ABSTRACT
The synthesis, characterization, and catalytic application of a new phosphine-free, well-defined, water-soluble, and air-stable Mn(II)-catalyst [Mn(L)(H2O)2Cl](Cl) ([1]Cl) featuring a 1,10-phenanthroline based tridentate pincer ligand, 2-(1H-pyrazol-1-yl)-1,10-phenanthroline (L), in dehydrogenative functionalization of alcohols to various N-heterocycles such as quinazolin-4(3H)-ones, quinolines, and quinoxalines are reported here. A wide array of multisubstituted quinazolin-4(3H)-ones were prepared in water under air following two pathways via the dehydrogenative coupling of alcohols with 2-aminobenzamides and 2-aminobenzonitriles, respectively. 2-Aminobenzyl alcohol and ketones bearing active methylene group were used as coupling partners for synthesizing quinoline derivatives, and various quinoxaline derivatives were prepared by coupling vicinal diols and 1,2-diamines. In all cases, the reaction proceeded smoothly using our Mn(II)-catalyst [1]Cl in water under air, affording the desired N-heterocycles in satisfactory yields starting from cheap and readily accessible precursors. Gram-scale synthesis of the compounds indicates the industrial relevance of our synthetic strategy. Control experiments were performed to understand and unveil the plausible reaction mechanism.
ABSTRACT
Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes.
Subject(s)
Cytokines/metabolism , Hemiplegia/physiopathology , Hypoxia/physiopathology , Intercellular Signaling Peptides and Proteins/metabolism , Osteoarthropathy, Primary Hypertrophic/physiopathology , Osteoarthropathy, Secondary Hypertrophic/physiopathology , Bradykinin/metabolism , Epidermal Growth Factor/metabolism , Ferritins/metabolism , Hemiplegia/complications , Hemiplegia/metabolism , Hepatocyte Growth Factor/metabolism , Human Growth Hormone/metabolism , Humans , Hypoxia/complications , Hypoxia/metabolism , Interleukin-6/metabolism , Osteoarthropathy, Primary Hypertrophic/metabolism , Osteoarthropathy, Secondary Hypertrophic/etiology , Osteoarthropathy, Secondary Hypertrophic/metabolism , Platelet-Derived Growth Factor/metabolism , Prostaglandins/metabolism , Serotonin/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , von Willebrand Factor/metabolismABSTRACT
A young woman presented with general malaise in relation to the metabolic condition ornithine transcarbamylase deficiency. Her ammonia level had risen to 229â µmol/L (normal range 0-59â µmol/L). She was treated using her emergency pack of intravenous medicines and made a complete response. We briefly discuss the need to make an urgent diagnosis, the 'mechanism' for checking serum ammonia levels and therapies.
Subject(s)
Ornithine Carbamoyltransferase Deficiency Disease/diagnosis , Urea Cycle Disorders, Inborn/diagnosis , Adult , Ammonia/blood , Arginine/therapeutic use , Female , Humans , Ornithine Carbamoyltransferase Deficiency Disease/drug therapy , Phenylbutyrates/therapeutic use , Sodium Benzoate/therapeutic use , Treatment Outcome , Urea Cycle Disorders, Inborn/drug therapyABSTRACT
PURPOSE: Triple negative breast cancer (TNBC) constitutes 10-15% of female breast cancers, and clinical guidelines recommend treatment with chemotherapy and surgery. We examined the recorded treatment and survival of women with TNBC in a population-based sample within the UK. METHODS: Cancer registration data for North East London women diagnosed between 2005 and 2007 were supplemented with pathology data on hormone receptor status to determine triple negative status. Receipt of surgery, chemotherapy, radiotherapy, hormone therapy, or surgery plus chemotherapy according to TNBC status was assessed using logistic regression, and adjusted for age, stage of disease and socioeconomic deprivation. Five-year survival according to TNBC status and treatment was estimated using the Kaplan-Meier method and Cox regression analysis examined adjusted all-cause mortality. RESULTS: Triple negative status could be determined for 1228 of 2394 women with breast cancer and 128 (10%) had TNBC. Compared to patients without TNBC, patients with TNBC were more likely to receive chemotherapy (fully adjusted odds ratio (OR) =4.21, 95% confidence interval (CI) 2.63-6.75) or surgery plus chemotherapy (fully adjusted OR = 2.52, 95% CI 1.61-3.93). Of patients with TNBC, those who received surgery plus chemotherapy had the greatest 5-year survival estimate (0.74, 95% CI 0.60-0.83). Overall, patients with TNBC had a higher risk of death (fully adjusted hazard ratio (HR) =1.69, 95% CI 1.24-2.30) compared to those without TNBC. CONCLUSIONS: This population-based study found that despite women with TNBC being more likely to receive chemotherapy, or surgery plus chemotherapy, they had a poorer overall survival than with those without TNBC.
