Acute health effects after exposure to chlorine gas released after a train derailment.

In January 2005, a train derailment on the premises of a textile mill in South Carolina released 42 to 60 tons of chlorine gas in the middle of a small town. Medical records and autopsy reports were reviewed to describe the clinical presentation, hospital course, and pathology observed in persons hospitalized or deceased as a result of chlorine gas exposure. Eight persons died before reaching medical care; of the 71 persons hospitalized for acute health effects as a result of chlorine exposure, 1 died in the hospital.

Rapid assessment of exposure to chlorine released from a train derailment and resulting health impact.

Objectives: After a train derailment released approximately 60 tons of chlorine from a ruptured tanker car, a multiagency team performed a rapid assessment of the health impact to determine morbidity caused by the chlorine and evaluate the effect of this mass-casualty event on health-care facilities.

Methods: A case was defined as death or illness related to chlorine exposure. Investigators gathered information on exposure, treatment received, and outcome through patient questionnaires and medical record review.

Panel classification of self-reported exposure histories: a useful exposure index after a mass-casualty event.

Objective: Although rapid epidemiologic investigations of toxic exposures require estimates of individual exposure levels, objective measures of exposure are often unavailable. We investigated whether self-reported exposure histories, when reviewed and classified by a panel of raters, provided a useful exposure metric.

Methods: A panel reviewed exposure histories as reported by people who experienced a chlorine release.

The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds.

We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from Trypanosoma cruzi in the micromolar range.

Steady-state kinetics of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi.

The kinetic mechanism for the reaction catalyzed by the hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi was analyzed to determine the feasibility of designing a parasite-specific mechanism-based inhibitor of this enzyme. The results show that the HPRT from T. cruzi follows an essentially ordered bi-bi reaction, and like its human counterpart also likely forms a dead end complex with purine substrates and the product pyrophosphate.

Interactions at the dimer interface influence the relative efficiencies for purine nucleotide synthesis and pyrophosphorolysis in a phosphoribosyltransferase.

Enzymes that salvage 6-oxopurines, including hypoxanthine phosphoribosyltransferases (HPRTs), are potential targets for drugs in the treatment of diseases caused by protozoan parasites. For this reason, a number of high-resolution X-ray crystal structures of the HPRTs from protozoa have been reported. Although these structures did not reveal why HPRTs need to form dimers for catalysis, they revealed the existence of potentially relevant interactions involving residues in a loop of amino acid residues adjacent to the dimer interface, but the contributions of these interactions to catalysis remained poorly understood.

Role of the long slender to short stumpy transition in the life cycle of the african trypanosomes.

It is shown using mouse models that the African trypanosomes exert a significant drain upon their host's carbohydrate (energy) resources; and that the higher the parasitemia, the greater the energy demand. It is, therefore, hypothesized that the long slender (LS) to short stumpy (SS) transition evolved, in part, to help control the parasitemia and to increase host survival time. It is also suggested that the SS population is heterogeneous.