Form III-like conformation and Form I-like packing in a chloroform channel solvate of the diuretic drug chlortalidone

Chlortalidone (CTD) is an antihypertensive drug for which only two solid state phases have been structurally elucidated thus far. Here, we have prepared a chloroform solvate thereof, namely, CTD Form IV, and its structure was compared to those of Form I and Form III. Its two conformers exhibit a dual structural feature in relation to the antecedent polymorphs. Both CTD molecules of Form IV adopt a Form III-like conformation, which is featured, if the conformation of CTD Form I is used as a reference, by a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted benzene and isoindolinyl rings. However, CTD Form IV assembles as in the Form I crystal packing despite the different stacking fashion of their centrosymmetric dimers. In contrast to Form I, there is no offset stacking in Form IV, which forces a bend of ca. 24 degrees between the planes passing through the isoindolinyl moieties of two [100]-stacked dimers. Chloroform molecules at a maximum stoichiometry of 0.25 mol per mol of the drug play a stabilizing role in the assembly of Form IV by filling the channels formed on the crystals.

The Azores Current System and the Canary Current from CTD and ADCP data

Se han eliminado páginas en blanco

El derecho a la libertad de empresa del artículo 38 de la constitución española : estudio sobre su interpretación y las dificultades para su desarrollo y aplicación

Programa de doctorado: Nuevas perspectivas del Derecho Privado

Modellazione CAD e studio di motorizzazione dell'aliante SG-38

Modellazione al CAD di un aliante sviluppato in Germania nei primi decenni dello scorso secolo e studio preliminare di fattibilità della motorizzazione del velivolo.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Formal speech stylistics and type A behavior in 38 subjects during nonstress interviews

Open-ended interviews of 90 min length of 38 patients were analyzed with respect to speech stylistics, shown by Schucker and Jacobs to differentiate individuals with type A personality features from those with type B. In our patients, Type A/B had been assessed by the Bortner Personality Inventory. The stylistics studied were: repeated words swallowed words, interruptions, simultaneous speech, silence latency (between question and answer) (SL), speed of speech, uneven speed of speech (USS), explosive words (PW), uneven speech volume (USV), and speech volume. Correlations between both raters for all speech categories were high. Positive correlations between extent of type A and SL (r = 0.33; p = 0.022), USS (r = 0.51; p = 0.002), PW (r = 0.46; p = 0.003) and USV (r = 0.39; p = 0.012) were found. Our results indicate that the speech in nonstress open-ended interviews of type A individuals tends to show a higher emotional tension (positive correlations for USS PW and USV) and is more controlled in conversation (positive correlation for SL).