Russell's Viper Envenomation Research Articles

Panhypopituitarism and Central Diabetes Insipidus Almost Three Decades After Russell's Viper Envenomation: A Remarkable Case Report and Literature Review.

Snakebite is a preventable yet often-neglected public health hazard with high chronic disability and mortality, mainly faced by rural communities in the tropics/subtropics. Endocrinological disorders following snakebite (especially Russell's viper in India) are notably underrecognized and can lead to remarkable morbidity, poor quality of life, and cardiovascular mortality. Anterior pituitary insufficiency has been the most common ailment following Russell's viper envenomation amid those endocrinological dysfunctions. On the contrary, the posterior pituitary and nearby hypothalamus mostly remain unharmed, so central diabetes insipidus is extremely rare following a viperid snakebite envenomation. The authors present a patient developing panhypopituitarism with evident spontaneous central diabetes insipidus 29 years after Russell's viper envenomation. Relevant investigations ruled out other possible etiologies, and he responded well to hormonal replacement therapy. Panhypopituitarism with concurrent central diabetes insipidus may occur following snakebite (especially in Russell's viper envenomation). Early recognition and proper management of these complications are quintessential to preventing further misdiagnosis, under-recognition, morbidity, impaired quality of life, and mortality.

Sodium oleate, arachidonate, and linoleate enhance fibrinogenolysis by Russell's viper venom proteinases and inhibit FXIIIa; a role for phospholipase A2 in venom induced consumption coagulopathy

Life-threatening symptoms produced by Russell's viper (RV, Daboia russelii) envenomation result largely from venom induced consumption coagulopathy (VICC). VICC is thought to be mediated to a large degree by venom serine and metalloproteinases, as well as by snake venom phospholipase A2 (svPLA2), the most abundant constituent of RV venom (RVV). The observation that the phenolic lipid anacardic acid markedly enhances proteolytic degradation of fibrinogen by RVV proteinases led us to characterize the chemical basis of this phenomenon with results indicating that svPLA2 products may be major contributors to VICC. ResultsOf the chemical analogs tested, the anionic detergents sodium dodecyl sulfate, sodium deoxycholate, N-lauryl sodium sarcosine, and the sodium salts of the fatty acids arachidonic, oleic and to a lesser extend linoleic acid were able to enhance fibrinogenolysis by RVV proteinases. Enhanced Fibrinogenolysis (EF) was observed with various venom size exclusion fractions containing different proteinases, and also with trypsin, indicating that conformational changes of the substrate and increased accessibility of otherwise cryptic cleavage sites are likely to be responsible for EF. In addition to enhancing fibrinogenolysis, sodium arachidonate and oleate were found to partially inhibit thrombin induced, factor XIIIa (FXIIIa) mediated ligation of fibrin chains. In clotting experiments with fresh blood RVV was found to disrupt normal coagulation, leading to small, partial clot formation, whereas RVV pretreated with the PLA2 inhibitor Varespladib induced rapid and complete clot formation (after 5 min) compared to blood alone. ConclusionThe observations that fatty acid anions and anionic detergents induce conformational changes that render fibrin(ogen) more susceptible to proteolysis by RVV proteinases and that RVV-PLA2 activity (which produces FFA) is required to render blood incoagulable in clotting experiments with RVV indicate a mechanism by which the activity of highly abundant RVV-PLA2 promotes degradation and depletion of fibrin(ogen) resulting in incoagulable blood seen following RVV envenomation (VICC).

Multiple Cerebral and Cerebellar Infarctions following Russell's Viper (Daboia Russelii) Envenomation - A Case Report

Ischemic stroke is a rare neurological complication following SriLankan Russell's viper envenomation. We report a case of a 44-year-old person, who developed multiple cerebral and cerebellar infarctions following SriLankan Russell's viper envenomation. The patient developed both local and systemic envenomation and was treated with Snake Venom Anti-Serum I.P. (VinsBioproducts Ltd). On day six, this patient developed left-sided hemiparesis. CT scan of the brain showed bilateral cerebellar, bilateral occipital, and right-sideparietal lobe infarctions.

