Effects of rosiglitazone, an antidiabetic drug, on Kv3.1 channels

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC 50 = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of –20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

Strategies for Manipulating T Cells in Cancer Immunotherapy

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state

An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC 50 = 18.9 µM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

Antidepressant drug paroxetine blocks the open pore of Kv3.1 potassium channel

In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to highfrequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an IC₅₀ value of 9.43 µM and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding (k₊₁) and unbinding (k₋₁) rate constants for the paroxetine effect were 4.5 µM⁻¹s⁻¹ and 35.8 s⁻¹, respectively, yielding a calculated K(D) value of 7.9 µM. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a usedependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.

Blockade of Kv1.5 by paroxetine, an antidepressant drug

Paroxetine, a selective serotonin reuptake inhibitor (SSRI), has been reported to have an effect on several ion channels including human ether-a-go-go-related gene in a SSRI-independent manner. These results suggest that paroxetine may cause side effects on cardiac system. In this study, we investigated the effect of paroxetine on Kv1.5, which is one of cardiac ion channels. The action of paroxetine on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Paroxetine reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 4.11 microM and 0.98, respectively. Paroxetine accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -30 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to 0 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.32. The binding (k(+1)) and unbinding (k(-1)) rate constants for paroxetine-induced block of Kv1.5 were 4.9 microM(-1)s(-1) and 16.1 s-1, respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 3.3 microM. Paroxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of paroxetine, were superimposed. Inhibition of Kv1.5 by paroxetine was use-dependent. The present results suggest that paroxetine acts on Kv1.5 currents as an open-channel blocker.

Blockade of Kv1.5 channels by the antidepressant drug sertraline

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been reported to lead to cardiac toxicity even at therapeutic doses including sudden cardiac death and ventricular arrhythmia. And in a SSRI-independent manner, sertraline has been known to inhibit various voltage-dependent channels, which play an important role in regulation of cardiovascular system. In the present study, we investigated the action of sertraline on Kv1.5, which is one of cardiac ion channels. The eff ect of sertraline on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Sertraline reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 0.71 microM and 1.29, respectively. Sertraline accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -20 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +10 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.16. Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of sertraline, were superimposed. Inhibition of Kv1.5 by sertraline was use-dependent. The present results suggest that sertraline acts on Kv1.5 currents as an open-channel blocker.

Effects of Horticultural Therapy for the Korean Elderly : A Systematic Literature Review

PURPOSE: This study was conducted to ascertain the effectiveness of horticultural therapy by analyzing researches on horticultural therapy applied to elderly Koreans. METHODS: We evaluated 401 research papers including dissertations on horticultural therapy applied to elderly Koreans from Jan. 2000 to Feb. 2016. We reviewed the appropriate 12 papers among them for the final analysis. RESULTS: Horticultural therapy had physiological and psychosocial effects. First of all, it showed the physiological effects of reducing stress hormones. Outdoor horticultural therapy improved the gross motor movements of the body. Indoor horticulture therapy improved delicate cognitive & operating functions. Second, horticultural therapy showed the psychosocial effects of reducing depression and improving cognitive functions, language abilities, comprehension, daily activity, life satisfaction and sociality. But the effects appeared differently dependent on the implementation protocol & period of horticultural therapy, as well as the professionalism of the therapists. Therefore, if horticultural therapy were to be administered through nursing, it should be based on its key principle, in other words, the principle of action-interaction-response of horticultural therapy. CONCLUSION: The results of this study will be useful for developing therapeutic interventions through nursing. Also they will be helpful in applying horticultural therapy programs in nursing practice.

Protective effect of rutin on splanchnic injury following ischemia and reperfusion in rats

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of rutin, a flavonoid having antiprostanoid, anti-inflammatory, antithrombotic, antioxidant effect, were investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state resulted in a fatal outcome within 120 min of reperfusion in many rats. Rutin was given as a bolus (1.28 mg/kg) 10 min prior to reperfusion. Administration of rutin significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p<0.05). Rutin treatment also resulted in a significant attenuation in the increase in plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. These results suggest that rutin provides beneficial effects in part by preserving endothelial function and attenuating neutrophil accumulation in the ischemic reperfused splanchnic circulation.

Factors associated with fetal losses after mid-trimester amniocentesis / 대한산부인과학회잡지

OBJECTIVE: To evaluate factors associated with fetal losses following mid-trimester diagnostic amniocentesis. METHODS: 412 pregnancy outcomes following amniocentesis were analyzed for each variables(maternal age, gestational age, indication for the amniocentesis, placental penetration by aspiration needle, needle touch by the fetus, color of amniotic fluid) with statistical methods(student t-test, chi-square test and multiple logistic regression test). RESULTS: Mean maternal age was 31.8+/-4.9 years, fetal loss rate was increased slightly with the age of the mother. If the indications were abnormally high maternal serum alpha-fetoprotein level, the pregnancy courses after the procedure were worse than other indication groups. In cases of discolored amniotic fluid, the dark brown discoloration made the pregnancy outcome poor. Gestational age at the time of the procedure, penetration of the placenta by the aspirating needle, needle touch during the procedure by the fetus, did not influence the outcomes after the procedure. CONCLUSION: Maternal age, indication as neural tube defect in triple test and dark brown discoloration of amniotic fluid are associated with fetal losses following mid-trimester diagnostic amniocentesis.

