RLS-0071 Moderated Elevated Myeloperoxidase Level and Activity in an Asymptomatic Subject in Clinical Trial RLS-0071-101.

BACKGROUND RLS-0071 is a dual-targeting peptide developed for the regulation of humoral and cellular inflammation via inhibition of neutrophil effectors, including myeloperoxidase and neutrophil extracellular trap formation (NETosis). The safety, pharmacokinetics, and pharmacodynamics of single and multiple doses of RLS-0071 were evaluated in a first-in-human clinical trial in healthy volunteers. Myeloperoxidase is the major peroxidase enzyme present in neutrophilic granules and contributes to cellular inflammation.

Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.

Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and other modifiable mechanisms of injury in HIE, we tested the dual-targeting anti-inflammatory peptide, RLS-0071 in an animal model of HIE.

Peptide inhibition of neutrophil-mediated injury after in vivo challenge with supernatant of Pseudomonas aeruginosa and immune-complexes.

Neutrophils are recognized for their role in host defense against pathogens as well as inflammatory conditions mediated through many mechanisms including neutrophil extracellular trap (NET) formation and generation of reactive oxygen species (ROS). NETs are increasingly appreciated as a major contributor in autoimmune and inflammatory diseases such as cystic fibrosis. Myeloperoxidase (MPO), a key neutrophil granule enzyme mediates generation of hypochlorous acid which, when extracellular, can cause host tissue damage.

Pediatric Tetanus in Central Pennsylvania.

Approximately 20% of the nationally reported tetanus infections in children aged 0 to 14 years that occurred in the United States between 2005 and 2015 were treated at Penn State Children's Hospital. With an electronic medical record search, we identified 5 cases of pediatric tetanus; 100% of these cases occurred in unimmunized children. Their median length of stay was 10 days, and the costs were significant.

Vaccine-Preventable Diseases Requiring Hospitalization.

Background: Plain children often have lower immunization rates than non-Plain children. Penn State Health Children's Hospital is a tertiary medical center with large nearby Plain (Amish and Mennonite) communities. We sought to describe the characteristics of children hospitalized with vaccine-preventable diseases (VPDs).

Therapeutic hypothermia modulates complement factor C3a and C5a levels in a rat model of hypoxic ischemic encephalopathy.

Background: Therapeutic hypothermia (HT) is the only intervention that improves outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). However, the multifactorial mechanisms by which HT impacts HIE are incompletely understood. The complement system plays a major role in the pathogenesis of ischemia-reperfusion injuries such as HIE.

Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats.

Background: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model.

Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus.

Background: Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations.

Peptide Inhibitor of Complement C1 (PIC1) Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1).

Complement inhibition significantly decreases red blood cell lysis in a rat model of acute intravascular hemolysis.

Background: Prevention of acute hemolytic transfusion reactions is a worldwide concern. The objective of this study was to develop a simple rat model of complement-mediated acute intravascular hemolysis.

Study Design And Methods: Human AB red blood cells (RBCs) were incubated with complement-sufficient or complement-deficient Wistar rat serum (WRS) in the presence and absence of human RBC antibody in vitro to elucidate the mechanism of hemolysis.

Acute MRSA sinusitis with intracranial extension and marginal vancomycin susceptibility.

Methicillin resistant Staphylococcus aureus (MRSA) is increasingly being described as a cause of acute sinusitis. We present a patient with acute MRSA sinusitis complicated by rapid intracranial extension, marginal vancomycin susceptibility (MIC = 2 mg/L), delayed drainage of intracranial abscess, and subsequent development of rifampin resistance. Given the relatively high risk of intracranial extension of severe acute bacterial sinusitis and high mortality associated with invasive MRSA infections, we suggest early surgical drainage of intracranial abscesses in these circumstances.