Possible role of central interleukins on the anorexigenic effect of lipopolysaccharide in chicks.

1. The purpose of the present study was to determine if central interleukin-1ß (IL1ß), interleukin-6 (IL6) and interleukin-8 (IL8) affect feeding behaviour in chicks (Gallus gallus) and examine if central interleukins are related to the lipopolysaccharide (LPS)-induced anorexia. 2. Intra-abdominal (IA) injection of LPS significantly suppressed feeding behaviour and significantly increased mRNA expression of IL1ß and IL8 in the diencephalon when compared to the control group, while IL6 tended to be increased. 3. Intracerebroventricular (ICV) injection of 200 ng IL1ß significantly decreased food intake at 60 min after the injection while IL6 and IL8 had no effect. 4. IA injection of these ILs (200 ng) had no effect on food intake in chicks. 5. ICV injection of 200 ng IL1ß did not affect water intake and plasma corticosterone concentration, suggesting that central IL1ß might not be related to the regulation of drinking behaviour and the hypothalamus-pituitary-adrenal axis. 6. The present study demonstrated that central IL1ß but not IL6 and IL8 might be related to the inhibition of feeding in chicks.

Long-term outcome of intravitreal ranibizumab treatment, compared with photodynamic therapy, in patients with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the functional outcomes of patients with polypoidal choroidal vasculopathy (PCV) who underwent intravitreal ranibizumab (IVR) treatment, compared with photodynamic therapy (PDT), after at least 2 years. METHODS: We retrospectively studied all the treatment-naïve patients with PCV who were scheduled to undergo IVR or PDT between August 2005 and June 2010. All the patients who had a 2-year or longer follow-up period were included in the study. The best-corrected visual acuity (BCVA) in the two groups was compared before treatment and at 3, 6, 12, 18 and 24 months after the initial treatment. The regression of the polyps was also assessed using indocyanine green angiography. RESULTS: A total of 77 patients were included in this study. Thirty-three eyes were treated with IVR, and 44 eyes were treated with PDT. Although no significant differences between the two groups were observed at baseline or at 3, 6, and 12 months after treatment, a significantly better BCVA was seen in the IVR group, compared with the PDT group, at 18 and 24 months after treatment (P=0.035 and P=0.021, respectively). No significant difference in the rate of polyp regression was observed between the two groups (P=0.092). CONCLUSION: IVR was well tolerated and maintained or improved the vision of patients with PCV, compared with PDT, as evaluated at 2-year follow-up examinations. PDT for the treatment of PCV might result in unfavorable outcomes, with no superiority to achieving the involution of polyps.

Exendin-4 protects pancreatic beta cells from the cytotoxic effect of rapamycin by inhibiting JNK and p38 phosphorylation.

It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.

Limited VH gene usage in B-cell clones established with nurse-like cells from patients with rheumatoid arthritis.

OBJECTIVES: Nurse-like stromal cells (NLC) in synovia and bone marrow of patients with rheumatoid arthritis (RA) can support pseudoemperipolesis, protect from apoptosis and enhance immunoglobulin production of peripheral blood B cells isolated from healthy individuals, suggesting the profound contribution of hyperactivation of B cells in RA. In the course of establishing RA-NLC from RA patients, we observed the growth of B cells in the presence of RA-NLC. METHODS: We cloned B cells from the synovium or bone marrow of RA patients using the limiting dilution technique. For established clones, nucleotide sequences of immunoglobulin and surface antigens were investigated. To investigate the dependence of these clones on NLC, differences in the proliferation and the amount of immunoglobulin produced in the presence or absence of NLC were compared. Immunocytochemical staining of various cells was performed using the antibody these clones produced. RESULTS: Nine B-cell clones established from RA patients showed RA-NLC-dependent growth. These B-cell clones expressed CD19, CD20, CD38, CD39 and CD40, suggesting that the cloned cells were mature and activated. All clones secreted immunoglobulins in culture media, which were specific for intracellular components of various cell lines, including RA-NLC. Interestingly, we found limited usage of immunoglobulin heavy-chain variable regions (VH) among B-cell clones from RA patients. These repertoires were reported to be detected preferentially in fetal livers. CONCLUSION: The present study provides a novel insight into the involvement of RA-NLC in the immunopathogenesis of RA via an autoreactive B cell development and/or activation mechanism.

