알파-1 아드레날린 수용체 길항제인 탐술로신이 척수손상 후 배뇨의 구심성 신경경로에서의 신경활성에 미치는 영향

이광염 가천대학교 대학원 2014 국내박사

Are urologists performing semi rigid ureteroscopic lithotripsy safe from radiation exposure? A guidance to reduce the radiation dose

김민회 가천대학교 대학원 2018 국내석사

Objective : To measure radiation exposure of urologists during ureteroscopic (URS) lithotripsy, and hence estimating the number of procedures that can be performed safely considering the annually permissible radiation dose, and to identify influential variables. Materials & Methods : The radiation exposure dose was measured at the neck, chest, arm, and hands of a single urologist who performed 49 URS lithotripsies. The number of annually performed URS lithotripsies was estimated based on the annual permissible occupational exposure radiation dose guidelines. The fluoroscopy screening time, tube voltage, and tube current were evaluated to determine their correlation with operative time, position, size, and Hounsfield unit (HU) values of the ureteral stones, and patients’ body mass index (BMI). Results : Our findings showed that 45 URS lithotripsies can be safely performed without a whole-body apron versus 1725 cases with; considering the permissible dose for the hands, 448 cases without radiation protection were possible. Significant correlations were observed between operative time and fluoroscopy screening time (P<0.001), ureteral calculi location and fluoroscopy screening time (P=0.027), HU value and fluoroscopy screening time (P=0.016), HU value and operative time (P=0.041), and tube current and patients’ BMI (P=0.009). Conclusion : Considering radiation exposure risk, protective gear is necessary to ensure safety and efficacy of URS lithotripsy. Efforts to reduce radiation dose before and during surgery are required when ureteral calculi are in upper locations or have large HU, or the patient has a high BMI.

The effects of treadmill exercise in alleviating the symptoms of depressive state by increasing the degree of glucocorticoid receptor and c-Fos expression in the rat pups undergoing maternal separation

이상철 가천대학교 대학원 2013 국내석사

모성분리모델은 생애 초기의 스트레스 모델로 많이 쓰이고 있으며, 우울증 증상을 유발시킨다. 운동은 우울증이나 불안과 같은 스트레스와 관련된 질환의 발병이나 증상을 감소시킨다. 본 연구를 통해 모성분리모델이 신경비뇨기적 배뇨장애 모델로서의 적합성을 알아보고자 하였으며, 트레드밀 운동이 모성분리를 경험한 새끼 쥐의 해마 치상회와 시상하부 뇌실곁핵에서 glucocorticoid 수용체와 c-Fos 발현에 미치는 영향을 규명하였다. 모성분리는 생후 1일째부터 하루 6시간씩 30일간 지속하였다. 운동군의 새끼 쥐는 생후 21일째부터 30일째까지 10일간 트레드밀 운동을 실시하였다. 본 실험 결과, 트레드밀 운동은 모성분리에 의한 우울증을 fluoxetine 만큼 경감시켰다. 또한 트레드밀 운동은 glucocorticoid receptor와 c-Fos 발현을 정상치에 가깝게 회복시켰다. 본 연구를 통하여 트레드밀 운동은 어머니와의 관계의 장애에 의한 소아 우울증의 치료에 도움이 될 것으로 보여진다

Long-term chemical castration induces depressive symptoms by suppressing serotonin expression in rats

