Conformational Change in the Mechanism of Inclusion of Ketoprofen in ß-Cyclodextrin: NMR Spectroscopy, Ab Initio Calculations, Molecular Dynamics Simulations, and Photoreactivity.

Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying several properties such as solubility, stability, bioavailability, and so on. The photoreactive behavior of the ß-CD/ketoprofen (KP) complex upon UV exposure showed a significant increase in photodecarboxylation, whereas the secondary degradation products by hydroxylation of the benzophenone moiety were inhibited. The results may account for an improvement of KP photophysical properties upon inclusion, thus better fostering its topical use. To correlate the structural details of the inclusion with these results, an NMR spectroscopic study of KP upon inclusion in ß-CD was performed. Effects of the magnetically anisotropic centers of KP, changing their orientations upon inclusion and giving chemical shift variations, were specifically correlated with the results of the molecular dynamic simulations and ab initio calculations. In the large variety of papers focusing on the structural analysis of ß-CD complexes, this work represents one of the few examples in which a detailed analysis of these simultaneous upfield-downfield NMR shifts of the same aromatic molecule upon inclusion is reported. Interestingly, the results demonstrate that the observed upfield and downfield shifts upon inclusion are not related to any direct magnetic role of ß-CD. The conformational change of KP upon the inclusion process consists of a slight reduction in the angle between the two phenyl rings and in a remarkable reduction in the mobility of the carboxyl group, the latter being one of the main contributions to the NMR resonance shifts. These structural details help in understanding the features of the inclusion complex and, eventually, the driving force for its formation.

Synchronous metastatic renal cell carcinoma to the genitourinary tract: two rare case reports and a review of the literature.

Synchronous metastasis of renal cell carcinoma (RCC) to the ureter or the bladder represents an extremely rare event. We report one case of synchronous metastasis of RCC to the ipsilateral ureter and one case of solitary synchronous metastasis of RCC to the urinary bladder. We review the literature and discuss possible mechanisms of dissemination. We discuss the surgical management of metastases from RCC as well as the surgical options in the treatment of these rare occurrences.

Does race affect postoperative outcomes in patients with low-risk prostate cancer who undergo radical prostatectomy?

OBJECTIVES: To assess the magnitude of racial disparities in prostate cancer outcomes following radical prostatectomy for low-risk prostate cancer. METHODS: We retrospectively reviewed our database of 2407 patients who under went radical prostatectomy and isolated 2 cohorts of patients with low-risk prostate cancer. Cohort 1 was defined using liberal criteria, and cohort 2 was isolated using more stringent criteria. We then studied pre- and postoperative parameters to discern any racial differences in these 2 groups. Statistical analyses, including log-rank, chi(2), and Fisher's exact analyses, were used to ascertain the significance of such differences. RESULTS: Preoperatively, no significant differences were found between the white and African-American patients with regard to age at diagnosis, mean prostate-specific antigen, median follow-up, or percentage of involved cores on prostate biopsy. African-American patients in cohort 1 had a greater mean body mass index than did white patients (26.9 vs 27.8, P = .026). The analysis of postoperative data demonstrated no significant difference between white and African-American patients in the risk of biochemical failure, extraprostatic extension, seminal vesicle involvement, positive surgical margins, tumor volume, or risk of disease upgrading. African-American patients in cohort 2 demonstrated greater all-cause mortality compared with their white counterparts (9.4% vs 3.1%, P = .027). CONCLUSIONS: In patients with low-risk prostate cancer treated with radical prostatectomy, there exist no significant differences in surrogate measures of disease control, risk of disease upgrading, estimated tumor volume, or recurrence-free survival between whites and African-Americans.