Anti-ganglioside antibodies alter presynaptic release and calcium influx

Acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti-ganglioside mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody-mediated muscle weakness in AMAN.     

Direct activation of transient receptor potential V1 by nickel ions

TRPV1 is a member of the transient receptor potential (TRP) family of cation channels. It is expressed in sensory neurons of the dorsal root and trigeminal ganglia as well as in a wide range of non-neuronal tissues. The channel proteins serve as polymodal receptors for various potentially harmful stimuli to prevent tissue damage by mediating unpleasant or painful sensations. Using Ca imaging and voltage-clamp recordings, we found that low millimolar doses of Ni²⁺ (NiSO₄) are able to induce non-specific cation currents in a capsaicin-sensitive population of cultured mouse trigeminal ganglion neurons. In addition, we show that NiSO₄ elicits intracellular Ca²⁺ transients and membrane currents in HEK293 and CHO cells heterologously expressing rat TRPV1. The use of voltage ramps from ?100 to +100 mV revealed a strong outward rectification of these currents. Application of NiSO₄ to the cytoplasmic face of inside-out membrane patches did not induce any currents. However, delivering NiSO₄ to the extracellular face during outside-out recordings, we observed a significant increase in open probability paralleled by a decrease in channel conductance. When combined with other TRPV1 agonists, NiSO₄ produces a bimodal effect on TRPV1 activity, depending on the strength and concentration of the second stimulus. Outwardly directed currents induced by low doses of capsaicin and nearly neutral pH values (～pH?=?7.0–6.5) were augmented by low doses of NiSO₄. In contrast, responses to stronger stimuli were reduced by NiSO₄. Moreover, we were able to identify amino acids involved in the effect of NiSO₄ on TRPV1.     

Encouraging maternal health service utilization: an evaluation of the Bangladesh voucher program

With the ultimate goal of reducing maternal and neonatal mortality, many countries have recently adopted innovative financing mechanisms to encourage the use of professional maternal health services. The current study evaluates one such initiative - a pilot voucher program in Bangladesh. The program provides poor women with cash incentives and free access to antenatal, delivery, and postnatal care, as well as cash incentives for providers to offer these services. We conducted a household survey of 2208 women who delivered in the 6 months before the survey (conducted in 2009) in 16 intervention and 16 matched comparison sub-districts. Probit and linear regressions are used to analyze the effects of residing in voucher sub-districts on the use of professional maternal health services and associated out-of-pocket expenditures. Using information on birth history, we conducted sensitivity analyses employing difference-in-differences methods, comparing women's reported births before and after the program's initiation in the intervention and comparison sub-districts. We found that the program significantly increased the use of antenatal, delivery, and postnatal care with qualified providers. Compared to women in matched comparison sub-districts, women in intervention areas had a 46.4 percentage point higher probability of using a qualified provider and 13.6 percentage point higher probability of institutional delivery. They also paid approximately Taka 640 (US$ 9.43) less for maternal health services, equivalent to 64% of the sample's average monthly household expenditure per capita. No significant effect of vouchers was found on the rate of Cesarean section. Our findings therefore support voucher program expansion targeting the economically disadvantaged to improve the use of priority health services. The Bangladesh voucher program is a useful example for other developing countries interested in improving maternal health service utilization.     

Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acid type A receptors

The gamma-aminobutyric acid type A (GABAA) receptor is the predominant Cl- channel protein mediating inhibition in the olfactory bulb and elsewhere in the mammalian brain. The olfactory bulb is rich in neurons containing both GABA and dopamine. Dopamine D1 and D2 receptors are also highly expressed in this brain region with a distinct and complementary distribution pattern. This distribution suggests that dopamine may control the GABAergic inhibitory processing of odor signals, possibly via different signal-transduction mechanisms. We have observed that GABAA receptors in the rat olfactory bulb are differentially modulated by dopamine in a cell-specific manner. Dopamine reduced the currents through GABA-gated Cl- channels in the interneurons, presumably granule cells. This action was mediated via D1 receptors and involved phosphorylation of GABAA receptors by protein kinase A. Enhancement of GABA responses via activation of D2 dopamine receptors and phosphorylation of GABAA receptors by protein kinase C was observed in mitral/tufted cells. Decreasing or increasing the binding affinity for GABA appears to underlie the modulatory effects of dopamine via distinct receptor subtypes. This dual action of dopamine on inhibitory GABAA receptor function in the rat olfactory bulb could be instrumental in odor detection and discrimination, olfactory learning, and ultimately odotopic memory formation.     

Post-traumatic upper eyelid retraction

Three unusual cases of posttraumatic upper eyelid retraction are described. They were observed following orbital trauma without apparent involvement of the superior rectus muscle after latency periods ranging from several months to years. As other reasons for the lid retraction were ruled out the question arises as to whether peripheral neurogenic or muscular upper eyelid retraction must be assumed to be a consequence of trauma, although this has never been described before.