Vascular endothelial growth factor and monocyte chemoattractant protein-1 in Behçet's patients with venous thrombosis.

OBJECTIVE: Vascular lesions can involve both arterial and venous systems which are often the major causes complicating the disease course of Behçet's disease (BD). Vascular endothelial growth factor (VEGF) is a stimulant of angiogenesis secondary to ischemia while monocyte chemoattractant protein 1 (MCP-1) is induced by shear stresses leading to vascular collateral development. MCP-1 has been also shown to contribute to the recanalization of venous thrombi. Tumor necrosis factor-alpha (TNF-alpha) is known to play a major role in the pathogenesis of BD. Furthermore, up-regulation of secreted MCP-1 and VEGF was observed following stimulation with TNF-alpha. In view of the above functions of VEGF, MCP-1 and TNF-alpha, we hypothesized that these factors may be important in the pathogenesis of thrombosis seen in BD. METHODS: A total of 36 patients with a diagnosis of BD were studied. BD patients were separated into 3 groups with respect to vascular involvement. Group BD-AT (n = 9) with acute thrombosis, BD-CT (n = 12) with chronic thrombosis and BD-MC (n = 15) with mucocutaneous involvement only. The control group (group H) was comprised of 20 healthy persons. In addition, patients with acute, DC-AT (n= 11) and patients with chronic DC-CT (n = 9) thrombosis without BD served as disease controls. Serum measurements of VEGF MCP-1 and TNF-alpha were performed by quantitative sandwich ELISA. The acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. RESULTS: The levels of VEGF were significantly higher in the patients in group BD-AT than either in group BD-CT or BD-MC (p = 0.03 and p < 0.001, respectively). However, no significant difference was found for VEGF levels of thrombotic patients regarding the cause (BD-AT vs. DC-AT, p = 0.063; BD-CT vs. DC-CT, p = 0.084) or the stage of thrombosis (DC-AT vs. DC-CT, p > 0.05). Both BD patients and disease controls with acute thrombosis had significantly higher levels of MCP-1 as compared to corresponding chronic thrombosis patients (BD-AT vs. DC-CT; p < 0.001; DC-AT vs. DC-CT, p < 0.001). Patients with BD and disease controls had significantly higher serum TNF-alpha level when compared with healthy subjects. No significant difference with respect to serum TNF-alpha level was noted when patient subgroups with BD and disease controls were compared with each other Serum levels of VEGF, MCP-1, and TNF-alpha were not found to be correlated with either ESR or CRP (p > 0.05). CONCLUSIONS: Increased levels of VEGF and MCP-1 detected in BD thrombosis suggest the possible role of those angiogenic cytokines in the pathogenesis. Although not specific for BD, detection of VEGF or MCP-1 levels seems to serve as an assay for differentiation of BD patients with acute thrombosis from chronic.

Soluble CD40 ligand levels in patients with hypertension.

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.

Antioxidant system activation in prostate cancer.

The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the levels of copper, zinc, and malondialdehyde were determined in 21 age-, sex-, and body-mass-index-matched prostate cancer patients; 50 patients diagnosed with benign prostatic obstruction (BPO) were compared to 50 healthy male subjects acting as controls. The patients were divided into two groups depending on the stage of the disease (group 1 [organ-confined] and group II [advanced disease]) and into three subgroups according to differentiation criteria: subgroup A (n = 5, Gleason sum 2-4, well differentiated); subgroup B (n = 9, Gleason sum 5-7, moderately differentiated), and subgroup C (n = 7, Gleason sum 8-10, poorly differentiated). The MDA levels were higher and the antioxidant activity and Zn levels lower in the prostate cancer groups than in the healthy control and BPO groups. These results confirm the value of therapies aimed at increasing the antioxidant capacity and encourage the use of plasma and erythrocyte Zn levels in the differential diagnosis of BPO and prostate cancer. The MDA levels can be used in the diagnosis and follow-up of prostate cancer.

The midnight-to-morning urinary cortisol increment method is not reliable for the assessment of hypothalamic-pituitary-adrenal insufficiency in patients with end-stage kidney disease.

