RESUMO
BACKGROUND: Atrial septal defects (ASDs) are one of the most common congenital cardiac abnormalities. Repair of these defects is a quite secure and routine operation. The most common complications were postoperative atrial arrhythmias, sinus arrhythmia, and atrioventricular (AV) blocks requiring pacemaker implantation, mediastinal bleeding, and transient ischemic attacks (TIAs) or strokes. Iatrogenic diversion of the inferior vena cava (IVC) to the left atrium (LA) during surgical closure of an ASD is a very rare complication. CASE REPORT: We reported a patient who had a history of cardiac surgery in another center at the age of seven and was introduced to our clinic with complaints of dyspnea and cyanosis of extremities on exertion. She underwent surgery in our center with diagnosis of iatrogenic diversion of IVC to LA. CONCLUSION: The most common mechanism suggested is a large eustachian valve being mistaken for the inferior rim of the ASD.
RESUMO
Ewing's sarcoma, characterized by pathognomonic t (11; 22) (q24; q12) and related chromosomal ETS family translocations, is a rare aggressive cancer of bone and soft tissue. Current protocols that include cytotoxic chemotherapeutic agents effectively treat localized disease; however, these aggressive therapies may result in treatment-related morbidities including second-site cancers in survivors. Moreover, the five-year survival rate in patients with relapsed, recurrent, or metastatic disease is less than 30%, despite intensive therapy with these cytotoxic agents. By using high-throughput phenotypic screening of small molecule libraries, we identified a previously uncharacterized compound (ML111) that inhibited in vitro proliferation of six established Ewing's sarcoma cell lines with nanomolar potency. Proteomic studies show that ML111 treatment induced prometaphase arrest followed by rapid caspase-dependent apoptotic cell death in Ewing's sarcoma cell lines. ML111, delivered via methoxypoly(ethylene glycol)-polycaprolactone copolymer nanoparticles, induced dose-dependent inhibition of Ewing's sarcoma tumor growth in a murine xenograft model and invoked prometaphase arrest in vivo, consistent with in vitro data. These results suggest that ML111 represents a promising new drug lead for further preclinical studies and is a potential clinical development for the treatment of Ewing's sarcoma.
RESUMO
Mandelalides A-D (1-4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E-L (5-12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells. Macrolides 1 and 2 inhibit mitochondrial function similar to oligomycin A and apoptolidin A, selective inhibitors of the mammalian ATP synthase (complex V). 1 inhibits ATP synthase activity from isolated mitochondria and triggers caspase-dependent apoptosis in HeLa cells, which are more sensitive to inhibition by 1 in the presence of the glycolysis inhibitor 2-deoxyglucose. Thus, mandelalide cytotoxicity depends on basal metabolic phenotype; cells with an oxidative phenotype are most likely to be inhibited by the mandelalides.
Assuntos
Apoptose/efeitos dos fármacos , Macrolídeos/química , Macrolídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Glicosilação , Células HEK293 , Células HeLa , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/metabolismoRESUMO
Recollection of the tunicate source of the mandelalides has provided new and known analogues that have facilitated expanded analyses of the disputed cancer cytotoxicity of mandelalide A following a number of recent reported total syntheses. Using newly characterized mandelalide E, reisolated natural mandelalides B and C, and synthetic mandelalide A, the cytotoxicity of the mandelalides is demonstrated to be strongly influenced by compound glycosylation and assay cell density. Glycosylated mandelalides reduced the viability of human cancer cells cultured at a high starting density with a rank order of potency A > B â« E, yet display dramatically reduced cytotoxic efficacy against low density cultures.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Macrolídeos/síntese química , Macrolídeos/farmacologia , Animais , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Glicosilação , Células HCT116 , Células HeLa , Humanos , Macrolídeos/química , Estrutura Molecular , Neoplasias , Estereoisomerismo , Urocordados/químicaRESUMO
BACKGROUND: Primary dysmenorrhea is a prevalent problem and its effects decrease the quality of life in many women across the world. The aim of this study was to research the effect of Teucrium polium compared to mefenamic acid on primary dysmenorrhea. MATERIALS AND METHODS: This triple-blind, randomized, clinical trial study was performed on 70 single female students between 20 and 30 years old educating in Shahid Beheshti University (Tehran, Iran) from October 2014 to February 2014.They were allocated randomly into two groups: In T. polium group (n = 35) who took 250 mg of T. polium powder q6h for the first 3 days of menstruation for two cycles. The second group (n = 35) received 250 mg mefenamic acid,. Dysmenorrhea severity was determined by visual analog scale (VAS). RESULTS: There were no differences between two groups for demographic or descriptive variables. Comprising the VAS showed that the participants in T. polium and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after the treatment (P < 0.05). No side effects were reported in the T. polium and Mefenamic Acid groups. CONCLUSION: T. polium was as effective as mefenamic acid in decreasing the pain severity in primary dysmenorrhea.