Biomedical subjects
Publications and source records attributed to A Roland.
Combinatorial chemistry is playing an increasingly prominent role in the process of drug discovery. A nucleic acid-based (NAB) scaffold can be engineered to create functional group and topological diversity in a library. Described herein is the parallel solid-phase synthesis of combinatorial libraries of nucleoside phosphoramidates, and the first evaluation of antiviral activity against hepatitis B virus (HBV).
Copper is often used to oxidize low density lipoprotein (LDL) in experiments in vitro and is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper, although estimates of LDL copper binding vary widely. We have developed and validated an equilibrium dialysis assay in a MOPS-buffered system to measure copper binding to LDL and have found 38.6+/-0.7 (mean+/-SEM, n=25) copper binding sites on LDL. The binding was saturated at a copper concentration of 10 micromol/L at LDL concentrations of up to 1 mg protein/mL. Copper-binding capacity increased progressively and markedly when LDL was oxidized to increasing extents. Chemical modification of histidyl and lysyl residues on apolipoprotein B-100 reduced the number of binding sites by 56% and 23%, respectively. As an example of the potential of this method to assess the effects of antioxidants on copper binding to LDL, we have shown that the flavonoids myricetin, quercetin, and catechin (but not epicatechin, kaempferol, or morin), at concentrations equimolar to the copper present (10 micromol/L), significantly decreased copper binding to LDL by 82%, 56%, and 20%, respectively.
Combinatorial assembly of nucleotide libraries and their antiviral evaluation against HSV-1 are described.
Solution-phase parallel synthesis of nucleotide library 1 consisting of 150 members is reported.
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The hepatoprotective activity of the rhisome of Cochlospermum tinctorium was investigated using carbon tetrachloride toxicity on mouse and tert-butyl hydroperoxide in vitro induction of lipid peroxidation and hepatocyte lysis. Aqueous, hydro-ethanolic and ethanolic extracts showed significant dose-dependent hepatoprotective actions. The ethanolic extract showed a hepatoprotective activity at lower doses than silymarin. The ethanolic and hydro-ethanolic extracts exhibited remarkable effects against the induction of lipid peroxidation and hepatocyte lysis; the aqueous extract showed comparatively weaker effects. These differences were related to the chemical composition of the extracts. Among the identified constituents of the drug, phenolic and polyphenolic compounds (gallic and ellagic acids, ellagitannins, flavonoids), carotenoids, triterpenes could be related to the biological activity.
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The long hiatus between Freud's seminal paper on countertransference in 1910 and the contributions of the 1950s on totalistic countertransference is analyzed in terms of historical factors and others intrinsic to psychoanalysis. Induced reactions in the psychoanalyst as transference in actuality is differentiated from classical countertransference and the growing literature on totalistic countertransference, as well as from transferences involving the usual displacement and projective mechanisms. Several cases are discussed to indicate the wide range of psychopathology in which induced reactions occur and their value in reconstruction. The reasons for the confusing use of the concept, countertransference, for a variety of psychological processes in the analyst are cited, and a new model of five categories centering around modes of communication are posited: empathic transitory identifications, preconscious associations and imagery, induced reactions to transferences, induced reactions as transference in actuality, and classical countertransference. The relationship of induced reactions to classical countertransference is discussed, as well as implications of induced reactions as transference in actuality for internalization theory, and implicitly for the psychology of the self. Finally, some clinical issues in the use of induced reactions are eluciated.
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Two neonates and four adults with herpes simplex virus (HSV) encephalitis were treated with cytosine arabinoside (Ara-C). A low dose of 40 to 160 mg per m(2) per day was given for 4 to 6 days by continuous intravenous infusion and, except in two cases, by intrathecal administration. In one patient, idoxuridine (IUdR) at the dose of 1 g every 4 h was also administered after 4 days of Ara-C therapy. Both neonates and two of four adults survived. Their clinical improvement was closely related in time to the onset of therapy with Ara-C (cases 1, 2, 3) and with IUdR (case 4). In one adult who died on the 27th day of illness of a massive pulmonary embolus, postmortem examination of the brain did not disclose viral inclusions, and viral culture was negative. In the other patient who died, however, brain culture postmortem was still positive for HSV despite 4 days of Ara-C therapy. Ara-C, in addition to IUdR, may be effective in HSV encephalitis treatment, but double-blind, controlled studies appear to be necessary with these agents.