Efficacy of Fuzheng Hejie Prescription in the Treatment of Respiratory Viral Infection in Children and Its Effect on Immune Function / 广州中医药大学学报

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P＜0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P＜0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P＜0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P＜0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P＜0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.

Study on efficacy and regulation of inflammatory factors with oseltamivir phosphate by different time series of interventions in a murine model of influenza A H1N1 virus infection / 中国药理学通报

Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir (Tamiflu) as a "tool drug" in view of the current situation of the too early the administration time of antiviral in vivo experiment, so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research. Methods Balb/c mice were randomly divided into six groups. The virus infection model was established by intranasal infection with influenza virus (0.25 TCID50). Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure. The body mass, survival rate, organ index, viral load and inflammatory factor content were measured. Results Compared with the blank control group, the body weight of the mice in the model group decreased and the lung index increased significantly (P < 0.05). The expression levels of 13 inflammatory factors in model 2 group were significantly different ( P < 0.05). Compared with the model-1 group ,the lung index and spleen index of the Tamiflu-1 group decreased significantly (P < 0.05). Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower (P <0.05) ,and the thy-mus index was significantly higher (P<0.05). The viral load was 0. 03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different (P < 0. 05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration, the lung inflammation damage is alleviated. Considering the latency, drug intervention is in line with the drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.

Interaction study of the antibacterial peptide urumin with the H1N1 HA protein of influenza A virus / 药学学报

Influenza A virus (H1N1) seriously affects the health of human and disrupts the development of global economic. The antimicrobial peptide urumin specifically binds to the conserved stem of the hemagglutinin (HA) protein of H1N1 virus, but its binding site and the mechanism of action are not clear. In this study, we investigated the possible binding sites and key amino acids for the interaction of urumin with HA protein by molecular docking and enzyme-linked immunosorbent assay (ELISA) experiments, suggesting that HA residues His32 (HA1), Asp19 (HA2), and Trp21 (HA2) are the key residues for the interaction of HA with urumin. Urumin's Arg4, Asn9, and Cys16 were associated with HA protein residues Asp19 (HA2), Trp21 (HA2), His32 (HA1), and Asn53 (HA2) form hydrogen bonding interactions, and Trp12 forms an aromatic π-stacking interaction with His32 (HA1) of HA, these interactions maintain the binding of urumin to HA protein. Wild-type HA and its alanine mutant [alanine substitutions His32 (HA1), Asp19 (HA2), and Trp21 (HA2)] were expressed in 293T cells. ELISA experiments showed that the affinity ability of urumin with HA wild-type was significantly higher than that of HA alanine mutant, suggesting that His32 (HA1), Asp19 (HA2), and Trp21 (HA2) may be the key residues for HA to interact with urumin. This study provides a theoretical and experimental basis for further modification and application of urumin.

As Repercussões Históricas da Pandemia da Gripe Influenza A (H1N1) no Brasil / Las Repercusiones Históricas de la Pandemia de Gripe de la Influenza a (h1n1) de Brasil / The Historical Repercussions of the Influenza Pandemic a (h1n1) in Brazil

Introdução: A pandemia da gripe influenza A (H1N1) ocorrida em 2009 foi considerada a primeira do Século XXI com importantes consequências para a saúde pública mundial. Objetivo: Analisar as repercussões da pandemia da gripe influenza A (H1N1) no Brasil. Método: Trata-se de um estudo histórico-social, cujas fontes diretas utilizadas foram documentos escritos. Discussão e Resultados: As estratégias empreendidas evidenciadas foram implementadas pelo Ministério da Saúde para conter o avanço da doença no país. Entre essas a Carta Aberta, a Nota Técnica sobre Emergência de Saúde Pública de Importância Internacional e o Plano Brasileiro de Preparação para Enfrentamento de uma Pandemia de Influenza. Considerações Finais: Evidenciamos que as autoridades de saúde investiram na luta contra a pandemia no contexto das recomendações da Organização Mundial da Saúde e das demandas de saúde da população brasileira frente aos desafios provocados pela gripe influenza A (H1N1).

