scholarly journals Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1540
Author(s):  
Beatriz Sierra ◽  
Ana Cristina Magalhães ◽  
Daniel Soares ◽  
Bruno Cavadas ◽  
Ana B. Perez ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dengue Fever ◽  
In Silico ◽  
Serotonin Receptor ◽  
Neglected Tropical Diseases ◽  
Dengue Infection ◽  
Severe Dengue ◽  
Functional Evaluation ◽  
Atpase Inhibitor ◽  
Serotonin Receptor Antagonist

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

SEROTONIN RECEPTOR ANTAGONIST INDUCES INDEFINITE SURVIVAL OF FULLY-ALLOGENEIC CARDIAC GRAFTS.

2004 ◽  
Vol 78 ◽  
pp. 599-600
Author(s):  
T Akiyoshi ◽  
Q Zhang ◽  
F Inoue ◽  
K Tanaka ◽  
O Aramaki ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
Serotonin Receptor Antagonist

scholarly journals Clinical profile of dengue fever in children: analysis of 2017 outbreak from Central Kerala, India

2018 ◽  
Vol 5 (6) ◽  
pp. 2265 ◽  
Author(s):  
Senthil Kumar K. ◽  
Rajendran N. K. ◽  
Ajith Brabhukumar C.
Keyword(s):  
Dengue Fever ◽  
Dengue Infection ◽  
Tertiary Care ◽  
Hemorrhagic Fever ◽  
Warning Signs ◽  
Clinical Profile ◽  
Severe Dengue ◽  
High Morbidity ◽  
Care Hospital ◽  
High Grade Fever

Background: In India, dengue epidemics are becoming more frequent (WHO, 2008). The majority of dengue viral infections are self-limiting, but complications may cause high morbidity and mortality. The objective of this study is to assess the clinical profile of the dengue infection in children less than 15 years of age and to evaluate the outcomes of dengue fever from March 2017 to July 2017 at the Pediatric Department of Karuna Medical College, the tertiary care hospital in Palakkad.Methods: In this retrospective study, medical records were reviewed and analyzed. Patients with suspected dengue infection were classified further into 2 groups, Dengue fever (probable dengue, dengue with warning signs) and ‘Severe Dengue’ (dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS) according to WHO.Results: A total of 77 cases were classified into 67 (87%) non-severe and 10 (13%) severe dengue cases. The most common age of presentation was above 10 yrs. The mean age of admission was 8.9 yrs. The most common presenting symptom was fever seen in 93% followed by vomiting in 68%. Elevation in Aspartate transaminase (SGOT) and thrombocytopenia were found in 32.4 %.Conclusions: High grade fever, vomiting, abdominal pain and skin rash with normal or low platelet count were the presenting features. Early diagnosis, monitoring and prompt supportive management can reduce mortality.

scholarly journals Epidemiological and Clinical Features of Dengue Infection in Adults in the 2017 Outbreak in Vietnam

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Bui Vu Huy ◽  
Le Nguyen Minh Hoa ◽  
Dang Thi Thuy ◽  
Nguyen Van Kinh ◽  
Ta Thi Dieu Ngan ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Dengue Fever ◽  
Clinical Features ◽  
Dengue Infection ◽  
Clinical Manifestations ◽  
Warning Signs ◽  
Severe Dengue ◽  
Severe Bleeding ◽  
Cross Sectional ◽  
Number Of Patients

Purpose. The clinical features and laboratory results of dengue-infected adult patients admitted to the hospital during the 2017 outbreak were analyzed in this study. Method. This is a cross-sectional study. 2922 patients aged 18 years or more with dengue fever in National Hospital for Tropical Diseases (NHTD) in the North and Hospital for Tropical Disease (HTD) in the South of Vietnam were recruited in this study. Result. Patients were admitted in the hospital around the year and concentrated from August to December, in 53/63 (84.0%) provinces in Vietnam, and patients in all ages were affected. The number of patients with dengue fever was 1675 (57.3%), dengue with warning signs 914 (31.3%), and severe dengue 333 (11.4%), respectively. Among patients with severe dengue, severe plasma leakage and dengue shock account for 238 (8.1%), severe organ impairment 73 (2.5%), and severe bleeding 22 (0.75%). The rate of mortality was 0.8%, and the outcome of dengue patients is worse in the elderly and people with underlying diseases. Conclusion. The 2017 dengue outbreak occurred in a larger scale than in the previous years in terms of time, location, and number of patients. More elderly patients were infected by dengue in this outbreak, and this may contribute to the mortality rate. Clinical manifestations of dengue patients in Southern Vietnam are more typical than the northern, but the rate of severe dengue is not different. The mortality risk and underlying conditions associated with dengue-infected elderly patients are worthy of further investigations in the future.