Proteomics and antivenom immunoprofiling of Russell's viper (Daboia siamensis) venoms from Thailand and Indonesia.

BackgroundThe Eastern Russell’s viper, Daboia siamensis, is a WHO Category 1 medically important venomous snake. It has a wide but disjunct distribution in Southeast Asia. The specific antivenom, D. siamensis Monovalent Antivenom (DsMAV-Thailand) is produced in Thailand but not available in Indonesia, where a heterologous trivalent antivenom, Serum Anti Bisa Ular (SABU), is used instead. This study aimed to investigate the geographical venom variation of D. siamensis from Thailand (Ds-Thailand) and Indonesia (Ds-Indonesia), and the immunorecognition of the venom proteins by antivenoms.Methods: The venom proteins were decomplexed with reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by in-solution tryptic digestion, nano-liquid chromatography-tandem mass spectrometry and protein identification. The efficacies of DsMAV-Thailand and SABU in binding the various venom fractions were assessed using an enzyme-linked immunosorbent assay optimized for immunorecognition profiling. Results: The two most abundant protein families in Ds-Thailand venom are phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitor (KSPI). Those abundant in Ds-Indonesia venom are PLA2 and serine protease. KSPI and vascular endothelial growth factor were detected in Ds-Thailand venom, whereas L-amino acid oxidase and disintegrin were present in Ds-Indonesia venom. Common proteins shared between the two included snaclecs, serine proteases, metalloproteinases, phosphodiesterases, 5’nucleotidases and nerve growth factors at varying abundances. DsMAV-Thailand exhibited strong immunorecognition of the major protein fractions in both venoms, but low immunoreactivity toward the low molecular weight proteins e.g. KSPI and disintegrins. On the other hand, SABU was virtually ineffective in binding all fractionated venom proteins. Conclusion: D. siamensis venoms from Thailand and Indonesia varied geographically in the protein subtypes and abundances. The venoms, nevertheless, shared conserved antigenicity that allowed effective immunorecognition by DsMAV-Thailand but not by SABU, consistent with the neutralization efficacy of the antivenoms. A specific, appropriate antivenom is needed in Indonesia to treat Russell’s viper envenomation.

Proteomics, functional characterization and antivenom neutralization of the venom of Pakistani Russell's viper (Daboia russelii) from the wild

The venom proteome of wild Pakistani Russell's viper (Daboia russelii) was investigated through nano-ESI-LCMS/MS of the reverse-phase HPLC fractions. A total of 54 venom proteins were identified and clustered into 11 protein families. Phospholipase A2 (PLA2, 63.8%) and Kunitz-type serine protease inhibitor (KSPI, 16.0%) were most abundant, followed by snake venom serine protease (SVSP, 5.5%, mainly Factor V activating enzyme), vascular endothelial growth factor (VEGF, 4.3%), snake venom metalloproteinase (SVMP, 2.5%, mainly Factor X activating enzyme) and phosphodiesterase (PDE, 2.5%). Other minor proteins include cysteine-rich secretory protein (CRiSP), snake venom C-type lectin/lectin-like protein (snaclec), nerve growth factor, L-amino acid oxidase and 5′-nucleotidase. PLA2, KSPI, SVSP, snaclec and SVMP are hemotoxic proteins in the venom. The study indicated substantial venom variation in D. russelii venoms of different locales, including 3 Pakistani specimens kept in the USA. The venom exhibited potent procoagulant activity on human plasma (minimum clotting dose = 14.5 ng/ml) and high lethality (rodent LD50 = 0.19 μg/g) but lacked hemorrhagic effect locally. The Indian VINS Polyvalent Antivenom bound the venom immunologically in a concentration-dependent manner. It moderately neutralized the venom procoagulant and lethal effects (normalized potency against lethality = 2.7 mg venom neutralized per g antivenom). Biological significanceComprehensive venom proteomes of D. russelii from different locales will facilitate better understanding of the geographical variability of the venom in both qualitative and quantitative terms. This is essential to provide scientific basis for the interpretation of differences in the clinical presentation of Russell's viper envenomation. The study revealed a unique venom proteome of the Pakistani D. russelii from the wild (Indus Delta), in which PLA2 predominated (~60% of total venom proteins). The finding unveiled remarkable differences in the venom compositions between the wild (present study) and the captive specimens reported previously. The integration of toxicity tests enabled the correlation of the venom proteome with the envenoming pathophysiology, where the venom showed potent lethality mediated through coagulopathic activity. The Indian VINS Polyvalent Antivenom (VPAV) showed binding activity toward the venom protein antigens; however the immunorecognition of small proteins and PLA2-dominating fractions was low to moderate. Consistently, the antivenom neutralized the toxicity of the wild Pakistani Russell's viper venom at moderate efficacies. Our results suggest that it may be possible to enhance the Indian antivenom potency against the Pakistani viper venom by the inclusion of venoms from a wider geographical range including that from Pakistan into the immunogen formulation.

