The Elevation in Preoperative Procalcitonin Is Associated with a Poor Prognosis for Patients Undergoing Resection for Colorectal Cancer.

BACKGROUND: Procalcitonin (PCT) is a well-known marker for bacterial infection; however, the clinical significance of PCT in the long-term prognosis after colorectal cancer (CRC) surgery remains unclear. METHODS: This is a retrospective review of 277 patients that underwent CRC surgery to investigate the relationship between preoperative PCT, clinicopathological condition, cancer-specific overall survival (OS), and relapse-free survival (RFS). RESULTS: Median follow-up interval was 5.0 years in all patients. Thirty-six patients developed recurrence, and 46 patients died due to recurrences or metastases of CRC. Preoperative PCT levels were highest in Stage IV patients. The cancer-specific OS in patients with Stage IV/PCT ≤0.05 ng/mL was significantly higher than those with Stage IV/PCT >0.05 ng/mL (3 years survival; 42.3 vs. 14.3%, p = 0.0413). On multivariate analysis, gender, TNM classification, and PCT were identified as significant risk factors for cancer-specific OS in patients with Stage I-III CRC. The cancer-specific OS rate of these patients with PCT ≥0.08 ng/mL, compared with PCT <0.08 ng/mL, was significantly decreased (5 years survival; 59.1 vs. 92.7%, p < 0.0001). TNM classification was finally identified as an independent risk factor for cancer-specific RFS in these patients by multivariate analysis. CONCLUSION: High preoperative PCT values in CRC patients appeared to be associated with poor OS but not RFS following surgical treatments.

Effects of wearing supportive underwear versus pelvic floor muscle training or no treatment in women with symptoms of stress urinary incontinence: an assessor-blinded randomized control trial.

INTRODUCTION AND HYPOTHESIS: In our previous single-arm pilot study, we reported that ready-made supportive underwear (shaper) was effective in elevating the bladder neck and reducing urinary incontinence (UI) symptoms. The aim of this study was to determine the effects of wearing a shaper compared with pelvic floor muscle training (PFMT) at home using a training compact disc with music, or no treatment, in an assessor-blinded randomized control trial, on reducing UI symptoms. METHODS: Participants aged 30-59 years with symptoms of stress urinary incontinence were randomly assigned to three groups: the shaper group, PFMT group, and no treatment group. The UI episodes/week and the Japanese version of the International Consultation on Incontinence Questionnaire Short-Form were compared between the baseline and the 6th or 12th week of the intervention period. RESULTS: Eighty-nine women who completed the 12-week intervention period were analyzed. After the 12-week intervention period, the improvement rate in UI symptoms (ratio of the case number in which the UI episodes/week decreased at least 50% from the baseline) was 73.3% (22/30 women) in the shaper group, 74.2% (23/31 women) in the PFMT group, and 25.0% (7/28 women) in the no treatment group. The improvement rate in UI symptoms in the shaper and PFMT groups was significantly higher than that in the no treatment group (both P < 0.001). CONCLUSIONS: Wearing supportive underwear (shaper) was almost as effective as PFMT at home in reducing UI symptoms.

Anti-endotoxin Properties of Polymyxin B-immobilized Fibers.

Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.

Endotoxin adsorption: Direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX).

Toraymyxin® is a medical device developed to adsorb circulating endotoxins in the blood using direct hemoperfusion therapy for patients with septic shock. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock. Since then, Toraymyxin has been safely used in more than 100,000 cases in emergency and intensive care units in Japan. Toraymyxin is currently available for use in the clinical setting in 14 countries worldwide. In this study, we reviewed and introduced the development, clinical use, and efficacy of Toraymyxin and commented on its anticoagulant use and cartridge clotting issue in the treatment of severe sepsis and septic shock. We also highlighted potential new applications of Toraymyxin for longer duration therapy and pulmonary diseases.

Pyomyositis at the surgical site in a patient with chronic myeloid leukemia: a case report and literature review.