Effectiveness of Serotonin-Receptor Antagonist Antiemetic Therapy over Successive Courses of Carboplatin-Based Chemotherapy

2002 ◽  
Vol 85 (3) ◽  
pp. 435-437 ◽  
Author(s):  
Margaret R. Markman ◽  
Gertrude Peterson ◽  
Barbara Kulp ◽  
Maurie Markman
Keyword(s):  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
Antiemetic Therapy ◽  
Serotonin Receptor Antagonist

scholarly journals 2565. A Novel Prognostic Gene Set for the Prediction of Severe Dengue

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S72-S72
Author(s):  
Makeda L Robinson ◽  
Timothy E Sweeney ◽  
Rina Barouch-Bentov ◽  
Malaya K Sahoo ◽  
Ana Maria Sanz ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Silico ◽  
Dengue Infection ◽  
Differentially Expressed Gene ◽  
Warning Signs ◽  
Severe Dengue ◽  
Blood Samples ◽  
Gene Set ◽  
Severity Scores ◽  
Pcr Assays

Abstract Background There is an urgent need for the identification of biomarkers predictive of severe dengue. Single cohort transcriptomic studies have not yielded a parsimonious gene set predictive of severe dengue. We hypothesized that integration of gene expression data from heterogeneous patient populations with dengue infection would yield a set of conserved genes that is predictive of severe dengue and generalizable across cohorts. Methods Ten dengue gene expression datasets were identified in publicly available microarray repositories. A novel integrated multicohort platform was used to detect differentially expressed gene transcripts between uncomplicated and severe dengue patients and validate the identified putative signature in silico and prospectively in a new cohort of 34 dengue patients in Colombia. Dengue diagnosis was made by NS1 antigen and anti-DENV IgM antibody and confirmed by RT-PCR assays, ELISA, and IgG avidity measurements. The expression level of the signature genes was measured via microfluidic qRT-PCR assays in blood samples collected longitudinally during the course of illness. Results Using the multicohort analysis to analyze 446 peripheral blood samples of patients with dengue infection from 7 publicly available gene expression datasets, we identified a 20 gene set that predicts the development of severe dengue. We in silico validated the diagnostic power of this gene set to separate severe dengue from dengue with or without warning signs in 3 independent datasets composed of 84 samples with a global area under the ROC curve (AUC) of 0.80 [95% CI 0.68–0.88]. We prospectively validated the gene set in a new cohort composed of 34 dengue patients from Colombia with an AUC of 0.89 [95% CI 0.81–0.97]. The severity scores measured in patients with severe dengue progressively declined in longitudinal samples. Conclusion Our data indicate that the identified 20 gene signature predicts the development of severe dengue in patients prior to its onset and suggest that dengue infection itself triggers this host response. These findings may provide new insight into the pathogenesis of severe dengue and have implications for the development of a prognostic molecular assay to identify patients at risk to develop severe dengue. Disclosures T. E. Sweeney, Inflammatix, Inc.: Employee and Shareholder, Salary. P. Khatri, Inflammatix, Inc: Scientific Advisor and Shareholder, Licensing agreement or royalty.

American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006

2006 ◽  
Vol 24 (18) ◽  
pp. 2932-2947 ◽  
Author(s):  
Mark G. Kris ◽  
Paul J. Hesketh ◽  
Mark R. Somerfield ◽  
Petra Feyer ◽  
Rebecca Clark-Snow ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Receptor Antagonist ◽  
Drug Combination ◽  
Serotonin Receptor ◽  
Controlled Trials ◽  
Delayed Emesis ◽  
Serotonin Antagonist ◽  
Randomized Controlled ◽  
American Society ◽  
Serotonin Receptor Antagonist

Purpose To update the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology. Update Methodology The Update Committee completed a review and analysis of data published from 1998 thru February 2006. The literature review focused on published randomized controlled trials, and systematic reviews and meta-analyses of published phase II and phase III randomized controlled trials. Recommendations The three-drug combination of a 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy of high emetic risk. For persons receiving chemotherapy of high emetic risk, there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics. These agents should be reserved for patients intolerant of or refractory to 5-HT3 serotonin receptor antagonists, neurokinin-1 receptor antagonists, and dexamethasone. The three-drug combination of a 5-HT3 receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide. For patients receiving other chemotherapy of moderate emetic risk, the Update Committee continues to recommend the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis. The Update Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk. Conclusion The Update Committee recommends that clinicians administer antiemetics while considering patients' emetic risk categories and other characteristics.

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