Protective effects of thymoquinone on the healing process of experimental left colonic anastomosis.

PURPOSE: Colorectal cancer is globally the third most common cancer. Anastomotic complications remain to be an important issue for colorectal surgery. The aim of this study was to investigate the protective effects of thymoquinone (TQ) on the healing process of left colonic anastomosis in an experimental model. METHODS: Thirty-two male rats were divided into two groups, as the TQ group and the control group. TQ was administered to the TQ group, whereas the control group was given a standard feed and water for 2 wk. Following the creation of a left colonic anastomosis, subjects in both groups were sacrificed on the postoperative (PO) third and seventh days. Anastomotic burst pressures were measured mechanically. Immunohistochemical stainings for proliferating cell nuclear antigen, cluster of differentiation (CD) 31, CD45 were performed, and the matrix metalloproteinase-2 levels were measured. Histologic total scores were calculated according to Ehrlich-Hunt model. A value of P < 0.05 was considered as statistically significant. RESULTS: One rat in the control group that died on the PO fourth day was excluded. Anastomotic burst pressures on the PO seventh day were higher in the TQ group than the control group (P < 0.01). Histopathological total scores on the PO third and seventh days were higher in the TQ group (P < 0.01). In addition, the TQ group revealed lower matrix metalloproteinase-2 scores on the PO third day and higher hydroxyproline levels on the PO seventh day (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: The use of TQ in colorectal surgery cases with left-sided colonic anastomosis resulted with increased anastomotic burst pressures and increased tissue hydroxyproline levels.

Differences in leptin, ghrelin, and glucagon-like peptide-1 levels between religious fasting and normal fasting

Background/aim: Leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) affect hunger, satiety feelings, and food intake. We hypothesized that during Ramadan, if the brain knows that the body will be hungry until sunset, there may be differences between leptin, ghrelin, and GLP-1 levels in Ramadan and non-Ramadan fasting. Materials and methods: This study had two phases. In the first phase, the participants were asked to skip the dawn meal of Ramadan (suhur), so that 12 h of fasting could be achieved. Participants ceased food intake at midnight, and at noon blood was drawn. Eight participants were selected as a subgroup. These participants gave blood three times a day to detect hormonal changes during Ramadan. Six months later, in the second phase, blood samples were obtained at noon from participants after 12 h of fasting. Results: Analysis was conducted on 30 patients [19 males (63.3%) and 11 females (36.7%)]. There was a significant difference in leptin, ghrelin, and GLP-1 levels between Ramadan fasting and non-Ramadan fasting (P = 0.04, P = 0.02, and P < 0.001, respectively). In the subgroup analysis, there was no statistically significant difference in leptin, ghrelin, and GLP-1 levels over time. Conclusion: The results of this study suggest that the nervous and gastrointestinal systems may behave differently in religious fasting than in nonreligious fasting.

The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer.

AIM OF THE STUDY: Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker that is stored in neutrophil granules. Recent studies revealed that NGAL expression increases in tissue samples of patients with inflammatory gastrointestinal system diseases and cancers. The aim of this study was to evaluate the diagnostic and predictive significance of plasma NGAL levels in various stages of adenoma-carcinoma sequence of colorectal cancer. Materials and Methods: Eighty cases were included in the study and separated into 3 groups. "Cancer Group" consisted of 27 colorectal cancer patients who underwent curative resection, whereas 24 patients with colorectal adenomatous polyps detected by colonoscopy were classified as the "Polyp Group", and 29 patients with normal colonoscopy findings were classified as the "Control Group". The serum NGAL, CEA and CA19-9 levels and histopathology findings were determined. Results: The mean plasma NGAL levels for control group, polyp group and cancer group were found to be 91.5 ng/ml, 139.6ng/ml and 184.3ng/ml, respectively. Plasma NGAL levels were found to be significantly higher in cancer group compared to the control group (p:0.006). Plasma NGAL levels were detected statistically significant and positive correlated with tumor diameter and number of metastatic lymph nodes (p:0.047, r:%38.6 and p:0.026, r:%42.8, respectively) in cancer group. Conclusions: We are of the opinion that pre-operative plasma NGAL level is a potential diagnostic biomarker for colorectal cancer patients. Although more comprehensive studies are needed for definitive judgments, serum NGAL levels may be used as a diagnostic and/or predictive biomarker for lymph node metastasis in patients with colorectal cancer.

