Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction

Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

PURPOSE: Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS: We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS: Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cho-lesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION: Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

Association of E-cadherin gene 3f-utr c/t polymorphism with endometriosis

Endometriosis [EM]is one of the most frequent diseases in gynecology; endometriotic cells display invasive characteristics, despite their benign histological appearance. Epithelial-cadherin [E-cadherin] is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. We investigated the relation between E-cadherin gene 3'-untranslated region [3'-UTR] C/T polymorphism and EM in 100 Egyptian women with EM and 100 women without EM. The polymerase chain reaction based restriction fragment length polymorphism was used to identify the digestible [C] and undigestible [T] polymorphism and compare the genotypes and allelic frequencies of this gene in both groups. The C allele frequency was significantly higher in the EM group than in the control group [odds ratio = 4.38, 95% confidence interval = 2.78-6.90], and the C/C and C/T genotype frequencies were significantly higher in the EM group than in the control group. E-cadherin gene 3'-UTR C/T polymorphism is a useful marker for predicting susceptibility to EM

Evaluation of specific biochemical indicators of Helicobactepylori-associated gastric cancer in Egypt

The aim of the study was to assess the accuracy of some specific biochemical indicators in discriminating between Helicobacter pylori-associated gastritis and H. pylori-associated stomach cancer [serum gastrin level, serum soluble E-cadherin and tissue COX-2 activity, as well as serodiagnostic markers for H. pylori infection] in order to find a simple diagnostic test that can reasonably predict the development of gastric cancer. The study participants comprised 20 patients with gastric carcinoma, 20 patients with positive H. pylori-associated gastritis and 20 individuals as the control group. Standard procedures and quality control measures were followed. Using cut-off values and ROC analysis to assess the diagnostic abilities of the biochemical indicators, E-cadherin showed the highest sensitivity [100%]. We suggest that close follow-up together with periodic endoscopic examination for all patients with persistent H. pylori infection and serum soluble E-cadherin level above 5 microg/mL is essential

High concentration of soluble form of vascular endothelial cadherin in sera of patients with prostate cancer

For many years, prostate-specific antigen [PSA] was used to screen prostate cancer [PC] patients. However, recent controversial findings have cast doubt on the accuracy of this biomarker for diagnostic and prognostic purposes, and have stimulated the search for new candidates. This study was conducted to determine the capability of a soluble adhesion molecule known as soluble vascular endothelial cadherin [sVE-cadherin] or CD144 to distinguish prostate cancer or benign prostate hyperplasia [BPH] patients from healthy individuals. Patients recently diagnosed as having PC [N=35] or BPH [N=35] and age-matched controls [N=30] were study enrolled. The concentration of sVE-cadherin and PSA was measured by ELISA. Gleason score in s with PC was determined by pathological examination of tumor biopsies. The concentration of sVE-cadherin in the serum of patients with PC and BPH was significantly higher hat in the healthy men. No association was found between the concentration of this soluble adhesion molecule and PSA values. Moreover, concentrations of sVE-cadherin did not correlate with Gleason scores in patients with PC. The high concentration of sVE-cadherin in our patients suggests that this bio-marker is a potentially tool to identify high-risk patients. However, further research in patients with PC and other pathological conditions is needed to support the efficacy of this molecule in PC screening

Evaluation of E- cadherin and telomerase expression in urothelial carcinoma of the urinary bladder

