This is a randomized double blinded controlled trial of 20-40 mg sodium nitrite tid in subjects with HFpEF. Primary outcomes are measures of physical function with non-invasive and invasive cardiopulmonary exercise testing, and fatigability, skeletal muscle bioenergetics, serology including inflammatory markers and platelet bioenergetics, quality of life measures.

开始日期2017-04-03

申办/合作机构

National Institute on Aging

NCT02888561 / Unknown statusN/A

The Impact of Dobutamine and Nitrite on Myocardial Supply and Demand in Heart Failure

Patients with poor heart function can, in certain situations, have a further weakening of the heart muscle such that it becomes difficult to provide enough blood to the brain and other organs. In these cases, heart function can be supported by the use of medicines or heart pumps. One of the most widely used medicines is Dobutamine, given as an infusion (a drip). Although Dobutamine has been in use for decades and does improve blood flow to the organs, previous studies have not shown any impact on recovery of heart muscle function and survival. Key to unravelling this discrepancy is to understand the precise effects of Dobutamine on the oxygen supply to, and oxygen usage by, the heart muscle. We also aim to find out whether simultaneous infusion of another drug called Nitrite (naturally occurring substance that is found in beetroot for example, much like GTN) can enhance the beneficial effects of Dobutamine on the oxygen supply-demand balance of the heart. In recent years, major advances in technology mean that it is now possible to obtain this information in patients undergoing coronary angiography procedures by making detailed measurements of heart muscle function and blood flow in the heart arteries using a conductance catheter (measures volume and pressure within the main pumping chamber of the heart) and the Combowire (dual pressure and flow sensor tip angioplasty guidewire). The aim of this study is to understand the effect of a brief infusion of Dobutamine and nitrite on heart muscle function, oxygen supply and oxygen usage through this use of this technology, directly following the patients routine coronary angiogram. Patients will have these measurements taken using the technology described above during the infusion of both dobutamine and nitrite, inserted through blood vessels that reach the heart.

开始日期2016-10-01

申办/合作机构

King's College London

NCT02463357 / Completed临床4期IIT

Three New Ideas to Protect Special Forces From the Stress of High Altitude

Acute Mountain Sickness (AMS) is a well-documented syndrome that affects 42% of non-acclimatized individuals traveling to altitudes above 10,000 feet. Decreased barometric pressure, which leads to low blood oxygen levels, is the primary casual factor of AMS. Symptoms of AMS are characterized by headache, nausea, vomiting, dizziness, fatigue and difficultly sleeping. Moreover, when people travel to high altitude, cognitive performance and endurance exercise capacity are impaired. Therefore, the goal of this research is to identify effective pharmacological agents that will help reduce the symptoms of AMS and improve physical and cognitive performance at high altitude.
The investigators will study the efficacy of the dietary supplement, quercetin, the drugs nifedipine (extended release) and methazolamide taken together, the drug metformin, and the drug nitrite in reducing symptoms of AMS and improving cognitive and exercise performance at high altitudes.

开始日期2015-08-01

申办/合作机构

University of Colorado Denver

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100 项与 Acidified nitrite 相关的专利（医药）

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项与 Acidified nitrite 相关的文献（医药）

2021-10-15·Infection and immunity2区 · 医学

AB569, a Novel, Topical Bactericidal Gel Formulation, Kills Pseudomonas aeruginosa and Promotes Wound Healing in a Murine Model of Burn Wound Infection

2区 · 医学

Article

作者: Satish, Latha ; Barry, Amanda ; Panmanee, Warunya ; Hassett, Daniel J.

Cutaneous thermal injuries from burns/explosives are a major cause of morbidity and mortality and represent a monumental burden on our current health care system. Injury severity is predominantly due to potentially lethal sepsis caused by multidrug-resistant (MDR) bacteria such as Pseudomonas aeruginosa (MDR-PA).