The effects of thrombomodulin and activated protein C on the pathogenesis of multiple sclerosis.

BACKGROUND: Various molecules of the coagulation cascade are thought to have varying roles in the pathophysiology of multiple sclerosis (MS). We aimed to find new information about the effects of the coagulation cascade molecules to develop new therapeutic strategies for MS. MATERIALS AND METHODS: Patients with MS were chosen from among patients who were followed up at our hospital. We examined the thrombomodulin (TM) and activated protein C (APC) serum levels in patients with MS and the healthy controls. The patient groups were determined as relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) according to the McDonald criteria and between ages of 18 and 70. RESULTS: A total of 244 participants, 122 patients with multiple sclerosis and 122 healthy volunteers were included in the study. There was no statistically significant difference in the APC and TM levels between the patients and the healthy controls (p>0.05), between the patients with RRMS and SPMS (p>0.05), and between the first day of acute relapse and 10th day of methylprednisolone therapy in the patients with RRMS (p=0.334; p=0.363). We detected a statistically positive correlation only between the expanded disability status scale (EDSS) scores and TM levels in the patient group (p=0.009). CONCLUSION: Treatment with methylprednisolone decreases EDSS score in RRMS relapse. The increase in EDSS is related to level of TM. The changes in level of TM and APC may be indicator for prognosis of MS or treatment modalities to MS.

Is Low Serum Klotho Level Associated with Alterations in Coronary Flow Reserve?

BACKGROUND: The Klotho gene, described as an "aging suppressor" gene, encodes a single-pass transmembrane protein. The extracellular part of Klotho is cleaved and released into the circulation where it may function as a vasculoprotective hormone. Coronary flow reserve (CFR) is accepted as a marker of coronary microvascular dysfunction when epicardial coronary stenosis is absent. There are no data regarding the relationship between serum Klotho levels and disorders in coronary microcirculation in healthy adults. We aimed to investigate the association between serum Klotho levels and alterations in coronary microcirculation in healthy adults using echocardiographic measurements of CFR. METHODS: Thirty-four healthy volunteers (median age: 34 [27-39], 14 males) were enrolled in this study. The study population was divided into two subgroups according to the median value of serum Klotho levels: a high Klotho (HK) group (n = 17, median age: 34 [30-38]; 6 males) and a low Klotho (LK) group (n = 17, median age: 32 [26-39]; 8 males). The analysis of coronary flow velocities was performed by transthoracic Doppler echocardiography. RESULTS: Hyperemic diastolic peak flow velocities and CFR were significantly higher in the HK group than in the LK group (70 [66-92] versus 61 [47-66], P = 0.003 and 3.0 [2.6-3.8] versus 2.2 [1.7-2.8], respectively, P = 0.001). Serum Klotho levels were positively correlated with CFR (P < 0.001). CONCLUSION: Serum Klotho levels correlate with CFR in a healthy population. Low serum Klotho levels may potentially identify patients with impaired CFR.

Fibroblast growth factor-23 but not sKlotho levels are related to diastolic dysfunction in type 1 diabetic patients with early diabetic nephropathy.

PURPOSE: To investigate the soluble Klotho (sKlotho) and fibroblast growth factor-23 (FGF-23) levels and echocardiographic findings in type 1 diabetic patients with no or early diabetic nephropathy. METHODS: A total of 147 subjects (mean age 34.1 ± 9.2 years, 55.8 % were females) including type 1 diabetic patients with glomerular filtration rate (GFR) >60 ml/min (n = 71, mean age 34.3 ± 9.5 years, 54.9 % were females) and healthy controls (n = 76, mean age 33.9 ± 9.1 years, 56.6 % were females) were included in this study. Data on demographic characteristics, blood biochemistry, urinalysis, diabetes-related complications and echocardiography were recorded. Serum levels for sKlotho and FGF-23 were determined by ELISA method. RESULTS: Patient and control groups were similar in terms of mean sKlotho (509.2 ± 183.5 and 547.6 ± 424.0 pg/ml, respectively) and FGF-23 (76.2 ± 15.6 and 77.2 ± 15.1 pg/ml, respectively) levels as well as echocardiographic findings. No significant correlation of sKlotho (pg/ml) and FGF-23 (pg/ml) levels with cardiac parameters was noted among diabetic patients. In subgroup analysis, the correlations between FGF-23 levels and isovolumic relaxation time (ms) and early diastolic velocity at medial/septal annulus (E'med) (m/s) were significant only in patients with early diabetic nephropathy (DN) but not in non-DN patients. No significant association of sKlotho levels with echocardiographic findings was noted. CONCLUSIONS: Our findings in young adult type 1 diabetic patients with GFR >60 ml/min versus healthy controls revealed no difference between groups in terms of sKlotho and FGF-23 levels and echocardiographic findings, while a significant correlation of FGF-23 (pg/ml) levels and diastolic dysfunction was noted only in patients with DN.

