scholarly journals A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms

2021 ◽  
Vol 12 ◽  
Author(s):  
Kavi Ratanabanangkoon
Keyword(s):  
Low Dose ◽  
Snake Venoms ◽  
Immunization Program ◽  
Immunization Protocol ◽  
Antibody Titers ◽  
Immunization Procedure ◽  
Time Required ◽  
Local Side ◽  
Successful Production ◽  
Lethal Toxins

This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund’s adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed ‘low dose, low volume multi-site’ was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand’s annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a ‘diverse toxin repertoire’ composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the ‘diverse toxin repertoire’, the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.

scholarly journals Production of a Plasma Derived Universal Antivenom against All Elapid Neurotoxic Snake Venoms

2021 ◽  
Vol 14 (4) ◽  
pp. 56-61
Author(s):  
Kavi Ratanabanangkoon
Keyword(s):  
Low Dose ◽  
Neglected Tropical Diseases ◽  
Medical Problem ◽  
Snake Venoms ◽  
Root Cause ◽  
Immunization Protocol ◽  
The World ◽  
Low Volume ◽  
Local Reactions ◽  
Local Side

Snakebite envenoming has killed about 138000 people and maimed 400,000 victims annually. WHO has designated this medical problem as one of the most neglected tropical diseases for which effective, affordable antivenoms (AVs) are urgently needed. Production of potent AV against neurotoxic venoms was difficult and was thought to be due to the low immunogenicity of the postsynaptic neurotoxins (PSNT) which cause death in the victims. However, it was showed that the use of ineffective adjuvant in the immunization of horse was the root cause. The highly effective Freund adjuvant (FA) causes severe local reactions and could not be used. A novel immunization protocol termed ‘low dose low volume multi-site’ was tested and shown to obliterate the local side effect and allow for the safe use of FA in horse. The immunization protocol led to the production of 7 highly potent monovalent AVs, and 2 potent polyvalent AVs, one against 4 neurotoxic venoms and another against 3 hematotoxic venoms. These AVs allow the treatment of snakebite victims without the need to identify the culprit snakes. Furthermore, we have tested a novel immunization strategy using ‘Diverse toxin repertoire’ of 12 Asian elapid toxin fractions. The resulting antiserum effectively neutralized at least 36 elapid venoms of 28 species encompassing 10 genera and from 20 countries on 4 continents, and most likely all the elapid neurotoxic snake venoms. These results indicate that effective universal antivenom against all elapid neurotoxic venoms of the world can be produced and save numerous lives.

Search mode for rapid detection of virus particles

1991 ◽  
Vol 49 ◽  
pp. 286-287
Author(s):  
O. E. Bradfute
Keyword(s):  
Electron Microscopy ◽  
Rapid Detection ◽  
Plant Virus ◽  
Low Dose ◽  
Search Mode ◽  
Virus Diseases ◽  
Virus Particles ◽  
Focus Image ◽  
Time Required ◽  
Rapid Switching

Electron microscopy is frequently used in preliminary diagnosis of plant virus diseases by surveying negatively stained preparations of crude extracts of leaf samples. A major limitation of this method is the time required to survey grids when the concentration of virus particles (VPs) is low. A rapid survey of grids for VPs is reported here; the method employs a low magnification, out-of-focus Search Mode similar to that used for low dose electron microscopy of radiation sensitive specimens. A higher magnification, in-focus Confirm Mode is used to photograph or confirm the detection of VPs. Setting up the Search Mode by obtaining an out-of-focus image of the specimen in diffraction (K. H. Downing and W. Chiu, private communications) and pre-aligning the image in Search Mode with the image in Confirm Mode facilitates rapid switching between Modes.

scholarly journals Insulin Autoimmune Syndrome Treated with Plasmapharesis

2020 ◽  
pp. 25-26
Author(s):  
Dr. Kavya Jonnalagadda ◽  
Dr. Praveen. V. Pavithran
Keyword(s):  
Low Dose ◽  
Serum Insulin ◽  
Oral Prednisolone ◽  
Symptomatic Improvement ◽  
Insulin Antibody ◽  
Autoimmune Syndrome ◽  
Dose Oral ◽  
High Insulin ◽  
History Of ◽  
Antibody Titers