2020-10-01·Nitric oxide : biology and chemistry2区 · 生物学

Acidified nitrite improves wound healing in type 2 diabetic rats: Role of oxidative stress and inflammation

2区 · 生物学

Article

作者: Khosrow Kashfi ; Mohammad Khaksari ; Reza Norouzirad ; Hamideh Afzali ; Sajad Jeddi ; Asghar Ghasemi

PURPOSE:

Decreased nitric oxide bioavailability in skin contributes to impaired wound healing in type 2 diabetes (T2D). This study aims at determining effects of acidified nitrite on wound closure as well as inflammatory and antioxidants markers in wound tissue of rats with T2D.

MAIN METHODS:

Skin wound was made on the back of rats 28 days after the induction of T2D (high-fat diet/low-dose of streptozotocin). Control and diabetic rats were subdivided into two subgroups: Untreated control (C), acidified nitrite-treated control (CN), untreated diabetes (D), and acidified nitrite-treated diabetes (DN). Acidified nitrite was applied once daily from day 3 to day 28 and the wounds were photographed for macroscopic changes. On days 3, 7, 14, 21, and 28 after wounding, wound levels of inflammatory and antioxidant markers were measured.

RESULTS:

Half closure time (CT50%) was significantly lower in acidified nitrite-treated diabetic rats compared to untreated ones (5.1 vs. 8.0 days, P < 0.001). Inflammatory response was delayed in diabetic rats and persistent inflammatory response was observed at day 14 after wounding. Acidified nitrite application restored the inflammatory response and antioxidant levels to control values.

CONCLUSIONS:

Acidified nitrite accelerated wound healing in rats with T2D by restoring delayed inflammatory response and augmentation of antioxidant defense.

2020-09-01·DNA and cell biology4区 · 生物学

A Novel Bactericidal Drug Effective Against Gram-Positive and Gram-Negative Pathogenic Bacteria: Easy as AB569

4区 · 生物学

Review

作者: Hassett, Daniel J. ; Meyer, Thomas J.

Global antibiotic resistance, driven by intensive antibiotic exposure/abuse, constitutes a serious challenge to all health care, particularly in an era when new antimicrobial development has slowed to a trickle. Recently, we published work demonstrating the discovery and partial mechanism of action of a novel bactericidal agent that is effective against both gram-positive and gram-negative multidrug-resistant bacteria. This drug, called AB569, consists of acidified nitrite (A-NO₂^-) and EDTA, of which there is no mechanism of resistance. Using both chemistry-, genetic-, and bioinformatics-based techniques, we first discovered that AB569 was able to generate bactericidal levels of nitric oxide (NO), while the EDTA component stabilized S-nitrosyl thiols, thereby furthering NO and downstream reactive nitrogen species production. This elegant chemistry triggered a paralytic downregulation of vital genes using RNA-seq involved in the synthesis of DNA, RNA, ATP, and protein in the representative ESKAPE pathogen, Pseudomonas aeruginosa.