Tartrate resistant acid phosphatase (TRAP) positive cells in rheumatoid synovium may induce the destruction of articular cartilage.

OBJECTIVE: To examine the role of tartrate resistant acid phosphatase (TRAP) positive mononuclear and multinucleated cells in the destruction of articular cartilage in patients with rheumatoid arthritis (RA). METHODS: The presence of TRAP positive cells in the synovial tissue of patients with RA was examined by enzyme histochemistry and immunohistochemistry. Expression of mRNAs for matrix metalloproteinases (MMPs) was assessed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis. Production of MMPs by mononuclear and multinucleated TRAP positive cells was examined by immunocytochemistry, enzyme linked immunosorbent assay (ELISA) of conditioned medium, and immunohistochemistry of human RA synovial tissue. In addition, a cartilage degradation assay was performed by incubation of (35)S prelabelled cartilage discs with TRAP positive cells. RESULTS: TRAP positive mononuclear cells and multinucleated cells were found in proliferating synovial tissue adjacent to the bone-cartilage interface in patients with RA. Expression of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-12 (macrophage metalloelastase), and MMP-14 (MT1-MMP) mRNA was detected in TRAP positive mononuclear and multinucleated cells by both RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 were produced by both TRAP positive mononuclear and multinucleated cells, whereas MMP-12 and MMP-14 were produced by TRAP positive multinucleated cells. MMP-2 and MMP-9 were detected in the conditioned medium of TRAP positive mononuclear cells. TRAP positive mononuclear cells also induced the release of (35)S from prelabelled cartilage discs. CONCLUSION: This study suggests that TRAP positive mononuclear and multinucleated cells located in the synovium at the cartilage-synovial interface produce MMP-2 and MMP-9, and may have an important role in articular cartilage destruction in patients with RA.

Mid-term clinical results of Graf stabilization for lumbar degenerative pathologies. a minimum 2-year follow-up.

BACKGROUND CONTEXT: Spinal fusion has some adverse effects, such as nonunion and pain at the site of grafted bone, and fusion with rigid spinal instrumentation especially may have the possibility of increasing mechanical stress on the segments adjacent to the site of fusion. The theory of the Graf system is that it will decrease adjacent disc deterioration because of maintenance of regional lordosis with flexibility and restriction of the motion of unstable segments without rigid spinal fusion. PURPOSE: To assess the clinical and radiologic results of Graf stabilization for lumbar degenerative disorders with minimal or mild instability. STUDY DESIGN: This is a retrospective study examining the mid-term results of Graf stabilization. PATIENT SAMPLE: In total, 59 patients underwent Graf ligamentoplasty and adequate decompression from April 1993 to September 1997. The subjects were 30 men and 29 women, and the mean age at the time of surgery was 60.6 years, ranging from 23 to 82 years. The average follow-up period was 3 years and 5 months, ranging from 2 years to 5 years and 10 months. OUTCOME MEASURES: We evaluated the surgical results using a scoring system, a visual analog scale, and radiological measurements. METHODS: The results were assessed according to a clinical scoring system established by the Japanese Orthopaedic Association (JOA score) and ratings based on a visual analog scale. Through analysis of x-ray images, the sagittal alignment (regional lordosis) and the range of motion (ROM) of the stabilized segments were measured in all cases, and the percentage of segments slipping and posterior disc height were determined for 29 patients with degenerative spondylolisthesis. RESULTS: Clinical scores and low back pain ratings based on a visual analog scale were significantly improved at the time of final follow-up compared with the preoperative values. Regional alignment of the operative segments was maintained in lordosis at the time of final follow-up. Preoperative ROM was significantly reduced at the time of final follow-up. There were no statistical differences in percentage of slippage or percentage of posterior disc height between the final follow-up values and the preoperative values. CONCLUSIONS: Our clinical results indicate that the Graf system is a suitable treatment option for mild and early lumbar degenerative diseases with minimum flexion instability of less than 10 degrees.

