Smoke Inhalation Injury

JERUSALEM, July 12 (Reuters) - Israeli prosecutors filed terrorism-related charges on Wednesday against two Jewish settlers, one accused of desecrating a mosque and the other of setting a fire in a home, during rampages against Palestinians that drew U.S. calls for accountability. The spree of vandalism and arson by hundreds of settlers in several villages and towns in the occupied West Bank last month followed the June 20 killing of four Israelis by Hamas gunmen. Some of the Palestinians who lost property were U.S. dual nationals. One defendant, in his early 30s, was among "a large number (of) rioters" who threw objects at buildings in Orif village, wrecked furniture and windows in its mosque and ripped up copies of the Koran and threw them to the floor, the indictment said. Their goal was "to arouse fear or shock in the community through a grave blow to the sacrosanct," it said. The second defendant, a 22-year-old off-duty soldier, was accused separately of taking part in a mob break-in at a home in Umm Safa village while a mother and her four children were present, forcing her to hide them in a closet. He set a patio chair alight and propped it the doorway, setting a fire that spread in the house and inflicting smoke-inhalation injuries on two of the children, the indictment said. The Honenu law firm representing the defendants denied the charges against them. It described the first as being wrongfully targeted by Israeli authorities and the second as having been misidentified and indicted "for media and populist purposes". The charges - including disorderly conduct, insulting religion, aggravated arson and aggravated assault - normally carry maximum prison terms ranging between three and 20 years. In the indictments, they were redesignated as "acts of terrorism" or "motivated by racism". Under Israeli law, that would enable the courts to as much as double the penalty for any of the counts on which it convicts. The indictments did not make clear what evidence will be brought. One of them appeared to have redacted the names of three prosecution witnesses, suggesting they might be confidential sources. The limited scale and pace of Israel's law-enforcement effort have left Palestinians unmoved, almost a decade since the stalling of U.S.-sponsored efforts to achieve their statehood goals through negotiations. The Palestinian Foreign Ministry described the settler rampages as "state-sponsored terrorism". Israel's hard-right government includes ministers who chafe at attributing the term terrorism to settlers. Writing by Dan Williams; Editing by Nick Macfie and Conor Humphries Our Standards: The Thomson Reuters Trust Principles.

Scientists identify WASH protein complex as a gatekeeper of neutrophil-driven inflammation. A team led by Scripps Research scientists has uncovered key details of an immune-cell process that frequently underlies excessive inflammation in the body. The findings could lead to new ways of preventing and/or treating inflammation-related conditions such as sepsis, arthritis, and coronary artery disease. In the study, published September 21, 2022 in Nature Communications, the researchers showed that a multi-protein "molecular machine" called WASH has a powerful role in restraining excessive inflammatory activity by neutrophils, immune cells that are important early responders against infections. "Our findings point to the possibility of future treatments that target this WASH-regulated pathway to inhibit neutrophil-driven inflammation while preserving most of neutrophils' anti-microbial effectiveness," says study senior author Sergio Catz, PhD, professor in the Department of Molecular Medicine at Scripps Research. Neutrophils are workhorses of the mammalian immune system, comprising about two-thirds of the white blood cells that circulate through our bloodstreams. They combat invading microbes by engulfing and digesting them, and by releasing a variety of antimicrobial molecules via a process called exocytosis. Many of the antimicrobial molecules that neutrophils release via exocytosis are potent enough to harm healthy cells. There is evidence that excessive and/or chronic release of these molecules at least partly underlies serious medical conditions and types of tissue injury, including the bacterial blood-infection condition known as sepsis, arthritis, "reperfusion" injury to cells after oxygen deprivation, smoke inhalation injury to lungs, inflammatory bowel disease, some cancers, and even the artery-thickening atherosclerosis that leads to heart attacks and strokes. Yet scientists still have a lot to learn about how this exocytosis process works. In the new study, Catz and his team illuminated the important role WASH plays in neutrophil exocytosis. Neutrophils, when they encounter signs of infection or inflammation, typically respond initially by releasing, via exocytosis, milder compounds within "gelatinase granules" -- capsule-like enclosures named for one of the enzymes found within them. A second type of exocytosis, triggered secondarily and usually only by more severe infection or inflammation, involves the release of "azurophilic granules," so-called because they are bound by a common blue stain. Azurophilic cargoes are far more potent and are more likely to damage bystander cells. The team showed that WASH normally facilitates the initial gelatinase granule response, which includes the release of compounds that help neutrophils adhere to and move around surfaces such as blood vessel walls. At the same time, WASH normally restrains the release of toxic azurophilic granules cargoes. In experiments, neutrophils without WASH released excessive amounts of azurophilic granules. Mice with these neutrophils had blood levels of toxic azurophilic molecules that are normally found in cases of harmful systemic inflammation. The mortality rate of such mice when experiencing an experimental sepsis-like condition was more than triple that of normal mice. "WASH seems to be an important molecular switch that controls neutrophils' responses to infection and inflammation by regulating the release of these two kinds of antimicrobial cargoes," Catz says. "When WASH is dysfunctional, the result is likely to be excessive and chronic inflammation." "In this study, using state-of-the-art cell biology approaches, we reveled how neutrophils control their timely response through sequential exocytosis, and have identified a molecular system that acts as the gatekeeper of this process," Catz adds. Catz and his colleagues are continuing to study WASH and other molecules involved in neutrophil exocytosis, with the goal of finding candidate drug molecules that can damp excessive azurophilic granule exocytosis -- to treat inflammatory conditions -- without impairing neutrophils' functions as immune first responders. The study's co-first authors were Senior Staff Scientist Jennifer Johnson, PhD, and postdoctoral researchers Elsa Meneses-Salas PhD, and Mahalakshmi Ramadass, PhD, all members of the Catz lab during the study. The research was funded in part by the National Institutes of Health (P01HL152958, R01HL088256, R01AR070837, R01DK110162).

