Combination of alfuzosin and tadalafil exerts in vitro an additive relaxant effect on human corpus cavernosum.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are a first-line treatment for erectile dysfunction (ED). Nevertheless, some patients do not respond to this treatment. Clinical data suggest that the addition of alpha1-adrenoceptor blocker, such as alfuzosin, commonly prescribed for lower urinary tract symptoms suggestive of benign prostatic hyperplasia, may be of benefit. Aim. Evaluation of the effect of alfuzosin, tadalafil or the combination of both on human corpus cavernosum. METHODS: Human cavernosal tissues were obtained from 10 patients undergoing penile surgery. Strips contractility was studied in organ baths. Concentration-response curves to tadalafil were generated on norepinephrine (NE, 1-10 microM)-precontracted strips in the presence of alfuzosin or vehicle. Frequency-response curves (FRC) to electrical field stimulation (EFS, 0-64 Hz, 3 ms, 10 seconds, 300 mA) were generated in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. EFS (20 Hz, 1 ms, 10 seconds, 300 mM)-induced nitrergic relaxation on NE-precontracted strips was studied in the presence of vehicle, alfuzosin, tadalafil, or both drugs combined. MAIN OUTCOME MEASURES: Functional measurement of cavernosal smooth muscle relaxation in the presence of tadalafil and alfuzosin. RESULTS: The relaxation induced by tadalafil (10(-10) to 10(-5) M) on precontracted strips was enhanced by alfuzosin at both 10(-8) and 10(-7) M. The combination of alfuzosin (3.10(-8) M) and tadalafil (10(-7) M) was more efficient to inhibit FRC-induced contractions than each compound alone. The combination of tadalafil (10(-6) M) and alfuzosin (10(-8) M) increased the relaxation induced by EFS and its effect was greater than tadalafil alone. In addition, the combination of tadalafil (10(-6) M) and alfuzosin (10(-7) M) prolonged EFS-induced relaxation to a greater extent than each compound alone. CONCLUSIONS: In vitro, the combination of alfuzosin and tadalafil is more efficient than each compound alone to relax adrenergic tone or to enhance nitrergic relaxation of the human corpus cavernosum. Such a combination deserves further investigation in placebo-controlled studies to evaluate its benefit in ED patients who are not sufficiently improved by PDE5 inhibitors.

Global mineralogical and aqueous mars history derived from OMEGA/Mars Express data.

Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activité (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history. Phyllosilicates formed by aqueous alteration very early in the planet's history (the "phyllocian" era) are found in the oldest terrains; sulfates were formed in a second era (the "theiikian" era) in an acidic environment. Beginning about 3.5 billion years ago, the last era (the "siderikian") is dominated by the formation of anhydrous ferric oxides in a slow superficial weathering, without liquid water playing a major role across the planet.

A 5-micron-bright spot on Titan: evidence for surface diversity.

Observations from the Cassini Visual and Infrared Mapping Spectrometer show an anomalously bright spot on Titan located at 80 degrees W and 20 degrees S. This area is bright in reflected light at all observed wavelengths, but is most noticeable at 5 microns. The spot is associated with a surface albedo feature identified in images taken by the Cassini Imaging Science Subsystem. We discuss various hypotheses about the source of the spot, reaching the conclusion that the spot is probably due to variation in surface composition, perhaps associated with recent geophysical phenomena.

Should a liver biopsy be done in patients with subclinical chronically elevated transaminases?

In 10% of the patients with chronic abnormal alanine aminotransferase (ALT) levels no cause is found. The prognosis of this liver disease, the increased risk of liver fibrosis regardless of the types of histological lesions and the need for a liver biopsy are unknown. Nearly 50% of these cases are explained by non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate, in patients with accidentally detected chronically elevated ALT levels, the prevalence of fibrosis and NASH, and the clinical and biological factors associated with each entity. Retrospectively, 67 patients (mean age, 46.6 +/- 12.1 years; 45 males) were included. All patients had a liver biopsy and were hepatitis B virus, hepatitis C virus, human immunodeficiency virus seronegative without alcohol, drug, autoimmune or genetically induced liver disease, with ALT > N (the upper limit of normal). NASH was evaluated according to necroinflammatory lesions and fibrosis. Fibrosis was evaluated according to the METAVIR score. Statistical analyses were performed using Student's t test, the Mann-Whitney rank-sum test and the chi-square test. Fibrosis scores were: F0, 37.3%; F1, 32.8%; F2, 26.9%; F3, 1.5%; and F4, 1.5%. NASH was absent in 59.7% and present in 40.3%. Significant differences were observed between F < 2 and F > or = 2 fibrosis patients for aspartate aminotransferase (AST) and ALT and between patients with NASH or without for body mass index. Overall, the risk of F > or = 2 fibrosis was increased in patients with AST > N, ALT > 2N or AST > N and ALT > 2N. The prevalence of F > or = 2 fibrosis and NASH in patients with unexplained chronic abnormal ALT are 30% and 40%, respectively. Since the risk of F > or = 2 fibrosis is significantly increased in patients with AST > N and/or ALT > 2N, liver biopsy should be performed only in patients with AST > N or ALT > 2N.

Perennial water ice identified in the south polar cap of Mars.

The inventory of water and carbon dioxide reservoirs on Mars are important clues for understanding the geological, climatic and potentially exobiological evolution of the planet. From the early mapping observation of the permanent ice caps on the martian poles, the northern cap was believed to be mainly composed of water ice, whereas the southern cap was thought to be constituted of carbon dioxide ice. However, recent missions (NASA missions Mars Global Surveyor and Odyssey) have revealed surface structures, altimetry profiles, underlying buried hydrogen, and temperatures of the south polar regions that are thermodynamically consistent with a mixture of surface water ice and carbon dioxide. Here we present the first direct identification and mapping of both carbon dioxide and water ice in the martian high southern latitudes, at a resolution of 2 km, during the local summer, when the extent of the polar ice is at its minimum. We observe that this south polar cap contains perennial water ice in extended areas: as a small admixture to carbon dioxide in the bright regions; associated with dust, without carbon dioxide, at the edges of this bright cap; and, unexpectedly, in large areas tens of kilometres away from the bright cap.

[Villo-glandular adenoma or polypoid dysplasia of esophagus: a case report]. / Polype tubulo-villeux ou dysplasie polypoïde de l'oesophage: une observation.

Gastrointestinal adenomas are neoplasms of glandular epithelium containing dysplasia of varying degrees. They are rare in esophagus. A case of villous tumor of the esophagus in a 71-year-old man is described. Histologically, this polypoid, villous lesion was developed on Barrett's esophagus and contained dysplastic epithelium and small adenocarcinomatous foci. This case illustrates that esophagus adenoma may be a premalignant lesion like other adenomas of the gastrointestinal tract. The term of polypoid dysplasia has therefore been recommended. This lesion, usually developed in gastric heterotopy or Barrett's esophagus, is often associated with high-grade dysplasia or carcinoma.