Can Serum Histone H4 Level Be a Biomarker in Ulcerative Colitis?

BACKGROUND/AIMS: Histones are a part of neutrophil extracellular trap molecules which were reported to have diagnostic values in some inflammatory diseases. We aimed to evaluate whether serum histone H4 can be a diagnostic and prognostic marker for ulcerative colitis. MATERIALS AND METHODS: This case-control study included 58 ulcerative colitis patients (34 males and 24 females) and 45 healthy controls (25 males and 20 females). The Mayo clinical scoring system was used for the clinical and endoscopic features. Truelove-Witt's method was applied to the histology activity index. The human histone H4 kit was used for the enzyme-linked immunosorbent assay of serum histone H4. RESULTS: Serum histone H4 was significantly lower in the ulcerative colitis group compared to the control groups [268 (14-1639) vs. 598 (310-2134) ng/L, P < .001, respectively]. Among the ulcerative colitis patients, there was no correlation between serum histone H4 and disease extent, Mayo clinical scoring, Mayo endoscopic activity subscoring, histology activity index, inflammatory markers, d-dimer, and leukocyte and neutrophil counts (r < 0.20, P > .05). Histone H4 levels were not statistically significant between the patients with no medication and those taking 5-aminosalicylate and/or other agents (P > .05). The receiver operating characteristic curve analysis revealed that serum histone H4 concentrations had a 0.782 (95%CI: 0.690-0.857, P < .001) diagnostic accuracy for ulcerative colitis. The specificity and sensitivity for the cutoff level of ≤364 ng/L were 88.9% and 72.4%, respectively. CONCLUSION: Decreased serum histone H4 values may be used as an auxiliary marker in the progression and diagnosis of ulcerative colitis. Further studies are needed to delineate this relationship between clinical and laboratory traits of ulcerative colitis and serum histone H4.

Can inflammatory indexes predict the spontaneous passage of common bile duct stones?

OBJECTIVES: We aimed to determine whether inflammatory indexes (II), including the neutrophil-lymphocyte ratio (NLR), the C-reactive protein (CRP) to albumin ratio (CAR), the CRP-lymphocyte ratio (CLR), and the systemic immune-inflammation index (SIII) can be diagnostic for common bile duct stones (CBDSs) excretion before endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUNDS: Because of the spontaneous clearance, it is mandatory to ascertain the presence of CBDSs before ERCP. METHODS: Retrospectively, we evaluated two groups. Group A included 96 records in which CBDSs existed in magnetic resonance cholangiopancreatography (MRCP) and ERCP. Group B included 36 records in which CBDSs existed in MRCP but not ERCP. IIs were calculated on presentation and before ERCP. RESULTS: Stone detection in ERCP had a 3.992-fold (95% 1.769-9.007) higher probability with a stone larger than 3.25 mm in MRCP. Before ERCP, CAR, and CLR values were higher in group A than in group B (3.88 [1.25-14.14] and 1.24 [0.50-9.66], p = 0.027 versus 8.79 [2.19-35] and 2.67 [1.02-20.05], p = 0.029, respectively). Higher CRP, CAR, and CLR values were considered significant for detecting a stone in ERCP (AUC: 0.627 [0.519-0.739], 0.625 [0.513-0.737], and 0.624 [0.514-0.734], respectively). CONCLUSION: Low CRP, CAR, and CLR values might associate with the spontaneous migration of CBDS.

Evaluation of platelet indices and pro-inflammatory cytokines in type 2 diabetic patients with retinopathy.

OBJECTIVE: The aim of this study was to investigate whether platelet parameters and pro-inflammatory cytokines associated with platelet activation could be surrogate markers of the diabetic retinopathy stages in type 2 diabetic patients. METHODS: This prospective case-control study included 108 type 2 diabetes mellitus patients and 48 healthy controls. After fundoscopic examination, patients were divided into three groups: no retinopathy, nonproliferative diabetic retinopathy, or proliferative retinopathy. Platelet selectin, interleukin-1alpha, and interleukin-6 values were measured by the enzyme-linked immunosorbent assay method. Homeostatic Model Assessment for Insulin Resistance formula was used to assess insulin resistance in patients. RESULTS: Mean platelet volume was lower and interleukin-1alpha was higher in the patients compared to the healthy controls (p=0.046 and p<0.001, respectively). In addition, a positive correlation between the platelet distribution width and HbA1C levels was observed in the patients (r=0.334, p<0.001). CONCLUSION: In the studies evaluating the utility of platelet indices and the associated cytokines in diabetic retinopathy, there is a need for the standardization of the measurements. All medications that can affect platelet activation should be taken into consideration.