Introduction: The Influenza Pandemic type A(H1N1), which occured in 2009, was considered the first of the twenty-first century with important consequences for all the public health systems around the world. Objective: To analyze the implications of the influenza pandemic A H1N1 on the public health system in Brazil. Method: qualitative research, with a socio-historical approach based on direct sources which consisted of written documents. Discussion and Results: The evidenced strategies were implemented by the Ministry of Health to contain the progress of the disease in the country. Among these strategies were an Open Letter, a Technical Note on Public Health Emergency of International Concern e and the Brazilian Preparation Plan for Coping with Pandemic Influenza. Final Considerations: It has been demonstrated that the Health Authorities invested in the fight against the Pandemic, meeting the recommendations of the World Health Organization as well as the health demands of the Brazilian population in the face of the challenges which the H1N1 epidemic represented.

Introducción: La Pandemia de Influenza tipo A (H1N1) ocurrió en 2009, fue considerada la primera del Siglo XXI con importantes consecuencias para la salud pública mundial. Objetivo: Analizar las implicaciones de la pandemia de gripe influenza A H1N1 en Brasil. Método: Investigación cualitativa, con abordaje histórico-social, dónde utilizaron como fuentes directas documentos escritos. Discusión Resultados: El Ministerio de la Salud implementó las estrategias emprendidas evidenciadas para contener el progreso de la enfermedad en el país. Entre ellas está la Carta Abierta, la Nota Técnica sobre Emergencia de Salud Pública de Importancia Internacional y el Plan Brasileño para el Enfrentamiento de una Pandemia de Influenza. Consideraciones finales: Podemos evidenciar que las autoridades de salud invirtieron en la lucha contra la Pandemia estando en concordancia con las ecomendaciones de la Organización Mundial de la Salud y de las demandas de salud de la población brasileña frente a los desafíos que impuso la epidemia H1N1.

A cross sectional analysis on the clinical presentation and outcome of H1N1 influenza patients in a tertiary care hospital in Central Kerala

Background: The World Health Organization raised pandemic H1N1 influenza alert level to phase 6 in June 2009 due to a widespread community transmission on two continents. The recent surge in positive H1N1 cases necessitates a revisit to the clinical profile of the 2009 pandemic. This study was aimed to analyse the clinical profile and outcome of swab positive H1N1 patients.Methods: A cross sectional analysis on the clinical presentation and primary out come in the confirmed H1N1 influenza cases was done. H1N1 confirmation was done using real time reverse transcriptase-Polymerase Chain Reaction in throat swab samples. The data were analysed statistically and presented in percentage.Results: Total 31 cases of severe H1N1 were included in the study. Majority of the cases (16/31) were between15 to 30 yrs of age. Among the total cases, 27 cases were females (87.1%) of which 11 cases were pregnant (35.5%). The predominant presenting symptoms were fever (100%), breathlessness (80.6%), body ache (45.2%), headache (29%) and sore throat (29%). Twenty three of the 31 patients (74.2%) survived while 8 succumbed to the illness (25.8%). All the patients required ICU admission and 8 underwent invasive ventilation. The mortality was high among the ventilated patients (p=0.0064).Conclusions: Pregnancy was associated with higher rate of complications. Early respiratory support did not help in preventing progression to respiratory failure in most of the patients. Vaccination, early recognition of the disease and prompt initiation of treatment appear to be the only way to reduce H1N1 disease progression and mortality.

Effect of Chuankezhi Injection on Prevention and Treatment of H1N1 Influenza Virus in Mice / 中国实验方剂学杂志

Objective: To evaluate the effect of Chuankezhi injection on mouse model of pneumonia induced by influenza A (H1N1) FM1 strain. Method: ICR mice were randomly divided into normal group, model group, tamiflu control group (27.5 mg·kg-1·d-1) and Chuankezhi injection group (1.5 mL·kg-1·d-1). In the death protection experiment, mice were infected with 2×half lethal dose (LD50) of influenza virus FM1.The Chuankezhi injection was given once a day for 4 days. The number of death animal within 14 days was counted. The mortality and the death protection rate were calculated. In the treatment experiment, mice were infected with 0.8×LD50 of influenza virus, and the Chuankezhi injection was given once a day for 4 days. On the 5th day after the infection, the levels of interleukin-8 (IL-8) in lung, prostaglandin E2 (PGE2) and vasopressin (AVP) in brain were tested by enzyme-linked immunosorbent assay (ELISA). The viral load of influenza virus in lung was tested by Real-time PCR. In the pre-treatment experiment, mice were given Chuankezhi injection once a day for 5 days. 1 hour after the last treatment, mice were infected with 0.8×LD50 influenza virus. 4 days after the infection, the lung index, spleen index, thymus index, and viral load in lung tissue were calculated. Result: Compared with normal group, the IL-8, PGE2 content, lung index and viral load in the lung tissue of model group were significantly increased (P2, and the viral load of influenza(PPPPConclusion: Chuankezhi injection could effectively prevent the mouse model of pneumonia induced by influenza A (H1N1) virus. The mechanism might be related to the reduction of inflammation and inhibiting viral replication.

