A5001656066- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Nitric Oxide and Endothelin Effects
- Neonatal Respiratory Health Research
- Eicosanoids and Hypertension Pharmacology
- Immune cells in cancer
- Infant Nutrition and Health
- Clinical Nutrition and Gastroenterology
- Respiratory Support and Mechanisms
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Asthma and respiratory diseases
- Trauma and Emergency Care Studies
- Heme Oxygenase-1 and Carbon Monoxide
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Traumatic Brain Injury and Neurovascular Disturbances
- Invertebrate Immune Response Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Advanced Glycation End Products research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience of respiration and sleep
- Cardiac Arrest and Resuscitation
- Intensive Care Unit Cognitive Disorders
- Diagnosis and Treatment of Venous Diseases
- Organ and Tissue Transplantation Research
University of Pittsburgh
2015-2024
McGowan Institute for Regenerative Medicine
2015-2024
Fundación A LA PAR
2024
Loro Parque Fundación
2024
University of Pittsburgh Medical Center
2018-2021
Indiana University – Purdue University Indianapolis
2020
University of Pennsylvania
2020
Methodist Hospital
2020
Orthopaedic Trauma Association
2020
University of Southern California
2020
Nitric oxide (NO) is a colorless gas at room temperature and one of the simplest molecules known, yet it has been implicated in wide variety regulatory mechanisms ranging from vasodilatation blood pressure control to neurotransmission. It also involved nonspecific immunity participates complex mechanism tissue injury as major mediator inflammatory processes apoptosis (1). This work focuses on role NO produced by inducible form nitric synthase (iNOS) autoimmune diseases. Although earliest...
Carbon monoxide (CO) has recently emerged as having potent cytoprotective properties; the mechanisms underlying these effects, however, are just beginning to be elucidated. In a rat model of lipopolysaccharide (LPS)-induced multiorgan failure, we demonstrate that exposure low concentration CO for only 1 h imparts defense against lethal endotoxemia and effectively abrogates inflammatory response. Exposure leads long-term survival >80% animals vs. 20% in controls. lung, suppressed LPS-induced...
We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions(21 °C) with hemoglobin-based oxygen carrier (HBOC) solution. MP (n=6) was compared to cold static (CSP; n=6) in porcine orthotopic liver transplants after 9 h of ischemia and 5-day follow-up. Recipients' peripheral blood, serial biopsies, solutions bile specimens were collected before, during preservation. Clinical laboratorial histological analyses performed addition mitochondrial...
Abstract The correlation between messenger RNA (mRNA) and protein abundances has long been debated. sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to changes. In this study, utilized set of 17 widely assessed immune wound healing mediators in the context canine volumetric muscle loss investigate mRNA abundances. Our data reveal an overall...
Background Complex biological processes such as acute inflammation induced by trauma/hemorrhagic shock/ (T/HS) are dynamic and multi-dimensional. We utilized multiplexing cytokine analysis coupled with data-driven modeling to gain a systems perspective into T/HS. Methodology/Principal Findings Mice were subjected surgical cannulation trauma (ST) ± hemorrhagic shock (HS; 25 mmHg), followed for 1, 2, 3, or 4 h in each case. Serum was assayed 20 cytokines NO2−/NO3−. These data analyzed using...
The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results hepatic hypoxia that drives inflammation. We hypothesize silico methods would help bridge hepatocyte data and T/HS, which the liver a primary site Primary mouse hepatocytes were cultured under (1% O2) or normoxia (21% for 1–72 h, both cell supernatants protein lysates assayed 18 inflammatory mediators by Luminex™ technology. Statistical analysis data-driven modeling employed...
A mathematical model of the human response to trauma replicates individual patient outcomes but predicts unexpected results in populations.
