Takahisa Tabata

Bacterial translocation and peptidoglycan translocation by acute ethanol administration.

Background: We examined bacterial translocation (BT) by acute ethanol administration, using a peptidoglycan detecting system. Methods: Rats were given 20% (v/w) ethanol (10 ml/kg body weight), and heparinized samples of portal blood were collected at specific time points after administration. Plasma peptidoglycan, β-glucan, and endotoxin concentrations of portal blood were measured. The rats were divided into three groups: a 20% ethanol group (20ET group), a 5% ethanol group (5ET group), and a control group. The groups were given 10 ml/kg body weight of either 20% (v/w) ethanol (20ET group), 5% (v/w) ethanol (5ET group), or distilled water (control group). Femoral arterial blood, portal blood, mesenteric lymph nodes (MLNs), spleen, and liver were cultured to assess BT. Plasma peptidoglycan, β-glucan, and endotoxin concentrations of femoral arterial blood and portal blood were measured. Results: The plasma peptidoglycan concentration of portal blood was significantly increased 24 h after the administration of 20% ethanol. There was no significant difference in the incidence and magnitude of viable BT to the MLNs, spleen, and liver among any of the groups at this time point. The rate of plasma peptidoglycan positivity and the plasma peptidoglycan concentration were increased significantly in the portal blood of the 20ET group 24 h after administration. Conclusions: Peptidoglycan was translocated into the portal blood by acute administration of 20% ethanol. Our findings suggest that viable bacterial flora may translocate from the intestine under the influence of ethanol, and BT may be one of the causes of chronic alcoholic liver disease.

A free radical scavenger, edaravone (MCI-186), diminishes intestinal neutrophil lipid peroxidation and bacterial translocation in a rat hemorrhagic shock model

Objective:To investigate the effects of edaravone, a novel free radical scavenger, on bacterial translocation induced by hemorrhagic shock. Design:Prospective, randomized, unblinded animal study. Setting:Surgical research laboratories of Shiga University of Medical Science. Subjects:Male specific-pathogen-free Sprague-Dawley rats. Interventions:The rats were randomly divided into three groups: conventional saline treatment, edaravone treatment, and sham shock induction. The saline and edaravone groups were subjected to hemorrhagic shock (mean arterial pressure of 30 mm Hg, for 30 or 60 mins). Rats were killed 30 or 60 mins after shock induction. Mesenteric lymph nodes were cultured for determination of bacterial translocation. Systemic plasma silkworm larvae plasma test, which can detect peptidoglycan and &bgr;-glucan, and endotoxin tests were performed. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE) was used to assess lipid peroxidation after shock. Measurements and Main Results:The incidence and magnitude of hemorrhagic-shock-induced bacterial translocation to mesenteric lymph nodes were reduced by edaravone. Hemorrhagic-shock-induced increase of plasma silkworm larvae plasma test was also reduced by edaravone. Immunohistochemistry for 4-HNE showed many 4-HNE-positive cells in the lamina propria of the ileum 60 mins after hemorrhagic shock. Double immunohistochemistry revealed that many of these 4-HNE-positive cells were also myeloperoxidase positive. Moreover, the percentage of double-labeled cells with 4-HNE and myeloperoxidase in myeloperoxidase-positive cells was significantly lower in the edaravone group than in the saline group. Conclusions:The present findings suggest that lipid peroxidation of intestinal neutrophils is involved in bacterial translocation during hemorrhagic shock and that edaravone is potentially useful in diminishing bacterial translocation after hemorrhagic shock.

A case of severe acute pancreatitis treated with CTR-001 direct hemoperfusion for cytokine apheresis.

Abstract:  Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro‐inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year‐old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR‐001 direct hemoperfusion (DHP) cartridge. His serum levels  of  pro‐inflammatory  cytokines  such  as  interleukin‐6 (IL‐6; 1649.1 ± 667.1–1257.1 ± 489.4 pg/mL, P = 0.013) decreased significantly after the CTR‐001 procedures. However tumor necrosis factor‐α (TNF‐α) (26.2 ± 1.7–24.3 ± 1.9 pg/mL, P = 0.087), IL‐1β (6.1 ± 2.9–3.49 ± 1.1 pg/mL, P = 0.477), IL‐8 (192.5 ± 33.4–229.5 ± 51.8 pg/mL, P = 0.754) and IL‐10 (14.4 ± 2.7–14.0 ± 1.9 pg/mL, P = 0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR‐001 cartridge was effective for reducing the pro‐inflammatory cytokines during severe acute pancreatitis.

Diagnostic and predictive value of the silkworm larvae plasma test for postoperative infection following gastrointestinal surgery.

