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) up-regulation and exhibited inhibitory effect on PI3 K/Akt signaling pathway in MCF-7/PTX cells. Taken together, SAA can reverse paclitaxel resistance through suppressing transgelin 2 expression by mechanisms involving attenuation of PI3 K/Akt pathway activation and ABC transporter up-regulation. These results not only provide insight into the potential application of SAA in reversing paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of transgelin 2 in the development of paclitaxel resistance in breast cancer.

  14. Salvianolic acid A inhibits angiotensin Ⅱ-induced proliferation of human umbilical vein endothelial cells by attenuating the production of ROS

    Institute of Scientific and Technical Information of China (English)

    Luan-luan YANG; Dong-ye LI; Yan-bin ZHANG; Man-yi ZHU; Dan CHEN; Tong-da XU

    2012-01-01

    To investigate the action of salvianolic acid A (SalA) on angiotensin Ⅱ (Ang Ⅱ)-induced proliferation of human umbilical vein endothelial cells (HUVECs) and the possible signaling pathways mediating this action.Methods:Cell proliferation was examined with MTT assay.The expression levels of Src phosphorylation (phospho-Src),Akt phosphorylation (phospho-Akt),and NADPH oxidase 4 (Nox4) in HUVECs were determined by Western blot.The production of reactive oxygen species (ROS) was estimated using fluorescence-activated cell sorting (FACS).Results:SalA (6.25-50 μmol/L) did not affect the viability of HUVECs.Treatment of HUVECs with Ang Ⅱ(1 μmol/L) markedly increased the cell viability; pretreatment of HUVECs with SalA (12.5,25,and 50 μmol/L) prevented Ang Ⅱ-induced increase of the cell viability in a concentration-dependent manner.Treatment of HUVECs with Ang Ⅱ(1 μmol/L) markedly up-regulated the protein expression levels of phospho-Src,phospho-Akt (473) and Nox4; pretreatment of HUVECs with SalA (12.5,25,and 50 μmol/L) blocked all the effects in a concentration-dependent manner.Treatment of HUVECs with Ang Ⅱ(1 μmol/L) dramatically increased ROS production in HUVECs; pretreatment of HUVECs with SalA (12.5,25,and 50 μmol/L) blocked the ROS production in a concentration-dependent manner.Conclusion:SalA inhibits Ang Ⅱ-induced proliferation of HUVECs via reducing the expression levels of phospho-Src and phospho-Akt (473),thereby attenuating the production of ROS.

  15. Detection of rotavirus species A, B and C in domestic mammalian animals with diarrhoea and genotyping of bovine species A rotavirus strains.

    Science.gov (United States)

    Otto, Peter H; Rosenhain, Stefanie; Elschner, Mandy C; Hotzel, Helmut; Machnowska, Patrycja; Trojnar, Eva; Hoffmann, Kathrin; Johne, Reimar

    2015-09-30

    Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and animals worldwide. In this study, 425 faecal samples were collected between 1999 and 2013 from diarrhoeic livestock and companion animals at different locations in Germany and tested for RVs. A previously published real-time RT-PCR assay was optimized for detection of a larger variety of RV species A (RVA) strains, and real-time RT-PCR assays for detection of RV species B (RVB) and C (RVC) were newly developed. The detection limits of the assays were 1.54×10(2), 3.95×10(2) and 3.60×10(3) genome copies for RVA, RVB and RVC, respectively. RVA was identified in 85.2% of bovine samples, 51.2% of porcine samples, 50.0% of feline samples, 43.2% of equine samples and 39.7% of canine samples. RVB was found in 3.0% of bovine samples, 2.7% of equine samples and 1.6% of porcine samples. RVC was detected in 31.0% of porcine samples, 21.7% of feline samples, 9.0% of canine samples and 6.0% of bovine samples. For genotyping, 101 RVA-positive bovine samples were further analysed by semi-nested RT-PCR. Genotype combination G6P[5] was most frequently detected (67.3% of samples), followed by G6P[11] (13.9%), G10P[5] (4.0%), G8P[11] (3.0%), G6P[1] (1.0%), and G10P[11] (1.0%). Mixed RVA infections were detected in 5.9% of samples; no or incomplete typing was possible in 4.0% of the samples. This first overview on RV species and RVA genotypes in diarrhoeic livestock and companion animals from Germany indicates a broad circulation of a large variety of RVs.

