Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity.</p> <p>Methods</p> <p>This cross-sectional study included 43 people with T2DM. Straight leg raise neurodynamic tests were performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip flexion range of motion (ROM), lower extremity muscle activity and symptom profile, intensity and location were measured at rest, first onset of symptoms (P1) and maximally tolerated symptoms (P2).</p> <p>Results</p> <p>The addition of ankle dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3° ± 6.5° at P1 and by 5.4° ± 4.9° at P2. Individuals in the T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM between PF/SLR and DF/SLR at P1 (1.4° ± 4.2°; paired t-test p = 0.34) or P2 (0.9° ± 2.5°; paired t-test p = 0.31). Movement induced muscle activity was absent during SLR with the exception of the tibialis anterior during DF/SLR testing. Increases in symptom intensity during SLR testing were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion induced more frequent posterior leg symptoms when taken to P2.</p> <p>Conclusions</p> <p>Consistent with previous recommendations in the literature, P1 is an appropriate test end point for SLR neurodynamic testing in people with T2DM. However, our findings suggest that people with T2DM and severe DSP have limited responses to SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch and the information gathered will be of limited clinical value.</p

Effect of N-1 and N-2 residues on peptide deamidation rate in solution and solid state

The deamidation kinetics of 7 model peptides (VYPNGA, VYGNGA, VFGNGA, VIGNGA, VGGNGA, VGPNGA, and VGYNGA) were studied at 70°C in pH 10 buffer solutions and at 70°C and 50% relative humidity in lyophilized solid formulations containing polyvinyl pyrrolidone (PVP). The disappearance of the model peptides from solution and solid-state formulations followed apparent first-order kinetics, proceeding to completion in solution. In the solid state, the reactions showed plateaus with ≈10% to 30% of the model peptides remaining; this was thought to be due to reversible complexation of the peptides and the PVP followed by slow dissociation of the complexes. The residues immediately N-terminal to asparagine (N-1, N-2) influenced the rate of deamidation significantly in the solid state but had minimal effect in solution. Increases in the volume and hydrophobicity of the N-1 and N-2 residues decreased the rate of deamidation in the solid state, but neither parameter alone adequately accounted for the observed effects. An empirical model using a linear combination of volume and hydrophobicity was developed; it showed that the influences of the volume and the hydrophobicity of the residues in the N-1 and N-2 positions are approximately equally important for the N-1 and N-2 residues