[Management of chromoblastomycosis, a challenge for limited-resource countries such as Madagascar]. / Prise en charge de la chromoblastomycose : un défi dans les pays à ressources limitées comme Madagascar.

INTRODUCTION: Chromoblastomycosis (CBM) is a chronic fungal infection of the skin and subcutaneous tissue caused by dematiaceous fungi. CBM lesions are recalcitrant and extremely difficult to eradicate. We report three cases of CBM with difficulties in therapeutic management. OBSERVATION: Three men aged 36, 50 and 67 years, all farmers, presented for between three and ten years with hyperkeratotic, scaly plaques with black dots on the right thigh and left leg, respectively. For all patients, mycological examination showed fumagoid cells, all of which were pathognomonic for CBM. PCR identified Fonsecaeanubica in one patient and Cladophialophoracarrionii in two patients. All patients received itraconazole 200mg/day for over 18 months. Two patients required combined therapy with terbinafine for seven months, which improved lesions; however, relapse occurred in one patient during the 5th month of this combined therapy and five months after the end of this treatment in the other. The patient on monotherapy (itraconazole) also presented recurrence of lesions five months after the end of treatment. DISCUSSION: Itraconazole is the standard therapy for CBM, with cure rates ranging from 15 to 80%. Success with itraconazole after eight to twelve months was reported by several authors. Fonsecaea and Cladophialophora are the most common species found in Madagascar, and while these organisms are susceptible to triazoles in vitro, clinical response is not so clear-cut. CONCLUSION: Although unavailable in Madagascar, posaconazole and isavoconazole appear to be effective in treating chromoblastomycosis.

Epidemiology and associated factors of atopic dermatitis in Malagasy children.

BACKGROUND: Little is known about the epidemiology and associated factors of childhood AD in the markedly different, low-income, tropical environment like Madagascar. METHODS: We aim to assess the epidemiology and associated factors of AD in individuals fewer than 15 years of age in Antananarivo Madagascar. It was a retrospective and descriptive study over a period of 7 years (2010 to 2016) in children 6 months to 14 years in the Department of Dermatology, Joseph Raseta Befelatanana Antananarivo Madagascar. The diagnosis of AD was based on clinical data. RESULTS: The prevalence of AD was 5.6% in children aged 6 months to 14 years. The details of 151 cases of atopic dermatitis were analyzed. The mean age of patients was 4 years. There was a female preponderance (sex ratio: 0.7). A family history of AD was noted in 56 cases (37%). No association between breast-feeding and AD was found. The age of onset of AD was before the age of 3 months in 7.5% and between 6 months to 5 years in 70%. Children born in March (dry season) had the highest risk of AD. Consultations for AD increased during the winter (from July to October; p = 0.005). However, the prevalence of AD was similar in urban and rural areas. CONCLUSION: Weather may have an impact on the prevalence of atopic dermatitis in Madagascar. No significant correlation was found between the duration of breastfeeding and AD, as well as urbanization.

ALK(R1275Q) perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN.

Overexpression of MYCN is a hallmark of neuroblastoma (NB). ALK(R1275Q), an activating mutation of ALK (anaplastic lymphoma kinase), has been found in sporadic and familial NB patients. In this report, we demonstrated that ALK(R1275Q) knock-in, MYCN transgenic compound mice developed NB with complete penetrance. Transcriptome analysis revealed that ALK(R1275Q) globally downregulated the expression of extracellular matrix (ECM)- and basement membrane (BM)-associated genes in both primary neuronal cells and NB tumors. Accordingly, ALK(R1275Q)/MYCN tumors exhibited reduced expression of ECM/BM-related proteins as compared with MYCN tumors. In addition, on MYCN transduction, ALK(R1275Q)-expressing neuronal cells exhibited increased migratory and invasive activities. Consistently, enhanced invasion and metastasis were demonstrated in ALK(R1275Q)/MYCN mice. These results collectively indicate that ALK(R1275Q) confers a malignant potential on neuronal cells that overexpress MYCN by impairing normal ECM/BM integrity and enhancing tumor growth and dissemination. Moreover, we found that crizotinib, an ALK inhibitor, almost completely inhibited the growth of ALK(R1275Q)/MYCN tumors in an allograft model. Our findings provided insights into the cooperative mechanism of the mutated ALK and overexpressed MYCN in the pathogenesis of NB and demonstrated the effectiveness of crizotinib on ALK(R1275Q)-positive tumors.

Arterial stiffness is increased in young women with endometriosis.

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Importance of early appropriate intervention including antibiotics and wound care for device-related infection in patients with left ventricular assist device.

