Increased plasma zonulin in patients with sepsis.

INTRODUCTION: Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. MATERIALS AND METHODS: Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). RESULTS: Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). CONCLUSION: We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

Supplemental postoperative oxygen and tissue oxygen tension in morbidly obese patients.

BACKGROUND: Subcutaneous tissue oxygen tension (PsqO(2)) is a major predictor for wound healing and the occurrence of wound infections. Perioperative subcutaneous wound and tissue oxygen tension is significantly reduced in morbidly obese patients. Even during intraoperative supplemental oxygen administration, PsqO(2) remains low. Tissue hypoxia is pronounced during surgery and might explain the substantial increase in infection risk in obese patients. It remains unknown whether long-term supplemental postoperative oxygen augments tissue oxygen tension. Consequently, we tested the hypothesis that 80% inspired oxygen administration during 12-18 postoperative hours significantly increases PsqO(2) compared to 30% inspired oxygen fraction. METHODS: After IRB approval and informed consent, 42 patients undergoing laparoscopic bariatric surgery were randomly assigned to receive either 80% inspired oxygen via a PULMANEX Hi-Ox Mask (Viasys MedSystems, Wheeling, IL) (10 L/min) or 30% oxygen via nasal cannula (2 L/min) after surgery until the next morning. PsqO(2) was measured with a temperature-corrected Clark-type electrode in the subcutaneous tissue of the upper arm and adjacent to the wound. RESULTS: Postoperative subcutaneous tissue oxygen tension was significantly increased in the Hi-Ox group: 58 (47.7, 74.1) mmHg vs. 43 (38.7, 55.2) mmHg, P = 0.002. Also, wound tissue oxygen tension was improved during supplemental oxygen administration: 75.2 (69.8, 95.5) mmHg vs. 52.4 (46.3, 66.1) mmHg, P < 0.001. CONCLUSION: Subcutaneous tissue oxygen tension was significantly increased by supplemental postoperative oxygen administration. Whether there is an effect on the incidence of wound infection in morbidly obese patients is matter of further research.

Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial.

BACKGROUND: Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery. METHODS: We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level. RESULTS: After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), P = 0.72. No two-way interactions with the treatment were statistically significant. CONCLUSION: Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer. IMPLICATIONS STATEMENT: The risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery. TRIAL REGISTRATION: Current Controlled Clinical Trials NCT00781352 http://www.clinicaltrials.gov.

Garlic at dietary doses does not impair platelet function.

BACKGROUND: In vitro studies suggest that various bioactive constituents of Allium sativum (garlic) inhibit platelet function. The extent, however, to which dietary doses of garlic influence platelet function remains unknown. Therefore, we tested the effect of raw garlic on platelet function using point-of-care monitoring devices sensitive for cyclooxygenase I-inhibition and platelet adhesion. METHODS: Whole blood from 18 healthy volunteers was investigated before and 5 h after ingestion of the study medication consisting of Greek tsatsiki with 4.2 g raw garlic (verum), or Greek tsatsiki without garlic (placebo), in a randomized, crossover, observer-blinded, placebo-controlled study. The potential long-term effects of garlic were investigated in five volunteers after daily ingestion of 4.2 g of raw garlic over 1 wk. Platelet function was assessed with the Platelet Function Analyzer (PFA-100), impedance aggregometry (Multiplate), and thrombelastographic Platelet Mappingtrade mark. In vitro experiments were performed to prove the sensitivity of the assays to garlic-induced platelet inhibition. RESULTS: Baseline values of platelet function were within normal range in all volunteers. Platelet function was not impaired by single and repeated oral consumption of Greek tsatsiki containing raw garlic in any point-of-care monitoring test used. CONCLUSIONS: Platelet function is not impaired by single and repeated oral consumption of a dietary dose of garlic in healthy volunteers. Dishes containing socially acceptable doses of raw garlic are unlikely to increase the risk of perioperative bleeding. Further studies are warranted to determine the potential additive effects of platelet-inhibiting drugs combined with garlic and other herbs.

The effects of test temperature and storage temperature on platelet aggregation: a whole blood in vitro study.

We systematically evaluated the effects of test temperature and storage temperature on platelet aggregation using flow cytometry and impedance aggregometry. Aliquots of citrated whole blood from 27 healthy adult male volunteers were stored at 37 degrees C and 22 degrees C. Aliquots were subjected to impedance aggregometry in response to collagen, adenosine diphosphate, ristocetin, and arachidonic acid performed at 22 degrees C, 34 degrees C, 37 degrees C, and 40 degrees C. The expression of activated fibrinogen receptor was determined on adenosine diphosphate-activated platelets at 22 degrees C and 37 degrees C by whole blood flow cytometry using PAC-1 for fluorescent staining. Aggregation induced by collagen, ristocetin, and arachidonic acid was not significantly different at the test temperatures of 34 degrees C and 37 degrees C but was significantly impaired at 22 degrees C. In contrast, adenosine diphosphate-induced aggregation was significantly increased at both 34 degrees C and 22 degrees C. Hyperthermia exclusively impaired collagen-induced aggregation. Storage temperature of 22 degrees C exclusively enhanced adenosine diphosphate- and collagen-induced aggregation compared with storage at 37 degrees C. The binding of PAC-1 was enhanced at test temperatures below 37 degrees C. Prewarming the antibody above 22 degrees C significantly decreased binding. Our results suggest that mild hypothermic test conditions have no relevant effect, whereas profound hypothermia induces defects in adhesion, thromboxane generation, and activation. The pathomechanism for the increased response to adenosine diphosphate at mild and profound hypothermia remains unclear. Storage temperature considerably affects the aggregation response to the agonists adenosine diphosphate and collagen but not to arachidonic acid and ristocetin. Flow cytometry using the temperature-labile antibody PAC-1 fails to assess temperature effects on platelet aggregability.