Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Prognostic importance of COX-2 expression in patients with colorectal cancer

A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3 cm or tm > or = 3 cm), tumor histopathological differentiation (poorly differentiated or moderately + well differentiated), number of metastatic lymph nodes (< 4 or 3 > or = 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome.     

An unexpected complication of acute pancreatitis: Intra-cardiac thrombus

Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement. Because of induction of systemic prothrombotic process by AP; some patients with underlying risk factors may develop an intra-cardiac thrombus. We present a 53 years-old-woman with moderate mitral stenosis and atrial fibrillation. However the patient was under warfarin treatment, she developed a big left atrial big thrombus which was originated from left atrial appendage after she was suffered from AP.     

Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue,psychological status,disease severity and other clinical parameters

Aim of the work: To evaluate the quality of life (QoL) in Familial Mediterranean Fever (FMF) patients, and determine its association with fatigue, depression, disease severity and other clinical parameters. Patients and methods: Sixty FMF patients were included. QoL was assessed by Short Form-36 (SF-36), depression by Hamilton Depression Scale (HDS), and fatigue by Fatigue severity scale (FSS). Disease severity score and Mutations of the Mediterranean fever (MEFV) gene were assessed. Results: The mean age of patients was 33.73 ± 9.81 years and disease duration 14.6 ± 12.1 years. They were 35 females and 25 males. FMF patients scored significantly higher in FSS (29.9 ± 17.6) and HDS (15.1 ± 8.5) compared to the control (10.6 ± 7.1 and 6.3 ± 9.4; p < 0.0001 respectively) while all SF36 sub-items except mental health were significantly lower (p < 0.05). MEFV gene mutation was present in 49 (81.7%) patients. The visual analogue scale of pain significantly negatively correlated with the FSS (p < 0.0001), HDS (p < 0.0001) and all SF36 sub-items except mental health (p < 0.0001). Disease duration, age of onset, and duration of attacks showed no significant correlation with FSS, HDS and SF36. Delay in diagnosis significantly correlated with FSS (p < 0.0001) and negatively with SF36 sub-items physical role (p = 0.02), general health (p = 0.01) and social functioning (p = 0.03). Age of diagnosis significantly correlated with FSS (p = 0.03) and negatively with SF36-vitality (p = 0.047). There was a significant effect of disease severity on QoL, fatigue and depression (p < 0.05). Conclusion: QoL is associated with fatigue, depression and disease severity in FMF patients. It should be used in routine clinical evaluation as an outcome measure in FMF.     

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls.

Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay.

Results: The mean age of RPL and control cases were 31.6?±?0.6 and 32.1?±?0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk.

Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.     

The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: Results from two reference hospitals and review of literature

Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes. The subgroup analysis between the patients who developed nephrotoxicity during colistin treatment and those that did not, showed no significant difference in terms of age, underlying disease, cause for PICU admission and type of infection required colistin treatment, P values were 0.615, 0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant nephrotoxic agent (P = 0,355). The majority of the patients (52%) were having primary or secondary immune deficiency in treatment failure group and the most common cause of PICU admission was sepsis in treatment failure group, P values were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children. However, the patients have to be followed for side effects throughout colistin treatment, not for only early stage. And the clinicians should be aware of increase in the rate of nephrotoxicity in patients those have been receiving a concomitant nephrotoxic agent.     

Black Grape and Garlic Extracts Protect Against Cyclosporine A Nephrotoxicity

The aim of this study was to determine if the natural antioxidant foods, dried black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two Sprague–Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the antioxidant food supplementation begun 3 days before CsA treatment and continued during the study period (totaling 13 days). In each group (control, CsA alone, CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract alone and black grape alone), there were 7 animals. At the end of the study period, the animals were sacrificed; their kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (xanthine oxidase enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes) parameters were measured in the kidney tissues of the groups. Histopathological examinations of the tissues were also performed.

It has been found that CsA creates oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which accelerates oxidation reactions in the kidney tissue. Supplementation with either dried black grape or aqueous garlic extract led to reduced malondialdehyde level in the kidney tissue possibly, by preventing oxidant reactions. In conclusion, the results suggest that impaired oxidant/antioxidant balance may play part in the CsA-induced nephrotoxicity, and some foods with high antioxidant power may ameliorate this toxicity, in agreement with studies with antioxidant vitamins.     

Correlation of molecular biomarker concentrations between synovial fluid and saliva of the patients with temporomandibular disorders

Objectives

The synovial membrane and fluid are involved in the pathogenesis of temporomandibular joint (TMJ) disorders. This study aims to assess the relationship between matrix metalloproteinase-2 (MMP-2), chemerin and prostaglandin (PGE₂) levels in the synovial fluid (SF) and saliva of patients with TMJ disorder regarding their role in inflammation and the value of being a candidate for predictive biomarkers in the disease. Also, it is aimed to find out whether chemerin’s main function triggers the formation inflammatory cytokine markers in the associated area.

Materials and methods

Thirty-two samples of SF and saliva were obtained from patients with disc displacement without reduction with limited opening (DDWORwLO). Mann-Whitney-U test was used for the comparisons of the biomarker levels in SF and saliva. The correlation between chemerin and BMI (Body Mass Index) is analyzed by non-parametric Spearman’s rho correlation coefficient.

Results

For all of the three biomarkers, statistically significant differences were found between SF and saliva. An unexpectedly high level expression of chemerin was observed in SF. A statistically significant, positive correlation was observed between PGE₂ -MMP-2, and chemerin-PGE₂ in saliva, chemerin and MMP-2 in SF, respectively (p = 0.031, r = 0.382 / p = 0.039, r = 0.366 / p = 0.032, r = 0.379). A positive correlation was determined between saliva and SF levels of PGE₂ (p = 0.016, r = 0.421).

Conclusions

Chemerin, MMP-2, and PGE₂ can play a role as an inflammatory factor for the development of TMJ disorder.

Clinical relevance

The search for molecular markers in TMJ and the inhibition of the associated molecular signaling mechanism is important to reduce joint inflammation and cartilage degradation.

     

Effects of glutamine on wound healing

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.