Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tacrolimus ointment (Protopic) is a topically applied macrolide lactone immunomodulator effective in the treatment of atopic dermatitis. Its mechanism of action primarily involves calcineurin inhibition, which interrupts cytokine gene expression and leads to the downregulation of T-cell activity. Tacrolimus ointment (0.03% and 0.1% for adults and 0.03% for children) is an effective treatment for atopic dermatitis of the trunk and limbs, as well as sensitive skin areas such as the face. Its efficacy is similar to or greater than that of hydrocortisone acetate 1%, hydrocortisone butyrate 0.1% and betamethsone valerate 0.12% ointments and pimecrolimus 1% cream. Systemic absorption of tacrolimus from the ointment is minimal, and adverse events, which are mostly associated with the application site and include skin burning and pruritus, tend to resolve early in treatment. Unlike topical corticosteroids, tacrolimus ointment is not associated with skin atrophy, and it is a well tolerated treatment for adults or children with atopic dermatitis, particularly when long-term treatment is indicated or the face or skin-fold regions are involved.
...
PMID:Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions. 1581 96

Drugs used for immunosuppression have been implicated in causing numerous long-term side effects including nephrotoxicity, glucose intolerance, and hyperlipidemia. In this study, we reviewed our pediatric liver transplant recipients in terms of glomerular filtration rate (GFR) as well as fasting glucose and lipid profiles. To date, 79 pediatric liver transplantations have been performed at our center: 24 transplantations of at least 5 months to a maximum of 7.3 years posttransplant are reviewed herein. The mean time posttransplantation was 2.1 years. Nine boys and 15 girls showed a distribution of 19 mixed race, 3 black, and 2 white patients. The mean age at the time of transplantation was 6.6 years (0.8-13.3 years) with 8 cases under the age of 3 years. All recipients started with Cyclosporine Neoral (CSA) as first line, but, at the time of testing, immunosuppression included 5 children on CSA and 19 on Tacrolimus. Radionuclide 51 Cr-EDTA Glomerular Filtration Rates (GFR) showed a range from 21 to 220 mL/min/1.73 m2 (mean 96.1, median 89.8). Seven cases had a GFR less than 75 mL/min/1.73 m2. Twenty-one children were on antihypertensives agents: 15 children on 1 agent and 6 children on 2 agents. On full fasting lipid profiles, the total cholesterol ranged from 2 to 7.9 mmol/L (mean 4.4). Only 1 child is currently on statin therapy. Fasting glucose ranged from 3.2 to 5.9 mmol/L (mean 4.1) No difference was observed in glucose values between CsA and Tacrolimus. Thus, immunosuppressive therapies, such as the calcineurin inhibitors, are known to cause nephrotoxicity, which is of concern in pediatric liver transplant recipients. Almost all our patients currently require antihypertensive therapy. At present, the renal function is adequate in the majority of the group, but this study needs to be extended to other pediatric liver transplant recipients with particular emphasis on those who are more than 5 years posttransplantation.
...
PMID:Nephrotoxic effects of immunosuppressant therapy in pediatric liver transplant recipients. 1584 75

Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease.
...
PMID:Cardiovascular risk estimates and risk factors in renal transplant recipients. 1591 88

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus.
...
PMID:Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis. 1608 74

Cyclosporine (CsA) nephrotoxicity is enhanced by sirolimus (SRL). Tacrolimus is perceived to be less nephrotoxic than CsA, and therefore, CsA has been largely replaced by tacrolimus (TAC) when calcineurin inhibitors are used with SRL. We analyzed 44 915 adult renal transplants in the Scientific Renal Transplant Registry (SRTR) from 2000 to 2004. Three thousand five hundred twenty-four (7.8%) patients received a baseline immunosuppressive regimen of TAC/SRL, with an inferior overall (log-rank p<0.001) and death-censored graft survival (p<0.001) as compared to TAC/MMF (N=27 007). This effect was confirmed in multivariate Cox models; the adjusted hazard ratio (AHR) for overall graft loss with TAC/SRL was 1.47 (95% CI=1.32, 1.63) and for CsA/SRL 1.38 (95% CI=1.20, 1.59) relative to TAC/MMF. These effects were most apparent in high-risk transplants. Six-month acute rejection rates were low (11.5-12.6%) and not different between groups. In summary, national data indicate that TAC/SRL as compared to TAC/MMF is associated with significantly worse renal allograft survival in all subgroups of patients and, in particular, higher-risk transplants. These results have to be interpreted in the context of the inherent limitations of any retrospective database analysis and evaluated in context with data from prospective clinical trials.
...
PMID:Sirolimus in combination with tacrolimus is associated with worse renal allograft survival compared to mycophenolate mofetil combined with tacrolimus. 1609 9

Since their approval, topical calcineurin inhibitors have proven to be effective medications in the treatment of atopic eczema. On March 10, 2005, the Food and Drug Administration (FDA) followed the advice of the Pediatric Advisory Council and issued a "black box warning" for the use of Protopic (Tacrolimus) und Elidel (Pimecrolimus). This FDA alert has caused worldwide uncertainty among parents and patients. Several dermatological societies have issued critical position statements. This report reviews the existing information underlying the warning and places it into the context of current knowledge.
...
PMID:[Current aspects of the therapy with topical calcineurin inhibitors]. 1614 99

