Molecular Mechanism of Jinchan Oral Liquid in the Treatment of Children with Respiratory Syncytial Virus Pneumonia Based on Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: Exploration of the underlying molecular mechanism of Jinchan Oral Liquid (JOL) in treating children with the respiratory syncytial virus (RSV) pneumonia to provide new evidence for the clinical application. METHODS: The active components and target genes of JOL were screened by the TCMSP database. The targets of RSV pneumonia were obtained from the GeneCards, OMIM, DrugBank, and PharmGKB database. Then, we constructed the active component-target network and screened the core genes. The overlaps were screened for PPI network analysis, GO analysis, and KEGG analysis. Finally, result validation was performed by molecular docking. RESULTS: According to the screening criteria of the ADME, 74 active compounds of JOL were obtained; after removing redundant targets, we selected 180 potential targets. By screening the online database, 893 RSV pneumonia-related targets were obtained. A total of 82 overlapping genes were chosen by looking for the intersection. The STRING online database was used to acquire PPI relationships, and 16 core genes were obtained. GO and KEGG analyses showed that the main pathways of JOL in treating RSV pneumonia include TNF signaling pathway and IL17 signaling pathway. The molecular docking results showed that the active compounds of JOL had a good affinity with the core genes. CONCLUSION: In this study, we preliminarily discussed the main active ingredients, related targets, and pathways of JOL and predicted the pharmacodynamic basis and the potential therapeutic mechanisms of RSV pneumonia. In summary, the network pharmacology strategy may be helpful for the discovery of multitarget drugs against complex diseases.

Modeling of fusion inhibitor treatment of RSV in African green monkeys.

Respiratory syncytial virus (RSV) is a respiratory infection that can cause serious illness, particularly in infants. In this study, we test four different model implementations for the effect of a fusion inhibitor, including one model that combines different drug effects, by fitting the models to data from a study of TMC353121 in African green monkeys. We use mathematical modeling to estimate the drug efficacy parameters, εmax, the maximum efficacy of the drug, and EC50, the drug concentration needed to achieve half the maximum effect. We find that if TMC353121 is having multiple effects on viral kinetics, more detailed data, using different treatment delays, is needed to detect this effect.

Efficacy and safety of Laggera pterodonta in children 3-24 months with acute bronchiolitis: a randomized controlled trial.

INTRODUCTION: Laggera pterodonta, a traditional Chinese medicine, has been commonly used in respiratory tract infections for more than hundreds of years without any randomized controlled trials to evaluate its efficacy and safety. OBJECTIVES: To evaluate the efficacy and safety of Laggera pterodonta in hospitalized children aged 3-24 months with acute bronchiolitis. METHODS: A double-blind, randomized-controlled trial was conducted in three tertiary hospitals of Kunming, China. A total of 133 acute bronchiolitis children with an initial episode of wheezing were randomly assigned to a control mixture or Laggera pterodonta mixture. All recruited patients were given three doses of the mixture every 24 h for 5 days. Clinical symptoms and responses including adverse events in both groups were assessed and laboratory tests were done at enrolment and then after 120 h. Analysis was performed based on an intention-to-treat principle. RESULTS: Significantly more hospitalized children fulfilled the discharge criteria at 96 h and 120 h in the Laggera pterodonta mixture group compared to the control group (97% vs 75.8% P < 0.001 and 98.5% vs 89.4% P = 0.03), respectively. Better responses on clinical severity score, respiratory rate, oxygen saturation, wheezing and heart rate were also detected in the Laggera pterodonta mixture group along with lower white blood cell count, platelet count and aspartate aminotransferase. Vomiting and diarrhea were more common in the control group. CONCLUSION: Laggera pterodonta mixture is effective and safe to be prescribed in hospitalized children with acute bronchiolitis.

Assessment of different functionalization methods for grafting a protein to an alumina-covered biosensor.

