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Prof. Sakthivel Vaiyapuri
University of Reading, UK

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0 Venom
0 platelets
0 Snakebite antivenom public health
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Symposium
Published: 25 March 2021 in PLOS Neglected Tropical Diseases
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Following a bite from a juvenile Russell’s viper (Daboia russelii), a priapism (painful erection) developed rapidly in a 16-year-old male and only subsided after administration of antivenom 3 hours later. Potential mechanisms for this snakebite-induced priapism are unclear but likely due to venom toxins causing nitric oxide (NO) release and subsequent vasodilation of endothelium in the corpus cavernosum, although the possible involvement of other mechanisms cannot be ruled out. We strongly believe that this unusual case report may lead to further scientific research in order to improve the clinical understanding of the pathophysiology of envenomation due to Russell’s viper bites. Although it is too early to speculate, further research may also discover the possibilities of developing venom-based candidate molecules to treat sexual dysfunction in males and females.

ACS Style

Subramanian Senthilkumaran; Harry F. Williams; Ketan Patel; Steven A. Trim; Ponniah Thirumalaikolundusubramanian; Sakthivel Vaiyapuri. Priapism following a juvenile Russell’s viper bite: An unusual case report. PLOS Neglected Tropical Diseases 2021, 15, e0009242 .

AMA Style

Subramanian Senthilkumaran, Harry F. Williams, Ketan Patel, Steven A. Trim, Ponniah Thirumalaikolundusubramanian, Sakthivel Vaiyapuri. Priapism following a juvenile Russell’s viper bite: An unusual case report. PLOS Neglected Tropical Diseases. 2021; 15 (3):e0009242.

Chicago/Turabian Style

Subramanian Senthilkumaran; Harry F. Williams; Ketan Patel; Steven A. Trim; Ponniah Thirumalaikolundusubramanian; Sakthivel Vaiyapuri. 2021. "Priapism following a juvenile Russell’s viper bite: An unusual case report." PLOS Neglected Tropical Diseases 15, no. 3: e0009242.

Journal article
Published: 21 January 2021 in F1000Research
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The ABO blood type has been reported to be associated with several diseases such as hepatitis and malaria. Recently, some studies have reported that people with O blood type are protected against COVID-19, while people with A blood type are more susceptible to contract this disease. Here, we analysed data from 5668 COVID-19 patients along with the same number of control samples in a study population in Iraq. Our analysis confirms that people with O blood type are protected partially against COVID-19. Notably, we demonstrate that people with RhD- are more susceptible to contract COVID-19 than people with RhD+ blood type. The blood types are associated with some clinical symptoms such as headache and asthenia of COVID-19, but there is no association with other symptoms. There is no association between blood types and deaths among COVID-19 patients. This study suggests that in addition to ABO, RhD blood type influences the susceptibility to contract COVID-19. Overall, we conclude that susceptibility/protection against COVID-19 may not be determined based only on blood types among the global population as this might vary based on a number of other factors such as ethnicity, geographical locations, occupation and the level of exposure to infected people.

ACS Style

Khalid R Majeed; Dhurgham Al-Fahad; Hayder H Jalood; Haider A Hantosh; Mrtatha K Ali; Sumiktsal Sakthivel; Harry F Williams; Jonathan M Gibbins; Ketan Patel; M. Fazil Baksh; Sakthivel Vaiyapuri. RhD blood type significantly influences susceptibility to contract COVID-19 among a study population in Iraq. F1000Research 2021, 10, 38 .

AMA Style

Khalid R Majeed, Dhurgham Al-Fahad, Hayder H Jalood, Haider A Hantosh, Mrtatha K Ali, Sumiktsal Sakthivel, Harry F Williams, Jonathan M Gibbins, Ketan Patel, M. Fazil Baksh, Sakthivel Vaiyapuri. RhD blood type significantly influences susceptibility to contract COVID-19 among a study population in Iraq. F1000Research. 2021; 10 ():38.

Chicago/Turabian Style

Khalid R Majeed; Dhurgham Al-Fahad; Hayder H Jalood; Haider A Hantosh; Mrtatha K Ali; Sumiktsal Sakthivel; Harry F Williams; Jonathan M Gibbins; Ketan Patel; M. Fazil Baksh; Sakthivel Vaiyapuri. 2021. "RhD blood type significantly influences susceptibility to contract COVID-19 among a study population in Iraq." F1000Research 10, no. : 38.

Research article
Published: 31 December 2020 in PLOS Neglected Tropical Diseases
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The lack of public awareness surrounding the dangers of snakebite envenomation (SBE) is one of the most critical factors contributing to SBE-induced complications, and subsequently exacerbating the number of deaths and disabilities resulting from SBE. In this study, we deployed a multifaceted community education programme to educate students, healthcare professionals and members of the public in rural areas of Tamil Nadu, India about the dangers of SBE, appropriate first aid measures and the ‘do’s and don’ts’ following a snakebite. An assessment of prior knowledge within these communities identified several misconceptions concerning snakes and SBE. Using a combination of direct engagement (estimated to reach over 200,000 people), information leaflets (200,000 distributed), posters, video documentaries, media and social media (>2.8 million engagements), over the course of one year (January to December 2019) we reached over 3 million people in rural Tamil Nadu (around 8% of population). Evaluation of community-based assemblies indicated that at least 90% of attendees were able to recall the key messages at the end of the events, and at least 85% were able to recall the key messages even after 12 months. Due to high demand, a one-day symposium was organised to provide clinical knowledge and training on SBE to 250 healthcare professionals in rural Tamil Nadu. Notably, an assessment of patient data (291 victims) collected from a snakebite referral hospital over the same 12-month period (2019) indicated that arrival time at hospital following a snakebite was significantly faster and the effective first aid measures were administered to patients who were aware of our activities compared to those that were not. Overall, our approach provides a framework on how to educate rural communities about the dangers of SBE and thereby, mitigate delayed SBE treatment leading to an overall reduction in SBE-induced mortality, morbidity, treatment costs and other socio-economic ramifications.

