Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presenilin-1 (PS1) is the gene responsible for the development of early-onset familial Alzheimer's disease. To probe the functions of PS1 on neuronal resistance to oxidative stress, we pharmacologically examined the death signals in PS1-deficient neurons induced by oxidative stress. Because the death of primarily cultured neurons lacking PS1 is caused by hydrogen peroxide in calcium-dependent manners in vitro [J Neurochem 78 (2001) 807], we tested the neuronal survival-promoting ability of inhibitors against calcium-dependent/cell death-related signaling molecules, such as ERKs, JNK, p38 MAP kinase, calcineurin, calpain, and nitric oxide synthase (NOS). All inhibitors tested failed to rescue the PS1-deficient neurons from the death with the exception of an inhibitor of NOS, N(G)-nitro-l-arginine methyl ester. Hemoglobin, a nitric oxide (NO) scavenger, also prevented the death of the mutant neurons. NADPH-diaphorase staining, which accounts for NOS activity, was enhanced in the mutant neurons. These results suggest that PS1 has a role for NOS activation in neurons and confers oxidative stress-resistance on neurons in calcium/NO-dependent manners.
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PMID:Presenilin-1-deficient neurons are nitric oxide-dependently killed by hydrogen peroxide in vitro. 1509 70

A highly selected subject group comprising pediatric recipients of liver (n = 36) and small intestine alone (n = 1) or multivisceral graft (n = 2) were converted to sirolimus maintenance therapy for tacrolimus-related side effects (n = 32) or by primary intent (n = 7). Indications were nephrotoxicity (n = 14), primary intent (n = 7), post-transplant lymphoproliferative disorder (n = 6), seizures (n = 4), recurrent acute rejection (n = 2), and cardiomyopathy (n = 1). Thirty subjects (78%) experienced successful conversion, with one subject requiring atorvastatin for hypercholesterolemia and hypertriglyceridemia. Nine subjects (22%) were converted back to tacrolimus for serious adverse events including acute rejection (n = 2), elevated liver function tests (n = 1), severe leucopenia (n = 1), non-compliance (n = 2), recurrent malignancy/death (n = 1), steatohepatitis (n = 1), and thrombocytopenic thrombotic purpura (n = 1). Among subjects with nephrotoxicity, significant benefit was seen only in those subjects with shorter time to rescue after transplantation (n = 8 of 14 subjects). Additional benefits included a significant decrease in mean serum creatinine from pretransplant values for the entire population, and elimination of antihypertensive treatment in all five subjects receiving it prior to conversion. Hemoglobin, serum cholesterol and triglycerides, white cell counts and platelets remained within normal limits for the duration of follow-up (36 month). Conversion from tacrolimus to sirolimus is successful in selected pediatric liver and intestine recipients. Chronic nephrotoxicity may be ameliorated by early conversion. Improvement in renal function and hypertension management, and absence of sirolimus-related adverse events argue for prospective evaluation of regimens in which mTOR inhibitors are used without calcineurin inhibitors in children.
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PMID:Replacing calcineurin inhibitors with mTOR inhibitors in children. 1591 Mar 98

Transplant teams face increasing challenges to manage diabetes following kidney transplantation. There is an increasing number of diabetics undergoing transplantation and there is an increased incidence of posttransplant diabetes mellitus (PTDM) due to a higher prevalence of obesity, increased use of steroids and calcineurin inhibitors, and the acceptance of older patients as potential candidates. The options for treating diabetes in the general population are expanding. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors is one of the new modalities of treatment. We report the cases of 8 patients who underwent kidney transplantation and were treated with the SGLT-2 inhibitor empagliflozin for their pre-existing diabetes or for the development of PTDM. They were followed for an average of 12 months. The average age of the patients was 42.5 years. All 8 patients were taking tacrolimus, mycophenolate, and prednisolone. Although creatinine increased slightly (from 88.5 mmol/L to 99.5 mmol/L) in the month after starting empagliflozin, it stabilized after that. Hemoglobin A1c decreased on average 0.85 g/dL. Urine protein decreased by 0.6 g per day and weight decreased on average 2.4 kg throughout the year. One patient discontinued the medication due to recurrent urinary tract infections.
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PMID:Use of Empagliflozin in Recipients of Kidney Transplant: A Report of 8 Cases. 3173 4