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.     

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.     

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.     

Ultrafast MR grid-tagging sequence for assessment of local mechanical properties of the lungs.

While MR imaging with tagged magnetization has shown great utility in the study of muscle mechanics, the evaluation of pulmonary mechanics has long been hindered by the technical difficulties in MR imaging of lung parenchyma. In this study, a fast MR grid-tagging technique is described for dynamic assessment of regional pulmonary deformation. The method is based on a fast FLASH sequence with short TR and short TE. Tagging was achieved by using double DANTE pulse train or inversion pulses. Our results show that this technique is able to detect changes of the tagging grid caused by physiological deformation of the lung. Quantitative analysis of the data shows that this method is capable of assessing local pulmonary mechanics. The application of this technique could improve our understanding of ventilatory control, and thus provide a unique metric for assessing pulmonary disorders. Magn Reson Med 45:24-28, 2001.     

Complement depletion suppresses Lewis rat experimental allergic neuritis

Lewis rats immunized with myelin and complete Freund's adjuvant were treated with cobra venom factor (CVF) which depletes the C3 component of complement. CVF given at day 9 delayed the onset of experimental allergic neuritis (EAN) by 2-3 days and when given at days 9 and 12 delayed the onset of EAN by 4-5 days. Lumbar nerve roots of CVF-treated rats had significantly less demyelination than those from control EAN rats.     

Re-treatment in endodontics

In order to achieve success in endodontics, major emphasis is placed on judicious instrumentation, microbial control, and complete obturation of the root canal system. During re-treatment of previously endodontically treated teeth, one may encounter a variety of different materials, which must be removed before these objectives can be achieved. The intent of this article is to present various methods that the practitioner may use in an attempt to safely remove these materials while adhering to sound endodontic principles. The article further emphasizes that removal of the previous filling material is only the initial step, which, when successfully accomplished, provides access to the root canal system so that therapy objectives can be carried out.     

Pedicled myocutaneous flap of latissimus dorsi muscle for reconstruction of anterior and middle skull defects: an alternative

Three cases are presented demonstrating the use of a pedicled myocutaneous flap of latissimus dorsi muscle to reconstruct large defects of the anterior and middle skull after ablative surgery for carcinoma. This method is proposed as an alternative to reconstruction with a free myocutaneous flap in selected patients.     

Epidural hematoma after outpatient epidural anesthesia.

IMPLICATIONS: Epidural hematoma is a rare complication of epidural anesthesia in healthy patients. Expedient diagnosis and treatment are essential to avoid permanent neurologic deficits. In an outpatient setting, patients should be instructed to communicate symptoms of severe back pain or weakness early.