A previous study reported that the midnight-to-morning urinary cortisol increment method could be used to reliably assess the insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. The principal aim of the present study is to verify whether the midnight-to-morning urinary cortisol increment is a reliable method for the assessment of the HPA axis in patients with various degrees of impaired kidney function. Fifty-six clinically stable patients with chronic kidney disease (CKD) and 14 healthy subjects were enrolled in the present study. Patients with CKD were divided on the basis of glomerular filtration rate (GFR) into the following arbitrary groups: mild (GFR: 60-89 ml/min/1.73 m2, no.=15), moderate (GFR: 30-59 ml/min/1.73 m2, no.=12) and severe kidney insufficiency (GFR: 15-29 ml/min/1.73 m2, no.=13), and hemodialysis patients. Plasma cortisol and ACTH levels were measured. The HPA axis was assessed by short Synacthen test and overnight dexamethasone suppression test. Double voided urine samples were collected at midnight and waking in the patients and the controls. Urinary free cortisol (UFC) and creatinine levels were measured and the UFC/creatinine ratio (Cort/Cr) was calculated. Then, the Cort/Cr increment was calculated as the morning Cort/Cr minus the midnight Cort/Cr. Baseline plasma cortisol levels were not significantly different between two groups. However, we found that CKD patients had significantly greater plasma ACTH levels than controls. The patients with CKD had also significantly lower morning UFC levels than controls and there was a progressive fall in morning UFC levels with decreasing GFR. The assessment of the HPA axis in patients with GFR lower than 29 ml/min was hampered by falsely abnormal responses to the midnight-to-morning urinary cortisol increment method. Plasma cortisol responded normally to exogenously administered ACTH, while plasma cortisol was suppressed by overnight dexamethasone administration in all patients with CKD. In conclusion, this method is not a reliable test for assessment of the HPA insufficiency in patients with GFR lower than 29 ml/min.

The relationship between carotid atherosclerosis and platelet aggregation in elderly.

The aim of this study is to assess the relationship between the carotid wall intima media thickness (IMT) and atheroma plaques due to atherosclerosis and platelet aggregation among elderly. The first stage of the study was performed by analyzing platelet aggregation in a total of 28 elderly patients divided into two groups. The first group consisted of 14 cases with carotid atheroma plaque (Patient group I) and the second group of patients were without carotid atheroma plaque (Control group I). At the second stage of the study, the cases were regrouped according to the carotid IMT. Patients with IMT above 1 mm (Patient group II, n=10) and under 1 mm (Control group II, n=14) were compared regarding platelet aggregation. Platelet aggregation was induced in the platelet-rich plasma using 5 micro M ADP, 0.2 mg/ml collagen and 1.2 mg/ml ristocetin. Between patients with and without atheroma, no difference was noted in terms of platelet aggregation. Between platelet aggregation results of patients with intimal thickness above and under 1 mm, no significant difference was also noted. Between elderly cases with or without atherosclerosis, there was no difference with respect to platelet aggregation. Platelet aggregation measurements cannot be used as a marker of atherosclerosis in elderly population.

Gonadotropin treatment restores in vitro interleukin-1beta and tumour necrosis factor-alpha production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism.

In the present study, we aimed to investigate the effects of testosterone deficiency and gonadotropin therapy on the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) from patients with idiopathic hypogonadotropic hypogonadism (IHH) in order to elucidate the modulatory role of androgen in cytokine production. Fifteen male patients with untreated IHH and 15 age-matched healthy male subjects were enrolled in the study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), sex hormone binding globulin (SHBG), prolactin, and IL-2 and IL-4 levels were also measured. In unstimulated cultures, IL-1beta and TNF-alpha secretion were not significantly different between patient and control groups. However, after stimulation with lipopolysaccharide (LPS), secretion of IL-1beta and TNF-alpha was significantly higher in cultures from untreated patients with IHH than in control subjects. Mean FSH, LH and FT levels were significantly lower, whereas SHBG, IL-2 and IL-4 levels were significantly higher in patients with IHH compared than in controls. In patients with IHH, FT negatively affected the serum levels of IL-4 and in vitro secretion of IL-1beta and TNF-alpha. In addition, IL-2 and IL-4 affected the in vitro secretion of IL-1beta in a positive manner. Gonadotropin therapy decreased both TNF-alpha and IL-1beta in PBMCs from patients with IHH. The levels of serum IL-2 and IL-4 were also decreased by therapy. In conclusion, in the present study, gonadotropin treatment restored the in vitro production of IL-1beta and TNF-alpha by PBMCs from patients with IHH, suggesting that androgen modulates proinflammatory cytokine production, at least directly through its effects on PBMCs. It seems probable that this effect plays an important role in the immunosuppressive action of androgens.

Transfusion-transmitted virus prevalence in subjects at high risk of sexually transmitted infection in Turkey.