BACKGROUND: Pyomyositis is a rare, subacute, deep pyogenic infection of the muscle tissue. This disease has been previously described in patients that were immunocompromised due to a hematological malignancy. CASE PRESENTATION: A 68-year-old man with a history of chronic myeloid leukemia was treated with imatinib. He was diagnosed with ascending colon cancer and underwent curative surgery. His postoperative course was uneventful, and he was healthy at 6 months after surgery, allowing for reinitiation of imatinib therapy. After the reinitiation of therapy, a computed tomography (CT) scan revealed a mass shadow in the right iliopsoas muscle. This lesion was clinically diagnosed as recurrent colon cancer with an abscess, which was resected surgically. A pathological examination uncovered both edema and inflammation. Two months after the second surgery, imatinib therapy was reinitiated; however, he again developed painful swelling and erythema in his right thigh. A CT scan revealed a similar shadow as described previously. He was then diagnosed with pyomyositis; he underwent incisional drainage and was administered linezolid. Following the treatment for pyomyositis, there was no cancer recurrence or evidence of any recurrent pyomyositis. CONCLUSIONS: Findings from this case suggest that both undergoing surgery and receiving imatinib therapy may modulate an individual's immune response, whereby the surgical site becomes more prone to infection and may predispose an individual to pyomyositis. The case report is followed by a discussion of the literature regarding this disease, including potential risk factors and the underlying pathogenesis.

[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].

PURPOSE: We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS: We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS: We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).

A complete response to mFOLFOX6 and panitumumab chemotherapy in advanced stage rectal adenocarcinoma: a case report.

BACKGROUND: Pathological complete remission of advanced stage rectal adenocarcinoma by chemotherapy alone is rare. A case of advanced stage, low-lying rectal adenocarcinoma in which a complete response to treatment was obtained with mFOLFOX6 and panitumumab (Pmab) is reported. CASE PRESENTATION: A 53-year-old man was referred to Shiga University of Medical Science hospital Shiga, Japan, complaining of bloody stool. Gastrointestinal endoscopy was performed, and advanced stage rectal adenocarcinoma was diagnosed. Computed tomography (CT) revealed regional lymph node metastases in the mesorectum. Neoadjuvant chemotherapy (NAC) with mFOLFOX6 and Pmab was planned.Endoscopy following four courses of chemotherapy revealed that the rectal cancer had been markedly reduced, and the results of biopsies of the rectal tumor were negative for cancer. On CT, the mesorectal lymph node metastases had disappeared. Total intersphincteric resection (ISR) with a handsewn coloanal anastomosis was performed. Histological examination showed a complete response to mFOLFOX6 and Pmab in advanced stage rectal cancer. CONCLUSION: The result seen in this case suggests that short-term NAC with mFOLFOX6 and Pmab was effective for low-lying rectal adenocarcinoma.

Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). CASE PRESENTATION: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. CONCLUSION: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

Transmembrane mucin MUC1 overexpression and its association with CD10⁺ myeloid cells, transforming growth factor-ß1 expression, and tumor budding grade in colorectal cancer.

The prognostic value of mucin expression has been reported in several studies. We examined the association between mucin expression and other previously reported prognostic factors, including infiltration of CD10⁺ myeloid cells, transforming growth factor-ß1 (TGF-ß1) expression, and tumor budding at invasion fronts. Immunohistochemical analysis of 206 colorectal samples was carried out to determine whether MUC1, MUC2, MUC4, and MUC5AC expression could predict the survival of colorectal cancer patients. Serial sections were stained for CD10, TGF-ß1, and pan-cytokeratin in order to detect tumor budding. As per multivariate analyses, MUC1 expression appeared to be the most significant predictor of both recurrence-free survival and overall survival. MUC4 was only significant to predict recurrence-free survival, and MUC5AC could be a good marker in stage IV colorectal cancers that require additional chemotherapy. MUC1 (CD227) expression was associated with infiltration of CD10⁺ myeloid cells, TGF-ß1 expression, and tumor budding grade. These findings suggest that MUC1 is indicative of poor prognoses that may be associated with immunosuppression and epithelial-mesenchymal transition. Furthermore, MUC1 expression appears to be a chemoattractant for CD10⁺ stromal cells.

The ability of endotoxin adsorption during a longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column in patients with septic shock.

The patients' hemodynamic conditions of septic shock due to intra-abdominal infection were improved by the longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX), reducing plasma endotoxins measured by the novel endotoxin detection method, named endotoxin scattering photometry (ESP) method; however, turbidimetric method could not detect endotoxins. We also observed the reduction in the endotoxin after passing through column by ESP method even after the longer duration of PMX. ESP method may more sensitively detect endotoxins than the ordinary turbidimetric method. Moreover, we demonstrated the ability of endotoxin adsorption in spite of the longer duration of PMX.