项与 Acidified nitrite 相关的新闻（医药）

2023-08-29

·Science Daily

New species of marine bacteria isolated from a deep-sea cold seep

Researchers have isolated a new strain of marine bacteria with unique characteristics from the ocean seabed. Researchers have isolated a new strain of marine bacteria with unique characteristics from the ocean seabed. The research, published today as a Reviewed Preprint in eLife, is described by the editors as an important study that advances our understanding of physiological mechanisms in deep-sea Planctomycetes bacteria, revealing unique characteristics such as being the only known species in the class of Phycisphaerae bacteria that uses a distinct budding model of division. It provides what the editors also say is convincing evidence that the new species is extensively involved in nitrogen assimilation and lives with a chronic virus (bacteriophage) that facilitates nitrogen metabolism. Nitrogen cycling by bacteria is an essential process that frees up nitrogen for building into nucleic acids, amino acids and proteins -- the building blocks of life. "Until recently, most research on the Planctomycetes family of bacteria has focused on strains in freshwater and shallow ocean environments, because of the logistical difficulties associated with sampling and cultivating deep-sea strains," says lead author Rikuan Zheng, a research associate at the Institute of Oceanology, Chinese Academy of Sciences, Beijing, China, and the National Laboratory for Marine Science and Technology, Qingdao, China. "Most Planctomycetes bacteria have been isolated using growth media that are nutritionally poor, so we wanted to see if using a nutrient-rich medium would make it possible to culture and further characterise members of this poorly understood family." To isolate the novel bacterium, the team took sediment samples from a deep-sea cold seep, where Planctomycetes bacteria are known to reside, and then encouraged their growth by supplementing a standard growth medium with the antibiotic rifampicin and sources of nitrogen. They cultured these enriched bacteria on agar and evaluated individual colonies further by gene sequencing. Among the bacteria, they identified a strain called ZRK32 that grew faster than others, and looked likely to be a member of the genus Poriferisphaera. To confirm this, the team compared the genetic similarities between this strain and other members of the Poriferisphaera genus and found that it was distinguishable from Poriferisphaera corsica, the only other species with a valid published name. This suggests that ZRK32 is a novel species -- which the team proposes to call Poriferisphaera hetertotrophicis. To learn more about this new species, the team studied its growth and how it multiplies. They found that, unlike other Planctomycetes family members, Poriferisphaera hetertotrophicis grows better in nutrient-rich media and multiplies via a budding mechanism, where parent cells create outgrowth buds that develop into daughter cells. As the Planctomycetes bacteria family is known to play an important role in nitrogen cycling, the team next explored whether this was also the case for Poriferisphaera hetertotrophicis. To test this, they looked at the effects of different nitrogen-containing substances -- nitrates, ammonia and nitrogen dioxide -- on Poriferisphaera hetertotrophicis growth. They found that adding nitrogen in the form of a nitrate or ammonia increased growth, whereas adding it as a nitrite inhibited growth. They also discovered that the addition of nitrate or ammonia caused the novel strain to release a bacteriophage -- a type of virus that infects bacteria. Bacteriophages are widely distributed across oceans and can regulate nitrogen metabolism in their host bacteria. This bacteriophage -- called phage-ZRK32 -- was able to increase the growth of Poriferisphaera hetertotrophicis and other marine bacteria dramatically by facilitating nitrogen metabolism. Even though the team's genetic analysis suggested Poriferisphaera hetertotrophicis contains all the necessary genes for metabolising nitrate and ammonia, chronic infection with this bacteriophage may help to further optimise nitrogen metabolism. "Our analyses indicate that strain ZRK32 is a novel species, which grows best in nutrient-rich media and releases a bacteriophage in the presence of nitrogen," concludes senior author Chaomin Sun, a Professor at the Institute of Oceanology, Chinese Academy of Sciences, and the National Laboratory for Marine Science and Technology. "This phage-ZRK32 is a chronic bacteriophagethat lives within its host without killing it. Our findings provide a novel insight into nitrogen metabolism in Planctomycetes bacteria and a suitable model to study the interactions between Planctomycetes and viruses."

微生物疗法

2021-03-30

·BioSpace

Turkish Ministry of Health Approves Increase in Patient Recruitment into the Phase II Trial for LSALT Peptide