INTRODUCTION: A left ventricular assist device (LVAD) is essential for treating patients with advanced heart failure. However, LVAD-related infection is a significant cause of mortality and morbidity, with bloodstream infection (BSI) especially associated with high mortality. We investigated the incidence of infectious complications in patients who received an LVAD and evaluated the effects of early and appropriate intervention for LVAD-related infection. METHOD: We retrospectively reviewed 27 consecutive patients who underwent continuous-flow LVAD (CF-LVAD; n = 16) or pulsatile-flow LVAD (PF-LVAD; n = 11) implantation at the National Cerebral and Cardiovascular Center between April 2011 and March 2013. Incidences of LVAD-related infections, such as drive-line infection in patients with CF-LVAD, cannula infection in patients with PF-LVAD, and BSI in patients with both types, were examined (follow-up period, 342 ± 229 days). The mandatory antibiotic prophylaxis protocol at our institution includes teicoplanin (400 mg) 2 days before LVAD implantation and doripenem (1000 mg) within 1 hour of skin incision. In addition, the driveline exit sites undergo sterile cleansing with diluted hydrogen peroxide and placement of an antimicrobial occlusive dressing for wound care, with dressing changes performed 2-3 times per day. RESULTS: More than 90% of all patients suffered from a drive-line infection within 12 months after LVAD implantation. However, BSI developed in only 12.5% of CF-LVAD and 10% of PF-LVAD patients within 12 months (log-rank test; P = .875). CONCLUSIONS: LVAD-related infections, such as drive-line and cannula infections, were common, whereas the incidence of BSI was low in our LVAD-implanted patients. Our results highlight the importance of early and appropriate intervention including antibiotics and wound care for device-related infections for reducing the incidence of potentially fatal BSI.

Increase in prominence of electrocardiographic J waves after a single dose of propofol in a patient with early ventricular repolarisation.

J waves appear on an electrocardiogram as an elevation of the J point in the terminal portion of the QRS complex. J waves are often benign, but may be associated with malignant ventricular arrhythmias. In some cases, such problems appear to have been precipitated by propofol infusions. We observed a sudden increase in J waves and profound hypotension following a single intravenous dose of propofol in an 84-year-old woman with early repolarisation in the inferior ventricular wall. When early repolarisation (as shown by electrocardiographic J waves) is observed in the inferior ventricular wall pre-operatively, patients should be carefully monitored. Myocardial ischaemia and the use of drugs that might worsen J waves should be avoided.

Ischaemic colitis during interferon treatment for chronic hepatitis C: report of two cases and literature review.

Ischaemic colitis is known to be a severe emergency complication of interferon (IFN) therapy. However, as ischaemic colitis is an infrequent complication of IFN therapy, limited information is available regarding the safety of resuming IFN therapy after resolution of ischaemic colitis and subsequent recurrence. Here, we report two cases of ischaemic colitis during IFN therapy for chronic hepatitis C. Ischaemic colitis was fully healed within 1 week after its onset and IFN withdrawal, and IFN therapy was resumed following patients' wishes to do so. Ischaemic colitis did not recur after the resumption of IFN therapy, and sustained virological response was achieved in both patients. In this report, we also summarize the findings of 11 cases of IFN-associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C.

Use of HOMA-IR in hepatitis C.

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent manner and contributes to steatosis, progression of fibrosis and resistance to interferon plus ribavirin therapy. Our understanding of HCV-induced IR has improved considerably over the years, but certain aspects concerning its evaluation still remain elusive to clinical researchers. One of the most important issues is elucidating the ideal method for assessment of IR in the setting of hepatitis C. The hyperinsulinaemic euglycaemic clamp is the gold standard method for determining insulin sensitivity, but is impractical as it is labour intensive and time-consuming. To date, all human studies except for four where IR was evaluated in the HCV setting, an estimation of IR has been used rather than direct measurements of insulin-mediated glucose uptake. The most commonly used estimation in the HCV population is the homeostasis model assessment of insulin resistance (HOMA-IR) which is calculated from a single measurement of fasting insulin and glucose. In this article, we review the use and reporting of HOMA in the literature and provide guidance on its appropriate as well as inappropriate use in the hepatitis setting.

Isolation and characterization of a novel short peptide associated with Crohn's disease.