Myeloid cells positive for CD10 at invasion front can predict poor outcome in stage II colorectal cancer.

BACKGROUND: Prediction of poor patient outcome as a effect of adjuvant therapy in stage II colorectal cancer (CRC) remains a matter of controversy. Tumor expression of CD10 and CD15 is reportedly related to poor outcome in CRC. In this study, we investigated whether the expression of CD10 and CD15 is a predictor of outcome and the effect of adjuvant therapy in stage II CRC. MATERIALS AND METHODS: Immunohistochemical analyses for CD10 and CD15 and some additional markers (CD11b, CD14, CD163, CD3, and CD20) were performed using paraffin sections of CRC specimens from 57 patients who had undergone curative surgical treatments between 1998 and 2004. Forty of these patients received postoperative adjuvant therapy. We distinguished between expression in tumor cells (tCD10 and tCD15), in stromal cells (sCD10), and infiltrating immune cells (iCD10 and iCD15). RESULTS: Expression of iCD10 was observed in 21.1% (12/57) of the specimens examined. Of all expression patterns, only iCD10 expression at the cancer invasion front was a useful predictor of a disease-free period and overall survival in stage II CRC. Adjuvant therapy improved the outcome of iCD10(+) patients. CD10(+) immune cells were heterogeneous in origin and partially overlapped the cells positive for myeloid lineage markers, including CD11b and CD15. CONCLUSIONS: iCD10 expression at the tumor invasion front is a useful marker for predicting a high risk of recurrence and mortality in stage II CRCs. CD10(+) immune cells appear to be of myeloid origin.

Results of the 2018 Japan Society for Blood Purification in Critical Care survey: current status and outcomes.

Background: The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018. Methods: We analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. Results: BPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality. Conclusion: This large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration : UMIN000027678. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00445-0.

Prognostic role of CD10⁺ myeloid cells in association with tumor budding at the invasion front of colorectal cancer.

The expression of CD10 in tumor cells has been reported to correlate with liver metastasis in colorectal cancer (CRC). However, fibroblasts and immune cells positive for CD10 at the tumor invasion front have not been comprehensively studied. We classified CD10 expression patterns into three types of cells, tumor cells (tCD10), stromal myofibroblasts (sCD10), and immune cells (iCD10), and investigated their correlation with the expression of transforming growth factor-ß (TGF-ß1) protein and tumor budding grade. Several cell surface markers were stained to detect the phenotype of iCD10(+) cells, including CD3, CD20, CD11b, CD14, CD15, and CD163. Specimens and follow-up data of 206 CRC patients were examined. In multivariate analysis, iCD10 could be an independent prognostic factor for both recurrence-free survival and overall survival in stage I-III CRC (hazard ratio, 2.522 [1.299-4.896], P = 0.006; 2.890 [1.357-6.157], P = 0.006, respectively). The expression of sCD10 and iCD10 was strongly correlated with TGF-ß1 expression in tumor cells and tumor budding grade. The phenotype of iCD10(+) cells was CD11b(+) and CD15(+) granulocytes. The infiltration of sCD10(+) fibroblasts and iCD10(+) granulocytes at the tumor invasion front might interact with TGF-ß1 protein expression and enhance tumor budding grade. The expression level of iCD10 at the tumor invasion front represented an independent prognostic biomarker in stage I-III CRC and could be integrated into a new staging system.

Involvement of TRPV1-containing peripheral sensory efferents in hemodynamic responses in a rat hemorrhagic shock model.