TORONTO, March 30, 2021 (GLOBE NEWSWIRE) -- Arch Biopartners Inc. (“Arch” or the “Company”) (TSX Venture: ARCH and OTCQB: ACHFF), announced today that it received approval from the Turkish Ministry of Health, Pharmaceuticals and Medical Devices Agency (MoH) to recruit up to twenty additional patients into the Phase II trial of its lead drug LSALT peptide (Metablok), targeting acute lung injury and acute kidney injury caused by inflammation in patients with severe cases of COVID-19. The approval from the MoH doubles the number of patients allowed into the Turkish arm of the trial from twenty to forty. The first twenty patients in Turkey have already been recruited into the trial and have completed treatment. Patient recruitment is expected to resume this week in two hospital sites in Istanbul and Ankara. Recent data have shown a second surge in new COVID-19 infections and hospitalizations in Turkey, with a new pandemic high of over 32,000 daily infections reported on March 29, 2021. Turkey experienced a similar surge in daily infections during December 2020. Hospitalization rates are currently at approximately 1% of infected cases, once again putting a strain on the Turkish hospital system. Patient recruitment in this 60-patient phase II trial continues in four clinical sites in Canada and the USA, with 46 patients recruited to date between North America and Turkey. “We appreciate the support of the Turkish Ministry of Health and the enthusiasm of our clinical sites in Turkey to recruit more patients into our trial during this difficult pandemic,” said Richard Muruve, CEO of Arch. About the Phase II trial for LSALT Peptide The Phase II trial is an international, multicenter, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide (Metablok) as prevention of organ inflammation known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2 (COVID-19) or new variants of the virus. ARDS is the leading cause of death in COVID-infected patients. AKI has been observed in approximately 35% of patients admitted to hospital with COVID-19 and is also a leading cause of mortality.1 The composite primary endpoint of the Phase II trial reflects the severe effects often experienced by hospitalized COVID-19 patients and deemed appropriate for LSALT peptide’s novel mechanism of action in blocking consequential inflammation in the lungs, kidneys, and other organs. Additional information about the Phase II trial can be found at: The Phase II results will be used to design the Phase III program, including greater patient numbers to more fully evaluate efficacy and safety in hospitalized patients at risk to inflammation in the lungs, kidneys or liver. About COVID-19 COVID-19 is the disease caused by the novel coronavirus SARS-CoV-2 that emerged in China in late 2019. Severe complications from COVID-19 are in large part due to excessive host immune responses to the virus that result in progressive lung inflammation and acute respiratory distress syndrome that often requires mechanical ventilation and critical care1. Patients with severe COVID-19 also experience multiple organ dysfunction including acute kidney injury, liver dysfunction, cardiac failure, and blood abnormalities. Treatment of severe COVID-19 has been primarily supportive, relying heavily on respiratory, infectious diseases, and critical care medicine. Survival rates and health care system capacity could both be improved with new treatments that prevent the severe manifestations of COVID-19, such as worsening lung inflammation (ARDS) and AKI experienced by patients infected with SARS-CoV-22 or the many variants that have emerged globally in recent months. 1 Hirsch JS et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020 doi: . 2 J. S. Ayres, Sci. Adv 10.1126/sciadv.abc1518 (2020) About Arch Biopartners Arch Biopartners Inc. is a clinical stage company focused on the development of innovative technologies that have the potential to make a significant medical or commercial impact. Arch is developing a pipeline of new drug candidates that inhibit inflammation in the lungs, liver and kidneys via the dipeptidase-1 (DPEP-1) pathway for multiple medical indications. Continuing under development in the Arch portfolio are: AB569, a potential new treatment for antibiotic resistant bacterial infections in wounds and the lungs; and ‘Borg’ peptide coatings that increase corrosion resistance and decrease bacterial biofilm on various medical grade metals and plastics. For more information on Arch Biopartners, its technologies and other public documents Arch has filed on SEDAR, please visit . The Company has 61,462,302 common shares outstanding. Forward-Looking Statements All statements, other than statements of historical fact, in this news release are forward looking statements that involve various risks and uncertainties, including, without limitation, statements regarding the future plans and objectives of the Company. There can be no assurance that such statements will prove to be accurate. Actual results and future events could differ materially from those anticipated in such statements. These and all subsequent written and oral forward-looking statements are based on the estimates and opinions of management on the dates they are made and are expressly qualified in their entirety by this notice. The Company assumes no obligation to update forward-looking statements should circumstances or management’s estimates or opinions change. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release For more information, please contact: Richard Muruve Chief Executive Officer Arch Biopartners, Inc. 647-428-7031 info@archbiopartners.com

2021-03-24

·BioSpace

Arch Biopartners Enters Exclusive License Agreement with the University of Cincinnati for AB569 Topical Wound Treatment