ACS Style

Stephen Paul Samuel; Soundararaj Chinnaraju; Harry F. Williams; Elamaran Pichamuthu; Mangaiyarkkarasai Subharao; Mohanraj Vaiyapuri; Sundhararajan Arumugam; Rajendran Vaiyapuri; M. Fazil Baksh; Ketan Patel; Steven A. Trim; Tracey E. Duncombe; Sakthivel Vaiyapuri. Venomous snakebites: Rapid action saves lives—A multifaceted community education programme increases awareness about snakes and snakebites among the rural population of Tamil Nadu, India. PLOS Neglected Tropical Diseases 2020, 14, e0008911 .

AMA Style

Stephen Paul Samuel, Soundararaj Chinnaraju, Harry F. Williams, Elamaran Pichamuthu, Mangaiyarkkarasai Subharao, Mohanraj Vaiyapuri, Sundhararajan Arumugam, Rajendran Vaiyapuri, M. Fazil Baksh, Ketan Patel, Steven A. Trim, Tracey E. Duncombe, Sakthivel Vaiyapuri. Venomous snakebites: Rapid action saves lives—A multifaceted community education programme increases awareness about snakes and snakebites among the rural population of Tamil Nadu, India. PLOS Neglected Tropical Diseases. 2020; 14 (12):e0008911.

Chicago/Turabian Style

Stephen Paul Samuel; Soundararaj Chinnaraju; Harry F. Williams; Elamaran Pichamuthu; Mangaiyarkkarasai Subharao; Mohanraj Vaiyapuri; Sundhararajan Arumugam; Rajendran Vaiyapuri; M. Fazil Baksh; Ketan Patel; Steven A. Trim; Tracey E. Duncombe; Sakthivel Vaiyapuri. 2020. "Venomous snakebites: Rapid action saves lives—A multifaceted community education programme increases awareness about snakes and snakebites among the rural population of Tamil Nadu, India." PLOS Neglected Tropical Diseases 14, no. 12: e0008911.

Review
Published: 06 December 2020 in Toxins
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Snakebite envenomation (SBE) is a high-priority, neglected tropical disease. This devastating occupational health hazard disproportionately affects rural farming communities in tropical countries. This is exacerbated by the distribution and densities of venomous snakes, incidence of encounters, and limited access to advanced healthcare, including antivenom. Before the development of antivenom, desperation and spiritual beliefs led patients to experiment with a wide range of traditional treatments. Many of these treatments still survive today, particularly in regions where access to healthcare is limited. Plants are a major source of bioactive molecules, including several lifesaving medications that are widely used to this day. However, much of the research into the use of traditional plant treatments for SBE are limited to preliminary analysis or have focused on techniques used to confirm antibody efficacy that are not suitable for non-antibody-containing treatments. Modern drugs are developed through a robust pharmaceutical drug discovery and development process, which applies as much to SBE as it does to any other disease. This review discusses specifically why research into ethnobotanical practices has failed to identify or develop a novel treatment for SBE and proposes specific approaches that should be considered in this area of research in the future.

ACS Style

Steven A. Trim; Carol M. Trim; Harry F. Williams; Sakthivel Vaiyapuri. The Failures of Ethnobotany and Phytomedicine in Delivering Novel Treatments for Snakebite Envenomation. Toxins 2020, 12, 774 .

AMA Style

Steven A. Trim, Carol M. Trim, Harry F. Williams, Sakthivel Vaiyapuri. The Failures of Ethnobotany and Phytomedicine in Delivering Novel Treatments for Snakebite Envenomation. Toxins. 2020; 12 (12):774.

Chicago/Turabian Style

Steven A. Trim; Carol M. Trim; Harry F. Williams; Sakthivel Vaiyapuri. 2020. "The Failures of Ethnobotany and Phytomedicine in Delivering Novel Treatments for Snakebite Envenomation." Toxins 12, no. 12: 774.

Journal article
Published: 29 November 2020 in Toxins
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Exotic snakebites (i.e. from non-native species) are a rare occurrence, but they present a unique challenge to clinicians treating these patients. Poison control centers are often contacted to assist in the management and care of these medical emergencies. In this study, we analyzed case records of the two Pennsylvania poison control centers from 2004 to 2018 to describe clinical features reported as a result of exotic snakebite envenomation. For the 15-year period reviewed, 18 exotic snakebites were reported with effects ranging from mild local tissue injury to patients who were treated with mechanical ventilation due to respiratory failure. The mean age of the patients was 35 years and males accounted for 83% of the cases. Antivenom, the only specific treatment, was administered in seven of 18 patients within an average of four h of envenomation. The procurement of antivenom against these exotic species may require substantial logistical efforts due to limited stocking of this rarely used treatment. Newer, targeted, small molecule treatments that are being currently investigated may aid in the treatment of snakebites in general. However, people should be cautious when handling these exotic species, and clinicians should be aware of these bites and relevant clinical effects in order to manage these when reported.

ACS Style

Stephen W. Miller; Kevin C. Osterhoudt; Amanda S. Korenoski; Ketan Patel; Sakthivel Vaiyapuri. Exotic Snakebites Reported to Pennsylvania Poison Control Centers: Lessons Learned on the Demographics, Clinical Effects, and Treatment of These Cases. Toxins 2020, 12, 755 .

AMA Style

Stephen W. Miller, Kevin C. Osterhoudt, Amanda S. Korenoski, Ketan Patel, Sakthivel Vaiyapuri. Exotic Snakebites Reported to Pennsylvania Poison Control Centers: Lessons Learned on the Demographics, Clinical Effects, and Treatment of These Cases. Toxins. 2020; 12 (12):755.

