Identification of a Forskolin-Like Molecule in Human Renal Cysts

Renal cyst enlargement is increased by adenosine cAMP, which is produced within mural epithelial cells. In a search for modulators of cAMP synthesis cyst fluids from 18 patients with autosomal dominant or recessive polycystic kidney disease (PKD) were analyzed, and in 15 of them, a stable lipophilic molecule that increased cAMP levels, stimulated transepithelial chloride and fluid secretion, and promoted the proliferation of human cyst epithelial cells was characterized. With the use of HPLC-mass spectrometry, a bioactive lipid with the same mass spectral fingerprint, the same chromatographic retention time, and the same biologic properties as forskolin, a widely known, potent adenylyl cyclase agonist, has been isolated and identified within the cyst fluid. Forskolin is synthesized by the plant Coleus forskohlii, but its appearance or compounds like it have not been reported in animals. The origin of forskolin in patients with PKD was not revealed by this study. Synthesis by mural cyst epithelial cells or an exogenous source are the most likely possibilities. Forskolin is sold for weight management and as a cardiovascular tonic in health stores and through the Worldwide Web. It is concluded that forskolin may have a role in promoting the enlargement of cysts in autosomal dominant PKD and recommended that patients avoid oral and parenteral preparations that contain this compound

Restoring Rivers and Floodplains for Habitat and Flood Risk Reduction: Experiences in Multi-Benefit Floodplain Management From California and Germany

Conventional flood control has emphasized structural measures such as levees, reservoirs, and engineered channels—measures that typically simplify river channels and cut them off from their floodplain, both with adverse environmental consequences. Structural measures tend to be rigid and not easily adapted to increased flooding regimes resulting from environmental change. Such actions also limit the natural hydrologic benefits of floodplains such as storing floodwaters, improving water quality, providing habitat for invertebrates and fish during periods of inundation, and supporting a multitude of cultural services. As these benefits are more widely recognized, policies are being adopted to encourage projects that reduce flood risks and restore floodplain ecosystems, while acknowledging the social-ecological context. The number of such projects, however, remains small. We assessed four multi-benefit floodplain projects (two in California, United States, and two in Germany) and characterized their drivers, history, and measures implemented. In both United States cases, the dominant driver behind the project was flood risk reduction, and ecosystem restoration followed, in one case inadvertently, in the other as a requirement to receive a subsidy for a flood risk reduction project. One German case was motivated by ecosystem restoration, but it was more widely accepted because it also offered flood management benefits. The fourth case was conceived in terms of balanced goals of flood risk reduction, ecosystem restoration, and recreation. We conclude that projects that both reduce flood risk and restore ecosystems are clearly possible and often cost-effective, and that they could be more widely implemented. The principal barriers are often institutional and regulatory, rather than technical

A cohort study reporting normal oximetry values in healthy infants under 4 months of age using Masimo technology

Objective: To determine sleeping saturation indices in healthy infants using a modern pulse oximeter with motion artefact extraction technology. Design: Prospective cohort. Setting: Home. Subjects: Healthy term infants. Intervention: Nocturnal pulse oximetry at home at 1 month of age (Recording 1) and repeated at age 3-4 months (Recording 2). Parents documented sleep times. Visi-Download software (Stowood Scientific) analysed data with artefact and wake periods removed. Main outcome measures: Saturations (SAT50), desaturation index &gt;4% (DI4) and &gt;3% (DI3) from baseline/hour, delta index 12 s (DI12s), minimum saturations (SATmin), percentage time with saturations below 90% and 92%. Results: Forty-five babies were studied at 1 month and 38 babies at 3-4 months. Mean (CI) SAT50, DI4, DI3, DI12s and SATmin (CI) were 97.05 (96.59 to 97.52), 16.16 (13.72 to 18.59), 25.41 (22.00 to 28.82), 0.96 (0.88 to 1.04) and 80.4% (78.8% to 82.0%) at 1 month, respectively, and 97.65 (97.19 to 98.12), 8.12 (6.46 to 9.77), 13.92 (11.38 to 16.47), 0.72 (0.65 to 0.78) and 84.7% (83.3% to 86.1%) at 3-4 months. Median (CI) percentage times with saturations below 90% and 92% were 0.39 (0.26 to 0.55) and 0.82 (0.60 to 1.23), respectively, at 1 month and 0.11 (0.06 to 0.20) and 0.25 (0.17 to 0.44) at 3-4 months. For paired samples (n=32) DI4 (P=0.006), DI3 (P=0.03), DI12s (P=0.001), percentage time with saturations below 90% (P=0.001) and 92% (P=0.000) all fell significantly and SATmin (P=0.004) rose between the two recordings. Conclusion: Desaturation indices are substantially higher in young infants than older children where a DI4 over 4 is considered abnormal. These decrease by 3-4 months of age but still remain elevated compared with older children.</p