Enabling a person with multiple disabilities and minimal motor behaviour to control environmental stimulation with chin movements

Purpose: To assess whether a young man with multiple disabilities and minimal motor behaviour would learn to control environmental stimulation using chin movements and a mechanical microswitch. Method: The study was carried out according to an ABAB design in which A represented baseline and B intervention phases. The chin movements controlled the stimulation only during the intervention phases. A 2-month post-intervention check was conducted. Results: The man increased the frequency of his chin movements, thus increasing the level of environmental stimulation, during the intervention phases. This performance was maintained at the post-intervention check. Conclusion: The use of chin movements is a practical strategy for enabling individuals with minimal motor movements to control environmental stimulation. Future research should examine whether similar types of movements may enable some individuals to control voice-output communication devices.     

U22, a Protocol to Quantify Symptoms Associated with Supraventricular Tachycardia

Background: The main indication for ablation of supraventricular tachyarrhythmias (SVTA) is symptomatic relief. Specific paroxysmal symptoms cannot be quantified with general measures of quality of life, such as with the SF-36 questionnaire. U22 is a new protocol which measures the effects of arrhythmia on well-being, the intensity of discomfort during an episode, the type and temporal characteristics of dominant symptoms, and the duration and frequency of episodes. Discrete 0–10 scales are used. Unlike SF-36, U22 can be used in individual patients.
Methods: U22 and SF-36 protocols were used in the symptomatic evaluation of 88 patients (mean age = 49.6 ± 16.4 years; 43 men), who underwent catheter ablation of SVTA.
Results: The U22 scores (SD) for (a) well-being (10 being best), (b) effects of arrhythmia on well-being (10 being worst), and (c) discomfort during arrhythmia (10 being worst) were 5.6 (2.7), 7.5 (2.8), and 8.0 (2.4), respectively. For comparison, the physical and mental component summaries of SF-36 were 45.3 (11.0) and 45.2 (12.1), respectively, slightly lower than the expected normal of 50. The intensity of dominant symptom scored by U22 was 9.7 (1.2), 10 being worst. In 29% of patients ≥4 symptoms were equally dominant. Multiple dominant symptoms in U22 were associated with a low general well-being in SF-36.
Conclusion: We found U22 useful to quantify symptoms associated with SVTA.     

Ca2+/calcineurin regulation of cloned vascular KATP channels: crosstalk with the protein kinase A pathway

Background and purpose:

Vascular ATP-sensitive potassium (K_ATP) channels are activated by cyclic AMP elevating vasodilators through protein kinase A (PKA). Direct channel phosphorylation is a critical mechanism, though the phosphatase opposing these effects is unknown. Previously, we reported that calcineurin, a Ca²⁺-dependent phosphatase, inhibits K_ATP channels, though neither the site nor the calcineurin isoform involved is established. Given that the type-2 regulatory (RII) subunit of PKA is a substrate for calcineurin we considered whether calcineurin regulates channel activity through interacting with PKA.

Experimental approach:

Whole-cell recordings were made in HEK-293 cells stably expressing the vascular K_ATP channel (K_IR6.1/SUR2B). The effect of intracellular Ca²⁺ and modulators of the calcineurin and PKA pathway on glibenclamide-sensitive currents were examined.

Key results:

Constitutively active calcineurin Aα but not Aβ significantly attenuated K_ATP currents activated by low intracellular Ca²⁺, whereas calcineurin inhibitors had the opposite effect. PKA inhibitors reduced basal K_ATP currents and responses to calcineurin inhibitors, consistent with the notion that some calcineurin action involves inhibition of PKA. However, raising intracellular Ca²⁺ (equivalent to increasing calcineurin activity), almost completely inhibited K_ATP channel activation induced by the catalytic subunit of PKA, whose enzymatic activity is independent of the RII subunit. In vitro phosphorylation experiments showed calcineurin could directly dephosphorylate a site in Kir6.1 that was previously phosphorylated by PKA.

Conclusions and implications:

Calcineurin Aα regulates K_IR6.1/SUR2B by inhibiting PKA-dependent phosphorylation of the channel as well as PKA itself. Such a mechanism is likely to directly oppose the action of vasodilators on the K_ATP channel.British Journal of Pharmacology (2009) 157, 554–564; doi:10.1111/j.1476-5381.2009.00221.x; published online 7 May 2009This article is commented on by Tammaro, pp. 551–553 of this issue and is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

芹菜甲素保护脑细胞的作用

以每周定时im马桑内酯0.9～1.5mg/kg三个月为实验性癫痫慢性发作模型。ig芹菜甲素700mg/kg能明显降低大鼠癲痫发作的程度和次数,延长潜伏期。脑形态学结果表明,芹菜甲素对大脑顶叶皮层细胞、胶质细胞和小脑蚓部蒲肯野细胞有一定的保护作用。同时观察的安定1.5～5mg/kg则无此作用。     

EGF促进RPE细胞β2肾上腺能受体诱导的cAMP形成：受体间交互作用分析

研究证实表皮生长因子(EGF)不影响培养人眼视网膜色常上皮(RPE)细胞cAMP的基础水平，但促进异丙肾上腺索激活β₂受体后诱导cAMP水平升高的效应，井呈量效信赖关系。EGF对腺嘌呤核苷A₂受体激动剂NECA诱导cAMP水子升高的效应没有明显影响．细胞增殖分析表明，EGF刺激人眼RPE细胞增殖，而DibutyrylcAMP和异丙肾上腺素抑制RGF刺激增殖的效应。结果提示，在人眼RPE细胞EGF和β₂受体之间存在受体间交互作用． （中华眼底病杂志，1995，11：25-27）     

The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is effective in treating intestinal adenomas in humans with Familial Adenomatous Polyposis (FAP) and in preventing intestinal tumors in the C57Bl/6J- Min+ (Min) mouse, an animal model of FAP. Sulindac is a prodrug metabolized by the liver and intestinal flora to a sulfone, which has no anti-inflammatory activity, and a sulfide, which is the active anti- inflammatory metabolite. In this study, we determined which of these metabolites is responsible for the anti-tumor effect of sulindac in Min mice. Min mice were treated with either sulindac sulfone or sulindac sulfide (0.5 +/- 0.1 mg/day). Min mice and homozygous C57Bl/6J-(+/+) normal litter-mates lacking the Apc mutation (+/+) were used as controls. At 110 days of age, all mice were euthanized and their intestinal tracts examined. Control Min mice had 33.2 +/- 6.6 tumors per mouse compared to 0.6 +/- 0.3 tumors for sulindac sulfide-treated Min mice (P < 0.001) and 21.9 +/- 4.5 tumors per mouse for sulindac sulfone-treated Min mice (P > 0.05). Decreased enterocyte apoptosis was observed in Min control mice and Min mice treated with sulindac sulfone. Sulindac sulfide restored to normal the level of apoptosis in the mucosa of Min animals and decreased levels of PGE2 in the small intestine of treated Min animals by 59% (P < 0.001). These data suggest that the anti-tumor effect of sulindac in Apc-deficient animals is mediated by the sulfide metabolite and correlates with suppression of tissue prostaglandin synthesis.