Chicago/Turabian Style

Stephen W. Miller; Kevin C. Osterhoudt; Amanda S. Korenoski; Ketan Patel; Sakthivel Vaiyapuri. 2020. "Exotic Snakebites Reported to Pennsylvania Poison Control Centers: Lessons Learned on the Demographics, Clinical Effects, and Treatment of These Cases." Toxins 12, no. 12: 755.

Original article
Published: 09 October 2020 in Journal of Thrombosis and Haemostasis
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Background Due to the difficulties in acquiring large numbers of megakaryocytes, the impact of inflammatory responses on these cells and their ability to produce fully functional platelets under various pathological conditions has not been investigated in detail. Objectives The primary objective of this study is to develop and functionally characterise a novel megakaryocyte NF‐κB reporter cell line in order to determine the effects of various inflammatory molecules on megakaryocytes and their signalling pathways. Methods A Meg‐01‐NF‐κB‐GFP‐Luc (Meg‐01R) cell line was developed by inserting a reporter NF‐κB‐GFP‐Luc cassette into normal Meg‐01 cells to produce luciferase following activation of NF‐κB to enable easy detection of pro‐inflammatory and reparative signalling. Results and conclusions Meg‐01 and Meg‐01R cells have comparable characteristics including the expression of both GPIb and integrin β3. Meg‐01R cells responded to various inflammatory molecules as measured by NF‐κB‐dependent bioluminescence. For example, inflammatory molecules such as TNFα and Pam3CSK4 increased NF‐κB activity, whereas an antimicrobial peptide, LL37, reduced its activity. Meg‐01R cells were also found to be sensitive to inhibitors (IMD0354 and C87) of inflammatory pathways. Notably, Meg‐01R cells were able to respond to LPS (non‐ultrapure) although it was not able to react to ultrapure LPS due to the lack of sufficient TLR4 molecules on their surface. For the first time, we report the development and characterisation of a novel megakaryocyte NF‐κB reporter cell line (Meg‐01R) as a robust tool to study the inflammatory responses/signalling of megakaryocytes upon stimulation with a broad range of inflammatory molecules that can affect NF‐κB activity.

ACS Style

Thomas M. Vallance; Jonathan J. Sheard; Yiming Meng; Enrico C. Torre; Ketan Patel; Darius Widera; Sakthivel Vaiyapuri. Development and characterization of a novel, megakaryocyte NF‐κB reporter cell line for investigating inflammatory responses. Journal of Thrombosis and Haemostasis 2020, 19, 107 -120.

AMA Style

Thomas M. Vallance, Jonathan J. Sheard, Yiming Meng, Enrico C. Torre, Ketan Patel, Darius Widera, Sakthivel Vaiyapuri. Development and characterization of a novel, megakaryocyte NF‐κB reporter cell line for investigating inflammatory responses. Journal of Thrombosis and Haemostasis. 2020; 19 (1):107-120.

Chicago/Turabian Style

Thomas M. Vallance; Jonathan J. Sheard; Yiming Meng; Enrico C. Torre; Ketan Patel; Darius Widera; Sakthivel Vaiyapuri. 2020. "Development and characterization of a novel, megakaryocyte NF‐κB reporter cell line for investigating inflammatory responses." Journal of Thrombosis and Haemostasis 19, no. 1: 107-120.

Journal article
Published: 02 September 2020 in Biomolecules
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Platelet-associated complications including thrombosis, thrombocytopenia, and haemorrhage are commonly observed during various inflammatory diseases such as psoriasis. Although several mechanisms that may contribute to the dysfunction of platelets during inflammatory diseases have been reported, knowledge on the primary molecules/mechanisms that underpin platelet-associated complications in such conditions is not fully established. Here, we report the significance of the mouse antimicrobial cathelicidin, mouse cathelicidin-related antimicrobial peptide (mCRAMP) (an orthologue of LL37 in humans), on the modulation of platelet reactivity during psoriasis using Imiquimod-induced psoriasis in mice as an inflammatory disease model for psoriasis vulgaris in humans. The activation of platelets during psoriasis is increased as evidenced by the elevated levels of fibrinogen binding and P-selectin exposure on the surface of platelets, and the level of soluble P-selectin in the plasma of psoriatic mice. The skin and plasma of psoriatic mice displayed increased levels of mCRAMP. Moreover, the plasma of psoriatic mice augmented the activation of platelets obtained from healthy mice. The effect of mCRAMP is partially mediated through formyl peptide receptor 2/3 (Fpr2/3, the orthologue to human FPR2/ALX) in platelets as a significant reduction in their activation was observed when FPR2/ALX-selective inhibitors such as WRW4 or Fpr2/3-deficient mouse platelets were used in these assays. Since the level of antimicrobial cathelicidin is increased in numerous inflammatory diseases such as psoriasis, atherosclerosis, and inflammatory bowel disease, the results of this study point towards a critical role for antimicrobial cathelicidin and FPR2/ALX in the development of platelet-related complications in such diseases.

ACS Style

Maryam F. Salamah; Thomas M. Vallance; Xenia Kodji; Divyashree Ravishankar; Harry F. Williams; Susan D. Brain; Sakthivel Vaiyapuri. The Antimicrobial Cathelicidin CRAMP Augments Platelet Activation during Psoriasis in Mice. Biomolecules 2020, 10, 1267 .

AMA Style

Maryam F. Salamah, Thomas M. Vallance, Xenia Kodji, Divyashree Ravishankar, Harry F. Williams, Susan D. Brain, Sakthivel Vaiyapuri. The Antimicrobial Cathelicidin CRAMP Augments Platelet Activation during Psoriasis in Mice. Biomolecules. 2020; 10 (9):1267.

Chicago/Turabian Style

Maryam F. Salamah; Thomas M. Vallance; Xenia Kodji; Divyashree Ravishankar; Harry F. Williams; Susan D. Brain; Sakthivel Vaiyapuri. 2020. "The Antimicrobial Cathelicidin CRAMP Augments Platelet Activation during Psoriasis in Mice." Biomolecules 10, no. 9: 1267.

