Influence of selective immunosuppressive drug regimens on the healing of exposed dogs' dental pulp capped with a recent calcium silicate-based cement.

OBJECTIVES: In the clinical medicine, immunosuppressive drugs are used for an assortment of disorders, while their effect on the pulp healing is a controversial issue. This study evaluated the effect of different immunosuppressive drugs on the healing capacity of mechanically exposed dogs' dental pulps after direct pulp capping (DPC) with calcium silicate-based cement. MATERIALS AND METHODS: Twelve healthy male dogs were randomly allocated into four equal groups, 3 dogs each: group I allocated as a control group where no drugs were received; group П given prednisone (Pred); group III given a combination of Pred and cyclosporine A (CsA); and group IV given triple dose including Pred, CsA, and mycophenolate mofetil (MMF) for 45 days before the operative procedures and until the dogs were euthanized. In each dog, 16 class V cavities were prepared on the labial surfaces of anterior teeth. Following mechanical exposure, the pulps were capped with Biodentine, calcium silicate-based cement. The pulpal tissues response to Biodentine was assessed 65 days postoperatively. RESULTS: The pulp healing response was inferior in the Pred-CsA- and Pred-CsA-MMF-treated groups compared with the control and Pred-treated groups (P < 0.05). Non-significant difference was found between control and Pred-treated groups (P > 0.05). CONCLUSIONS: Within the limitation of this study, DPC with calcium silicate-based cement performed under strict aseptic condition for traumatically exposed dental pulp can be considered as a successful treatment option for those who receiving Pred immunosuppressive therapy. Meanwhile, DPC with those receiving a combination of Pred, CsA, and/or MMF immunosuppressive drug regimens demonstrated unfavorable results. CLINICAL RELEVANCE: Direct capping of mechanically exposed pulps with calcium silicate-based cement performed with special care for preventing infection considered a suitable strategic measure for preserving pulp vitality in patients receiving corticosteroid immunosuppressive drug.

Effect of 16% carbamide peroxide bleaching gel on enamel and dentin surface micromorphology and roughness of uremic patients: an atomic force microscopic study.

OBJECTIVES: To investigate the effect of 16% carbamide peroxide bleaching gel on surface micromorphology and roughness of enamel and root dentin of uremic patients receiving hemodialysis using atomic force microscopy (AFM). METHODS: A total of 20 sound molars were collected from healthy individuals (n=10) and uremic patients (n=10). The roots were separated from their crowns at the cemento-enamel junction. Dental slabs (3 mm x 2 mm x 2 mm) were obtained from the buccal surface for enamel slabs and the cervical third of the root surface for dentin slabs. Dental slabs were then flattened and serially polished up to #2500-grit roughness using silicon carbide abrasive papers. Half of the slabs obtained from healthy individuals and uremic patients were stored in artificial saliva and left without bleaching for control and comparison. The remaining half was subjected to a bleaching treatment using 16% carbamide peroxide gel (Polanight, SDI Limited) 8 h/day for 14 days and stored in artificial saliva until AFM analysis was performed. Statistical analysis of the roughness average (Ra) results was performed using one-way ANOVA and Bonferroni post hoc multiple comparisons test. RESULTS: The micromorphological observation of bleached, healthy enamel showed exaggerated prism irregularities more than non-bleached specimens, and this observation was less pronounced in bleached uremic enamel specimens with the lowest Ra. Bleached healthy dentin specimens showed protruded peritubular dentin and eroded intertubular dentin with the highest Ra compared to bleached uremic dentin. CONCLUSIONS: The negative effects of the bleaching gel on uremic tooth substrates are less dramatic and non-destructive compared to healthy substrates because uremia confers different micromorphological surface changes.

Influence of selective immunosuppressive drugs on the healing of exposed dogs' dental pulp capped with mineral trioxide aggregate.

