RESUMEN
Carbon-14 (14 C)-labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs) are required for phase 0/I to phase III mass balance and micro-dosing clinical trials. In some cases, this may involve the synthesis of 14 C-labelled peptides, and the analysis can be performed by accelerated mass spectrometry (AMS). The 14 C-peptide is typically prepared by the solid-phase peptide synthesis (SPPS) approach using custom-made glassware for the key coupling steps. Further modification of the purified 14 C-peptide can then be performed.
Asunto(s)
Radioisótopos de Carbono/química , Péptidos/química , Péptidos/síntesis química , Biotinilación , Técnicas de Química Sintética , Disulfuros/química , Marcaje Isotópico , Modelos Moleculares , Conformación ProteicaRESUMEN
IMPORTANCE: Although research on quality of life and dermatologic conditions is well represented in the literature, information on teledermatology's effect on quality of life is virtually absent. OBJECTIVE: To determine the effect of store and forward teledermatology on quality of life. DESIGN: Two-site, parallel-group, superiority randomized controlled trial. SETTING: Dermatology clinics and affiliated sites of primary care at 2 US Department of Veterans Affairs medical facilities. PARTICIPANTS: Patients being referred to a dermatology clinic were randomly assigned, stratified by site, to teledermatology or the conventional consultation process. Among the 392 patients who met the inclusion criteria and were randomized, 326 completed the allocated intervention and were included in the analysis. INTERVENTIONS: Store and forward teledermatology (digital images and a standardized history) or conventional text-based consultation processes were used to manage the dermatology consultations. Patients were followed up for 9 months. MAIN OUTCOME MEASURES: The primary end point was change in Skindex-16 scores, a skin-specific quality-of-life instrument, between baseline and 9 months. A secondary end point was change in Skindex-16 scores between baseline and 3 months. RESULTS: Patients in both randomization groups demonstrated a clinically significant improvement in Skindex-16 scores between baseline and 9 months with no significant difference by randomization group (P = .66, composite score). No significant difference in Skindex-16 scores by randomization group between baseline and 3 months was found (P = .39, composite score). CONCLUSIONS: Compared with the conventional consultation process, store and forward teledermatology did not result in a statistically significant difference in skin-related quality of life at 3 or 9 months after referral. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488293.
Asunto(s)
Calidad de Vida/psicología , Derivación y Consulta , Enfermedades de la Piel/psicología , Telemedicina , Anciano , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fotograbar , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/terapia , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Synthetic methodology has been established suitable for the preparation of combretastatin A-1 (CA1) and its corresponding phosphate prodrug salt (CA1P) in high specific activity radiolabeled form. Judicious selection of appropriate phenolic protecting groups to distinguish positions on the A-ring from the B-ring of the stilbenoid was paramount for the success of this project. Methylation of the C-4' phenolic moiety by removal of the tert-butyldimethylsilyl protecting group in the presence of methyl iodide was accomplished in excellent yield without significant Z to E isomerization. This step (carried out with (12)C-methyl iodide as proof of concept in this study) represents the process in which a (14)C radioisotope could be incorporated in an actual radiosynthesis. CA1 is a natural product isolated from the African bush willow tree (Combretum caffrum) that has important medicinal value due, in part, to its ability to inhibit tubulin assembly. As a prodrug, CA1P (OXi4503) is in human clinical trials as a vascular disrupting agent.
Asunto(s)
Difosfatos/síntesis química , Profármacos/síntesis química , Estilbenos/síntesis química , Animales , Combretum/química , Difosfatos/química , Humanos , Plantas Medicinales/química , Profármacos/química , Estereoisomerismo , Estilbenos/químicaRESUMEN
The new tripodal fac-functionalized building block, fac-ruthenium(II) tris-(5-hydroxymethyl-2,2'-bipyridine), has been synthesized as a single geometric isomer and used as starting point in the isolation of a kinetically inert heterometallic helicate by the stepwise inclusion of additional 2,2'-bipyridine chelating groups followed by a second metal ion. This stepwise synthetic methodology gives access to a new range of chiral nanoscale structures inaccessible by traditional self-assembly procedures.