Radiation Toxins Research Articles

Antiradiation vaccine : immunoprophylaxis of acute radiation syndromes - radioprotective efficiency.

Current medical management of Acute Radiation Syndromes does not include immune prophylaxis based on Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement therapy and supportive therapy. A large amount of antigens isolated from bacterias (flagellin and derivates), plants, different types of venoms (honeybees, scorpions, snakes) can produce a nonspecific stimulation of immune system of mammals and protect against of irradiation. But only radiation toxins stimulate a specific antigenic stimulation of antibody synthesis. Active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 30 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly diminishes mortality rate (100%) and improves survival rate up to 60% compare with 0% survival rate among irradiated animals in control groups. The SRD molecules were isolated from Lymphatic Systems of animals that were irradiated with high doses of irradiation and had clinical and laboratory picture of Cerebral Acute Radiation Syndrome, Cardiovascular Acute Radiation Syndrome, Gastrointestinal Acute Radiation Syndrome and Hematological Acute Radiation Syndrome. Our classification of radiation toxins include 4 major groups: 1.SRD-1, neurotoxic radiation toxins; 2.SRD-2, neurovascular radiation toxins; 3.SRD-3, non-Bacterial Gastrointestinal Radiation Toxins; 4.SRD-4, Hematopietic Radiation Toxins. Radiation toxins possess both toxic and immunological properties. But mechanisms of immune-toxicity by which radiation toxins stimulate development of ARS are poorly understood. We have compared lethal toxicity of radiation toxins and a potential for neutralization of their toxic activity by specific antibodies to radiation toxins. Blocking antiradiation antibodies induce an immunologically specific effect and possess inhibiting effects to radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity and radiation induced cytolysis of selected sensitive to radiation groups of cells. Blocking Antiradiation Antibodies are immunologically specific and can be produced by immunization with different radiation toxins isolated from irradiated mammals. We propose that Specific Antiradiation Antibodies targeted to radiation induced Toxins. Specific Antiradiation Antibodies neutralize toxic properties of radiation toxins. Antiradiation Antibodies in different phases of Acute Radiation Syndromes can compete with cytotoxic lymphocytes and prevent cytolysis mediated by cytotoxic lymphocytes .

Differential diagnosis of Acute Radiation Syndromes by Enzyme Immune-Assay (EIA)

Differential diagnosis of Acute Radiation Syndromes by the method of immune enzyme assay is a very efficient tool of biological dosimetry and evaluation of acute radiation disease. We use as biological markers the group of essential Radiotoxins - high molecular weight glycoproteins with specific antigenic properties. A molecular weight of radiation toxins was 200-250 kDa. High doses of radiation induce the formation of radiation toxins in the organs and tissues of irradiated animals. After whole body irradiation, cellular macromolecules and cells and mitochondrial outer and inner wall membranes are damaged by long-lived radiation-induced free radicals, reactive oxygen species and fast, charged particles of radiation. High doses of radiation induce breaks in the chemicals bonds of macromolecules (proteins,lipids,carbohydrates,DNA molecules) and cross-linking reactions via chemically active processes. These processes result in creation of novel modified macromolecules that possess specific toxic and antigenic properties defined by the type and doses of irradiation by which they are generated. After formation, Radiation toxins migrate from irradiated tissues to interstitial fluid and accumulate in the lymphatic and blood transportation system. Radiation toxins isolated from the lymph of irradiated animals are classified as hematotoxic, neurotoxic, and enteric non-bacterial(GI) Radiation Toxins, and they play an important role in development of Hematopoietic, Cerebrovascular, Cardiovascular and Gastro- Intestinal Acute Radiation Syndromes(ARS). Four Groups and Seven distinct Toxins derived from post-irradiated animals have been designated as Specific Radiation Determinants (SRD): SRD-1(Neuro-toxic radiation toxin generated by Cerebrovascular ARS), SRD-2(Vascular-toxic radiation toxin generated by Cardiovascular ARS), SRD-3(Enteric non-bacterial radiation toxins generated by the Gastrointestinal form of ARS), and SRD-4(Hematotoxic radiation toxins generated by hematological, bone marrow form of ARS ). SRD-4 is further subdivided into four groups depending on the severity of the ARS induced: SRD-4/1, mild ARS; SRD-4/2, moderate ARS; SRD-4/3, severe ARS and SRD-4/4, extremely severe ARS. We postulate that the SRD-1 and the SRD-2 radiation toxins produce toxicity for central and peripheral nervous system. Determination of high levels of SRD-1, SRD-2,SRD-3 and SRD-4 in the periferal blood allowed to recognize early periods of Cerebrovascular, Cardiovascular, Gastrointestinal and Hematopoietic forms of ARS. The important goal of an early assessment with Enzyme Immune Assay is the accurate description of the Acute Radiation Syndromes at initial phases. Early and precise differential diagnosis allow doctors to provide an effective medical management of ARS.

Medical management of Acute Radiation Syndromes:Immunotherapy by Antiradiation Immunoglobulin G .

