Phuoc-Tan DiepUniversity Hospitals Of Morecambe Bay NHS Foundation Trust · Department of Pathology
Phuoc-Tan Diep
MBChB. FRCPath. PGCert Med Ed.
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25
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Introduction
Skills and Expertise
Publications
Publications (25)
Open Access after comparing the morbidity patterns of cOViD-19 infections, variations of oxytocin levels and some properties of the neurohormone oxytocin, the authors put forward their hypothesis that oxytocin might constitute a safe, inexpensive and readily available treatment for this disease.
Available free above at:
DOI: 10.1016/j.mehy.2020.110329
Or here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528823/
Background
Oxytocin is a nonapeptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Historically, this molecule has been involved as a key factor in the formation of infant attachment, maternal behavior and pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. In the last de...
Objectives
In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring...
Hypothesis: SARS-CoV-2 amplifies pre-existing dysbiosis induced mucosal inflammation and this can cause a severe systemic inflammatory disease. The microbial flora perturbation can persist long after the virus has been eliminated leading to a wide range of long Covid symptoms. Evidence: Dysbiosis induced mucosal inflammation increases with age and...
Disruption of immune and neuroendocrine system function has been shown to play a key role in COVID-19. Oxytocin is vitally important for the immune and neuroendocrine systems. However, oxytocin dysfunction might occur in COVID-19 leading to autoimmune disease. Intranasal oxytocin may be effective in turning off an overactive immune system. This cou...
Oxytocin is a TRPV1 agonist with the ability to desensitise this receptor and therefore, through this mechanism, could decrease the severity of ARDS in COVID-19, as well as numerous other pathways. This provides another mechanism for this multi-faceted hormone which has shown multiple other potential benefits against COVID-19, strengthening the rat...
Oxytocin is a hormone with broad implications for general health. This hormone has anti-inflammatory and antioxidant protective effects and has received particular attention due to the pandemic of COVID-19. This review examines materials on the role of microbial symbiosis in COVID-19 and the effect of microbiota on oxytocin. It opens new potential...
Cold water swimming is thought to provide mental and physical health benefits, although the details of the potential signalling pathways involved in the body have not yet been fully established. We know that brown fat/brown adipose tissue is important in thermogenesis, thereby possibly helping in training the body to adapt to cold stimuli. As a res...
Diagnostic pitfalls have been widely documented on atypical naevi, a group of pigmented lesions that occupy a grey portion between benign and malignant variants. As malignant melanoma is associated with a high mortality rate it is vital we have a reliable diagnostic testing method for these challenging lesions. A pilot study was proposed using dual...
A convincing cure for COVID-19 remains elusive, but beyond the horizon looms long-COVID. However, here, we propose a treatment: oxytocin. In this hypothesis paper we provide an under-lying mechanism for long COVID: the oxytocin neuron could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin. It is postulated that the reduction in p...
Are Covid-19 GI symptoms due to Oxytocin dysfunction?
Diabetes is a comorbidity associated with an increased risk of severe COVID-19. Gliptins are anti-diabetic drugs that inhibit dipeptidyl peptidase-4 (DPP4) and they have been proposed as a possible treatment for COVID-19 patients with and without diabetes due to their immunomodulatory properties. Oxytocin has also been proposed as a treatment for C...
1. Introduction
2. UK COVID-19 Therapeutics Advisory Panel response
3. Early proposal for oxytocin as a treatment for COVID-19
1. Introduction.
This is a request for help. I have submitted the following early proposal to the UK COVID-19 Therapeutics Advisory Panel. It was put on hold as can be seen by abstracts from the email received by me.
O...
See published version:
https://www.researchgate.net/publication/350855923_Melanocytic_lesions_A_pilot_study_using_dual_HMB-45Ki67_staining_with_a_new_depth_measurement_to_aid_diagnosis
With more than 72 million worldwide recorded cases of COVID-19 so far in 2020, 1.2 million deaths and more than 43 million people recovering from the virus, there a huge risk of further viral spread and mortalities, as well as severe health issues emerging in many survivors. This paper explores the COVID-19 infection mechanism and pathology from a...
With more than 72 million worldwide recorded cases of COVID-19 so far in 2020, 1.2 million deaths and more than 43 million people recovering from the virus, there a huge risk of further viral spread and mortalities, as well as severe health issues emerging in many survivors. This paper explores the COVID-19 infection mechanism and pathology from a...
Available free at the link above:
DOI 10.1016/j.mehy.2020.110360
Or here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657032/
After comparing the morbidity patterns of COViD-19 infections, variations of oxytocin levels and some properties of the neurohormone oxytocin, the authors put forward their hypothesis that oxytocin might constitute a safe, inexpensive and readily available treatment for this disease.
Cholecystitis can result in complications if not completely treated. These include gallbladder empyema, perforation and cholecystoenteric fistula.
We report the first incidence of cholecystitis resulting in a gallstone fistula with a gastric duplication cyst. A 71 year old patient presented with generalised peritonism that was worst in the epigastr...
Questions
Questions (9)
Does anyone know if oxytocin can be measured in body fluids (specifically saliva) using Fourier-transform infrared spectroscopy?
Thanks
Phuoc-Tan
This paper below says that there is interaction between oxytocin and heparin.
However the paper is very chemistry based and I do not understand it.
These phrases were of interest:
"This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-O- and N-sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de-N-sulfation is a traditional method for decreasing the anticoagulation properties of heparin. "
My question is,
does oxytocin increase the anticoagulant properties of heparin?
i.e. does having low oxytocin mean one is more likely to clot?