Capillary Leak Syndrome Following Snakebite Envenomation.

Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and hemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion. There are no other proven effective treatment modalities, except a few reports of successful treatment with plasmapheresis. Methylprednisolone pulse therapy, terbutaline, aminophylline, and intravenous immunoglobulin are other treatment modalities tried.

Unveiling the complexities of Daboia russelii venom, a medically important snake of India, by tandem mass spectrometry

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

Acute hypopituitarism complicating Russell's viper envenomation: case series and systematic review.

Chronic hypopituitarism following Russell viper envenomation (RVE) is a rare but well-recognized syndrome. The clinical features, associations, management and outcomes of RVE associated-acute hypopituitarism (AHP) are not well described. To describe the clinical features, intensive care unit (ICU) management and outcomes of a series of patients with RVE-AHP and identify the clinical associations of RVE-AHP. We describe a series of patients with prospectively identified AHP related to RVE and describe our findings comparing RVE with and without AHP and a systematic search of literature on AHP related to RVE. We identified nine cases of AHP related to RVE. Unexplained hypoglycemia (100%) and hypotension (66.7%) were the most common findings at presentation. AHP occurred after a median of 9 (range, 2-14) days after severe envenomation and was associated with multi-organ dysfunction, lower platelet counts, more bleeding and transfusions when compared to patients with RVE alone. The presence of clinically defined capillary leak syndrome, disseminated intravascular coagulation and mortality were not different from those without AHP. Our systematic search yielded 12 cases of AHP related to RVE; data on associated clinical manifestations, therapy and ASV administration were not available in most reports. AHP is a very rare complication of RVE. Unexplained hypoglycemia and hypotension should prompt evaluation for AHP in RVE. AHP is associated with severe RVE, multi-organ dysfunction, bleeding and need for transfusion. Prompt treatment with steroids may reduce mortality related to AHP in RVE.

Acute kidney injury following Russell’s viper bite in the pediatric population: a 6-year experience

Snake bite continues to be an important public health problem in tropical countries, and Russell's viper is common in south-Asian countries such as India, Sri Lanka, and Myanmar. Russell's viper envenomation can cause acute kidney injury (AKI) by various mechanisms. Few studies address AKI following Russell's viper bite in the pediatric population. In this study, we report our center's 6-year experience of such pediatric patients and identify the poor prognostic factors.

