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Blockade of Kv1.5 channels by the antidepressant drug sertraline

  • Lee, Hyang Mi;Hahn, Sang June;Choi, Bok Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.193-200
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    • 2016
  • 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 effect 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 $IC_{50}$ value and a Hill coefficient of $0.71{\mu}M$ 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.

Management of Femoropopliteal Vascular Injuries after Trauma: Surgical Outcomes (외상 후 대퇴-오금 혈관손상의 치료: 수술 성적)

  • Chang, Sung Wook;Han, Sun;Ryu, Kyoung Min;Ryu, Jae-Wook
    • Journal of Trauma and Injury
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    • v.28 no.1
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    • pp.15-20
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    • 2015
  • Purpose: Vascular injuries caused by traffic, industrial accidents and by outside activities have increased in Korea. Especially, vascular injuries to the extremities can lead to limb loss and even mortality if they are not appropriately treated. The aim of the study was to evaluate the surgical outcomes of femoropopliteal vascular management after trauma. Methods: The medical records of 12 patients with femoropopliteal vascular injuries who were treated at Dankook University Hospital from 2011 to 2013 were reviewed. Iatrogenic vascular injuries were excluded. The clinical data including the causes of injury, associated injuries and surgical outcomes were analyzed retrospectively. Results: All patients were male, with a mean age of $46.8{\pm}16.3years$ (range: 26~69 years). The causes of vascular injuries were four traffic accidents, three industrial accidents, two iron plates, one outside activity, one glass injury and one knife injury. The average transit time between the place of the accident place and the emergency department was $3.0{\pm}2.1$ (0.5~12.5) hours, and the average preparation time for surgery was $8.0{\pm}6.7$ (1.7~23.3) hours. The anatomic injuries included the popliteal vessel in seven cases and the femoral vessel in five cases. The average Injury Severity Score (ISS) was $12.0{\pm}5.0$ (5~17), and the average Mangled Extremity Severity Score (MESS) was $5.7{\pm}2.1$ (2~9). The operation methods were four interposition grafts, three end-to-end anastomoses, two direct repairs and three patch angioplasties. One case required amputation of the injured extremity. Conclusion: Early recognition and revascularization of the injured vessel are mandatory to reduce limb loss and to obtain satisfactory outcomes. Therefore, careful/rapid evaluation of the vascular injuries and timely/successful surgical treatment are the keys to salvaging an injured limb.

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Percutaneous Absorption Characteristics of Tacrine in Alzheimer-type Dementia Treatment (Alzheimer형 치매치료제인 Tacrine의 경피 투과 특성 연구)

  • Lee, Han-Seob
    • Journal of the Korean Applied Science and Technology
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    • v.29 no.4
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    • pp.552-560
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    • 2012
  • Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution, and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stop if the drug dosage lead to side effect. Polysaccharide, such as karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO) were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, tacrine contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in tacrine such as lipophilic drug in vitro. We used glycerin, PEG 400, and PEG 800 as enhancers. Therefore, transdermal absorption of tacrine could be improved by changing vehicle composition or by using penetration enhancers. Especially it would be anticipated that the high permeation efficacy could be obtained by using vehicle that has enhancing effect for itself and by adding enhancers to it.

Percutaneous Absorption Characteristics of Antidepressant Paroxetine (항우울제인 Paroxetine의 피부 투과 특성 연구)

  • Jung, Duck-Chae;Hwang, Sung-Kwy;Oh, Se-Young
    • Journal of the Korean Applied Science and Technology
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    • v.28 no.2
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    • pp.170-177
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    • 2011
  • Transdermal drug delivery(TDS) offers many important advantages. For instance, it is easy and painless, it protects the active compound from gastric enzymes, and it avoids the hepatic first-pass effect. Also, it is simple to terminate the therapy if any adverse or undesired effect occurs. But skin is a natural barrier, and only a few drugs can penetrate the skin easily and in sufficient quantities to be effective. Therefore, in recent years, numerous studies have been conducted in the area of penetration enhancement. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stopped if the drug dosage lead to side effect. Polysaccharide, such as xanthan gum and algin were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers and drug contents. Among these polysaccharide, the permeation rate of Paroxetine such as lipophilic drug was the fastest in xanthan gum matrix in vitro. We used glycerin, PEG400 and PEG800 as enhancers. Since dermis has more water content(hydration) than the stratum corneum, skin permeation rate at steady state was highly influenced when PEG400 was more effective for lipophilic drug. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate.