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

BACKGROUND: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. PATIENTS AND METHODS: Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. RESULTS: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. CONCLUSION: Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

The effects of heparin coating of oxygenator fibers on platelet adhesion and protein adsorption.

UNLABELLED: Platelet adhesion on the cardiopulmonary bypass oxygenator membrane is associated with impaired hemostasis. We investigated the effects of heparin coating of the oxygenator membrane on protein adsorption and platelet adhesion on the surface. Noncoated and heparin-coated polypropylene membranes were incubated in whole blood with small- (1 U/mL) or large-dose (5 U/mL) heparin as an anticoagulant for 3 h at 37 degrees C. The amount of platelets adhering on each fiber was assessed by using enzyme immunoassays using monoclonal antibodies directed against CD42b (GP Ib) and CD61 (GP IIb/IIIa). Platelet activation was assessed by measuring plasma guanosine monophosphate 140 levels. The amount and composition of the adsorbed proteins on the surface were analyzed by using a bicinchoninic acid protein assay and by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting technique. The heparin coating of the fibers significantly reduced platelet adhesion on the surface. However, platelet activation was reduced by heparin coating only with small-dose heparinization. The adsorption of platelet adhesive proteins such as fibrinogen and von Willebrand factor was not altered, whereas that of fibronectin was increased by heparin coating. We conclude that heparin coating of the oxygenator fibers can decrease platelet adhesion without affecting adsorption of major adhesive proteins. Surface heparin coating is associated with an increased fibronectin adsorption on the fibers. IMPLICATIONS: Heparin coating can reduce platelet adhesion and activation in the presence of small-dose heparinization, potentially reducing the inflammatory response and activation of thrombosis and fibrinolysis.

[Invasive amebiasis at an institution for the mentally retarded in Hyogo Prefecture].

An outbreak of amebiasis caused by Entamoeba histolytica occurred at an institution for mentally retarded persons in Hyogo Prefecture. Twelve out of a total of 49 admitted persons exhibited E. histolytica cysts in their stool, and 13 including persons in whom no cysts had been detected showed positive serological reactions for E. histolytica infection. However, neither the cyst nor the antibody against the organism was detected in the staff members of the institution. Indirect fluorescence antibody test and sandwich enzyme-linked immunosorbent assay with a monoclonal antibody specific for pathogenic strains of E. histolytica revealed that all trophozoite strains grown from cysts in stool samples from five patients were pathogenic. Epidemiological analysis strongly suggested that a patient in the institution had been infected with an organism from a patient outside the institution, and that infection may have spread among the admitted persons due to abnormal behavior. Administration of metronidazole resulted in effective elimination of the cysts from the stool of the cyst-carriers.

The effect of cryotherapy on intraarticular temperature and postoperative care after anterior cruciate ligament reconstruction.

The objective of this study was to elucidate how cryotherapy after anterior cruciate ligament reconstruction affects intraarticular temperature and clinical results. A prospective and randomized study was performed on 21 knees of 21 patients. The ligament reconstruction was performed by single-incision arthroscopy using autogenous hamstring tendon. On completion of the surgery, thermosensors were implanted in the suprapatellar pouch and the intracondylar notch, and the intraarticular temperature was monitored while the joint was cooled. Cooling was performed in one group at 5 degrees C (N = 7) and in another at 10 degrees C (N = 7), for 48 hours. A control group (N = 7) did not undergo cryotherapy. The cooled groups showed three temperature phases: a low-temperature phase immediately after the ligament reconstruction, followed by a temperature-rising phase and a thermostatic phase. The control group had no low-temperature phase and immediately entered a thermostatic phase. During the low-temperature phase in the treated groups, the temperature of the suprapatellar pouch and of the intercondylar notch were significantly lower than the body temperature. The pain score and the number of times an analgesic had to be administered were both significantly lower in the 10 degrees C group than in the control group. Blood loss was significantly less in the 5 degrees C group than in the control group.

Disseminated retinoblastoma successfully treated with myeloablative chemotherapy--implication for molecular detection of minimal residual disease.

