The role of human leukocyte antigen tissue groups in hepatitis B virus vaccination in Turkey.

BACKGROUND/PURPOSE: Between 5% and 10% of the vaccinated population responds less well to standard vaccination schedules irrespective of hepatitis B virus (HBV) vaccination. This manuscript aims at describing possible correlation of different major histocompatibility complex (MHC) Class-I and MHC Class-II haplotype to anti-HBV humoral responsiveness following HBV vaccination. MATERIALS AND METHODS: The study was conducted on 944 vaccinated hospital staff members and concentrated on the 38 nonresponders as defined by enzyme-linked immunosorbent assay (ELISA) results. In order to define significance of the different haplotypes from the nonresponders, their frequency was compared to the frequency of the same haplotype in 18 randomly selected responders. Human leukocyte antigen (HLA)-A and HLA-B antigens were typed among total mononuclear cells using a standard two-stage microlymphocytotoxicity test. The typing method of HLA Class-II is based on a technique that involves amplification of the second exon of different HLA Class-II genes by PCR. RESULTS: Positive correlations were found between four HLA-DR (HLA-DRB1*04X, DRB1*0401X, DRB1*11/13, and DRB1*0401X0201) haplotypes and nonresponders but there was a negative correlation with one Class-I (HLA-B13). CONCLUSION: This study suggested that certain HLA types are associated with nonresponsiveness to vaccination. The different HLA of ethnic groups should also be kept in mind when evaluating the response to hepatitis vaccination. The different HLA gene frequencies of ethnic groups should be examined in further large-scale population-based studies.

Immunocompetent cell level as a diagnostic reference for pulpal pathosis of primary teeth.

OBJECTIVE: The present study was designed to measure changes in the level of immunocompetent cells as healthy pulp becomes inflamed in order to evaluate the use of CD4+/CD8+ and B/CD3+ lymphocyte ratios as a diagnostic reference for pulpal pathosis in primary teeth pulp. DESIGN: Based on clinical and radiographic examinations, 113 carious and non-carious primary teeth were grouped as healthy teeth, teeth with reversible pulpitis and teeth with irreversible pulpitis. Following dental extraction, pulp samples were collected from all teeth, and 81 of the samples were found to be suitable for flow-cytometric analysis of lymphocyte subset. Kolmogorov-Smirnov's test, One-way ANOVA and Tukey's Post Hoc tests were used for statistical analysis. RESULTS: Statistical analysis revealed no increases in the mean percentages of T, B and CD4+ lymphocytes in inflamed pulp when compared to healthy pulp. However, both CD8+ and NK cell numbers decreased in line with progressive inflammation. Whereas the CD4+/CD8+ ratios increased in accordance with the severity of pulpitis, B/T ratios remained unaffected. CONCLUSIONS: Immunocompetent cell levels did not change in line with progressive inflammation; therefore, the use of CD4+/CD8+ and B/CD3+ lymphocyte ratios cannot be used as a diagnostic reference for pulpal pathosis in primary teeth.

Force feedback facilitates multisensory integration during robotic tool use.

The present study investigated the effects of force feedback in relation to tool use on the multisensory integration of visuo-tactile information. Participants learned to control a robotic tool through a surgical robotic interface. Following tool-use training, participants performed a crossmodal congruency task, by responding to tactile vibrations applied to their hands, while ignoring visual distractors superimposed on the robotic tools. In the first experiment it was found that tool-use training with force feedback facilitates multisensory integration of signals from the tool, as reflected in a stronger crossmodal congruency effect with the force feedback training compared to training without force feedback and to no training. The second experiment extends these findings by showing that training with realistic online force feedback resulted in a stronger crossmodal congruency effect compared to training in which force feedback was delayed. The present study highlights the importance of haptic information for multisensory integration and extends findings from classical tool-use studies to the domain of robotic tools. We argue that such crossmodal congruency effects are an objective measure of robotic tool integration and propose some potential applications in surgical robotics, robotic tools, and human-tool interaction.

Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation.

OBJECTIVE: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. MATERIALS AND METHODS: The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. RESULTS: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. CONCLUSION: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. CONFLICT OF INTEREST: None declared.

Extending the body to virtual tools using a robotic surgical interface: evidence from the crossmodal congruency task.

The effects of real-world tool use on body or space representations are relatively well established in cognitive neuroscience. Several studies have shown, for example, that active tool use results in a facilitated integration of multisensory information in peripersonal space, i.e. the space directly surrounding the body. However, it remains unknown to what extent similar mechanisms apply to the use of virtual-robotic tools, such as those used in the field of surgical robotics, in which a surgeon may use bimanual haptic interfaces to control a surgery robot at a remote location. This paper presents two experiments in which participants used a haptic handle, originally designed for a commercial surgery robot, to control a virtual tool. The integration of multisensory information related to the virtual-robotic tool was assessed by means of the crossmodal congruency task, in which subjects responded to tactile vibrations applied to their fingers while ignoring visual distractors superimposed on the tip of the virtual-robotic tool. Our results show that active virtual-robotic tool use changes the spatial modulation of the crossmodal congruency effects, comparable to changes in the representation of peripersonal space observed during real-world tool use. Moreover, when the virtual-robotic tools were held in a crossed position, the visual distractors interfered strongly with tactile stimuli that was connected with the hand via the tool, reflecting a remapping of peripersonal space. Such remapping was not only observed when the virtual-robotic tools were actively used (Experiment 1), but also when passively held the tools (Experiment 2). The present study extends earlier findings on the extension of peripersonal space from physical and pointing tools to virtual-robotic tools using techniques from haptics and virtual reality. We discuss our data with respect to learning and human factors in the field of surgical robotics and discuss the use of new technologies in the field of cognitive neuroscience.

Haptic handles for robotic surgery.

Robotic surgery, i.e. master-slave telemanipulators for surgery, is rapidly developing. One of the key components is the surgeon's console, and, within the console, especially the "handles" (the "joysticks") for manipulation control. Two examples of haptic (force-feedback) handle designs developed and realized at the LSRO lab are briefly presented along with design considerations (ergonomics, usability). Incidence on patient safety and patient benefit and future trends in this field are hinted at, especially the possibilities offered VR in this context.

[Prognostic value of serum TNF-alpha, IL-10, leptin and CRP levels in newborns with septicemia]. / Sepsisli yenidoganlarda serum TNF-alpha, IL-10, leptin ve CRP düzeylerinin prognostik degeri.

This study was aimed to investigate the prognostic value of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), leptin and C-reactive protein (CRP) levels in newborn sepsis. A total of 57 newborns with nosocomial sepsis and 30 healthy newborns were included to the study. Serum TNF-alpha, IL-10, leptin (Biosource, Belgium) and CRP (Dade Behring, Germany) levels were investigated by ELISA methodology before the initiation of the therapy (day 0) and on the third and fifth days of therapy. Initial leptin levels were found to be high in the control group (p = 0.00) and CRP levels were found to be high in the patient group (p = 0.00). No significant difference was detected for IL-10 and TNF-alpha levels (p > 0.05). CRP levels were significantly higher in the patient group than the controls on the third day of the therapy (p = 0.001), however, no significant difference was detected for the other parameters (p > 0.05). On the fifth day of the therapy CRP (p = 0.023) and leptin (p = 0.00) levels were significantly high in the patient group and TNF-alpha in the control group (p = 0.00) while no significant difference was observed for IL-10 levels (p > 0.05). Mortality rate was 24.5%. When the mean TNF-alpha, IL-10, leptin and CRP levels on the 0th, 3rd and 5th days were analysed for alive (n = 43) and dead (n = 14) newborns with sepsis, it was observed that TNF-alpha, IL-10 and CRP levels were related with poor prognosis (p < 0.05). The ROC analysis performed for the determination of the prognostic performance of TNF-alpha and IL-10 revealed that these parameters had predictive value about mortality when their levels were above certain cut-off values (on the 5th day of therapy for IL-10 > 1.8 ng/ml and for TNF-alpha > 21.1 ng/ml). It can be concluded that besides routine laboratory parameters, serum TNF-alpha and IL-10 levels at the initiation of therapy and afterwards may help to predict prognosis and guide treatment in newborns with sepsis.

Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis.

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.

Tissue levels of adiponectin in breast cancer patients.

BACKGROUND: Adiponectin is a new adipocyte-secreted protein and associated with insulin-resistant status, such as type 2 diabetes mellitus and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was recently documented. On the other hand, the association of tissue adiponectin levels with breast cancer has not been previously reported. Thus, in the present study, the relationship between tissue adiponectin levels and breast cancer was evaluated. METHODS: We analyzed the correlation between tissue adiponectin levels and the occurrence of breast cancer in a case-control study comprising 27 women with diagnosed and histologically confirmed breast cancer and 33 women with fibroadenoma. In addition, the association of tissue adiponectin levels with the various classical risk factors, such as body mass index, menopausal status and, tumor size, stage, lymph node status, hormonal status were also studied. RESULTS: Tissue adiponectin levels in patients with breast cancer (0.75 +/- 0.06) were significantly higher than those in controls (0.68 +/- 0.1) (P = 0.02). The high tissue adiponectin levels were associated with significantly (P = 0.001) an increased risk for breast cancer compared with those in the low tissue adiponectin levels (OR, 1.34; 95% CI, 1.12-1.84) in breast cancer patients. In addition, postmenopausal women with the high tissue adiponectin levels showed a significantly (P = 0.003) an increased risk for breast cancer compared with women in low tissue adiponectin levels (OR, 1.63; 95% CI, 1.23-1.90). The correlation between BMI and breast cancer was not found (P > 0.05). Furthermore, the status of estrogen receptor, progesterone receptor, HER-2/neu receptor and lymph nodes involvement were established, no effect on the tissue adiponectin levels in patients with breast cancer and no correlations were detected among tumor stage, tumor size and the levels of tissue adiponectin (P > 0.05). CONCLUSION: Our results suggest that the high tissue adiponectin levels significantly detected in breast cancer patients and associated with an increased risk for breast cancer.

Intranasal fungi and chronic rhinosinusitis: what is the relationship?

OBJECTIVES: The aim of this study was to investigate the effects of intranasal fungi on chronic rhinosinusitis (CRS). METHODS: Forty-one patients with CRS were included in the study. The patients were put into 2 groups, with and without intranasal fungi as detected by polymerase chain reaction, and were compared in terms of different laboratory and clinical parameters of CRS. A chi2 test was used to analyze statistical differences between the 2 groups. RESULTS: Serum eosinophilia, eosinophilia in the nasal mucus, prick and intradermal test positivity for fungi, elevated total IgE, fungal-specific IgE, prevalence of symptoms, frequency of bronchial asthma, aspirin sensitivity, and nasal polyposis did not differ significantly between the 2 groups of patients (p > .05). CONCLUSIONS: The findings of this study failed to reveal a clear correlation between the presence of fungi in the nasal passage and various factors that are assumed to be involved in the pathogenesis or clinical course of CRS. If fungi have a role in the pathogenesis of CRS, it may be via other mediators and reactions rather than IgE and type I hypersensitivity. However, the sample size was relatively small, and further studies with more cases are needed on the same topic.

Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?

