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

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 an incredibly complex pathophysiology due to the vast number of unique toxins/proteins found in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a group I 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 was completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 M, while it is partially potentiated by calcium chloride. Molecular docking studies demonstrate 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

Dynamic Mechanical Analysis of Bio-Based and Synthetic Petroleum Based Polymer Foams with Powder Type Organic Filler at Prolonged Ultra-Violet Exposure

Wood powder filler that have been added in the bio-based and epoxy polymer foams can be proved that it have ability to strengthen the structure of polymer foams. In this study, ‘Meranti’ type wood filler has been used as the filler. This study was developed to observe the pore size of each sample when expose to different hours of UV irradiation exposure using Optical Microscopy (OM). This study was also to compare the mechanical properties of every sample with different ratio filler of 0 wt%, 5 wt%, 10 wt%, 15wt% and 20 wt% at different hours of UV irradiation exposure which is 0 hour until 6,000 hours with increment of 2,000 hours. The testing was run by DMA Q800 TA machine. The samples that have 40 x 10 x 5 mm size were clamped in the machine to get the result of their mechanical properties. From the DMA testing, the results will show the value of tan delta, loss modulus and storage modulus. The value of tan delta shows that higher ratio filler will give the high value of tan delta. The epoxy polymer foams with powder filler have the highest value of tan delta compare to bio-based polymer foams. It proves that the higher filler ratio, the lower value of tan delta can be recorded.  The result of storage and loss modulus was found to increase as the more filler ratio filler in the polymer foams. The higher the loss modulus and storage modulus, the lower the temperature. Bio-based polymer foams with high powder filler ratio can dissipate more energy as energy are lost as heat during UV irradiation exposure

Dynamic Mechanical Analysis of Synthetic epoxy (E) and Bio-epoxy Polymer Foam Integrated with Wood Filler Under 8000 hours Exposure to UV Irradiation

The  most  common  sustainable  solution  for  polyurethane  (PU)  materials  is  their  production  using renewable resources reducing the dependency on the consumption of petroleum-based oil products. This research presents results from an experimental study on the dynamic mechanical and viscoelastic properties such as storage modulus, E', loss modulus, E'' and damping coefficient, tan δ of syntactic epoxy (E) and bio-epoxy polymer foam loading with different ratio of flakes and powder filler 0, 5, 10, 15 and 20 %wt after exposed to UV irradiation for 8000  h.  Dynamic  mechanical  analysis  (DMA)  of  the  blended  were  performed  over  a  temperature  range  of  25–180°C for (E) and (B) polymer foam  under frequency of 1 Hz. The results demonstrated that the E20L specimen with the highest filler ratio gives the maximum storage modulus and loss modulus value (0.3125 MPa), (0.0625 MPa) respectively among other filler ratio due to bonding between foam and filler resulting in increased viscosity of the synthetic-epoxy PUs foam. Among  others,  the  bio-epoxy  PUs  foam  (B5P)  has  the  highest  storage  value (3.956 MPa) and loss modulus (17.213 MPa) indicating that bio-epoxy PU foams can dissipate energy faster than synthetic-epoxy  polymer  foams.  TG analysis  showed  that  the  synthetic  epoxy  (E)  polymer  foam  had higher  Tg value and E5L (1.2) archived  the highest value compared to the bio-epoxy foams which had much less repeatable results due to the less homogeneous structure of polyols.compulsory