OBJECTIVE: To assess the possible sexual transmission of virus and to identify the prevalence of TTV viremia in Turkey and its association with other hepatotropic viruses. METHODS: Serum samples were collected from 81 subjects (74 prostitutes and seven homosexual men) at high risk of sexually transmitted infection and from 81 healthy controls (74 females and seven males). Sera of patients and controls were tested for TTV, hepatitis A virus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Also, serum alanine and aspartate aminotransferases were measured. RESULTS: The prevalence rates of TTV viremia in the risk group and control group were 86.4% and 82.7%, respectively. There was a statistical difference in mean age between TTV-infected and uninfected subjects (38.6 +/- 9.9 versus 32.2 +/- 6.1 years, respectively, P < 0.001). Prevalence rates of TTV infection in subjects with positive anti-HAV and positive anti-HBc were high when compared with subjects who were negative for these. CONCLUSION: We suggest that TTV infection has a diverse route of transmission, and its prevalence increases with age; also, the prevalence rate of TTV is high in certain risk groups. The prevalence rates of TTV in the group at risk for sexual transmission (86.4%) and in the control group (82.7%) were among the highest ever reported in the world. Also, we suggest that TTV generally does not cause clinical disease, in spite of this high prevalence.

The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome.

Although the effects of androgen deficiency in the immune system have long been appreciated, little is known about the immunological features of patients with Klinefelter's syndrome (KS). On the other hand, interest in androgens as a possible treatment for some autoimmune diseases is growing. In the present study, some immunological parameters were evaluated in 26 patients with KS prior to androgen replacement treatment (ART) and the results were compared with those in 19 healthy control subjects. Patients were then treated with testosterone for 6 months and the pre- and post-treatment findings were compared. Serum levels of IgG, IgA, IgM, C3c and C4 were measured by nephelometry and lymphocyte subsets and CD4+/CD8+ ratios were examined by flow cytometry. IL-2 and IL-4 levels were measured by ELISA. Pretreatment levels of the serum IgA, IgG, IgM, IL-2 and IL-4 of the patients were higher than those of the controls and were all decreased significantly following ART. The pretreatment absolute numbers and percentages of CD3+, CD4+, CD19+ cells and CD4+/CD8+ ratios of patients with KS were higher than those of the controls and were all decreased with ART. Percentages of CD8+ cells were increased significantly, while C3 and C4 levels were both significantly decreased after ART. It is concluded that the lack of testosterone in patients with KS enhances cellular and humoral immunity and that ART may suppress this.

The effects of gonadotropin treatment on the immunological features of male patients with idiopathic hypogonadotropic hypogonadism.

There is a significant line of evidence for a role of androgens in the modulation of the immune system. However, little is known about immunological features of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and the potential effects of gonadotropin treatment. Thus, the objective of this study was to evaluate the levels of selected soluble immune parameters [IgA, IgG, IgM, C3c, C4, interleukin-2 (IL-2), and IL-4], the CD4+/CD8 ratio, and counts of total lymphocyte and some subpopulation of lymphocytes (CD3+, CD4+, CD8+, and CD19+ cells) before and after gonadotropin treatment in men with IHH. Twenty-nine IHH patients and 19 age-matched healthy controls were included in the study. The patients were treated with human menopausal gonadotropin/hCG for 6 months. The pretreatment levels of serum Igs, C3c, IL-2, and IL-4 in the patients were significantly higher than those in the controls (P<0.001 for all). After treatment, all Igs (P<0.001), C3c (P<0.01), and IL-2 and IL-4 levels (P<0.005) were decreased significantly compared to pretreatment levels. Pretreatment lymphocyte counts (P<0.05); the percentages of CD3+ cells (P<0.001), CD4+ cells (P< 0.001), and CD19+ cells (P<0.001); and the CD4/CD8+ ratio in the patient group were significantly higher (P<0.05) than those in the controls. After treatment, the lymphocyte count (P<0.001); CD3+ (P<0.01), CD4+ (P<0.001), and CD19+ (P<0.005) cells; and the CD4-/CD8+ ratio (P<0.001) were decreased, but CD8+ cells were increased significantly (P<0.001). In summary, lack of testosterone action results in the enhancement of cellular and humoral immunity. The results of this study allowed us to conclude that testosterone deficiency affects both cell-mediated and humoral immunity, and these may be modulated with gonadotropin therapy in male patients with IHH.

Clostridium difficile infection in patients with reactive arthritis of undetermined etiology.

In this study Clostridium difficile infection, which has been reported to induce reactive arthritis (ReA), was investigated in patients with ReA of undetermined etiology. One hundred patients with acute arthritis were included to in the study. The diagnosis of arthritis and/or infectious agents that are capable of causing ReA were determined in 69 of them. The remaining 31 patients (study group) with ReA of undetermined etiology were further investigated for C. difficile Toxin A (CDTA). The control groups were consisted of hospitalized patients and outpatients who had no history of diarrhea, arthritis, and antibiotic use. CDTA positive patients (19.4% of the study group) were treated only with oral vancomycin and evaluated for the prognosis of diarrhea and/or arthritis. The results strongly suggested C. difficile infection can induce ReA, especially in patients with antibiotic-associated colitis.