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Most of the localization studies for PDE11 have been for PDE11A mRNA products. The data for protein are less certain as few highly specific antisera have been described. There also is likely to be substantial differences in expression between species. Nevertheless, it is clear that the PDE11A variants demonstrate differential tissue expression. In humans, PDE11A1 mRNA is most prominent in skeletal muscle and prostate (Fawcett et al., 2000; Yuasa et al., 2001a). PDE11A3 mRNA is found specifically in testis and PDE11A4 mRNA is highly expressed in prostate (Yuasa et al., 2000). PDE11A protein localization studies have been somewhat contradictory in their findings, probably because of differences in the specificity of the antibodies used. PDE11A1 protein was originally detected in prostate and skeletal muscle (Fawcett et al., 2000), although a later study did not detect PDE11A1 protein in any tissues (Loughney et al., 2005). In fact, only PDE11A4 protein has been verified and is found in prostate, pituitary, heart, and liver. Another study suggested that PDE11A is widely expressed, and immunohistochemistry using an antibody reported to recognize all PDE11A variants localized it to the epithelial, endothelial, and smooth muscle cells of many tissues, but at highest levels in the prostate, testis, kidney, adrenal gland, colon, and skin (D'Andrea et al., 2005). However, a separate study did not find any PDE11 protein expression in human testis (Loughney et al., 2005). As with many PDEs, it is still not clear if the same tissue, cellular, and subcellular localization is found among species. Future work will hopefully rectify the discrepancies regarding the tissue expression of PDE11A.
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Psychological factors are responsible for about 10%-20% of all cases of ED. It is often a secondary reaction to an underlying physical cause. In some cases, the psychological effects of ED may stem from childhood abuse or sexual trauma. However, the most common psychological causes of ED include:
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"Pulmonary arterial pressure -- when it is elevated -- is a poor prognostic sign and reducing its levels should be of help," he said. "However, more testing is needed to see if those changes in pulmonary arterial pressure are translated into better clinical outcomes and not into any unwanted side effects."
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In a second study based in Italy, researchers from four medical centers recruited 291 men who had both type-2 diabetes and silent CHD discovered by stress testing and confirmed by x-ray angiography. Of these subjects, 118 had erectile dysfunction at the beginning of the study. The study subjects were followed for four years with all instances of major adverse coronary events (MACE) documented. Results of the study indicated that those who had erectile dysfunction at the beginning of the study were twice as likely to experience a major adverse coronary event. This particular study also happened to conclude that taking a cholesterol-lowering statin drug reduced the risk for an adverse major coronary event by one third.
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They then reviewed studies on the safety of sildenafil (brand name Viagra) for patients with congestive heart failure. Because medications for erectile dysfunction also have an effect on blood vessels and circulation, they can be dangerous when mixed with heart medications, sometimes leading to fatal drops in blood pressure.
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A physical examination can give clues to systemic problems. For example, if the penis is not sensitive to touching, a problem in the nervous system may be the cause. Abnormal secondary sex characteristics, such as hair pattern or breast enlargement, can point to hormonal problems, which would mean that the endocrine system is involved. The examiner might discover a circulatory problem by observing decreased pulses in the wrist or ankles. And unusual characteristics of the penis itself could suggest the source of the problem—for example, a penis that bends or curves when erect could be the result of Peyronie's disease.
A small percentage of men undergo vascular reconstructive surgery to improve blood flow to the penis. Revascularization involves bypassing blocked veins or arteries by transferring a vein from the leg and attaching it so that it creates a path to the penis that bypasses the area of blockage. Young men with only local arterial blockage are the best candidates for this procedure. It may restore function in 50% to 75% of men.
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