26 research outputs found
Motion of Souls
Frustrated schoolteacher, Anto Hogan, a Dubliner living in San Diego is a peripatetic romantic, sometimes an angry husband, and at other times a son haunted by an inability to communicate with his father. Anto is also condemned to regret the break-up of his relationship with his first love, Una O’Brien. From Anto and Jane’s initial thrill and hopes for their prospective parenthood, the marriage is ripped apart by Jane’s miscarriage. Anto’s naïve friendship with Jane’s friend, Lucia threatens to end the marriage. He decides to take a trip home to Ireland to see his family and get some perspective on his marriage. Whilst at home, his father suffers an aneurysm and Anto’s trip becomes a nightmare, within which he deals with his fractured relationship with his brother, Donal. Anto flies back to America and when he gets to JFK finds out his father has taken a turn for the worse. Anto returns to Ireland for the funeral and tries to mend fences with his mother and brother. Anto discovers family secrets that undermine his whole being and he returns to Una O’Brien’s grave before going back to California to put the pieces of his life back together. Back in America, Anto understands that he is condemned to love and be loved only by the specter of Una O’Brien. Motion of Souls examines what it means to be obsessed by ghosts, how to gain a better understanding of one’s own psyche, and how to transcend a shattered marriage and the uncovered lies of childhood. Set in Ireland and California, and spanning thirty years of Anto Hogan’s life, Motion of Souls presents the reader with a flawed, yet somehow sympathetic main character, who discovers how to live on his own terms
Chemical Factors Involved in Accumulation and Retention of Fentanyl in Hair after External Exposure or In Vivo Deposition
This paper is available online at http://www.dmd.org ABSTRACT: The levels of fentanyl extractable from mouse hair after chronic systemic administration and the suitability of externally loaded hair samples for establishing control and comparison samples were determined. Additionally, the effects of chemical modification of specific polar functionalities within the hair protein matrix on the deposition and recovery of fentanyl in hair subjected to external loading were determined. BALB/c mice entering a second phase of synchronized hair growth were treated ip with fentanyl (0.02, 0.05, or 0.10 mg/kg) on Monday, Wednesday, and Friday for 3 weeks. At that time, fentanyl concentrations in hair, as determined by GC/ MS, were 0.025-0.050 ng/mg of hair. Hair samples exposed to fentanyl in phosphate buffer (ionized drug) showed no significant accumulation of drug into the hair, as determined by loss of fentanyl from the loading solution or by extraction of the hair. Hair samples exposed to nonionized fentanyl in methanolic solution (10, 50, and 100 ng/ml) showed significant accumulation of drug in the hair and significant removal of drug from the incubation solution. Fentanyl removal from solution plateaued after 24 hr, suggesting equilibration between fentanyl in solution and fentanyl in the hair. A mass balance between drug lost from the incubation solution and drug recovered from hair samples suggests that 94% of accumulated fentanyl is tightly bound to the hair matrix or resides in water-inaccessible compartments within the hair. These results suggest that fentanyl accumulation after in vivo administration differs, in the nature of storage, from fentanyl accumulation from external solutions and that external spiking of hair may not provide suitable control samples. Chemical modification of hair protein functionalities (reaction with diazomethane to esterify carboxylic acid groups or with acetic anhydride and pyridine to acetylate amine and hydroxyl functionalities) led to reproducible protein structure modification, as demonstrated by Fourier transform-IR and by pH titration. Hair from BALB/c mice was used. The accumulation of fentanyl was examined in hair samples exposed to fentanyl in methanol or methylene chloride solutions (10 ng/ml, 24 hr). Fentanyl was recovered from hair by 24-hr extraction in phosphate buffer, pH 6. Esterification of hair resulted in significantly less uptake of nonionized fentanyl from a methanolic solution and significantly lower recovery of drug from hair, relative to untreated hair, suggesting that carboxylic acid functionalities are necessary for the incorporation of drug. Acetylation of hair resulted in increased removal of fentanyl from methylene chloride solutions and increased recovery of fentanyl. This is consistent with the creation or expansion of a less polar compartment. Fentanyl uptake from a methanolic solution was also greater in acetylated hair. These results demonstrate that solution-accessible ionizable functionalities of hair play a significant role in the accumulation and retention of nonionized fentanyl from organic solutions
Titanocene Difluorides with Improved Cytotoxic Activity
Titanocene difluorides can be obtained by halide metathesis of the respective titanocene dichlorides with trimethyltin fluoride (Me3SnF), giving access to a new class of cytotoxic active substances. Furthermore, an improved method for the synthesis of diaryl-substituted titanocene dichlorides is presented
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Proliferative and anti-proliferative effects of titanium- and iron-based metallocene anti-cancer drugs
In previous work we have found that Cp2TiCl2 and its corresponding deriv. of tamoxifen, Titanocene tamoxifen, show an unexpected proliferative effect on hormone dependent breast cancer cells MCF-7. In order to check if this behavior is a general trend for titanocene derivs. we have tested two other titanocene derivs., Titanocene Y and Titanocene K, on this cell line. Interestingly, these two titanocene complexes behave in a totally different manner. Titanocene K is highly proliferative on MCF-7 cells even at low concns. (0.5 .mu.M), thus behave almost similarly to Cp2TiCl2. This proliferative effect is also obsd. in the presence of bovine serum albumin (BSA). In contrast, Titanocene Y alone has almost no effect on MCF-7 at a concn. of 10 .mu.M, but exhibits a significant dose dependent cytotoxic effect of up to 50% when incubated with BSA (20-50 .mu.g/mL). This confirms the crucial role played by the binding to serum proteins in the expression of the in vivo, cytotoxicity of the titanocene complexes. From the hydridolithiation reaction of 6-p-anisylfulvene with LiBEt3H followed by transmetallation with iron dichloride [bis-[(p-methoxy-benzyl)cyclopentadienyl]iron(II)] (Ferrocene Y) was synthesized. This complex, which was characterized by single crystal X-ray diffraction, contains the robust ferrocenyl unit instead of Ti assocd. with easily leaving groups such as chlorine and shows only a modest cytotoxicity against MCF-7 or MDA-MB-231 cells