Secretory event in intestinal grafts during preservation ischemia.

BACKGROUND: Ischemia triggers secretion of proteins from the intestine, including type II secretory phospholipase A2 (sPLA2). This "secretory event" was studied in intestinal grafts during the first few hours of preservation by measuring total protein, sPLA2, and other enzymes in the UW preservation solution over time. The effect of PX-13, a PLA2 inhibitor, was also studied. MATERIALS AND METHODS: Twenty-five centimeter intestinal grafts were harvested from Lewis rats, flushed, and preserved in UW solution +/- PX-13 at 4 degrees C. UW samples from 0 to 48 h (n = 5 each) were analyzed for total protein, sPLA2, lactate dehydrogenase (LDH), N-acetylglucosamine (NAGA), and lysozyme. Nonpreserved grafts were homogenized in PBS as tissue controls. Standard biochemical methods were used for all assays. RESULTS: Total protein increased rapidly by 5 min, continued to rise more slowly until 30 min, and then stabilized. The most significant increase in sPLA2 activity occurred between 90 and 180 min. NAGA increased most markedly between 30 and 180 min, while LDH increased in the first 30 min, although the level of both enzymes was negligible compared to tissue enzyme. Lysozyme levels were minimal at all times. PX-13 decreased sPLA2 activity markedly at all time points. CONCLUSION: Total protein levels increased before sPLA2, suggesting that sPLA2 may be secreted in response to other proteins or enzymes released even earlier during preservation (e.g., cytokines). These elevations do not appear to be caused by cell death. Phospholipase A2 secretion may be blocked, and this may greatly improve the outcome of intestinal preservation.

Symposium on geriatrics--Part I: Drug prescribing for elderly patients.

OBJECTIVE: To describe the pharmacokinetic and pharmacodynamic changes that occur with aging and to discuss common problems noted with the use of medications often prescribed for elderly patients. DESIGN: We searched the medical literature, reviewed pertinent articles, and summarized drug-related information applicable to geriatric patients. RESULTS: Use of medications is common in the elderly population; most elderly persons take two or more different medications each day. Aging is associated with anatomic and physiologic changes that can have an effect on how medications are handled. Such changes include alterations in various volumes of drug distribution and in drug absorption, metabolism, and clearance. Elderly patients may also have increased or decreased drug effects because of alteration in receptor response. These changes in pharmacokinetics and pharmacodynamics may result in a prolonged drug half-life, an increased potential for drug toxicity, and a greater likelihood for adverse drug reactions. CONCLUSION: Medications for elderly patients should be prescribed only after the anatomic and physiologic changes of aging are understood and with increased surveillance for potential drug toxicity or adverse drug reactions.