Immunoglobulins is an important part of Acquired Immunity and participate in such important immunological processes as recognition, regulation and elimination of foreign antigens. At the present time, Intravenous Immunoglobulins are used for an efficient therapy for immune deficiency syndromes, thrombocytopenias, inflammatory reactions, modulation of autoimmunity and a wide range of hematologic disorders. Traditionally, the treatment of Acute Radiation Syndromes (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and stem cell transplantation. However, results of treatment of ARS remain limited and in cases of severe radiation injury insufficient. Studies of therapy effects of Anti-radiation Immunoglobulin G in vivo have established that specific antibodies to Radiation Toxins of SRD group can be important, effective part of medical management of ARS and can play a significant role in neutralization of radiation induced toxicity. Multiple-organ failure at Acute Radiation Syndromes is a major cause of mortality after high doses of gamma irradiation. Radiation Toxins of Specific Radiation Deteminant group(neuro-toxic, neuro-vascular-toxic, entero-toxic, hemato-toxic) play an important role in development of Acute Radiation Syndromes and development of multi-organ involvement and multi-organ failure. Radiation Toxins possess high toxic properties. Radiation Neurotoxin isolated from lymphatic system of irradiated animals (with a clinical picture of cerebral radiation syndrome) and injected to healthy animals in toxic doses 0.03 mg/kg, 0.5 mg/kg, 10.0 mg/kg, 15.0 mg/kg had initiated development of acute failure of blood circulation and breathing ventilation. Death of laboratory animals had occurred within 5 min-3 days after injection of toxic doses of Radiation Neuro-Toxin and depended on a concentration and a type of active substance of Radiation Toxins. Hyper-immunization of non-irradiated animals by non-toxic doses of Radiation Toxins were provided. The immunoglobulin fraction of pooled hyperimmune anti-radiation plasma was separated. Immunoglobulines to Radiation Toxins were used for a treatment of Acute Radiation Syndromes and the efficacy of this bio-pharmaceutical agent was initially evaluated. Therapeutic application of Specific Anti-radiation Immunoglobulin had significantly diminished mortality rate at Acute Radiation Syndromes and was much more effective compare with natural immunoglobulins preparations and irradiated forms of natural irradiated immunoglobulins.

Delayed cell death and bystander effects in the progeny of Chinook Salmon Embryo cells exposed to radiation and a range of aquatic pollutants

Purpose: To determine whether delayed and bystander effects can be seen in both a non malignant teleost fish cell line, (CHSE) and a malignant teleost fish cell line (EPC) when exposed to low doses of ionising radiation and genotoxic pollutants.Methods: Teleost fish cells were briefly exposed to radiation and chemical toxins at low doses. Clonogenic survival was measured in the exposed population and the distant progeny of exposed cells to assess early and delayed cell death. Clonogenic survival was also measured in cultures, which received medium from briefly exposed cells to determine bystander effects.Results: The dose response pattern for both early and delayed cell death was found to differ for different stressors. Different mechanisms of cell death appear to be involved in the early cytotoxic effect and the delayed effect. No delayed cell death occurred in a transformed fish cell line (EPC). Bystander effects occurred in CHSE cells and were similar in intensity to previously reported mammalian cell bystander effects. Conclusions: The results may have implications for radiation and environmental protection of biota. They demonstrate that damage caused by low doses of radiation and common aquatic pollutants is not only similar but occurs in both acute and delayed forms.

Emerging infections: microbial threats to health

I n 1900, infectious disease was the leading cause of mortality in the USA, accounting for at least 37% of deaths. By 1950, this had been reduced to 6.8%, and by 1989 to 2.8%, with corresponding improvements in life expectancy 1-3. These numbers of course must be taken with a grain of salt, given the eventual pre-emptive role of infection in chronic illness, and the possibility that many disorders have an unrecognized infectious etiology. Further, the relative importance of sanitation, health education and nutrition, in comparison with medical interventions such as immunization and antibiotic treatment, has remained in contentious debate 4,s. Nevertheless, the reduction in mortality caused by infection has been trumpeted as the conquest of infectious disease (e.g. Ref. 6), indeed as a glorious tribute to public health and medical science. In consequence, health research since 1950 has increasingly emphasized chronic constitutional afflictions such as cancer, cardiovascular disease and psychiatric disorder, to the relative neglect of infection. Likewise, environmental anxieties are focused on radiation and chemical toxins rather than arthropod vectors and airborne contagion. Our complacency about the triumph of humans over microorganisms has been shaken by the global HIV pandemic. In truth, the majority of the world's population has never been relieved of its load of malaria, tuberculosis, diarrheal disease and a host of parasitoses. It has taken AIDS to provoke a new look at the threats to human health from infections recently thought to be conquered. Responding to a global challenge These concerns were taken up by a recent study of the United States Institute of Medicine task force on emergent infections 7. Our report was the product of a broad collective effort, which promptly reached an unanimous conclusion that these threats urgently needed to be brought to the attention of policymakers and the public. Our recommendations had to do mainly with (1) the strengthening of disease surveillance systems (especially for viruses) globally; (2) wider availability of existing vaccines and the removal of legal disincentives to the development of new ones; (3) acceleration of the technology to enable vaccines against new strains to be developed on a time scale commensurate with the spread of infection; (4) vector control; and (5) public education. Perhaps the most important message is that infection knows no national boundaries, and we will pay dearly if we ignore the smoldering of infection anywhere. No single infectious agent is a unique target of concern. During the committee's deliberations, multiple drug-resistant tuberculosis emerged as a major public health threat in New York City dare one say that this was predictable from the time of its first appearance a few years ago in immunocompromised people with AIDS? Historically, the influenza epidemic of 1918-1919 was the most recent previous pandemic to have a major effect on mortality statistics in the USA. Many believe that a recurrence of such a lethal