E-cadherin is a transmembrane glycoprotein involved in intercellular adhesion. A loss or reduction in e-cadherin expression has been linked to the invasive phenotype of a wide variety of human neoplasms. including bladder tumors. Human telomerase reverse transcriptase [hTERT] is a catalytic subunit of telomerase and is a potentially useful diagnostic marker for cancers in many neoplasms, increased telomerase activity is associated with poor clinical outcomes. The objective of the present study was to evaluate the immunohistochemical expression and the potential prognostic value of E-cadherin and telomerase catalytic subunit [hTERT]in urothelial carcinoma of the urinary bladder by comparing them to other prognostic parameters as tumor grade, depth of invasion, and stage. The study comprised 54 patients with bladder tumors who underwent TUR or cystectomy. Formalin fixed paraffin sections from the tumors were processed with a hot, citric acid antigen retrieval method, followed by immunostaining using a monoclonal antibody E-cadherin [NCL-E-cad] Novocastra, mouse monoclonal antibody NCL-L-hTERT [Novovastra]and peroxidase detection system [Novocastra]. Showed loss of normal membrane E-cadherin immunoreactivity in 49 [90.7%] patients. Abnormal expression of E-cadherin was associated with muscle invasive disease [p = 0.0002] and high grade tumors [p = 0.0002].Telomerase [hTERT] was detected in 5 1/54 [94.4%] of urothelial carcinoma, and negative in all normal urothelium adjacent to the neoplasm in cystectomy specimens. No association was found between telomerase and other prognostic factors. In bladder cancer altered E-cadheri n expression is associated with the degree of invasiveness, and tumor grade. However, Telomerase [hTERT] detection by immunostaining is a highly sensitive diagnostic marker for urothelial malignancy but its value as a prognostic marker needs further assessment

Differential expression of E-cadherin in ductal and lobular breast carcinomas and its biologic and diagnostic value

E-cadherin is a calcium dependent epithelial cell adhesion molecule. Loss of E-cadherin function has been associated with aggressive behavior in various malignancies. In this study, we analyzed the pattern of E-cadherin expression in 25 invasive carcinomas [15 ductal and 10 lobular] and 14 in slat carcinomas [10 ductal and 4 lobular] to determine its role in the morphogenesis of breast carcinoma. E-cadherin was Semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. Our results proved a highly significant correlation of E-cadherin membrane expression with the histologic phenotype of the tumor. While preserved [strong] to reduced membrane expression was seen in all invasive and in situ ductal carcinomas as in normal mammary epithelium, 90% [9/10] of invasive lobular carcinoma [ILC] and 75% [3/4] of lobular carcinoma in situ [LCIS] cases showed complete loss of E-cadherin expression. The only E-cadherin positive ILC case was diagnosed histologically as pleomorphic variant and was associated with solid ductal carcinoma in situ [DCIS] component. This tumor most probably represents an example of invasive ductal carcinoma [IDC]. Reduced E-cadherin expression increased significantly from DCIS [20%] to IDC [66.7%]. A highly significant difference between E-cadherin expression in IDC and ILC [P = 0.0001] and a significant difference between DCIS and LCIS [P = 0.004] were found. So we concluded that in tumors with histologically equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic tool for differentiation of the ductal and lobular carcinomas of the breast

Granulocyte macrophage colony stimulating factor: role in induction of monocyte CD14 receptor and adhesion molecules expression in chronic liver diseases

This study included 36 chronic liver disease [CLD] patients who suffered from viral hepatitis and / or schistosomiasis and 12 age and sex matched healthy individuals who represent the control group. The study aimed at clarifying the role of rhGM-CSF on the release of sICAM-1 and sCD14 from PBMNC. According to the severity of liver disease, patients were classified to Child A, B and C groups. All patients and controls were subjected to thorough history taking and clinical examination, a full routine laboratory investigation including hemogram, liver function tests and hepatitis markers. PB mononuclear cell culture was performed to all the study groups with and without the addition of rhGM-CSF to the culture media. Afterwards, slCAM-1 and sCDl4 were measured in culture supernatant fluid using ELISA technique, Levels of sICAM-1 in culture supernatants with and without addition of rhGM-CSF showed significant progressive increase with advancement of CLD which may reflect the increase ofsICAM-1 in sera of CLD patients with progression of the disease. As well, the addition of rhGM-CSF to PBMNC culture resulted in a significant reduction of sICAM-1 level in culture supernatants in control and patients groups in comparison to its level without the addition of rhGM-CSF. There was a significant progressive increase in sCD14 level with the advancement of the disease. The increase in sCD14 level with and without addition of rhGM-CSF was significant in all patients groups in comparison to the control group. As well, the addition of rhGM-CSF to culture media led to significant reduction of sCD14 concentration in supernatants in control group and in each of the patients groups in comparison to their levels without the addition of rhGM-CSF. It can be concluded that rhGM-CSF might be considered as one of the potential future tools against defective monocyte functions in CLDs. Using rhGM-CSF to improve monocyte functions will be associated with reduction of sICAM-1 and sCD14 levels which might be implicated or contribute to liver pathology