Summary The effect of the hemicholium-3 analog, DMAE, on endplate currents (EPC) was investigated in the transected cutaneous pectoris muscle of the frog using a conventional two-microelectrode voltage clamp. At a low concentration (5 M), DMAE produced a long-lasting decrease in the rate constant of decay () and an increase in the peak current amplitude (Ip). At higher concentrations (10–100 M), DMAE produced biphasic changes characterized by a transient, marked decrease of and increase of Ip followed by a long-lasting marked increase of and decrease of Ip. When DMAE was removed from the bath recovery from block was asymmetrical in that recovered more quickly than did Ip. Pretreatment with neostigmine or collagenase partially antagonized the initial effects without affecting the steady state effects of DMAE, indicating that the initial effects of DMAE may be, at least in part, due to inhibition of the enzyme acetylcholinesterase. The drug reverses the normal voltage dependence of without altering the single exponential nature of decay of the EPC. The inward EPC was more markedly blocked than outward EPC, resulting in a highly non-linear current-voltage relation with Ip decreasing with increasing hyperpolarization. This effect may indicate that DMAE causes a voltage-dependent block of closed acetylcholine-activated ion channels. 相似文献
Background: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation.
Methods: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined.Results: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells.
Conclusions: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop. 相似文献
To evaluate the natural course of end plate marrow (Modic) changes (MC) in the cervical spine on MRI scans of patients with neck pain. A few longitudinal studies have assessed the development of MC over time in the lumbar spine but only two recent studies evaluated MC in the cervical spine in asymptomatic volunteers and those with whiplash. Thus, this study now reports on the natural course of MC in the cervical spine in symptomatic patients.
Methods
From the cervical MRI scans of 426 neck pain patients (mean age 61.2 years), 64 patients had follow-up MRI studies. The prevalence and types of MC were retrospectively assessed on the follow-up scans and compared to the original MRI findings.
Results
With an average of 2.5 years between the two MRI scans, the prevalence of MC type 1 (MC1) noted at baseline (7.4 % or 19 motion segments) slightly increased (8.2 % or 21 segments) but the prevalence of MC2 (14.5 % or 37 segments) increased considerably (22.3 % or 57 segments). In addition, 14 new MC1 segments and 8 new MC2 segments were noted. Twelve segments with MC1 at baseline converted to MC2 at follow-up. No conversion from MC2 to MC1 or reverting to a normal image was observed.
Conclusions
MC in the cervical spine are a dynamic phenomenon similar to the lumbar spine. 相似文献
This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N=8/group) for 16 days. Following this intervention period, pre- and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant (P<0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential. 相似文献
Cadmium (0.125-1 mM) was found to inhibit the isometric response of the isolated rat hemidiaphragm during indirect stimulation, but not during direct stimulation. This effect of cadmium (1 mM) was completely reversed by ethyleneglycol bis-(aminoethyl)-N,N,N',N'-tetra-acetic acid (2 mM) or by L-cysteine (2 mM) but only partially by increased calcium. Cadmium (10 micronM) significantly reduced the quantal release of transmitter in the isolated phrenic diaphragm and a concentration of 0.1 mM frequently caused a complete failure of the endplate response after 30 min. The effect of cadmium on neuromuscular transmission could not be readily reversed by washing with cadmium-free solution. Miniature endplate potential frequency and amplitude were not significantly affected by cadmium (0.1 or 0.5 mM). The results suggest that the effect of cadmium on the isolated phrenic nerve-diaphragm is due largely to inhibition of calcium function at presynaptic nerve terminals. 相似文献