  16. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo; Beom; Eom; Hokyung; Kim; Jinchae; Kim; Un-Chul; Paek; Byeong; Ha; Lee

    2003-01-01

    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  17. An update to "The cost-effectiveness of rotavirus vaccination: comparative analyses for five European countries and transferability in Europe".

    Science.gov (United States)

    Jit, Mark; Mangen, Marie-Josée J; Melliez, Hugues; Yazdanpanah, Yazdan; Bilcke, Joke; Salo, Heini; Edmunds, W John; Beutels, Philippe

    2010-11-01

    A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to remain valid. Vaccination remains cost-effective in Finland only when using plausible tender prices.

  18. In vitro neutralisation of rotavirus infection by two broadly specific recombinant monovalent llama-derived antibody fragments

    NARCIS (Netherlands)

    F. Aladin (Farah); A.W.C. Einerhand (Sandra); J. Bouma (Janneke); S. Bezemer (Sandra); P. Hermans (Pim); D. Wolvers (Danielle); K. Bellamy (Kate); L.G.J. Frenken (Leon); J. Gray (Jim); M. Iturriza-Gómara (Miren)

    2012-01-01

    textabstractRotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (refe

  19. An update of cost-effectiveness of rotavirus vaccination in indonesia: Takinga birth-dose vaccination strategy into account

    NARCIS (Netherlands)

    Suwantika, A.A.; Setiawan, D.; Atthobari, J.; Postma, M.J.

    2014-01-01

    Objectives: Rotavirus infection was reported as the major cause of severe diarrhea in children under 5-years-old in Indonesia. A low cost rotavirus vaccine to protect infants from birth has been developed for developing countries, such as Indonesia. This study aims to update our initial analysis on

  20. An update to "The cost-effectiveness of rotavirus vaccination : Comparative analyses for five European countries and transferability in Europe"

    NARCIS (Netherlands)

    Jit, Mark; Mangen, Marie-Josee J.; Melliez, Hugues; Yazdanpanah, Yazdan; Bilcke, Joke; Salo, Heini; Edmunds, W. John; Beutels, Philippe

    2010-01-01

    A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to rem

  1. Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

    Science.gov (United States)

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

    2013-01-01

    Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bacteria, viruses. protozoa and fungi was positive in 425 (49.76%) cases. From this number the test on bacteria was positive in 248 (58.62%) cases, on viruses it was positive in 165 (39.0%), on protozoa in 9 (2.12%) cases and on fungi only one case. Rotavirus was the most frequent one in viral test, it was isolated in 142 (86.06%) cases, adenoviruses were found in 9 (5.45%) cases and noroviruses in only one case. The same feces sample that contained rotavirus and adenoviruses were isolated in five cases, whereas rotavirus with bacteria was isolated in the same feces sample in five cases. The biggest number of cases 62 (43.66%) were of the age 6-12 months, whereas the smallest number 10 (7.04%) cases were of the age 37-60 months. There were 76 (53.52%) of cases of male gender, from rural areas there were 81 (57.04%) cases and there were 58 (40.80%) cases during the summer period. Among the clinical symptoms the most prominent were diarrhea, vomiting, high temperature, whereas the different degree of dehydration were present in all cases (the most common one was moderate dehydration). The most frequent one was isonatremic dehydration in 91 (64.08%) cases, less frequent one was hypernatremic dehydration in 14 (9.85%) cases. The majority of cases (97.89%) had lower blood pH values, whereas 67 (47.17%) cases had pH values that varied from 7.16 -7.20 (curve peak), normal values were registered in only 3 (2.11%) cases. Urea values were increased in 45 (31.07%) cases (the maximum value

  2. Rotaviruses as a cause of nosocomial, infantile diarrhoea in Northern Brazil: pilot study

    Directory of Open Access Journals (Sweden)