The specificity of biosensors is typically obtained by surface biofunctionalization, which enables the selective binding of biomolecules. This critical step is sensitive to the nature of materials and to the overall experimental conditions. Here, we provide a comprehensive study of several biofunctionalization methods, including the layer-by-layer technique and both the gas-phase and liquid-phase silanizations, and we propose a new maleimide-based protocol for grafting a protein to a sensor covered by alumina. This method was then validated by making a respiratory syncitial virus-specific biosensor.

Seasonal invasive pneumococcal disease in children: role of preceding respiratory viral infection.

OBJECTIVE: Our objective was to demonstrate correlations between invasive pneumococcal disease in children and circulating respiratory viruses. METHODS: This retrospective study included 6 winter respiratory viral seasons (2001-2007) in Intermountain Healthcare, an integrated health system in the Intermountain West, including Primary Children's Medical Center in Salt Lake City, Utah. Children <18 years of age who were hospitalized with either invasive pneumococcal disease in any Intermountain Healthcare facility or culture-confirmed invasive pneumococcal disease at Primary Children's Medical Center were included. We analyzed the correlation between invasive pneumococcal disease and circulating respiratory viruses. RESULTS: A total of 435 children with invasive pneumococcal disease and 203 with culture-confirmed invasive pneumococcal disease were hospitalized in an Intermountain Healthcare facility or Primary Children's Medical Center during the study period. During the same period, 6963 children with respiratory syncytial virus, 1860 with influenza virus, 1459 with parainfluenza virus, and 818 with adenoviruses were evaluated at Primary Children's Medical Center. A total of 253 children with human metapneumovirus were identified during the last 5 months of the study. There were correlations between invasive pneumococcal disease and seasonal respiratory syncytial virus, influenza virus, and human metapneumovirus activity. The correlation with invasive pneumococcal disease was strong up to 4 weeks after respiratory syncytial virus activity. For influenza virus and human metapneumovirus, the correlations were strong at 2 weeks after activity of these viruses. Pneumonia was the most common clinical disease associated with culture-confirmed invasive pneumococcal disease, mostly attributable to serotypes 1, 19A, 3, and 7F. CONCLUSIONS: In the post-pneumococcal conjugate vaccine era, seasonal increases in respiratory syncytial virus, influenza virus, and human metapneumovirus infections in children were associated with increased pediatric admissions with invasive pneumococcal disease, especially pneumonia caused by nonvaccine serotypes.

Etiología viral en la infección respiratoria aguda baja en recién nacidos / Viral etiology of lower respiratory tract infection in newborns

Con el objetivo de determinar la etiología de la infección respiratoria aguda baja en los recién nacidos hospitalizados en la Unidad de Neonatología y conocer algunas características epidemiológicas clínicas, de tratamiento y evolución, se estudiaron prospectivamente 260 recién nacidos hospitalizados por infección respiratoria aguda baja entre agosto de 1995 y septiembre de 1998. En 150 de ellos (57,7 por ciento) se aisló virus respiratorio sincicial mediante inmunofluorescencia y en dos de ellos se encontró asociación con virus parainfluenza. No se aisló adenovirus ni virus influenza A y B. El 80,5 por ciento correspondió a RN de término, sin predominio por sexo. El promedio de edad al ingreso fue de 19,3 días, siendo los síntomas más frecuentes tos (84,6 por ciento), dificultad respiratoria (66,7 por ciento), coriza (64,0 por ciento) y rechazo alimentario (58,8 por ciento). El manejo fue básicamente kinésico y con broncodilatadores. Menos de la mitad de los casos requirió oxigenoterapia y sólo el 7,3 por ciento necesitó ventilación mecánica. en el 55,4 por ciento de los RN se indicó antibióticos, suspendiéndose en el 66,7 por ciento de ellos al conocerse la etiología viral. La evolución clínica fue benigna con un promedio de estadía hospitalaria de 10,8 días y una letalidad de 0,67 por ciento. Se concluye que en los recién nacidos hospitalizados por infección respiratoria aguda baja predominó la etiología viral, aislándose virus respiratorio sincicial en todos los casos en que el examen de inmunofluorescencia fue positiva. La evolución fue sastisfactoria sin requerir el uso de antibióticos. Se observó además una muy baja tasa de infección intrahospitalaria con las estrictas medidas de aislamiento implementadas y reforzadas especialmente durante los meses de invierno y primavera