Phage display technology has been utilized to select target molecules against circulating antibodies. The aims of this study were to isolate a peptide that binds with serum from Crohn's disease (CD) patients and to examine its diagnostic and pathogenic significance. A phage display library was constructed using cDNA from Caco-2 cells. Affinity selection using this cDNA library and serum samples from patients with CD was then performed. Phage clones that specifically reacted with the CD sera were then selected using a phage enzyme-linked immunosorbent assay (ELISA). After the DNA sequences of the selected phages were determined and converted to amino acid sequences, the synthesized peptides were examined using an ELISA. The effect of the synthesized peptides on cytokine release from cultured blood mononuclear cells was investigated. An ELISA analysis for TCP-353 demonstrated that while 61·7% of the samples from CD patients were seroreactive, seroreactivity was less common among patients with ulcerative colitis (7·3%), acute colitis (0%) or colon cancer (11·4%) and among normal subjects (2·8%). The induction of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α release, but not IL-10 release, in response to TCP-353 peptide was enhanced in CD mononuclear cells only. We isolated a novel peptide that specifically binds to CD sera and stimulates the proinflammatory responses of CD mononuclear cells. TCP-353 may have diagnostic, pathogenic and therapeutic significance with regard to the treatment of CD.

Meta-analysis: insulin resistance and sustained virological response in hepatitis C.

BACKGROUND: A higher baseline homeostasis model assessment of insulin resistance (HOMA-IR) score has sometimes predicted a poorer sustained virological response (SVR) rate to peginterferon/ribavirin therapy in treatment-naïve chronic hepatitis C patients. AIM: To perform a meta-analysis to evaluate the impact of HOMA-IR on SVR in hepatitis C. METHODS: Relevant studies were identified by searching Medline and EMBASE. We identified 17 publications that addressed the influence of insulin resistance on SVR. The random effect model of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4, Madrid, Spain. RESULTS: Normal insulin sensitivity was associated with a higher rate of SVR [odds ratio (OR) 2.86 (95%CI: 1.97-4.16)] in comparison with insulin resistance. Moreover, in separate analysis by genotype selecting studies that used HOMA-IR > 2 as cut-off defining insulin resistance, SVR was higher in patients with HOMA-IR < 2 in all genotypes: HCV-1 [OR: 2.16 (95%CI: 1.51-3.08)], HCV-2&3 [OR: 3.06 (95%CI: 1.06-8.82)] and HCV-4 [OR: 6.65(95%CI: 2.51-17.61)]. Studies reporting no association between HOMA and SVR included easy-to-cure cohorts, analysed variables strongly related with insulin resistance like body mass index, steatosis, hyper γGT, age and fibrosis and reported differences in handling and interpretation of HOMA-IR. CONCLUSION: Elevated HOMA-IR was associated with a lower cure rate of patients with hepatitis C treated with Peg-IFN-α/ribavirin irrespective of genotype, and the more difficult-to-treat cohort, the better the HOMA-IR prediction. HOMA-IR is, as a surrogate marker of insulin resistance, susceptible to some biases derived from both handling and interpretation.

Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis.

BACKGROUND: Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). AIM: To assess the efficacy of cisplatin in lipiodol emulsion combined with 5-fluorouracil (5-FU) for patients with HCC and portal vein tumour thrombosis. METHODS: The study subjects were 51 patients with the above-specified criteria who received injection of cisplatin suspension in lipiodol emulsion followed by intra-arterial infusion of 5-FU. The primary objective was to determine tumour response to the treatment, while the secondary objectives were safety and tolerability. Independent factors for survival were also assessed. RESULTS: Ten patients had complete response and 34 patients had partial response (response rate, 86.3%). The median survival for all 51 patients was 33 months, while that for 10 complete response patients and 21 patients who showed disappearance of HCC following additional therapies was 39 months. The single factor that significantly influenced survival was therapeutic effect. Treatment was well tolerated and severe toxicity was infrequent, with only grade 3 toxicity (thrombocytopenia) in one patient. CONCLUSIONS: The present study demonstrated the efficacy of hepatic arterial infusion chemotherapy using cisplatin-lipiodol emulsion and 5-FU without serious adverse effects in patients with unresectable HCC and portal vein tumour thrombosis.

Pathophysiological role of pigment epithelium-derived factor (PEDF) in hepatic disorders.

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with a potent neuronal differentiating activity. Recently, PEDF is found to be a highly effective inhibitor of pathological angiogenesis in both cell culture and animal models. Further, it has also been shown to have neuroprotective, anti-oxidative and anti-inflammatory properties, any of which could potentially be exploited as a therapeutic option for the treatment of cardiometabolic disorders, neurodegenerative disease and cancers. However, as far as we know, there are few comprehensive reviews to deal with the involvement of PEDF in hepatic disease. This article summarizes the pathophysiological role of PEDF for various liver diseases such as hepatic insulin resistance, alcoholic and nonalcoholic liver disease, and hepatocellular carcinoma, and its potential therapeutic implication in these devastating disorders.