    Rosa Helena P. Gusmão

    1995-12-01

    Full Text Available Faecal samples were obtained from 190 children, aged 0 to 5 years, admitted to a public hospital in Belém, Pará, Brazil. These patients were placed in a pediatric ward with 40 beds distributed in six rooms. Case were classified into three groups: (a nosocomial: children who developed gastroenteritis 72 hr or later after admission; (b community-acquired: patients admitted either with diarrhoea or who had diarrhoea within 72 hr following admission; (c non-diarrhoeic: those children who had no diarrhoea three days before and three days after collection of formed faecal sample. Specimens were routinely processed for the presence of rotaviruses, bacteria and parasites. Rotaviruses were detected through enzyme-linked immunosorbent assay (ELISA and subsequently serotyped/electrophoretyped. Rotaviruses were the most prevalent enteropathogens among nosocomial cases, accounting for 39 % (9/23 of diarrhoeal episodes; on the other hand, rotaviruses ocurred in 8.3 % (11/133 and 9 % (3/34 of community-acquired and non-diarrhoeic categories, respectively. Mixed infections involving rotavirus and Giardia intestinalis and rotavirus plus G. intestinalis and Entamoeba histolytica were detected in frequencies of 8.6 and 4.3 %, respectively, in the nosocomial group. The absence of bacterial pathogens in this category, and the unusual low prevalence of these agents in the other two groups may reflect the early and routine administration of antibiotics following admission to this hospital. Rotavirus serotype 2 prevailed over the other types, accounting for 77.8 % of isolates from nosocomial diarrhoeal episodes. In addition, at least five different genomic profiles could be observed, of which one displayed an unusual five-segment first RNA cluster. Dehydration was recorded in all cases of hospital-acquired, rotavirus-associated diarrhoea, whereas in only 57 % of nosocomial cases of other aetiology. It was also noted that nosocomial, rotavirus-associated diarrhoeal

  3. The Comparition of the Efficacy of Two Different Probiotics in Rotavirus Gastroenteritis in Children

    Directory of Open Access Journals (Sweden)

    Özlem Erdoğan

    2012-01-01

    Full Text Available Objectives. The aim of the study is to compare the clinical effectiveness of the probiotics—Saccharomyces boulardii and Bifidobacterium lactis—in children who had been diagnosed with rotavirus gastroenteritis. Materials and methods. Seventy five patients aged between 5 months–5 years diagnosed as rotavirus gastroenteritis were included in the study. The patients diagnosed as rotavirus gastroenteritis by latex agglutination test in stool were divided into 3 groups of twenty-five patients each: First group was given oral rehydration therapy and rapid refeeding with a normal diet with Saccharomyces boulardii (spp. I-745, second group was given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis (spp. B94, culture number:∘118529 and third group received only oral rehydration therapy and rapid refeeding with a normal diet. Results. The duration of diarrhea was shorter in the group given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis and Saccharomyces boulardii than the group given only oral rehydration therapy and rapid refeeding with a normal diet. Conclusion. Bifidobacterium lactis has a complemental role in the treatment of rotavirus gatroenteritis and other probiotics may also have a beneficial effect in rotavirus gastroenteritis compared with the therapy included only oral rehydration therapy and rapid refeeding with a normal diet.

  4. Nitazoxanide in Acute Rotavirus Diarrhea: A Randomized Control Trial from a Developing Country

    Science.gov (United States)

    Mahapatro, Samarendra; Mahilary, Nijwm; Satapathy, Amit Kumar

    2017-01-01

    Background. Acute diarrhea is one of the leading causes of childhood mortality, with rotavirus being an important pathogen. Nitazoxanide, an antiparasitic agent, has been shown to inhibit rotavirus. Objective. This double-blind, randomized trial was designed to study the role of nitazoxanide in acute rotavirus diarrhea. Methods. Of 174 children (12 months to 5 years) with acute diarrhea, 50 rotavirus positive cases were randomized. The intervention group received syrup nitazoxanide twice daily (100 mg in 12–47 months, 200 mg in ≥4 yr) for 3 days along with standard treatment of diarrhea. Duration of diarrhea was the primary outcome measure. Results. The median duration (hrs) of diarrhea (54 versus 80; 95% CI: –26 [–13.2 to –38.8]) and hospitalization (68 versus 90; 95% CI: –22 [–12.98 to –31.02]) was significantly shorter in the nitazoxanide group. No significant difference was seen in the median duration (hrs) of fever or vomiting or the proportion of children requiring parenteral rehydration. There was no report of any adverse events. Conclusions. Oral nitazoxanide is effective and safe in the management of acute rotavirus diarrhea in Indian children (CTRI REF/2016/10/012507). PMID:28331496

