Ricin: An Ancient Story for a Timeless Plant Toxin.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation.

Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis.

Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay" vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals-especially mice-but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including F. tularensis. Since live attenuated-but not killed or subunit-vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies holarctica or F. novicida, or against non-respiratory challenge with virulent subsp. tularensis (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. tularensis, the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. holarctica, F. novicida, and subsp. tularensis, and heterologous vaccines developed using viral or bacterial vectors to express F. tularensis immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development-safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the higher standard of having efficacy ≥LVS in the demanding mouse model of tularemia. These latter include LVS with deletions in purMCD, sodBFt , capB or wzy; LVS ΔcapB that also overexpresses Type VI Secretion System (T6SS) proteins; FSC200 with a deletion in clpB; the single deletional purMCD mutant of F. tularensis SCHU S4, and a heterologous prime-boost vaccine comprising LVS ΔcapB and Listeria monocytogenes expressing T6SS proteins.

Abordando la problemática de las armas biológicas en el siglo XXI: el papel de una red de prevención 2.0 / No disponible

El uso estratégico de la enfermedad en la guerra ha demostrado ser una amenaza para la humanidad desde hace mucho tiempo; sin embargo, la naturaleza cambiante tanto de la ciencia como de Ia seguridad tiene, al combinarse, el potencial idóneo para estimular la adopción de nuevas (y clásicas) armas biológicas. Este breve artículo se inicia con la descripcion de algunos de estos cambios antes de considerar los medios y las medidas establecidas para hacer frente al desafío de las armas biológicas. Posteriormente, se procederá a delinear una red de prevención 2.0, compuesta por hebras que se refuerzan mutuamente, con la que se pretende formar un marco para un enfoque más holistico que sirva para hacer frente al desafío de las armas biológicas en el siglo XXI (AU)

The strategic use of disease in Warfare has long proven a menace to humankind; however, the changing nature of both science and security has the potential to encourage the assimilation of new (and old) biological weapons. This short article begins by outlining some of these changes before considering the means and measures in place to deal with the challenge of biological weapons. It proceeds to outline a Web of Prevention 2.0, comprised of mutually reinforcing strands that are intended to form a framework for a more holistic approach to dealing with the challenge of biological Weapons around the globe ln the 21st century (AU)

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2).

One Health and paradigms of public biobanking.

In this paper, the authors consider the idea of the public biobank governance framework with respect to the innovative paradigm of One Health. The One Health initiative has been defined as an integrative and interdisciplinary effort to improve the lives and well-being of human beings and non-human animals, as well as to preserve the environment. Here, we use this approach as a starting presumption with respect to institutional design. We examine the theoretical and legal framework underlying the concept of biobanking that, being public orientated, is for the public good. We suggest that this account of research practice does not ethically correlate with One Health principles. Instead, we argue that One Health requires a model of biobanking that is based on universal goods, that is, goods that serve human beings as well as non-human animals and the environment, and which we define in detail. Our purpose is to begin a discussion on how One Health principles might be implemented in health initiatives.

An overview of anthrax infection including the recently identified form of disease in injection drug users.

PURPOSE: Bacillus anthracis infection (anthrax) can be highly lethal. Two recent outbreaks related to contaminated mail in the USA and heroin in the UK and Europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world. METHODS: This review summarizes the microbiology, pathogenesis, diagnosis, and management of anthrax. RESULTS AND CONCLUSIONS: Anthrax, a gram-positive bacterium, has typically been associated with three forms of infection: cutaneous, gastrointestinal, and inhalational. However, the anthrax outbreak among injection drug users has emphasized the importance of what is now considered a fourth disease form (i.e., injectional anthrax) that is characterized by severe soft tissue infection. While cutaneous anthrax is most common, its early stages are distinct and prompt appropriate treatment commonly produces a good outcome. However, early symptoms with the other three disease forms can be nonspecific and mistaken for less lethal conditions. As a result, patients with gastrointestinal, inhalational, or injectional anthrax may have advanced infection at presentation that can be highly lethal. Once anthrax is suspected, the diagnosis can usually be made with gram stain and culture from blood or tissue followed by confirmatory testing (e.g., PCR). While antibiotics are the mainstay of anthrax treatment, use of adjunctive therapies such as anthrax toxin antagonists are a consideration. Prompt surgical therapy appears to be important for successful management of injectional anthrax.

Challenges in disposing of anthrax waste.

Disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. While many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. The Interagency Biological Restoration Demonstration's (IBRD) purpose was to holistically assess all aspects of an anthrax incident and assist in the development of a plan for long-term recovery. In the case of wide-area anthrax contamination and the follow-on response and recovery activities, a significant amount of material would require decontamination and disposal. Accordingly, IBRD facilitated the development of debris management plans to address contaminated waste through a series of interviews and workshops with local, state, and federal representatives. The outcome of these discussions was the identification of 3 primary topical areas that must be addressed: planning, unresolved research questions, and resolving regulatory issues.

Anthrax--update on diagnosis and management.

Human anthrax is difficult to contain. This is primarily because it is a zoonotic disease and the disease has never been contained in the livestock of India due to lack of adequate vaccination facilities. Animal anthrax is very common in many parts of India. The problem of anthrax is further compounded by lack of awareness on the part of village folk who unwittingly handle the hide and share the dead animal meat and this causes cutaneous and gastrointestinal forms of anthrax respectively. Hemorrhagic meningitis and pulmonary anthrax, the other forms of anthrax, carry a risk of nearly cent percent mortality. Characteristic gram positive rods abundantly found in the smear of the cerebrospinal fluid, blood etc. make diagnosis certain in most of the cases. Resistance to penicillin, the drug of choice, now being occasionally reported, may become a confounding factor while attempting successful control of the disease. Other antibiotics which are found to be very effective are doxycycline and ciprofloxacin. Fear of use of anthrax spores as a biological weapon has also given a new dimension to the problem.