A useful marker for detecting minimal residual disease (MRD) has not been established yet in retinoblastoma. We assessed neuroendocrine protein gene product 9.5 (PGP9.5) expression, one of the markers for detecting MRD in neuroblastoma, in a patient with disseminated retinoblastoma. A 3-year-old boy with disseminated retinoblastoma in multiple bones and marrow was referred to our hospital. He received intensive treatment and has maintained CR for 48 months following myeloablative chemotherapy with hematopoietic stem cell transplantation (SCT). PGP9.5 expression was serially assessed by RT-PCR in peripheral blood mononuclear cells (PBMC), bone marrow cells (BMC) and mobilized peripheral blood stem cells (PBSC). Initially, his BMC consisted of 96% tumor cells which were proved to express PGP9.5 by RT-PCR. Moreover, PBMC were found to be positive for PGP9.5 indicating the presence of tumor cells in the peripheral blood. After intensive chemotherapy, PGP9.5 expression became negative in both PBMC and BMC. Prior to SCT, PBSC and BMC transplants were confirmed negative for PGP9.5 expression. It is suggested that PGP9.5 expression is a useful marker for evaluating therapeutic effects as well as detecting MRD in retinoblastoma.

In vitro comparison study of CD63 and CD62P expression after contacting leukocyte filters.

CD63 and CD62P have been recognized as platelet activation markers. This study investigated the secretion of these antigens to compare the platelet activation between a newly developed stainless steel leukocyte filter (SSLF) and 7 polyester or polyurethane commercially available leukocyte filters. Flow cytometry demonstrated that the SSLF initiated significantly smaller effects in terms of mean fluorescence intensity of CD63 (p<0.03) and of the amount of CD62P expressing platelets (p<0.002) compared to the polyurethane filters. However, there was no statistical difference between the SSLF and polyester filters. The result of this study suggests that the SSLF caused less platelet activation than the polyurethane filters and has biocompatible characteristics comparable to the currently available polyester filters. Stainless steel was selected because of its physicochemical conductivity. With these results, further evaluation of the SSLF will be continued in an attempt to develop an active immunomodulator using this unique characteristic.

Allogeneic class I major histocompatibility complex gene transfer in murine neuroblastoma in vivo.

In vivo intratumoral gene transfer of allogeneic class I major histocompatibility complex (MHC) genes augments the immune response against weak tumor antigens. In this study, mice inoculated with the allogeneic MHC molecule (H-2Kb), had transduced-murine neuroblastoma C1300S3 cells showed prolonged survival relative to non-transduced or neo transduced tumors (p < 0.005). Interestingly, direct in vivo gene transfer of H-2Kb plasmid DNA complexed with HVJ-liposomes into S3 tumors was highly efficient, resulting in transduction of 8% of the interstitial cells within the tumor but rarely within tumor cells. Regression of established tumors and prolonged survival occurred in 50% of mice injected with H-2Kb, in contrast to no tumor regression in mice receiving control plasmid (p < 0.005). This study concludes that interstitial cells could serve as an important target of intratumoral gene transfer, and further that HVJ-liposome complexes could be a vehicle for in vivo gene transfer.

Evaluation of platelet adhesion and activation on materials for an implantable centrifugal blood pump.