Communication
Published: 19 August 2020 in Toxins
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In the field of antivenom research, development, and manufacture, it is often advised to follow the World Health Organization’s (WHO) guidelines for the production, control, and regulation of snake antivenom immunoglobulins, which recommend the use of preincubation assays to assess the efficacy of snakebite therapeutics. In these assays, venom and antivenom are mixed and incubated prior to in vivo administration to rodents, which allows for a standardizable comparison of antivenoms with similar characteristics. However, these assays are not necessarily sufficient for therapeutics with significantly different pharmacological properties than antibody-based antivenoms, such as small molecule inhibitors, nanoparticles, and other modalities. To ensure that the in vivo therapeutic utility of completely novel toxin-neutralizing molecules with no history of use in envenoming therapy and variable pharmacokinetics is properly evaluated, such molecules must also be tested in preclinical rescue assays, where rodents are first challenged with appropriate doses of venoms or toxins, followed by the administration of neutralizing modalities after an appropriate time delay to better mimic the real-life scenarios faced by human snakebite victims. Such an approach takes the venom (or toxin) toxicokinetics, the drug pharmacokinetics, and the drug pharmacodynamics into consideration. If new modalities are only assessed in preincubation assays and not subjected to evaluation in rescue assays, the publication of neutralization data may unintentionally misrepresent the actual therapeutic efficacy and suitability of the modality being tested, and thus potentially misguide strategic decision making in the research and development of novel therapies for snakebite envenoming.

ACS Style

Cecilie Knudsen; Nicholas Casewell; Bruno Lomonte; José Gutiérrez; Sakthivel Vaiyapuri; Andreas Laustsen. Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins 2020, 12, 528 .

AMA Style

Cecilie Knudsen, Nicholas Casewell, Bruno Lomonte, José Gutiérrez, Sakthivel Vaiyapuri, Andreas Laustsen. Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins. 2020; 12 (9):528.

Chicago/Turabian Style

Cecilie Knudsen; Nicholas Casewell; Bruno Lomonte; José Gutiérrez; Sakthivel Vaiyapuri; Andreas Laustsen. 2020. "Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy." Toxins 12, no. 9: 528.

Journal article
Published: 22 June 2020
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Duchenne Muscular Dystrophy is a devastating disease caused by the absence of a functional rod-shaped cytoplasmic protein called dystrophin. Several avenues are being developed aimed to restore dystrophin expression in boys affected by this X-linked disease. However, its complete cure is likely to need combinational approaches which may include regimes aimed at restoring muscle mass. Augmenting muscle growth through the manipulation of the Myostatin/Activin signalling axis has received much attention. However, we have recently shown that while manipulation of this axis in wild type mice using the sActRIIB ligand trap indeed results in muscle growth, it also had a detrimental impact on the testis. Here we examined the impact of administering a powerful Myostatin/Activin antagonist in two mouse models of Duchenne Muscular Dystrophy. We report that whilst the impact on muscle growth was not always positive, both models showed attenuated testis development. Sperm number, motility and ultrastructure were significantly affected by the sActRIIB treatment. Our report suggests that interventions based on Myostatin/Activin should investigate off-target effects on tissues as well as muscle.

ACS Style

Danielle Vaughan; Oliver Kretz; Ali Alqallaf; Robert Mitchell; Jennie L Von Der Heide; Sakthivel Vaiyapuri; Antonios Matsakas; Arja Pasternack; Henry Collins-Hooper; Olli Ritvos; Randy Ballesteros; Tobias B. Huber; Helge Amthor; Abir Mukherjee; Ketan Patel. Diminution in sperm quantity and quality in mouse models of Duchenne Muscular Dystrophy induced by a myostatin-based muscle growth-promoting intervention. 2020, 30, 8904 .

AMA Style

Danielle Vaughan, Oliver Kretz, Ali Alqallaf, Robert Mitchell, Jennie L Von Der Heide, Sakthivel Vaiyapuri, Antonios Matsakas, Arja Pasternack, Henry Collins-Hooper, Olli Ritvos, Randy Ballesteros, Tobias B. Huber, Helge Amthor, Abir Mukherjee, Ketan Patel. Diminution in sperm quantity and quality in mouse models of Duchenne Muscular Dystrophy induced by a myostatin-based muscle growth-promoting intervention. . 2020; 30 (2):8904.

Chicago/Turabian Style

Danielle Vaughan; Oliver Kretz; Ali Alqallaf; Robert Mitchell; Jennie L Von Der Heide; Sakthivel Vaiyapuri; Antonios Matsakas; Arja Pasternack; Henry Collins-Hooper; Olli Ritvos; Randy Ballesteros; Tobias B. Huber; Helge Amthor; Abir Mukherjee; Ketan Patel. 2020. "Diminution in sperm quantity and quality in mouse models of Duchenne Muscular Dystrophy induced by a myostatin-based muscle growth-promoting intervention." 30, no. 2: 8904.

Journal article
Published: 09 May 2020 in Toxins
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Snakebite envenomation causes over 140,000 deaths every year, predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with incredibly complex pathophysiology due to the vast number of unique toxins/proteins present in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a Group I (PI) metalloprotease (CAMP-2) from the venom of the western diamondback rattlesnake, Crotalus atrox. Its sensitivity to matrix metalloprotease inhibitors (batimastat and marimastat) was established using specific in vitro experiments and in silico molecular docking analysis. CAMP-2 shows high sequence homology to atroxase from the venom of Crotalus atrox and exhibits collagenolytic, fibrinogenolytic and mild haemolytic activities. It exerts a mild inhibitory effect on agonist-induced platelet aggregation in the absence of plasma proteins. Its collagenolytic activity is completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 μM, while it is partially potentiated by calcium chloride. Molecular docking studies have demonstrated that batimastat and marimastat are able to bind strongly to the active site residues of CAMP-2. This study demonstrates the impact of matrix metalloprotease inhibitors in the modulation of a purified, Group I metalloprotease activities in comparison to the whole venom. By improving our understanding of snake venom metalloproteases and their sensitivity to small molecule inhibitors, we can begin to develop novel and improved treatment strategies for snakebites.