Structure-function relationships of PEDF.

Pigment epithelial-derived factor (PEDF) is a 50-kDa secreted glycoprotein that belongs to the noninhibitory serpin. It has an alpha/beta core serine-protease inhibitor domain, 3 major beta-sheets, and 10 alpha-helices. Although PEDF does not inhibit either serine or cysteine proteinases, PEDF exerts diverse physiological activities including anti-angiogenesis, anti-vasopermeability, anti-tumor, and neurotrophic activities. Recent studies have shown that a variety of peptides derived from PEDF possess activities similar to those of the parent molecule through interactions with the extracellular matrix, binding to PEDF receptors, nuclear localization and phosphorylation. Thus, peptides derived from PEDF have therapeutic potential for various diseases and therefore, it is important to clarify the structure-function relationship of PEDF. In this review, we summarize structural features of PEDF that could affect various target organs such as blood vessels, tumors, and the central nervous system. In addition, since PEDF is recently identified as a regulator for glucose and lipid metabolism, we also discuss PEDF structures specially related to insulin-sensitizing and triglyceridereducing properties.

Pneumomediastinum is a frequent but minor complication during esophageal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIM: Esophageal perforation caused by endoscopic submucosal dissection (ESD) induces serious pneumomediastinum. In the absence of endoscopically detected perforation, postprocedural pneumomediastinum may occur. The aim of this study was to evaluate the association between the clinical factors/courses and pneumomediastinum revealed by chest computed tomography (CT) with special reference to an exposed muscle layer during esophageal ESD. PATIENTS AND METHODS: A total of 58 patients undergoing ESD for esophageal neoplasms between February 2003 and June 2007 also underwent both chest radiography and chest CT within 1 hour after ESD. We studied the association between findings on CT scan and tumor-related and technical factors of esophageal ESD by uni- and multivariate analyses. We also analyzed the clinical factors/courses experienced by all patients. RESULTS: Pneumomediastinum was detected in 18 / 58 patients (31 %) by chest CT compared with only 1 / 58 patients (1.7 %) by chest radiography. ESD-induced exposure of the muscular layer (32 patients) was the only significant factor for pneumomediastinum (18 / 32; P < 0.0001). Clinical factors such as fever, white blood cell count, and C-reactive protein were significantly increased in the group positive for both endoscopically exposed muscular layer and pneumomediastinum (+/+, n = 18) compared with the (-/-) group (n = 26) in the early phase (day 1) after ESD. However, these factors did not affect the length of the fasting period or the length of hospital stay. CONCLUSIONS: In esophageal ESD, pneumomediastinum detected by chest CT only does not cause clinically significant complication. Endoscopic muscle exposure during ESD is a significant risk factor for pneumomediastinum, which causes mild inflammation in the early post-ESD phase.

Branched-chain amino acids and pigment epithelium-derived factor: novel therapeutic agents for hepatitis c virus-associated insulin resistance.

Recent clinical studies have shown that patients with chronic liver disease are insulin resistant. Of all etiologies of chronic liver disease including non-alcoholic fatty liver disease, the one that causes the most sever insulin resistance is hepatitis C virus (HCV) infection. Since insulin resistance promotes inflammatory and fibrogenic reactions in the liver, thus leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC) in patients with HCV infection, amelioration of insulin sensitivity may inhibit the progression of HCV-associated liver disease, and could improve the survival of these patients. HCV directly causes insulin resistance through HCV core protein-elicited proteasomal degradation of insulin receptor substrates and subsequent inactivation of intracellular insulin signaling molecules such as Akt. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and/or triglyceride accumulation-induced nuclear factor-kappaB (NF-kappaB) activation in the liver is shown to play a role in insulin resistance in patients with HCV-related chronic liver disease as well. We, along with others, have recently found that branched-chain amino acids (BCAAs) and pigment epithelium-derived factor (PEDF) could improve the HCV-associated insulin resistance via suppression of NF-kappaB and preservation of insulin signaling pathway. In this review, we discuss the mechanisms for the actions of BCAAs and PEDF, and their clinical implications in insulin resistance of chronic liver disease in patients with HCV infection. We also discuss here which chemical structures could contribute to insulin-sensitization in patients with HCV infection.

Clinical trial: comparison of alendronate and alfacalcidol in glucocorticoid-associated osteoporosis in patients with ulcerative colitis.