Percutaneous absorption Characteristics of Anti hyperlipidemia Gel Ointment using Fibric acid (Fibric acid를 이용한 항고지혈증 겔 연고의 경피 흡수 특성)

  • Jung, Duck-Chae;Hwang, Sung-Kwy;Oh, Se-Young
    • Journal of the Korean Applied Science and Technology
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    • v.27 no.4
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    • pp.407-414
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    • 2010
  • New biological treatments were being developed at a record place, but their potential could be compromised by a significant obstacle: the delivery of these drugs into a body. Pharmaceutical delivery is now nearly as important as product. New systems are being developed, and Drug Delivery Markets Series cover these new systems. Transdermal Delivery System(TDS) is often used as a method of drug dosage into the epidermic skin. An approach used to delivery drugs through the skin for therapeutic use as an alternative to oral, intravascular, subcutaneous and transmucosal routes. Various transdermal drug delivery technologies are described including the use of suitable formulations, carriers and penetration enhancers. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other methods of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stopped if the drug dosage lead to side effect. Polysaccharides, such as karaya gum and glucomannan, were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, drug contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in fibric acid(ciprofibrate) such as lipophilic drug in vitro. We used glycerin, PEG400 and PEG800 as enhancers. Since dermis has more water content(hydration) than the stratum corneum, skin permeation rate at steady state was highly influenced when PEG400 was more effective for lipophilic drug. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate. Especially, this result suggests a possible use of polysaccharide gel ointment matrix as a transdermal delivery system of anti-hyperlipoproteinemic agent.

Case Study: Cost-effective Weed Patch Detection by Multi-Spectral Camera Mounted on Unmanned Aerial Vehicle in the Buckwheat Field

  • Kim, Dong-Wook;Kim, Yoonha;Kim, Kyung-Hwan;Kim, Hak-Jin;Chung, Yong Suk
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.64 no.2
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    • pp.159-164
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    • 2019
  • Weed control is a crucial practice not only in organic farming, but also in modern agriculture because it can lead to loss in crop yield. In general, weed is distributed in patches heterogeneously in the field. These patches vary in size, shape, and density. Thus, it would be efficient if chemicals are sprayed on these patches rather than spraying uniformly in the field, which can pollute the environment and be cost prohibitive. In this sense, weed detection could be beneficial for sustainable agriculture. Studies have been conducted to detect weed patches in the field using remote sensing technologies, which can be classified into a method using image segmentation based on morphology and a method with vegetative indices based on the wavelength of light. In this study, the latter methodology has been used to detect the weed patches. As a result, it was found that the vegetative indices were easier to operate as it did not need any sophisticated algorithm for differentiating weeds from crop and soil as compared to the former method. Consequently, we demonstrated that the current method of using vegetative index is accurate enough to detect weed patches, and will be useful for farmers to control weeds with minimal use of chemicals and in a more precise manner.

A Sensitive, Efficient, and Cost-Effective Method to Determine Rotigotine in Rat Plasma Using Liquid-Liquid Extraction (LLE) and LC-MRM

  • Kim, Ji Seong;Jang, Yong Jin;Kim, Jin Hee;Kim, Jin Hwan;Seo, Jae Hee;Park, Il-Ho;Kang, Myung Joo;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.13 no.4
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    • pp.146-151
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    • 2022
  • Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson's disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH-DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over previous methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00-115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the development of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

