Immunoreactivity and neutralization capacity of Philippine cobra antivenom against Naja philippinensis and Naja samarensis venoms

2020 ◽  
Author(s):  
Choo Hock Tan ◽  
Praneetha Palasuberniam ◽  
Francis Bonn Blanco ◽  
Kae Yi Tan
Keyword(s):  
Low Dose ◽  
Lethal Dose ◽  
The Philippines ◽  
Knowledge Gap ◽  
High Efficacy ◽  
Neutralization Capacity ◽  
Median Lethal Dose ◽  
Venomous Snakes ◽  
Allopatric Species

Abstract Background The Philippine cobra (Naja philippinensis) and Samar cobra (Naja samarensis) are two WHO Category 1 medically important venomous snakes in the Philippines. Philippine cobra antivenom (PCAV) is the only antivenom available in the country, but its neutralization capacity against the venoms of N. philippinensis and hetero-specific N. samarensis has not been reported. This knowledge gap greatly hinders the optimization of antivenom use in the region. Methods This study examined the immunological binding and neutralization capacity of PCAV against the two cobra venoms using WHO-recommended protocols. Results In mice, both venoms were highly neurotoxic and lethal with a median lethal dose of 0.18 and 0.20 µg/g, respectively. PCAV exhibited strong and comparable immunoreactivity toward the venoms, indicating conserved venom antigenicity between the two allopatric species. In in vivo assay, PCAV was only moderately effective in neutralizing the toxicity of both venoms. Its potency was even lower against the hetero-specific N. samarensis venom by approximately two-fold compared with its potency against N. philippinensis venom. Conclusion The results indicated that PCAV could be used to treat N. samarensis envenomation but at a higher dose, which might increase the risk of hypersensitivity and worsen the shortage of antivenom supply in the field. Antivenom manufacturing should be improved by developing a low-dose, high-efficacy product against cobra envenomation.

Sensitive Tumor Cell Line for Annonaceous Acetogenins and High Therapeutic Efficacy at a Low Dose for Choriocarcinoma Therapy

2021 ◽  
Vol 17 (10) ◽  
pp. 2062-2070
Author(s):  
Hui Ao ◽  
Hao-Wen Li ◽  
Li-Kang Lu ◽  
Jing-Xin Fu ◽  
Mei-Hua Han ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Low Dose ◽  
Drug Loading ◽  
Lethal Dose ◽  
Tumor Cell Line ◽  
A431 Cells ◽  
Annonaceous Acetogenins ◽  
New Type

Annonaceous acetogenins (ACGs) have attracted much attention because of excellent antitumor activity. However, the lack of selectivity and the accompanying serious toxicity have eventually prevented ACGs from entering clinical application. To decrease the side effects of ACGs, the cytotoxicity of ACGs on 10 types of tumor cell lines was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test to identify one that was very sensitive to ACGs. Meanwhile, ACGs nanoparticles (ACGs-NPs) were prepared using poloxamer 188 (P188) as an excipient so as to solve the problem of poor solubility and the in vivo delivery of ACGs. ACG-NPs were 163.9±2.5 nm in diameter, negatively charged, and spherical with a high drug loading content (DLC) of 44.9±1.2%. MTS assays demonstrated that ACGs had strong cytotoxicity against JEG-3, HeLa, SiHa, MCF-7, A375, A2058, A875, U-118MG, LN- 229, and A431 cells, among which JEG-3 cell line was extremely sensitive to ACGs with a 50% inhibitory concentration (IC50) value of 0.26 ng/mL, a very encouraging discovery. ACGs-NPs demonstrated very good dose-dependent antitumor efficacy in a broad range of 45?1200 μg/kg on JEG-3 tumor-bearing mice. At a very low dose (1200 μg/kg), ACGs-NPs achieved a high tumor inhibition rate (TIR) of 77.6% through oral administration, displaying a significant advantage over paclitaxel (PTX) injections that are currently used as first-line anti-choriocarcinoma drugs. In the acute toxicity study, the half lethal dose (LD50) of ACGs-NPs was 135.5 mg/kg, which was over 100 times as of the effective antitumor dose, indicating good safety of ACGs-NPs. ACGs-NPs show promise as a new type of and potent anti-choriocarcinoma drug in the future.

scholarly journals Percutaneous Toxicity and Decontamination of Soman, Vx, and Paraoxon in Rats Using Detergents

2013 ◽  
Vol 64 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Jan Misík ◽  
Růžena Pavliková ◽  
Kamil Kuča
Keyword(s):  
Survival Rate ◽  
Military Personnel ◽  
Wistar Rats ◽  
Organophosphorus Compounds ◽  
Lethal Dose ◽  
Distilled Water ◽  
Median Lethal Dose ◽  
Agricultural Pesticides ◽  
Male Wistar Rats

Highly toxic organophosphorus compounds (OPs) were originally developed for warfare or as agricultural pesticides. Today, OPs represent a serious threat to military personnel and civilians. This study investigates the in vivo decontamination of male Wistar rats percutaneously exposed to paraoxon and two potent nerve agents - soman (GD) and VX. Four commercial detergents were tested as decontaminants - NeodekontTM, ArgosTM, DermogelTM, and FloraFreeTM. Decontamination performed 2 min after exposure resulted in a higher survival rate in comparison with non-decontaminated controls. The decontamination effectiveness was expressed as protective ratio (PR, median lethal dose of agent in decontaminated animals divided by the median lethal dose of agent in untreated animals). The highest decontamination effectiveness was consistently achieved with ArgosTM (PR=2.3 to 64.8), followed by DermogelTM (PR=2.4 to 46.1). NeodekontTM and FloraFreeTM provided the lowest decontamination effectiveness, equivalent to distilled water (PR=1.0 to 43.2).

scholarly journals Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Eleanor Gaunt ◽  
Helen M Wise ◽  
Huayu Zhang ◽  
Lian N Lee ◽  
Nicky J Atkinson ◽  
...  
Keyword(s):  
Host Response ◽  
Influenza A ◽  
Low Dose ◽  
Lethal Dose ◽  
Antibody Responses ◽  
Clinical Severity ◽  
Viral Loads ◽  
A Genome ◽  
Cpg Dinucleotide

Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability of echovirus 7 (Tulloch et al., 2014). Here, we show that that influenza A virus (IAV) with maximised frequencies of these dinucleotides in segment 5 showed comparable attenuation in cell culture compared to unmodified virus and a permuted control (CDLR). Attenuation was also manifested in vivo, with 10-100 fold reduced viral loads in lungs of mice infected with 200PFU of CpG-high and UpA-high mutants. However, both induced powerful inflammatory cytokine and adaptive (T cell and neutralising antibody) responses disproportionate to their replication. CpG-high infected mice also showed markedly reduced clinical severity, minimal weight loss and reduced immmunopathology in lung, yet sterilising immunity to lethal dose WT challenge was achieved after low dose (20PFU) pre-immunisation with this mutant. Increasing CpG dinucleotide frequencies represents a generic and potentially highly effective method for generating safe, highly immunoreactive vaccines.

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

Ciamexon in low-dose streptozotocin induced diabetes mellitus. In vivo and in vitro studies

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S120-S121
Author(s):  
TH. LINN ◽  
H. GERMANN ◽  
B. HERING ◽  
R. BRETZEL ◽  
K. FEDERLIN
Keyword(s):  
Diabetes Mellitus ◽  
Low Dose ◽  
In Vitro Studies ◽  
Streptozotocin Induced Diabetes

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

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