Is serum Klotho protective against atherosclerosis in patients with type 1 diabetes mellitus?

OBJECTIVE: Klotho deficiency is associated with several metabolic disorders. Two dimensional (2D) longitudinal strain (LS) of left ventricle (LV), carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of brachial artery and epicardial fat thickness (EFT) have been reported to be early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and these early predictors of atherosclerosis in patients with type 1 diabetes mellitus (DM). METHODS: The study included 45 type 1 diabetic patients and 35 controls. Serum Klotho levels were determined by ELISA method. The patient group was also divided into two subgroups according to serum Klotho levels: high (HK) and low Klotho (LK) groups. EFT, CIMT and FMD were measured according to appropriate recommendations. Speckle tracking analysis was performed using the Echopac software. RESULTS: The patient group had significantly lower serum Klotho (p=0.001), FMD (p<0.001) and LS of LV (p<0.001) values, but larger EFT (p<0.001) and CIMT (p<0.001) values than controls. LK subgroup had also significantly lower FMD (p<0.001) and LS of LV (p<0.001) but larger EFT (p=0.002) and CIMT (p<0.001) values than HK subgroup. CONCLUSION: Serum Klotho may have a protective effect against atherosclerosis and endothelial dysfunction in type 1 DM.

Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is a type 1 tubular cell transmembrane protein that is found in high levels in early stages of acute kidney injury and is stated to have predictive value in the early diagnosis of chronic kidney diseases. In this study, the hypothesis was that higher levels of KIM-1 would be detected in hypertensive patients for the early detection of nephropathy. With this goal, urinary KIM-1 levels of hypertensive cases were compared with those of healthy controls, and associations of KIM-1 levels with microalbuminuria and glomerular filtration rate (GFR) were investigated. METHODS: The study included a total of 80 patients aged ≥20 years (55 male, 25 female, mean age: 57.21±9.12 years). The patient group consisted of 40 patients (28 males, 12 females, mean age: 57.58±8.79 years) who had had hypertension for at least 5 years, and the control group consisted of 40 healthy subjects (27 female, 13 male, mean age: 56.85±9.53 years). Groups were compared based on demographic, anthropometric and biochemical data, and urinary KIM-1 levels. Correlation analysis was made to assess the association of KIM-1 levels with microalbuminuria and GFR. Levels of urinary KIM-1 enzyme were measured using linked immunosorbent assay (ELISA). RESULTS: KIM-1 levels were found to be 0.86±0.48 ng/mg creatinine in the patient, and 0.71±0.46 pg/mL in the control groups (P>0.05). A positive correlation was detected between KIM-1 levels and both systolic blood pressure and duration of disease (r=0.308, P=0.032 and r=0.339, P=0.032, respectively). CONCLUSIONS: While not supporting the hypothesis that KIM-1 levels may increase in hypertensive patients as an early indicator of hypertensive nephropathy, these findings suggested that this molecule might be associated with kidney injury in hypertensive nephropathy due to its positive correlation with the duration of hypertension.

Low Serum Level of Klotho Is an Early Predictor of Atherosclerosis.