A totally implantable centrifugal artificial heart has been developed in which a pivot bearing supported centrifugal pump is used as a blood pump. The following have been adopted as blood contacting materials in our pump: titanium alloy (Ti-6A1-4V) for the housing and impeller, alumina ceramic (Al2O3) for the male pivots, and ultrahigh molecular weight polyethylene (PE) for the female pivots. Greater antithrombogenicity is required for an implantable blood pump. To examine the thrombogenicity of these materials, we evaluated in vitro platelet adhesion and activation, which may play key roles in thrombogenesis on foreign surfaces. Ti-6A1-4V, Al2O3, and PE were compared with polycarbonate (PC), silicone carbide (SiC), and pure titanium (pTi). Platelet adhesion was assessed using monoclonal antibody (CD61) directed against glycoprotein IIIa. Platelet activation was evaluated by measuring P-selectin (GMP-140) released from irreversibly activated platelets. Each material with a surface area of 16.6 cm2 was incubated with 2.5 ml of plasma or 2.5 ml of heparinized fresh whole blood for 3 h at 37 degrees C. The optical density (OD) at a wavelength of 450 nm for CD61 was 0.93+/-0.35 in PC, 0.34+/-0.13 in PE, 0.27+/-0.13 in pTi, 0.26+/-0.01 in Al2O3, 0.21+/-0.04 in SiC, and 0.12+/-0.12 in Ti-6A1-4V. The GMP-140 levels of the tested materials were not significantly different from the control value (45.9+/-7.2 ng/ml). These results indicate that Al2O3, PE, and Ti-6A1-4V, which are incorporated into our implantable centrifugal pump, have satisfactory antithrombogenic properties in terms of platelet adhesion. However, platelet activation by any material was not observed under the static condition in this study.

Changes in muscle strength properties caused by harvesting of autogenous semitendinosus tendon for reconstruction of contralateral anterior cruciate ligament.

A prospective study was conducted of how the muscle strength of the donor knee is affected by harvesting of the autogenous semitendinosus tendon (St) for use as a substitute graft material in cruciate ligament reconstruction. There were 25 patients from whom only the St was harvested from the contralateral (i.e., healthy/donor) knee. Using a Biodex System II (Biodex, New York, NY), the strength of the donor knee was measured during both extension and flexion, both before and 12 months after the tendon harvesting procedure. A comparative study was made of the preharvest and postharvest values for the peak torque and peak torque angle in the isokinetic contraction. There were no statistically significant differences between the preharvest and postharvest peak torque values of the donor knee. However, the peak torque angle decreased significantly after the tendon harvest; the range of the mean decrease was from 11.7 degrees to 15.0 degrees. This indicates that there was a change to a small flexion angle (P < .05). After the tendon harvest, regardless of the applied angular velocity, more than 80% of the cases showed a change of torque curve shape in which there was no peak in the latter half, and the position of the peak was shifted to the left. In conclusion, the results of this study indicate that harvesting of the autogenous St does not affect the peak torque, but the peak torque angle during flexion of the donor knee is reduced.

Provirus load in patients with human T-cell leukemia virus type 1 uveitis correlates with precedent Graves' disease and disease activities.

We previously demonstrated the increased provirus load in the peripheral blood of patients with human T-cell leukemia virus type 1 (HTLV-1) uveitis (HU). To delineate the relevance of the increased provirus load to clinical and immunologic parameters, we studied the correlation between them. Seventy-nine HU patients (24 male and 55 female) were included in the study, with their informed consent. Plasma samples and genomic DNA of the peripheral blood mononuclear cells were isolated and the provirus load was estimated by semi-quantitative polymerase chain reaction of the gag region sequence. Serum levels of anti-HTLV-1 antibodies and soluble IL-2R were determined by electrochemiluminescence immuno assay and by ELISA, respectively. Disease activities were assessed and graded 0 to 4 according to the evaluation system. Recurrence of the disease during the follow-up period was diagnosed ophthalmologically. The provirus load was significantly higher in the HU patients after Graves' disease (GD) than in those without GD (P<0.05). It correlated with disease activities assessed in terms of vitreous inflammation and interval to recurrence (both P<0.05). In the HU patients without GD, it correlated with the serum levels of soluble IL-2 receptor (P<0.01), and nearly with those of HTLV-1 antibody (P=0.063). These correlations were not found in the HU patients after GD under methimazole treatment. The results suggested a direct involvement of HTLV-1-infected cells in the pathogenesis of uveitis, and raise the possibility that hyperthyroidism may contribute to the clonal expansion of HTLV-1-infected cells.

[Management for osteoporosis in a society composed largely of elderly people--from a practical orthopaedic point of view].