노주환 가천대학교 대학원 2018 국내석사

서론 진행된 전립선 암의 대표적인 치료법으로 거세가 널리 적용되고 있지만, 부작용에 대한 연구는 제한적이다.성적 행동의 감소와 우울증은 주요 부작용 중 하나인 것으로 주목되고 있지만 실제 부작용 인지와 근본적인 메커니즘은 아직 입증되지 않았다. 세로토닌 (5-HT) 시스템은 우울 증상과 같은 기분 변화에 관여하는 중요한 신경 전달 물질 중 하나로 우리는 장기간의 수술적 및 화학적 거세가 실제 성기능, 우울 증상 및 세로토닌 발현에 미치는 영향을 쥐의 뇌에서 조사했다. 대상 및 방법 성체 수컷 Sprague-Dawley rats (n = 40, 300 ± 10 g, 10 weeks) 를 3개월간 가수술 그룹(A), 양측고환절제술 그룹(B), goserelin 주사 그룹 (C), bicalutamide 치료 그룹 (D)의 네 그룹으로 나누었다.(n = 10 in each group) 성적 행동은 비디오 모니터링 시스템을 통해 mount latency, mount frequency, intromission latency, 그리고 intromission frequency 측정을 통해 분석하였다. 우울정도를 감별하기 위해 강제 수영 검사가 시행되었다. Dorsal raphe nuclei (DRN) 에 있는 5-HT 및 tryptophan hydroxylase (TPH)-양성 세포를 확인하기 위해 면역조직화학검사를 수행하였다.Western blot 5-HT1A and TPH와 같은 단백질 발현을 측정하기 위해 시행되었다. 결과 성적 행동은 그룹 A,D에 비해 그룹B,C에서 억제되었다. 그룹B,C,D의 부동 시간과 수영 시간,등반 시간은 그룹A 보다 감소하였다.(P < 0.05). DRN에서의 TPH 와 5-HT 는 그룹B, C ,D 에서 그룹A보다 감소하였다.(P < 0.05). 5-HT1A receptor와 TPH 단백질의 발현은 그룹B, C ,D 에서 그룹A보다 감소하였다.(P < 0.05). 결론 성적 행동은 testosterone의 기능이 아닌 수치에 영향을 더욱 받는다.장기간 동안의 수술적 및 화학적 거세는 DRN에서의 5-HT1A receptor 및 5-HT, TPH 발현의 감소로 우울증과 같은 상태를 유발시킨다.

구강점막 줄기세포의 이식이 척수 손상에 의한 신경인성 방광에 미치는 영향

조영삼 가천대학교 대학원 2014 국내박사

척수손상 (spinal cord injury)은 인간이 겪게 되는 모든 손상 중에서도 가장 치명적인 손상 중 하나로 심각한 장애를 초래하며, 신체의 기능적 변화를 초래하는 상태이다. 척수 손상시 대뇌조절능력이 저하되거나 배뇨반사궁 (micturition reflex) 및 신경근육계의 변화로 인해 신경인성 방광 (neurogenic bladder)을 초래하며 요실금, 빈뇨, 급박뇨 그리고 배뇨곤란과 같은 다양한 증상을 유발시킨다. 현재까지 척수 손상 후 발생하는 신경인성 방광의 치료는 표준적 방법 (golden standard)이 없는 실정이나, 최근 줄기세포 (stem cell)를 이용한 세포치료가 부각되고 있다. 그러나 현재 임상에서 사용되고 있는 세포치료법은 자가골수 단구세포 (mononuclear cell)을 이용하고 있으나, 신경세포로 분화가 가능한 중간엽 줄기세포 (mesenchymal stem cell)의 숫자가 적기 때문에 최근 비강 및 구강의 점막 (mucosa)의 줄기세포를 통한 치료방법이 연구되고 있다. 따라서 본 연구에서는 척수손상에 의해 유발된 신경인성 방광 흰쥐에 구강점막줄기세포 (oral mucosa stem cell)을 손상 부위에 이식하여 척수조직의 회복과 배뇨기능의 변화에 대하여 알아보았다. 실험동물은 13 주령된 Sprague-Dawley 계열 암컷 흰쥐 30마리를 사용하였으며, 집단분류는 대조군, 척수손상 유발군, 척수손상 유발 후 구강점막줄기세포 이식군 등 총 3집단으로 분류하였다. 척수손상의 유발은 흉추 11번 부위의 극돌기를 절삭한 후 수술용 드릴을 이용하여 직경 1 mm, 깊이 2 mm의 구멍을 뚫은 뒤 미세바늘을 이용하여 직접적으로 손상을 주었다. 구강점막줄기세포의 이식은 동일한 실험동물의 구강점막을 채취한 후 처리를 거친 줄기세포를 22 gauge 정맥 카테타를 이용하여 손상부위에 100 μl 투여하였다. 구강점막줄기세포 이식에 따른 조직의 변화를 확인하기 위해 hematoxylin & eosin 염색을 실시하였으며, 세포사멸과 세포증식의 확인은 terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 평가와 Ki67 면역조직화학법 (immunohistochemistry)을 실시하였다. 또한 배뇨기능을 확인하기 위한 방광내압측정법 (cystometry)과 배뇨중추경로 (neuronal voiding tract)에서 c-Fos 와 NGF 면역조직화학법을 수행하였다. 본 연구결과, 척수손상 후 구강점막줄기세포의 이식은 척수손상으로 증가된 TUNEL 양성세포수를 억제하였으며, 세포증식을 증가시킴으로써 조직학적 재생을 촉진시키는 것으로 나타났다. 또한, 척수손상은 배뇨중추경로에서의 c-Fos 와 NGF 양성세포수를 증가시켰으나 구강점막줄기세포의 이식은 척수손상으로 증가된 c-Fos 와 NGF 양성세포수를 의미있게 감소시키는 것으로 나타났다. 이러한 결과는 척수손상으로 증가된 수축압력과 수축시간을 억제시킴으로써 신경인성 방광증상 개선에 효과적인 것으로 나타났다. 본 연구를 통해 구강점막줄기세포의 치료는 척수손상의 정도를 경감시킴으로써 신경인성 방광증상을 경감시키고 회복하는데 효과적인 치료방법이라고 사료된다. Spinal cord injury (SCI) is a tremendous trauma causing severe and permanent disability. The primary damage of SCI is occurred by real mechanical tissue disruption immediately after trauma followingthe secondary damage which is mediated by complex cellular and molecular processes. Even though stem cell transplantation has been tried as a promising option and various cell types are applied to the SCI patients, there is no definite efficient method yet.As one of the challenging therapies for this,we adopted oral mucosa transplantation (OMT).We investigated the effects of OMTas the treatment method of SCI by evaluation of voiding function, apoptotic neuronal cell death and cell proliferation in the spinal cord, and expression c-Fos and nerve growth factor (NGF) in the neuronal voiding centers (MPA, vlPAG, PMC spinal cord L4-L5). For this study, a cystometry, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for SMA-α, Ki-67, NGF, and c-Fos were performed. Adult female Sprague-Dawley rats (10 weeks of age, 250 ± 10g) were used in this experiment. Rats were randomly divided into three groups (n = 10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and OMT group. For the induction of SCI, surgical drill used grind of spinous process, and drill a hole in vertebral arch (T10-T11). After drill a hole, using a needleuniformly gives damage in the spinal cord. Next, the oral mucosa is transplanted through the hole. SCI significantly increased apoptotic neuronal cell death in spinal cord, and decreased voiding pressure and time in cystometery. Moreover, expressions c-Fos and NGF were significantly suppressed in the neuronal voiding centers by SCI. However, OMT enhanced SMA- α and Ki-67 expressions of damage area in the spinal cord, and decreased apoptotic neuronal cell death by SCI. In addition, OMT increased the SCI-induced decreased NGF and c-Fos expressions in the neuronal voiding centers, and also voiding pressure and time increased in the cystometry. We demonstrated a beneficial effect of OMT and indicated that OMT were involved play a role of voiding function recovery and neurological recovery role in SCI-induced neuronal cell death.