Myocardial protection by recombinant soluble P-selectin glycoprotein ligand-1: Suppression of neutrophil and platelet interaction following ischemia and reperfusion

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with 75 X 106 PMNs, with 75 X 106 platelets, or with 75 X 106 PMNs+75 X 106 platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of 5 ~ 10% (p < 0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p < 0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

Assessment of Coronary Artery Bypass Graft Patency Using Three Dimensional Coronary Angiography by Electron Beam Tomography

BACKGROUNDS: The development of a noninvasive, accurate imaging technique for assessing coronary artery bypass graft patency is of major clinical importance because increasing numbers of patients have undergone coronary artery bypass surgery. The electron beam tomography, by virtue of its rapid data acquisition time and good spatial resolution, may be useful in this regard. The purpose of this study is to determine the accuracy of three-dimensional coronary angiography by electron beam tomography (EBT) in the assessment of patency of coronary artery bypass grafts. METHODS: Twenty-five patients who had undergone coronary artery bypass graft surgery were included. All patients underwent EBT and conventional coronary angiography for the evaluation of the status of bypass grafts. Three dimensional reconstruction of the heart and bypass grafts were performed and compared with selective angiography of the bypass grafts. RESULTS: Fifty-seven saphenous vein grafts (SVG) and 22 left internal mammary artery (LIMA) were evaluated for occlusion or patency. The sensitivity and specificity of EBT in the evaluation of LIMA patency were 80%, 82.4%, respectively. The sensitivity and specificity of EBT in the evaluation of SVG patency were 91.7% and 91.1%, respectively. The sensitivity and specificity of EBT in the evaluation of SVG according to the coronary territory were : 1) SVG to left anterior descending artery 100%, 100%:2) SVG to diagonal branch 100%, 100%:3) SVG to left circumflex artery 100%, 88.9%:4) SVG to right coronary artery 75%, 85.7%. CONCLUSION: Three-dimensional coronary angiography by electron beam tomography is a promising, useful and relatively accurate diagnostic technique for the evaluation of graft patency in patients who had undergone coronary artery bypass graft surgery.

Assessment of Coronary Artery Bypass Graft Patency Using Three Dimensional Coronary Angiography by Electron Beam Tomography

BACKGROUNDS: The development of a noninvasive, accurate imaging technique for assessing coronary artery bypass graft patency is of major clinical importance because increasing numbers of patients have undergone coronary artery bypass surgery. The electron beam tomography, by virtue of its rapid data acquisition time and good spatial resolution, may be useful in this regard. The purpose of this study is to determine the accuracy of three-dimensional coronary angiography by electron beam tomography (EBT) in the assessment of patency of coronary artery bypass grafts. METHODS: Twenty-five patients who had undergone coronary artery bypass graft surgery were included. All patients underwent EBT and conventional coronary angiography for the evaluation of the status of bypass grafts. Three dimensional reconstruction of the heart and bypass grafts were performed and compared with selective angiography of the bypass grafts. RESULTS: Fifty-seven saphenous vein grafts (SVG) and 22 left internal mammary artery (LIMA) were evaluated for occlusion or patency. The sensitivity and specificity of EBT in the evaluation of LIMA patency were 80%, 82.4%, respectively. The sensitivity and specificity of EBT in the evaluation of SVG patency were 91.7% and 91.1%, respectively. The sensitivity and specificity of EBT in the evaluation of SVG according to the coronary territory were : 1) SVG to left anterior descending artery 100%, 100%:2) SVG to diagonal branch 100%, 100%:3) SVG to left circumflex artery 100%, 88.9%:4) SVG to right coronary artery 75%, 85.7%. CONCLUSION: Three-dimensional coronary angiography by electron beam tomography is a promising, useful and relatively accurate diagnostic technique for the evaluation of graft patency in patients who had undergone coronary artery bypass graft surgery.

A Case of Heterotopic Pregnancy / 대한산부인과학회잡지

Heterotopic pregnancy describes the rare coexistence of intrauterine and extrauterine gestations. The commonly accepted incidence is 1:30,000 but the actual number is significantly higher. This condition remains difficult to diagnose and potentially dangerous to both mot- her and fetus. The incidence has risen after wider use of ovulation induction and the adve- nt of techniques of assisted reproduction. We report a case of simultaneous intrauterine pregnancy and tubal pregnancy.

Three cases of ovarian pregnancy / 대한산부인과학회잡지

No abstract available.

A case of ruptured interstitial pregnancy with 19 weeks gestation / 대한산부인과학회잡지

No abstract available.

Two cases of conjoined twins / 대한산부인과학회잡지

No abstract available.