Potassium Currents in Isolated Deiters' Cells of Guinea Pig

Deiters'' cells are the supporting cells in organ of Corti and are suggested to play an important role in biochemical and mechanical modulation of outer hair cells. We successfully isolated functionally different K⁺ currents from Deiters'' cells of guinea pig using whole cell patch clamp technique. With high K⁺ pipette solution, depolarizing step pulses activated strongly outward rectifying currents which were dose-dependently blocked by clofilium, a class III anti-arrhythmic K⁺ channel blocker. The remaining outward current was transient in time course whereas the clofilium-sensitive outward current showed slow inactivation and delayed rectification. Addition of 5 mM tetraethylammonium (TEA) further blocked the remaining current leaving a very fast inactivating transient outward current. Therefore, at least three different types of K⁺ current were identified in Deiters'' cells, such as fast activating and fast inactivating current, fast activating slow inactivating current, and very fast inactivating transient outward current. Physiological role of them needs to be established.     

Social network effects on post-traumatic stress disorder (PTSD) in female North Korean immigrants

Objectives

The goal of this paper is to examine the social network effects on post-traumatic sdress disorder (PTSD) in female North Korean immigrants who entered South Korea in 2007. Specifically, it attempts to verify if the density and composition of networks make a difference after controlling for the network size.

Methods

A multivariate logistic regression is used to probe the effects of social networks using the North Korean Immigrant Panel data set. Because the data set had only completed its initial survey when this paper was written, the analysis was cross-sectional.

Results

The size of the support networks was systematically related to PTSD. Female North Korean immigrants with more supporting ties were less likely to develop PTSD, even after controlling for other risk factors (odds-ratio for one more tie was 0.8). However, once we control for the size of the network, neither the density nor the composition of the networks remains statistically significant.

Conclusions

The prevalence of the PTSD among female North Korean immigrants is alarmingly high, and regardless of the characteristics of supporting network members, the size of the supporting networks provides substantial protection. This implies that a simple strategy that focuses on increasing the number of supporting ties will be effective among North Korean immigrants who entered South Korea in recent years.     

Social Network Characteristics and Body Mass Index in an Elderly Korean Population

Objectives

Research has shown that obesity appears to spread through social ties. However, the association between other characteristics of social networks and obesity is unclear. This study aimed to identify the association between social network characteristics and body mass index (BMI, kg/m²) in an elderly Korean population.

Methods

This cross-sectional study analyzed data from 657 Koreans (273 men, 384 women) aged 60 years or older who participated in the Korean Social Life, Health, and Aging Project. Network size is a count of the number of friends. Density of communication network is the number of connections in the social network reported as a fraction of the total links possible in the personal (ego-centric) network. Average frequency of communication (or meeting) measures how often network members communicate (or meet) each other. The association of each social network measure with BMI was investigated by multiple linear regression analysis.

Results

After adjusting for potential confounders, the men with lower density (<0.71) and higher network size (4-6) had the higher BMI (β=1.089, p=0.037) compared to the men with higher density (>0.83) and lower size (1-2), but not in the women (p=0.393). The lowest tertile of communication frequency was associated with higher BMI in the women (β=0.885, p=0.049), but not in the men (p=0.140).

Conclusions

Our study suggests that social network structure (network size and density) and activation (communication frequency and meeting frequency) are associated with obesity among the elderly. There may also be gender differences in this association.     

Direct modulation of Ca(2+)-activated K(+) current by H-89 in rabbit coronary arterial smooth muscle cells

The effects of H-89, a potent and selective inhibitor of protein kinase A (PKA) on Ca(2+)-activated K(+) (BK(Ca)) channels in coronary arterial smooth muscle cells were examined using a patch-clamp technique. In inside-out configuration, H-89 increased the NP(o) of the BK(Ca) channel, but it reduced the dwell time of BK(Ca) currents. In whole-cell configuration, H-89 markedly increased BK(Ca) currents in a concentration-dependent manner. The EC(50) was 0.470+/-0.0741 microM based on dwell time, 0.582+/-0.0691 microM based on the NP(o), and 0.519+/-0.0295 microM based on the whole-cell current, respectively. H-85, which is an inactive form of H-89, increased BK(Ca) currents, similar to the result of H-89. The other PKA inhibitors (Rp-8-CPT-cAMPs and KT 5720) and protein phosphatase inhibitor (okadaic acid, 1 microM) had little effect on BK(Ca) currents and did not significantly alter the stimulatory effects of 1 microM H-89. These findings suggest that H-89 increases the BK(Ca) current independently of PKA.     

