We conducted a randomized, double-blind trial to compare the efficacy of preincisional and postincisional wound infiltration with 1% lidocaine (40 mL) on the postoperative pain of 37 patients scheduled for elective inguinal herniotomy. The demand for additional postoperative analgesics occurred earlier in those who received lidocaine infiltration after incision (165 min) than in those who received preincisional lidocaine (225 min, P less than 0.05). The preincisional lidocaine infiltration group also had fewer patients requiring supplemental analgesics (58%) than the postincisional group (94%) (P less than 0.05). We conclude that preincisional infiltration of the surgical wound with lidocaine is a more effective method of providing postoperative analgesia than is postincisional infiltration.

The present study was undertaken to investigate fat metabolism after a high-fat meal [50 energy percent (E%) fat] in formerly obese subjects with a familial history of obesity. Twelve normal-weight postobese women (PO) and 12 closely matched controls were given the test meal after a 2-day carbohydrate-rich weight-maintenance diet (58 E% carbohydrate). Whereas the thermic effect of the meals was similar in the two groups, postprandial fat oxidation was 2.5 times more suppressed in PO compared with controls (P < 0.05). A similarly enhanced suppression of arterialized plasma concentrations of nonesterified fatty acids was seen postprandially in PO (P < 0.05), possibly due to a more marked suppression of epinephrine and a reduced glucagon response in PO than in controls. Moreover, the postprandial plasma triglyceride response was attenuated and only amounted to 43% of that in controls (P < 0.05). This may be explained by a more pronounced increase in gastric inhibitory polypeptide in PO, giving rise to a higher adipose tissue lipoprotein lipase activity. No other differences were found in plasma substrates and hormones or in subjective appetite scores. In conclusion, a metabolic and hormonal pattern favoring lipid storage was observed in postobese subjects after a high-fat meal.

Polyethylenimines (PEIs) are among the most efficient polycationic non-viral transfectants. PEI architecture and size not only modulate transfection efficiency, but also cytotoxicity. However, the underlying mechanisms of PEI-induced multifaceted cell damage and death are largely unknown. Here, we demonstrate that the central mechanisms of PEI architecture- and size-dependent perturbations of integrated cellular metabolomics involve destabilization of plasma membrane and mitochondrial membranes with consequences on mitochondrial oxidative phosphorylation (OXPHOS), glycolytic flux and redox homeostasis that ultimately modulate cell death. In comparison to linear PEI, the branched architectures induced greater plasma membrane destabilization and were more detrimental to glycolytic activity and OXPHOS capacity as well as being a more potent inhibitor of the cytochrome c oxidase. Accordingly, the branched architectures caused a greater lactate dehydrogenase (LDH) and ATP depletion, activated AMP kinase (AMPK) and disturbed redox homeostasis through diminished availability of nicotinamide adenine dinucleotide phosphate (NADPH), reduced antioxidant capacity of glutathione (GSH) and increased burden of reactive oxygen species (ROS). The differences in metabolic and redox imprints were further reflected in the transfection performance of the polycations, but co-treatment with the GSH precursor N-acetyl-cysteine (NAC) counteracted redox dysregulation and increased the number of viable transfected cells. Integrated biomembrane integrity and metabolomic analysis provides a rapid approach for mechanistic understanding of multifactorial polycation-mediated cytotoxicity, and could form the basis for combinatorial throughput platforms for improved design and selection of safer polymeric vectors.

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