A NEW BIOPOLYMER FOR REFRESHMENT

  • Bozou, J.C.;Gautry, L.;Pianelli, G.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.480-490
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    • 2003
  • An innovative biopolymer known as the Rhizobian gum has been developed in France, which shows some dramatic refreshing effect on the skin. The origin of this innovative project takes its source in the natural environment, and in particular the natural environment of the roots of sunflowers and wheat, where a symbiotic bacterium has been discovered. It is a Rhizobium bacterium, which is hosted by the roots, and which is able to synthesize a specific polymer showing a dramatic water binding capacity. This polymer is in particular synthesized in period of drought, and its biological role is to concentrate the small amount water present in the soil in order to take it available for the root, which becomes then able to absorb it. This vital mechanism allows the plant to survive despite a severe climatic environment. This basic research has been conducted in collaboration whit the French National centre of scientific Research (CNRS), and has lead to the isolation of the Rhizobium bacteria. Rhizobian gum is a branched biopolymer consisting in the repetition of a polysaccharide unit of 3 molecules of glucose, 3 molecules of galactose and 1 molecule of glucuronic acid, whit one pyruvate group an average 1.6 acetyl groups. The fresh effect of Rhizobian gum is a strong sensorial impact that 100 % of the consumers are able to perceive, and which is judged very pleasant by most of them. In addition to this, a large majority of consumers are perceived, and which is judge very pleasant by most of them. In addition to this, a large majority of consumers also feel a very pleasant relaxing sensation. Smoothness and softness are also felt by most consumers and qualified positively by most of them. These qualities guarantee a strong impact on today's consumers.

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A NEW BIOPOLYMER FOR REFRESHMENT

  • Bozou, J.C.;Gautry, L.;Pianelli, G.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.50-60
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    • 2003
  • An innovative biopolymer known as the Rhizobian gum has been developed in France, which shows some dramatic refreshing effect on the skin. The origin of this innovative project takes its source in the natural environment, and in particular the natural environment of the roots of sunflowers and wheat, where a symbiotic bacterium has been discovered. It is a Rhizobium bacterium, which is hosted by the roots, and which is able to synthesize a specific polymer showing a dramatic water binding capacity. This polymer is in particular synthesized in period of drought, and its biological role is to concentrate the small amount water present in the soil in order to take it available for the root, which becomes then able to absorb it. This vital mechanism allows the plant to survive despite a severe climatic environment. This basic research has been conducted in collaboration whit the French National centre of scientific Research (CNRS), and has lead to the isolation of the Rhizobium bacteria. Rhizobian gum is a branched biopolymer consisting in the repetition of a polysaccharide unit of 3 molecules of glucose, 3 molecules of galactose and 1 molecule of glucuronic acid, whit one pyruvate group an average 1.6 acetyl groups. The fresh effect of Rhizobian gum is a strong sensorial impact that 100 % of the consumers are able to perceive, and which is judged very pleasant by most of them. In addition to this, a large majority of consumers are perceived, and which is judge very pleasant by most of them. In addition to this, a large majority of consumers also feel a very pleasant relaxing sensation. Smoothness and softness are also felt by most consumers and qualified positively by most of them. These qualities guarantee a strong impact on today's consumers.

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Biological soil crusts impress vegetation patches and fertile islands over an arid pediment, Iran

  • Sepehr, Adel;Hosseini, Asma;Naseri, Kamal;Gholamhosseinian, Atoosa
    • Journal of Ecology and Environment
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    • v.46 no.1
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    • pp.31-40
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    • 2022
  • Background: Plant vegetation appears in heterogeneous and patchy forms in arid and semi-arid regions. In these regions, underneath the plant patches and the empty spaces between them are covered by biological soil crusts (moss, lichen, cyanobacteria, and fungi). Biological soil crusts lead to the formation and development of fertile islands in between vegetation patches via nitrogen and carbon fixation and the permeation of runoff water and nutrients in the soil. Results: The present study has investigated the association of biological soil crusts, the development of fertile islands, and the formation of plant patches in part of the Takht-e Soltan protected area, located in Khorasan Razavi Province, Iran. Three sites were randomly selected as the working units and differentiated based on their geomorphological characteristics to the alluvial fan, hillslope, and fluvial terrace landforms. Two-step systematic random sampling was conducted along a 100-meter transect using a 5 m2 plot at a 0-5 cm depth in three repetitions. Fifteen samplings were carried out at each site with a total of 45 samples taken. The results showed that the difference in altitude has a significant relationship with species diversity and decreases with decreasing altitude. Results have revealed that the moisture content of the site, with biocrust has had a considerable increase compared to the other sites, helping to form vegetation patterns and fertile islands. Conclusions: The findings indicated that biological crusts had impacted the allocation of soil parameters. They affect the formation of plant patches by increasing the soil's organic carbon, nitrogen, moisture and nutrient content provide a suitable space for plant growth by increasing the soil fertility in the inter-patch space.