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Intracavernous injection of 20 μg of prostaglandin E1 (PGE1) was carried out in 130 impotent patients. The erectile response was compared to the results of arteriological investigations including nocturnal penile tumescence and rigidity monitoring (NPTR) in 59 patients. The response of 60 patients positively categorized as exclusively psychogenic or vasculogenic was also compared to the pattern of the response to 80 mg of papaverine observed in a previous study by the same authors. The PGE1 test may not discriminate psychogenic from wholly organic patients since its results are not correlated to those of NPTR. It helps for the screening of vasculogenic impotence. Lack of response or a partly rigid response is consistent with this actiology but is not specific for it. A fully response makes it unlikely. Compared to papaverine, PGE1 induces less non rigid responses in psychogenic patients (15% versus 35% with papaverine) and more fully rigid responses in vasculogenic patients (respectively 12% and 5 %). Consequently the specificity of the PGE1 test is higher but its sensitivity lower than that of papaverine so that there is no clear difference in the effectiveness of the tests. Nevertheless the PGE1 test should be preferred, because it is safer. Prolonged erections occured in only 5 patients, and all ceased spontaneously. However 4 presented severely painful erections. 相似文献
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C Allard V Desgagné J Patenaude M Lacroix L Guillemette MC Battista M Doyon J Ménard JL Ardilouze P Perron L Bouchard MF Hivert 《Epigenetics》2015,10(4):342-351
Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10−11; N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. 相似文献
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Ramesh JL Kandimalla Willayat Yousuf Wani Binukumar BK Kiran Dip Gill 《Journal of biomedical science》2012,19(1):2
Background
One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage. 相似文献38.
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Jessica L Childs-Disney Meilan Wu Alexei Pushechnikov Olga Aminova Matthew D Disney 《ACS chemical biology》2007,2(11):745-754
Herein, we report the development of a microarray platform to select RNA motif-ligand interactions that allows simultaneous screening of both RNA and chemical space. We used this platform to identify the RNA internal loops that bind 6'- N-5-hexynoate kanamycin A ( 1). Selected internal loops that bind 1 were studied in detail and commonly display an adenine across from a cytosine independent of the size of the loop. Additional preferences are also observed. For 3 x 3 nucleotide loops, there is a preference for purines, and for 2 x 2 nucleotide loops there is a preference for pyrimidines neighbored by an adenine across from a cytosine. This technique has several advantageous features for selecting RNA motif-ligand interactions: (1) higher affinity RNA motif-ligand interactions are identified by harvesting bound RNAs from lower ligand loadings; (2) bound RNAs are harvested from the array via gel extraction, mitigating kinetic biases in selections; and (3) multiple selections are completed on a single array surface. To further demonstrate that multiple selections can be completed in parallel on the same array surface, we selected the RNA internal loops from a 4096-member RNA internal loop library that bound a four-member aminoglycoside library. These experiments probed 16,384 (4 aminoglycoside x 4096-member RNA library) interactions in a single experiment. These studies allow for parallel screening of both chemical and RNA space to improve our understanding of RNA-ligand interactions. This information may facilitate the rational and modular design of small molecules targeting RNA. 相似文献
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