TORONTO, March 24, 2021 (GLOBE NEWSWIRE) -- Arch Biopartners Inc.. (“Arch” or the “Company”) (TSX Venture: ARCH and OTCQB: ACHFF), announced today it has entered into an exclusive agreement with the University of Cincinnati (UC) to license new patent claims for an AB569 topical wound application designed to prevent, treat and heal burn/blast wound infections. AB569 was invented by Dr. Daniel Hassett at UC to target multi-drug resistant infections that are difficult to treat in the lungs, wounds of soldiers (burns or blast), surgical incisions and diabetic skin ulcers. This new agreement builds on the existing license of AB569 that Arch has with UC. “With this new license, Arch now has a commercial path to develop the topical wound gel version of AB569 for clinical use. We look forward to exploring opportunities where Arch can support human trials targeting the prevention and treatment of antibiotic resistant infections in wounds,” said Richard Muruve, CEO of Arch Biopartners. Burn or blast injuries are a major cause of morbidity and mortality, particularly in the military. In some cases this is due to sepsis, which is often preceded by wound infection that delays wound healing. A significant challenge in treating bacterial infections is their inherent or acquired antibiotic resistance. AB569 has been shown to kill multi-drug resistant (MDR) Gram-negative (G-) bacteria such as Pseudomonasaeruginosa, that is responsible for over half of all severe burn infections, and identified as a “major pathogen” by the Centers for Disease Control and Prevention(1). Treatment strategies for burn wound infections are currently challenging and limited due to the ability of G- bacteria to readily adapt through mutations, often in response to multiple antibiotic regimens. Hence, there is a critical need to develop novel and effective antimicrobials such as AB569 for the prevention, treatment and healing of burn/blast wounds that are complicated by G- infection. About AB569 AB569 is a synergistic antimicrobial tandem of slightly acidified sodium nitrite and EDTA that has the critical advantage over conventional antibiotics in that it down regulates many of the genes in the bacterium responsible for survival. In a recent publication in the Proceedings of the National Academy of Sciences, Dr. Hassett’s group showed that AB569 caused a catastrophic loss of the capacity to support vital core biosynthetic and metabolic pathways of multi-drug resistant pathogen, Pseudomonas aeruginosa. These include the synthesis of DNA, RNA, protein, ATP and the ability of bacteria to breathe by both aerobic and anaerobic respiration. PNAS Link: PloS One Synopsis and Link: Acinetobacter baumannii infections have historically been a major clinical challenge for both military and civilian health professionals, especially during the Iraq/Afghanistan conflicts. In the context of combat medical care and acquired wound, burn, blast and ventilator-associated pneumonia (VAP) infections, Acinetobacter baumannii represents a formidable multi-drug resistant (MDR-AB) pathogen and, as such, is a top 10 CDC priority organism. In another recent publication, Dr. Hassett’s group showed that AB569 is effective at killing Acinetobacter baumannii. For more details, please access the following link: References: 1. Hodle AE, Richter KP, Thompson RM. 2006. Infection control practices in U.S. burn units. J Burn Care Res 27:142-151. About Arch Biopartners Arch Biopartners Inc. is a clinical stage company focused on the development of innovative technologies that have the potential to make a significant medical or commercial impact. Arch is developing a pipeline of new drug candidates that inhibit inflammation in the lungs, liver and kidneys via the dipeptidase-1 (DPEP-1) pathway for multiple medical indications. Continuing under development in the Arch portfolio are: AB569, a potential new treatment for antibiotic resistant bacterial infections in wounds and the lungs; and ‘Borg’ peptide coatings that increase corrosion resistance and decrease bacterial biofilm on various medical grade metals and plastics. For more information on Arch Biopartners, its technologies and other public documents Arch has filed on SEDAR, please visit . The Company has 61,462,302 common shares outstanding. Forward-Looking Statements All statements, other than statements of historical fact, in this news release are forward looking statements that involve various risks and uncertainties, including, without limitation, statements regarding the future plans and objectives of the Company. There can be no assurance that such statements will prove to be accurate. Actual results and future events could differ materially from those anticipated in such statements. These and all subsequent written and oral forward-looking statements are based on the estimates and opinions of management on the dates they are made and are expressly qualified in their entirety by this notice. The Company assumes no obligation to update forward-looking statements should circumstances or management’s estimates or opinions change. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release For more information, please contact: Richard Muruve Chief Executive Officer Arch Biopartners, Inc. 647-428-7031 info@archbiopartners.com

