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Rat Liver AT1 Receptor Binding Analysis for Drug Screening
Lee, Bu Yean,Kong, Jae Yang,Lee, Sung Hou,Shin, Hwa Sup 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1
The only compounds with antagonistic activity via AT₁, receptor, one of two subtypes of angiotensin II (AII) receptor, have been demonstrated to block the vasoconstriction effects of All and thereby provide therapeutic potential. This initiated the search for compounds with high specific affinity to ATI receptor and their effective screening methods. The radioligand binding assay for the All receptor is regarded as the primary method for the evaluation of AT₁ receptor antagonists for their activity. In this paper, we characterized the liver AT₁, receptor and describe the efficient method of the radioligand binding assay using rat liver as a source of AT₁ receptor. Equilibrium binding studies with rat adrenal cortex, adrenal medulla, liver and bovine adrenal showed that the specific bindings of [³H] All were saturable in all tissues and the Scatchard plots of those data were linear, suggesting a single population of binding sites. Hill slopes were very near to the unity in all tissues. Kinetic studies of [³H] All binding in rat liver homogenates yielded two association rate constants, 4.10 X 10^7 M^(-1)min^(-1) and 4.02 X 10^9 M^(-1)min^(-1), with a single dissociation rate constant, 7.07 X 10^(-3) min^(-1), possibly due to the partial dissociation phenomenon. The rank order of inhibition potencies of [³H] All binding in rat liver was All>Sarile>Losartan>PD 123177. Rat liver homogenates revealed to have very high density of homogeneous population of the AT₁, receptor subtype, as the specifically bound [³H] All was not inhibited by PD 123177, the nonpeptde antagonist of AT₂. The results of this study demonstrated that the liver homogenates from rats could be the best receptor preparation for the AT₁1 receptor binding assay and provide an efficient system for the screening of newly synthesized candidate compounds of AT₁, receptor antagonist.
The mouse as a model for the study of penile erection: moving towards a smaller animal
Piao, Shuguang,Ryu, Ji-Kan,Shin, Hwa-Yean,Han, Jee-Young,Lee, Hong-Sik,Suh, Jun-Kyu Scriptor Publisher ApS 2007 International journal of andrology Vol.30 No.5
<P>Summary</P><P>We evaluated erectile haemodynamics in mice and characterized the corpus cavernosum morphologically. Four-month-old male BALB/c mice and Sprague–Dawley rats were used. The following stimulation parameters were tested to achieve maximal erectile responses: voltage, 1–6 V; frequency, 6–24 Hz; pulse width, 1 msec; duration, 1 min (<I>n</I> = 7 per group). In a separate group of mice and rats (<I>n</I> = 10 per group), we measured systemic arterial pressure by use of either a 24-gauge angiocatheter or smaller calibre PE-10 tubing. Cavernous tissues from mice, rats or patients with psychogenic erectile dysfunction were stained for factor VIII, <I>&agr;</I>-actin and Masson trichrome. Electrical stimulation of the cavernous nerve in mice produced voltage-dependent erectile responses of up to 5 V, with the highest response at a frequency of 12 Hz. The maximal intracavernous pressure recorded at this stimulation parameter was comparable with that in rats. A PE-10 catheter was more reliable for measuring systemic arterial pressure in mice than was a 24-gauge angiocatheter, and the values recorded were similar between mice and rats. The content of endothelial cells, smooth muscle cells and collagen was similar between mice and rats. However, the cavernous tissue of both animals contained lesser amounts of smooth muscle cells and greater amounts of collagen than that of humans (<I>p</I> < 0.01). These results suggest that the mouse is a useful and technically feasible model for the study of penile erection and has functional and structural properties similar to those of rats.</P>
Ryu, Ji-Kan,Cho, Chung-Hyun,Shin, Hwa-Yean,Song, Sun U.,Oh, Seung-Min,Lee, Minhyung,Piao, Shuguang,Han, Jee-Young,Kim, In-Hoo,Koh, Gou Young,Suh, Jun-Kyu Elsevier 2006 MOLECULAR THERAPY Vol.13 No.4
<P><B>Abstract</B></P><P>Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.</P>
Cho, Tai Soon,Park, No Sang,Lee, Bu Yean,Kong, Jae Yang,Jung, Yi Sook,Shin, Hwa Sup 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.4
Antinociceptive and desensitizing effects of systemically administered capsaicinoids (capsaicin and KR25018) were investigated in guinea pig. Nociceptive sensitivity to chemical stimulus was examined to test sensory function, and the content of substance P-like immunoreactivity (SP-LI) in bronchi was determined as a peripheral marker of capsaicin-sensitive primary afferent neurons. Guinea pigs were pretreated s.c. with several doses of capsaicin (1, 2.5, 5, 10 mg/kg) or KR25018 (1, 2.5, 5, 10 mg/kg) one week prior to the experiments. Frequency of eye wiping was significantly decreased by capsaicin and KR25018 in a pretreatment dose-dependent manner. In capsaicin- or KR25018-pretreated guinea pigs, there was a significant loss of SP-LI in bronchial tissue extracts. In summary, a newly synthesized capsaicin analogue KR25018 exhibited antinociceptive effect against chemical stimulus in guinea pig, with comparable potency to capsaicin. This desensitizing activity of capsaicin or KR25018 might be related to the loss of SP-LI in peripheral afferent nerves.
