Opipramolium fumarate

In the crystal structure of the title salt {systematic name: 4-[3-(5H-dibenz[b,f]azepin-5-yl)prop­yl]-1-(2-hy­droxy­eth­yl)piperazin-1-ium (2Z)-3-carb­oxy­prop-2-enoate}, C23H30N3O+·C4H3O4 −, the piperazine group in the opipramol cation is protonated at only one of the N atoms. In the cation, the dihedral angle between the two benzene rings is 53.5 (6)°. An extensive array of inter­molecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds and weak inter­molecular N—H⋯O, C—H⋯O and C—H⋯π inter­actions dominate the crystal packing

Methyl 2-(4-hy­droxy­benzo­yl)benzoate

In the title compound, C15H12O4, the dihedral angle between the benzene rings is 64.0 (6)°. In the crystal, mol­ecules are linked by O—H⋯O hydrogen bonds, forming C(8) chains propagating in [10] and the packing is reinforced by weak C—H⋯O inter­actions

9-[3-(Dimethyl­amino)­prop­yl]-2-trifluoro­meth­yl-9H-thioxanthen-9-ol

In the title compound, C19H20F3NOS, the dihedral angle between the mean planes of the two benzene rings attached to the thioxanthene ring is 41.8 (7)°; the latter has a slightly distorted boat conformation. The F atoms are disordered over three sets of sites [occupancy ratio = 0.564 (10):0.287 (10):0.148 (5)] and the methyl groups are disordered over two sets of sites [occupancy ratio = 0.72 (4):0.28 (4)]. The crystal packing is stabilized by O—H⋯N and C—H⋯S hydrogen bonds and weak C—H⋯Cg inter­actions

2,2-Diphenyl-4-(piperidin-1-yl)butanamide

In the title compound, C21H26N2O, the dihedral angle between the mean planes of the two benzene rings is 81.1 (9)°. The piperidine ring is in a chair conformation. The crystal packing is stabilized by N—H⋯N and N—H⋯O hydrogen bonds and weak inter­molecular C—H⋯O inter­actions

2,2-Diphenyl­acetamide

In the title compound, C14H13NO, which has two mol­ecules in the asymmetric unit, the dihedral angles between the mean planes of the benzene rings are 84.6 (7) and 85.0 (6)°. N—H⋯O hydrogen bonds [forming R 2 2(8) ring motifs] and C—H⋯O hydrogen bonds dominate the crystal packing, forming zigzag chains parallel to the a axis. In addition, weak inter­molecular C—H⋯π inter­actions are observed

Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis

Neuroblastoma is a childhood tumor of the peripheral nervous system that remains largely uncurable by conventional methods. Mannitol induces apoptosis in neuroblastoma cell types and insulin-like growth factor I (IGF-I) protects these cells from hyperosmotic-induced apoptosis by affecting apoptosis-regulatory proteins. In the current study, we investigate factors that enable SH-SY5Y neuroblastoma cells to survive in the presence of an apoptotic stimulus. When SH-SY5Y cells are exposed to high mannitol concentrations, more than 60% of the cells are apoptotic within 48 h. Normal CS prevents hyperosmotic-induced apoptosis in a dose-dependent manner, with 0.6% CS protecting 50% of the cells, and 3% CS rescuing more than 70% of the cells from apoptosis. Serum also delays the commitment point for SH-SY5Y cells from 9 h to 35 h. A survey of several growth factors, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), fibroblast growth factor (FGF), and IGF-I reveals that IGF-I is a component of serum necessary for protection of neuroblastoma cells from death. Mitochondrial membrane depolarization occurs in greater than 40% of the cells after mannitol exposure and caspase-3 activation is increased in high mannitol conditions after 9 h. IGF-I blocks both the mitochondrial membrane depolarization and caspase-3 activation normally induced by hyperosmotic treatment in neuroblastoma cells. Our results suggest that (1) IGF-I is a key factor in serum necessary for protection from death and (2) IGF-I acts upstream from the mitochondria and the caspases to prevent apoptosis in human neuroblastoma. J. Cell. Physiol. 182:24–32, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34442/1/3_ftp.pd

Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and Caveolin-1

Abstract Background In the current study we investigated the role of caveolin-1 (cav-1) in pancreatic adenocarcinoma (PC) cell migration and invasion; initial steps in metastasis. Cav-1 is the major structural protein in caveolae; small Ω-shaped invaginations within the plasma membrane. Caveolae are involved in signal transduction, wherein cav-1 acts as a scaffolding protein to organize multiple molecular complexes regulating a variety of cellular events. Recent evidence suggests a role for cav-1 in promoting cancer cell migration, invasion and metastasis; however, the molecular mechanisms have not been described. The small monomeric GTPases are among several molecules which associate with cav-1. Classically, the Rho GTPases control actin cytoskeletal reorganization during cell migration and invasion. RhoC GTPase is overexpressed in aggressive cancers that metastasize and is the predominant GTPase in PC. Like several GTPases, RhoC contains a putative cav-1 binding motif. Results Analysis of 10 PC cell lines revealed high levels of cav-1 expression in lines derived from primary tumors and low expression in those derived from metastases. Comparison of the BxPC-3 (derived from a primary tumor) and HPAF-II (derived from a metastasis) demonstrates a reciprocal relationship between cav-1 expression and p42/p44 Erk activation with PC cell migration, invasion, RhoC GTPase and p38 MAPK activation. Furthermore, inhibition of RhoC or p38 activity in HPAF-II cells leads to partial restoration of cav-1 expression. Conclusion Cav-1 expression inhibits RhoC GTPase activation and subsequent activation of the p38 MAPK pathway in primary PC cells thus restricting migration and invasion. In contrast, loss of cav-1 expression leads to RhoC-mediated migration and invasion in metastatic PC cells.http://deepblue.lib.umich.edu/bitstream/2027.42/112733/1/12943_2005_Article_110.pd

Health and Economic Burden of Post-Partum Staphylococcus aureus Breast Abscess

Objectives: To determine the health and economic burdens of post-partum Staphylococcus aureus breast abscess. Study design We conducted a matched cohort study (N = 216) in a population of pregnant women (N = 32,770) who delivered at our center during the study period from 10/1/03–9/30/10. Data were extracted from hospital databases, or via chart review if unavailable electronically. We compared cases of S. aureus breast abscess to controls matched by delivery date to compare health services utilization and mean attributable medical costs in 2012 United States dollars using Medicare and hospital-based estimates. We also evaluated whether resource utilization and health care costs differed between cases with methicillin-resistant and -susceptible S. aureus isolates. Results: Fifty-four cases of culture-confirmed post-partum S. aureus breast abscess were identified. Breastfeeding cessation (41%), milk fistula (11.1%) and hospital readmission (50%) occurred frequently among case patients. Breast abscess case patients had high rates of health services utilization compared to controls, including high rates of imaging and drainage procedures. The mean attributable cost of post-partum S. aureus breast abscess ranged from $2,340–$4,012, depending on the methods and data sources used. Mean attributable costs were not significantly higher among methicillin-resistant vs. –susceptible S. aureus cases. Conclusions: Post-partum S. aureus breast abscess is associated with worse health and economic outcomes for women and their infants, including high rates of breastfeeding cessation. Future study is needed to determine the optimal treatment and prevention of these infections

Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner

BACKGROUND: Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [(15)O]H(2)O) and cerebral metabolic rate of glucose utilization (CMR(glu); based on [(18) F]-2-fluoro-2-deoxy-d-glucose ([(18) F]FDG)). By using kinetic modeling, quantitative CBF and CMR(glu) values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMR(glu) and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMR(glu) is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated. METHODS: Thirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [(15)O]H(2)O scan and a dynamic [(18) F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods. RESULTS: After quality control, 9 CMR(glu) and 11 CBF scans were available for analysis. Average GM CMR(glu) values were 0.33 ± 0.04 μmol/cm(3) per minute, and average CBF values were 0.43 ± 0.09 mL/cm(3) per minute. Good correlation between NLR and parametric CMR(glu) measurements was obtained as well as between NLR and parametric CBF values. For CMR(glu) Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates. CONCLUSION: Nonlinear regression analysis, allowing for the derivation of regional CBF and CMR(glu) values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMR(glu) measurements do not require invasive arterial sampling to define the input function. TRIAL REGISTRATION: ClinicalTrials.gov NCT0062608

2-(4-Fluoro­phen­yl)-1-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline monohydrate

In the title compound, C25H15FN4·H2O, the fused ring system is essentially planar [maximum deviation of 0.0822 (14) Å]. The imidazole ring makes dihedral angles of 76.83 (7) and 32.22 (7)° with the phenyl group attached to nitro­gen and the fluoro­benzene group to carbon, respectively. The dihedral angle between the two phenyl rings is 72.13 (7)°. Inter­molecular O—H⋯N, O—H⋯F, C—H⋯F, C—H⋯O and C—H⋯N hydrogen bonds are found in the crystal structure