Hymenoptera Stings and the Acute Kidney Injury

Hymenoptera stings are a health concern. Apidae (bees), Vespidae (hornets, yellow jackets and wasps) and Formicidae (ants) are medically-important stinging insects under the order Hymenoptera. Clinical features from simple skin manifestations to severe and fatal organ injury are due to the hypersensitivity reactions and/ or the toxic effects of the venom inoculated. Here we discuss on Hymenoptera stings involving apids (honey bees) and vespids (wasps, hornets and yellow jackets) and their effect on renal function and associated morphological changes in the kidney. Despite the differences in venom composition and quantity released per sting in two insect groups, both lead to similar medical consequences, such as localised normal allergic reactions, mild to severe anaphylaxis and shock and multiple organ and tissue injury leading to multiple organ failure. Acute kidney injury (AKI) is one of the unusual complications of Hymenoptera stings and has the basis of both immune-mediated and toxic effects. Evidence has proven that supportive therapy along with the standard medication is very efficient in completely restoring the kidney function without any recurrence

Voltage-Gated Sodium Channel Modulation by a New Spider Toxin Ssp1a Isolated From an Australian Theraphosid

Given the important role of voltage-gated sodium (NaV) channel-modulating spider toxins in elucidating the function, pharmacology, and mechanism of action of therapeutically relevant NaV channels, we screened the venom from Australian theraphosid species against the human pain target hNaV1.7. Using assay-guided fractionation, we isolated a 33-residue inhibitor cystine knot (ICK) peptide (Ssp1a) belonging to the NaSpTx1 family. Recombinant Ssp1a (rSsp1a) inhibited neuronal hNaV subtypes with a rank order of potency hNaV1.7 > 1.6 > 1.2 > 1.3 > 1.1. rSsp1a inhibited hNaV1.7, hNaV1.2 and hNaV1.3 without significantly altering the voltage-dependence of activation, inactivation, or delay in recovery from inactivation. However, rSsp1a demonstrated voltage-dependent inhibition at hNaV1.7 and rSsp1a-bound hNaV1.7 opened at extreme depolarizations, suggesting rSsp1a likely interacted with voltage-sensing domain II (VSD II) of hNaV1.7 to trap the channel in its resting state. Nuclear magnetic resonance spectroscopy revealed key structural features of Ssp1a, including an amphipathic surface with hydrophobic and charged patches shown by docking studies to comprise the interacting surface. This study provides the basis for future structure-function studies to guide the development of subtype selective inhibitors

Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section

Background: Intrathecal morphine is commonly used for post caesarean analgesia. However, their use is frequently associated with the incidence of troublesome side effects such as nausea, vomiting and pruritus. Various mechanisms have been postulated for the opioid-induced pruritus, with a variety of medications with different mechanisms of actions formulated for the prevention and treatment. But, the results are inconsistent and hence the prevention and treatment of opioid-induced pruritus still remains a challenge. Ondansetron which is antiemetic, non-sedative and has no antianalgesic effect is an antagonist to 5-HT3 receptor, the receptor with which opioids interacts and imparts its effects. Ondansetron, thus, would be an attractive treatment strategy for both opioid-induced pruritus and post-operative nausea and vomiting. Methods: After the approval from institutional review committee and written consent received from the patient, 50 healthy parturients of ASA I and II physical status undergoing caesarean section under spinal anaesthesia were enrolled for the study. They were randomly categorized into placebo group (2 ml normal saline) and treatment group (2 ml of 4 mg ondansetron), each group containing 25 patients. Pruritus and post-operative nausea and vomiting scores were recorded up to 24 hours after the administration of intrathecal morphine. Statistical analysis was performed using chi-square test. Results: The incidence, severity and necessity of treatment for pruritus in the treatment group was significantly reduced compared to the placebo group (16% vs 88%). Similarly, the risk of post-operative nausea and vomiting in the treatment group was less compared to the placebo group (8% vs 56%). Conclusion: Prophylactic administration of ondansetron to parturients receiving intrathecal morphine for post-operative analgesia provides a significant reduction of intrathecal morphine-induced pruritus and nausea and vomiting

Spider knottin pharmacology at voltage-gated sodium channels and their potential to modulate pain pathways

Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain

Acute renal failure following multiple hornet stings

Hornet stings are medically important stings which can cause allergic manifestations and, in severe cases, may lead to the unusual complication of acute renal failure (ARF) and other systemic complications. ARF results from toxic or ischaemic acute tubular necrosis in a setting of haemolysis or rhabdomyolysis or both and acute allergic interstitial nephritis. Venom from hornet stings can also contribute to myocardial injury or liver impairment. Here, we report three cases of hornet stings leading to ARF. Case 1 and Case 3 recovered their renal function and body physiology after a 38-day and 15-day stay in the hospital, respectively, whereas Case 2 died. They were meticulously supported by haemodialysis along with the combination of various drug regimens