ACS Style

Harry J. Layfield; Harry F. Williams; Divyashree Ravishankar; Amita Mehmi; Medha Sonavane; Anika Salim; Rajendran Vaiyapuri; Karthik Lakshminarayanan; Thomas M. Vallance; Andrew B. Bicknell; Steven A. Trim; Ketan Patel; Sakthivel Vaiyapuri. Repurposing Cancer Drugs Batimastat and Marimastat to Inhibit the Activity of a Group I Metalloprotease from the Venom of the Western Diamondback Rattlesnake, Crotalus atrox. Toxins 2020, 12, 309 .

AMA Style

Harry J. Layfield, Harry F. Williams, Divyashree Ravishankar, Amita Mehmi, Medha Sonavane, Anika Salim, Rajendran Vaiyapuri, Karthik Lakshminarayanan, Thomas M. Vallance, Andrew B. Bicknell, Steven A. Trim, Ketan Patel, Sakthivel Vaiyapuri. Repurposing Cancer Drugs Batimastat and Marimastat to Inhibit the Activity of a Group I Metalloprotease from the Venom of the Western Diamondback Rattlesnake, Crotalus atrox. Toxins. 2020; 12 (5):309.

Chicago/Turabian Style

Harry J. Layfield; Harry F. Williams; Divyashree Ravishankar; Amita Mehmi; Medha Sonavane; Anika Salim; Rajendran Vaiyapuri; Karthik Lakshminarayanan; Thomas M. Vallance; Andrew B. Bicknell; Steven A. Trim; Ketan Patel; Sakthivel Vaiyapuri. 2020. "Repurposing Cancer Drugs Batimastat and Marimastat to Inhibit the Activity of a Group I Metalloprotease from the Venom of the Western Diamondback Rattlesnake, Crotalus atrox." Toxins 12, no. 5: 309.

Journal article
Published: 03 December 2019 in Scientific Reports
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Platelets are small circulating blood cells that play essential roles in the maintenance of haemostasis via blood clotting. However, they also play critical roles in the regulation of innate immune responses. Inflammatory receptors, specifically Toll-like receptor (TLR)-4, have been reported to modify platelet reactivity. A plethora of studies have reported controversial functions of TLR4 in the modulation of platelet function using various chemotypes and preparations of its ligand, lipopolysaccharide (LPS). The method of preparation of LPS may explain these discrepancies however this is not fully understood. Hence, to determine the impact of LPS on platelet activation, we used ultrapure preparations of LPS from Escherichia coli (LPSEC), Salmonella minnesota (LPSSM), and Rhodobacter sphaeroides (LPSRS) and examined their actions under diverse experimental conditions in human platelets. LPSEC did not affect platelet activation markers such as inside-out signalling to integrin αIIbβ3 or P-selectin exposure upon agonist-induced activation in platelet-rich plasma or whole blood whereas LPSSM and LPSRS inhibited platelet activation under specific conditions at supraphysiological concentrations. Overall, our data demonstrate that platelet activation is not largely influenced by any of the ultrapure LPS chemotypes used in this study on their own except under certain conditions.

ACS Style

Thomas M. Vallance; Divyashree Ravishankar; Dina A. I. Albadawi; Harry Layfield; Jonathan Sheard; Rajendran Vaiyapuri; Philip Dash; Ketan Patel; Darius Widera; Sakthivel Vaiyapuri. Effect of ultrapure lipopolysaccharides derived from diverse bacterial species on the modulation of platelet activation. Scientific Reports 2019, 9, 1 -12.

AMA Style

Thomas M. Vallance, Divyashree Ravishankar, Dina A. I. Albadawi, Harry Layfield, Jonathan Sheard, Rajendran Vaiyapuri, Philip Dash, Ketan Patel, Darius Widera, Sakthivel Vaiyapuri. Effect of ultrapure lipopolysaccharides derived from diverse bacterial species on the modulation of platelet activation. Scientific Reports. 2019; 9 (1):1-12.

Chicago/Turabian Style

Thomas M. Vallance; Divyashree Ravishankar; Dina A. I. Albadawi; Harry Layfield; Jonathan Sheard; Rajendran Vaiyapuri; Philip Dash; Ketan Patel; Darius Widera; Sakthivel Vaiyapuri. 2019. "Effect of ultrapure lipopolysaccharides derived from diverse bacterial species on the modulation of platelet activation." Scientific Reports 9, no. 1: 1-12.

Journal article
Published: 21 October 2019 in Experimental Cell Research
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Aberrant activation of signalling pathways has been postulated to promote age related changes in skeletal muscle. Cell signalling activation requires not only the expression of ligands and receptors but also an appropriate environment that facilitates their interaction. Here we first examined the expression of SULF1/SULF2 and members of RTK (receptor tyrosine kinase) and the Wnt family in skeletal muscle of normal and a mouse model of accelerated ageing. We show that SULF1/SULF2 and these signalling components, a feature of early muscle development are barely detectable in early postnatal muscle. Real time qPCR and immunocytochemical analysis showed gradual but progressive up-regulation of SULF1/SULF2 and RTK/Wnt proteins not only in the activated satellite cells but also on muscle fibres that gradually increased with age. Satellite cells on isolated muscle fibres showed spontaneous in vivo satellite cell activation and progressive reduction in proliferative potential and responsiveness to HGF (hepatocyte growth factor) and dysregulated myogenic differentiation with age. Finally, we show that SULF1/SULF2 and RTK/Wnt signalling components are expressed in progeric mouse muscles at earlier stage but their expression is attenuated by an intervention that promotes muscle repair and growth.

