Expression of Nitric Oxide Synthase and Nitric Oxide Levels in Peripheral Blood Cells and Oxidized Low-Density Lipoprotein Levels in Saliva as Early Markers of Severe Dengue (original) (raw)

Expression of inducible nitric oxide synthase, nitric oxide and salivary oxidized LDL as early markers of severe dengue

2019

Objectives: To identify suitable biomarkers during early stages of dengue to predict which patients would develop severe forms of dengue before the warning signs appear. Methods: Expression of inducible nitric oxide synthase (iNOS) and resultant changes in nitric oxide (NO) and oxidized low density lipoprotein (oxLDL) levels in plasma and saliva were analyzed. Results: Expression of iNOS in patients who later developed dengue hoemorrhagic fever (DHF) showed significant (P<0.05) down regulation compared to dengue fever (DF) patients while those who later developed DHF showed a corresponding significant (P<0.05) decrease of plasma NO levels (18.1±3.1 µM) compared to DF patients (23.6±4.4 µM) within 4 days from fever onset. OxLDL levels in plasma showed a decrease in patients who later developed DHF compared to DF patients although this value was significantly different only within 3 days from fever onset. The salivary NO levels did not show a significant difference. However, salivary oxLDL levels were significantly (P<0.05) low in patients who later developed DHF (0.6±0.2 ng/mL) compared to DF patients (1±0.4 ng/mL) collected within 4 days from fever onset. Conclusions: The expression level of iNOS, plasma NO and salivary oxLDL levels may serve as early markers of severity of dengue infection.

SHORT REPORT: INCREASED LEVEL OF SERUM NITRIC OXIDE IN PATIENTS WITH DENGUE

2002

Nitric oxide (NO) has been involved in several infectious diseases. Virus dengue is capable of inducing increased levels of NO when cocultured with human Kupffer and spleen cells. However, no reports describe the levels of NO in patients with dengue infection. Increased levels of NO were found in patients with the classic form of the disease; however, in the hemorrhagic form of the disease, similar levels to those of healthy controls were found. In vitro studies showed no increased levels of NO when human platelets were incubated with the virus. Increased NO in classical dengue could be important in the evolution from the nonhemorrhagic to the hemorrhagic forms of dengue.

Oxidative Stress Biomarkers as Prognostic Indicators of Severity in Patients With Dengue

Global Journal of Health Science

There is evidence for the role of oxidative stress in severe dengue pathogenesis. However, previous observational studies presents certain methodological limitations, which may affect its internal and external validity. This study was a case-control analysis of patients with severe dengue and dengue with warning signs, to evaluate the serum protein carbonyls-PCOs and lipid hydroperoxides-LOOHs levels and activities of superoxide dismutases-SODs (MnSOD, Cu/ZnSOD and total SOD), as potential prognosis indicators of severity in dengue patients, using binary logistic regression analysis and strategy of double cross-validation. Therefore, the study population was subdivided into a derivation group (pediatric patients, Barranquilla-Colombia) and an external validation group (children and adults patients, National Institute of Health of Peru). PCOs was the only oxidative stress markers that showed a strongest association with the severity of dengue, both in children and adults. In the deri...

Serum nitric oxide in children with dengue infection

Asian Pacific journal of allergy and immunology, 2005

One hundred and ten patients (M/F = 67/43) from King Chulalongkorn Memorial Hospital and the provincial hospitals of Uttaradit, Ayudhaya, and Sakonnakorn, who were clinically diagnosed with dengue infection and serologically confirmed by ELISA anti-Dengue IgM and IgG were recruited. Their serum NO level was measured using commercially available assay kits to investigate its correlation with the severity of the dengue infection: dengue fever (DF), DHF I/II, and DHF III/IV or dengue shock syndrome (DSS). Serum NO levels were also measured in 38 healthy controls (M/F = 19/19). Serum NO levels in dengue patients were lower than those of the controls (control = 168.18 +/- 24.10 micromol/l, DF = 124.94 +/- 36.79 micromol/l, DHF I/II = 99.69 +/- 33.42 micromol/l, and DHF III/IV = 120.63 +/- 46.26 micromol/l; p < 0.05). Serum NO levels in patients with DHF I/II were significantly lower than in those with DHF III/IV. These preliminary data revealed that levels of serum NO in dengue patien...