Thank you.
Phuoc-Tan
The interaction between oxytocin and heparin
Einat Schnur and Timothy Robert Rudd
DOI: 10.1039/D0RA04204H
Abstract
Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides. The latter oligosaccharides were chosen as they represent sequences found within the polysaccharide dalteparin. Furthermore, the carbohydrate chemical space was investigated by comparing the interaction between OXT and four chemically derivatived heparin hexasaccharides; I2S-A6SNS (DP6), I2OH-A6SNS (DP6-2OH, de-2-O-sulfated hexasaccharide), I2S-A6OHNS (DP6-6OH, de-6-O-sulfated hexasaccharide) and I2S-A6SNAc (DP6-NAc, de-N-sulfated hexasaccharide). The interactions between the peptide and oligosaccharides were studied using a series of 13C–1H and 15N–1H HSQC NMR experiments, at a range of temperatures. This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-O- and N-sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de-N-sulfation is a traditional method for decreasing the anticoagulation properties of heparin. Furthermore, low temperature experiments of the OXT[thin space (1/6-em)]:[thin space (1/6-em)]FP complex indicate that hydrogen-bonding is very important for the interaction between the peptide and oligosaccharide.
Does anyone know if oxytocin and bradykinin (both nonapeptides) can mutually inhibit each others receptors?
It seems that bradykinin is able to inhibit oxytocin and vasopressin in toads and rats (see below), so possibly in human too.
Thank you for your help.
Phuoc-Tan
Inhibition of the permeability response to vasopressin and oxytocin in the toad bladder: Effects of bradykinin, kallidin, eledoisin, and physalaemin
M R Furtado
PMID: 24174237 DOI: 10.1007/BF02431969
Receptor-binding characteristics and contractile responsiveness of the myometrium following prolonged infusion of bradykinin and oxytocin in rats
T. Engstrom, A. Atke, and H. Vilhardt
Is there a form of oxytocin which has the disulfide bond reduced to two thiols?
(Further to my earlier question, I have learnt a bit more about linear oxytocin).
This is not the linear oxytocin which has a break at Tyr-Cys but retains the disulfide bond.
If there is a linear type oxytocin with two thiols could this function like glutathione in redox reactions. Could this linear form be oxidised back to cyclic oxytocin (with a disulfide bond)?
Oxytocin is known to be an antioxidant, could this be part of the mechanism?
Can it partner with glutathione and vitamin C?
I would be grateful for any thoughts.
Phuoc-Tan
This is a question regarding oxytocin and Redox reactions.
Cyclic oxytocin has a disulfide bond. As far as I understand this is the oxidised form.
Linear oxytocin has two thiols. As far as I understand this is the reduced form.
(Update: Does the current known linear oxytocin still have a disulfide bond because it is cleaved at Tyr-Cys?
Does this mean that reduction would lead to a disulfide break which would essentially form a new type of oxytocin: linear-thiol-oxytocin?)
Can nitric oxide oxidise linear oxytocin to form cyclic oxytocin in the blood?
Thank you for any answers.
Phuoc-Tan
Could oxytocin be transported intracellularly via caveolae and RAGE?
Could this be how oxytocin affects mitochondria?
RAGE transports oxytocin across the blood brain barrier (Yamamoto) via an intracellular mechanism.
RAGE appears to be present within caveolae (Lisanti).
Caveolae appear to interact with mitochondria (Foster).
Some GPCRs have been identified in mitochondria (Bordt); does anyone know if oxytocin receptors have been identified in mitochondria?
Is it reasonable to hypothesise that oxytocin could effect mitochondria via caveolae and RAGE?
Thank you.
Phuoc-Tan
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Refs
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RAGE regulates oxytocin transport into the brain
Yasuhiko Yamamoto & Haruhiro Higashida
Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease.
Michael P Lisanti
The caveolar-mitochondrial interface: regulation of cellular metabolism in physiology and pathophysiology
Cerrone R. Foster
Bordt EA, Smith CJ, Demarest TG, Bilbo SD, Kingsbury MA. Mitochondria, Oxytocin, and Vasopressin: Unfolding the Inflammatory Protein Response. Neurotox Res. 2019 Aug;36(2):239-256. doi: 10.1007/s12640-018-9962-7. Epub 2018 Sep 27. PMID: 30259418; PMCID: PMC7416501.
Can we reduce minimum SOCIAL DISTANCE and TRANSMISSION RATE of COVID-19 by breathing through our nose because of NITRIC OXIDE which is ANTIVIRAL?
1. Nitric oxide is produced in the paranasal sinuses (a, b).
2. Nitric oxide is released into the nose when we breath through the nose rather than the mouth.
3. Nitric oxide is antiviral (c, d) and increases oxygenation (e).
4. Humming is beneficial because it can increase nitric oxide by around 15 times (f).
References
a) Nitric Oxide and the Paranasal Sinuses
Jon O. Lundberg
b) High Nitric Oxide Production in Human Paranasal Sinuses
J O Lundberg
c) Role of Nasal Nitric Oxide in the Resolution of Experimental Rhinovirus Infection
Scherer P Sanders
d) Does Nitric Oxide Play a Critical Role in Viral Infections?
Carol Shoshkes Reiss
e) Inhaled Nitric Oxide to Improve Oxygenation for Safe Critical Care Transport of Adults With Severe Hypoxemia
Nicholas R. Teman
f) Humming Greatly Increases Nasal Nitric Oxide
Eddie Weitzberg
