Absence Of Calcium Channel Blockers Research Articles

The Role of MDR1 C3435T Gene Polymorphism on Gingival Hyperplasia in Turkish Renal Transplant Patients Treated With Cyclosporine in the Absence of Calcium Channel Blockers

ObjectiveTo investigate the occurrence of MDR1 C3435T gene polymorphisms in the Turkish renal transplant patients treated with cyclosporine (CsA), and correlate these findings with prevalence and degree of gingival hyperplasia (GH). MethodsBefore to renal transplantation, dental treatment and oral hygiene education of 300 renal disease patients was completed. Peripheral blood samples were collected from 154 renal transplant recipients on CsA treatment without calcium channel blockers. MDR1 C3435T gene polymorphism and GH were analyzed at posttransplant month 6. ResultsNo difference was detected among groups for age, posttransplant period, creatine levels, serum concentration of CsA, or plaque and bleeding indices (P > .05). Out of all transplanted patients, 42.8% were found to have the heterozygote genotype. This was reduced to 37.5% when individuals with GH were taken into account. However, when degree of GH was analyzed, those with severe GH were found to have the heterozygote genotype significantly more often (P < .05). ConclusionsThe MDR1 gene polymorphism is not associated with GH frequency, but may be associated with GH severity.

Gingival Overgrowth Among Patients Medicated With Cyclosporin A and Tacrolimus Undergoing Renal Transplantation: A Prospective Study

The aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT). This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). The individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento-enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals. The mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P = 0.03), 90 (P = 0.004), and 180 (P = 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P = 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P <0.001) in both groups. Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA.

Gingival Overgrowth in Renal Transplant Subjects Medicated With Tacrolimus in the Absence of Calcium Channel Blockers

The results from reports analyzing the occurrence of gingival overgrowth (GO) induced by tacrolimus are controversial. In addition, the role of pharmacological and periodontal variables on the development and severity of GO have not been well-established. Therefore, the aim of the present study was to determine the effect of potential risk variables for GO in a Brazilian population comprising renal transplant recipients medicated with tacrolimus in the absence of calcium channel blockers. Demographic, pharmacological, and periodontal data, recorded from 125 subjects selected to participate in the study, was analyzed with the use of the independent sample t test, the chi-squared statistic, or Mann-Whitney test. The effects of risk variables on GO scores were subsequently examined using multivariate regression analysis and general linear model. The prevalence of clinically significant GO (> or =30%) in the study population was of 7.25%. These subjects showed greater averages of plaque scores (P=0.0043) as well as papillary bleeding index (P=0.0026) when compared to subjects with GO <30%. Papillary bleeding index, time since transplant and azathioprine dosage were significant in the univariate and multivariate models (adjusted R=43.8%), whereas plaque index was significant only in the univariate model. This study revealed that, in the absence of calcium channel blockers, gingival inflammation, represented by the papillary bleeding index, was a variable associated with Tcr-induced GO, indicating the importance of periodontal maintenance of subjects under Tcr immunosuppressive regimens.

Incidence of tacrolimus‐induced gingival overgrowth in the absence of calcium channel blockers: a short‐term study

The aim of this study was to determine the incidence and severity of gingival overgrowth (GO) induced by tacrolimus (Tcr) compared with ciclosporin A (CiA) in the absence of calcium channel blockers (CCB) in renal transplant recipients. Forty patients (20 Tcr and 20 CiA) were evaluated before and 30 and 90 days after kidney transplantation. Demographic (age, gender) and periodontal parameters were recorded for all patients. Patients taking CCB at any time during the study were excluded from the investigation. The mean GO score was significantly lower (p=0.014) in the Tcr group (6.4%) compared with the CiA group (17.9%) after 90 days of immunosuppressive therapy. At 90 days post-transplant, clinically significant GO was observed in four patients of the CiA group and in two of the Tcr group. This difference was not statistically significant (0.66). No significant difference in the incidence of clinically significant GO was observed between the CiA and Tcr groups up to 90 days of immunosuppressive therapy.

Demographic, Pharmacologic, and Periodontal Variables for Gingival Overgrowth in Subjects Medicated With Cyclosporin in the Absence of Calcium Channel Blockers

The role of cyclosporin in the absence of calcium channel blockers and the associated risk variables of development and severity of gingival overgrowth have not yet been properly established. The present study was conducted to determine the effect of potential risk variables for gingival overgrowth severity in Brazilian renal transplant subjects medicated with cyclosporin in the absence of any calcium channel blockers. A cross-sectional study was conducted in a public hospital in Belo Horizonte, Brazil. Demographic, pharmacologic, and periodontal data, recorded from 194 subjects taking cyclosporin in the absence of calcium channel blockers, were analyzed using independent sample t, chi2 statistic, or Mann-Whitney U tests. The effects of potential risk variables of gingival overgrowth severity were determined using backward stepwise regression analysis. The prevalence of clinically significant gingival overgrowth was 34.5% (N = 67). These subjects presented a significantly higher papillary bleeding index and a higher plaque index compared to those without clinically significant gingival overgrowth. When all demographic, pharmacologic, and periodontal data were evaluated in relation to gingival overgrowth severity, time since transplant, papillary bleeding index, serum cyclosporin concentration, and prednisolone and azathioprine dosages were significant in the univariate modeling (P <0.05) and remained significant when evaluated in the multivariate modeling (P <0.0001; adjusted R2 = 39.4%). In the absence of calcium channel blockers, this study showed that pharmacologic variables, such as cyclosporin serum concentration, prednisolone and azathioprine dosages, and time since transplant, are strongly related to gingival overgrowth. In addition, the periodontal variable papillary bleeding index highlighted the primary role of inflammation on the pathogenesis and severity of gingival overgrowth.