The Klotho gene, identified as an 'aging suppressor' gene, encodes a single-pass transmembrane protein. The extracellular domain of Klotho is cleaved and released in the blood stream, where it may function as a vasculoprotective hormone. Carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery and epicardial fat thickness (EFT) have been reported as early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and early atherosclerotic predictors, including EFT, FMD and CIMT in healthy adults. Fifty healthy volunteers were enrolled in this study, consisting of 21 males and 29 females with median age of 32 years. They were free of known risk factors for cardiovascular diseases. Serum Klotho levels were determined by the ELISA method. The study population was divided into two groups (n = 25 for each) according to the median serum Klotho level (459.4 pg/mL): higher Klotho (HK) group (613.6 pg/mL; ranges of 501.2-772.6 pg/mL) and lower Klotho (LK) group (338.7 pg/mL; ranges of 278.8-430.3 pg/mL). EFT was measured by transthoracic echocardiography, and CIMT and FMD were measured with standard procedures. The LK group showed lower values of FMD (p = 0.012) and larger values of EFT (p = 0.01) and CIMT (p < 0.001), compared to the HK group. Thus, the low serum Klotho levels were associated with increased EFT and CIMT and with the decreased FMD in the study population. We propose that the lower serum Klotho level is a newly identified predictor of atherosclerosis.

Levels of F2 isoprostane in Behcet's disease: Correlation with cardiometabolic risk factors.

OBJECTIVE: Behcet's disease (BD) is a chronic inflammatory disease and recent findings suggest a role of oxidative stress in the pathogenesis of BD. Free radical-induced oxidative stress is also involved in the pathogenesis of cardiovascular and other rheumatic diseases. Oxidative stress may be detected in vivo by measuring F2 isoprostanes. Here, we measured plasma levels of F2 isoprostane in patients with BD and evaluated the correlation of F2 isoprostane with cardiometabolic risk factors. METHODS: Forty-three patients with BD in remission and 37 age- and sex-matched controls were recruited for the study. Blood samples were obtained to determine F2 isoprostane, C-reactive protein levels, erythrocyte sedimentation rate, and other biochemical parameters. Homeostasis model assessment insulin resistance and body mass index were calculated. Systolic blood pressure, diastolic blood pressure, and waist circumference were measured. RESULTS: Plasma F2 isoprostane, fasting plasma glucose, triglyceride, and C-reactive protein levels were significantly higher in patients with BD compared with healthy controls, whereas high-density lipoprotein cholesterol levels were significantly lower in patients with BD. F2 isoprostane levels did not correlate with cardiometabolic risk factors, C-reactive protein levels, or erythrocyte sedimentation rate. CONCLUSION: High levels of F2 isoprostane in patients with BD indicate oxidative stress. Antioxidant therapeutic approaches could potentially affect the course of this disease.

Levels of pentraxin 3 and relationship with disease activity in patients with ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis is a chronic inflammatory disease of the sacroiliac joint and vertebral column. Pentraxin (PTX) 3 is an acute phase protein known to be associated with chronic inflammation. This study was performed to test the hypothesis that serum PTX3 levels might be elevated as a marker of inflammation in patients with ankylosing spondylitis. MATERIAL AND METHODS: A total of 73 patients older than 20 years (48 males, 25 females, mean age 32.30 ± 6.40 years) were included. The ankylosing spondilitis group consisted of 46 patients (18 females, 28 males, mean age 33.30 ± 6.12 years) diagnosed with ankylosing spondilitis by the Modified New York Criteria, and the control group consisted of 27 healthy individuals (7 females, 20 males, mean age 30.59 ± 6.62 years). Groups were compared by demographic, anthropometric, biochemical data, and by serum PTX3 levels. The ankylosing spondilitis group was also divided into 2 subgroups (active or remission) by disease activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and compared by serum PTX3 levels. PTX3 was measured with the enzyme linked immunosorbent method. RESULTS: PTX3 levels were higher in the ankylosing spondylitis group compared to the control group (0.29 ± 0.83 ng/mL vs. 0.09 ± 0.06 ng/mL, p=0.009). Levels of serum PTX3 were similar in groups with active and remitted ankylosing spondilitis (0.34 ± 0.99 ng/mL vs 0.37 ± 1.15 ng/mL, p>0.05). No correlation was determined between PTX3 and disease activity (p>0.05). CONCLUSION: These results are supportive of the hypothesis that levels of serum PTX 3 might be elevated in association with inflammation in patients with ankylosing spondylitis; however, results also demonstrate that there is no significant correlation with disease activity.

