Necrotizing pancreatitis: pathophysiology, diagnosis, and acute care management.

Severe acute necrotizing pancreatitis is a disease that is caused by premature activation of pancreatic enzymes. Cytokine release contributes to systemic manifestations such as systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), adult respiratory distress syndrome (ARDS), and sepsis. Diagnosis is based on a history of abdominal pain, laboratory values such as serum amylase and lipase levels, and CT scan. Medical management focuses on fluid and electrolyte balance, antibiotic therapy, pain control, and decreasing systemic complications. Surgery is indicated when infectious pancreatic necrosis has been identified. This article addresses incidence and etiology; pathophysiology; clinical manifestations; diagnostics; and medical and surgical patient care management.

Microbial populations of Botrytis cinerea-inoculated strawberry fruit exposed to four volatile compounds.

Aerobic, microaerophilic, coliform, and mold populations of Botrytis cinerea-inoculated strawberry fruit not exposed (control) or exposed to low and high quantities of four volatile compounds during storage at 2 degrees C were determined after storage for 7 days and after removal of the volatile and transfer to 22 degrees C for 3 days. Fruit harvested at the ripe stage were inoculated with 10(6) conidia B. cinerea per ml and were placed in plastic containers containing no volatile compound (control) or two quantities of (E)-2-hexenal (10 or 100 microliters), (E)-2-hexenal diethyl acetal (30 or 300 microliters), benzaldehyde (30 or 300 microliters), or methyl benzoate (12 or 60 microliters). The fruit containers were overwrapped with a low-density polyethylene film, sealed, stored at 2 degrees C for 7 days, and then transferred to 22 degrees C for 3 days. Aerobic, microaerophilic, and coliform populations of fruit exposed to volatile compounds tended to be lower than the controls after storage at 2 degrees C for 7 days and, depending on the volatile compound, similar, lower, or higher than the controls after transfer and storage at 22 degrees C. However, due to variability in initial aerobic, microaerophilic, and coliform populations of the fruit used in the different trials (P < 0.05), none of the differences between control and treatment and between treatments within a sample time were significant (P > 0.05). Strawberry fruit exposed to 100 microliters of (E)-2-hexenal was the only treatment that did not show a significant increase in mold populations after transfer and storage at 22 degrees C for 3 days. Additional studies are needed to determine if (E)-2-hexenal can be used in combination with other postharvest storage conditions, such as low temperature and controlled/modified atmosphere, to delay mold spoilage and extend the shelf life of the strawberry.

Structural and stereoelectronic requirements for the inhibition of mammalian 2,3-oxidosqualene cyclase by substituted isoquinoline derivatives.

2,3-Oxidosqualene lanosterol-cyclase (OSC; EC 5.4.99.7) is an attractive target for the design of compounds that block hepatic cholesterol biosynthesis. (4a alpha, 5 alpha, 6 beta, 8a beta)-Decahydro-5,8a-dimethyl-2-(1,5,9-trimethyldecyl)-6- isoquinolinol (1) and simplified analogs have been devised to inhibit this enzyme by mimicking the postulated pro-C-8 high-energy intermediary carbocation occurring during the cyclization-rearrangement pathway. In order to gain an understanding into the mechanism by which these types of molecules inhibit OSC, we have synthesized a series of substituted isoquinoline derivatives 3 and investigated the structural and stereoelectronic requirements, and their stringency, that make 3 potential high-energy intermediate analogs of OSC. Determination of the IC50 values of the different compounds with rat liver microsomal cyclase, allowed the study of the relative importance of (i) the nature and the stereochemistry of the nitrogen side chain, (ii) the presence of methyl groups at C-5 and C-8a (ring junction), (iii) the presence and stereochemistry of the C-6 hydroxyl group, (iv) the nature of the ring junction, and (v) the absolute configuration of the bicyclic system. The resulting structure-activity relationships seem to validate the mechanism of action of these inhibitors as analogs of a pro-C-8 high-energy intermediate and delineate the minimal requirements for the design of efficient isoquinoline-based, or simplified, OSC inhibitors.