In our previous studies, we found higher synovial fluid (SF) levels of angiogenic ELR(+) CXC chemokines such as CXCL1, CXCL5, CXCL6 and CXCL8, which play an important role in neutrophil migration and angiogenesis, and more abundant synovial CXCR2 chemokine receptor expression in patients with rheumatoid arthritis (RA) than those with Behçet's disease (BD), familial Mediterranean fever and osteoarthritis (OA). As a continuation of our previous studies, we investigated synovial levels of angiostatic non-ELR CXC chemokines (CXCL4, CXCL9 and CXCL10) in patients with RA, BD, spondyloarthritis (SpA), and OA. Seventy (17 RA, 15 BD, 19 SpA, and 19 OA) patients were enrolled in the study. The levels of CXCL4, CXCL9, and CXCL10 were measured by ELISA. The SF levels of CXCL4 in patients with RA were higher than those of the patients with BD, SpA, and OA (P = 0.007, P = 0.022, and P = 0.017, respectively). No difference was found with respect to CXCL4 levels among the BD, SpA, and OA patients. The synovial CXCL9 levels of patients with RA and SpA were found to be higher than those of the patients with OA (P = 0.002 and P = 0.005, respectively), while no statistically significant difference was detected among the other groups. With regard to SF CXCL10 levels, patients with RA had higher levels as compared to patients with OA (P = 0.002), but no significant difference was found among the other groups. CXCL9 correlated with CXCL4 and CXCL10 (P < 0.05 for both) in patients with RA. No correlation was found in other parameters. The angiostatic non-ELR CXC chemokines were expressed in synovial inflammation. We proposed that angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR (+) CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA. In addition, as CXCL-9 and CXCL-10 play crucial role in inflammation characterized by Th1 polarization, we suggested that they may contribute to the commencement and the perpetuation of synovitis seen in these groups of arthritides.

Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever.

Th1 type polarization has been implicated in the pathogenesis of familial Mediterranean fever (FMF). Interleukin-12 (IL-12) and IL-10 are proinflammatory cytokines, which play crucial role in Th1 and Th2 type immune response, respectively. IL-18 has a dual effect on T cell response: it was recognized as an IFN-gamma-inducing factor in T cells; acting in synergy with IL-12, leading to the development of Th1 type immune responses. But, in the absence of IL-12, IL-18 can promote the production of Th2 cytokines and take part in allergic inflammation. The aim of this study is to measure serum levels of IL-10, IL-12, and IL-18 in patients with FMF, and to investigate the relationship of their expressions with FMF attacks. Serum IL-10, IL-12, and IL-18 levels from patients with FMF were investigated. Thirty-one FMF patients with attack-free, 24 FMF patients with attack and 20 healthy controls were enrolled in the study. The levels of IL-10, IL-12p70 and IL-18 were measured by ELISA. Serum IL-10 levels were not different in FMF patients with attack and attack-free, and healthy controls. Serum IL-12 levels in FMF patients both with attack and attack-free were significantly higher than healthy controls (P = 0.002 and P = 0.047, respectively). There were no differences between FMF patients with attack and attack-free with regard to serum IL-12 levels. Serum IL-18 levels in FMF patients with attack and attack-free were significantly higher than healthy controls (P < 0.001 for both groups). With respect to serum IL-18 levels, no difference was found between FMF patients with attack and attack-free. Our results suggest that IL-12 and IL-18 contribute to the establishment of Th1 polarization seen in FMF and play a part in its pathogenesis. Detection of increased levels of IL-12 and IL-18 in patients with inactive disease implies that they seem to assist Th1 activation and subclinical inflammation persisting during the attack-free period of the disease.

Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy.

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-alpha, TGF-beta1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-alpha) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-beta1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-beta1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

Expression of CXCR-1 and CXCR-2 chemokine receptors on synovial neutrophils in inflammatory arthritides: does persistent or increasing expression of CXCR-2 contribute to the chronic inflammation or erosive changes?