Potentiation of cyclic AMP-mediated proopiomelanocortin gene promoter activity by calcium channel blockers in a pituitary cell line

Although it is known that the expression of proopiomelanocortin, a precursor protein of adrenocorticotropic hormone, can be affected by a variety of drugs, the effects of calcium channel blockers have not been studied. This study examined the effect of calcium channel blockers on proopiomelanocortin gene expression. Mouse pituitary tumor cells stably transfected with approximately 0.7 kb of the rat proopiomelanocortin 5′ promoter–luciferase fusion gene were stimulated by potassium chloride, corticotropin-releasing hormone (CRH) or forskolin, in the presence or absence of calcium channel blockers (nifedipine, verapamil and diltiazem). Assessments were made of proopiomelanocortin gene promoter activity and cyclic adenosine 3′,5′-monophosphate (cyclic AMP) efflux. A dose-dependent enhancement of CRH- or forskolin-stimulated proopiomelanocortin promoter activity was observed with nifedipine and verapamil, but not diltiazem. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by nifedipine and verapamil. In the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor, enhancement of proopiomelanocortin promoter activity and cyclic AMP efflux by nifedipine and verapamil was not observed. It was concluded that the inhibition of phosphodiesterase is a probable mechanism for the effect of nifedipine and verapamil on CRH or forskolin induction of proopiomelanocortin gene expression.

Risk factors for gingival overgrowth in patients medicated with ciclosporin in the absence of calcium channel blockers

This study investigates the effect of a range of potential risk factors on the severity of gingival overgrowth in transplant patients medicated with ciclosporin in the absence of any calcium channel blockers. One hundred dentate solid organ transplants medicated with ciclosporin (but not calcium channel blockers or phenytoin) were recruited for the study. Demographic, pharmacological and periodontal data were recorded and gingival overgrowth assessed from stone models. Univariate analysis identified the duration of transplant, papilla bleeding index, creatinine serum concentration, azathioprine and prednisolone dosage as risk factors for overgrowth severity. Multivariate modelling, excluding the periodontal parameters, gave a predictive model that included dosages of ciclosporin, azathioprine, prednisolone and weight (p<0.0001, adjusted-R2=19%). Adding the periodontal variables strengthened the model (p<0.0001, adjusted-R2=34.5%). The explanatory models in this study contain a number of variables that moderate inflammation (azathioprine and prednisolone) or are markers of it (papilla bleeding index). Dosage of each of the three immunosuppressants was identified as a risk factor for the severity of gingival change. This observation appears to have been masked by the effects of the calcium channel blockers in earlier studies.

Lipid Metabolism and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Role of Factors Modulating Cytosolic Calcium.

Animal studies indicate that insulin resistance and glucose intolerance leading to dyslipidemia in uremic rats are associated with increased cytosolic calcium ([Ca++ i]). The resistance and intolerance are reversed with verapamil, but recur after its discontinuation. This finding suggests that hyperparathyroid-induced [Ca ++ i] increase is responsible for the metabolic derangement. We retrospectively examined, over a 12-year period, the effects of factors that lower [Ca ++ i] on total serum cholesterol and triglycerides in 332 hemodialysis (HD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on morbidity and mortality outcomes related to atherosclerotic vascular disease. Patients with diabetes mellitus were excluded, because their dyslipidemia and vascular disease are mediated via a different mechanism. Four groups emerged: group I [high parathormone (PTH) in the absence of calcium channel blockers (CCBs), n = 107], representing the highest [Ca++ i]; group II (high PTH in the presence of CCBs, n = 76) and group III (lower PTH in the absence of CCBs, n = 66), representing intermediate [Ca ++ i]; and group IV (lower PTH in the presence of CCBs, n = 83) representing the lowest [Ca ++ i]. The theoretically lower [Ca ++ i] was achieved via CCB therapy or lower PTH, or both. The mean serum cholesterol in group I was 322 ± 24 mg/dL and the level of triglycerides was 398 ± 34 mg/dL. Group II had mean serum cholesterol of 196 ± 16 mg/dL and triglycerides of 157 ± 17 mg/dL. Group III had a mean serum cholesterol of 202 ± 19 mg/dL and triglycerides of 160 ± 15 mg/dL. Group IV had a mean serum cholesterol of 183 ± 9 mg/dL and triglycerides of 94 ± 6 mg/dL. The differences in cholesterol and triglyceride levels among four groups were significant (p < 0.001) by one-way analysis of variance (ANOVA). The incidence of cardiovascular morbidity and mortality events was 61% in group I, 24% in group II, 28% in group III, and 18% in group IV (χ 2 = 47.7, p < 0.001). We conclude that, in non diabetic HD patients, hyperparathyroidism, especially in the absence of CCBs, is associated with severe dyslipidemia and increased risk of cardiovascular morbidity and mortality. Dyslipidemia may be related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++ i]. Lowering [Ca++ i] by decreasing PTH or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term cardiovascular morbidity and mortality. Prospective randomized studies, with actual measurement of [Ca ++ i], are needed to verify the results of this study.