Evaluation of platelet indices and pro-inflammatory cytokines in type 2 diabetic patients with retinopathy

SUMMARY OBJECTIVE: The aim of this study was to investigate whether platelet parameters and pro-inflammatory cytokines associated with platelet activation could be surrogate markers of the diabetic retinopathy stages in type 2 diabetic patients. METHODS: This prospective case-control study included 108 type 2 diabetes mellitus patients and 48 healthy controls. After fundoscopic examination, patients were divided into three groups: no retinopathy, nonproliferative diabetic retinopathy, or proliferative retinopathy. Platelet selectin, interleukin-1alpha, and interleukin-6 values were measured by the enzyme-linked immunosorbent assay method. Homeostatic Model Assessment for Insulin Resistance formula was used to assess insulin resistance in patients. RESULTS: Mean platelet volume was lower and interleukin-1alpha was higher in the patients compared to the healthy controls (p=0.046 and p<0.001, respectively). In addition, a positive correlation between the platelet distribution width and HbA1C levels was observed in the patients (r=0.334, p<0.001). CONCLUSION: In the studies evaluating the utility of platelet indices and the associated cytokines in diabetic retinopathy, there is a need for the standardization of the measurements. All medications that can affect platelet activation should be taken into consideration.

Vagococcus fluvialis first isolated from the ascitic fluid of a patient with cirrhosis.

Ascites is the most common complication of the decompansated cirrhosis. The most common organisms isolated in patients with ascidic fluid infections and spontaneous bacterial peritonitis (SBP) are intestinal pathogens including Escherichia coli, Gram-positive cocci (mainly Streptococcus species) and Enterococci. As an infectious pathogen Vagococcus spp. can be isolated from animals such as pigs, cats, horses and fishes and also rarely in humans. In this paper, we present a case of Vagococcus fluvialis peritonitis which is the first one reported in a cirrhotic patient with ascites.

Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis.

BACKGROUND/AIMS: We aimed to semi-quantitatively investigate prohibitin-2 (Phb-2) and stomatin-like protein-2 (Slp-2) expressions in patients with ulcerative colitis (UC) and healthy controls using the immunohistochemical (IHC) method. We also aimed to evaluate the correlations between the activity of UC and the expressions of these two proteins. MATERIALS AND METHODS: Ninety-five patients with UC (82 males and 13 females) and 38 healthy controls (35 males and 3 females) were included. Clinical and endoscopic activities of UC were assessed. Conventional laboratory activation parameters and severity of inflammation measures were used for the evaluation of histological activity. IHC staining of biopsy samples for the two proteins were semi-quantitatively applied, similar to previously described methods for colon adenocarcinomas. RESULTS: IHC scores of Phb-2 were lower but Slp-2 scores were higher in the UC group than in the healthy controls (p<0.05 and p=0.003, respectively). Phb-2 scores were positively correlated with clinical and histological activities (r=0.364, p<0.05 and r=0.220, p<0.032, respectively). In the UC group, endoscopic activity scores, C-reactive protein levels, and sedimentation rates were also positively correlated with Phb-2 scores (r=0.279, p<0.05, r=0.216, p<0.05, and r=0.216, p<0.05, respectively). IHC scores of Slp-2 were not significantly correlated with the activity parameters of UC. However, there was a significant positive correlation between the expressions of Phb-2 and Slp-2 proteins (p<0.001). CONCLUSION: Phb-2 may serve as a valuable new biomarker for predicting the severity of all UC activity parameters. The therapeutic effectiveness of both Phb-2 and Slp-2 should be taken into consideration.

Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in patients with familial Mediterranean fever.

