Association between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

ObjectivesMonocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at ?2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population.Design and methodsA total of 290 Tunisian patients with hypertension and 390 normotensive controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsA significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (χ² = 8.02, p = 0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11–1.91), p = 0.004]. The association between the ?2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionThe present study showed a significant and independent association between the ?2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian population.     

Relationship between toll-like receptor 2 nonsynonymous single nucleotide polymorphisms and the effectiveness of Bacille Calmette-Guérin immunotherapy in preventing recurrence of superficial bladder cancer: A prospective study

Background: Intravesical Bacille Calmette-Guérin (BCG) immunotherapy has been used for several decades as a prophylactic approach against recurrence of superficial bladder cancer. However, its effectiveness has been both variable and unpredictable. Typically, cancer BCG-immunotherapy aims to redirect or modulate both innate and adaptive immune responses. The consequences of gene polymorphisms in several key immuno-regulatory molecules on the heterogeneity of the response to BCG-immunotherapy have been investigated.Objective: The aim of this study was to evaluate the association of toll-like receptor (TLR) 2 polymorphisms (arginine to glutamine substitution at position 753 [Arg753Gln] and arginine to tryptophan substitution at position 677 [Arg677Trp]) and the outcome of BCG-immunotherapy.Methods: This prospective study was conducted during a 3-year period from June 2006 to July 2009. Consecutive patients were recruited during a 1-year period and followed for 2 years at the Department of Urology, Charles Nicolle Hospital, Tunis, Tunisia. Patients with superficial bladder tumors at stage Ta (noninvasive papillary carcinoma) or T1 (where the tumor has grown from the layer of cells lining the bladder into the connective tissue below but has not grown into the muscle layer of the bladder) of any grade were eligible; carcinoma in situ cases were excluded. The TLR2 Arg753Gln and Arg677Trp polymorphisms were studied in peripheral blood DNA from patients treated with BCG-immunotherapy after transurethral resection.Results: A total of 112 consecutive patients were enrolled (101 men and 11 women; mean age, 63.9 years [range, 25–85 years]) and completed the 2-year followup. Polymerase chain reaction amplification followed by direct sequencing of the region containing the TLR2 single-nucleotide polymorphism (SNP) of interest did not detect Arg753Gln or Arg677Trp in any of the study participants belonging to either of 2 groups: responders (n = 67) and nonresponders (n = 45) to BCG-immunotherapy.Conclusions: No patients included in the study were found to have the 2 known TLR2 nonsynonymous SNPs, and the relative importance of these polymorphisms could not be definitely determined. However, a significant proportion of patients without these polymorphisms responded to BCG-immunotherapy, suggesting that these genetic variants are not critical in the effectiveness of this approach for preventing recurrence of the tumor.     

The association of endothelial cell signaling,severity of illness,and organ dysfunction in sepsis

Introduction  

Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.     

Effect of a self-etch primer/adhesive on the shear bond strength of orthodontic brackets

Conventional adhesive systems use 3 different agents (an enamel conditioner, a primer solution, and an adhesive resin) during the bonding of orthodontic brackets to enamel. A unique characteristic of some new bonding systems in operative dentistry is that they combine the conditioning and priming agents into a single product. Combining conditioning and priming saves time and should be more cost-effective to the clinician and, indirectly, to the patient. The purpose of this study was to determine the effects of the use of a self-etch primer on the shear bond strength of orthodontic brackets and on the bracket/adhesive failure mode. Brackets were bonded to extracted human teeth according to 1 of 2 protocols. In the control group, teeth were etched with 37% phosphoric acid. After the sealant was applied, the brackets were bonded with Transbond XT (3M Unitek, Monrovia, Calif) and light cured for 20 seconds. In the experimental group, a self-etch acidic primer (ESPE Dental AG, Seefeld, Germany) was placed on the enamel for 15 seconds and gently evaporated with air, as suggested by the manufacturer. The brackets were then bonded with Transbond XT as in the first group. The present in vitro findings indicate that the use of a self-etch primer to bond orthodontic brackets to the enamel surface resulted in a significantly (P = .004) lower, but clinically acceptable, shear bond force (mean, 7.1 +/- 4.4 MPa) as compared with the control group (mean, 10.4 +/- 2.8 MPa). The comparison of the adhesive remnant index scores indicated that there was significantly (P = .006) more residual adhesive remaining on the teeth that were treated with the new self-etch primer than on those teeth that were bonded with the use of the conventional adhesive system.     

Identification of novel retinal target genes of thyroid hormone in the human WERI cells by expression microarray analysis

Using the human WERI-Rb1 cell line as a model system, we performed a genome-wide search for retinal target genes of thyroid hormone (TH) via expression microarray analysis followed by quantitative real-time RT-PCR verification. We identified 12 novel retinal targets of TH, including 10 up-regulated genes (OPN1MW, OPN1LW, TIMP3, RP1L1, GNGT2, CRX, ARR3, GCAP1, IMPDH1, and PDE6C) and 2 down-regulated genes (GNGT1 and GNB3). In addition, we found a number of novel TH-targets that are not currently known to be retinal genes. This is the first report of human retinal targets regulated by thyroid hormone.