Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage-colony stimulating factor (GM-CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c-kit and IL-6 receptors, in long-term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes. Disorders studied include Fanconi's anaemia (FA, n = 16), idiopathic aplastic anaemia (AA, n = 11), Seckel's syndrome (n = 2), dyskeratosis congenita (n = 2), Shwachman-Diamond syndrome (n = 1), thrombocytopenia with absent radii syndrome (n = 1), acquired amegakaryocytosis (n = 1), paroxysmal nocturnal haemoglobinuria (n = 1) and acquired agranulocytosis (n = 1). IL-6 and GM-CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL-6 and GM-CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients' groups and controls in expression of the other cytokines or cytokine receptors studied.
 ...
PMID:The expression of cytokine and cytokine receptor genes in long-term bone marrow culture in congenital and acquired bone marrow hypoplasias. 751 72

Although nephrotoxicity of cidofovir and adefovir is well established, no renal side effects have been observed yet with tenofovir, which is the third member of this family. The authors report the case of a patient who had Fanconi syndrome, nephrogenic diabetes insipidus, and acute renal failure during treatment with tenofovir, a nucleotide reverse transcriptase inhibitor that recently has been approved by the Food and Drug Administration for treatment of patients infected with human immunodeficiency virus.
 ...
PMID:Fanconi syndrome and renal failure induced by tenofovir: a first case report. 1246 55

Long-term alterations to body metabolism have become apparent with the prolonged use of antiretroviral nucleoside analogue reverse transcriptase inhibitors (NRTIs). The NRTIs differ in the mechanisms, potency and probably also tissue specificity of mitochondrial toxicity. One group of NRTIs, the so-called "d-drugs" (zalcitabine> didanosine>stavudine) are relatively strong inhibitors of g-polymerase and thus cause a time- and dose-dependent decrease in the intracellular levels of mitochondrial DNA (mtDNA). The most important target organs of d-drugs are the liver, skeletal muscle, peripheral nerves and probably also the subcutaneous adipose tissue of lipoatrophic subjects. Hyperlactataemia may be observed. Zidovudine is an inhibitor of the mitochondrial adenine nucleotide translocator, binds to adenylate kinase and may also be converted into stavudine triphosphate in vivo. Persistent hyperlactataemia, mtDNA depletion and isolated cases of mitochondrial encephalomyopathies have been observed in babies under perinatal exposure with zidovudine. Nucleotide analogues such as tenofovir are avidly taken up into renal tubular epithelia. Isolated cases of renal failure and Fanconi syndrome require further investigation. Mitochondrial toxicity cannot yet be adequately monitored and predicted. Drugs with potential additive or synergistic toxicity, such as valproate, should be used with caution. Didanosine interacts with allopurinol, hydroxyurea and ribavirin. In established mitochondrial toxicity, cessation of the offending NRTI remains the most effective therapeutic intervention because vitamin cocktails and l-carnitine have, at best, only a marginal effect.
 ...
PMID:Update on mitochondrial toxicity: where are we now? 1283 62

Tenofovir is a nucleotide reverse transcriptase inhibitor for treatment of human immunodeficiency virus (HIV) infection. Several cases of renal failure associated with tenofovir therapy recently have been reported. A 54-year-old man with HIV experienced decreasing renal function and Fanconi's syndrome secondary to tenofovir therapy. His condition gradually improved after discontinuation of the drug. The available medical literature for reported cases of tenofovir-related nephrotoxicity indicates that this complication is apparently rare. However, our case report and literature review underscore the importance of monitoring renal function when treating patients with any nucleotide reverse transcriptase inhibitor.
 ...
PMID:Tenofovir-related nephrotoxicity: case report and review of the literature. 1504 Jun 57

We report a case of Fanconi syndrome associated with the use of tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor used in the treatment of HIV infection. A 56-year-old HIV-infected man was admitted to the hospital with a chief complaint of severe, progressive weakness. His HIV infection was well controlled by antiretroviral therapy; other medical problems included hepatitis C and chronic renal insufficiency. About 2 weeks before presentation, the patient had received an influenza vaccination, which was followed by a generalized viral syndrome of several days' duration. Next, weakness developed and culminated in an inability to walk; this prompted the patient's presentation at the hospital. Urine chemistry, electrolyte panel, and clinical presentation were consistent with Fanconi syndrome, a generalized proximal tubular dysfunction involving proteins, glucose, uric acid, and electrolytes. Along with our Case Report, we review 25 cases of Fanconi syndrome previously reported in the literature.
 ...
PMID:Fanconi syndrome associated with use of tenofovir in HIV-infected patients: a case report and review of the literature. 1604 78