A 66-year male with a history of Central Serous Retinopathy presented with recurrent episodes of hypoglycemia. On evaluation, he was found to have insulin-mediated hypoglycemia with serum insulin of 300uIU/ml, C peptide 27.51ng/ml, when the blood glucose was 46mg/dl. High insulin levels above 100uIU/ml, led to suspicion of Autoimmune hypoglycemia and were confirmed by a high anti-insulin antibody titer of 300U/ml. Imaging was negative for Insulinoma. The patient was started on low dose oral prednisolone under ophthalmological monitoring, but as there was no symptomatic improvement, the dose was increased following which there was a flare-up of CSR. The patient was initiated on plasmapheresis following which his hypoglycemia improved with drop in anti-insulin antibody titers to 29U/ml. The patient was maintained on low dose steroids, which were tapered and stopped over the next six months with complete resolution of hypoglycemia and normalization of anti-insulin antibody titers.

scholarly journals Safety and immunogenicity of a primary yellow fever vaccination under low-dose methotrexate therapy—a prospective multi-centre pilot study1

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
Silja Bühler ◽  
Veronika Katharina Jaeger ◽  
Gilles Eperon ◽  
Hansjakob Furrer ◽  
Christoph A Fux ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Neutralizing Antibodies ◽  
Low Dose ◽  
Yellow Fever Virus ◽  
Serum Samples ◽  
Post Vaccination ◽  
Dose Methotrexate ◽  
Yellow Fever Vaccination ◽  
First Time ◽  
Local Side

Abstract Background More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls. Methods We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (≤20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28. Results Patients´ and controls’ median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3–10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n = 5 vs n = 2, Day 7: n = 9 vs n = 7, Day 10: n = 3 vs n = 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n = 2, controls: n = 6). On Day 28, all vaccinees were seroprotected. Conclusions First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results.

Dose-dependent viremia and the differential immunoglobulin response of hamsters to Powassan virus

1972 ◽  
Vol 18 (5) ◽  
pp. 655-661 ◽  
Author(s):  
Max A. Chernesky ◽  
Patricia J. Whittaker-Haines
Keyword(s):  
Neutralizing Antibodies ◽  
Low Dose ◽  
Gamma Globulin ◽  
High Dose ◽  
Post Inoculation ◽  
Anamnestic Response ◽  
Powassan Virus ◽  
Antibody Titers ◽  
Density Analysis ◽  
Dose Dependent

Hamsters injected subcutaneously with a single "low-dose" inoculum (10 mouse LD50) of Powassan virus developed viremia titering 106.2 mouse LD50 per milliliter of blood whereas hamsters receiving a "high-dose" inoculum of 105.0 mouse LD50 of virus developed a viremia of only 104.5 mouse LD50 per milliliter.Hemagglutination-inhibiting (HI) antibodies were first detected 7 days following the "low-dose" inoculation and attained maximum titers of 160. The HI antibody response to the "high-dose" virus inoculation began on the 5th day, at a time when viremia was present, and antibody titers did not exceed 40. Sucrose-density analysis and 2-mercaptoethanol treatment of sera revealed that IgM antibodies were induced by both inocula but animals receiving a low dose of virus produced higher IgG responses than did animals receiving a high dose of virus. Neutralizing antibodies, which did not appear until 30 days post inoculation, were present at a log neutralizing index (NI) of 2.0 at 60 days in animals receiving 10 mouse LD50 of virus and at a log NI of 1.0 in those receiving 105.0 mouse LD50. The NI of IgG was equal to the index for total gamma globulin in samples that contained both IgM and IgG as demonstrated by the HI test.Animals originally exposed to a "low-dose" inoculum produced a more prolonged anamnestic response when challenged 63 days later with 105.0 mouse LD50 of virus than did animals receiving a second inoculum containing only 103.0 or 10 mouse LD50 of virus. In contrast, poor secondary antibody responses were elicited by challenge doses of 105.0, 103.0, or 10 mouse LD50 of virus in animals that originally had received a "high-dose" of virus. IgM and IgG classes of antibody were induced in all secondary responses and the log NI of each group of animals was elevated by about 1 during anamnesis.

HYDROGEN AT THE Si/SiO2 INTERFACE: FROM ATOMIC-SCALE CALCULATIONS TO ENGINEERING MODELS

2004 ◽  
Vol 14 (02) ◽  
pp. 575-580
Author(s):  
S. N. RASHKEEV ◽  
D. M. FLEETWOOD ◽  
R. D. SCHRIMPF ◽  
S. T. PANTELIDES
Keyword(s):  
Density Functional ◽  
Low Dose ◽  
Positive Charge ◽  
Rate Sensitivity ◽  
Atomic Scale ◽  
Interface Trap ◽  
Proton Mobility ◽  
Trap Formation ◽  
Hole Trapping ◽  
Time Required