  5. Nitazoxanide in Acute Rotavirus Diarrhea: A Randomized Control Trial from a Developing Country

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    Samarendra Mahapatro

    2017-01-01

    Full Text Available Background. Acute diarrhea is one of the leading causes of childhood mortality, with rotavirus being an important pathogen. Nitazoxanide, an antiparasitic agent, has been shown to inhibit rotavirus. Objective. This double-blind, randomized trial was designed to study the role of nitazoxanide in acute rotavirus diarrhea. Methods. Of 174 children (12 months to 5 years with acute diarrhea, 50 rotavirus positive cases were randomized. The intervention group received syrup nitazoxanide twice daily (100 mg in 12–47 months, 200 mg in ≥4 yr for 3 days along with standard treatment of diarrhea. Duration of diarrhea was the primary outcome measure. Results. The median duration (hrs of diarrhea (54 versus 80; 95% CI: –26 [–13.2 to –38.8] and hospitalization (68 versus 90; 95% CI: –22 [–12.98 to –31.02] was significantly shorter in the nitazoxanide group. No significant difference was seen in the median duration (hrs of fever or vomiting or the proportion of children requiring parenteral rehydration. There was no report of any adverse events. Conclusions. Oral nitazoxanide is effective and safe in the management of acute rotavirus diarrhea in Indian children (CTRI REF/2016/10/012507.

  6. Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

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    Hammarström Lennart

    2007-09-01

    Full Text Available Abstract Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti – rotavirus antibodies in a mouse model of rotavirus diarrhea. Results Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. Conclusion The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.

  7. Changes in Childhood Diarrhea Incidence in Nicaragua Following 3 Years of Universal Infant Rotavirus Immunization

    Science.gov (United States)

    Becker-Dreps, Sylvia; Paniagua, Margarita; Dominik, Rosalie; Cao, Hongyuan; Shah, Naman K.; Morgan, Douglas R.; Moreno, Gilberto; Espinoza, Félix

    2011-01-01

    Background While the pentavalent rotavirus vaccine was highly efficacious against rotavirus diarrhea in clinical trials, the vaccine’s effectiveness under field conditions in the developing world is unclear. In October, 2006, Nicaragua became the first developing nation to implement universal infant immunization with the pentavalent rotavirus vaccine. To assess the impact of the immunization program, we examined the incidence of diarrhea episodes between 2003 and 2009 among children in the state of León, Nicaragua. Methods We extracted data on diarrhea episodes from health ministry records. We used scaled Poisson regression models to estimate diarrhea incidence rate ratios (IRR) for the period following the program’s implementation to the period before implementation. Results Following implementation of the immunization program, diarrhea episodes among infants were reduced (IRR 0.85, 95% confidence interval [CI] 0.71–1.02) during the rotavirus season, but appear to have increased during other months. Conclusions While the immunization program appears effective in reducing diarrhea episodes during the rotavirus season, a large burden of diarrhea persists during the remainder of the year. PMID:20881511

  8. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings.

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    Benjamin A Lopman

    Full Text Available INTRODUCTION: Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. METHODS: We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. RESULTS: Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. DISCUSSION: The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES and vaccination program (e.g. additional doses may bring improvements.

  9. Molecular characterisation of a bovine-like rotavirus detected from a giraffe

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    O'Shea Helen

    2008-11-01

    Full Text Available Abstract Background Rotavirus (RV, is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf. Results This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis, presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. Detailed sequence analysis of VP4 and VP7 revealed significant identity at the amino acid sequence level to Bovine RV (BoRV. Conclusion This study demonstrates the need for continuous surveillance of RV strains in various animal populations, which will facilitate the identification of rotavirus hosts not previously reported. Furthermore, extending typical epidemiology studies to a broader host range will contribute to the timely identification of new emerging strain types.