In the past 20 yr, a dramatic improvement has been achieved in the outcome of children with hepatoblastoma by combining cisplatin based chemotherapy and surgery. Treatment of patients in the USA is an exception to the rule that all patients should receive neoadjuvant chemotherapy. It is paramount that surgical resection be complete, both macro- and microscopically. Complete tumor resection can be achieved after chemotherapy with a partial hepatectomy when the intrahepatic extent is limited to 1-3 sectors. In multifocal (and solitary) hepatoblastomas invading all four liver sectors, and in centrally located tumors with close proximity to the major veins, the SIOPEL-1 study and an extensive review of the world experience have shown that primary transplantation provides high, long term, disease-free survival rate in the range of 80%. In contrast, the results of rescue transplants for incomplete tumor resection or disease recurrence after partial hepatectomy are disappointing (in the range of 30%). Hazardous attempts at partial hepatectomy in children with extensive hepatoblastoma should be discouraged. Guidelines are provided for early referral of children with extended hepatoblastoma to a transplant surgeon. There is a trend for a better patient survival after living related liver transplantation. Patients who will become candidates to liver transplantation should be treated with chemotherapy following the same protocols as for children undergoing a partial hepatectomy. There is a concern about cumulative nephrotoxicity of calcineurin inhibitors and chemotherapeutic drugs. Recent data suggest that these patients tolerate lower Tacrolimus trough blood levels than those transplanted for non-malignant conditions, without increasing the risk of acute rejection. Due to the rarity of the disease, these children should be treated in specialized centers.
...
PMID:Liver transplantation for hepatoblastoma: indications and contraindications in the modern era. 1617 10

Tacrolimus is an immunosuppressive drug that has been used widely in organ transplantation and topically for atopic dermatitis. Tacrolimus exerts its immunosuppressive effects by the inhibition of calcineurin, leading to interference with T-cell activation. As T-cell activation plays a major role in the pathogenesis of rheumatoid arthritis, there has been an interest in the use of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological properties of tacrolimus have the potential of suppressing the production of inflammatory cytokines, improvement of joint inflammation, improvement of bone and cartilage destruction, improvement of functional status and relief from arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics, clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid arthritis.
...
PMID:Tacrolimus in rheumatoid arthritis. 1637 Sep 26

Bullous pemphigoid (BP) is a cutaneous autoimmune disease predominantly affecting older patients which can cause death either due to severe clinical manifestations or due to the side effects of systemic immunosuppressive treatment. Topical treatment with corticosteroids is an established alternative to systemic treatment. However, prolonged application is accompanied by side effects such as skin atrophy. Recently, the immunomodulatory calcineurin antagonists tacrolimus and pimecrolimus have been introduced for topical treatment of skin diseases. Tacrolimus has been reported to be effective in several inflammatory skin disorders such as atopic dermatitis, psoriasis, lichen planus, lupus erythematosus and pyoderma gangraenosum. Efficacy has also been described in the topical treatment of BP in some cases. Here we present the case of a 89 year old patient with BP. He was treated with 0.1% tacrolimus ointment, which was able to control the disease. We briefly review the literature and discuss the potential role of tacrolimus as a novel option for the topical treatment of BP.
...
PMID:[Topical treatment of bullous pemphigoid with tacrolimus. Case report with brief literature review]. 1637 15

In the present study, we aimed to determine whether tacrolimus (FK506) and cyclosporine A act directly on human osteoclast precursors obtained from patients with rheumatoid arthritis (RA) and influence monocyte-osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL) in vitro, the stage at which differentiation was affected and the manner in which tacrolimus or cyclosporine A affected the osteoclast signaling pathway. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF). Tacrolimus or cyclosporine A was added to these cultures to determine the effect on the osteoclast differentiation. Osteoclast formation was determined by assessing the number of tartrate resistant acid phosphatase (TRAP) staining cells and measuring the extent of lacunar resorption. The expression of osteoclast transcription factors, such as TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells c1 (NFATc1), c-Fos, c-Jun, microphthalmia transcription factor (MITF) and PU.1 in mononuclear cells (MNCs) was assayed by quantitative reverse transcription-polymerase chain reaction. Addition of tacrolimus or cyclosporine A resulted in a decrease in the number of TRAP-positive multinucleated cells (TRAP+ MNCs) and a decrease in the extent of lacunar resorption pit formation as compared to the control cultures; thus, human monocyte-osteoclast differentiation was more effectively inhibited at the late stage and addition of tacrolimus or cyclosporine A resulted in a decrease in the mRNA expression of NFATc1, c-Jun, and MITF at the late stage. Our results suggest that tacrolimus or cyclosporine A acts directly on human osteoclast precursors in RA patients and exerts their immunosuppressive effects on human monocyte-osteoclast formation via targeting both the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or MITF.
...
PMID:Tacrolimus and cyclosporine A inhibit human osteoclast formation via targeting the calcineurin-dependent NFAT pathway and an activation pathway for c-Jun or MITF in rheumatoid arthritis. 1658 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---