scholarly journals Effect of Indian Polyvalent Antivenom in the Prevention and Reversal of Local Myotoxicity Induced by Common Cobra (Naja naja) Venom from Sri Lanka In Vitro

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 308
Author(s):  
Umesha Madhushani ◽  
Prabhani Thakshila ◽  
Wayne C. Hodgson ◽  
Geoffrey K. Isbister ◽  
Anjana Silva

Bites by many Asiatic and African cobras (Genus: Naja) cause severe local dermonecrosis and myonecrosis, resulting in permanent disabilities. We studied the time scale in which two Indian polyvalent antivenoms, VINS and Bharat, remain capable of preventing or reversing in vitro myotoxicity induced by common cobra (Naja naja) venom from Sri Lanka using the chick biventer cervicis nerve-muscle preparation. VINS fully prevented while Bharat partially prevented (both in manufacturer recommended concentrations) the myotoxicity induced by Naja naja venom (10 µg/mL) when added to the organ baths before the venom. However, both antivenoms were unable to reverse the myotoxicity when added to organ baths 5 and 20 min post-venom. In contrast, physical removal of the venom from the organ baths by washing the preparation 5 and 20 min after the venom resulted in full and partial prevention of the myotoxicity, respectively, indicating the lag period for irreversible cellular injury. This suggests that, although the antivenoms contain antibodies against cytotoxins of the Sri Lankan Naja naja venom, they are either unable to reach the target sites as efficiently as the cytotoxins, unable to bind efficiently with the toxins at the target sites, or the binding with the toxins simply fails to prevent the toxin-target interactions.

1993 ◽  
Vol 83 (1) ◽  
pp. 127-132 ◽  
Author(s):  
H.T.R. Peiris ◽  
J. Hemingway

AbstractCulex quinquefasciatus Say from Peliyagoda, Sri Lanka, has elevated esterases A2 and B2. In vitro insecticide metabolism studies on the temephos-selected Sri Lankan Cutex quinquefasciatus strain, Pel RR, showed that fenitrothion was hydrolysed more rapidly than malathion. A significantly larger amount of fenitrothion was metabolized in Pel RR compared to the insecticide susceptible Pel SS strain, but the amount of malathion metabolized in the two strains was not significantly different. There was more esterase hydrolysis of fenitrothion than oxidase or glutathione S-transferase metabolism in Pel RR, which suggests that the elevated esterases in this strain have both metabolic and sequestering functions and that the relative importance of the two roles depends on the insecticide used. Genetic crosses of the temephos resistant and susceptible strains, showed that both resistance and elevated esterase activity were inherited as semi-dominant multi-genic characters. Hydrolysis of 2-naphthyl acetate was highest in the Pel RR strain, lowest in the Pel SS and intermediate in the F1 cross of the two strains. A minor maternal effect on resistance occurred with backcrosses involving resistant (F1) females, which gave consistently and significantly lower mortalities than those involving resistant (F1) males.


Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 558
Author(s):  
Kin Ying Wong ◽  
Kae Yi Tan ◽  
Nget Hong Tan ◽  
Christeine Ariaranee Gnanathasan ◽  
Choo Hock Tan

Inadequate effectiveness of Indian antivenoms in treating envenomation caused by the Spectacled Cobra/Indian Cobra (Naja naja) in Sri Lanka has been attributed to geographical variations in the venom composition. This study investigated the de novo venom-gland transcriptomics and venom proteomics of the Sri Lankan N. naja (NN-SL) to elucidate its toxin gene diversity and venom variability. The neutralization efficacy of a commonly used Indian antivenom product in Sri Lanka was examined against the lethality induced by NN-SL venom in mice. The transcriptomic study revealed high expression of 22 toxin genes families in NN-SL, constituting 46.55% of total transcript abundance. Three-finger toxins (3FTX) were the most diversely and abundantly expressed (87.54% of toxin gene expression), consistent with the dominance of 3FTX in the venom proteome (72.19% of total venom proteins). The 3FTX were predominantly S-type cytotoxins/cardiotoxins (CTX) and α-neurotoxins of long-chain or short-chain subtypes (α-NTX). CTX and α-NTX are implicated in local tissue necrosis and fatal neuromuscular paralysis, respectively, in envenomation caused by NN-SL. Intra-species variations in the toxin gene sequences and expression levels were apparent between NN-SL and other geographical specimens of N. naja, suggesting potential antigenic diversity that impacts antivenom effectiveness. This was demonstrated by limited potency (0.74 mg venom/ml antivenom) of the Indian polyvalent antivenom (VPAV) in neutralizing the NN-SL venom. A pan-regional antivenom with improved efficacy to treat N. naja envenomation is needed.