Inhibition of acetylcholine-activated K(+) currents by U73122 is mediated by the inhibition of PIP(2)-channel interaction.

1. We have investigated the effect of U73122, a specific inhibitor of phospholipase C (PLC), on acetylcholine-activated K(+) currents (I(KACh)) in mouse atrial myocytes. 2. In perforated patch clamp mode, I(KACh) was activated by 10 microM acetylcholine. When atrial myocytes were pretreated with U73122 or U73343, I(KACh) was inhibited dose-dependently (half-maximal inhibition at 0.12+/-0.0085 and 0.16+/-0.0176 microM, respectively). The current-voltage relationships for I(KACh) in the absence and in the presence of U73122 showed that the inhibition occurred uniformly from -120 to +40 mV, indicating a voltage-independent inhibition. 3. When U73122 was applied after I(KACh) reached steady-state, a gradual decrease in I(KACh) was observed. The time course of the current decrease was well fitted to a single exponential, and the rate constant was proportional to the concentration of U73122. 4. When K(ACh) channels were directly activated by adding 1 mM GTP gamma S to the bath solution in inside-out patches, U73122 (1 microM) decreased the open probability significantly without change in mean open time. When K(ACh) channels were activated independently of G-protein activation by 20 mM Na(+), open probability was also inhibited by U73122. 5. Voltage-activated K(+) currents and inward rectifying K(+) currents were not affected by U73122. 6. These findings show that inhibition by U73122 and U73343 of K(ACh) channels occurs at a level downstream of the action of G beta gamma or Na(+) on channel activation. The interference with phosphatidylinositol 4,5-bisphosphate (PIP(2))-channel interaction can be suggested as a most plausible mechanism.     

Identifying Hidden Sexual Bridging Communities in Chicago

Bridge populations can play a central role in the spread of human immunodeficiency virus (HIV) by providing transmission links between higher and lower prevalence populations. While social network methods are well suited to the study of bridge populations, analyses tend to focus on dyads (i.e., risk between drug and/or sex partners) and ignore bridges between distinct subpopulations. This study takes initial steps toward moving the analysis of sexual network linkages beyond individual and risk group levels to a community level in which Chicago’s 77 community areas are examined as subpopulations for the purpose of identifying potential bridging communities. Of particular interest are “hidden” bridging communities; that is, areas with above-average levels of sexual ties with other areas but whose below-average AIDS prevalence may hide their potential importance for HIV prevention. Data for this analysis came from the first wave of recruiting at the Chicago Sexual Acquisition and Transmission of HIV Cooperative Agreement Program site. Between August 2005 through October 2006, respondent-driven sampling was used to recruit users of heroin, cocaine, or methamphetamine, men who have sex with men regardless of drug use, the sex partners of these two groups, and sex partners of the sex partners. In this cross-sectional study of the sexual transmission of HIV, participants completed a network-focused computer-assisted self-administered interview, which included questions about the geographic locations of sexual contacts with up to six recent partners. Bridging scores for each area were determined using a matrix representing Chicago’s 77 community areas and were assessed using two measures: non-redundant ties and flow betweenness. Bridging measures and acquired immunodeficiency syndrome (AIDS) case prevalence rates were plotted for each community area on charts representing four conditions: below-average bridging and AIDS prevalence, below-average bridging and above-average AIDS prevalence, above-average bridging and AIDS prevalence, and above-average bridging and below-average AIDS prevalence (hidden bridgers). The majority of the 1,068 study participants were male (63%), African American (74%), and very poor, and the median age was 44 years. Most (85%) were sexually active, and 725 provided useable geographic information regarding 1,420 sexual partnerships that involved 57 Chicago community areas. Eight community areas met or came close to meeting the definition of hidden bridgers. Six areas were near the city’s periphery, and all eight areas likely had high inflows or outflows of low-income persons displaced by gentrification. The results suggest that further research on this method is warranted, and we propose a means for public health officials in other cities to duplicate the analysis.     

