Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Serum proteins of brown hare (Lepus europaeus Pallas, 1778) were studied by the use of 1D PAGE, 2D agarose-PAGE, immunoblotting, inhibitions of trypsin and chymotrypsin, and specific staining for esterase. 2. Some serum proteins were identified, and easily interpretable polymorphisms were found in transferrin alpha 1B glycoprotein, protease inhibitors ATC2, ATC3 and AT1, esterase ES1 and in an unidentified postalbumin PO. 3. On the basis of family studies the evidence was obtained that the variants observed in these polymorphic proteins are under genetic control by codominant alleles of autosomal loci.
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PMID:Intraspecific variation in serum proteins of brown hare (Lepus europaeus Pallas, 1778). 829 56

History of angioedema is a contraindication for ACE-inhibitors. Angioedema is caused by: 1. a decreased degradation of bradykinin, 2. a defect in C 1-esterase-inhibitor with the increased generation of bradykinin or 3. other trigger mechanisms as food, pollen and stress. AT1 receptor antagonists do not inhibit the degradation of bradykinin. Thus angioedema is no contraindication for AT1 receptor antagonists. In patients with an anamnestic angioedema or ACE-induced angioedema AT1 receptor antagonists can be given under close monitoring provided that there is strong indication for inhibition of the renin-angiotensin system.
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PMID:[Are AT1 receptor antagonists an alternative to ACE inhibitors in angioedema?]. 1806 33

The Renin-angiotensin system, besides blood pressure regulation, affects learning and memory as evidenced by improvement of cognition in hypertensive patients being treated with AT1 receptor blockers like candesartan. The present study examined the influence of candesartan on memory impairment induced by intracerebral streptozotocin (IC STZ 0.5 mg/kg) in mice. Candesartan (0.05 mg/kg and 0.1 mg/kg, i.p.) was given for 14 days following IC STZ administration. The dose of 0.1 mg/kg significantly improved latency period in passive avoidance test. Further, treatment with 0.1 mg/kg candesartan for 14 days significantly improved spatial memory in mice in water maze test also. In another group, after memory impairment in mice following IC STZ administration, memory improving effect of a 7 days treatment with 0.1 mg/kg candesartan lasted only for 3 subsequent days in water maze task. IC STZ increased oxidative stress but pretreatment with 0.1 mg/kg candesartan decreased oxidative stress as indicated by a decrease in MDA and increase in GSH. Further, candesartan decreased free radicals as evidenced by flow cytometry. IC STZ affected cholinergic system also by increasing acetylcholine esterase activity that was restored by pretreatment with 0.1 mg/kg candesartan. Locomotor activity and serum glucose level remained unaffected by candesartan treatment. These results suggest that AT1 receptors play a facilitatory role in STZ induced memory deficit and corroborate number of human studies that AT1 receptor blockers can be used therapeutically against cognitive decline in hypertensive patients.
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PMID:Candesartan improves memory decline in mice: involvement of AT1 receptors in memory deficit induced by intracerebral streptozotocin. 1910 28

Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include BRCA1, BRCA2, p53, PTEN, CHEK2 and ATM. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.
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PMID:Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: evidence that they exert tumoricidal effects via tumor tropism (review). 2273 97

Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application.
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PMID:Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats. 2438 59