Soundararajan Periasamy

Retracted: Expression of angiotensin II and its receptors in cyclosporine‐induced gingival overgrowth

BACKGROUND AND OBJECTIVES The renin-angiotensin system (RAS) is considered as a hormonal circulatory system involved in maintaining blood pressure, electrolyte and fluid homeostasis. RAS components can be synthesized in local tissues and are found to play a role in gingival overgrowth. The drug-induced gingival overgrowth (DIGO) is a fibrotic condition, which is associated with multiple factors, including inflammation and adverse drug effects such as cyclosporine A. This study was directed forward to the identification of the angiotensinogen, angiotensin II (Ang II) and its receptors AT₁ /AT₂ expression in DIGO tissues and cyclosporine-treated human gingival fibroblast cells. MATERIAL AND METHODS Gingival samples were obtained from patients with cyclosporine-induced gingival overgrowth, chronic periodontitis and normal healthy subjects. The total RNA was isolated and reverse transcription-polymerase chain reaction was performed for angiotensinogen, Ang II and AT₁ /AT₂ receptor. Ang II protein was estimated from tissue by enzyme immunoassay. The expression of Ang II and its receptors were also examined in gingival fibroblast cells treated with cyclosporine. RESULTS Ang II mRNA and protein expression was significantly higher in patients with DIGO than in patients with periodontitis and healthy subjects. The AT₁ mRNA was expressed more than AT₂ in all examined tissues. In gingival fibroblasts, Ang II and AT₁ expressions were increased with cyclosporine incorporation compared to controls. CONCLUSION These results suggest that cyclosporine can modulate local expression of RAS components such as angiotensinogen, Ang II and its receptors in gingival tissues and gingival fibroblast cells.

Expression of TNF-α and RANTES in drug-induced human gingival overgrowth

Objectives: Regulated on activation, normal T cell expressed and secreted (RANTES) is a chemokine that is produced by fibroblasts, lymphoid and epithelial cells of the mucosa in response to various external stimuli. RANTES expression has been demonstrated in a variety of diseases characterized by inflammation, including asthma, transplantationassociated accelerated atherosclerosis, endometriosis and fibrosis. RANTES mRNA is quickly up-regulated by tumor necrosis factor (TNF)-α stimulation. Cyclosporine A (CsA) is widely used in organ transplant patients, often causing various side-effects including gingival overgrowth, which is fibrotic in nature. This study was carried out to assess the mRNA expression of TNF-α and RANTES in healthy individual, chronic periodontitis and CsAinduced gingival overgrowth tissues. Materials and Methods: Gingival tissue samples were collected from chronic periodontitis, CsAinduced gingival overgrowth patients and healthy individuals. Total RNA was isolated and reverse transcription polymerase chain reaction (RT-PCR) was performed for TNF-α and RANTES expression. Results: The results suggest that CsAinduced gingival overgrowth tissues expressed significantly increased TNF-α and RANTES compared to control and chronic periodontitis. Conclusion: The findings of the present study suggest that CsA can modify the expression of TNF-α and RANTES in drug-induced human gingival overgrowth.

A comparison of oral and dental manifestations in diabetic and non-diabetic uremic patients receiving hemodialysis

Background: The purpose of the study was to evaluate the oral and dental findings of uremic patients receiving hemodialysis and to compare the Results between diabetic and non-diabetic groups. Materials and Methods: A total of 100 patients undergoing hemodialysis were classified into diabetic and non-diabetic groups and examined for uremic oral manifestations, dental caries (DMFT), and periodontal status (CPITN). Mann-Whitney test of significance has been applied for analyzing DMFT score and chi-square test is used for analyzing CPITN score. Results: Of the study group, 46% were diabetic and only 11% of them did not have any oral manifestation. Oral manifestations observed were xerostomia and uremic odor, which contributed to 47 (23%) and 37 (17%), respectively. Hyperpigmentation was present in 26 (12%), macroglossia in 23 (11%), and uremic tongue coating in 24 (11%). Mucosal petechiae were seen in 17 patients contributing to 8% of total patients. Eleven patients had tongue pallor (5%), 9 patients had glossitis with depapillation (4%), and 7 patients had dysgeusia (3%). Angular cheilitis and gingival swelling were seen in 5 patients (2%). Conclusion: The oral and dental manifestations were higher in prevalence in the study group. However, there was no significant difference between the two groups.

