Highly potent neurotensin analog that causes hypothermia and antinociception.

The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo5 degrees C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic.

GRF-induced GH response in attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a type of disruptive behavior of unknown etiology with a prevalence of 2.5-5% in school-age children. The useful evaluation of the GRF-induced GH response as a marker in some mental disorders led us to study the response of GH to the exogenous administration of GRF (1-29) NH2 (150 micrograms, i.v.) in ADHD children (N = 12, age = 7.78 +/- 1.66 years) and healthy children (N = 6; age = 8.73 +/- 2.24 years) in order to evaluate the functioning of the somatotropinergic system (GRF-SS-GH-SM axis) and using this neuroendocrine test as a potential diagnostic marker and/or a therapeutic predictor in ADHD. While controls (CS) showed a maximum GH response to GRF 15 min after injection (37.15 +/- 29.56 ng/ml; basal GH = 5.49 +/- 4.71 ng/ml), ADHD children (basal GH = 2.28 +/- 1.66 ng/ml) exhibited a lower response with a plateau from 15 (21.32 +/- 10.00 ng/ml) to 60 min (26.48 +/- 23.72 ng/ml). Serum GH levels at 90 (17.23 +/- 14.45 vs. 5.99 +/- 2.82 ng/ml, p less than 0.05) and 120 min (11.89 +/- 8.63 vs. 4.12 +/- 1.66 ng/ml, p less than 0.05) were significantly higher in ADHD than in CS. According to the GRF-induced GH response elicited in ADHD, two different populations of patients can be distinguished; one group with high response of GH (AUC = 3372.21 +/- 1127.61 ng.min/ml) and another group with a hyporeactive GH (AUC = 1567.46 +/- 726.0 ng.min/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular matrix, biotensegrity and tumor microenvironment. An update and overview.

The extracellular matrix (ECM) constitutes a three-dimensional network that surrounds all cells, organs and tissues in the body. It forms a biophysical filter for protection, nutrition and cell innervation, as well as the medium for facilitating immune response, angiogenesis, fibrosis and tissue regeneration. It is the mechanism by which mechanical forces are transmitted to the basement membrane which, through the integrins, supports the tensegrity system and activates the epigenetic mechanisms of the cell. A review and update on current knowledge on this topic reveals how disturbance of the ECM leads to a loss of efficient filtering, nutrition, elimination, and cell denervation functions, in addition to loss of regeneration capacity and disorders in mechanotransduction. Furthermore, such disturbance results in a loss of substrate, and with it the ability to provide a proper immune response against tumor, toxic and infectious agents. Reciprocal communication between ECM stromal and parenchymatous cells directs gene expression. The oncogenic capacity of the stroma derives from the associated cells as well as from the tumor cells, the angiogenic microenvironment and from an alteration in tensegrity; all of which are dependent on the ECM. It has been shown that the malignant phenotype is reversible by correction of the altered cues of the ECM.