Indian Ornamental Tarantula (Poecilotheria regalis) Venom Affects Myoblast Function and Causes Skeletal Muscle Damage.

Envenomation by the Indian ornamental tarantula (Poecilotheria regalis) is medically relevant to humans, both in its native India and worldwide, where they are kept as pets. Muscle-related symptoms such as cramps and pain are commonly reported in humans following envenomation by this species. There is no specific treatment, including antivenom, for its envenomation. Moreover, the scientific knowledge of the impact of this venom on skeletal muscle function is highly limited. Therefore, we carried out this study to better understand the myotoxic properties of Poecilotheria regalis venom by determining its effects in cultured myoblasts and in the tibialis anterior muscle in mice. While there was no effect found on undifferentiated myoblasts, the venom affected differentiated multinucleated myotubes resulting in the reduction of fusion and atrophy of myotubes. Similarly, intramuscular administration of this venom in the tibialis anterior muscle in mice resulted in extensive muscle damage on day 5. However, by day 10, the regeneration was evident, and the regeneration process continued until day 20. Nevertheless, some tissue abnormalities including reduced dystrophin expression and microthrombi presence were observed on day 20. Overall, this study demonstrates the ability of this venom to induce significant muscle damage and affect its regeneration in the early stages. These data provide novel mechanistic insights into this venom-induced muscle damage and guide future studies to isolate and characterise individual toxic component(s) that induce muscle damage and their significance in developing better therapeutics.

Peripheral Arterial Thrombosis following Russell's Viper Bites.

Envenomings by Russell's viper ( Daboia russelii ), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A 2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.

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 laboratory 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 the bacterial profiles of SBE-induced infections and antibiotic susceptibility. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensitivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining the bacterial profiles of SBE victims with a specific focus on Russell's viper envenomation. The most frequently found bacteria in the bites of SBE victims were Staphylococcus aureus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem, and amikacin were some of the most effective antibiotics for commonly grown bacteria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclave, cefixime, and tetracyclin were the least effective antibiotics for common bacteria found in the 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.

Rapid development of a salivary calculus in submandibular gland and its potential causes in a young victim following Russell's viper bite.

Russell's viper bites are known to cause a range of haemotoxic, neurotoxic, myotoxic, cytotoxic and nephrotoxic complications. However, the impact of Russell's viper bites as well as bites from other venomous snakes on sialolithiasis has not been previously reported. Here, we present an interesting case where a Russell's viper bite induced the rapid development of a calculus in submandibular gland in a 10-year-old boy. Upon admission, the victim did not show any symptoms of swelling and/or pain around his oral cavity. He received antivenom treatment to normalise his coagulation parameters, however, on day three he developed swelling and extreme pain around his right mandibular region. An ultrasound investigation revealed the presence of a calculus in his submandibular gland, which was removed using a minor surgical procedure. The histopathological examination revealed this as a poorly calcified salivary calculus, which is composed of cell debris, mucopolysaccharides and lipids. The mechanisms behind its rapid development following a snakebite are unclear although this could be linked to excessive inflammation or modifications to the composition of saliva induced by venom toxins or other unknown factors. This report reveals an unusual complication induced by a Russell's viper bite and alerts clinicians who treat snakebites to be aware of such envenomation effects. Moreover, this will lead to novel research to explore the relationship between venom toxins and functions of salivary glands.

Splenic rupture and subsequent splenectomy in a young healthy victim following Russell's viper bite.

Splenic rupture and/or splenectomy is/are not uncommon in clinical arena. Here we present this case of extensive haemorrhage-induced splenic rupture which resulted in splenectomy in a young healthy male (who did not have any previous medical conditions) following a Russell's viper bite. He developed upper abdominal and shoulder pain on his left side along with hypotension and reduced level of haemoglobin on the third day following bite despite antivenom treatment. Following confirmation of splenic rupture and haemoperitoneum by ultrasound and computed tomography scans, an emergency splenectomy was performed using laparotomy. Although Russell's viper bites are known to induce bleeding complications, splenic rupture due to haemorrhage in spleen has not been previously reported. Russell's viper venom toxins such as metalloproteases, serine proteases and phospholipase A2 might have affected the vascular permeability resulting in excessive bleeding and increased pressure in the spleen leading to rupture. Further investigations are required to underpin the impact of snake venom toxins on the architecture and functions of spleen. However, the clinicians who treat snakebites should be aware of this type of rare complications so as to provide appropriate management for such victims.

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 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h 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 h 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 h 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.