Immunohistochemical Localization of Epithelial Mesenchymal Transition Markers in Cyclosporine A Induced Gingival Overgrowth

INTRODUCTION Cyclosporine, an immunosuppressive agent used in the management of renal transplant patients is known to produce Drug Induced Gingival Overgrowth (DIGO) as a side effect. Several mechanisms have been elucidated to understand the pathogenesis of DIGO. Recently, epithelial mesenchymal transition has been proposed as a mechanism underlying fibrosis of various organs. AIM The aim of the study was to investigate if Epithelial Mesenchymal Transition (EMT) operates in Cyclosporine induced gingival overgrowth. MATERIALS AND METHODS The study involved obtaining gingival tissue samples from healthy individuals (n=17) and subjects who exhibited cyclosporine induced gingival overgrowth (n=18). Presence and distribution of E-Cadherin, S100 A4 and alpha smooth muscle actin (α-SMA) was assessed using immunohistochemistry and cell types involved in their expression were determined. The number of α- SMA positive fibroblasts were counted in the samples. RESULTS In control group, there was no loss of E-Cadherin and a pronounced staining was seen in the all layers of the epithelium in all the samples analysed (100%). S100 A4 staining was noted in langerhans cells, fibroblasts, endothelial cells and endothelial lined blood capillaries in Connective Tissue (CT) of all the samples (100%) while α - SMA staining was seen only on the endothelial lined blood capillaries in all the samples (100%). However in DIGO, there was positive staining of E-Cadherin only in the basal and suprabasal layers of the epithelium in all the samples (100%). Moreover there was focal loss of E-Cadherin in the epithelium in eight out of 18 samples (44%). A break in the continuity of the basement membrane was noted in three out of 18 samples (16%) on H & E staining. CONCLUSION Based on the analysis of differential staining of the markers, it can be concluded that EMT could be one of the mechanistic pathways underlying the pathogenesis of DIGO.

Assessment of abdominal aortic calcification in predialysis chronic kidney disease and maintenance hemodialysis patients

Vascular calcification is associated with increased morbidity and mortality among chronic kidney disease (CKD) patients. The aim of the study was to assess the abdominal aortic calcification (AAC) in predialysis CKD patients and patients on hemodialysis (HD) and to study the risk factors associated with it. In this prospective study, 205 patients were including 104 patients with predialysis CKD and 101 patients were on maintenance hemodialysis. AAC was assessed using lateral lumbar radiography. Blood urea nitrogen, serum creatinine, albumin, calcium, phosphorus, highly sensitive C-reactive protein (hsCRP) and total cholesterol were analyzed. AAC was observed in 26 % of predialysis CKD patients and 34% in HD patients. Using multivariate analysis, the age (P = 0.001) was identified as independent predictor for the presence of AAC in predialysis patients, and for HD, the predictors were age (P = 0.025), time on dialysis (P = 0.001), hsCRP (P = 0.002), and corrected calcium (P = 0.030). In conclusion, the prevalence of AAC varies mainly with age and glomerular filtration rate levels in predialysis CKD patients. Advanced age, time on dialysis, and inflammation may be associated with presence and extent of AAC in HD patients. Further research into the risk factors and outcome for AAC is warranted.

Role of endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism on the progression of renal disease in autosomal dominant polycystic kidney disease

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder, and it is mainly associated with renal cyst formation. Several studies have also shown that these mutations regulate the physiology of epithelial tissues and determine renal cyst formation and growth in polycystic kidney disease (PKD). Nitric oxide (NO) is also considered to be an important factor involved in the deterioration of renal function. Objectives: The aim of the current study is to determine the frequency of NOS3 27-bp VNTR in ADPKD patients and to investigate the role of NOS3 27-bp VNTR genotypes in the modification of progression of renal disease in ADPKD.Patients and Methods: The hypothesis was investigated by studying the South Indian population of 53 ADPKD patients and 94 unrelated healthy controls. The genotyping was performed by polymerase chain reaction and electrophoresis. Genotypes were compared between ADPKD and controls using the χ2-test. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on the progress of chronic kidney disease (CKD). A stratified analysis was also performed to assess the evidence of the modification of hypertension-CKD relationship among VNTR genotypes. Results: The NOS3 4a allele frequencies were 21.3% and 13.2% respectively for controls and ADPKD groups. The NOS3 VNTR genotypes and alleles were not associated with ADPKD. The univariate analysis showed that age, hypertension and NOS3 VNTR influenced the advancement of CKD. Conclusion: The present study confirms the significant association between the 27-bp VNTR and CKD advancement among the ADPKD patients in the South Indian population.

Histochemical Expression of Mast Cell Chymase in Chronic Periodontitis and Cyclosporine-Induced Gingival Overgrowth

Mast cell (MC) mediators play a vital role in fibrosis. The purpose of this study was to investigate the MCs and their enzyme chymase in gingival tissues showing drug-induced gingival overgrowth (DIGO) and also to evaluate the correlation of MC counting and expression with the chronic periodontitis. In this study, 30 samples, including cyclosporine-induced gingival overgrowth, chronic periodontitis (10 for each), and ten normal gingival tissues, were collected. We analyzed the histochemical expression of MC chymase in all the collected tissues. In addition, the number of MCs was counted for each deparaffinized section stained with toluidine blue. Furthermore, total RNA was extracted from tissue samples, and RT-PCR was performed for MC chymase. The numbers of MCs were found to be increased in relative lesions compared to normal gingival tissues (). Moreover, chymase-containing MCs in DIGO tissues showed striking differences from those of control subjects and chronic periodontitis (). The RT-PCR analysis further revealed that MC chymase mRNA increased significantly in DIGO tissues. In conclusion, although the MCs were less numerous in numbers, the cells exhibited significant expression of chymase enzyme suggesting the involvement of MCs in DIGO.