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Two bistable multivibrators based on the operational transresistance amplifier (OTRA) are presented. The first topology consists of only one OTRA and a positive feedback network. The second multivibrator utilises a single-pole double-throw (SPDT) switch along with a bias voltage source to shift the hysteresis loop into either the right-half-part or the left-half-part of the νi–νo plane. These two proposed circuits have a common attractive feature. That is, both clockwise and counter-clockwise hysteresis operations can be fulfilled with an additional SPDT switch connected to different configurations. In order to extend the applications, a general multiple-output configuration is also suggested. The presented bistable multivibrators are simple and versatile. The operation principles are described in detail. Theoretical analyses are verified by the experimental results on the prototype circuits. [ABSTRACT FROM AUTHOR]

Two squarewave generators consisting of only one operational transresistance amplifier and minimum external passive elements are presented. The first circuit is a general multivibrator that can produce an approximately symmetrical squarewave with a fixed duty cycle and a variable frequency. The second one can further independently control the on- and off-duty cycles of a squarewave by adjusting the values of the passive elements. These proposed squarewave generators are described and analysed. The experimental results and the recorded waveforms confirm the theoretical analysis and verify the feasibility of the presented schemes. [ABSTRACT FROM AUTHOR]

Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity. Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. Results: In whole cell current recordings mognolol reversibly increased the amplitude of K2+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 μM) but not by glibenclamide (10 μM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1 .5 μM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound. [ABSTRACT FROM AUTHOR]

Background: The effects of the anti-anginal drug fendiline on intracellular Ca2+ concentrations ([Ca2+]i) in human PC3 prostate cancer cells were examined.Methods: [Ca2+]i was measured using the fluorescent dye fura-2.Results: Fendiline (0.5-100 microM) increased [Ca2+]i in a concentration-dependent manner. Ca2+ removal partly inhibited the Ca2+ signals. In Ca2+-free medium, pretreatment with 100 microM fendiline inhibited most of the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), and pretreatment with thapsigargin abolished the fendiline-induced [Ca2+]i increases. Adding 3 mM Ca2+ increased [Ca2+]i in cells pretreated with 0.5-200 microM fendiline in Ca2+-free medium. Pretreatment with 1 microM U73122 to block the formation of inositol-1.4.5-trisphosphate (IP3) did not alter fendiline-induced internal Ca2+ release.Conclusions: The anti-anginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+]i may lead to cell injury and death, the long-term effect of fendiline on the function of prostate cancer cells should be investigated. [ABSTRACT FROM AUTHOR]

This study investigated the effect of the anti-anginal drug, fendiline, on intracellular free Ca[sup 2+] levels ([Ca[sup 2+]][sub i]) in HA/22 human hepatoma cells by using fura-2 as a fluorescent Ca[sup 2+] dye. Fendiline (1–100 M) increased [Ca[sup 2+]][sub i] with an EC[sub 50] of 25 M. Removal of extracellular Ca[sup 2+] reduced the [Ca[sup 2+]][sub i] signals by 51±5%. Fendiline (10 M)-induced Ca[sup 2+] release was abolished by pretreatment with 1 M thapsigargin (an endoplasmic reticulum Ca[sup 2+] pump inhibitor). Inhibition of phospholipase C with 2 M 1-(6-((17-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122) did not alter 10 M fendiline-induced Ca[sup 2+] release. Several other calmodulin antagonists, such as phenoxybenzamine (100–200 M), trifluoperazine (5–50 M), and fluphenazine-N-chloroethane (2–100 M), had no effect on [Ca[sup 2+]][sub i]. Together, it was found that fendiline increased [Ca[sup 2+]][sub i] in human hepatoma cells by discharging Ca[sup 2+] from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-independent manner and by inducing Ca[sup 2+] entry. This effect of fendiline does not appear to be via antagonism of calmodulin. Human & Experimental Toxicology (2001) 20, 359–364. [ABSTRACT FROM AUTHOR]

Objective: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population., Methods: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing., Results: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features., Conclusion: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists., Competing Interests: All authors have disclosed no conflicts of interest.