Características del uso intrahospitalario de antibióticos en las infecciones respiratorias agudas bajas: campaña de invierno 1996 / Characteristics of the intrahospitalary use of antibiotics in acute lower respiratory infections: winter campaign, 1996

La mayoría de las infecciones respiratorias agudas bajas de los niños son de naturaleza viral y se deben mayoritariamente al virus respiratorio sincicial. Pueden, sin embargo, complicarse con infecciones bacterianas lo que implica el empleo de antibióticos. Esto encarece el tratamiento y complica el manejo de los pacientes. El trabajo se basa en la revisión de un material de 133 niños con infecciones respiratorias agudas bajas que recibieron antibióticos. Se describen las características clínicas de los pacientes, sus factores de gravedad y los resultados de algunos exámenes realizados (hemograma, sedimentación, proteína C reactiva, inmunofluorescencia indirecta), Se analizan las razones que justifican la administración de antibióticos, destacando que en 8,4 por ciento de los enfermos no parece haber existido una causa clara que lo explique. La penicilina y la quemicetina fueron los principales antibióticos utilizados

Infección respiratoria aguda baja e infección viral en lactantes: evolución clínica intrahospitalaria / Acute lower respiratory infection and viral infection in infants: intrahospitalary clinical evolution

Se hizo una vigilancia de virus respiratorios en 1593 niños menores de dos años ingresados por infección respiratoria aguda baja (IRAB) al Hospital Roberto del Río, entre mayo 1988 y diciembre 1992, tomando muestras de aspirado nasofaríngeo para aislamiento viral e inmunofluorescencia indirecta. Se detectó VRS en 457 (28,7 por ciento), adenovirus en 310 (19,5 por ciento), influenza en 30 (1,8 por ciento) y para influenza en 22 (1,4 por ciento). El VRS se detectó preferentemente en los meses fríos y los adenovirus (ADV) durante todo el año. Se estudió la evolución intrahospitalaria de 213 lactantes, con detección de VRS y/o adenovirus al ingreso, considerando la duración de la hospitalización y uso de oxígeno, corticoides y broncodilatadores. Sólo fue significativa la mayor estadía hospitalaria de los casos ADV positivos (promedio 10,5 ds) en relación a los con VRS (promedio 7,0 ds) o sin virus detectado (x 6,5 ds)

[Ezhu intravenous injection in treating infantile respiratory syncytial virus pneumonia and its therapeutical mechanism].

Ezhu Intravenous Injection (EII) in treating respiratory syncytial virus (RSV) pneumonia was studied. 45 patients in therapeutic group were treated with 0.04% EII in dose of 20 ml/kg/day for 7-14 days. 20 patients in the control group were treated with Huayu decoction, its efficacy on RSV pneumonia has been confirmed. The results showed that all the patients of both groups were cured and there were no statistic differences in the average days of clearing up the temperature, dyspnea and wheezing (P > 0.05). Experimental studies showed that the isolation rate of RSV on the 5th and 8th day in the therapeutic group were lower than that of infected and glucose control groups. The difference was significant (P < 0.001 and P < 0.0001). Pathological examination showed that on 5th day in infected and control group there were epithelial damages and bronchial lumen obstruction, peri-bronchial and periseptal edema, eosinophilic leucocytes and inflammatory infiltrations. The endothelial cells of alveolar capillaries swelled, platelet aggregations and thrombi occurred in its lumens. On 8th day the platelet aggregations diminished, but cellular infiltrations and damages of bronchial epithelium still existed. In therapeutic group on 5th day most of the alveolar capillary endothelial cells were normal with mild edema only. The platelet aggregation were much less than the infected and control groups. No peribronchial and peri-septal edema was observed. The results of both clinical and experimental studies showed that EII had good therapeutic effect on RSV pneumonia with no adverse reaction.