Tran Trung Tin,Dang Van Chien,Ki-Jong Gil,Yong-Bin Shin,Young-Lim Choi,Yean-Hwa Lee,Jong-Wook Kim 한국정보기술학회 2017 한국정보기술학회논문지 Vol.15 No.3
The goal of this paper is to implement a haptic interface device for virtual reality application for the patients with MCI(Mild Cognitive Impairment) to recover their lost memory. The physical therapy for treatment of MCI is being developed as a complementary method for the treatment of memory impairment in the elderly. To produce a VR treatment program for memory recovery, the interactive program running on a virtual environment needs to be designed to be reminiscent of the memories in the past with a smart block haptic device that uses the force feedback mechanism from the user’s hands. To this end, we propose the smart block scheme implemented with an embedded system based on the virtual reality application to support treating and recovering memory for the elderly patients.
Lim Hyun Ju,Moon Eunsoo,Kim Kyungwon,Suh Hwagyu,Park Jeonghyun,Kim Du-Ri,Park Jong-Hwan,Shin Myung-Jun,Lee Yean-Hwa 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.5
Objective It is necessary to identify the mental health types of young women considering the importance of the mental health during the peripartum period. This study aimed to classify the mental health types in a community sample of young women with pre-pregnancy, pregnancy, or the postpartum period.Methods A total of 293 young women during pre-pregnancy, pregnancy, or the postpartum period were included in this study. The clinical characteristics of depression, anxiety, perceived stress, and quality of life were assessed. The clinical characteristics of the subject were classified by cluster analysis and compared by analysis of variance.Results From the cluster analysis, the subjects were classified into three groups. Cluster 1 showed significantly lower depression and anxiety and higher quality of life than those of cluster 2 and 3. Cluster 2 demonstrated significantly higher depression and anxiety and lower quality of life than those of cluster 3 and 1. Cluster 3 represented the intermediate levels between cluster 2 and 1.Conclusion This study suggested that young women during pre-pregnancy, pregnancy, or the postpartum period might be in a good mental health group, a high-risk group requiring active monitoring, or a group in need of treatment. By monitoring mental health, the groups with high risk or requiring treatment could be discovered and proper management for prevention or improvement of mental health and quality of life can be provided.
Yoon, Sang-Hwal,Lee, Young-Mi,Kim, Ju-Eun,Lee, Sook-Hee,Lee, Joo-Hee,Kim, Jae-Yean,Jung, Kyung-Hwa,Shin, Yong-Chul,Keasling, Jay D.,Kim, Seon-Won Wiley Subscription Services, Inc., A Wiley Company 2006 Biotechnology and bioengineering Vol.94 No.6
<P>To increase expression of lycopene synthetic genes crtE, crtB, crtI, and ipiHP1, the four exogenous genes were cloned into a high copy pTrc99A vector with a strong trc promoter. Recombinant Escherichia coli harboring pT-LYCm4 produced 17 mg/L of lycopene. The mevalonate lower pathway, composed of mvaK1, mvaK2, mvaD, and idi, was engineered to produce pSSN12Didi for an efficient supply of the lycopene building blocks, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Mevalonate was supplied as a substrate for the mevalonate lower pathway. Lycopene production in E. coli harboring pT-LYCm4 and pSSN12Didi with supplementation of 3.3 mM mevalonate was more than threefold greater than bacteria with pT-LYCm4 only. Lycopene production was dependent on mevalonate concentration supplied in the culture. Clump formation was observed as cells accumulated more lycopene. Further clumping was prevented by adding the surfactant Tween 80 0.5% (w/v), which also increased lycopene production and cell growth. When recombinant E. coli harboring pT-LYCm4 and pSSN12Didi was cultivated in 2YT medium containing 2% (w/v) glycerol as a carbon source, 6.6 mM mevalonate for the mevalonate lower pathway, and 0.5% (w/v) Tween 80 to prevent clump formation, lycopene production was 102 mg/L and 22 mg/g dry cell weight, and cell growth had an OD<SUB>600</SUB> value of 15 for 72 h. © 2006 Wiley Periodicals, Inc.</P>