Two contrasting behaviors have been observed for H in Si / SiO 2 structures: a) Radiation experiments established that protons released in SiO 2 migrate to the Si / SiO 2 interface where they induce new defects; b) For oxides exposed first to high-temperature annealing and then to molecular hydrogen, mobile positive charge believed to be protons can be cycled to and from the interface by reversing the oxide electric field. First-principles density functional calculations identify the atomic-scale mechanisms for the two types of behavior and conditions that are necessary for each. Using the results of the atomic-scale calculations we develop a model for enhanced interface-trap formation at low dose rates due to space charge effects in the base oxides of bipolar devices. We find that the hole trapping in the oxide cannot be responsible for all the Enhanced Low-Dose-Rate Sensitivity (ELDRS) effects in SiO 2, and the contribution of protons is also essential. The dynamics of interface-trap formation are defined by the relation between the proton mobility (transport time of the protons across the oxide) and the time required for positive-charge buildup near the interface due to trapped holes. The analytically estimated and numerically calculated interface-trap densities are found to be in very good agreement with available experimental data.

scholarly journals Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation.

1999 ◽  
Vol 46 (2) ◽  
pp. 239-248 ◽  
Author(s):  
V S Slyshenkov ◽  
S N Omelyanchik ◽  
A G Moiseenok ◽  
N E Petushok ◽  
L Wojtczak
Keyword(s):  
Gamma Radiation ◽  
Low Dose ◽  
Pantothenic Acid ◽  
Beta Carotene ◽  
Thiobarbituric Acid ◽  
Free Radical Biol ◽  
60Co Source ◽  
Nadh Ratio ◽  
Time Required ◽  
Radioprotective Agent

Rats were exposed to a total dose of 0.75 Gy of gamma radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously (Slyshenkov, V.S., Omelyanchik, S.N., Moiseenok, A.G., Trebukhina, R.V. & Wojtczak, L. (1998) Free Radical Biol. Med. 24, 894-899), in livers of animals not supplied with either pantothenol or beta-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose gamma radiation.

Response of Rainbow Trout (Salmo gairdneri) to Antigens of Aeromonas hydrophila

1966 ◽  
Vol 23 (10) ◽  
pp. 1487-1494 ◽  
Author(s):  
George Post
Keyword(s):  
Rainbow Trout ◽  
Antibody Titer ◽  
Aeromonas Hydrophila ◽  
Synthesis Method ◽  
Phagocytic Index ◽  
Salmo Gairdneri ◽  
Antibody Synthesis ◽  
Humoral Antibody ◽  
Antibody Titers ◽  
Immunization Procedure

Rainbow trout (Salmo gairdneri) produced antibodies specific for Aeromonas hydrophila. Two parenteral routes yielded no measurable difference in rate of antibody synthesis. Method of bacterin suspension indicated adjuvant suspension was superior in maintenance of humoral antibody and challenge protection when compared to saline suspension of the organism.Antibody synthesis from adjuvant-suspended bacterin lagged approximately 30 days behind the rate of synthesis by fish receiving saline suspended bacteria. The highest measurable antibody titer reached by an individual was 1:64. Individuals receiving saline suspended bacterin showed evidence of loss of titer approximately 2 months after the last antigen inoculation. Definite decrease in titer was noted 5 months after the last antigen inoculation and the return to a probable nonimmune class by approximately one-half of the individuals 7 months after the last inoculation. All individuals receiving adjuvant-suspended bacterin remained in the probable immune class for as long as 6 months following the last bacterin inoculation, but only approximately one-half of the individuals remained in the probable immune class 7 months postinoculation.All fish receiving a weighed quantity of killed A. hydrophila orally each day for 9 consecutive months showed presence of humoral A. hydrophila antibody. This immunization procedure produced 50% of the individuals with humoral antibody titers considered to be in the probable immune class.Fish receiving no immunization remained with negative antibody titers throughout the experimental period.Definite protection was given fish which had been immunized by parenteral inoculation.Similar protection was given after immunization by either intramuscular or intraperitoneal routes. Fish receiving either saline or adjuvant-suspended bacterin parenterally showed analogous protection when challenged by the specific bacteria. Fish receiving oral bacterin received questionable protection against parenteral challenge of the specific organism.Phagocytosis was found to occur to a greater extent in immunized rainbow trout than in nonimmunized rainbow trout. An average phagocytic index of parenterally immunized rainbow trout was 1.08. Nonimmunized rainbow trout of the same age and egg source had an average phagocytic index of 0.30. The opsonic index was 3.6.

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