ACS Style

Ketan Patel; Biggy Simbi; Olli Ritvos; Sakthivel Vaiyapuri; Gurtej K. Dhoot. Dysregulated cell signalling and reduced satellite cell potential in ageing muscle. Experimental Cell Research 2019, 385, 111685 .

AMA Style

Ketan Patel, Biggy Simbi, Olli Ritvos, Sakthivel Vaiyapuri, Gurtej K. Dhoot. Dysregulated cell signalling and reduced satellite cell potential in ageing muscle. Experimental Cell Research. 2019; 385 (2):111685.

Chicago/Turabian Style

Ketan Patel; Biggy Simbi; Olli Ritvos; Sakthivel Vaiyapuri; Gurtej K. Dhoot. 2019. "Dysregulated cell signalling and reduced satellite cell potential in ageing muscle." Experimental Cell Research 385, no. 2: 111685.

Journal article
Published: 25 August 2019 in European Journal of Pharmacology
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Isorhapontigenin is a polyphenolic compound found in Chinese herbs and grapes. It is a methoxylated analogue of a stilbenoid, resveratrol, which is well-known for its various beneficial effects including anti-platelet activity. Isorhapontigenin possesses greater oral bioavailability than resveratrol and has also been identified to possess anti-cancer and anti-inflammatory properties. However, its effects on platelet function have not been reported previously. In this study, we report the effects of isorhapontigenin on the modulation of platelet function. Isorhapontigenin was found to selectively inhibit ADP-induced platelet aggregation with an IC50 of 1.85 μM although it displayed marginal inhibition on platelet aggregation induced by other platelet agonists at 100 μM. However, resveratrol exhibited weaker inhibition on ADP-induced platelet aggregation (IC50 > 100 μM) but inhibited collagen induced platelet aggregation at 50 μM and 100 μM. Isorhapontigenin also inhibited integrin αIIbβ3 mediated inside-out and outside-in signalling and dense granule secretion in ADP-induced platelet activation but interestingly, no effect was observed on α-granule secretion. Isorhapontigenin did not exert any cytotoxicity on platelets at the concentrations of up to 100 μM. Furthermore, it did not affect haemostasis in mice at the IC50 concentration (1.85 μM). In addition, the mechanistic studies demonstrated that isorhapontigenin increased cAMP levels and VASP phosphorylation at Ser157 and decreased Akt phosphorylation. This suggests that isorhapontigenin may interfere with cAMP and PI3K signalling pathways that are associated with the P2Y12 receptor. Molecular docking studies emphasised that isorhapontigenin has greater binding affinity to P2Y12 receptor than resveratrol. Our results demonstrate that isorhapontigenin has selective inhibitory effects on ADP-stimulated platelet activation possibly via P2Y12 receptor.

ACS Style

Divyashree Ravishankar; Dina A.I. Albadawi; Vishaant Chaggar; Pabitra H. Patra; Harry F. Williams; Maryam Salamah; Rajendran Vaiyapuri; Philip R. Dash; Ketan Patel; Kimberly A. Watson; Sakthivel Vaiyapuri. Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation. European Journal of Pharmacology 2019, 862, 172627 .

AMA Style

Divyashree Ravishankar, Dina A.I. Albadawi, Vishaant Chaggar, Pabitra H. Patra, Harry F. Williams, Maryam Salamah, Rajendran Vaiyapuri, Philip R. Dash, Ketan Patel, Kimberly A. Watson, Sakthivel Vaiyapuri. Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation. European Journal of Pharmacology. 2019; 862 ():172627.

Chicago/Turabian Style

Divyashree Ravishankar; Dina A.I. Albadawi; Vishaant Chaggar; Pabitra H. Patra; Harry F. Williams; Maryam Salamah; Rajendran Vaiyapuri; Philip R. Dash; Ketan Patel; Kimberly A. Watson; Sakthivel Vaiyapuri. 2019. "Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation." European Journal of Pharmacology 862, no. : 172627.

Review
Published: 25 June 2019 in International Journal of Molecular Sciences
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Cardiovascular diseases represent a major cause of mortality and morbidity in the world, and specifically, thrombotic conditions such as heart attacks and strokes are caused by unwarranted activation of platelets and subsequent formation of blood clots (thrombi) within the blood vessels during pathological circumstances. Therefore, platelets act as a primary therapeutic target to treat and prevent thrombotic conditions. Current treatments are limited due to intolerance, and they are associated with severe side effects such as bleeding complications. Hence, the development of novel therapeutic strategies for thrombotic diseases is an urgent priority. Flavonoids are naturally occurring plant-derived molecules that exert numerous beneficial effects in humans through modulating the functions of distinct cell types. However, naturally occurring flavonoids suffer from several issues such as poor solubility, lipophilicity, and bioavailability, which hinder their efficacy and potency. Despite these, flavonoids act as versatile templates for the design and synthesis of novel molecules for various therapeutic targets. Indeed, several synthetic flavonoids have recently been developed to improve their stability, bioavailability, and efficacy, including for the modulation of platelet function. Here, we provide insight into the actions of certain natural flavonoids along with the advantages of synthetic flavonoids in the modulation of platelet function, haemostasis, and thrombosis.

ACS Style

Thomas M. Vallance; Divyashree Ravishankar; Dina A. I. Albadawi; Helen M. I. Osborn; Sakthivel Vaiyapuri. Synthetic Flavonoids as Novel Modulators of Platelet Function and Thrombosis. International Journal of Molecular Sciences 2019, 20, 3106 .

AMA Style

Thomas M. Vallance, Divyashree Ravishankar, Dina A. I. Albadawi, Helen M. I. Osborn, Sakthivel Vaiyapuri. Synthetic Flavonoids as Novel Modulators of Platelet Function and Thrombosis. International Journal of Molecular Sciences. 2019; 20 (12):3106.