INTRODUCTION: Immunosuppressive drugs are used in clinical medicine for a variety of disorders, but their effects on the reparative capacity of the dental pulp are unknown. This study evaluated the influence of selected immunosuppressive drugs on pulpal tissue healing after direct pulp capping of mechanically exposed dog's teeth with mineral trioxide aggregate (MTA). METHODS: Ten healthy male dogs were assigned into 5 experimental groups: a control group in which no drug was received and 4 experimental groups in which the immunosuppressive drugs prednisone, mycophenolate mofetil, sirolimus, and cyclosporine A were administered 45 days before the operative procedures and until the dogs were killed. Class V cavities were prepared on the buccal surfaces of 12 teeth in each dog. In each cavity, the pulp was exposed and capped with MTA. The pulpal tissue responses to capping material were assessed 65 days postoperatively. RESULTS: Compared with the control group, variable responses was recorded in the groups treated with mycophenolate mofetil, sirolimus, and cyclosporine A, which were characterized by moderate to severe inflammatory reactions, tissue necrosis, and total absence of hard tissue bridging. Pulpal tissue responses in the group treated with prednisone were characterized by inflammatory cell infiltration, limited tissue necrosis, as well as partial to complete hard tissue bridging. CONCLUSIONS: From these findings, it seemed evident that acceptable repair of the dentin-pulp complex, eg, wound healing with hard tissue formation after capping with MTA, is unlikely with mycophenolate mofetil, sirolimus, or cyclosporine A immunosuppressive drug therapy.

Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two-year results of a prospective randomized study.

BACKGROUND/AIMS: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial. METHODS: This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16-45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group). RESULTS: After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted. CONCLUSION: We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome.

Long-term results of two unconventional agents in steroid-dependent nephrotic children.

Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.

Co-administration of ketoconazole to tacrolimus-treated kidney transplant recipients: a prospective randomized study.

BACKGROUND: Since the introduction of calcineurin inhibitors, there has been a significant improvement in the results of solid organ transplantation, including graft and patient survival. However, high cost, chronic nephrotoxicity and other side effects stand as major challenges for long-term use of these drugs. The long-term safety and financial benefits of the combination ketoconazole-cyclosporine previously studied. However, data about the effect of the addition of ketoconazole addition to tacrolimus-treated patients are scarce. Therefore, this study was conducted to evaluate the safety and financial impact of that combination. METHODS: The subjects of this work included 70 live-donor stable kidney transplant recipients receiving tacrolimus. Their age ranged from 16 to 45 years. Among them, 54 were males and 16 were females. All of them were 6 months or more post-transplantation. Patients were randomly divided into two equal groups. Group I patients initially received ketoconazole 100 mg/day in addition to their usual treatment, while group II patients were considered a control. Patients were followed-up for 6 months. RESULTS: Concomitant ketoconazole-tacrolimus resulted in marked reduction of tacrolimus dose (by 58.7%) and cost (by 56.9%). It also resulted in significant improvement in graft function and fungal skin infection, in addition to a decrease of gastrointestinal episodes and hospitalization. CONCLUSION: We conclude that ketoconazole-tacrolimus combination in kidney transplant recipients is safe, has outstanding impact on treatment costs and improves patient and graft outcome.

Long-term outcome of live donor kidney transplantation for renal amyloidosis.

BACKGROUND: The short-term outcome of kidney transplantation in patients with amyloidosis has been reported. The aim of this study is to investigate long-term results in patients with renal amyloidosis. METHODS: We studied results of renal transplantation in 23 amyloidotic transplant recipients compared with those in a control group of 47 nonamyloidotic patients. Amyloidosis was secondary to familial Mediterranean fever (FMF) in 16 patients, whereas it was primary (idiopathic) in 7 transplant recipients. The 2 groups were homogeneous regarding age, sex, HLA matching, immunosuppression, and duration of transplantation. RESULTS: Five- and 10-year actuarial graft survival rates were similar in both groups (79.35% versus 84.04% and 65.92% versus 56.61%, respectively ). Five- and 10-year actuarial patient survival rates also were similar (80% versus 94% and 68% versus 87%, respectively). Moreover, 72.4% of controls experienced at least 1 rejection episode, whereas only 43.5% of amyloidotic transplant recipients experienced 1 or more such events (P = 0.02). Nonetheless, mean serum creatinine concentrations did not differ between the 2 groups during the observation period. Maintenance colchicine therapy prevented the recurrence of both FMF symptoms and amyloidosis. Recurrence was documented in only 1 amyloidotic transplant recipient (4.3%) 10 years posttransplantation. Significant gastrointestinal (GI) problems were more frequent in amyloidotic patients (65% versus 38%; P = 0.03). Amyloidotic patients with GI problems, except for 2 patients, were administered cyclosporine. Eleven of these patients had FMF, which appeared to reflect the effects of both cyclosporine and colchicine. Infections were similar in the groups; whereas amyloidotic patients had significantly lower blood pressures. CONCLUSION: In our experience, long-term (5 to 10 years) outcome of live related donor kidney transplantation in patients with amyloidosis is similar to that in the general transplant population.