Influences of hypoxia inducible factor-1α on the expression of inflammatory cytokines in mice with influenza A (H1N1) virus infection / 中华微生物学和免疫学杂志

Objective@#To analyze the changes in the expression of hypoxia inducible factor-1α (HIF-1α) and inflammatory cytokines and to investigate the role of HIF-1α in regulating the production of inflammatory cytokines during influenza A (H1N1) virus infection.@*Methods@#BALB/c mice were injected with H1N1 virus to establish the mouse model of H1N1 virus infection. Fifteen BALB/c mice were randomly divided into three groups: control group, H1N1 virus group and H1N1 virus+ HIF-1α inhibitor group. Inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) in samples of serum and lung tissues were detected by Luminex and ELISA. Levels of HIF-1α in serum and lung tissue samples were detected by Western blot and ELISA, respectively.@*Results@#Compared with the control group, the levels of inflammatory cytokines in serum (IL-6, TNF-α, IL-1β and IL-10) and lung tissues (IL-6 and TNF-α) and the expression of HIF-1α in serum and lung tissues in the H1N1 virus group were significantly increased. The levels of HIF-1α, IL-6, TNF-α IL-1β and IL-10 in lung tissues in H1N1 virus+ HIF-1α inhibitor group were significantly lower than those of the H1N1 virus group.@*Conclusion@#During H1N1 virus infection, the levels of inflammatory cytokines and HIF-1α were significantly increased. The production of inflammatory cytokines was significantly reduced after inhibiting HIF-1α expression, suggesting that HIF-1α might promote the production of inflammatory cytokines.

Immunologic mechanisms of Yinhua Pinggan granule and San-ao decoction against influenza virus / 中国中药杂志

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus . The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.

Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus / 中国中药杂志

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus ， the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods， and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER)， median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4， TLR7， MyD88 and TRAF6 in MDCK cells at 24， 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92，1.59 g·L⁻¹ respectively， the TI values were 12.53， 38.78 respectively， and when the concentration of Mahuang Tang was 5.00 g·L⁻¹， ER values were 50.21%， 98.41% respectively， showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile， as compared with the virus group， the virus load was significantly inhibited in Mahuang Tang groups， and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4， TLR7，MyD88 and TRAF6 at 24， 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.

Improvement Effects of Qingre Jiedu Soft Capsule on Mice Infected by Influenza A H1N1 Virus / 中国药房

OBJECTIVE:To observe the antiviral effects of Qingre jiedu soft capsule(ADSC)against influenza A H1N1 virus in vivo,and to provide a experimental support for clinical therapy of influenza A H1N1 virus. METHODS:BALB/c mice were ran-domly divided into normal control group,model control group,positive drug high-dose,medium-dose and low-dose groups [oselta-mivir phosphate capsule,0.04,0.02,0.01 g/(kg·d)] and ADSC high-dose,medium-dose and low-dose groups [1.5,0.75,0.375 g/(kg·d)].Except for normal control group,others groups were given influenza A H1N1 virus with titer 1.6×10-5.2 via nasal cavity to induce poisoned mice model;6-8 h after modeling,they were given relevant medicine intragastrically,once a day,for 5 days. After medication,the change of body weight within 7 d were observed in mice;the mortality and death prevention rate within 15 d,mean survival days(MSDs)were calculated in mice.Other mice were selected and grouped,and they were given same drugs as above. 8 h after last medication,lung index and inhibition rate of lung index were determined in mice.RESULTS:In model control group,the body weight of mice decreased significantly since 5th day,and mice death was beginning to occur since 8th day(mortal-ity of 85.7% within 15 d);the lung index was increased significantly compared to normal control group (P<0.01). Both ADSC and oseltamivir phosphate capsule could slow down the decrease of body weight in mice,decreased the mortality and lung index of mice,and prolonged MSDs;the MSDs of mice in ADSC high-dose,positive drug high-dose and medium-dose groups were signifi-cantly higher than model control group(P<0.05),and lung index was significantly lower than model control group except that of ADSC low-dose group(P<0.05). CONCLUSIONS:ADSC has certain antiviral effect against influenza A H1N1 virus in vivo.

