Neurotensin(8-13): comparison of novel analogs for stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 and receptor binding to human brain and intact N1E-115 cells

Neurotensin(8-13), the carboxyl-terminal portion of neurotensin, is 4-50 times more potent than native neurotensin in binding to intact neuroblastoma N1E-115 cells and human brain tissue and in stimulation of intracellular cyclic GMP production and inositol phospholipid hydrolysis in clone N1E-115 (Gilbert JA and Richelson E, Eur J Pharmacol 99: 245-246, 1984; Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986; Kanba KS et al., J Neurochem 46: 946-952, 1986; and Kanba KS and Richelson E, Biochem Pharmacol 36: 869-874, 1987). A series of novel analogs of neurotensin (8-13) was synthesized, and a structure-activity study was done comparing the abilities of these peptides to stimulate intracellular cyclic GMP production in intact neuroblastoma clone N1E-115 and to inhibit the binding of [3H]neurotensin to these cells and to membranal preparations from human brain. A direct correlation was found for each analog between its EC50 for biochemical activity and its KD for binding ability in studies with clone N1E-115. Furthermore, a strong correlation existed for each peptide between its KD for binding to neurotensin receptors on these cells and its KD for binding to neurotensin receptors in human brain tissue. In this study, the residues that were important to the biochemical and binding activities of neurotensin (8-13) proved to be identical to the amino acids that are necessary for the functional integrity of native neurotensin (Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986.     

Childhood scoliosis: MR imaging

The spinal cords of 28 scoliosis patients between the ages of 1 month and 17 years were examined with magnetic resonance (MR) imaging. Complete visualization was obtained in all cases. In 15 patients (53%) neuropathologic abnormalities demonstrated by MR imaging significantly affected their clinical course, including tethered cords (n = 7), syringomyelia (n = 5), Arnold-Chiari I malformation (n = 4), spinal cord tumors (n = 2), Arnold-Chiari II malformation (n = 3), and diastematomyelia (n = 1). The advantages of MR imaging in the evaluation of the scoliotic spine in children include a high sensitivity for the occult conditions associated with scoliosis, good anatomic demonstration of the cord, and absence of bone artifacts. MR imaging is recommended as a primary imaging modality in scoliosis, following conventional radiography.     

Paradoxical increase of positive answers to the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) questionnaire during a period of decreasing alcohol consumption: results from two population-based surveys in Ile-de-France, 1991 and 2005

AIMS: To describe trends of responses to the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) questionnaire during a period of declining alcohol consumption, in a country with no temperance history. DESIGN: Two random-sample surveys, conducted in 1991 and 2005, respectively. SETTING: The adult population of Ile-de-France. PARTICIPANTS: A total of 1183 subjects in 1991 and 5382 subjects in 2005. MEASUREMENTS: Responses to CAGE questions, obtained by face-to-face interviews in 1991 and by telephone in 2005. RESULTS: were standardized on the 2005 population structure. FINDINGS: The proportion of subjects giving at least two positive answers has increased by 4.2 times; the biggest increase was observed for the Guilt question (4.8 times) and the smallest for the Eye-opener question (2.6 times). Several increases were higher for women than for men: 12.9 times versus 3.3 times for two or more positive answers, 9.8 times versus 3.8 times for the Guilt question. Increases did not vary consistently by age. CONCLUSION: These paradoxical trends do not support the use of CAGE in general population surveys. They confirm previous reports suggesting that CAGE was sensitive to community temperance level. They might reflect the emergence of a temperance movement in France, with stronger impact among women. This movement might be responsible for the fall in alcohol consumption.     

Refusal Skill Ability: An Examination of Adolescent Perceptions of Effectiveness

This pilot study examined whether refusal assertion as defined by a proven drug prevention program was associated with adolescent perceptions of effectiveness by comparing two sets of coded responses to adolescent videotaped refusal role-plays (N = 63). The original set of codes was defined by programmatic standards of refusal assertion and the second by a group of high school interns. Consistency with programming criteria was found for interns’ ratings of several indicators of verbal and non-verbal assertiveness. However, a strategy previously defined by the program as effective was perceived as ineffective by adolescents while another deemed ineffective and problematic by intervention developers was viewed as effective. Interns endorsed presenting detailed and reasonable arguments as an effective refusal strategy while short, simple statements were deemed ineffective. This study suggests the importance of including adolescent perspectives in the design, delivery, and evaluation of drug prevention strategies.     

Qualification of Biomarkers for Drug Development in Organ Transplantation

The drug development process is dependent upon having established end points for measuring drug efficacy and adverse effects. New drug development in organ transplantation suffers from having end points which are either outdated or which do not serve the purpose of addressing the current critical drug therapy problems. Numerous biomarkers have been examined in organ transplantation, but almost all would be classified as exploratory for drug development purposes. Some of the possible pathways out of this dilemma include investigator- or consortium-initiated research that would qualify the biomarkers as either probable or known valid biomarkers, help in identification of new end points in transplantation and their associated biomarkers, co-development of a new biomarker and drug for transplantation and the use of new clinical trial design methods which facilitate enriched or stratified transplant patient populations. With new biomarkers and new study design methodologies for drug development, improvement in the drug development process for transplantation is a real possibility that the transplant clinical and research community can help to bring about.     

Cardiac magnetic resonance imaging assessment of regional and global left atrial function before and after catheter ablation for atrial fibrillation

Background  

Ablation of the left atrium and pulmonary veins antrum (PVAI) can be an effective treatment of atrial fibrillation (AF). However, there is discrepancy in the literature regarding the effect extensive ablation has on left atrial (LA) function. We sought to evaluate the effect that AF ablation procedures has on global and regional wall motion as assessed by cardiovascular magnetic resonance imaging (MRI).