Russell's viper envenomation induces rectus sheath haematoma

Snakebite envenomation causes systemic and local manifestations, which result from the individual or synergistic actions of multiple venom components. The pathological hallmarks of medically important venomous snakes such as the Indian Russell's viper (Daboia russelii) are well known. Envenomation by Russell’s viper is typically characterised by coagulopathies, muscular damage, nephrotoxicity, and neurotoxicity. However, recent reports have revealed several unusual complications that provide a better understanding of Russell’s viper envenomation effects. To further strengthen this, here, we report a case of Russell's viper bite that induced acute abdominal pain, which was intensified on day two and conservatively treated under medical supervision. Both Fothergill and Carnett signs were positive for this patient. An ultrasound imaging revealed a dissimilar dense mass, and the abdominal computed tomography scan confirmed rectus sheath haematoma. The clinical management involved the administration of polyvalent antivenom, packed red blood cells, fresh frozen plasma, and platelets. The patient recovered gradually and was discharged from the hospital eight days after the bite. Overall, this case presentation shares an uncommon experience and adds new insights into the complex series of rare pathological events associated with Russell's viper bites in India. The scientific documentation of relatively infrequent entities based on an ongoing living assessment of medical experiences, for example, this rectus sheath haematoma, constitutes valuable guidance for an adequate diagnosis and timely treatment. Essential awareness among clinicians and further research on understanding the molecular relationship between Russell’s viper venom and rectus sheath haematoma will improve patient outcomes and understanding of this condition, respectively

Renewable Polymer/ Thermoplastics Polyethylene Blended with Enhanced Mechanical and UV Stability Properties

Blends of Renewable Polymer (RP) and thermoplastic polyethylene (LDPE and HDPE) may contribute to make recycling more economically attractive. In this study, the monomer is mixed with flexible isocynate as a crosslinker, these mixture is called Renewable Polymer. Renewable polymers are mixed in a Low-density polyethylene (LDPE) and High-density polyethylene (HDPE) with a ratio of 5%, 10%, 15%, 20%, 25% and 30%. The aim of this work to make LDPE/RP and HDPE/RP blends injected via injection molding and to evaluate their mechanical properties via tensile test. Accelerated weathering test up for 500 hours, 1000 hours, 1500 hours, 2000 hours, 2500 hours and 3000 hours. The blends yielded tensile strength and maximum elongation at break curves very dependent on their composition, especially regarding the presence of necking. The tensile strength increase at 500 hours, while maximum elongation at break were found to decreased with increase of UV irradiation hours. In conclusion, RP content and UV irradiation time play significant roles in controlling mechanical properties of the RP-blended with LDPE and HDPE synthetic polymer, thus providing the opportunity to modulate polymer properties

Mechanical Properties of Renewable Polymer with Thermoplastics Endurance to Ultraviolet irradiation Exposure

At present the disposal of waste tyre rubber (WTR) has become a major waste management problem in the world. Therefore in this study, polymer blended based on Polyethylene which is Low Density Polyethylene (LDPE) or High Density Polyethylene (HDPE), with Renewable Polymer (RP) and waste tyre rubber (WTR) is prepared via injection molding. Blended polymer such as LDPE/RP/WTR and HDPE/RP/WTR is known as LRT and HRT respectively. The preparation of polymer blend steps start with the preparation of RP. The RP is prepared by crosslinking the renewable monomer with Polymethane Polyphenyl Isocyanate (MDI) at composition ratio of 1:0.5. The second steps involved by adding 10 gm of liquid RP prepared earlier on with fixed amount of LDPE and HDPE of 100 gm. Then the blended LDPE/RP or HDPE/RP namely as LR or HR respectively is further added with WTR with different percentages ratio of 5 %, 10 % and 15 %. The manually blended polymer mixture and filler is then melt mixing using injection moulding to fabricate the tensile specimen for mechanical tensile test and physical determination such as density, distribution of WTR in polymer blend and surface fracture morphology using scanning electron microscope. The samples were then exposed to UV irradiation exposure in UV Accelerated Weathering for 500, 1000, 1500, 2000, 2500 and 3000 hours to evaluate the photostability of the polymer blends. The optimum amount of WTR ratio composition is at 5 % for both LRT and HRT blends which indicate the stability of polymer blends towards UV irradiation exposure at 1000 hours

Mechanical Properties of Renewable Polymer with Thermoplastics Endurance to Ultraviolet irradiation Exposure