Oxidative-nitrosative stress and dengue disease: a systematic review of in vivo/in vitro studies

Revista Cubana de Medicina Tropical, 2015

Objective : In this systematic review the aim was to summarise the in vivo / in vitro evidence on the role of oxidative-nitrosative stress in pathogenesis of dengue. Methods : We searched electronic databases (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) using the term: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide, and nitric oxide synthase. Articles were selected for review by title and abstract excluding letter, review, epidemiological studies, and duplicates studies. Selected articles were reviewed for used animal model or cell cultures, original purposes, strain of virus or type of antibody, main outcomes, methods, and oxidative-nitrosative stress markers values. Results: In total, 4330 non-duplicates articles were identified from computerized searches of reference databases, of whic...

Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults

Journal of Infectious Diseases, 2015

In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF.

Oxidative stress induced changes in plasma protein can be a predictor of imminent severe dengue infection

Acta Tropica, 2008

Objectives: Oxidative stress in dengue viral infection has been suggested and severity of it was found to be associated with progress of illness. Hence assessing oxidative stress mediated changes in plasma proteins can be an early biomarker for prediction of severe dengue infection. Design and methods: Thirty two dengue hemorrhagic fever (DHF), 21 dengue shock syndrome (DSS), 27 dengue fever (DF) and 63 age and sex matched controls, were included in this study. Blood samples were collected on the 3rd day of fever. Protein carbonylation (PCOs) and protein-bound sulphydryl (PBSH) group levels were determined by spectrophotometric method and analyzed as predictor of dengue hemorrhagic fever and dengue shock syndrome. Results: About 80-84% of cases presented with no signs of DHF/DSS at the time of sampling. Dengue infected individuals had significantly elevated PCOs and low PBSH group levels than the controls. Using one-way ANOVA we found a significant difference with high PCOs and low PBSH group levels between DHF and DSS when compared with DF (P < 0.001). However, no difference was observed in PBSH group levels between DHF and DSS. A significant difference in PCOs to PBSH ratio was observed among DF, DHF and DSS (P < 0.001). Linear regression analysis revealed that duration of hospitalization is dependent on PCOs and PBSH group levels. Receiver operator curve (ROC) analysis indicated that 5.22 nmol/mg protein PCOs; 1.08 PCOs to PBSH group levels ratio were optimal cutoff value for predicting DHF with sensitivity and specificity of 87.5% and 74.1%; 96.9% and 81.5%, respectively. For DSS prediction, 6.13 nmol/mg protein PCOs; 1.16 PCOs to PBSH group levels ratio were found as effective cutoff with sensitivity and specificity of 81% and 71.9%; 95.2% and 56.2%, respectively. Conclusion: Oxidative stress has been observed to develop since early days of onset of dengue infection. Plasma PCOs, PCOs to PBSH group ratio were found to very well predict DHF/DSS.

‘Nitric Oxide’ A Dual Performer in Dengue Virus Infection

Iranian Journal of Medical Microbiology

Background and Aim: The study was conducted to assess the role of Nitric Oxide (NO) in the pathogenesis of Dengue fever (DF). Materials and Methods: A total of 150 patients with positive Dengue serology and 50 candidates as controls in the age group of 15-65 years were included in the study. NO levels were measured by Griess Nitrate Method (Cadmium granules modified). Results: The rise in NO was observed in 24 (20.86%) patients out of 115 DF patients, while it was raised in only 01 (2.8%) case out of 35 patients of DHF and the difference was observed to be statistically significant. NO level was within normal limits (Normal Range-24.8-77.6µmol/L) in 92% (n=50) healthy controls and was raised in (NO value>77.66µmol/L) 4% healthy controls. A positive correlation was observed in the serum NO levels with platelet count. The majority of the patients in the study (41.33%) were in the age group of 21-30 years of age, followed by were < 20 yrs (30%) and 31-40 yrs (12.67%). Male:female ratio observed was 1.78:1. DF was diagnosed in 115 (76.67%) patients, while DHF was diagnosed in 35 (23.33%) patients, while no case of DSS was diagnosed. Conclusion: NO plays a protective role in DF, while in DHF patients, the absence of rising NO levels may be one of the contributory factors leading to the progression of the disease and increased morbidity. NO levels can guide the physician about the evolution of a case of Dengue.

Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017

Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however the association of endothelial nitric oxide pathways with disease severity is unknown. We performed a prospective observational study in two Vietnamese hospitals, assessing patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperaemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability was evaluated using peripheral artery tonometry (EndoPAT) and plasma levels of L-arginine, Arginase-1 and ADMA were measured at serial time-points. The main outcome of interest was plasma leakage severity. 314 patients were enrolled, median age of the participants was 21 (IQR 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness (OFI). Considering dengue patien...