Chicago/Turabian Style

Thomas M. Vallance; Divyashree Ravishankar; Dina A. I. Albadawi; Helen M. I. Osborn; Sakthivel Vaiyapuri. 2019. "Synthetic Flavonoids as Novel Modulators of Platelet Function and Thrombosis." International Journal of Molecular Sciences 20, no. 12: 3106.

Review
Published: 20 June 2019 in Toxins
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Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA2 inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late to effectively treat SBE. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, with new treatments and diagnostics rapidly emerging. Here we critically review the urgent necessity for the development of diagnostic tools and improved therapeutics to mitigate the deaths and disabilities caused by SBE.

ACS Style

Harry F. Williams; Harry J. Layfield; Thomas Vallance; Ketan Patel; Andrew B. Bicknell; Steven A. Trim; Sakthivel Vaiyapuri. The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites. Toxins 2019, 11, 363 .

AMA Style

Harry F. Williams, Harry J. Layfield, Thomas Vallance, Ketan Patel, Andrew B. Bicknell, Steven A. Trim, Sakthivel Vaiyapuri. The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites. Toxins. 2019; 11 (6):363.

Chicago/Turabian Style

Harry F. Williams; Harry J. Layfield; Thomas Vallance; Ketan Patel; Andrew B. Bicknell; Steven A. Trim; Sakthivel Vaiyapuri. 2019. "The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites." Toxins 11, no. 6: 363.

Original article
Published: 29 April 2019 in Journal of Thrombosis and Haemostasis
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Essentials The role of formyl peptide receptor 1 (FPR1) and its ligand, fMLF, in the regulation of platelet function, hemostasis, and thrombosis is largely unknown. Fpr1-deficient mice and selective inhibitors for FPR1 were used to investigate the function of fMLF and FPR1 in platelets. N-formyl-methionyl-leucyl-phenylalanine primes platelet activation and augments thrombus formation, mainly through FPR1 in platelets. Formyl peptide receptor 1 plays a pivotal role in the regulation of platelet function. Formyl peptide receptors (FPRs) play pivotal roles in the regulation of innate immunity and host defense. The FPRs include three family members: FPR1, FPR2/ALX, and FPR3. The activation of FPR1 by its high-affinity ligand, N-formyl-methionyl-leucyl-phenylalanine (fMLF) (a bacterial chemoattractant peptide), triggers intracellular signaling in immune cells such as neutrophils and exacerbates inflammatory responses to accelerate the clearance of microbial infection. Notably, fMLF has been demonstrated to induce intracellular calcium mobilization and chemotaxis in platelets that are known to play significant roles in the regulation of innate immunity and inflammatory responses. Despite a plethora of research focused on the roles of FPR1 and its ligands such as fMLF on the modulation of immune responses, their impact on the regulation of hemostasis and thrombosis remains unexplored. To determine the effects of fMLF on the modulation of platelet reactivity, hemostasis, and thrombus formation. Selective inhibitors for FPR1 and Fpr1-deficient mice were used to determine the effects of fMLF and FPR1 on platelets using various platelet functional assays. N-formyl-methionyl-leucyl-phenylalanine primes platelet activation through inducing distinctive functions and enhances thrombus formation under arterial flow conditions. Moreover, FPR1 regulates normal platelet function as its deficiency in mouse or blockade in human platelets using a pharmacological inhibitor resulted in diminished agonist-induced platelet activation. Since FPR1 plays critical roles in numerous disease conditions, its influence on the modulation of platelet activation and thrombus formation may provide insights into the mechanisms that control platelet-mediated complications under diverse pathological settings.

ACS Style

Maryam F. Salamah; Divyashree Ravishankar; Rajendran Vaiyapuri; Leonardo A. Moraes; Ketan Patel; Mauro Perretti; Jonathan Gibbins; Sakthivel Vaiyapuri. The formyl peptide fMLF primes platelet activation and augments thrombus formation. Journal of Thrombosis and Haemostasis 2019, 17, 1120 -1133.

AMA Style

Maryam F. Salamah, Divyashree Ravishankar, Rajendran Vaiyapuri, Leonardo A. Moraes, Ketan Patel, Mauro Perretti, Jonathan Gibbins, Sakthivel Vaiyapuri. The formyl peptide fMLF primes platelet activation and augments thrombus formation. Journal of Thrombosis and Haemostasis. 2019; 17 (7):1120-1133.

Chicago/Turabian Style

Maryam F. Salamah; Divyashree Ravishankar; Rajendran Vaiyapuri; Leonardo A. Moraes; Ketan Patel; Mauro Perretti; Jonathan Gibbins; Sakthivel Vaiyapuri. 2019. "The formyl peptide fMLF primes platelet activation and augments thrombus formation." Journal of Thrombosis and Haemostasis 17, no. 7: 1120-1133.

Journal article
Published: 26 February 2019 in Scientific Reports
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The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma.

ACS Style

Saleh Omairi; Kwan-Leong Hau; Henry Collins-Hooper; Charlotte Scott; Sakthivel Vaiyapuri; Silvia Torelli; Federica Montanaro; Antonios Matsakas; Ketan Patel. Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres. Scientific Reports 2019, 9, 1 -12.

AMA Style

Saleh Omairi, Kwan-Leong Hau, Henry Collins-Hooper, Charlotte Scott, Sakthivel Vaiyapuri, Silvia Torelli, Federica Montanaro, Antonios Matsakas, Ketan Patel. Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres. Scientific Reports. 2019; 9 (1):1-12.

Chicago/Turabian Style

Saleh Omairi; Kwan-Leong Hau; Henry Collins-Hooper; Charlotte Scott; Sakthivel Vaiyapuri; Silvia Torelli; Federica Montanaro; Antonios Matsakas; Ketan Patel. 2019. "Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres." Scientific Reports 9, no. 1: 1-12.