Blunt trauma patients may present with similar demographics and injury severity yet differ regard to survival. We hypothesized that this divergence was due different trajectories of systemic inflammation utilized computational analyses define these differences.Retrospective clinical study experimental in mice.Level 1 center laboratory.From a cohort 493 victims blunt trauma, we conducted pairwise, retrospective, case-control who survived over 24 hours but ultimately died (nonsurvivors; n =...
Shock states induce the expression of inducible nitric oxide synthase (iNOS) in both Kupffer cells and hepatocytes liver, but little is known about its subcellular localization these cells. Studies were undertaken to characterize location iNOS response sepsis. By immunofluorescence analysis, intraperitoneal challenge with bacterial lipopolysaccharide induced cytosolic punctate labeling hepatocytes. Cultured rat exposed interferon gamma, interleukin 1, tumor necrosis factor α showed protein...
The decomposition of benzenesulphohydroxamic acid (Piloty's acid; PA) and some its derivatives has been reported to yield nitroxyl ions (NO-), a species with potent vasodilator properties. In previous study we demonstrated that the oxidative breakdown PA results in formation nitric oxide (NO) suggested NO rather than NO- may account for vasorelaxant Using isolated aortic rings organ baths, now show high concentrations cysteine potentiate response PA, whereas responses Angeli's salt (AS),...
Abstract Necrotizing enterocolitis (NEC), a severe intestinal inflammation in neonates, occurs following bacterial colonization of the gut. LPS-induced production inflammatory factors immature enterocytes may be factor NEC. Previously, we described p38 MAPK-dependent expression cyclooxygenase-2 (COX-2) rat IEC-6 cells. In this study, examine COX-2 newborn epithelium and further characterize mechanisms regulation enterocytes. Induction NEC by formula feeding/hypoxia increased phospho-p38...
Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses drive the pathology various diseases including T/HS traumatic brain injury (TBI). is finely tuned, dynamic, highly-regulated process not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, regeneration. The driven by cytokines...
Objective: To gain insights into individual variations in acute inflammation and physiology. Design: Large-animal study combined with mathematical modeling. Setting: Academic large-animal computational laboratories. Subjects: Outbred juvenile swine. Interventions: Four swine were instrumented subjected to endotoxemia (100 µg/kg), followed by serial plasma sampling. Measurements Main Results: Swine exhibited various degrees of lung injury, including one death severe injury (PaO2/FIO2 ratio...
Clinical outcomes following trauma depend on the extent of injury and host's response to injury, along with medical care. We hypothesized that dynamic networks systemic inflammation manifest differently as a function severity in human blunt trauma.From cohort 472 survivors studied institutional review board approval, three Injury Severity Score (ISS) subcohorts were derived after matching for age sex: mild ISS (49 patients [33 males 16 females, aged 42 ± 1.9 years; 9.5 0.4]); moderate 1.9;...
To define the impact of prehospital hypotension on dynamic, systemic acute inflammatory response to blunt trauma.Retrospective study.Tertiary care institution.Twenty-two hypotensive trauma patients matched with 28 normotensive patients.None.From a cohort 472 survivors studied following institutional review board approval, two stringently subcohorts were derived. Twenty-two who sustained (15 males and 7 females; age, 45 ± 3.8; Injury Severity Score, 20.7 1.8) (20 8 46.1 2.5; 20.8 1.3). Serial...
Objective: Blunt trauma and traumatic spinal cord injury induce systemic inflammation that contributes to morbidity. Dysregulated neural control of postinjury is likely exaggerated in patients with injury. We used silico methods discern dynamic inflammatory networks could distinguish from blunt trauma. Design: Retrospective study. Settings: Tertiary care institution. Patients: Twenty-one severely injured thoracocervical matched 21 without Intervention: None. Measurements Main Results: Serial...
Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which driven in part by monocytes/macrophages stimulated injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 an endogenous DAMP involved various inflammatory diseases, though its mechanism action unclear. Circulating levels human blunt trauma nonsurvivors were significantly lower than those survivors (P < 0.001). Human monocytic THP-1 cells expressed...