RESUMO
Many organophosphorus compounds (OPs) are potent cholinesterase inhibitors, accounting for their use as insecticides and, unfortunately, also as nerve agents. Each year there are approximately 3 million pesticide poisonings world-wide resulting in 220,00 deaths. In 1990, there were 1.36 million kg of chlorpyrifos, 4.67 million kg of diazinon and 1.23 million kg of ethyl parathion manufactured in the USA (data supplied by the USEPA). In addition to exposure risks during pesticide manufacturing, distribution and use, there are risks associated with the major international effort aimed at destroying the arsenals of nerve agents, including soman and sarin. The United States has pledged to destroy approximately 25,000 tons of chemical agents by the end of the decade. The high density lipoprotein (HDL)-associated enzyme paraoxonase (PON1) contributes significantly to the detoxication of several OPs (Fig. 1). The insecticides parathion, chlorpyrifos and diazinon are bioactivated to potent cholinesterase inhibitors by cytochrome P-450 systems. The resulting toxic oxon forms can be hydrolysed by PON1, which also hydrolyses the nerve agents soman and sarin (Fig. 1). PON1 is polymorphic in human populations and different individuals also express widely different levels of this enzyme. The Arg192 (R192) PON1 isoform hydrolyses paraoxon rapidly, while the Gln192 (Q191) isoform hydrolyses paraoxon slowly. Both isoforms hydrolyse chlorpyrifos-oxon and phenylacetate at approximately the same rate. The role of PON1 in OP detoxication is physiologically significant. Injected PON1 protects against OP poisoning in rodent model systems and interspecies differences in PON1 activity correlate well with observed median lethal dose (LD50) values. We report here a simple enzyme analysis that provides a clear resolution of PON1 genotypes and phenotypes allowing for a reasonable assessment of an individual's probable susceptibility or resistance to a given OP, extending earlier studies on this system. We also show that the effect of the PON1 polymorphism is reversed for the hydrolysis of diazoxon, soman and especially sarin, thus changing the view of which PON1 isoform is considered to be protective.
Assuntos
Esterases/sangue , Esterases/genética , Compostos Organofosforados/metabolismo , Sarina/metabolismo , Soman/metabolismo , Arildialquilfosfatase , Substâncias para a Guerra Química/metabolismo , Substâncias para a Guerra Química/farmacologia , Resistência a Medicamentos/genética , Esterases/efeitos dos fármacos , Homozigoto , Humanos , Isoenzimas , Compostos Organofosforados/farmacologia , Polimorfismo Genético , Sarina/farmacologia , Soman/farmacologia , América do SulRESUMO
A study was undertaken to identify the common micro-organisms occuring in induced sputum specimens from HIV-infected/non-infected individuals with pulmonary manifestations in Trinidad. Only 13 percent of HIV seropositive patients with pneumonia were found to be positive for P. carinii. This low yield may have been due to low prevalence of the P. carinii in Trinidad or to prior antibiotic therapy. Active mycobacterial infection was demonstrated in only 13 percent HIV seropositive patients with pneumonia, though 43 percent HIV patients had a clinical diagnosis of tuberculosis. This may have been due to the low sensitivity of the acid-fast technique. The most common microbial pathogen is identified in HIV patients with pneumonia was Candida sp. Followed by gram negative bacteria. A listing is made of the various organisms occuring singly or mixed in HIV seropositive and HIV seronegative patients (AU)
Assuntos
Humanos , HIV , Infecções Bacterianas , Trinidad e Tobago , Região do CaribeRESUMO
G-banded karyotypes of Rattus norvegicus fibroblast cells at the late prophase, prometaphase, early metaphase, mid and late metaphase, and diagrammatic representation of the banding patterns at the 450-band level are presented. High-resolution G-banded rat chromosomes were prepared following the actinomycin D pretreatment technique. Silver-stained nucleolus organizer regions (Ag-NORS) were found in chromosome pairs 3, 11 and 12 of the rat karyotype.