BACKGROUND/AIMS: Serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are well-known inflammatory biomarkers, with a diagnostic potential for various diseases. The aim of the present study was to determine the potential diagnostic applications of serum MMP-9 and TIMP-1 concentrations in patients with familial Mediterranean fever (FMF). MATERIALS AND METHODS: A total of 66 male FMF patients and 40 age-matched healthy subjects were included in this research. TIMP-1 and MMP-9 levels with conventional inflammation markers were determined. Pearson correlation analysis was used to determine the correlation between the characteristics of patients and the laboratory data. RESULTS: In patients with FMF, serum MMP-9 levels and MMP-9/TIMP-1 ratios were found to be significantly elevated in both acute episode and asymptomatic periods (p=0.0001 and p=0.0001, respectively). There was no significant difference between TIMP-1 levels. A significant negative correlation between patients' current age and TIMP-1 level in patients with acute episodes was detected (p=0.0008, r=-0.52). Moreover, a moderate negative correlation was noticed between erythrocyte sedimentation rate and TIMP-1 level in patients with acute episodes (p=0.01, r=-0.39). Additionally, a moderate negative correlation was found between the duration of colchicine use and MMP-9 and TIMP-1 levels during the attack period (p=0.04, r=-0.36 and p=0.02, r=-0.39, respectively). CONCLUSION: Our findings demonstrate that a significant MMP-9/TIMP-1 imbalance exists in patients with FMF, which reflects an ongoing inflammation in both FMF periods. Thus, the increased MMP-9 levels observed in FMF patients could rationalize therapeutic targeting to MMPs.

Mean Platelet Volume is Reduced in Acute Appendicitis.

OBJECTIVES: Acute appendicitis (AA) is the most common indication for emergency abdominal surgery, although it remains difficult to diagnose. In this study, we investigated the the clinical utility of mean platelet volume in the diagnosis of acute appendicitis. METHODS: The medical records of 241 patients who had undergone appendectomy between June 2013 and March 2014 were investigated retrospectively. Sixty patients who had undergone at least one complete blood count during preoperative hospital admission and who had no other active inflammatory conditions at the time the sample was taken were included in the study. Mean platelet volume and leukocyte count values were determined in each patient at hospital admission and during active acute appendicitis. Age, sex, mean platelet volume and leukocyte counts were recorded for each patient. RESULTS: The mean age of patients was 33.15±10.94 years and the male to female ratio was 1.5:1. The mean leukocyte count prior to acute appendicitis was 7.42±2.12×10(3)/mm(3). Mean leukocyte count was significantly higher (13.14±2.99×10(3)/mm(3)) in acute appendicitis. The optimal leukocyte count cutoff point for the diagnosis of acute appendicitis was 10.10×10(3)/mm(3), with sensitivity of 94% and a specificity of 75%. The mean platelet volume prior to acute appendicitis was 7.58±1.11 fL. Mean platelet volume was significantly lower (7.03±0.8 fL) in acute appendicitis. The optimal mean platelet volume cutoff point for the diagnosis of AA was 6.10 fL, with a sensitivity of 83% and a specificity of 42%. Area under the curve for leukocyte count diagnosis was 0.67 and 0.69 for the diagnosis of AA by mean platelet volume. CONCLUSIONS: Mean platelet volume was significantly decreased in acute appendicitis. Mean platelet volume can be used as a supportive diagnostic parameter in the diagnosis of acute appendicitis.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats.

AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1ß and the leukocyte count. RESULTS: When the results of serum amylase, lipase, TNF-α and IL-1ß levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Classic Mediterranean type of epiglottic Kaposi sarcoma.

Kaposi sarcoma is a malignant, multifocal, vascular, and low-grade tumor that mostly occurs in mucocutaneous sites. Kaposi sarcoma is usually associated with acquired immunodeficiency syndrome and involves lymphatic nodes and visceral organs. In this report, an 81-year-old man with epiglottic Kaposi sarcoma who screened negative for human immunodeficiency virus is presented.

Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever?