Inhibitory effect of geniposide against influenza A/H1N1 virus / 中国药科大学学报

@#The aim of this study was to explore the protective effects of geniposide against Influenza A(H1N1)pdm09 virus in vitro and in vivo. In vitro, geniposide was administered as a precaution drug, a direct deactivation drug or a treatment drug at different doses. Peramivir was applied as a positive control. The quantitative colorimetric MTT assay was applied to test both the cytotoxicity of geniposide on Madin-Darby Canine Kidney(MDCK)cells and the cytopathogenic effect(CPE)of geniposide on MDCK cells infected by influenza A(H1N1)virus. The viral inhibitory rate of geniposide on NT0901 was also calculated. In vivo, we presented a mouse model of influenza A(H1N1)pdm09 virus infection. Geniposide(5, 10, or 20 mg/kg)or peramivir(30mg/kg)were used as treatment procedures. Lung index and the survival rate were calculated to evaluate the therapeutic effects of geniposide or peramivir on NT0901-infected mice. Haematoxylin and eosin(H&E)stain was used to access the pathological alterations of lung tissues. The study in vitro demonstrated that the TD50(median toxic dose)of geniposide was higher than 1 040 μmol/L. Besides, the EC50(concentration for 50% of maximal effect)of geniposide administered for precaution, direct deactivation and therapy were 91. 90, 96. 25, 87. 68 μmol/L, respectively. These results suggested that geniposide could block the damage of NT0901 on MDCK cells in a dose-dependent manner. The results in vivo showed that geniposide could significantly alleviate the lung index elevation and inflammatory responses in lung tissues induced by NT0901, reduce the mortality of infected mice and extend their survival time. In conclusion, our investigation indicates that geniposide is highly effective in inhibiting cytopathogenic effect and acute lung injury caused by influenza A(H1N1)pdm09 virus. Geniposide may be a potential therapeutic agent for the suppression of influenza virus.

Genotyping Influenza Virus by Next-Generation Deep Sequencing in Clinical Specimens

Rapid and accurate identification of an influenza outbreak is essential for patient care and treatment. We describe a next-generation sequencing (NGS)-based, unbiased deep sequencing method in clinical specimens to investigate an influenza outbreak. Nasopharyngeal swabs from patients were collected for molecular epidemiological analysis. Total RNA was sequenced by using the NGS technology as paired-end 250 bp reads. Total of 7 to 12 million reads were obtained. After mapping to the human reference genome, we analyzed the 3-4% of reads that originated from a non-human source. A BLAST search of the contigs reconstructed de novo revealed high sequence similarity with that of the pandemic H1N1 virus. In the phylogenetic analysis, the HA gene of our samples clustered closely with that of A/Senegal/VR785/2010(H1N1), A/Wisconsin/11/2013(H1N1), and A/Korea/01/2009(H1N1), and the NA gene of our samples clustered closely with A/Wisconsin/11/2013(H1N1). This study suggests that NGS-based unbiased sequencing can be effectively applied to investigate molecular characteristics of nosocomial influenza outbreak by using clinical specimens such as nasopharyngeal swabs.

Construction of microRNA Let-7b-mediated recombinant influenza A (H1N1) virus with mutated PB1 / 医学研究生学报

Objective Vaccination is a most effective method for the prevention of severe diseases caused by pandemic influenza and microRNA ( miRNA) mediated gene silencing has offered a novel approach to the construction of new vaccines.Our study aimed to construct a recombinant influenza A ( H1 N1 ) virus with the PB1 gene that carries the target fragment of miRNA Let-7b. Methods After comparing the sequence of the A/Nanjing/108/2009 H1N1 viral fragments with that of Let-7b, we selected PB1 as the optimal gene sequence, inserted the Let-7b binding target gene into PB1, ligated the modified fragments with pDP 2000, and named the recombinant plasmids pDP-mu-PB1 and pDP-sclb-PB1, respectively.We co-transfected the MDCK and 293T cells with the recombinant and other seven plasmids and injected the supernatant into the allantoic cavity of the chickenembryo for virus propagation, followed by detection of the virus by hemagglutination ( HA) assay and measurement of the viral titer by TCID50 .We amplified the viral cRNA by RT-PCR and identified the viruses by agarose gel electrophoresis and nucleotide sequence analysis. Results PB1 was the optimal sequence ( 83 bp -107bp) for the attenuation of viruses.The HA-titers of miRT-H1N1 and scbl-H1N1 were 1∶32 and 1∶64, and their viral loads were 4.68 ×105 and 7.94 ×104 TCID50/mL, respectively.Nucleotide sequence analysis showed the expected fragment in the rescued virus. Conclusion A recombinant strain vaccine was successfully constructed, which has laid the foundation for fur-ther assessment of virulence.

