Admission levels of asymmetric and symmetric dimethylarginine predict long-term outcome in patients with community-acquired pneumonia

Vögeli, Alaadin; Ottiger, Manuel; Meier, Marc; Bernasconi, Luca; Kulkarni, Prasad S.; Huber, Andreas; Henzen, Christoph; Hoess, Claus; Thomann, Robert V.; Zimmerli, Werner; Müeller, Beat; Schuetz, Philipp

doi:10.1186/s12931-017-0502-4

Cited by 9 publications

(8 citation statements)

References 45 publications

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“…We detected increased acylcarnitines, glycerophospholipids and sphingolipids during VAP infection. Similar trends of plasma lipid metabolism have been reported in VAP patients (31).…”

Section: Resultssupporting

confidence: 87%

Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia

Pathak

McGilvrey

et al. 2020

Preprint

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Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is utilized in hospitals for VAP diagnosis and guiding treatment options. While BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their utility has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC-MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. Days prior to VAP diagnosis, detection of pathogen peptides with species level specificity in ETA may increase specificity over culture-based diagnosis. Our findings suggest that ETA may provide early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore facilitate its diagnosis and treatment.Graphical abstract

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“…We detected increased acylcarnitines, glycerophospholipids and sphingolipids during VAP infection. Similar trends of plasma lipid metabolism have been reported in VAP patients (31).…”

Section: Resultssupporting

confidence: 87%

Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia

Pathak

McGilvrey

et al. 2020

Preprint

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“…Elevated ADMA points towards ROS induced proteolysis of methylated proteins ( Figure 7C). Its inhibitory action on nitric oxide synthase (NOS) was measured as a decrease in the ratio of Nitro-Tyr (p = 0.371) to Tyr (p < 0.05), ( Figure 7C) also previously reported in community-acquired pneumonia (32). We detected significantly increased acylcarnitines, glycerophospholipids and sphingolipids during VAP infection.…”

Section: Vap Patients Harbor Metabolic Signatures Of Oxidative Stresssupporting

confidence: 80%

Molecular Profiling of Innate Immune Response Mechanisms in Ventilator-associated Pneumonia

Pathak

McGilvrey

et al. 2020

Molecular & Cellular Proteomics

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Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is utilized in hospitals for VAP diagnosis and guiding treatment options. While BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their utility has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC-MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients’ ETA which may have potential utility in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.

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“…They also showed an association with disease severity as assessed with the pneumonia severity index. 41 N. sativa has been reported to contain amino acids and vitamin supplements. 42 Raising arginine levels by supplementing this amino acid in critically ill patients showed controversial results.…”

Section: N Sat I Va P Ot E N T I a L T H E R A P E U T I C E F F Ec T Smentioning

confidence: 99%

Nigella Sativa Immunomodulatory Activity as a Potential Treatment of Novel Coronavirus (2019-nCoV) - A Review of Current Literature

2020

hbT

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had been reported worldwide. The disease is transmitted via inhalation or contact with infected droplets. The incubation period ranges from 2 to 14 days and can reach up to 21 days. Many people are asymptomatic. The estimated fatality rate ranges from 2−3%. Special molecular tests are being used to detect the virus in respiratory secretions. Elevated levels of C-reactive protein have been detected in the blood sample, while the white blood cell counts were considered normal. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Current treatment options are essentially supportive, as the role of antiviral agents is yet to be established. Preventative measures can be utilized to slow the spread of infection, such as isolation of suspected cases or those with mild symptoms and strict infection control measures at hospitals. Though the virus is far more infectious than its two ancestors, Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 2019-nCoV has a lower mortality rate. To date, the impact of this pandemic is uncertain, and the global research community is working diligently to find a satisfactory therapy. Several reports on Nigella sativa have been published, motivating us to review recent publications to summarize and investigate its possible therapeutic effect on the immune response and its potential to treat bacterial and viral infections, including COVID-19. For the advanced stage of the disease, we suggest using biological targeted magnetic hyperthermia. This can be used as adjuvant therapy, namely pseudo-adjuvant magnetic hyperthermia (PAMH).

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Admission levels of asymmetric and symmetric dimethylarginine predict long-term outcome in patients with community-acquired pneumonia

Cited by 9 publications

References 45 publications

Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia

Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia

Molecular Profiling of Innate Immune Response Mechanisms in Ventilator-associated Pneumonia

Nigella Sativa Immunomodulatory Activity as a Potential Treatment of Novel Coronavirus (2019-nCoV) - A Review of Current Literature

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