BACKGROUND: Mechanisms underlying hemodynamic disturbance in hemorrhagic shock are not completely understood. Transient receptor potential vanilloid 1-expressing afferents are involved in hemorrhagic shock pathology, and transient receptor potential vanilloid 1 antagonist, capsazepine, acts on the central nervous system to improve mortality in a rat hemorrhagic shock model. In contrast, transient receptor potential vanilloid 1-positive efferents promote vasoactive reactions through the release of neuropeptides, including calcitonin gene-related peptides. This study aimed to investigate whether transient receptor potential vanilloid 1-positive peripheral sensory efferents are involved in hemodynamic responses after hemorrhagic shock. METHODS: Male rats underwent hemorrhagic shock (mean arterial pressure 30 mm Hg for 90 min, followed by resuscitation for 30 min) and received capsazepine (5 µM/kg) 30 min after shock induction. A separate cohort of rats subjected to hemorrhagic shock received hCGRP8-37 (300 µg/kg), a calcitonin gene-related peptide receptor antagonist, at 30, 60, or 90 minutes after shock induction. The 24-hour survival rate, mean arterial pressure, heart rate, arterial blood gas, and plasma calcitonin gene-related peptide levels were measured. Tissue blood flow and oxygenation both in the mesentery and skeletal muscle were also assessed. RESULTS: Capsazepine treatment prevented the hemorrhagic shock-induced increase in plasma calcitonin gene-related peptide levels, and hCGRP8-37 treatment improved the 24-h survival rates after hemorrhagic shock at a time-dependent manner. The hCGRP8-37- or capsazepine-treated rats exhibited tissue oxygenation and metabolic conditions comparable to those in control rats at the end of the experiment. CONCLUSION: Transient receptor potential vanilloid 1 plays a crucial role in hemodynamic responses to hemorrhagic shock, partly via calcitonin gene-related peptide release, involved in its peripheral sensory-efferent functions. The hCGRP8-37 appears to improve peripheral circulatory failure, which may be useful as adjunct treatment after hemorrhagic shock.

Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials: Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Real-time magnetic resonance-guided microwave coagulation therapy for pelvic recurrence of rectal cancer: initial clinical experience using a 0.5 T open magnetic resonance system.

PURPOSE: This study aims to evaluate consecutive cases of recurrent rectal cancer in the pelvic cavity treated with microwave coagulation therapy using real-time navigation by an open magnetic resonance system. METHODS: Nine recurrent pelvic lesions in 8 patients after curative resection of rectal cancer were treated with real-time magnetic resonance-guided microwave coagulation therapy as a palliative local therapy to reduce tumor volume and/or local pain. Clinical and pathological data were collected retrospectively by reviewing medical records and clinical imaging results. RESULTS: Seven patients received other treatments before real-time magnetic resonance-guided microwave coagulation. Six patients had distant synchronous metastases. Three patients underwent surgery under lumbar anesthesia. Microwave coagulation was performed percutaneously in 5 lesions and under laparotomy in 4 lesions. Although adverse events related to microwave coagulation (skin necrosis and nerve injury) were observed, no fatal complications occurred. Local re-recurrence was observed in 2 of 9 ablated lesions. Except for 1 patient who died of chronic renal failure, the remaining 7 patients died of cancer. Median overall survival after microwave coagulation for all patients was 10 months (range, 4-37 mo). Median overall survival after discovery of pelvic recurrence in all patients was 22 months (range, 9-42 mo). CONCLUSIONS: The benefits of using an open magnetic resonance system in the pelvic cavity include the abilities to treat tumors that cannot be visualized by other modalities, to demonstrate internal architectural changes during treatment, to differentiate treated vs untreated areas, and to allow adjustments to the treatment plan during the procedure. Additional studies are required to clarify the efficacy of tumor coagulation for local control.

Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis.

BACKGROUND: Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, which increases the plasma APN concentration. MATERIALS AND METHODS: Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone. RESULTS: APN deficiency resulted in significant increases in the plasma levels of TNF-alpha, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-alpha, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis. CONCLUSION: These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.

Preparation of insulin-containing microcapsules by a layer-by-layer deposition of concanavalin A and glycogen.

The sugar sensitive microcapsules were prepared by a layer-by-layer deposition of concanavalin A (Con A) and glycogen on a calcium carbonate particle containing fluorescein-labeled insulin (F-insulin). The Con A/glycogen multilayer capsules were formed through sugar-lectin interactions by using inner and outer poly(ethyleneimine)/poly(vinyl sulfate) multilayers as supports, while without the supports the microcapsules could not be formed. Fluorescent microscope observations revealed that the capsules thus prepared are spherical in shape with 3-10 microm diameter. The microcapsules released encapsulated F-insulin upon addition of sugars. This is because the added sugars replace glycogen in the binding site of Con A, resulting in the enhanced permeability of the microcapsules to insulin.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.