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Article ; Online: The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis: A review.

Nahama, Alexis / Ramachandran, Roshni / Cisternas, Alvaro Francisco / Ji, Henry

Medicine in drug discovery

2020 Volume 5, Page(s) 100033

Abstract: Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected ... ...

Abstract	Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points towards 80% expected fatality for patients progressing to advanced pulmonary disease, even when hospitalized in the intensive care unit. This is particularly true among the patient population over 65. Novel life-saving strategies are desperately needed to mitigate the high mortality that will be associated with the late stage SARS-CoV-2 viral infection associated with the fatal respiratory distress. We hypothesize that the morbidity, severity of the disease, and underlying physiological events leading to mortality are closely linked to the TRPV1 expressing neuronal system (afferent/efferent neurons) in the lungs. TRPV1 expressing cells are responsible for pain transmission, inflammation and immunomodulation throughout the entire pulmonary system and are modulating the processes associated with localized cytokine release (storm) and overall rapid disease progression. We suggest that therapeutic approaches targeting TRPV1 containing nerve fibers in the lungs will modulate the inflammatory and immune signal activity, leading to reduced mortality and better overall outcomes. We also propose to further explore the use of resiniferatoxin (RTX), an ultra-potent TRPV1 agonist currently in clinical trials for cancer and osteoarthritis pain, as a possible ablating agent of TRPV1 positive pulmonary pathways in patients with advanced COVID-19 disease.
Keywords	covid19
Language	English
Publishing date	2020-04-04
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-0986
ISSN (online)	2590-0986
DOI	10.1016/j.medidd.2020.100033
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Unintended consequences of COVID-19 safety measures on patients with chronic knee pain forced to defer joint replacement surgery.

Cisternas, Alvaro F / Ramachandran, Roshni / Yaksh, Tony L / Nahama, Alexis

Pain reports

2020 Volume 5, Issue 6, Page(s) e855

Abstract: In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. ...

Abstract	In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. Deferring elective joint replacement surgeries for an unknown period is likely to decrease the incidence of infection with SARS-CoV-2 but is likely to have detrimental effects in individuals suffering from chronic knee pain. These detrimental effects extend beyond the discomfort of osteoarthritis (OA) and the inconvenience of rescheduling surgery. Disabling pain is a driving factor for individuals to seek medical intervention, including pharmacological palliative treatment and surgical procedures. The need for surgical intervention due to chronic pain as for knee and hip replacement is now put on hold indefinitely because access to surgical care has been limited. Although a moderate delay in surgical intervention may not produce a significant progression of OA within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by OA severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, nonopiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.
Keywords	covid19
Language	English
Publishing date	2020-10-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2471-2531
ISSN (online)	2471-2531
DOI	10.1097/PR9.0000000000000855
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pain Treatment in the Companion Canine Model to Validate Rodent Results and Incentivize the Transition to Human Clinical Trials.

Iadarola, Michael J / Brown, Dorothy Cimino / Nahama, Alexis / Sapio, Matthew R / Mannes, Andrew J

Frontiers in pharmacology

2021 Volume 12, Page(s) 705743

Abstract: One of the biggest challenges for analgesic drug development is how to decide if a potential analgesic candidate will work in humans. What preclinical data are the most convincing, incentivizing and most predictive of success? Such a predicament is not ... ...

Abstract	One of the biggest challenges for analgesic drug development is how to decide if a potential analgesic candidate will work in humans. What preclinical data are the most convincing, incentivizing and most predictive of success? Such a predicament is not unique to analgesics, and the pain field has certain advantages over drug development efforts in areas like neuropsychiatry where the etiological origins are either unknown or difficult to ascertain. For pain, the origin of the problem frequently is known, and the causative peripheral tissue insult might be observable. The main conundrum centers around evaluation of translational cell- and rodent-based results. While cell and rodent models are undeniably important first steps for screening, probing mechanism of action, and understanding factors of adsorption, distribution metabolism and excretion, two questions arise from such studies. First, are they reliable indicators of analgesic performance of a candidate drug in human acute and chronic pain? Second, what additional model systems might be capable of increasing translational confidence? We address this second question by assessing, primarily, the companion canine model, which can provide particularly strong predictive information for candidate analgesic agents in humans. This statement is mainly derived from our studies with resiniferatoxin (RTX) a potent TRPV1 agonist but also from protein therapeutics using a conjugate of Substance P and saporin. Our experience, to date, is that rodent models might be very well suited for acute pain translation, but companion canine models, and other large animal studies, can augment initial discovery research using rodent models for neuropathic or chronic pain. The larger animal models also provide strong translational predictive capacity for analgesic performance in humans, better predict dosing parameters for human trials and provide insight into behavior changes (bladder, bowel, mood, etc.) that are not readily assessed in laboratory animals. They are, however, not without problems that can be encountered with any experimental drug treatment or clinical trial. It also is important to recognize that pain treatment is a major veterinary concern and is an intrinsically worthwhile endeavor for animals as well as humans.
Language	English
Publishing date	2021-08-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.705743
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Safety and efficacy of intravesical instillation of resiniferatoxin in healthy cats: A preliminary study.