Urinary NGF, TGF-ß1, TIMP-2 and bladder wall thickness predict neurourological findings in children with myelodysplasia.

PURPOSE: Dimercapto-succinic acid scintigraphy and urodynamic studies are gold standards to evaluate renal scarring and neurogenic bladder dysfunction, respectively. We sought to establish the value of bladder wall thickness together with urine NGF, TGF-ß1 and TIMP-2 to predict the urodynamic profile and upper urinary tract damage in children with myelodysplasia. MATERIALS AND METHODS: A total of 80 children with myelodysplasia underwent urodynamic investigation, bladder wall thickness measurement and dimercapto-succinic acid scintigraphy with basic neurourological evaluation. Two study and 2 control groups were created according to presence or absence of renal scarring on dimercapto-succinic acid scan (study and control groups 1) and according to detrusor leak point pressure greater or less than 40 cm H2O (study and control groups 2). Urine samples were analyzed with ELISA. RESULTS: The study population consisted of 44 girls and 36 boys with a median ± SD age of 7.2 ± 3.6 years (range 2 to 17). Study and control groups 1 consisted of 35 and 45 children with abnormal and normal dimercapto-succinic acid scan findings, respectively. Study and control groups 2 included 30 and 50 children with detrusor leak point pressure greater and less than 40 cm H2O, respectively. Bladder wall thickness and urinary levels of TGF-ß1, NGF and TIMP-2 were significantly increased in both study groups compared to controls. CONCLUSIONS: Urine markers and bladder wall thickness measurement may predict urinary tract impairment in children with myelodysplasia. Such markers may differentiate at risk patients with either renal scarring or high detrusor leak point pressure, and decrease the need for urodynamics and renal scintigraphy.

Effect of Helicobacter pylori eradication on serum ghrelin and obestatin levels.

AIM: To investigate changes in serum ghrelin and obestatin levels before and after Helicobacter pylori (H. pylori) eradication. METHODS: A total of 92 patients presenting with symptoms of dyspepsia were enrolled in the study. Upper endoscopy was performed on all patients and used to diagnose H. pylori infection according to the presence of characteristic histopathological findings; seventy patients were diagnosed with H. pylori infection and the remaining 22 non-infected patients were classified as healthy controls. H. pylori eradication was accomplished by administering the classical triple therapy drug regimen, consisting of lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg tid for 14 d. The eradication of H. pylori was assessed with C¹4-urea breath test, which was performed at eight weeks after treatment. Levels of serum active ghrelin and obestatin were assessed at beginning of the study (prior to treatment) and after eight weeks. The levels were comparatively analyzed between the H. pylori negative control group, the H. pylori eradicated group, and the H. pylori non-eradicated group. RESULTS: A total of 92 patients, 50 females and 42 males with a mean age of 38.2 ± 11.9 years (range: 19-64), were analyzed. H. pylori eradication success was achieved in 74.3% (52/70) of H. pylori positive patients. The initial levels of ghrelin in the H. pylori positive and control cases were 63.6 ± 19.8 pg/mL and 65.1 ± 19.2 pg/mL (P = 0.78), respectively, and initial obestatin levels were 771 ± 427 pg/mL and 830 ± 296 pg/mL (P = 0.19), respectively. The difference between the initial levels and the week 8 levels of ghrelin and obestatin in the control group was insignificant [4.5% (P = 0.30) and -0.9% (P = 0.65), respectively]. The difference between the initial and week 8 levels of ghrelin and obestatin in the H. pylori non-eradicated group were also insignificant [0.9% (P = 0.64) and 5.3% (P = 0.32), respectively]. The H. pylori eradicated group had a greater change in obestatin levels when compared to the control and the non-eradicated groups (148 ± 381 pg/mL vs -12 ± 138 pg/mL and -72.8 ± 203 pg/mL, respectively, P = 0.015), while decreases in ghrelin levels were insignificant (-7.2 pg/mL vs -1.4 pg/mL and -1.9 pg/mL, respectively, P = 0.52). The ghrelin/obestatin ratio for the initial and week 8 levels changed significantly in only the H. pylori eradicated group (0.11 vs 0.08, respectively, P = 0.015). For overweight patients (as designated by body mass index), we observed significant increases in obestatin levels in the eradicated group as compared to non-eradicated group (201 ± 458 pg/mL vs -5 ± 81 pg/mL, respectively, P = 0.02). In the H. pylori-eradicated group, the levels did not differ between the sexes for ghrelin (-6.3 ± 26.9 pg/mL vs -8.0 ± 24.0 pg/mL, respectively, P = 0.97) or obestatin (210 ± 390 pg/mL vs 96 ± 372 pg/mL, respectively, P = 0.23). CONCLUSION: Serum levels of ghrelin decreased while obestatin levels increased in H. pylori eradicated subjects, especially in overweight and male patients.

