Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator.

Efforts to explore possible relationships between nitric oxide (NO) and antioxidant enzymes in an Escherichia coli model have uncovered a possible interaction between sodium nitroprusside (SNP), a potent, NO-donating drug, and the ferric uptake regulator (Fur), an iron(II)--dependent regulator of antioxidant and iron acquisition proteins present in Gram-negative bacteria. The enzymatic profiles of superoxide dismutase and hydroperoxidase during logarithmic phase of growth were studied via non-denaturing polyacrylamide gel electrophoresis and activity staining specific to each enzyme. Though NO is known to induce transcription of the manganese-bearing isozyme of SOD (MnSOD), treatment with SNP paradoxically suppressed MnSOD expression and greatly enhanced the activity of the iron-containing equivalent (FeSOD). Fur, one of six global regulators of MnSOD transcription, is uniquely capable of suppressing MnSOD while enhancing FeSOD expression through distinct mechanisms. We thus hypothesize that Fur is complacent in causing this behaviour and that the iron(II) component of SNP is activating Fur. E. coli was also treated with the SNP structural analogues, potassium ferricyanide (PFi) and potassium ferrocyanide (PFo). Remarkably, the ferrous PFo was capable of mimicking the SNP-related pattern, whereas the ferric PFi was not. As Fur depends upon ferrous iron for activation, we submit this observation of redox-specificity as preliminary supporting evidence for the hypothesized Fur-SNP interaction. Iron is an essential metal that the human innate immune system sequesters to prevent its use by invading pathogens. As NO is known to inhibit iron-bound Fur, and as activated Fur regulates iron uptake through feedback inhibition, we speculate that the administration of this drug may disrupt this strategic management of iron in favour of residing Gram-negative species by providing a source of iron in an otherwise iron-scarce environment capable of encouraging its own uptake. However, these gains may be counteracted by the oxidative consequences of iron and NO, as the former can catalyse the formation of toxic free radical species while the latter can inhibit enzymes and contribute to the formation of other toxic compounds. The potential consequences of SNP on microbial growth warrant future investigation.

Acquired immunodeficiency syndrome (AIDS).

PIP: This review article on acquired immunodeficiency syndrome (AIDS) covers its epidemiology, clinical spectrum, and etiology. Despite intensive efforts, the cause and pathogenesis of this syndrome remain unknown and effective therapy is not yet available. In addition, the clinical presentation of AIDS is variable, ranging from generalized lymphadenopathy to dermatologic lesions, pneumonias, enteritis, ophthalmologic lesions, disseminated disease, malignancies, neurologic conditions, paresthesias, radiculopathies, seizures, and psychiatric manifestations. The population at risk for AIDS icludes homosexual or bisexual men (71% of cases), intravenous drug abusers (17%), those born in Haiti who recently migrated to the US (5%), and hemophiliacs (1%). 6% of cases reported to the US Centers for Disease Control (CDC) fall in none of these categories. 47% of AIDS patients are 30-39 years of age at time of diagnosis. The CDC's strict surveillance definition of AIDS represents only 1 end of the clinical spectrum and could result in an underestimate of the size of the problem. It ignores the prodromal or milder forms of AIDS-related illnesses that have less clearly defined clinical courses. The persistent, irreversible immunosuppression characteristic of this syndrome creates a complex management problem for physicians, but the early recognition of AIDS by emergency and primary care physicians may improve the grim prognosis for AIDS victims.^ieng