Blockade of the HERG human cardiac K(+) channel by the antidepressant drug amitriptyline

1. Amitriptyline has been known to induce QT prolongation and torsades de pointes which causes sudden death. We studied the effects of amitriptyline on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on the rapidly activating delayed rectifier K(+) current (I(Kr)) in rat atrial myocytes. 2. The amplitudes of steady-state currents and tail currents of HERG were decreased by amitriptyline dose-dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by amitriptyline is voltage dependent. IC(50) for amitriptyline block of HERG current was progressively decreased according to depolarization: IC(50) values at -30, -10, +10 and +30 mV were 23.0, 8.71, 5.96 and 4.66 microM, respectively. 3. Block of HERG by amitriptyline was use dependent: exhibiting a much faster block at higher activation frequency. Subsequent decrease in frequency after high activation frequency resulted in a partial relief of HERG blockade. 4. Steady-state block by amitriptyline was obtained while depolarization to +20 mV for 0.5 s was applied at 0.5 Hz: IC(50) was 3.26 microM in 2 mM [K(+)](o). It was increased to 4. 78 microM in 4 mM [K(+)](o), suggesting that the affinity of amitriptyline on HERG was decreased by external K(+). 5. In rat atrial myocytes bathed in 35 degrees C, 5 microM amitriptyline blocked I(Kr) by 55%. However, transient outward K(+) current (I(to)) was not significantly affected. 6. In summary, the data suggest that the block of HERG currents may contribute to arrhythmogenic side effects of amitriptyline.     

Conventional Epi-LASIK and lamellar epithelial debridement in myopic patients with dermatologic keloids

We report the outcome of conventional epipolis laser in situ keratomileusis (Epi-LASIK, flap-on) and lamellar epithelial debridement (LED; Epi-LASIK, flap-off) in myopic patients with dermatologic keloids. Three patients, who were all noted to be susceptible to keloid scarring, received conventional Epi-LASIK in their right eyes and LED in their left eyes. The patients were followed-up for 6 to 21 months after their surgeries, and the outcomes were then evaluated. In case 1, the preoperative spherical equivalent (SE) was -6.5 diopters (D) in the right eye (OD) and -6.25 D in the left eye (OS). At 21 months postoperatively, the uncorrected visual acuity (UCVA) was 20 / 12.5 in both eyes. In case 2, the preoperative SE was -5.25 (OD) / -6.00 (OS). After six months, the postoperative UCVA was 20 / 12.5 in both eyes. In case 3, the preoperative SE was -4.5 (OD) / -2.0 (OS). The UCVA at the six-month follow-up was 20 / 12.5 in both eyes. No adverse events, including corneal haze, occurred in any of the patients. All three of our patients reported excellent visual outcomes following both conventional Epi-LASIK and LED, despite their histories of keloid formation. The present cases suggest that both Epi-LASIK and LED may be safe and effective techniques for myopic patients with dermatologic keloids.     

Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage

Clinical evidence that the blockade of IL-1β in type-2 diabetic patients improves glycemia is indicative of an autoinflammatory mechanism that may trigger adiposity-driven pancreatic damage. IL-1β is a key contributor to the obesity-induced inflammation and subsequent insulin resistance, pancreatic β-cell dysfunction, and the onset of type 2 diabetes. Our previous studies demonstrated that the ceramides activate the Nod-like receptor family, pyrin domain containing 3 (Nlrp3) inflammasome to cause the generation of mature IL-1β and ablation of the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling. However, it remains unclear whether the posttranslational processing of active IL-1β in pancreas is regulated by the NLRP3 inflammasome or whether the alternate mechanisms play a dominant role in chronic obesity-induced pancreatic β-cell exhaustion. Here we show that loss of ASC, a critical adaptor required for the assembly of the NLRP3 and absent in melanoma 2 inflammasome substantially improves the insulin action. Surprisingly, despite lower insulin resistance in the chronically obese NLRP3 and ASC knockout mice, the insulin levels were substantially higher when the inflammasome pathway was eliminated. The obesity-induced increase in maturation of pancreatic IL-1β and pancreatic islet fibrosis was dependent on the NLRP3 inflammasome activation. Furthermore, elimination of NLRP3 inflammasome protected the pancreatic β-cells from cell death caused by long-term high-fat feeding during obesity with significant increase in the size of the islets of Langerhans. Collectively, this study provides direct in vivo evidence that activation of the NLRP3 inflammasome in diet-induced obesity is a critical trigger in causing pancreatic damage and is an important mechanism of progression toward type 2 diabetes.