Barletta, Michele / Gordon, Julie / Escobar, André / Mitchell, Krista / Trenholme, H Nicole / Grimes, Janet A / Jiménez-Andrade, Juan M / Nahama, Alexis / Cisternas, Alvaro

Frontiers in veterinary science

2023 Volume 9, Page(s) 922305

Abstract: Objectives: To evaluate the safety of intravesical application of resiniferatoxin (RTX) in healthy cats and its effects on calcitonin gene-related peptide (CGRP) and substance P (SP) produced by C-fibers.: Methods: Seven adult female cats received ... ...

Abstract	Objectives: To evaluate the safety of intravesical application of resiniferatoxin (RTX) in healthy cats and its effects on calcitonin gene-related peptide (CGRP) and substance P (SP) produced by C-fibers. Methods: Seven adult female cats received either 25 mL of saline (control; Results: Intravesical RTX was well tolerated and plasma concentrations were below the quantifiable limits except for one cat receiving 1 μg/mL. Mild to moderate histopathological changes, including epithelial changes, edema, and blood vessel proliferation, were observed at lower doses (0.2 and 1 μg/mL), and were more severe at the higher dose (2 μg/mL). C-fiber ablation was observed in the urinary bladder tissue at all doses, as shown by an apparent reduction of both CGRP and SP immunoreactive axons. Conclusion: A dose of 25 μg (1 μg/mL) of RTX instilled in the urinary bladder of healthy cats appeared to decrease the density of SP and CGRP nerve axons innervating bladder and induced moderate changes in the bladder tissue.
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.922305
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis

Alexis Nahama / Roshni Ramachandran / Alvaro Francisco Cisternas / Henry Ji

Medicine in Drug Discovery, Vol 5, Iss , Pp - (2020)

A review

2020

Abstract	Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points towards 80% expected fatality for patients progressing to advanced pulmonary disease, even when hospitalized in the intensive care unit. This is particularly true among the patient population over 65. Novel life-saving strategies are desperately needed to mitigate the high mortality that will be associated with the late stage SARS-CoV-2 viral infection associated with the fatal respiratory distress.We hypothesize that the morbidity, severity of the disease, and underlying physiological events leading to mortality are closely linked to the TRPV1 expressing neuronal system (afferent/efferent neurons) in the lungs. TRPV1 expressing cells are responsible for pain transmission, inflammation and immunomodulation throughout the entire pulmonary system and are modulating the processes associated with localized cytokine release (storm) and overall rapid disease progression.We suggest that therapeutic approaches targeting TRPV1 containing nerve fibers in the lungs will modulate the inflammatory and immune signal activity, leading to reduced mortality and better overall outcomes. We also propose to further explore the use of resiniferatoxin (RTX), an ultra-potent TRPV1 agonist currently in clinical trials for cancer and osteoarthritis pain, as a possible ablating agent of TRPV1 positive pulmonary pathways in patients with advanced COVID-19 disease. Keywords: COVID-19, SARS-CoV-2, cytokine, ARDS, inflammation, TRPV1, lung, resiniferatoxin
Keywords	Pharmacy and materia medica ; RS1-441 ; covid19
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unintended consequences of COVID-19 safety measures on patients with chronic knee pain forced to defer joint replacement surgery

Alvaro F. Cisternas / Roshni Ramachandran / Tony L. Yaksh / Alexis Nahama

PAIN Reports, Vol 5, Iss 6, p e

2020 Volume 855

Abstract: Abstract. In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis ... ...

Abstract	Abstract. In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. Deferring elective joint replacement surgeries for an unknown period is likely to decrease the incidence of infection with SARS-CoV-2 but is likely to have detrimental effects in individuals suffering from chronic knee pain. These detrimental effects extend beyond the discomfort of osteoarthritis (OA) and the inconvenience of rescheduling surgery. Disabling pain is a driving factor for individuals to seek medical intervention, including pharmacological palliative treatment and surgical procedures. The need for surgical intervention due to chronic pain as for knee and hip replacement is now put on hold indefinitely because access to surgical care has been limited. Although a moderate delay in surgical intervention may not produce a significant progression of OA within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by OA severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, nonopiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.
Keywords	Anesthesiology ; RD78.3-87.3 ; covid19
Subject code	796
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Wolters Kluwer
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis

Nahama, Alexis / Ramachandran, Roshni / Cisternas, Alvaro Francisco / Ji, Henry

Medicine in Drug Discovery

A review

2020 Volume 5, Page(s) 100033

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ISSN	2590-0986
DOI	10.1016/j.medidd.2020.100033
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The role of afferent pulmonary innervation in poor prognosis of acute respiratory distress syndrome in COVID-19 patients and proposed use of resiniferatoxin (RTX) to improve patient outcomes in advanced disease state: A review

Nahama, Alexis / Ramachandran, Roshni / Cisternas, Alvaro Francisco / Ji, Henry

Med Drug Discov

Abstract: Acute respiratory distress is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. ... ...

Abstract	Acute respiratory distress is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points towards 80% expected fatality for patients progressing to advanced pulmonary disease, even when hospitalized in the intensive care unit. This is particularly true among the patient population over 65. Novel life-saving strategies are desperately needed to mitigate the high mortality that will be associated with the late stage SARS-CoV-2 viral infection associated with the fatal respiratory distress. We hypothesize that the morbidity, severity of the disease, and underlying physiological events leading to mortality are closely linked to the TRPV1 expressing neuronal system (afferent/efferent neurons) in the lungs. TRPV1 expressing cells are responsible for pain transmission, inflammation and immunomodulation throughout the entire pulmonary system and are modulating the processes associated with localized cytokine release (storm) and overall rapid disease progression. We suggest that therapeutic approaches targeting TRPV1 containing nerve fibers in the lungs will modulate the inflammatory and immune signal activity, leading to reduced mortality and better overall outcomes. We also propose to further explore the use of resiniferatoxin (RTX), an ultra-potent TRPV1 agonist currently in clinical trials for cancer and osteoarthritis pain, as a possible ablating agent of TRPV1 positive pulmonary pathways in patients with advanced COVID-19 disease.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #31659
Database	COVID19

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Article ; Online: Executive summary of the CATalyst Council's cat-friendly practice makeover study.

Tennyson, Brian / Brunt, Jane / Nahama, Alexis

Journal of the American Veterinary Medical Association

2012 Volume 241, Issue 1, Page(s) 58–62

MeSH term(s)	Animals ; Cats ; Communication ; Community Participation ; Education, Veterinary ; Hospitals, Animal/manpower ; Hospitals, Animal/organization & administration ; Humans ; Marketing/organization & administration ; Pilot Projects ; Veterinary Medicine/organization & administration ; Veterinary Medicine/statistics & numerical data ; Veterinary Medicine/trends
Language	English
Publishing date	2012-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.241.1.58
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Article ; Online: Novel decoy cellular vaccine strategy utilizing transgenic antigen-expressing cells as immune presenter and adjuvant in vaccine prototype against SARS-CoV-2 virus.

Ji, Henry / Yan, Ying / Ding, Beibei / Guo, Wenzhong / Brunswick, Mark / Niethammer, Andreas / SooHoo, Williams / Smith, Robin / Nahama, Alexis / Zhang, Yanliang

Medicine in drug discovery

2020 Volume 5, Page(s) 100026

Abstract: A novel approach modifying cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination) in the prevention of COVID-19 disease is currently being explored. Our approach entails utilizing SARS-CoV-2 Spike antigen- ... ...

Abstract	A novel approach modifying cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination) in the prevention of COVID-19 disease is currently being explored. Our approach entails utilizing SARS-CoV-2 Spike antigen-expressing, non-replicating cells as carriers and presenters of immunogenic antigens, so called "I-cells". By using irradiated cells as presenting vehicles of SARS-CoV-2 viral antigens(s) in a cellular context, these presented viral proteins can be recognized by the host immune system, thus, an efficient protective immune response might be elicited. Another advantage of this strategy is that the manufacturing process is scalable and yields uniform cell products allowing for "off-the-shelf" frozen supply availability. To prevent engraftment and proliferation of the cells after administration, the cells will be irradiated post-harvesting abolishing in vivo replication potential. Specifically, immunoreactive Spike-1 proteins from SARS-CoV-2 are expressed on the surface of irradiated target I-cells. Utilizing this innovative strategy, these viral antigen-displaying decoy cells will be developed as a vaccine to protect against COVID-19 disease.
Keywords	covid19
Language	English
Publishing date	2020-03-25
Publishing country	Netherlands
Document type	Journal Article
ISSN	2590-0986
ISSN (online)	2590-0986
DOI	10.1016/j.medidd.2020.100026
Database	MEDical Literature Analysis and Retrieval System OnLINE

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