Digestive and cardiovascular responses to core and animal-reminder disgust.

The two-stage model of disgust differentiates between core and animal-reminder (AR) disgust [Rozin P., Fallon A., 1987. A perspective on disgust. Psychological Review 94, 23-41]. This study investigates whether core and A-R disgust elicit distinct physiological reaction patterns. Further, in line with the idea that A-R disgust is critically involved in blood phobia and may explain typical phenomenology of psychopathological symptoms (e.g., dizziness), we investigated whether physiological patterns (if present) would differ specifically for A-R disgust between high and low blood-fearful participants. Therefore, high (n=30) and low (n=30) blood-fearful individuals engaged in guided imagery of core disgust, A-R disgust, and neutral stimuli. Overall, both disgust scripts lead to increased activity in the digestive component of the autonomic nervous system (ANS). For cardiac components, sympathetic activity decreased, whereas no parasympathetic reactivity was observed compared to the neutral script. No differences were observed in physiological reactivity between the A-R and core disgust scripts. Meanwhile, in line with the idea that disgust is involved in blood phobia, subjective symptoms of vomit and dizziness did differentiate between high and low blood-fearful participants, as subjective symptoms were most pronounced in the high blood-fearful group. Contrary to our expectations, increases in subjective symptoms were apparent for both disgust types and not specifically for A-R disgust. So, physiological reactivity appeared relatively independent of type of disgust elicitor which, in turn, may reflect a general hard-wired protective mechanism to prevent contamination with pathogens.

2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia.

Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.

Design of immunoliposomes directed against human ovarian carcinoma.

Factors (protein/lipid ratio, pH of incubation medium, incubation time, anchor molecule density in the bilayer) affecting the covalent binding of anti-ovarian carcinoma Fab' to liposomes containing the anchor molecule MPB-PE (N-(4-(p-maleimidophenyl)butyryl)phosphatidylethanolamine) were explored. Standard experimental conditions were chosen and information on the relevant physicochemical parameters of the liposome dispersions was collected (mean particle diameter, size distribution, charge). The reproducibility of standard immunoliposomes prepared in subsequent batches in terms of Fab' binding, particle size and charge was established. In addition, preservation of immunoreactivity, no marker loss, and no aggregation/fusion was found for the standard immunoliposomes over a period of at least 3 weeks at 4 degrees C. In vitro up to 35,000 immunoliposomes were estimated to bind per human ovarian carcinoma cell. Internalization of the immunoliposomes could not be demonstrated. Electron micrographs showed binding of specific immunoliposomes to human ovarian carcinoma cells growing intraperitoneally in athymic nude mice.