BACKGROUND/AIM: Familial Mediterranean fever (FMF), the most frequent periodic fever syndrome, is an autosomal recessive inherited disease that predominantly affects eastern Mediterranean populations. Fetuin-A is a well known negative acute-phase protein. Studies of this glycoprotein as a marker of inflammation in FMF are limited. We have investigated the relationship between serum levels of fetuin-A and inflammatory markers in patients with FMF before, during, and after FMF attacks. METHODS: Sixty-seven patients with FMF were enrolled in this study. Serum fetuin-A, seruloplasmin, fibrinogen, C reactive protein (CRP), white blood cell count (WBC), calcium, and erythrocyte sedimentation rate (ESR) were measured three times: during the attack-free period, 12 h after FMF attacks, and 7 days after FMF attacks. Plasma fetuin-A concentration was measured by use of an enzyme-linked immunoassay (ELISA) kit. Correlations and differentiation between the serum fetuin-A and other inflammatory markers in patients with FMF were investigated by use of the paired-samples T test and the Pearson correlation test (p < 0.01). RESULTS: Serum fetuin-A levels of all FMF patients in the attack period were significantly lower than in the attack-free period (p < 0.001). In contrast, serum seruloplasmin (p < 0.05), fibrinogen (p < 0.001), CRP (p < 0.05), WBC (p < 0.05), and ESR (p < 0.05) were all significantly higher than in the attack-free period. Plasma fetuin-A is significantly and inversely highly correlated with the other inflammatory markers. CONCLUSION: Fetuin-A might be a novel indicator of disease activity in patients with FMF and could be used as an adjunctive marker for differentiation of FMF attacks. The negative correlation between serum fetuin-A and other inflammatory markers may also be indicative of inflammation-dependent downregulation of fetuin-A expression in FMF patients.

Malignant biliary obstruction significantly increases serum lipid levels: a novel biochemical tumor marker?

BACKGROUND/AIMS: We aimed to investigate the alterations in serum lipid levels due to biliary obstruction associated with benign and malignant cases. Also, we aimed to examine the possibility of the theory that extremely high serum lipid levels can predict the malignant biliary obstruction in the differantial diagnosis. METHODOLOGY: Three hundred twenty two patients who were performed endoscopic retrograde cholangiopancreatography with the intrahepatic and extrahepatic cholestasis were reviewed in the period from September 2007 to October 2010. RESULTS: In the malignant obstruction group, meaningfully higher total cholesterol (p<0,001), low-density lipoprotein (p>0.05) and triglycerides (p<0.05) were observed but high-density lipoprotein (p<0.05) levels were lower. The receiver operating characteristic analysis showed that total cholesterol (246.74 mg/dL or less, sensitivity: 84.3%, specificity: 83.3%, area under the curve: 0.705 (0.620-0.790) (p<0.001)) and high-density lipoprotein cholesterol (area under the curve: 0.577 (0.444-0.710)) were predictors of malignant biliary obstruction. CONCLUSIONS: Serum lipid profile may be used as an applicant marker to identify malignant reasons of the obstructive jaundice.

An extremely uncommon case of parasitic infection presenting as eosinophilic ascites in a young patient.

We report the case of a 24-year-old male patient admitted for recent ascites and splenomegaly of unknown origin. The patient was referred to our institution with complaints of diarrhea, epigastric pain, abdominal cramping and weight loss over the past three weeks. The acute onset presented with colicky abdominal pain and peritoneal effusion. History revealed reduced appetite and weight gain of 7 kg over the last one month. His past medical history and family history was negative. He had no history of alcohol abuse or viral hepatitis infection. Laboratory data revealed normal transaminases and bilirubin levels, and alkaline phosphatase and gammaglutamyltransferase were within normal range. A diagnostic laparoscopy was performed which showed free peritoneal fluid and normal abdominal viscera. Upper gastrointestinal system endoscopy performed a few days later revealed diffuse severe erythematous pangastritis and gastroduodenal gastric reflux. Duodenal biopsies showed chronic nonspecific duodenitis. Antrum and corpus biopsies showed chronic gastritis. The ascitic fluid was straw-colored and sterile with 80% eosinophils. Stool exam was negative for parasitic infection. Treatment with albendazole 400 mg twice daily for 5 days led to the disappearance of ascites and other signs and symptoms. Three months after albendazole treatment the eosinophilic cell count was normal. The final diagnosis was consistent with parasitic infection while the clinical, sonographic and histological findings suggested an eosinophilic ascites. We emphasize the importance of excluding parasitic infection in all patients with eosinophilic ascites. We chose an alternative way (albendazole treatment) to resolve this clinical picture. With our alternative way for excluding this parasitic infection, we treated the patient and then found the cause.