How can push-off be preserved during use of an ankle foot orthosis in children with hemiplegia? A prospective controlled study.

Several studies indicated that walking with an ankle foot orthosis (AFO) impaired third rocker. The purpose of this study was to evaluate the effects of two types of orthoses, with similar goal settings, on gait, in a homogeneous group of children, using both barefoot and shoe walking as control conditions. Fifteen children with hemiplegia, aged between 4 and 10 years, received two types of individually tuned AFOs: common posterior leaf-spring (PLS) and Dual Carbon Fiber Spring AFO (CFO) (with carbon fibre at the dorsal part of the orthosis). Both orthoses were expected to prevent plantar flexion, thus improving first rocker, allowing dorsiflexion to improve second rocker, absorbing energy during second rocker, and returning it during the third rocker. The effect of the AFOs was studied using objective gait analysis, including 3D kinematics, and kinetics in four conditions: barefoot, shoes without AFO, and PLS and CFO combined with shoes. Several gait parameters significantly changed in shoe walking compared to barefoot walking (cadence, ankle ROM and velocity, knee shock absorption, and knee angle in swing). The CFO produced a significantly larger ankle ROM and ankle velocity during push-off, and an increased plantar flexion moment and power generation at pre-swing compared to the PLS (<0.01). The results of this study further support the findings of previous studies indicating that orthoses improve specific gait parameters compared to barefoot walking (velocity, step length, first and second ankle rocker, sagittal knee and hip ROM). However, compared to shoes, not all improvements were statistically significant.

The hydrophobic moment of the amphipathic helix of salmon calcitonin and biological potency.

The formation of an amphipathic helix in the central portion of calcitonin contributes to the potency of this hormone. We have synthesized a number of analogs of salmon calcitonin, containing deletions in the region of the peptide which is thought to form an amphipathic helix. There is no direct relationship between the hydrophobic moment of the helix and the biological activity of the peptide. For example, salmon des-Leu19-calcitonin and des-Ser13-calcitonin both have lower helical hydrophobic moments but have greater or equal biological potency compared with the native hormone. We suggest that other conformational features, such as flexibility and helix-forming potential, are also important in determining biological potency.

Conformational flexibility and biological activity of salmon calcitonin.

We have assessed the biological activity of salmon calcitonin I (sCT) using an in vivo biological assay of hypocalcemic activity in rats. The changes in biological activity observed are explained on the basis of changes in the conformational properties of the hormone analogues. Helical content in the presence and absence of lipids and detergents was assessed by using circular dichroism, and the section of the molecule that folds into a helix was predicted on the basis of the helix-coil transition theory of Mattice and co-workers. In the amino acid sequence of sCT, residue 8 is valine and residue 16 is leucine. The synthetic calcitonin derivatives [Gly8]sCT and [Ala16]sCT have higher biological activity than the native hormone although they have a lower helical content. The increased biological activity of these derivatives is ascribed to an increase in their conformational flexibility resulting from the substitution of amino acid residues with less bulky side chains and less tendency to form helical structures. The derivative [Met8]sCT has less substitution than sCT on the beta-carbon at position 8, but it has increased helix-forming potential in the region of residues 8-12. These two factors affect conformational flexibility in opposite ways, resulting in the biological activity of [Met8]sCT being slightly higher than that of sCT. However, increased conformational flexibility does not always increase biological activity. Substitution of the L-arginine at residue 24 for a D-arginine has little effect on the conformational properties or biological activity of sCT. However, [Gly8, D-Arg24]sCT is less active than sCT, [Gly8]sCT, or [D-Arg24]sCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Conformational requirements for activity of salmon calcitonin.

A series of deletion-substitution analogs of salmon calcitonin (SCT) have been prepared containing combinations of a glycine substitution in position 8 and deletions of serine-2 and tyrosine-22. Biological activity of the analogs with respect to native SCT were determined in the rat hypocalcemic assay and by studying stimulation of cAMP formation and competition for binding of 125I-labeled SCT in T47 D human breast cancer cells. It was found that each of the analogs retained full potency, irrespective of the means of assessment. It is suggested that conservation of the alpha-helical region of SCT, along with the overall tertiary structure, are more important for peptide potency than chain length per se.

Calcitonin-induced anorexia in rats: a structure-activity study by intraventricular injections.

The anorectic potency of salmon, porcine and human calcitonins (sCT, pCT and hCT, respectively) and two sCT-fragments were compared in rats. Intraventricular injections of sCT (0.062 and 0.031 nmole/animal) significantly reduced the normal feeding and body weight. The effect appeared to be dose-dependent, reversible and lasted longer than 6 hr. No anorexia ensued, however, on injections of mammalian hormones though tested in relatively high doses (pCT: up to 3.7 nmole, hCT: 3.7 nmole). The C-terminal fragments of sCT, sCT (10-32) and sCT (22-32) were also found to be devoid of anorectic activity; but when administered with sCT, the longer fragment (1.2 nmole) significantly decreased the effect of sCT and even the shorter one (18 nmole) tended to act as an antagonist. This property was not recorded with pCT and hCT in the doses examined. On the one hand, these results indicate a novel specificity of the anorectic receptor in rat brain; and on the other hand, they seem to strongly argue against the hypothesis that in mammals thyroidal calcitonin secreted postprandially might participate in the regulation of subsequent feeding, unless the presence of the sCT-like molecule can be detected in mammals. All the more because detection of such a molecule must await development of a specific assay, the antagonistic property of the sCT fragment found herein would have use for clarifying the physiological significance of the anorectic receptor which is possibly in the hypothalamus.

A novel effect of salmon calcitonin on in vitro Ca-uptake by rat brain hypothalamus: the regional and hormonal specificities.

It was found that salmon calcitonin-I (sCT) inhibited in vitro 45Ca2+-uptake by rat brain hypothalamus blocks in a dose-dependent manner. The minimum effective concentration was estimated to be 10 nM or less. The effect appeared to be specific to the hypothalamus and was not observed with the pons plus medulla oblongata or the cerebral cortex. Two C-terminal fragments of the fish hormone, sCT (10-32) and sCT (22-32), and porcine calcitonin failed to inhibit the ion-uptake though tested in concentrations abolishing 125I-sCT binding to these brain tissues, indicating that the whole structure of sCT is essential for the inhibitory effect but not for the binding. Another finding to be noted was a possible dependency of this effect on the integrity of the cell membrane structure. A crude synaptosomal fraction subsequently prepared from sCT-exposed hypothalamus blocks exhibited a decreased uptake of 45Ca2+, while a corresponding fraction from unexposed tissue did not respond to the hormone. These characteristics of this novel in vitro effect of sCT suggest its possible relevancy to the anorectic effect which also appears to be specific to the fish hormone.