Disease relevance of STN

• In the present study, we evaluated the clinical significance of this new carbohydrate antigen, STN, in patients with epithelial ovarian cancer [1].
• In 9.6% of patients with benign gynecologic diseases and 0% of pregnant women, there were elevated levels of STN antigen [1].
• Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD) [2].
• Globus pallidus (GPi) DBS in 1 case and subthalamic (STN) DBS in the second case produced full resolution of end of day dyskinesia [3].
• These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism [4].

Psychiatry related information on STN

• These findings suggest that Parkinson's disease patients with lower intelligence test scores and less education benefit more with regards to depressive symptomatology after STN-DBS than patients with higher scores and education [5].
• OBJECTIVE: To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women [6].
• OBJECTIVE: To examine the association of statin use with both prevalence and incidence of dementia and AD [7].
• The potential for statin treatment as an adjunct to dietary modification is also discussed [8].
• We believe this gap reflects the reduced patient compliance frequently observed in clinical practice settings, rather than any inherent difference in statin responsiveness of a practice versus a trial population [9].

High impact information on STN

• The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group [10].
• We have determined the predictive power of the same methodology for angiographically defined CAD using plasma samples from groups of male patients, classified by statin treatment, who had normal coronary arteries (NCAs) or CAD [11].
• Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection [12].
• Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes [12].
• Structural mechanism for statin inhibition of HMG-CoA reductase [13].

Chemical compound and disease context of STN

• However, the attenuation of the changes in [14C]-2DG uptake in the GPl and STN of "long-term" MPTP-treated marmosets suggest that the striato-GPl and GPl-STN outputs closely reflect motor function in this primate model of Parkinson's disease [14].
• Nine Parkinson's disease patients (age 61.7 +/- 11.1 years) were scanned ON and OFF STN stimulation and nine others (age 60.0 +/- 9.3 years) were scanned ON and OFF an individual titrated intravenous levodopa infusion [15].
• These new neurochemical data suggest that STN-HFS-induced forelimb dyskinesia is mediated by glutamate, probably via the direct activation of STN axons, shedding light on the mechanisms of STN-HFS in PD [16].
• CONCLUSIONS: Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels [17].
• Rosuvastatin is a new statin that has been shown to achieve significantly greater reductions in LDL cholesterol compared with pravastatin, simvastatin, and atorvastatin in primary hypercholesterolemia and enabled greater proportions of patients to achieve LDL cholesterol goals [18].

Biological context of STN

• Using the technique of flow cytometry to examine the large number of nonreplicating fibroblasts in confluent cultures, we have found that statin is mostly expressed in those cells showing the least amount of DNA content, whose growth is blocked at the G0/G1 stage of the cell cycle [19].
• Kinetic analysis shows that 50% of the cell population lose their statin expression at 12 h after replating, before the actual events of mitosis [19].
• Toxicology clusters of DataStar, DIALOG, DIMDI and STN are listed and compared [20].
• The metabolic effects of the two interventions differed in the STN and medial prefrontal cortex, with relative increases with stimulation in the former structure and decreases in the latter [15].
• CONTEXT: Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known [21].

Anatomical context of STN

• These results suggest that the expression of statin may be regulated by a fine mechanism controlling the transition from the nonreplicating to the replicating state, and that the protein is structurally associated with the nuclear envelope [19].
• Statin, a 57,000-D protein characteristically found in nonreplicating cells, was identified by a monoclonal antibody produced by hybridomas established from mice injected with extracts of in vitro aged human fibroblasts (Wang, E., 1985, J. Cell Biol., 100:545-551) [19].
• Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion [2].
• Also, STN stimulation raised the emotional activation of the anterior cingulate and lowered the activity of the putamen [22].
• Lesioned areas included n. ventralis anterior (VA), ventralis lateralis (VL), n. ventralis posterolateralis pars oralis (VPLo), pars caudalis (VPLc) n. subthalamus (STN) and n. centrum medianum (CM) [23].

Associations of STN with chemical compounds

• L-dopa moderately increased RCGU in the STN; this effect was reproduced by D1 and D2 agonists and was blocked completely only by combined D1 and D2 antagonist pretreatment [24].
• The anticonvulsant effects of the CH(2)Cl(2)/CH(3)OH extract were also investigated on seizures induced by pentylenetetrazol (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) and thiosemicarbazide (TSC 50 mg/kg) [25].
• Cholesterol lowering with statin drugs: evidence in women [26].
• Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more [27].
• Cerivastatin was the most commonly implicated statin [28].

Physical interactions of STN

• This mevastatin-mediated antagonism was completely abolished by geranylgeranylpyrophosphate, suggesting that geranylgeranyl modification is needed to activate the eNOS mRNA destabilizing factor--a mechanism responsible for statin-mediated eNOS upregulation [29].
• Targeting the statin-binding site within LFA-1 or regulating LFA-1 affinity by inhibiting prenylation of the small GTPases could prove useful to treat inflammatory, autoimmune diseases and possibly viral infections, including HIV-1 [30].
• Differences in statin structure and binding characteristics may partially contribute to differences in potency of HMG-CoA reductase inhibition and other pharmacologic properties [31].

Regulatory relationships of STN

• Addition of geranylgeranyl PPi reverses statin-induced loss of ERK1/2 phosphorylation and apoptosis [32].
• In freshly isolated RMEC, RT-PCR and hybridization using specific oligonucleotide probes to CIITA promoter sequences identify only the statin-sensitive gammaIFN-induced promoter IV of CIITA [33].
• Effects of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells [34].
• These experiments demonstrate for the first time that Id1 can be up-regulated and p53 down-regulated by a statin in HDMECs [35].
• We have previously shown that statin treatment down-regulated ABCA1 expression in human macrophages, probably by inhibiting synthesis of the LXR ligand 24(S),25-epoxycholesterol [36].

Other interactions of STN

• While CA 125 antigen levels were elevated in 74.6% and STN antigen levels were elevated in 50.0% of the same population, the use of both assays indicated the sensitivity of detection of 83.8% in the population studied [1].
• Statin-mediated KLF2 expression was followed by the up-regulation of several of its downstream transcriptional targets [37].
• Rosuvastatin, a relatively novel potent mevalonate pathway inhibitor that is not metabolized significantly by CYP3A4, is a more appropriate statin to combine with either erlotinib or gefitinib [38].
• The constitutive expression of statin, a nuclear protein associated with the nonproliferating state, was comparably expressed in normal and WS senescent cells [39].
• TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia [40].

Analytical, diagnostic and therapeutic context of STN

• Immunoblotting analysis confirms the disappearance of statin in cells that have reentered the cycling process [19].
• With the use of a radioimmunoassay developed to detect STN antigen in serum, elevated (greater than or equal to 32.6 U/mL) antigen levels were observed in 50.0% of patients with ovarian cancer [1].
• Clinical trials of gene therapy are currently underway using adeno-associated virus to deliver AADC to the striatum, the trophic factor nurturin to the striatum, and GAD to the STN [41].
• We did a quantitative meta-analysis to improve understanding of the variability and clinical significance of cognitive dysfunction after STN DBS [42].
• DESIGN, SETTING, AND PATIENTS: Retrospective cohort study including 34 501 enrollees in the New Jersey Medicaid and Pharmaceutical Assistance to the Aged and Disabled programs who were 65 years of age and older, initiated statin treatment between 1990 and 1998, and who were followed up until death, disenrollment, or December 31, 1999 [43].

References