Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal sepsis in rats.

Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not 2CLP. In male Sprague-Dawley rats, hepatic necrosis, as determined by serum alpha-glutathione S-transferase (alpha-GST) levels, was significantly but equally elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and morphological examination, was minimal after both CLP and 2CLP. Regeneration, assayed by staining tissue for incorporation of exogenously administered bromodeoxyuridine, was present after CLP but not after 2CLP. To further substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB, LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein kinase-linked proliferative pathway and progression through the cell cycle. Therefore, failed hepatocyte regeneration may be a manifestation of hepatic dysfunction in fulminant sepsis.

Sepsis-induced depression of rat glucose-6-phosphatase gene expression and activity.

Sepsis in rats decreases the hepatic expression of the gluconeogenic enzyme glucose-6-phosphatase (G6Pase). The aim of this study was to investigate the relationship among G6Pase transcription, mRNA, enzymatic activity, and serum glucose levels at different intervals during mild or fulminant sepsis. Both fulminant and mild sepsis immediately decreased hepatic G6Pase mRNA levels. In mild sepsis, levels began to recover late in the time course. Serum glucose levels were maintained in mild sepsis but decreased markedly in fulminant sepsis. G6Pase transcription after fulminant sepsis decreased and never recovered. A similar transcriptional decrease was noted in mild sepsis, but some recovery occurred in this state. Histochemistry after mild sepsis revealed a decrease in G6Pase protein and enzymatic activity that paralleled transcription. These studies suggest that changes in G6Pase transcription and activity are early markers for sepsis-induced alterations in hepatic function. Mechanisms other than gene expression and enzymatic activity serve to maintain glucose levels in mild sepsis, but in the fulminant disorder, compensatory mechanisms fail and hypoglycemia develops.

The intellectual decline of the health care left.

The health care left-a traditional source of critique and reform-has become intellectually less competent and politically less effective in carrying out its historic role in the continuing great debate over health policies and programs. Its credibility has diminished in recent years as it has come to operate on a series of undocumented assumptions: 1) that malevolence and greed are at the roots of adverse decision-making in health-care policies and programs; 2) that budgetary constraints are little more than convenient alibis to account for programmatic inadequacies; 3) that treachery, lack of social commitment and careerism are the major explanations for the behavior of public health professionals; and 4) that substantive progress in social legislation and service delivery has not occurred. A self-respecting health care left that wishes to be taken seriously once more will revive its former allegiance to objective empirical data, will abandon simplistic explanations and will eschew inflated rhetoric and habitual invective.