Tenofovir (Viread) is a nucleotide reverse transcriptase inhibitor introduced into the United States in 2001. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleoside analogs. It is now increasingly recognized as a cause of acquired Fanconi's syndrome (FS) in human immunodeficient individuals. We describe a case of a patient with AIDS, who, after starting tenofovir therapy, developed myalgias, renal failure, and profound electrolyte abnormalities compatible with the classic features of FS. On discontinuation of tenofovir and replacement of electrolytes, the individual improved clinically with normalization of his renal failure and electrolyte abnormalities. With the success of tenofovir in the anti-HIV drug market, practitioners should remain alert to the possibility of the development of FS. Frequent urine, renal, and electrolyte parameters should be measured at regular intervals following initiation of tenofovir therapy.
 ...
PMID:Acquired Fanconi's syndrome associated with tenofovir therapy. 1702 23

Tenofovir, a new nucleotide reverse transcriptase inhibitor that has good antiviral activity against drug-resistant strains of HIV, is structurally similar to cidofovir and adefovir and seems to be less nephrotoxic. Nephrotoxicity of cidofovir and adefovir is well established and they have been associated with increase for acute renal insufficiency due to tubular toxicity, possibly induced via mitochondrial deplection. Tenofovir has little mithocondrial toxicity in in vitro assays and early clinical studies. However some cases of renal tubular dysfuntion and renal failure related to tenofovir treatment have been published recently. Increased plasma concentrations of didanosine were observed after the adition of tenofovir and protease inhibitors can interact with the renal transport of organic anions leading to proximal tubular intracellular accumulation of tenofovir, yield Fanconi syndrome-type tubulopathy. We present a case in wich acute renal failure and proximal tubular dysfunction developed after therapy with tenofovir in a patiente with HIV who had suffered from complications of didanosine treatment. Although nephrotoxicity certainly occurs much less frequently with tenofovir that it does with other nuclotide analogues, use of tenofovir by patients with underlying renal disfuntion, for longer durations and/or associated with didanosine or lopinavir-ritonavir, might be associated with renal toxicity. Patients receiving tenofovir must be monitored for sings of tubulopathy with simple tests such us glycosuria, phosphaturia, proteinuria, phosphoremia and renal function, as well as assessment for signs of mithocondrial toxicity when a nucleoside analogue is being administered, and therapy should be stopped to avoid the risk of definitive renal failure.
 ...
PMID:[Acute renal failure and proximal renal tubular dysfuntion in a patient with acquired immunodeficiency syndrome treated with tenofovir]. 1711 9

Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor with activity against both HIV and the hepatitis B virus. It has had minimal nephrotoxic effects in early clinical trials, but as clinical use has widened, case reports describing tenofovir-induced renal tubular damage, Fanconi's syndrome and diabetes insipidus have been described. The authors review the pharmacokinetics, mechanism of action and clinical uses of tenofovir disoproxil fumarate. The large clinical trials, as well as the case reports of tenofovir-induced kidney injury, are also reviewed. The potential mechanism of renal damage is discussed and recommendations for evaluation and treatment of tenofovir-induced kidney injury are given.
 ...
PMID:Tenofovir-induced kidney injury. 1736 61

Tenofovir disoproxil fumarate (TDF) is a commonly used HIV antiretroviral. A relatively uncommon adverse effect of this drug is Fanconi syndrome. What is known about this toxicity, especially in regards to concomitant medication use and outcomes, is limited to isolated case reports and small case series. Therefore, a retrospective review of the FDA Adverse Event Reporting System from 2001 through 2006 was conducted to examine demographics, concomitant medication use, outcomes, and temporal trends in reporting of Fanconi syndrome associated with TDF use. In this large case series of 164 subjects who met the case definition for Fanconi syndrome, the majority (83%) of the subjects received protease inhibitors (PI) with TDF; specifically, 74% of the total received a ritonavir-boosted PI. Didanosine was the most commonly (43%) prescribed nucleoside reverse transcriptase inhibitor (NRTI). The combination of didanosine with boosted PI was frequently observed (34%), and in particular, didanosine plus lopinavir/ritonavir was documented for 22%. Nearly half (46%) of the total were hospitalized. Fracture (2%) and requirement for dialysis (2%) were infrequent while Fanconi syndrome contributed to death in 2% of these subjects. Patients receiving ritonavir-boosted protease inhibitors or didanosine with tenofovir should be closely monitored for development of nephrotoxicity. Although reporting biases and the exclusion of reports with serious confounding conditions likely affected the estimation of outcomes in this case series, severe complications of tenofovir-associated Fanconi syndrome were uncommon.
 ...
PMID:Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. 1826 Aug

We report a case of the nucleoside reverse transcriptase inhibitors, stavudine and lamivudine inducing Fanconi syndrome in a patient. The presence of simultaneous lactic acidosis suggests mitochondrial toxicity within the proximal renal tubular cells as the likely pathogenesis. We recommend that both the above nucleosides be added to the list of antiretroviral drugs that can induce Fanconi syndrome and that patients on stavudine and lamivudine be monitored carefully for early signs of Fanconi syndrome.
 ...
PMID:Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy. 1858 Jun 19


1 2 Next >>