OBJECTIVE: To analyze the CXCR-1 and CXCR-2 chemokine receptor expression on peripheral blood neutrophils (PBN) and synovial fluid neutrophils (SFN) of patients with rheumatoid arthritis (RA) and Behçet's disease (BD) (characterized by erosive and non-erosive arthritis, respectively), and to compare them with those of patients with osteoarthritis (OA). METHODS: We used flow cytometry to investigate the expression of CXCR-1 and CXCR-2 chemokine receptors on PBN and SFN of fifty-five (22 RA, 22 BD and 11 OA) age and sex-matched patients. RESULTS: In respect to chemokine receptor expression on neutrophils isolated from patients with RA, mean fluorescein intensity (MFI) of CXCR-1 chemokine receptors on PBN from active and inactive RA patients, and SFN from patients with RA were 151 (90-395), 129 (81-539) and 136 (64-220), respectively, and there were not statistically significant difference each other. But MFI of CXCR-2 chemokine receptors on SFN of patients with RA was 18 (10-32), and significantly higher than PBN of active and inactive RA patients (MFI: 10 (6-15) and 12 (7-16), P=0.002 and 0.037, respectively). In respect to chemokine receptor expression on neutrophils isolated from patients with BD, MFI of CXCR-1 chemokine receptors on PBN of active BD patients was 245 (97-844), and higher than PBN of active RA patients and SFN of BD patients (MFI: 151 (90-395) and 134 (61-231), P=0.047 and 0.017, respectively). MFI of CXCR-2 chemokine receptors on PBN of active and inactive BD patients, and SFN of patients BD were 10 (6-14), 10 (2-16), and 12 (8-24), respectively, there were not statistically significant difference each other. MFI of CXCR-1 chemokine receptors on SFN from patients with RA, BD, and OA were 136 (64-220), 134 (61-231), and 114 (60-180), respectively, and there was no difference between the study groups. MFI of CXCR-2 chemokine receptors on SFN of patients with RA was 18 (10-32), and higher than patients with BD and OA (MFI: 12 (8-24) and 11 (9-18), P=0.037 and 0.005, respectively), though there was no difference between last two groups. CONCLUSION: Our study points that CXCR-1 and CXCR-2 chemokine receptors of SFN may have diverse functions in the course of inflammatory arthritides. These results indicate that CXCR-2 chemokine receptor might play more critical role in long lasting accumulation of neutrophils within the synovial fluid of patients with RA.

Ceftriaxone-related hemolysis and acute renal failure.

A 5-year-old girl with no underlying immune deficiency or hematologic disease was treated with a combination of ceftriaxone and ampicilline-sulbactam for pneumonia. On the ninth day of the therapy, she developed oliguria, paleness, malaise, immune hemolytic anemia (IHA) and acute renal failure (ARF). Laboratory studies showed the presence of antibodies against ceftriaxone. Acute interstitial nephritis (AIN) was diagnosed by renal biopsy. The patient's renal insufficiency was successfully treated with peritoneal dialysis without any complications. The patient recovered without any treatment using steroids or other immunosuppressive agents.

Tissue levels of adiponectin, tumour necrosis factor-alpha, soluble intercellular adhesion molecule-1 and heart-type fatty acid-binding protein in human coronary atherosclerotic plaques.

BACKGROUND: There is little information available about any link between the levels of adiponectin, intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-alpha (TNF-alpha) and heart-type fatty acid-binding protein (H-FABP) in coronary atherosclerotic plaque specimens. AIM: To analyse tissue levels of adiponectin, ICAM-1, TNF-alpha and H-FABP in the plaques obtained from coronary artery bypass grafting (CABG) and to evaluate whether there is any relationship between these variables and other characteristics. PATIENTS AND METHODS: Coronary artery specimens from 37 consecutive patients (28 men and nine women) at time of CABG procedure and preprocedural blood samples were obtained. Tissue concentrations of adiponectin, ICAM-1, TNF-alpha and H-FABP in the atherosclerotic plaques were measured. RESULTS: Blood glucose and tissue levels of TNF-alpha and ICAM-1 were negatively correlated with tissue levels of adiponectin, whereas TNF-alpha was positively correlated with ICAM-1 in atherosclerotic plaques. In addition, there was a positive correlation between blood glucose and tissue levels of both TNF-alpha and ICAM-1. TNF-alpha and ICAM-1 levels in atherosclerotic plaques appear to progressively increase whereas adiponectin levels progressively decrease with smoking status. Atherosclerotic tissue levels of these substances are also altered in diabetes. CONCLUSIONS: The data are in accord with those in prior publications on the detection and quantification of various inflammatory cytokines in atherosclerotic plaques. Our results indicate that diabetic state and smoking, in addition to other physiopathological mechanisms, may create a chronic inflammatory situation in the atherosclerotic process.

Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet's disease. Does interleukin-1beta play a major role in Behçet's synovitis?

The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1beta, TNF-alpha and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet's disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1beta, TNF-alpha and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-alpha and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1beta levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1beta between BD and RA patients. Among patients with RA, positive correlations were found between TNF-alpha and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1beta, were expressed in relatively small quantities in Behçet's synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet's arthritis. We suggest that IL-1beta may be involved in the pathogenesis of Behçet's synovitis.

Lipid profile and anticardiolipin antibodies in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a multisystem disorder characterized by a relapsing inflammatory process of unknown etiology. It is well known that atherothrombosis in systemic inflammatory disorders is closely related to coagulation and lipid metabolism abnormalities. The purpose of this study was to investigate some parameters of lipid metabolism, lipoprotein (a) [Lp(a)] and anticardiolipin antibody (ACA) levels and the relationship of these parameters with the clinical activity of BD. METHODS: Thirty three patients with BD (15 active, 18 inactive cases) and 20 healthy controls participated in the study. After performing a detailed physical exam, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), apoprotein A and B (apo-A, apo-B), Lp(a), and ACA levels (ACA-IgG and IgM) were measured in all participants. RESULTS: Patients with active BD had higher ESR, CRP and Lp(a) levels, and lower apo-A and HDL-C levels compared with the patients with inactive BD and healthy controls. ACA-IgG and IgM levels were higher in patients with active BD than healthy controls but not higher than patients with inactive BD. On the other hand, ACA-IgG level was higher in active and inactive cases with vascular involvement than in those of active and inactive cases without vascular involvement. In the analyses of correlation, in active BD patients we found a positive correlation between CRP and Lp(a) levels. CONCLUSIONS: Our findings suggest that Lp(a) behaves as an acute phase reactant and ACA levels are increased in patients with active BD. Data from patients with active BD may be compatible with the serum profile, which is accepted as a risk for the development of atherothrombosis.

Lack of association between Vitamin D receptor FokI polymorphism and alopecia areata.

Vitamin D receptor (VDR) is expressed in the hair follicle and the lack of it leads to alopecia. In this study, we investigated whether there was a relationship between VDR FokI gene polymorphism and alopecia areata (AA). This is the first study investigating the relationship between VDR gene polymorphism and AA. Twenty-five patients with the extensive forms of AA (alopecia totalis; AT, alopecia universalis; AU and AT/AU) and 27 healthy control subjects were genotyped. Their genotypes were determined by a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. The genotypes were classified as FF (absence of the FokI site) and ff (presence of the FokI site). Allele frequencies for F and f alleles were 76.0% and 24.0% in the alopecic group and 72.2% and 27.7% in the control group (p > 0.05). The frequencies for the FF, Ff and ff genotypes were 56.0%, 40.0% and 4.0% in the patient group, and 48.1%, 48.1% and 3.7% in the control group, respectively. No statistically significant differences were observed in the frequencies of the VDR FokI genotype between the patient and the control groups. However, to conclude that there is no relationship between VDR gene polymorphism and AA, the VDR FokI polymorphism should be further studied in other populations, larger groups, and the distribution of other VDR polymorphisms such as BsmI, Tru9I, ApaI, TaqI and polyA.