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适应症	最高研发状态	国家/地区	公司	日期
细菌感染	临床1期	美国	Arch Biopartners, Inc.	2018-02-10
假单胞菌感染	临床1期	美国	University of Cincinnati (Ohio)	2014-03-22
伯克霍尔德氏菌属感染	临床前	美国	University of Cincinnati (Ohio)	-
葡萄球菌感染	临床前	美国	University of Cincinnati (Ohio)	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02463357 (CTgov)	临床4期	高原反应	148	Quercetin (Quercetin)	醖構鹹艱鬱繭簾醖壓襯(構襯製憲鹽構淵鑰鬱鏇) = 範築顧願網製窪顧簾繭襯獵壓鹽範顧鏇網築製 (獵鏇艱鹽鑰衊網齋顧糧, 鑰簾餘糧簾鑰獵糧鏇構 ~ 築憲夢簾糧遞選夢獵觸) 更多	-	2021-03-30
				Methazolamide+Nifedipine extended release (Nifedipine+Methazolamide)	醖構鹹艱鬱繭簾醖壓襯(構襯製憲鹽構淵鑰鬱鏇) = 選衊艱積築憲衊鹹廠夢襯獵壓鹽範顧鏇網築製 (獵鏇艱鹽鑰衊網齋顧糧, 廠餘齋觸觸鹹夢蓋膚廠 ~ 襯廠選構鏇齋淵糧選蓋) 更多
NCT02918552 (ONOH, CTgov)	临床2期	射血分数保留型心力衰竭	15	sodium nitrite (Sodium Nitrite)	製蓋衊糧夢齋簾衊襯膚(衊餘淵鑰鑰壓鹹積網憲) = 齋築鹽觸衊鏇齋願廠簾製蓋繭簾衊鑰顧齋鹹餘 (鬱範觸淵獵壓膚鏇鏇顧, 壓觸構顧餘顧襯獵淵觸 ~ 蓋積鬱廠願糧鏇鹽繭願) 更多	-	2020-01-22
				placebo (Placebo)	製蓋衊糧夢齋簾衊襯膚(衊餘淵鑰鑰壓鹹積網憲) = 艱鬱糧積餘鹹選構積觸製蓋繭簾衊鑰顧齋鹹餘 (鬱範觸淵獵壓膚鏇鏇顧, 齋構構膚獵壓築選餘築 ~ 襯觸壓遞蓋鹽鹽蓋憲製) 更多
NICE trial (ASN2019)	N/A	内皮功能障碍 vWF \| IL-17 \| vascular adhesion molecule-1 ... 更多	70	Sodium nitrite + Isoquercetin	築願憲積構獵鬱蓋廠網(簾鹹醖憲壓艱範構淵糧) = 淵齋築鏇蓋夢鹹願簾衊顧遞膚衊積糧艱衊顧蓋 (蓋醖繭襯觸衊襯糧製製, -0.07 ~ 2.32)	积极	2019-11-05
				Placebo	築願憲積構獵鬱蓋廠網(簾鹹醖憲壓艱範構淵糧) = 鬱製鬱蓋齋製選衊鹽遞顧遞膚衊積糧艱衊顧蓋 (蓋醖繭襯觸衊襯糧製製, -0.86 ~ 1.53) 更多
NCT01932606 (CTgov)	临床2期	射血分数保留型心力衰竭 \| 肺性高血压	28	Nitrite	衊願窪築範齋衊夢網憲(壓製遞鏇鹹齋獵艱艱鑰) = 餘選憲鬱鏇壓壓糧鏇願願積壓夢遞顧製遞簾顧 (淵選憲鏇觸構簾鏇鬱醖, 廠鑰憲觸獵範鑰鹹鑰蓋 ~ 築夢鬱鏇範遞壓廠網糧) 更多	-	2016-02-15