Stress induced in heart and other tissues by rat dermal exposure to JP-8 fuel.

Limited information is available regarding the development of systemic organ stress by dermal exposure to JP-8 fuel. In this study, the systemic stress potential of this fuel is evaluated in a rat model subjected to dermal applications of JP-8 for 7 days at 300 microl per day. Tissue histology indicated that JP-8 induces morphological alterations that suggest that tissue stress in the heart is more substantial than stress in the kidney and liver. Immunoblot analysis of tissues revealed increased levels of the inducible heat shock protein 70 (HSP70) in the heart, kidney, and liver after this dermal JP-8 exposure. This exposure also leads to increased levels of heme oxygenase-1 (HO-1/HSP3) in the liver. Additionally during this exposure, a negative regulator of inflammation, IkappaBalpha (inhibitor of NF-kappaB), was increased in the liver, slightly increased in the kidney, and not increased in the heart. Two regions of the rat brain were also examined and HSP70 and IkappaBalpha were increased in the cerebellum but not significantly increased in the cortex. This study indicates dermal JP-8 exposure causes systemic alterations that are associated with cytoprotective activities (e.g., in the liver) as well as potentially toxic mechanisms (heart and kidney).

Mercuric ion inhibition of eukaryotic transcription factor binding to DNA.

Mercury has harmful effects in both rodents and humans. In rodent tissue culture cells exposed to HgCl(2), the metal ions were observed to concentrate in cell nuclei and to associate with chromatin. Thus, transcription factors and other proteins associated with chromatin are possible targets of mercuric ion toxicity. In this study, mercuric ions were found to inhibit the DNA binding activity of the Cys(2)His(2) zinc finger proteins transcription factor IIIA (TFIIIA) and Sp1. These factors are prototypes of the largest eukaryotic protein superfamily. Neither the presence of excess zinc ions nor beta-mercaptoethanol prevented inhibition by mercuric ions. Mercuric ions also inhibited DNA binding by the non-zinc finger protein AP2. Zinc finger-DNA binding was inhibited when both TFIIIA/5S RNA complex and TFIIIA alone were preincubated with concentrations as low as 15 microM mercuric ion. Inhibition occurred in less than 1 min and was not readily reversible. Mercuric ions also inhibited the digestion of DNA by the restriction enzymes BamHI or EcoRI. Inhibition of transcription factors as well as potentially other DNA binding proteins by micromolar concentrations of mercuric ion suggests additional biochemical mechanisms for mercury toxicity in promoting disease via alterations in gene transcription patterns.

Fatal aortic thrombosis in a neonate during infusion of epsilon-aminocaproic acid.

Hemorrhagic complications are common in patients placed on extracorporeal life support (ECLS), especially in those who have additional risk factors. Several centers use epsilon-aminocaproic acid (EACA) in their high-risk ECLS patients in an attempt to decrease the incidence of such complications, despite the fact that no controlled trials have been performed examining the risks and benefits of its use. The authors report the case of a neonate who had fatal aortic thrombosis during EACA administration. Also included is a discussion of the use of EACA in patients who require cardiopulmonary bypass.

Extracorporeal membrane oxygenation and early-onset group B streptococcal sepsis.

Recently, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy for newborns with overwhelming early-onset group B streptococcal sepsis. To determine which clinical factors best predict mortality and to evaluate the outcome of this therapy, a retrospective examination of the clinical course and outcome of ECMO-eligible newborns with early-onset group B streptococcal sepsis was undertaken. The study period was divided into two phases based on when ECMO was initially used at Kosair Children's Hospital as therapy for septic neonates. Phase 1 (pre-ECMO) was the period from January 1, 1982, through June 15, 1986, and phase 2 (ECMO) from June 16, 1986, through December 31, 1989. Newborns with gestational age greater than or equal to 34 weeks, birth weight greater than or equal to 2000 g, and evidence of early-onset group B streptococcal sepsis were eligible for study. Only newborns who received mechanical ventilation were evaluated. Sixteen patients from phase 1 met the above criteria. Of those, 10 exhibited no sign of hypotension and all survived. Of the 6 patients with hypotension, 3 died. Forty patients were identified from phase 2. Seven patients remained normotensive and all survived. Thirty-three patients were hypotensive, of which 15 received ECMO and 13 survived. Of the 18 who did not receive ECMO, 7 died. Regarding all hypotensive newborns, those who did not receive ECMO had a trend toward lower survival (P less than .06) and were more likely to die if they were of lower birth weight, manifested a persistent acidosis (pH less than or equal to 7.25), and had an absolute neutrophil count less than 500 cells/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extracorporeal membrane oxygenation on leukocyte function in neonates.

The impact of extracorporeal membrane oxygenation (ECMO) on neonatal leukocyte content and function was examined in six patients. Patients were treated with ECMO for a mean of 134 h (range 44-246 h). Absolute neutrophil counts decreased from 14679 +/- 2291/mm3 to 7791 +/- 1672/mm3 after 2 h of ECMO. However, neutrophil phagocytosis and oxidative burst remained unchanged during the first 48 h of bypass. Monocyte counts also decreased during bypass, and at times were undetectable in 50% of patients. Monocyte HLA-DR content was decreased compared to normal cord blood prior to initiation of ECMO, and remained low throughout ECMO. However, the content increased significantly after termination of bypass. Plasma C3a levels increased transiently, paralleled by an increase in neutrophil CR3 expression. While moribund infants had some impairment of host defenses prior to ECMO, there was no further impact of ECMO per se on the parameters measured, other than transient complement activation and decreased monocyte counts.