Clinical considerations for evaluation, risk factors, and management of depression symptomatology in patients with prostate cancer undergoing androgen deprivation therapy

박현준 가천대학교 대학원 2018 국내석사

Purpose: To identify factors affecting depressive symptoms in patients undergoing androgen-deprivation therapy (ADT) to treat prostate cancer. Methods: Forty-five patients visiting the psychiatry department without referral because of depressive symptoms while undergoing ADT participated in this study. To assess depressive symptoms, the Beck Depression Inventory (BDI) was used. To identify variables influencing symptoms, multiple linear regression analysis was performed with BDI scores as well as current age, age at the time when ADT began, the type and length of ADT, disease response to ADT, androgen dependence, serum testosterone level, and whether concurrent chemotherapy was administered to treat the progression of prostate cancer during treatment with ADT. Results: Patients scored an average of 18 points (range: 0–40 points) on the BDI. Eleven (24.4%) patients were classified into the mild depression category, 7 (15.6%) patients were classified into the moderate depression category, and 12 (26.7%) patients were classified into the severe depression category. Of the clinical variables affecting BDI scores, the type of ADT drug (P<0.001), serum testosterone level (P=0.003), and age at diagnosis (P<0.001) were significant. Conclusions: Depression occurring in an elderly person for the first time is difficult to treat and recurs easily. We found a high likelihood for depression to occur in patients diagnosed with prostate cancer at age 70 or older and undergoing ADT. Depression must be diagnosed and treated appropriately, especially if depressive symptoms change in these high-risk patients.