  10. Prevalence of Rotavirus, Adenovirus, Norovirus, and Astrovirus Infections and Coinfections among Hospitalized Children in Northern France▿

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    Tran, Adissa; Talmud, Déborah; Lejeune, Benoît; Jovenin, Nicolas; Renois, Fanny; Payan, Christopher; Leveque, Nicolas; Andreoletti, Laurent

    2010-01-01

    From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P = 0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments. PMID:20305010

  11. Rotavirus G2P[4] detection in fresh vegetables and oysters in Mexico City.

    Science.gov (United States)

    Quiroz-Santiago, Carolina; Vázquez-Salinas, Carlos; Natividad-Bonifacio, Ivan; Barrón-Romero, Blanca Lilia; Quiñones-Ramírez, Elsa Irma

    2014-11-01

    Rotaviruses are the principal cause of dehydration caused by diarrhea in children younger than 2 years of age. Although these viral infections have mainly been associated with ingestion of fecally contaminated food and water, few studies have addressed the presence of the virus in food that is consumed raw or slightly cooked. In this work, 30 oyster samples and 33 vegetable samples were examined for the presence of rotavirus genotypes to evaluate their potential to produce gastrointestinal infections. The rotaviruses were identified by reverse transcriptase PCR amplification of the VP7 gene. G and P genotyping was also performed by reverse transcriptase PCR, with a detection sensitivity of up to 15 PFU/ml. Rotaviruses were found in 17 (26.9%) of 63 samples (10 oysters and 7 vegetables). The G2 genotype was found in 11 (64.7%) of 17 of the rotavirus strains, and 16 (94.1%) of 17 had the P[4] genotype. The combined genotypes found most frequently were G2P[4] (10 [58.82%] of 17), GNTP[4] (6 [35.29%] of 17), and G2P[NT] (1 [5.8%] of 17).

  12. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  13. Whole genome analysis of Vietnamese G2P[4] rotavirus strains possessing the NSP2 gene sharing an ancestral sequence with Chinese sheep and goat rotavirus strains.

    Science.gov (United States)

    Do, Loan Phuong; Doan, Yen Hai; Nakagomi, Toyoko; Gauchan, Punita; Kaneko, Miho; Agbemabiese, Chantal; Dang, Anh Duc; Nakagomi, Osamu

    2015-10-01

    Because imminent introduction into Vietnam of a vaccine against Rotavirus A is anticipated, baseline information on the whole genome of representative strains is needed to understand changes in circulating strains that may occur after vaccine introduction. In this study, the whole genomes of two G2P[4] strains detected in Nha Trang, Vietnam in 2008 were sequenced, this being the last period during which virtually no rotavirus vaccine was used in this country. The two strains were found to be >99.9% identical in sequence and had a typical DS-1 like G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation. Analysis of the Vietnamese strains with >184 G2P[4] strains retrieved from GenBank/EMBL/DDBJ DNA databases placed the Vietnamese strains in one of the lineages commonly found among contemporary strains, with the exception of the NSP2 and NSP4 genes. The NSP2 genes were found to belong to a previously undescribed lineage that diverged from Chinese sheep and goat rotavirus strains, including a Chinese rotavirus vaccine strain LLR with 95% nucleotide identity; the time of their most recent common ancestor was 1975. The NSP4 genes were found to belong, together with Thai and USA strains, to an emergent lineage (VIII), adding further diversity to ever diversifying NSP4 lineages. Thus, there is a need to enhance surveillance of locally-circulating strains from both children and animals at the whole genome level to address the effect of rotavirus vaccines on changing strain distribution.

  14. Highly sensitive detection of the group A Rotavirus using Apolipoprotein H-coated ELISA plates compared to quantitative real-time PCR