Comparison of pulmonary pathological changes in mice infected with H7N9 influenza virus and pandemic H1N1 influenza virus / 中国实验动物学报

Objective To analyze and compare the pathological changes of lung tissue in mice infected with the novel H7N9 influenza virus and 2009 pandemic H1N1 influenza virus, respectively, and to preliminarily study the mecha-nisms of acute lung injury induced by those virus infection .Methods SPF 6-week old BALB/c mice ( body weight 18-20 g, male∶female=1∶1) (n=3 in each subgroup) were intranasally infected with H7N9 virus and H1N1 virus, respec-tively.The behavior and survival time of mice after virus infection were observed and the survival rates were analyzed .The heart, liver, spleen, lung, kidney, intestines, and brain were collected at indicated time points for histopathological exami-nation using H&E staining .The distribution of virus antigen was detected by immunohistochemistry .The neutrophil infiltra-tion was also observed .The correlation of lung injury with virus replication and host immune responses was analyzed .Re-sults The lung and spleen injury of mice infected with H 7N9 virus was slighter and their survival rate (100%) was high-er than those of mice infected with H1N1 virus.The damages of the lung and spleen in H1N1virus-infected mice were more severe than that in H7N9 virus-infected mice, and all the 10 mice in this group died within 9 days after virus inoculation . The distributions of both the virus antigens were mainly in the bronchial epithelial cells , a few stromal cells and alveolar ep-ithelial cells .The levels of virus replication in the two groups were not significantly different .There were more intense neu-trophil infiltration in the lung and inflammatory response in the H 1N1 virus-infected mice than those in the H7N9 virus-in-fected mice .Conclusions There are some differences of the pathological characteristics and extent of lung injury in the mice infected with H7N9 virus and H1N1 virus, respectively.The virus replication is a precipitating factor but not the deci-sive factor of the lung injury , and there is a close relationship between the host immune responses and acute lung injury .

Effectiveness Analysis Through Enzyme-Linked Immunosorbent Assay Examination of Antibody After Pandemic H1N1 2009 Influenza Vaccination

BACKGROUND: A pandemic influenza outbreak started in 2009 by the number of patients discharged each year. But the result of H1N1 influenza vaccination is maintained for research and less state. The purpose of this study was to measure the antibody titers after H1N1 influenza vaccination toestimate demands of different standard vaccination in patients with chronic diseases and elderly patients. METHODS: From March 2010 to February 2011, we retrospectively reviewed the medical records of 55 patients admitted to a tertiary hospital. The H1N1 virus antibody titer of each patient was measured through enzyme-linked immunosorbent assay. Titers were measured post vaccination on day 1 and at 1, 3 and 6 months. RESULTS: A total of 55 patients were enrolled in this study. The comorbidities looked at were malignancy, cardiovascular disease, diabetes mellitus, renal disease, cerebrovascular disease, hematologic disease and infectious disease. Five patients (9.1%) had no comorbidities. Patients in their 50's had the highest positive response rate (58.3%). The antibody titers at 1 month after vaccination were not associated with the number of comorbidities. The ratio of positive response increased gradually at baseline (16.4%) to 1 month (47.8%). After 6 months, there remained no positive response. CONCLUSION: The H1N1 antibodies were unstable as the values of the titer changed at follow-up (1 month, 3 months, and 6 months). The positive response rates of those in their 50's and those who had chronic diseases were higher than others. The positive response rates showed that the ability to generate antibodies did not decrease with age or disease conditions.