Alpha1-Adrenergic Antagonist Can Influence Memory Function? Effect of Alpha1-Adrenergic Antagonist, Tamsulosin, on Activation of NMDA Receptor in Hippocampus of Rats

김창희 가천대학교 대학원 2015 국내박사

Alpha1 (α1)-adrenoceptor antagonists have widely been used for the treatment of overactive bladder (OAB) syndrome. OAB is characterized by urgency usually with frequency and nocturia. Treatment drugs act on peripheral tissues and on the central nervous system, because of their ability to readily cross the blood-brain barrier. It has been suggested that α1-adrenoceptor antagonists enhance brain function. In the present study, we investigated the effect of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory and spatial learning ability in rats. The step-down avoidance test for short-term memory and radial 8-arm maze test for spatial learning ability were conducted. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to evaluate the effect of tamsulosin on the level of apoptosis in the hippocampal dentate gyrus. Patch clamp recording was used to evaluate the effects of tamsulosin on the ionotropic glutamate receptor-mediated ion currents, such as N-methyl-D-aspartate (NMDA) receptor-, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-, and kainate (KA) receptor-mediated ion currents, in the hippocampal CA1 neurons. The present results showed that tamsulosin treatment improved short-term memory and spatial learning ability without alteration of the level of apoptosis. The amplitude of NMDA-induced ion current was significantly increased by tamsulosin application in a dose-dependent manner. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin application. The present study showed that tamsulosin might enhance memory functions through activation of NMDA receptor-mediated ion current in the hippocampus.

Is the selective neurotomy of dorsal nerves of penis supposed to be an alternative method for the treatment of premature ejaculation ? : clinical approaches based on case report and the literatures

장주현 가천대학교 대학원 2013 국내석사

Premature ejaculation is the most common form of male sexual dysfunction and has been shown to have a negative impact on the patient’s and his partner’s sexual satisfaction, interpersonal relationships, and quality of life. However, there is no a universally agreed-on definition and no established pathophysiology of premature ejaculation, which has made it difficult to treat and cure premature ejaculation although several therapeutic modalities have been supposed. The selective neurotomy of dorsal nerves of penis for the treatment of premature ejaculation are commonly reported from several countries and has shown not only the effectiveness in delaying ejaculation, improving ejaculatory control, and reducing penile hypersensitivity but also the negligible adverse effects. In this study, based on the previous reports and the clinical case that reduction of penile sensitivity and increase of perceived ejaculation control ability after two surgical procedures at intervals was achieved, the effectiveness and safety of the selective neurotomy of dorsal nerves of penis for premature ejaculation was investigated.

Effects of Surgical and Chemical Castration on Spatial Learning Ability in Relation with Cell Proliferation and Apoptosis in Hippocampus

심영진 가천대학교 대학원 2015 국내석사

Introduction.Chemical castration using luteinizing hormone-releasing hormone (LHRH) agonists and anti-androgens is alternative to the surgical castration. Goserelin and bicalutamide are drugs used for chemical castration.The effects of chemical castration on sexual functions are well documented, however the possibility that chemical castration might induce undesirable effects on brain functions has been raised. Aim.We investigated the effects of chemical castration and surgical castration on the spatial learning ability and the relations with cell proliferation and apoptosis in hippocampus. Methods.Surgical castration was performed by bilateral orchiectomy and chemical castration was induced by treatment with goserelin and bicalutamide for 28 days. Radial 8-arm maze test for spatial learning ability, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU), dobulecortin (DCX), caspase-3 were conducted. Western blot for brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), Bax and Bcl-2 in the hippocampus were also conducted. Main Outcome Measures.We compared the effects of goserelin and bicalutamide on the spatial learning ability with orchiectomy in relation with cells proliferation and apoptosis in the hippocampus. Results.Orchiectomy deteriorated spatial learning ability with suppressing cell proliferation and enhancing apoptosis in the hippocampus. Treatment with goserelin and bicalutamide did not exert any effects on spatial learning ability. Cell proliferation and apoptosis were not altered by treatment with goserelin and bicalutamide. Conclusions.Surgical castration deteriorates spatial learning ability, in contrast, chemical castration dose not impair spatial learning ability.

Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder

Ji-Hyeon Park 가천대학교 대학원 2014 국내석사

Purpose: The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats. Methods: Adult female Sprague-Dawley rats, weighing 250 ± 10 g (9 weeks old), were used in this study. The animals were divided into five groups (n = 8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted. Results: Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment. Conclusions: Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.