Conference abstract
Published: 22 February 2019 in Toxicon
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ACS Style

Harry F. Williams; Ben A. Mellows; Robert Mitchell; Harry J. Layfield; Maryam Salamah; Rajendran Vaiyapuri; Andrew B. Bicknell; Henry Collins-Hooper; Ketan Patel; Sakthivel Vaiyapuri. Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. Toxicon 2019, 159, S13 -S14.

AMA Style

Harry F. Williams, Ben A. Mellows, Robert Mitchell, Harry J. Layfield, Maryam Salamah, Rajendran Vaiyapuri, Andrew B. Bicknell, Henry Collins-Hooper, Ketan Patel, Sakthivel Vaiyapuri. Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. Toxicon. 2019; 159 ():S13-S14.

Chicago/Turabian Style

Harry F. Williams; Ben A. Mellows; Robert Mitchell; Harry J. Layfield; Maryam Salamah; Rajendran Vaiyapuri; Andrew B. Bicknell; Henry Collins-Hooper; Ketan Patel; Sakthivel Vaiyapuri. 2019. "Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease." Toxicon 159, no. : S13-S14.

Research article
Published: 29 January 2019 in PLOS Neglected Tropical Diseases
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Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage. Snakebite is a major neglected tropical disease that affects thousands of people in the rural areas of developing countries. As well as the deaths, snakebites result in a significant number of disabilities including permanent loss of limbs that alter the lifestyle of the victims. Snake venom is a mixture of different proteins with diverse functions; one of these major protein groups present in viper venoms are metalloproteases that primarily induce muscle damage. The mechanisms behind the development of snakebite (metalloprotease)-induced permanent muscle damage are poorly studied. Here, we have purified a metalloprotease (CAMP) from the venom of the Western diamondback rattlesnake, and characterised its function in mice. To determine the actions of CAMP in the development of permanent muscle damage, it was injected into the muscle of mice in a parallel comparison with cardiotoxin I (from the venom of the Red spitting cobra). The effects of these proteins on muscle regeneration were analysed at 5 and 10 days after injection. The results demonstrate that through a combination of effects on the structural scaffolds surrounding the tissues, blood vessels and regeneration, CAMP significantly affects the muscles, thereby leading to permanent muscle damage.

ACS Style

Harry F. Williams; Ben A. Mellows; Robert Mitchell; Peggy Sfyri; Harry J. Layfield; Maryam Salamah; Rajendran Vaiyapuri; Henry Collins-Hooper; Andrew B. Bicknell; Antonios Matsakas; Ketan Patel; Sakthivel Vaiyapuri. Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. PLOS Neglected Tropical Diseases 2019, 13, e0007041 .

AMA Style

Harry F. Williams, Ben A. Mellows, Robert Mitchell, Peggy Sfyri, Harry J. Layfield, Maryam Salamah, Rajendran Vaiyapuri, Henry Collins-Hooper, Andrew B. Bicknell, Antonios Matsakas, Ketan Patel, Sakthivel Vaiyapuri. Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. PLOS Neglected Tropical Diseases. 2019; 13 (1):e0007041.

Chicago/Turabian Style

Harry F. Williams; Ben A. Mellows; Robert Mitchell; Peggy Sfyri; Harry J. Layfield; Maryam Salamah; Rajendran Vaiyapuri; Henry Collins-Hooper; Andrew B. Bicknell; Antonios Matsakas; Ketan Patel; Sakthivel Vaiyapuri. 2019. "Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease." PLOS Neglected Tropical Diseases 13, no. 1: e0007041.

Journal article
Published: 15 December 2018 in Toxins
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Snakebite envenomation is an affliction currently estimated to be killing upwards of 100,000 people annually. Snakebite is associated with a diverse pathophysiology due to the magnitude of variation in venom composition that is observed worldwide. The haemolytic (i.e., lysis of red blood cells) actions of snake venoms are well documented, although the direct impact of venoms on haemoglobin is not fully understood. Here we report on the varied ability of a multitude of snake venoms to oxidise haemoglobin into methaemoglobin. Moreover, our results demonstrate that the venom of an elapid, the black necked spitting cobra, Naja nigricollis, oxidises oxyhaemoglobin (Fe2+) into methaemoglobin (Fe3+) in a time- and concentration-dependent manner that is unparalleled within the 47 viper and elapid venoms evaluated. The treatment of venom with a reducing agent, dithiothreitol (DTT) is observed to potentiate this effect at higher concentrations, and the use of denatured venom demonstrates that this effect is dependent upon the heat-sensitive proteinaceous elements of the venom. Together, our results suggest that Naja nigricollis venom appears to promote methaemoglobin production to a degree that is rare within the Elapidae family, and this activity appears to be independent of proteolytic activities of venom components on haemoglobin.

ACS Style

Harry F. Williams; Paul Hayter; Divyashree Ravishankar; Anthony Baines; Harry J. Layfield; Lorraine Croucher; Catherine Wark; Andrew B. Bicknell; Steven Trim; Sakthivel Vaiyapuri. Impact of Naja nigricollis Venom on the Production of Methaemoglobin. Toxins 2018, 10, 539 .

AMA Style

Harry F. Williams, Paul Hayter, Divyashree Ravishankar, Anthony Baines, Harry J. Layfield, Lorraine Croucher, Catherine Wark, Andrew B. Bicknell, Steven Trim, Sakthivel Vaiyapuri. Impact of Naja nigricollis Venom on the Production of Methaemoglobin. Toxins. 2018; 10 (12):539.

Chicago/Turabian Style

Harry F. Williams; Paul Hayter; Divyashree Ravishankar; Anthony Baines; Harry J. Layfield; Lorraine Croucher; Catherine Wark; Andrew B. Bicknell; Steven Trim; Sakthivel Vaiyapuri. 2018. "Impact of Naja nigricollis Venom on the Production of Methaemoglobin." Toxins 10, no. 12: 539.