Copeptin is a predictive biomarker of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis remains a common intraabdominal disease with a complex pathophysiology. The overall outcome has improved, but specific treatment remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of copeptin in the initial phase of predicted severe acute pancreatitis. METHODS: Between August 2008 and December 2011, 57 patients with acute pancreatitis and 30 healthy individuals were included in the study. Four blood samples, for serum copeptin measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent 3 samples were taken at 12, 24, and 48 hours after the onset of pain. RESULTS: Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients. CONCLUSIONS: Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.

Myocardial performance after successful intervention for native aortic coarctation.

Coarctation of the aorta is associated with increased risk for hypertension in adulthood, despite successful repair. The intrinsic mechanisms underscoring hypertension and left ventricular performance in these patients, however, remains to be determined. Our objective was to evaluate left ventricular performance by means of echocardiographic and biochemical parameters at midterm follow-up in normotensive children who have had undergone successful surgical or catheter interventional treatment of coarctation with a residual gradient of less than 20 mmHg at rest. We studied prospectively 14 patients with native aortic coarctation who underwent surgery or balloon angioplasty, the cohort made up of equal numbers of boys and girls, and having a mean age of 8.5 plus or minus 4 years. We also studied 30 age-matched healthy subjects, measuring mitral inflow pulsed wave signals, isovolumic relaxation and contraction times, myocardial performance index parameters, and levels of B-type natriuretic peptide and endothelin-1 in both groups. We found no differences in systolic blood pressure at rest between the patients and their controls. The ventricular septal diastolic dimensions, left ventricular posterior wall dimensions, mitral valve E wave, deceleration time, isovolumic relaxation time, isovolumic contraction time and myocardial performance index were all significantly increased in the patients. Levels of plasma B-type natriuretic peptide and endothelin-1 were also significantly higher in the patients when compared to the control group. We conclude that aortic coarctation is a chronic disease characterized by persistency of myocardial and vascular alterations. The elevated levels of plasma b-type natriuretic peptide and endothelin-1 may be indicative of late onset hypertension after successful treatment of native coarctation in early childhood.

Serum hyaluronic acid levels in patients with ankylosing spondylitis.

Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial inflammation and disease severity in AS.

Docosahexaenoic acid (omega-3) blocks voltage-gated sodium channel activity and migration of MDA-MB-231 human breast cancer cells.

Omega-3 polyunsaturated fatty acids have been suggested to play an important role in cancer prevention/progression, on the one hand, and in modulation of membrane ion channels on the other. We investigated whether docosahexaenoic acid would influence the in vitro migration of MDA-MB-231 human breast cancer cells. An important follow-up question was whether any effect would involve voltage-gated Na(+) channels, shown previously to occur in human breast cancer in vitro and in vivo and to correlate with metastatic potential. Short-term (acute) and long-term (24-72 h) application of docosahexaenoic acid suppressed the activity of the channel activity in a dose-dependent manner. At the working concentrations of docosahexaenoic acid used (0.05-0.5 microM), there was no effect on proliferation. Long-term treatment with docosahexaenoic acid down-regulated mRNA and protein (total and plasma membrane) levels of neonatal Nav1.5 voltage-gated Na(+) channel, known to be predominant in these cells. Docosahexaenoic acid suppressed migration of the MDA-MB-231 cells to the same extent as tetrodotoxin, a highly specific blocker of voltage-gated Na(+) channels, but the two effects were not additive. It was concluded that the docosahexaenoic acid-induced suppression of cellular migration occurred primarily via down-regulation of voltage-gated Na(+) channel (neonatal Nav1.5) mRNA and functional protein expression.