Tularemia - zoonosis carrying a potential risk of bioterrorism.

Tularemia, otherwise known as “rabbit fever”, is a zoonotic disease caused by a gram-negative intracellular bacterium - Francisella tularensis. The species is considered as a potential bioterrorism agent due to its high infectivity, the fact of being relatively easy to culture, the absence of human vaccine, and the potential for spreading through aerosol. In the Czech Republic, infection is usually caused by a tick bite, less frequently by a mosquito bite, direct contact with infected animals, or ingestion of contaminated water. The aim of this review is to provide a comprehensive view of tularemia, its diagnosis, clinical symptoms and treatment, along with the military perspective on a potential risk of F. tularensis to be misused as a biological weapon.

[Therapy of organophosphate poisoning in animals]. / Terapie otrav organofosfáty u zvírat

Per os intoxication of sheep with O-ethyl S-(2-dimethylaminoethyl)methyl phosphonium thioate (EDMM) in the dose of 0.209 mg per kg of live weight, that means p.o. LD50 (2 h), can be therapeutically mastered by means of an antidotal mixture of the reactivator of cholinesterase (trimedoxim) and of the cholinolytic (atropine), which is commercially available in the SPOFA preparation TMB-4 compos. for human purposes, if the effective dose of the reactivator was 10.0 mg per kg of live weight and if it was applied intravenously, and if the dose of the cholinolytic consisted, per 1 kg of live weight, of 0.08 mm. The antidotal mixture was applied, when the degree of the muscarinic and nicotinic symptoms and the corresponding degree of the inhibition of erythrocytary and plasmatic cholinesterase were on such a level which, according to the classification criteria, we consider a severe grade of intoxication with a dubious diagnosis.

[Therapy of domestic animals affected by alkylphosphates]. / Lécba hospodárských zvírat zasazených alkylfosfáty.

Sheep were studied for the possibility of treatment after parenteral (intramuscular) intoxication with EDMM (methylthiophosphorous acid O-ethyl-S-2-dimethylamino-ethylester) and with EDIM (methylthiophosphorous acid O-ethyl-S-2-diisopropyl-aminoethylester). In both cases of intoxication, the therapy was based on a system of an anticholinergic and cholinesterase reactivator administered singly at a time of the maximum development of the clinical signs of poisoning and maximum inhibition of both erythrocytic (AChE, E.C.3.1.1.7.) and plasma (BChE, E.C.3.1.1.8.) cholinesterase. The optimum therapeutic system requires the administration of 20.0 mg atropine s. c. pro toto and 10.0 mg trimedoxim per kg 1. w. i. v. In both cases of poisoning with doses = LD50 in i. m. administration, the mentioned system was actually positive. In a single administration irrespective of the doses of the used drugs, the system does not guarantee survival after ingestion of anticholinesterasic doses above LD50.

[Antidotal effect of TMB-4 compos. Spofa in sheep intoxicated with O-ethyl S-(2-dimethylaminoethyl) methyl phosphonothioate]. / Antidotní efekt TMB-4 compos. (Spofa) u ovcí intoxikovaných o-etyl S-(2-dimetylaminoetyl)metyl-fosfonotioátem

A single application of a mixture of cholinolytic and reactivator of cholinesterase (TMB-4 compos. SPOFA) administered intravenously in the dose of 10.0 mg of trimedoxim per kg of live weight to sheep for 60 minutes after an intramuscular intoxication with O-ethyl S-(2-dimethylaminoethyl) methyl phosphonothioate (EDMM) in the dose of 0.00835 mg per kg of live weight (i.m. LD50, 2h) produces an immediate clinical effect. The reactivation of the erythrocytary acetyl cholinesterase (AChE, E.C.3.1.1.7.) examined in 15 minutes after the administration of the antidotal mixture is almost 100 p.c., the reactivation of the plasmatic butyryl cholin esterase (ChE, E.C.3.1.1.8.) approx. from 70 to 80 p. c. Restitution ad integrum occurred not later than in 14 days after the intoxication.

[Treatment with antidotes in sheep perorally intoxicated]. / Antidotní terapie u ovcí intoxikovaných per os trichlórfonem

In a model of sheep perorally intoxicated with a 200.0 mg kg-1 trichlorphon dose, the effectivity of the worked out therapeutical procedure was confirmed; the procedure consisted in the administration of an anticholinergic (20.0 mg of 1.1% atropine s. c. pro toto) and cholinesterase reactivator (30.0 mg of 10% trimedoxime kg-1 i. m.) mixture 4 hours after the administration of the noxious agent. A determination of the erythrocytic acetylcholinesterase (AChE, E.C.3.1.1.7.) and plasmatic butyrylcholinesterase (BChE, E.C.3.1.1.8.) activities in the intoxicated sheep should be considered a decisive clinical and diagnostical test for taking veterinary-therapeutical, veterinary-hygienical or veterinary-sanitary measures in intoxications with anti-cholinesterase substances on the whole.

[Effect of cyclophosphamide on themetabolism of erythrocytes]. / Vliv cyklofosamidu na metabolismus erytrocytu

Cyclophosphamide was applied i.p. in the dose of 100 mg kg-1 to rats. After one, two, three, and seven days the animals were killed and in the collected heparinized blood the incorporation of o-phosphate 32P in erythrocytes was determined in vitro at 37 degrees C and in 35 minutes. Decreased incorporation in animals with Cyclophosphamide indicated, compared with the control, disturbed metabolism of phosphate. The method can be applied as a criterion of secondary toxic effects in the treatment of cancerostatics of alkylation type.