A Novel Heparin-dependent Inhibitor of Activated Protein C That Potentiates Consumptive Coagulopathy in Russell's Viper Envenomation

The activation of coagulation factors V and X by Russell's viper venom (RVV) has been implicated in the development of consumptive coagulopathies in severely envenomed patients. However, factor Va is prone to inactivation by activated protein C (APC), an important serine protease that negatively regulates blood coagulation. It is therefore hypothesized that APC may be down-regulated by some of the venom components. In this study, we managed to isolate a potent Kunitz-type APC inhibitor, named DrKIn-I. Using chromogenic substrate, DrKIn-I dose-dependently inhibited the activity of APC. Heparin potentiated the inhibition and reduced the IC(50) of DrKIn-I by 25-fold. DrKIn-I, together with heparin, also protected factor Va from APC-mediated inactivation. Using surface plasmon resonance, DrKIn-I exhibited fast binding kinetics with APC (association rate constant = 1.7 × 10(7) M(-1) s(-1)). Direct binding assays and kinetic studies revealed that this inhibition (K(i) = 53 pM) is due to the tight binding interactions of DrKIn-I with both heparin and APC. DrKIn-I also effectively reversed the anticoagulant activity of APC and completely restored the thrombin generation in APC-containing plasma. Furthermore, although the injection of either DrKIn-I or RVV-X (the venom factor X-activator) into ICR mice did not significantly deplete the plasma fibrinogen concentration, co-administration of DrKIn-I with RVV-X resulted in complete fibrinogen consumption and the deposition of fibrin thrombi in the glomerular capillaries. Our results provide new insights into the pathogenesis of RVV-induced coagulopathies and indicate that DrKIn-I is a novel APC inhibitor that is associated with potentially fatal thrombotic complications in Russell's viper envenomation.

New insights into the functions and N‐glycan structures of factor X activator from Russell’s viper venom

The coagulation factor X activator from Russell's viper venom (RVV-X) is a heterotrimeric glycoprotein. In this study, its three subunits were cloned and sequenced from the venom gland cDNAs of Daboia siamensis. The deduced heavy chain sequence contained a C-terminal extension with four additional residues to that published previously. Both light chains showed 77-81% identity to those of a homologous factor X activator from Vipera lebetina venom. Far-western analyses revealed that RVV-X could strongly bind protein S, in addition to factors X and IX. This might inactivate protein S and potentiate the disseminated intravascular coagulation syndrome elicited by Russell's viper envenomation. The N-glycans released from each subunit were profiled and sequenced by MALDI-MS and MS/MS analyses of the permethyl derivatives. All the glycans, one on each light chain and four on the heavy chain, showed a heterogeneous pattern, with a combination of variable terminal fucosylation and sialylation on multiantennary complex-type sugars. Amongst the notable features were the presence of terminal Lewis and sialyl-Lewis epitopes, as confirmed by western blotting analyses. As these glyco-epitopes have specific receptors in the vascular system, they possibly contribute to the rapid homing of RVV-X to the vascular system, as supported by the observation that slower and fewer fibrinogen degradation products are released by desialylated RVV-X than by native RVV-X.

P.3.a.021 Examination of specific genetic aspects of the dopaminergic neurotransmission and neuronal plasticity in neurocognitive subgrouping of schizophrenia

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.c.016 Diabetes and impaired glucose tolerance in the treatment of schizophrenia - interim assessment of prevalence and investigation of genetic predictors

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.a.012 Low concentration of plasma nitric oxide metabolites in schizophrenic patients

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.b.003 Validation of visuospatial navigation as a measure of episodic memory in schizophrenia

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.a.035 Psychoeducation and compliance in the treatment of the patients with schizophrenia

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.a.037 Quality of life in bipolar type I disorder and schizophrenia in remission:clinical and neurocognitive correlates

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.a.043 Neuropsychological measures for cognitive affective dysregulation in paranoid schizophrenia: implications for functional neuroimaging research

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.2.e.017 Safety, tolerability and ef .cacy of rapidly-initiated quetiapine in acutely ill patients with bipolar I disorder

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

P.3.a.018 Vitamin D deficiency and impaired parathormone metabolism as a risk factor of low bone mineral density in patients with diagnosis of schizophrenia treated with second generation antipsychotics

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.