A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation.

Resolution of inflammation is an active counter-regulatory mechanism involving polyunsaturated fatty acid-derived proresolving lipid mediators. Postoperative intestinal motility disturbances, clinically known as postoperative ileus, occur frequently after abdominal surgery and are mediated by a complex inflammation of the intestinal muscularis externa. Herein, we tested the hypothesis that proresolving lipid mediators are involved in the resolution of postoperative ileus. In a standardized experimental model of postoperative ileus, we detected strong expression of 12/15-lipoxygenase within the postoperative muscularis externa of C57BL/6 mice, predominately located within CX3CR1(+)/Ly6C(+) infiltrating monocytes rather than Ly6G(+) neutrophils. Mass spectrometry analyses demonstrated that a 12/15-lipoxygenase increase was accompanied by production of docosahexaenoic acid-derived lipid mediators, particularly protectin DX and resolvin D2, and their common precursor 17-hydroxy docosahexaenoic acid. Perioperative administration of protectin DX, but not resolvin D2 diminished blood-derived leukocyte infiltration into the surgically manipulated muscularis externa and improved the gastrointestinal motility. Flow cytometry analyses showed impaired Ly6G(+)/Ly6C(+) neutrophil extravasation after protectin DX treatment, whereas Ly6G(-)/Ly6C(+) monocyte numbers were not affected. 12/15-lipoxygenase-deficient mice, lacking endogenous protectin DX synthesis, demonstrated increased postoperative leukocyte levels. Preoperative intravenous administration of a docosahexaenoic acid-rich lipid emulsion reduced postoperative leukocyte infiltration in wild-type mice but failed in 12/15-lipoxygenase-deficient mice mice. Protectin DX application reduced leukocyte influx and rescued 12/15-lipoxygenase-deficient mice mice from postoperative ileus. In conclusion, our results show that 12/15-lipoxygenase mediates postoperative ileus resolution via production of proresolving docosahexaenoic acid-derived protectin DX. Perioperative, parenteral protectin DX or docosahexaenoic acid supplementation, as well as modulation of the 12/15-lipoxygenase pathway, may be instrumental in prevention of postoperative ileus.

p38 Mitogen-activated protein kinase is required for electroacupuncture restoration of CD4+/CD8+ homeostasis and cytokine expression in a rodent model of surgical trauma.

Cumulative evidences addressed that electroacupuncture (EA) was favorably effective in the treatment of trauma stress-induced immunodeficiency and physical disorders. However, the salutary effects of EA under operation trauma conditions mediated via p38 MAPK remain unknown. Hence, our study aimed to further investigate the effects of EA on CD4(+)/CD8(+) homeostasis and cytokine expressions, and evaluate the p38 MAPK signaling regulatory mechanism of EA effects.

Modulation of matrix metalloproteinase activity by EDTA prevents posterior capsular opacification.

PURPOSE: To evaluate the effect of ethylenediaminetetraacetic acid (EDTA) on posterior capsular opacification (PCO) of rabbits and to assess its effect on intraocular tissues. METHODS: Modulation of matrix metalloproteinase (MMP) activity in the aqueous following cataract surgery in rabbits and its prevention by different doses of EDTA was determined by zymography. For evaluation of PCO, lensectomized rabbits were intracamerally injected with single dose of either 5 mg EDTA or normal saline. After one month, the degree of PCO was determined by slitlamp biomicroscopy, Miyake-Apple view, and histology of the lens capsule. The effect of EDTA on intra ocular pressure (IOP), corneal endothelial cells, and the retina was evaluated by tonometry, specular microscopy and scanning electron microscopy, and electroretinography. The concentration of EDTA in the aqueous was determined by high performance liquid chromatography (HPLC) at different time points. RESULTS: The MMP activity was significantly increased in the aqueous of the operated eyes, and EDTA reduced the degree of increase in a dose-dependent manner. EDTA treatment significantly reduced the degree of PCO (p<0.05). Histopathology of the lens capsule showed a reduction in the number of proliferating and migrating cells as well as MMP2 expression in the EDTA-treated eyes. EDTA treatment did not change the IOP; density, morphology and ultrastructure of the corneal endothelial cells; and electroretinography (ERG). EDTA was detectable in the aqueous humor up to 72 h following a single intracameral injection. CONCLUSIONS: EDTA reduces the degree of PCO by suppressing the MMP activity and it is not toxic to intra ocular structures at the concentration used.

Impact of food and herbal medication on calcineurin inhibitor dose in renal transplant patients: a cross-sectional study.

The incidence and severity of interactions of herbal products with calcineurin inhibitor (CNI) metabolism in renal transplant recipients have not been systematically investigated. These patients have a high rate of herbal product consumption, including products interfering with CNI metabolism. The study aimed at identifying an impact of herbs and foods on CNI metabolism in a cohort of renal transplant recipients by conducting dietary interviews (1) in patients with very low and high CNI maintenance dose requirements and (2) by retrospective analysis of unexplained marked deviations from CNI baseline trough levels. Of 73 renal transplant recipients, 59 were treated with a CNI-based immunosuppressive regimen. Seven patients with an exceptionally high or low CNI dose were interviewed. Five of these seven patients had not consumed any plant product with known influence on CNI metabolism. In one patient chicory-coffee and bitter chocolate had been suspected as contributing to high CNI dose requirement, but the dose could not be lowered after discontinuation of these foods. Participating nephrologists reported three as yet unexplained temporary deviations from baseline CNI trough levels, of which two could be linked to newly started consumption of high volumes of herbal teas and the other to St. John's wort. Consumption of herbal products within the study cohort had no detectable impact on maintenance doses of CNI. However, herbal products, and specifically teas when consumed by the liter, could be linked to temporary strong deviations from CNI trough levels. The study demonstrates that as yet unnoticed herbal interactions with CNI can be detected by detailed dietary analysis, but that the overall impact on maintenance doses of CNI appears to be low.

Effects of electrical muscle stimulation combined with voluntary contractions after knee ligament surgery.

The aim of the present study is to compare the effect of electrical muscle stimulation combined with voluntary muscle contractions with a program only with voluntary muscle contractions during immobilization in casts after anterior cruciate ligament surgery. Twenty-three patients, 7 women and 16 men with a mean age of 28 yr, were randomized into two groups: an experimental group (13 patients) and a control group (10 patients). Post-operatively, the patients were immobilized for 3 wk in a full leg cast with the knee flexed at an angle of 20 degrees to 30 degrees and then in a knee cast for another 3 wk. All patients had a standard program with quadriceps muscle contractions. In addition, the experimental group received electrical stimulation of the quadriceps muscle 4 X 10 min, 3 times.wk-1, at a frequency of 30 Hz. During each stimulation, the patients were requested to contract the quadriceps muscle voluntarily as well. When pre-operative measurements were compared with those at the end of the immobilization period (6 wk after the operation), a significantly larger reduction in the knee extension isometric muscle strength was found for the control group than for the experimental group. In comparisons of the data of the male subjects only, this difference was still seen to be significant. The cross-sectional area of the quadriceps muscle measured with computed tomography was significantly less reduced during the immobilization period in the experimental group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)