BACKGROUND: Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. AIM: To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. METHODS: Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 microg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. RESULTS: Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. CONCLUSION: Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.

Validating a Markov model of treatment for hepatitis C virus-related hepatocellular carcinoma.

OBJECTIVE: We created and validated a Markov model to simulate the prognosis with treatment for HCV-related hepatocellular carcinoma (HCC) for assessment of cost-effectiveness for alternative treatments of HCC. METHOD: Markov state incorporated into the model consisted of the treatment as a surrogate for HCC stage and underlying liver function. Retrospective data of 793 patients from three university hospitals were used to determine Kaplan-Meier survival curves for each treatment and transition probabilities were derived from them. RESULTS: There was substantial overlap in the 95% CIs of the Markov model predicted and the Kaplan-Meier survival curves for each therapy. The predicted survival curves were also similar with those from the nationwide survey data supporting the external validity of our model. CONCLUSIONS: Our Markov model estimates for prognosis with HCC have both internal and external validity and should be considered applicable for estimating cost-effectiveness related to HCC.

Pigment epithelium-derived factor (PEDF) ameliorates advanced glycation end product (AGE)-induced hepatic insulin resistance in vitro by suppressing Rac-1 activation.

Advanced glycation end products (AGEs) could be implicated in insulin resistance. However, the molecular mechanisms underlying this are not fully understood. Since pigment epithelium-derived factor (PEDF) blocks the AGE-signaling pathways, we examined here whether and how PEDF improves insulin resistance in AGE-exposed hepatoma cells, Hep3B cells. Proteins were extracted from Hep3B cells, immunoprecipitated with or without insulin receptor substrate-1 (IRS-1) antibodies, and subjected to Western blot analysis. Glycogen synthesis was measured using [ (14)C]-d-glucose. AGE induced Rac-1 activation and increased phosphorylation of IRS-1 at serine-307 residues, JNK, c-JUN, and IkappaB kinase in association with decreased IkappaB levels in Hep3B cells. PEDF or overexpression of dominant negative Rac-1 blocked these effects of AGE on Hep3B cells. Further, AGEs decreased tyrosine phosphorylation of IRS-1, and subsequently reduced the association of p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by PEDF. Our present study suggests that PEDF could improve the AGE-elicited insulin resistance in Hep3B cells by inhibiting JNK- and IkappaB kinase-dependent serine phosphorylation of IRS-1 via suppression of Rac-1 activation. PEDF may play a protective role against hepatic insulin resistance in diabetes.

Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-elicited hepatic insulin resistance via peroxisome proliferator-activated receptor-gamma activation.

This study examined whether telmisartan, a unique angiotensin II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, improved insulin resistance in advanced glycation end-product (AGE)-exposed human hepatoma (Hep3B) cells. AGE increased phosphorylation of insulin receptor substrate-1 (IRS-1) at serine-307 residues in Hep3B cells. It also decreased tyrosine phosphorylation of IRS-1 and, subsequently, reduced the association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by telmisartan. The insulin-sensitizing properties of telmisartan in AGE-exposed Hep3B cells were significantly blocked by GW9662, an inhibitor of PPAR-gamma. Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma. Telmisartan may play a protective role against hepatic insulin resistance in diabetes.

Development of granulocyte and monocyte adsorptive apheresis in the rat dextran sodium sulfate-induced colitis model.

Granulocytapheresis (GCAP) selectively removes large numbers of granulocytes and monocytes from peripheral blood by adsorptive apheresis, and in patients with ulcerative colitis GCAP has been associated with significant efficacy. However, the mechanism(s) of efficacy of this strategy is poorly understood. This rat model of dextran sodium sulfate (DSS)-induced colitis was to investigate the effect of GCAP on tumor necrosis factor (TNF)-alpha release by peripheral leukocytes. By using mini columns, an experimental GCAP setting was developed and applied to the DSS-induced colitis model. The production of TNF-alpha by lipopolysaccharide-activated leukocytes in whole blood was measured by enzyme-linked immunosorbent assay. In rats that received GCAP with columns containing leukocytapheresis carriers, TNF-alpha release by leukocytes was significantly (p < 0.05) suppressed, while no change in TNF-alpha production was seen in rats that received GCAP with sham columns. This first experimental setting in the rat colitis model suggests that GCAP is feasible in animals and should shed light on the mechanism(s) of GCAP in clinical settings. Given that TNF-alpha is a major inflammatory cytokine, down-modulation of TNF-alpha might represent one mechanism of antiinflammatory effects of GCAP.