Objective:To determine whether the silkworm larvae plasma (SLP) test is a reliable diagnostic marker of infection in patients with infectious complications following gastrointestinal surgery. Design:Prospective study. Setting:Department of Surgery, University Hospital, Shiga University of Medical Science. Patients:One hundred and twelve adult patients undergoing gastrointestinal surgery Interventions:None. Measurements and Main Results:Thirty-nine of 112 patients developed infectious complications (infected group). Seven patients with sepsis (severely infected group) and 32 patients without sepsis (minor infected group) were observed. The operation time, blood loss, and age were significantly greater in both infected groups than in the noninfected group. The systemic inflammatory response syndrome score on postoperative day (POD) 1 and POD7 was highest in the severely infected group. The increase in C-reactive protein on POD3 and POD7 was significantly higher in both infected groups than in the noninfected group. White blood cell counts on POD7 were elevated significantly higher in the severely infected group than in the other groups. Immediately after surgery, SLP activity significantly increased compared with presurgery in all groups and was significantly higher in the minor and severely infected groups than in the noninfected group. The increased SLP activity returned to preoperative levels in the minor and noninfected groups; however, SLP activity in the severely infected groups remained high throughout the observational period. The most significant factor and time point that predicted infectious complications were the SLP test on POD1; sensitivity 66.7%, specificity 90.4%, positive and negative predictive values 78.8% and 83.5%. The area under the receiver operating characteristic curve for the SLP test was 0.813 ± 0.046. Conclusions:The SLP test appears to be a useful marker of diagnosis and prediction of infectious complications following gastrointestinal surgery. Moreover, the SLP test may be able to evaluate not only the existence but also the severity of infection in surgical patients.

Association of the Plasma Platelet-Derived Microparticles to Platelet Count Ratio with Hospital Mortality and Disseminated Intravascular Coagulopathy in Critically Ill Patients

AIM The role of platelet-derived microparticles (PDMPs) in the crosstalk between coagulopathy and inflammation in critically ill patients remains unclear. The aim of this cohort observational study was to investigate the associations between the PDMP levels and hospital mortality or disseminated intravascular coagulopathy (DIC). METHODS This study included 119 patients who were admitted to the ICU. The PDMP levels were measured using an enzyme-linked immunosorbent assay three times a week, for a total of 372 samples. We calculated the maximum (max) PDMP value, max PDMP/platelet (PDMP/Plts) ratio (converted to the PDMP levels per 10(4) platelets) and nadir platelet count during the ICU stay. Baseline patient data and scores, including the Japanese Association for Acute Medicine (JAAM) DIC score, were collected, and potential predictors were analyzed for possible associations with hospital mortality. RESULTS The max PDMP/Plts ratio was significantly different comparing the survivors (n=98: median, 2.54) and non-survivors (n=21: median 17.59; p＜0.001). There was a weak but statistically significant negative correlation between the max PDMP level and nadir platelet count (r=-0.332, p＜0.001). The max PDMP level and max PDMP/Plts ratio were higher in the DIC group (81.48 and 9.27, respectively) than in the non-DIC group (34.88 and 2.35, p=0.001 and p＜0.001, respectively). The max PDMP/Plts ratio was the only variable found to be independently associated with hospital mortality according to a multivariate logistic regression analysis. CONCLUSIONS PDMPs are involved in the development of DIC but are not related to hospital mortality. There is a good association between the PDMP/Plts ratio and hospital mortality and/or DIC in critically ill patients.

Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.

ABSTRACT Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841–0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812–0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Hyperoxic Condition Prevents Bacterial Translocation and Elevation of Plasma Microorganism Components During Hemorrhagic Shock

To evaluate the influence of hyperoxic conditions on bacterial translocation (BT) and microorganism components during hemorrhagic shock, rats were divided into a group breathing 100% oxygen and a group breathing room air. The groups were then subjected to hemorrhagic shock. Systemic blood and mesenteric lymph nodes were cultured for BT, and systemic plasma concentrations of microorganism components were measured by the silkworm larvae plasma (SLP) test and the endotoxin test. Hyperoxic conditions prevented both BT and plasma SLP-reactive substance (peptidoglycan and beta-glucan) elevation during hemorrhagic shock. Our findings suggest that hyperoxic treatment might improve host conditions during hemorrhagic shock.

Pulmonary function diagnosis based on diaphragm movement using dynamic flat-panel detector imaging: an animal-based study

Pulmonary function is generally evaluated based on the overall capacity of both lungs; this evaluation is performed by a pulmonary functional test using a spirometer. Diaphragm movement has a direct association with pulmonary function. Therefore, evaluation of diaphragm motion is also helpful for estimating pulmonary function in the lung unit. The purpose of this study was to investigate the utility of dynamic analysis of the diaphragm using dynamic flat-panel detector (FPD) imaging for pulmonary function assessment in the lung unit. Sequential chest radiographs of four pigs (body weight approximately 20−30 kg) were obtained using a dynamic FPD system under respiratory control with a ventilator (100, 200, 300, 400, and 500 mL). Diaphragm excursion was measured and then analyzed the correlation with inspired volume. We also created porcine models of atelectasis by a catheter procedure and investigated whether lungs affected by atelectasis could be detected as reduced diaphragm excursion. To facilitate visual evaluation, temporal cross-sectional images were created, with the x-axis representing time, using a linear interpolation method. There was a strong correlation between inspired volume and diaphragm excursion (r = 0.96). In porcine models of atelectasis, diaphragm movement of an affected lung was restricted and was reduced, on average, to 44% of that in unaffected lungs. Reduction in diaphragm movement was also observed in the temporal cross-sectional images. Dynamic FPD imaging allows for relative pulmonary function assessment based on diaphragm movement, and unilateral abnormalities could be detected as reduced diaphragm excursion, even with a normal inspired volume.