Total synthesis of rapamycin.

For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product

Frequency doubling technology, optical coherence technology and pattern electroretinogram in ocular hypertension

<p>Abstract</p> <p>Background</p> <p>To assess which of three methods, namely, optical coherence tomography (OCT), pattern electroretinogram (PERG) or frequency-doubling technology (FDT), is the most sensitive and specific for detecting early glaucomatous damage in ocular hypertension (OH).</p> <p>Methods</p> <p>Fifty-two patients with OH (24 men and 28 women, mean age of 56 ± 9.6 years) with an intraocular pressure (IOP) > 21 mmHg and fifty-two control patients (25 men and 27 women, mean age of 54.8 ± 10.4 years) with IOP < 21 mmHg, were assessed. All the patients had normal visual acuity, normal optic disk and normal perimetric indices.</p> <p>All subjects underwent OCT, FDT and PERG. Data were analyzed with unpaired <it>t</it>-tests, Chi-square test and Receiver Operating Characteristic (ROC) curve analyses.</p> <p>Results</p> <p>In patients with OH, OCT showed retinal nerve fiber layer (RNFL) thinner than in control group in the superior quadrant (130.16 ± 10.02 vs 135.18 ± 9.27 μm, respectively; p < 0.011) and inferior quadrant (120.14 ± 11.0 vs 132.68 ± 8.03 μm; p < 0.001). FDT showed a significantly higher pattern standard deviation (PSD) (3.46 ± 1.48 vs 1.89 ± 0.7 dB; p < 0.001). With respect to PERG, only the amplitude showed significant differences (p < 0.044) between the two groups. ROC curve analysis revealed a sensitivity and specificity of 92% and 86%, respectively, for FDT-PSD (with an area under the ROC curve of 0.940), whereas with OCT, a sensitivity of 82% and a specificity of 74% was recorded in the inferior RNFL quadrant (with an area under the ROC curve of 0.806) finally with PERG amplitude we found a sensitivity of 52% and specificity of 77% (with an area under the ROC curve of 0.595).</p> <p>Conclusions</p> <p>FDT is the most sensitive and specific method for detecting early glaucomatous damage in eyes with OH, and together with OCT, can be useful in identifying those patients who may develop glaucoma.</p> <p>Trial registration</p> <p>ISRCT number: ISRCTN70295497</p