Pretreatment with Ibuprofen Augments Circulating Tumor Necrosis Factor-α, Interleukin-6, and Elastase during Acute Endotoxinemia

Plasma levels of tumor necrosis factor-α (TNFα), interleukin-1 (IL-1),and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNFα concentrations with maximal levelsat 90 min (369 ± 44 pg/ml, P < .001 vs. saline controls, n = 7). The rise in TNF-α was followed by a rise in plasma IL-6 (27 ± 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNFα levels(627 ± 136 pg/ml) at 120 min and IL-6 peaks (113 ± 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNFα was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenaseinhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulatio

Objective hypoesthesia and pain after transabdominal preperitoneal hernioplasty: a prospective, randomized study comparing tissue adhesive versus spiral tacks

Background: Irritation of inguinal nerves with laparoscopic hernia repair may cause chronic neuralgia and hypoesthesia. Hypoesthesia in particular is generally not assessed objectively. We objectively investigated hypoesthesia and chronic pain after transabdominal preperitoneal inguinal hernia repair (TAPP) with titanium spiral tacks (STs) compared with tissue adhesive (TA) for mesh fixation. Methods: Mesh fixation in 80 TAPP procedures was randomized to fixation with ST (n=40) or TA (n=40). The outcome parameters included hypoesthesia assessed with von Frey monofilaments, early postoperative and chronic pain with the visual analog scale (VAS), morbidity (surgical-site infection, hematoma/seroma, relapse of hernia, trocar hernia), and recovery time to normal activity. Results: Median (range) follow-up was 38 (13-56) months. Demographic and baseline parameters were similar in the two groups. Prevalence of hypoesthesia was significantly higher at all postoperative times in the ST group (6weeks: 32 vs. 6%; 6months: 38 vs. 14%; 12months: 34 vs. 13%; 13-56months: 32 vs. 4%). Mean hypoesthesia scores over all time points were significantly higher in the ST group. The percentages of regions with hypoesthesia (abdominal, inguinal, or genitofemoral) following all procedures were higher in the ST group after 6weeks (14 vs. 2%), 6months (15 vs. 5%), and 13-56months (22 vs. 4%). The intensity of pain decreased significantly in both groups over time. Conclusions: Postoperative hypoesthesia depends on the method of mesh fixation during TAPP and is significantly reduced with TA compared with staplin

Quantifying system disturbance and recovery from historical mining-derived metal contamination at Brotherswater, northwest England

The final publication is available at Springer via https://doi.org/10.1007/s10933-016-9907-1Metal ore extraction in historical times has left a legacy of severe contamination in aquatic ecosystems around the world. In the UK, there are ongoing nationwide surveys of present-day pollution discharged from abandoned mines but few assessments of the magnitude of contamination and impacts that arose during historical metal mining have been made. We report one of the first multi-centennial records of lead (Pb), zinc (Zn) and copper (Cu) fluxes into a lake (Brotherswater, northwest England) from point-sources in its catchment (Hartsop Hall Mine and Hogget Gill processing plant) and calculate basin-scale inventories of those metals. The pre-mining baseline for metal contamination has been established using sediment cores spanning the past 1,500 years and contemporary material obtained through sediment trapping. These data enabled the impact of 250 years of local, small-scale mining (1696 – 1942) to be quantified and an assessment of the trajectory towards system recovery to be made. The geochemical stratigraphy displayed in twelve sediment cores show strong correspondence to the documented history of metal mining and processing in the catchment. The initial onset in 1696 was detected, peak Pb concentrations (>10,000 µg g-1) and flux (39.4 g m-2 y-1) corresponded to the most intensive mining episode (1863-1871) and 20th century technological enhancements were reflected as a more muted sedimentary imprint. After careful evaluation, we used these markers to augment a Bayesian age-depth model of the independent geochronology obtained using radioisotope dating (14C, 210Pb, 137Cs and 241Am). Total inventories of Pb, Zn and Cu for the lake basin during the period of active mining were 15,415 kg, 5,897 kg and 363 kg, respectively. The post-mining trajectories for Pb and Zn project a return to pre-mining levels within 54-128 years for Pb and 75-187 years for Zn, although future remobilisation of metal-enriched catchment soils and floodplain sediments could perturb this recovery. We present a transferable paleolimnological approach that highlights flux-based assessments are vital to accurately establish the baseline, impact and trajectory of mining-derived contamination for a lake catchment

Effects of medium- and long-chain fatty acids on whole body leucine and glucose kinetics in man

Elevation of plasma concentrations of nonesterified fatty acids (NEFA) has been reported to result in protein sparing and in impaired insulin-mediated glucose metabolism. To assess the influence of the chain length of fatty acids on these effects, medium-chain (MC) and long-chain (LC) fatty acid-containing lipid emulsions (2 mg/kg/min each) combined with heparin were administered during 390 minutes to 25 healthy overnight-fasted male subjects. Whole body leucine flux (a parameter of whole body protein breakdown) decreased during MC triglycerides (MCT) by 20% (P textless.005). Irreversible leucine catabolism (oxidation of [1-(13)C]-leucine) decreased during LC triglycerides (LCT) by 40% (P textless.01) but not during MCT when compared to controls receiving glycerol infusions. MCT administration resulted in a marked (52 %, P textless.001) decrease of alpha-ketoisocaproate (alpha-KIC) concentration, suggesting diminished leucine transamination and decreased leucine nonoxidative disappearance (P textless.015). Hyperinsulinemia (30 to 40 microU/mL, euglycemic clamping) resulted in decreased leucine flux and oxidation during both lipid infusions, particularly during MCT. The increase in glucose disappearance during hyperinsulinemia in subjects receiving MCT or LCT was less than in controls, and endogenous glucose production measured by 6,6-D(2)-glucose infusions was less suppressed (P textless.01). Thus, elevation of plasma LC fatty acids (but not of MC fatty acids) results in decreased leucine oxidation (protein catabolism). This protein-sparing effect of LCT appears to be dissociated from fatty acid effects on glucose metabolism; both MCT and LCT diminished insulin`s ability to increase glucose disappearance and to decrease hepatic glucose production