RESUMEN
Background Severe traumatic brain injury (TBI) is one of the leading public health problems across the world. TBI is associated with high economic costs to the healthcare system specially in developing countries. Decompressive craniectomy is a procedure in which an area of the skull is removed to increase the volume of intracranial compartment. There are various techniques of decompressive craniectomy used that include subtemporal and circular decompression, and unilateral or bilateral frontotemporoparietal decompression. Objective The aim of this study was to compare the outcome of decompressive craniectomy for the management of severe TBI versus conservative management alone at the Department of Neurosurgery, Abbasi Shaheed Hospital, Karachi, Pakistan. Methods The study (randomized controlled trial) was conducted from February 1, 2014, till June 30, 2017. Results A total of 136 patients were included after following the inclusion criteria. They were randomly assigned to two groups, making it 68 patients in each study group. There were 89 males and 47 females. All the patients received standard care recommended by the Brain Trauma Foundation. The mortality rate observed at 6 months in decompressive craniectomy was 22.05%, while among conservative management group, it was 45.58%. Difference in mortality of both groups at 6 months was significant. Total 61.76% (42) of patients from decompressive craniectomy group had a favorable outcome (Glasgow outcome scale: 4-5) at 6 months. While among conservative management group, total 35.29% (24) had a favorable outcome (Glasgow outcome scale: 4-5). Difference in Glasgow outcome scale at 6 months of both groups was significant. Conclusion In conclusion, decompressive craniectomy is simple, safe, and better than conservative management alone.
RESUMEN
Phenylalanine-linked pyrrolo[1,2-a]benzimidazoles were successfully designed to target melanoma cells in vitro. Our design utilised three molecular targets: a phenylalanine pump, the reducing enzyme DT-diaphorase, and IMP dehydrogenase. We describe the synthesis of these compounds as well as the results of in vitro, in vivo, and QSAR studies.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Bencimidazoles/química , Bencimidazoles/uso terapéutico , IMP Deshidrogenasa/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Bencimidazoles/farmacología , Dominio Catalítico , Línea Celular Tumoral , Humanos , IMP Deshidrogenasa/química , IMP Deshidrogenasa/metabolismo , Neoplasias Pulmonares/patología , Melanoma/patología , Ratones , Ratones SCID , Modelos Moleculares , Fenilalanina/química , Fenilalanina/farmacología , Fenilalanina/uso terapéutico , Pirroles/química , Pirroles/farmacología , Pirroles/uso terapéutico , Relación Estructura-Actividad Cuantitativa , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A series of substituted quinoline-5,8-diones were synthesized and evaluated as inhibitors of the chaperone protein Hsp90 using two assays: competition for binding to C-terminal ATP-binding site and competition for binding to N-terminal ATP-binding site. In addition, the ability of the compounds to induce the heat shock response was determined using a reporter fibroblast cell line. Of all the compounds assayed, only 6-aziridinyl-2-biphenylquinoline-5,8-dione induced a heat shock response and did so without interacting at the ATP binding sites of Hsp90. COMPARE analysis was carried out on quinoline-5,8-diones active in the National Cancer Institute's 60-cell line screen with the goal of discovering quinoline-5,8-dione structures that interact with other cellular targets (molecular targets) important for cancer chemotherapy. COMPARE analysis led to the discovery of a combretastatin-like quinoline-5,8-dione structure that, in fact, inhibited angiogenesis.