1988 ◽  
Vol 67 (3) ◽  
pp. 240???246 ◽  
Author(s):  
A. F. L. Van Der Spek ◽  
J. T. Zupan ◽  
B. J. Pollard ◽  
M. A. Schork

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 377 ◽  
Author(s):  
Qing Liang ◽  
Tam Minh Huynh ◽  
Nicki Konstantakopoulos ◽  
Geoffrey K. Isbister ◽  
Wayne C. Hodgson

The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of N. atra venom, as well as examining the efficacy of three Chinese monovalent antivenoms (N. atra antivenom, Gloydius brevicaudus antivenom and Deinagkistrodon acutus antivenom) and an Australian polyvalent snake antivenom. In the chick biventer cervicis nerve-muscle preparation, N. atra venom (1–10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese N. atra antivenom (0.75 U/mL) or Australian polyvalent snake antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese antivenom (0.75 U/mL) or Australian polyvalent antivenom (3 U/mL) at the t90 time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. N. atra antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, G. brevicaudus antivenom (24 U/mL), D. acutus antivenom (8 U/mL) and Australian polyvalent snake antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, N. atra venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC50) of 2.8 ± 0.48 μg/mL. N. atra antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent snake antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither G. brevicaudus antivenom or D. acutus antivenom were able to prevent the cytotoxicity. This study indicates that Chinese N. atra monovalent antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of N. atra venom but the clinical effectiveness of the antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper antivenoms (i.e., G. brevicaudus and D. acutus antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study.


INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (08) ◽  
pp. 28-34
Author(s):  
T. Kumar ◽  
◽  
A Sahu ◽  
V Jain

The current study was aimed to investigate the antifilarial activity of aqueous and ethyl acetate extracts of the leaves of Lannea coromandelica. Both extracts were screened for their total flavonoid content chromatographically. The total amount of flavonoid present in ethyl acetate is much greater than in aqueous extract. Aqueous extract produced initial stimulation effect in whole worm followed by reversible paralysis, whereas on the nerve muscle preparation, the effect was depressant. In the same manner ethyl acetate extract produces irreversible paralysis. The concentrations required to inhibit the movement of the whole worm and nerve muscle preparation for aqueous extract of leaves of L. coromandelica were 300 and 60 µg/mL, respectively, whereas ethyl acetate extract caused inhibition of the whole worm and nerve muscle preparation at 160 and 15 µg/mL, respectively. LC50 and LC90 were 21 and 30 ng/mL, respectively for aqueous, which were 16 and 24 ng/mL for ethyl acetate extracts.


Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Qing Liang ◽  
Tam Minh Huynh ◽  
Yen Zhi Ng ◽  
Geoffrey K. Isbister ◽  
Wayne C. Hodgson

Bungarus multicinctus, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1–10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t90 time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus antivenom (60 U/mL), at the t20 or t50 time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t90 values. Repeated washing of the preparation with physiological salt solution, commencing at the t20 time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.


1985 ◽  
Vol 54 (02) ◽  
pp. 413-414 ◽  
Author(s):  
Margarethe Geiger ◽  
Bernd R Binder

SummaryWe have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbAlc values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.


2020 ◽  
Vol 6 ◽  
pp. 93-100
Author(s):  
Gisa Jähnichen

The Sri Lankan Ministry of National Coexistence, Dialogue, and Official Languages published the work “People of Sri Lanka” in 2017. In this comprehensive publication, 21 invited Sri Lankan scholars introduced 19 different people’s groups to public readers in English, mainly targeted at a growing number of foreign visitors in need of understanding the cultural diversity Sri Lanka has to offer. This paper will observe the presentation of these different groups of people, the role music and allied arts play in this context. Considering the non-scholarly design of the publication, a discussion of the role of music and allied arts has to be supplemented through additional analyses based on sources mentioned by the 21 participating scholars and their fragmented application of available knowledge. In result, this paper might help improve the way facts about groups of people, the way of grouping people, and the way of presenting these groupings are displayed to the world beyond South Asia. This fieldwork and literature guided investigation should also lead to suggestions for ethical principles in teaching and presenting of culturally different music practices within Sri Lanka, thus adding an example for other case studies.


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