[Analysis on vaccination willingness and related factors of influenza, pneumonia, and herpes zoster vaccine among people over 50 years old in Minhang district of Shanghai].

Objective: To determine the knowledge of influenza, pneumonia, herpes zoster and related vaccines, willingness to vaccinate under multiple payment scenarios, and corresponding risk factors among people over 50 years old in Minhang District of Shanghai. Methods: A total of 1 672 respondents aged 50-69 from 13 communities/towns in Minhang district of Shanghai were included in this study using a stratified random sampling strategy on December 2020. The knowledge of influenza, pneumonia, herpes zoster and vaccines was investigated using a questionnaire, and the differences in the willingness under multiple payment scenarios were determined using chi-square test. The consistency in the willingness under multiple payment scenarios was compared using Cohen's Kappa and the risk factors of the willingness was determined using ordinal logistic regression. Results: The average age of 1 672 respondents was (60.48±5.96) years old, including 777 (46.47%) males and 895 (53.53%) females. A total of 1 350 subjects (80.74%) had local household registration in Shanghai. The proportion of the willingness to vaccinate for themselves, spouses, and parents under any payment scenario was determined to be 80.6% (influenza vaccine), 81.5% (pneumonia vaccine), and 74.0% (herpes zoster vaccine). The willingness to vaccinate against influenza and pneumonia under multiple payment scenarios remained stable (Kappa value ≥0.6), while that against herpes zoster infection was inconsistent (Kappa value ≤0.35). Logistic regression analysis showed that respondents who had higher knowledge of influenza and influenza vaccine [OR (95%CI): 1.111 (1.054-1.170), 1.182 (1.126-1.240), respectively], aged 50-59 [1.305 (1.085-1.531)] and local household registration in Shanghai [1.372 (1.079-1.721)] had higher willingness to vaccinate against influenza, while males had lower willingness [0.733 (0.551-0.910)]. Respondents who had higher knowledge of pneumonia and pneumonia vaccine [OR (95%CI): 1.837 (1.152-2.517), 2.217 (1.541-2.893), respectively] had higher willingness to receive pneumonia vaccine. Respondents aged 50-59 [1.327 (1.059-1.537)] and with local household registration in Shanghai [2.497 (1.417-4.400)] were more likely to be vaccinated against herpes zoster, while those with middle school degree or below [0.664 (0.396-0.992)] and high school degree [0.559 (0.324-0.964)] were less likely to be vaccinated. Conclusion: Among people aged over 50 years old in Minhang district of Shanghai, the willingness to vaccinate for themselves, spouses, and parents against influenza, pneumonia and herpes zoster infection is quite different under multiple payment scenarios, especially for herpes zoster vaccine.

Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58.

BACKGROUND AND PURPOSE: Modulation of K(v)7/M channel function represents a relatively new strategy to treat neuronal excitability disorders such as epilepsy and neuropathic pain. We designed and synthesized a novel series of pyrazolo[1,5-a] pyrimidin-7(4H)-one compounds, which activate K(v)7 channels. Here, we characterized the effects of the lead compound, QO-58, on K(v)7 channels and investigated its mechanism of action. EXPERIMENTAL APPROACH: A perforated whole-cell patch technique was used to record K(v)7 currents expressed in mammalian cell lines and M-type currents from rat dorsal root ganglion neurons. The effects of QO-58 in a rat model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve, were also examined. KEY RESULTS: QO-58 increased the current amplitudes, shifted the voltage-dependent activation curve in a more negative direction and slowed the deactivation of K(v)7.2/K(v)7.3 currents. QO-58 activated K(v)7.1, K(v)7.2, K(v)7.4 and K(v)7.3/K(v)7.5 channels with a more selective effect on K(v)7.2 and K(v)7.4, but little effect on K(v)7.3. The mechanism of QO-58's activation of K(v)7 channels was clearly distinct from that used by retigabine. A chain of amino acids, Val(224)Val(225)Tyr(226), in K(v)7.2 was important for QO-58 activation of this channel. QO-58 enhanced native neuronal M currents, resulting in depression of evoked action potentials. QO-58 also elevated the pain threshold of neuropathic pain in the sciatic nerve CCI model. CONCLUSIONS AND IMPLICATIONS: The results indicate that QO-58 is a potent modulator of K(v)7 channels with a mechanism of action different from those of known K(v)7 openers. Hence, QO-58 shows potential as a treatment for diseases associated with neuronal hyperexcitability.

Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery: a whole-cell voltage- and current-clamp study.

BACKGROUND AND PURPOSE: Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined. EXPERIMENTAL APPROACH: Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments. KEY RESULTS: 18beta- & 18alpha-GA concentration-dependently increased membrane input resistance (R(in)) of in situ VSMCs, with a maximal input conductance (G(in)=1/R(in)) reduction of 92% & 77% and IC(50) of 2.0 & 4.4 microm, respectively. 18betaGA (30 microM) resulted in a R(in) of 2.2 GOmega and C(in) of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GOmega & 6.1 pF). The GAs (> or =30 microM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18betaGA also activated a non-selective cation conductance while 18alphaGA inactivated a voltage-independent K+-conductance. ACh induced an outward current in VSMCs in situ at -40 mV, with a positive slope I/V relation and a reversal potential near E(K). The ACh-induced current was attenuated by 18beta- & 18alphaGA with an IC(50) of 4.3 & 7.8 microM, respectively. CONCLUSIONS AND IMPLICATIONS: 18betaGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at > or =30 microM while causing a mild depolarization by a complex conductance alteration. 18betaGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18alphaGA at 30-100 microM failed to fully block the gap junctions while exerting side actions.

Inhibitory effect of baclofen on GABA-induced depolarization and GABA-activated current in primary sensory neurons.

It has been established that GABAA and GABAB receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole-cell patch-clamp recordings. Baclofen, a specific GABAB receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABAA receptor. In experiments with intracellular recording, GABA (0.3-1000 microM)- and muscimol (100-1000 microM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 microM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 microM) and two specific GABAA receptor agonists, muscimol (10 microM) and isoguvacine (50 microM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 microM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABAA receptor and the physiological significance implicated are discussed.

Modulatory effects of gonadorelin on GABA-induced depolarization and GABA-activated current in rat spinal ganglion neurons.

AIM: To explore the modulatory effects of gonadorelin on GABA-induced depolarization and GABA-activated current in membrane of rat primary sensory neurons. METHODS: Intracellular recordings and whole-cell patch clamp techniques were performed on neurons in rat spinal ganglia (SG) preparation and neurons freshly isolated from rat SG, respectively. Drugs were applied by superfusion and/or by bath application. RESULTS: In the majority of neurons GABA (10 mumol.L-1 -1 mmol.L-1) induced a depolarization, which was blocked by bicucullin (100 mumol.L-1). Pretreatment with gonadorelin (50 mumol.L-1) decreased the GABA-induced depolarization by 79 +/- 22% (n = 29), while gonadorelin elicited no effect or slight depolarization alone. In 6 of 11 cells, GABA-activated currents were also inhibited by pretreatment with gonadorelin (50 mumol.L-1), while in 5 of 11 cells, there was no change or a slight potentiation. CONCLUSION: Gonadorelin exerts an inhibitory effect on GABA-induced depolarization and GABA-activated current in the primary sensory neurons.

[Modulatory effects of substance P on the membrane responses mediated by GABAA and GABAB receptors in DRG neurons].

Intracellular recordings were performed on the neurons of young rat DRG to study the modulatory effects of SP on the responses mediated by GABAA and GABAB receptors. In the majority of the neurons (20/30) the GABA induced depolarization was suppressed to 50.8 +/- 20.2% by preapplication of SP (5 x 10(-6)-4 x 10(-5) mol/L), which applied alone had no effect or only caused a slight depolarization. In addition, SP could increase APD50 by 28.7 +/- 9.1% in many neurons (10/18), and the baclofen-induced shortening of 20.6 +/- 2.9% in APD50 could abolished (4/12) or even reverse to a lengthening of 19.3 +/- 8.9% in APD50 (8/12) by the preapplication of SP. Moreover, it was found that the activation of GABAB receptors could inhibit the succeeding response mediated by GABAA receptors. Since the soma of the DRG neuron is generally considered as an accessible model for the primary afferent terminals, the results suggest that SP which is released in the dorsal horn during nociceptive stimulation can antagonize the responses mediated by GABAA and GABAB receptors.