Aging of Japanese population in recent years is advancing at unexpected speed. The incidence of osteoporosis and fracture increase rapidly with aging of the population. Since 1970, at opening of our department, I have expected that a society would be composed largely of elderly people. To prevent elderly people from being beg-ridden and demented, I have made efforts to prevention and treatment of osteoporosis. Purpose of this paper is to show concerning the screening of osteoporosis in this area of Hakodate city and southern part of Hokkaido, and to report our treatment for osteoporosis. There are many ways of measuring bone mineral density (BMD), and dual energy X-ray absorptiometry (DEXA) is the simplest and the most accurate. Concerning of diagnosis of osteoporosis, we investigated the change of the BMD after hip surgery. On the other hand, we also reported the effectiveness of Vitamin-K for osteoporosis. No studies have ever been tried to clarify about this treatment. We are making efforts to enlighten the people on prevention, early diagnosis and treatment of osteoporosis.

Docosahexaenoic/arachidonic acid omega-hydroxylation system and differentiation in the human colonic adenocarcinoma cell line, Caco-2.

The homogenate from Caco-2 cells of day 13 or 15 after subculturing had high omega-hydroxylation activity of docosahexaenoic acid (22:6(n-3)) or arachidonic acid (20:4(n-6)). Activity, maximal at pH 8.0, was inhibited in the presence of CO or metyrapone and in the absence of NADPH. Omega-hydroxylation activity of lauric acid in the homogenate was not detected. Apparent Michaelis constant (Km) values for 22:6(n-3) and 20:4(n-6) were found to be 4 and 7 microM. Omega-hydroxylation activity considerably increased with growth up to day 13 and then decreased until day 20 even though alkaline phosphatase (ALP) and leucine-aminopeptidase (LAP) activity increased with growth to day 20. Metyrapone in cultures caused omega-hydroxylation, ALP and LAP activity to decrease, while sodium butyrate dose-dependently increased that of omega-hydroxylation, ALP and an endogenous endonuclease and decreased lactate dehydrogenase (LDH) activity in culture medium. The omega-hydroxylation system thus appears quite likely to be associated with cytochrome P450, differentiation and/or apoptosis rather than cytotoxic cell death of Caco-2 cells. Substrate specificity, however, differed from that of human cytochrome P450 4A11.

Current therapeutic apheresis technologies for inflammatory bowel disease.

A large number of physicians have indicated that patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) respond to current apheresis technology treatment. However, the mechanism of the apheresis procedure is undefined for patients with IBD. IBD appears to be caused by a complex of interactions from the genes, environment, and the immune system; therefore, the immune system plays a crucial role in the inflammatory responses. In this process, lots of interactions occur simultaneously, and they cross relate with each other. This review paper briefly discusses the etiology and pathogenesis of IBD and attempts to elucidate the mechanism that occurs after apheresis treatment.

Double filtration plasmapheresis maintains normal adhesion molecule levels.

Levels of plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) increase in patients with peripheral vascular or ischemic heart disease. These factors are related to the progression of atherosclerosis. Furthermore, these substances and thrombomodulin (TM) are indicators for assessing the degree of damage to the endothelium. To evaluate the effect of double filtration plasmapheresis (DFPP) on these molecules, the plasma levels of vWF, sICAM-1, sVCAM-1, and TM were measured in 4 familial hypercholesterolemia (FH) patients who underwent treatment with DFPP at 2 week intervals for more than 3 years. The levels of sVCAM-1 and sICAM-1 in hypercholesterolemia patients with ischemic heart disease as a control was 773 +/- 109 and 334 +/- 82 ng/ml. These values were higher than the normal value. In the FH patients who underwent DFPP treatment, the average sICAM-1 levels were 221 +/- 47 and 197 +/- 36 ng/ml before and after, respectively. The average sVCAM-1 levels were 601 +/- 87 and 486 +/- 60 ng/ml. There were no significant differences between the pre- and post-DFPP values. The activities of plasma vWF before and after DFPP treatment were 158 +/- 23 and 45 +/- 9%. The levels of plasma TM before and after treatment were 3.0 +/- 0.3 and 3.4 +/- 0.5 FU/ml. From these results, it is suggested that DFPP treatment does not damage the endothelium and may prevent the progression of atherosclerosis by removing the substances that induce the production of sICAM-1 and sVCAM-1 due to long-term treatment.