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    Veas Francisco

    2011-02-01

    Full Text Available Abstract Background The principle of a capture ELISA is binding of specific capture antibodies (polyclonal or monoclonal to the surface of a suitable 96 well plate. These immobilized antibodies are capable of specifically binding a virus present in a clinical sample. Subsequently, the captured virus is detected using a specific detection antibody. The drawback of this method is that a capture ELISA can only function for a single virus captured by the primary antibody. Human Apolipoprotein H (ApoH or β2-glycoprotein 1 is able to poly-specifically bind viral pathogens. Replacing specific capture antibodies by ApoH should allow poly-specific capture of different viruses that subsequently could be revealed using specific detection antibodies. Thus, using a single capture ELISA format different viruses could be analysed depending on the detection antibody that is applied. In order to demonstrate that this is a valid approach we show detection of group A rotaviruses from stool samples as a proof of principle for a new method of capture ELISA that should also be applicable to other viruses. Results Stool samples of different circulating common human and potentially zoonotic group A rotavirus strains, which were pretested in commercial EIAs and genotyped by PCR, were tested in parallel in an ApoH-ELISA set-up and by quantitative real-time PCR (qPCR. Several control samples were included in the analysis. The ApoH-ELISA was suitable for the capture of rotavirus-particles and the detection down to 1,000 infectious units (TCID50/ml. Subsets of diagnostic samples of different G- and P-types were tested positive in the ApoH-ELISA in different dilutions. Compared to the qPCR results, the analysis showed high sensitivity, specificity and low cross-reactivity for the ApoH-ELISA, which was confirmed in receiver operating characteristics (ROC analysis. Conclusions In this study the development of a highly sensitive and specific capture ELISA was demonstrated by

  15. Study on epidemiological characteristics of cluster A rotavirus from stool specimens of patients with acute diarrhea%腹泻患者粪便标本中A组轮状病毒感染特征分析

    Institute of Scientific and Technical Information of China (English)

    孙亚萍; 宋士利; 张心会; 檀薇; 陈燕

    2012-01-01

    目的:分析病毒性腹泻患者中人轮状病毒( Human Rotavirus,HRV)的感染情况及毒株流行特点.方法:收集杭州市239份疑似病毒性腹泻患者粪便标本分别应用酶联免疫吸附法及RT-PCR法进行HRV抗原及核酸检测..其中HRV阳性核酸应用巢式RT-PCR进行轮状病毒分型检测.结果:239份粪便标本中HRV抗原阳性为44份(18.4%),HRV核酸阳性为55份(23.0%),其中G血清分型:G3型15份(27.3%),G1型9份(16.4%),G2型为7份(12.7%),G9型为1份(1.8%),G2 +G3混合感染1份(1.8%),未分型22份(40%).结论:A组轮状病毒是婴幼儿病毒性腹泻的重要病原体,同时也可引起成人腹泻散发流行,成人A组轮状病毒流行季节和流行株与婴幼儿一致,G3为主要流行株,且同时存在多种血清型流行,未分型标本的比例较大有待深入研究.%Objective;To analyze the infectious status and epidemiological characteristics of acute viral diarrhea caused by cluster A human rotavirus. Methods: A total of 239 stool specimens from suspected cases with acute virus diarrhea were collected in Hangzhou. IDEIATM kits of Lanzhou institute for biological products were used for antigen detection of human rotavirus. The nucleic acid identifications of the rotavirus were determined by RT - PCR, and the positive samples of HRV nucleic acid were analyzed for genotypes by nested - PCR. Results: Among 239 detected stool specimens,rotavirus antigen positive was 44 cases( 18. 4% ) . Rotavirus nucleic acid positive was 55 cases(23.0% ) , the serotypes were G3(15 cases, 27. 3% ) , Gl (9 cases, 16.4% ) , G2(7 cases, 12. 7% ) , G9 (1 case, 1.8%), G2 + G3 (1 case, 1.8%) and unidentified ones (22 cases, 40% ). Conclusion: Cluster A rotavirus remained the most important pathogen causing diarrhea among infants and sporadic epidemic case with acute diarrhea among adults. The epidemic season and serotype of group A rotavirus in adults are all just the same as those in infant and children. G3

  16. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

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    Cotton, James A; Motta, Jean-Paul; Schenck, L Patrick; Hirota, Simon A; Beck, Paul L; Buret, Andre G

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  17. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

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    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  18. Protein-loosing enteropathy associated with rotavirus infection in an infant

    Institute of Scientific and Technical Information of China (English)

    Tadashi Iwasa; Nobuyuld Matsubayashi

    2008-01-01

    Rotavirus is an acute enteric pathogen in infants and children.We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis,and evaluated the immunological profile in peripheral blood lymphocytes.Laboratory examinations showed lymphopenia,hypoproteinemia,hypoalbuminemia,hypogammaglobulinemia,and elevation of alpha-1-antitrypsin (a1-AT) clearance.Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4positive lymphocytes.Moreover,the excessive increase of T cells producing IFN-gamma(IFN-γ) was found,which plays an important role in the protection against viral infection.The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability,which may play a triggering role in protein-loosing enteropathy.