At present the disposal of waste tyre rubber (WTR) has become a major waste management problem in the world. Therefore in this study, polymer blended based on Polyethylene which is Low Density Polyethylene (LDPE) or High Density Polyethylene (HDPE), with Renewable Polymer (RP) and waste tyre rubber (WTR) is prepared via injection molding. Blended polymer such as LDPE/RP/WTR and HDPE/RP/WTR is known as LRT and HRT respectively. The preparation of polymer blend steps start with the preparation of RP. The RP is prepared by crosslinking the renewable monomer with Polymethane Polyphenyl Isocyanate (MDI) at composition ratio of 1:0.5. The second steps involved by adding 10 gm of liquid RP prepared earlier on with fixed amount of LDPE and HDPE of 100 gm. Then the blended LDPE/RP or HDPE/RP namely as LR or HR respectively is further added with WTR with different percentages ratio of 5 %, 10 % and 15 %. The manually blended polymer mixture and filler is then melt mixing using injection moulding to fabricate the tensile specimen for mechanical tensile test and physical determination such as density, distribution of WTR in polymer blend and surface fracture morphology using scanning electron microscope. The samples were then exposed to UV irradiation exposure in UV Accelerated Weathering for 500, 1000, 1500, 2000, 2500 and 3000 hours to evaluate the photostability of the polymer blends. The optimum amount of WTR ratio composition is at 5 % for both LRT and HRT blends which indicate the stability of polymer blends towards UV irradiation exposure at 1000 hours

Multifaceted community health education programs as powerful tools to mitigate snakebite-induced deaths, disabilities, and socioeconomic burden

Snakebite envenoming (SBE) predominantly affects rural impoverished communities that have limited access to immediate healthcare. These communities often hold numerous myths/misbeliefs about snakes and SBE. Moreover, healthcare professionals who practice in rural regions often work in unstable situations with limited medical infrastructure and therefore, lack sufficient knowledge/experience and confidence in the clinical management of SBE. Due to the lack of reliable statistics on the true burden of SBE, developing health policies for this condition by relevant authorities may be difficult. Hence, it is critical to improve awareness about SBE among rural communities, healthcare professionals and health authorities using robust multifaceted community health education approaches. Here, we describe the design, development, implementation, and impact of distinctive community health education approaches that we used in India and Brazil. A wide range of educational tools including information leaflets, posters, pocket guides, learning materials for healthcare professionals and short/ long video documentaries were developed in local languages and used to engage with target communities through direct assemblies as well as mass/traditional and social media. Notably, we used diverse methods to determine the impact of our programs in improving awareness, treatment-seeking behaviour, and clinical practice. The people-centred approaches that we used were inclusive and highly impactful in instigating fundamental changes in the management of SBE among rural communities. The resources and approaches presented in this article can be easily adapted for wider use in other countries in order to collectively reduce SBEinduced deaths, disabilities and socioeconomic ramifications

Neutrophil gelatinase-associated lipocalin acts as a robust early diagnostic marker for renal replacement therapy in patients with Russell’s viper bite-induced acute kidney injuries

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 hours to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 hours timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase-associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 hours in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 hours to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies

The effectiveness of antibiotics in managing bacterial infections on bite sites following snakebite envenomation

Snakebite envenomation (SBE) is a life-threatening medical emergency with a high mortality rate. Common secondary complications following SBE such as wound infections are significant due to their impact on worsening local tissue damage and causing systemic infection. Antivenoms are not effective to treat wound infections following SBE. Moreover, in several rural clinical settings, broad-spectrum antibiotics are often used without clear guidelines or based on limited laborato-ry data resulting in undesirable side effects and exacerbated treatment costs. Therefore, robust antibiotic strategies should be developed to tackle this critical issue. Currently, there is limited information available on bacterial profiles of SBE-induced infections and antibiotic susceptibil-ity. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensi-tivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining bacterial profiles of SBE victims with a specific focus on Russell’s viper enven-omation. The most frequently found bacteria at the bites of SBE victims were Staphylococcus au-reus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem and amikacin were some of the most effective antibiotics for commonly grown bacte-ria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclav, cefixime and tetracyclin were the least effective antibiotics for common bacteria found in wound swabs of SBE victims. These data provide robust guidance for infection management following SBE and offer useful insights to aid in designing effective treatment protocols for SBE with serious wound infections in rural areas where laboratory facilities may not be readily available