Priming for local and systemic antibody memory responses to bovine respiratory syncytial virus: effect of amount of virus, virus replication, route of administration and maternal antibodies.

We studied the conditions under which calves can be primed for mucosal and serum antibody memory responses against bovine respiratory syncytial virus (BRSV), and the relationship between such responses and protection against the virus. Calves were primed via the respiratory tract with a low or high amount of live virus, with killed virus, or intramuscularly with live virus. Calves were challenged via the respiratory tract. Priming with live virus via the respiratory tract induced primary antibody responses in serum and on the mucosae, which were identical after the low and the high amount of virus. These responses were suppressed by maternal antibodies. Intramuscular priming of seronegative calves induced serum IgG1 and sometimes serum IgM and IgG2 responses, but no responses were detected on the mucosae. Sera of calves primed by the intramuscular or the respiratory route recognized the same viral proteins. No responses were observed after priming with killed virus, or after intramuscular priming of calves with maternal antibodies. After challenge, mucosal and serum antibody memory responses developed in calves that had been primed via the respiratory tract with live virus, whether they had maternal antibodies or not. One colostrum-fed calf showed a mucosal memory response, although serum responses were still suppressed by maternal antibodies. None of the calves thus primed shed virus after challenge. Intramuscular priming also primed for mucosal and serum memory responses after challenge, which however started perhaps slightly later and were not associated with protection against virus shedding. Priming with killed virus, or with live virus intramuscularly in the presence of maternal antibodies proved least effective in inducing memory and protection against virus shedding. Thus, protection against virus shedding was afforded by priming with live virus via the respiratory tract, both in calves with an without maternal antibodies. Protection was associated with a strong and rapid mucosal antibody memory response, but the reverse was not necessarily true. Protection against virus excretion had no relationship to titers of serum neutralizing or serum IgG1 or nasal IgA antibodies at the time of challenge.

Evaluation of ethylenediaminetetraacetic acid, tetrasodium salt dihydrate (EDTA)-Tween 20 treatment versus protease digestion of formalin-fixed tissue sections for detection of bovine respiratory syncytial virus antigen in infected ovine lung.

The efficacy of protease and ethylenediaminetetraacetic acid, tetrasodium salt dihydrate (EDTA)-Tween 20 in unmasking bovine respiratory syncytial virus (BRSV) antigens in formalin-fixed lung tissue was compared using avidin-biotin immunoperoxidase procedure. Tissues were taken from experimentally infected lambs. BRSV antigen stained in both techniques. Treatment with EDTA-Tween 20 resulted in more intense staining of BRSV infected cells, more uniform cytoplasmic staining, less non-specific background, and superior cellular detail in comparison to protease digestion.

Experimental infection of calves with respiratory syncytial virus.

Three bovine isolates and one human isolate of RS virus were given intranasally to gnotobiotic, colostrum-deprived and conventional calves. All isolates produced a biphasic pyrexia associated with a serous nasal discharge. Virus was recovered from nasal secretions 4-10 days after inoculation from nasal, tracheal and bronchial mucosae and lung of animals killed 7-13 days after inoculation. Infection did not produce any macroscopic lesions, but histologically there was a focal degenerative rhinitis and a catarrhal bronchiolitis with the occasional formation of syncytia in bronchioles and alveoli.

Immunity to infections of the respiratory system in man and animals.

Itis probable that RS virus is an important etiological agent in the bovine respiratory disease syndrome. This is the conclusion of groups of workers in Europe and Japan. In this country, significant levels of neutralizing antibody have been detected in 81 percent of cattle tested, while paired sera groups showed seroconversions of between 17 and 29 percent. RS virus has also been isolated from diseased calves and such isolates produce pyrexia and rhinitis in experimentally infected calves. The virus is localised in the respiratory tract. Serum antibody responses have not been consistent but it is likely that moderate serum antibody levels indicate that the animal is protected. These antibody levels can be achieved by injection of a formalin inactivated antigen. Calves vaccinated in this way showed no definite evidence of exacerbation of disease when challenged with infectious virus.