  19. Comparative study on the mechanisms of rotavirus inactivation by sodium dodecyl sulfate and ethylenediaminetetraacetate

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    Ward, R.L. (Sandia Labs., Albuquerque, NM); Ashley, C.S.

    1980-06-01

    This report describes a comparative study on the effects of the anionic detergent sodium dodecyl sulfate and the chelating agent ethylenediaminetetraacetate on purified rotavirus SA-11 particles. Both chemicals readily inactivated rotavirus at quite low concentrations and under very mild conditions. In addition, both agents modified the viral capsid and prevented the adsorption of inactivated virions to cells. Capsid damage by ethylenediaminetetraacetate caused a shift in the densities of rotavirions from about l.35 to about 1.37 g/ml and a reduction in their sedimentation coefficients. Sodium dodcyl sulfate, on the other hand, did not detectably alter either of these physical properties of rotavirions. Both agents caused some alteration of the isoelectric points of the virions. Finally, analysis of rotavirus proteins showed that ethylenediaminetetraacetate caused the loss of two protein peaks from the electrophoretic pattern of virions but sodium dodecyl sulfate caused the loss of only one of these same protein peaks.

  20. Simultaneous Detection of Group A Rotavirus in Swine and Rat on a Pig Farm in Brazil

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    Paloma de Oliveira Tonietti

    2013-01-01

    Full Text Available This study investigated the occurrence of rotavirus in porcine and Rattus norvegicus, at the same time, on a pig farm in the city of Jaguariúna, São Paulo, Brazil. Swine ( and rat ( fecal samples were analyzed by nested RT-PCR assay. Rotavirus occurred in seven porcine and two rat samples. A total of three pig and one rat samples were further submitted to genetic sequencing. The partial NSP5 gene phylogeny showed that all strains were segregated in the genotype H1. These results point toward a cross-species transmission between rats and pigs on the surveyed farm and represent the first detection of rotavirus in Rattus norvegicus in Brazil.

  1. 婴幼儿腹泻A群轮状病毒G和P的基因分型研究%Molecular genotyping analysis of group A rotavirus in children

    Institute of Scientific and Technical Information of China (English)

    杨爱平; 汪敏; 许文龙; 张国祥

    2012-01-01

    目的 研究浙江萧山医院婴幼儿童腹泻标本中人轮状病毒( Human Rotavirus)毒株的感染情况及G和P基因型流行特点.方法 收集该院2009年8月至2010年8月腹泻儿童15 233份粪便标本采用酶联免疫吸附试验、逆转录-巢式聚合酶链反应进行轮状病毒病原检测,将128份阳性标本进行VP7和VP4基本分型.结果 15233份婴幼儿腹泻标本中有2706份标本为轮状病毒阳性,阳性率17.8%;男孩和女孩检出率差异无统计学意义,以6~12月龄段检出率最高;对128份阳性标本进行G血清分型和P基因分型,G1型53份(41.4%)、G3型38份(29.7%)、G1G3型17份(13.3%)、G未分型20份(15.6%);P[8]型72份(56.3%)、P[4]型16份(12.5%)、P[8]P[4]型3份(2.3%)、P未分型37份(28.9%),G血清型和P基因型的组合以G1P [8]为主,占29.7% (38/128).结论 浙江萧山医院A群轮状病毒G血清以G1型为主,其次为G3型,P基因型以P[8]型为主.%Objective To analyze the epidemic characteristics of group A rotavirus in children by serotyping G and genotyping P. Method 15 233 samples of patients with diarrhea under 5years from August 2009 to August 2010 were collected for detection of rotavirus. The 128 rotavirus antigen-positive stool specimens were enrolled for serotyping G and genotyping P by RT-Nest PCR. Result The rotavirus existed in 17.7% (2706/15233) of the stool specimens. There was no significant differences between genders. The highest detectable rate exsited in children aged 6-12 month. Of the total 128 G serotyping, Gl accounted for 41.4%, G3 29.7%, G1G3 13.3% and non-typeable 15. 6%. 72 (56.3%) of the strains were P [ 8