A Case of Systemic Lupus Erythematosus Occurring after H1N1 Influenza Vaccination / 대한내과학회지

The recent worldwide outbreak of H1N1 has led to the universal administration of H1N1 influenza vaccination, including in South Korea. Several complications have been reported with use of H1N1 influenza vaccine, but systemic lupus erythematosus (SLE) has not been reported as a complication until now. Here, we report a case of SLE occurrence after H1N1 influenza vaccination. A 17-year-old girl who had not been diagnosed with SLE was hospitalized with fever, myalgia, and arthralgia after H1N1 influenza vaccination. Laboratory tests revealed increased levels of antinuclear antibody and anti-ds-DNA antibody, and decreased levels of C3 and C4 as well as proteinuria. The pathological findings confirmed a diagnosis of lupus nephritis. The patient was treated with high-dose corticosteroid and hydroxychloroquine. This is the first report of SLE following H1N1 influenza vaccination in South Korea.

Hemophagocytic lymphohistiocytosis associated with H1N1 virus infection and visceral leishmaniasis in a 4.5-month-old infant / Linfohistiocitose hemofagocítica associada pela infecção do vírus H1N1 e leishmaniose visceral em um bebê de 4,5 meses de vida

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

É relatado um caso de um menino de 4,5 meses de idade, da Turquia, com linfohistiocitose hemofagocítica (HLH) associado à coinfecção com o vírus H1N1 e leishmaniose visceral. Como a leishmaniose visceral pode imitar doenças hematológicas como HLH, é importante afastar essa condição clínica antes de iniciar a terapia imunossupressora. No caso relatado, o tratamento com anfotericina B lipossomal resultou em uma resolução dramática das anomalias clínicas e laboratoriais.

Pandemic influenza A/H1N1 virus in a swine farm house in Sicily, Italy.

This report describes a pandemic A/H1N1 (H1N1 pdm) virus outbreak occurred in December, 2009 in a swine farm used as research facility (Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione) for preclinical studies, located in Sicily, Italy. All the 13 pigs of the farm, showed cough, fever, inappetence and weakness. At the same time, an unvaccinated worker of the stabling showed influenza-like symptoms. RNAv extracted from two swabs collected from infected pigs resulted positive by Real Time RT-PCR for Influenza A virus. Furthermore, after growth on embryonated eggs, viral isolates were identified by Real Time RT-PCR specific for H1N1 pdm virus and characterized antigenically. Sequencing of the whole genome was also performed. All sera taken from animals and from the worker were tested by a competitive Influenza A ELISA and by the haemoagglutination inhibition test. Serological findings confirmed the circulation of influenza virus H1N1 pdm in pigs and the presence of specific antibodies against H1N1 pdm in human serum. The results of this study seem to support a H1N1 pdm transmission from man to animals showing the importance of serological and virological investigation to control the pig farms and the importance of close cooperation between the different authorities like veterinarian and human public.

Influenza due to a Novel Influenza A (H1N1)/09 Virus.

The influenza A(H1N1) virus originating in Mexico has shaken the political, economical and health system of the whole world. It produces flu like symptoms in human body and is responsible for producing high morbidity than mortality.

Comparative study of pandemic (H1N1) 2009, swine H1N1, and avian H3N2 influenza viral infections in quails

Quail has been proposed to be an intermediate host of influenza A viruses. However, information on the susceptibility and pathogenicity of pandemic H1N1 2009 (pH1N1) and swine influenza viruses in quails is limited. In this study, the pathogenicity, virus shedding, and transmission characteristics of pH1N1, swine H1N1 (swH1N1), and avian H3N2 (dkH3N2) influenza viruses in quails was examined. Three groups of 15 quails were inoculated with each virus and evaluated for clinical signs, virus shedding and transmission, pathological changes, and serological responses. None of the 75 inoculated (n = 45), contact exposed (n = 15), or negative control (n = 15) quails developed any clinical signs. In contrast to the low virus shedding titers observed from the swH1N1-inoculated quails, birds inoculated with dkH3N2 and pH1N1 shed relatively high titers of virus predominantly from the respiratory tract until 5 and 7 DPI, respectively, that were rarely transmitted to the contact quails. Gross and histopathological lesions were observed in the respiratory and intestinal tracts of quail inoculated with either pH1N1 or dkH3N2, indicating that these viruses were more pathogenic than swH1N1. Sero-conversions were detected 7 DPI in two out of five pH1N1-inoculated quails, three out of five quails inoculated with swH1N1, and four out of five swH1N1-infected contact birds. Taken together, this study demonstrated that quails were more susceptible to infection with pH1N1 and dkH3N2 than swH1N1.