US Food and Drug Administration Review Allows for High Volume Production of ZYESAMI® (aviptadil) Shelf Life of ZYESAMI Now Extended from 62 Days to 150 Days RADNOR, Pa., Nov. 11, 2021 (GLOBE NEWSWIRE) -- NRx Pharmaceuticals (NASDAQ: NRXP), today announced receipt of the US Food and Drug Administration’s (FDA) response to NRx’s October 8 submission of updated manufacturing information for ZYESAMI® (aviptadil). The completion of this review, without the imposition of any clinical hold by the FDA, enables NRx to distribute ZYESAMI, produced at commercial scale, under Good Manufacturing Practices (GMP) for clinical trials and other future purposes approved in future regulatory actions. NRx looks forward to working with the FDA to complete the chemistry, manufacturing, and controls (CMC) review that will ultimately be required for any potential drug approval. Prior to the COVID pandemic, ZYESAMI was never manufactured as a commercial drug for intravenous use. Between March and May 2020, NRx formulated aviptadil based on historical files and initiated an FDA-approved, phase 2b/3 clinical trial by producing ZYESAMI in an FDA-inspected 503b pharmacy. Until now, ZYESAMI was manufactured for clinical trials purposes in handmade, 300 dose batches, with a limited shelf life of 62 days. The FDA has now reviewed a GMP manufacturing process at a batch size of 10,000 – 100,000 doses with a current shelf life of 150 days and identified no basis for a clinical hold. “This represents the first time aviptadil has been manufactured in an FDA-inspected commercial GMP environment for intravenous and inhaled use and passed regulatory review of manufacturing and CMC. With the help of our partners at Nephron Pharmaceuticals, we have validated the analytic techniques required to test the purity, potency, and stability of our medicine as required by the FDA and other regulators. We have advanced a generic ingredient (aviptadil) into a modern drug that meets GMP specifications, and that can be manufactured at commercial scale, cost, and shelf life,” said Prof Jonathan Javitt, MD MPH Chairman and CEO NRx Pharmaceuticals. “While we continue to focus on proving clinical safety and efficacy in the treatment of COVID-19, we now have an investigational drug platform, reviewed by FDA, that enables us to investigate the use of ZYESAMI in both intravenous and inhaled form for a myriad of other lethal conditions that cause lung injury. Those conditions include Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), acute smoke inhalation, sarcoidosis, and checkpoint inhibitor pneumonitis, to name a few. The manufacturing information reviewed by the FDA will become part of our submission for New Drug Approval, while also providing support for a renewed EUA submission at such time as we have additional data to present.” About NRx Pharmaceuticals NRx Pharmaceuticals (NRx) draws upon more than 300 years of collective, scientific, and drug-development experience to bring improved health to patients. Its investigational product, ZYESAMI® (aviptadil) for patients with COVID-19, has been granted Fast Track designation by the US Food and Drug Administration (FDA) and is currently undergoing phase 3 trials funded by the US National Institutes of Health, the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, and the Medical Countermeasures program, part of the US Department of Defense. The FDA has additionally granted Breakthrough Therapy Designation, a Special Protocol Agreement, and a Biomarker Letter of Support to NRx for NRX-101, an investigational medicine to treat suicidal bipolar depression. NRX-101 is currently in Phase 3 trials, with readouts expected in 2022. In July 2021, the Government of Israel awarded NRx the exclusive worldwide right to develop and market the BriLife™ COVID vaccine developed by the Israel Institute for Biological Research. NRx is led by executives who have held senior roles at Allergan, J&J, Lilly, Novartis, Pfizer, and the US FDA. NRx is chaired by Prof Jonathan Javitt, MD, MPH, who has held leadership roles in six biotechnology startup companies with public exits and been appointed to advisory roles in four US Presidential Administrations. The NRx board includes Dr. Sherry Glied, former US Assistant Secretary for Health (ASPE), Daniel E. Troy, JD, former Chief Counsel of the US FDA, Chaim Hurvitz, former director of Teva and President of the Teva International Group, and General H.R. McMaster, Ph.D. (US Army, Ret.) the 26th United States National Security Advisor. Cautionary Note Regarding Forward-Looking Statements This announcement of NRx Pharmaceuticals, Inc. includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995, which may include, but are not limited to, statements regarding our financial outlook, product development, business prospects, and market and industry trends and conditions, as well as the company’s strategies, plans, objectives, and goals. These forward-looking statements are based on current beliefs, expectations, estimates, forecasts, and projections of, as well as assumptions made by, and information currently available to, the company’s management. The company assumes no obligation to revise any forward-looking statement, whether as a result of new information, future events, or otherwise. Accordingly, you should not place reliance on any forward-looking statement, and all forward-looking statements are herein qualified by reference to the cautionary statements set forth above. MEDIA CONTACT: Jack Hirschfield Head of Corporate Communications, NRx jhirschfield@nrxpharma.com 512-674-5163 INVESTOR RELATIONS Eric Goldstein LifeSci Advisors egoldstein@lifesciadvisors.com 646-791-9729 SOURCE NRx Pharmaceuticals