• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.387-392
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• 2008

Alfuzosin, an Alphal-adrenoceptor antagonist is used for the treatment of patients with voiding and in a lesser extent storage lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). The objective of this study was to formulate sustained release alfuzosin HCl granules and assess their formulation variables. The $Eudragit^{(R)}$ as a polymer, sustained release membrane, and dibutyl sebacate (DBS) as a plasticizer were used. Multi-coated alfuzosin HCl delivery systems composed of sugar sphere, various excipients, $Eudragit^{(R)}$ and HPMC (hydroxy propyl methyl cellulose), Cellulose Acetate were prepared by fluid-bed coater. Membrane layer were used $Eudragit^{(R)}$ RS PO and NE 30D. And the alfuzosin HCl coated beads were coated immediate release drug layer for initial burst. Its dissolution test was carried out compared to conventional products ($XATRAL^{(R)}$ XL). The release rate of drug from coated beads was higher than that from $XATRAL^{(R)}$ XL in pH 6.8.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.471-475
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• 2004

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

• International Neurourology Journal
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• 제22권4호
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• pp.252-259
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• 2018

Purpose: Naftopidil ((${\pm}$)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. Methods: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in $A{\delta}$ or C fibers. Naftopidil or prazosin, an ${\alpha}1$-adrenoceptor blocker, was perfused at $100{\mu}M$ or $10{\mu}M$, respectively. Results: Bath-applied $100{\mu}M$ naftopidil significantly decreased the peak amplitudes of $A{\delta}$ and C fiber-evoked EPSCs to $72.0%{\pm}7.1%$ (n=15) and $70.0%{\pm}5.5%$ (n=20), respectively, in a reversible and reproducible manner. Bath application of $100{\mu}M$ prazosin did not inhibit $A{\delta}$ or C fiber-evoked EPSCs. Conclusions: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve ${\alpha}1$-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

• 대한본초학회지
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• 제33권1호
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• pp.71-76
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• 2018

Objectives : This study was performed to investigate the single oral toxicity of HBX-6 in Sprague-Dawley (SD) rats. Methods : Twenty SD rats were randomly assigned to four groups of 5 rats each and were administrated singly to female and male SD rats, as an oral dose of 2000 mg/kg. HBX-6 is a newly combined Korean herbal medicine formula 30 % Ethanol extract derived from The Dongui Bogam. Now we are developing the prescription for the aim of improving benign prostatic hyperplasia (BPH) without undesirable side effects. HBX-6 is composed of nine medicinal herbs: Aconiti Lateralis Radix Preparata, Corni Fructus, Cistanchis Herba, Psoraleae Semen, Dendrobii Herba, Morindae Radix, Cuscutae Semen, Trigonellae Semen, Foeniculi Fructus. Animals were monitored for the mortality and changes in the body weight, clinical signs, gross observation and necropsy findings for the 14 days according to "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity - Fixed Dose Procedure" of OECD Test Guideline. Results : We could not find any mortality. Compared with the control group, significant weight change was not observed in the experimental group. After administration, the more common symptoms were not observed. There were no gross abnormalities in all cases. Conclusions : Taken together, these results suggest that the approximate lethal dose of HBX-6 in both female and male SD rats were considered as over 2000 mg/kg.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1943-1948
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• 2012

Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2835-2838
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• 2013

Background: Prostate cancer features a substantial incidence and mortality burden, similarly to breast cancer, and it ranks among the top ten specific causes of death in males. Objective: To explore the situation of prostate cancer in a healthy population cohort in Eastern Nepal. Materials and Methods: This study was conducted in the Department of General Surgery at B. P. Koirala Institute of Health Sciences, Dharan, Nepal from July 2010 to June 2011. Males above 50 years visiting the Surgical Outpatient Department in BPKIHS were enrolled in the study and screening camps were organized in four Teaching District Hospitals of BPKIHS, all in Eastern Nepal. Digital rectal examination (DRE) was conducted by trained professionals after collecting blood for assessment of serum prostatic specific antigen (PSA). Trucut biopsies were performed for all individuals with abnormal PSA/DRE findings. Results: A total of 1,521 males more than 50 years of age were assessed and screened after meeting the inclusion criteria. The vast majority of individuals, 1,452 (96.2%), had PSA ${\leq}4.0$ ng/ml. Abnormal PSA (>4 ng/ml) was found in 58 (3.8%). Abnormal DRE was found in 26 (1.72%). DRE and PSA were both abnormal in 26 (1.72%) individuals. On the basis of raised PSA or abnormal DRE 58 (3.84%) individuals were subjected to digitally guided trucut biopsy. Biopsy report revealed benign prostatic hyperplasia in 47 (3.11%) and adenocarcinoma prostate in 11 (0.73%). The specificity of DRE was 66.0%with a sensitivity of 90.9% and a positive predictive value of 38.5%. The sensitivity of PSA more than 4ng/ml in detecting carcinoma prostate was 100% and the positive predictive value for serum PSA was 19.0% Conclusions: The overall cancer detection rate in this study was 0.73% and those detected were locally advanced. Larger community-based studies are highly warranted specially among high-risk groups.

• Journal of Korean Medical Science
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• 제33권47호
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• pp.303.1-303.10
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• 2018

Background: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. Methods: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. Results: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (${\geq}T3b$) (odds ratio [OR], 3.005; confidence interval [CI], 1.212-7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079-16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). Conclusion: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2255-2258
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• 2016

Background: Awareness about prostate cancer has increased in the community, and prostate cancer screening examinations, including prostate specific antigen (PSA) assays, are now widely available. Prior to the PSA era, up to 27% of prostate cancers were detected incidentally at the time of transurethral resection of prostate (TURP). After PSA testing became widely available, the incidence of incidentally detected carcinoma prostate in TURP specimens without prior diagnosis reduced to 5-13%. However, the incidence of incidentally detected carcinoma prostate has been reported to vary across the globe since various factors can influence the identification of this malignancy in TURP specimens. In this paper, we focus on rates of incidentally detected prostate cancer in TURP specimens in our hospital and correlate it with various parameters. Materials and Methods: This retrospective study of histopathological findings of biopsy specimens was conducted for patients undergoing TURP during a period of 5 years from April 2010. The inclusion criteria were patients diagnosed with benign prostatic hyperplasia (BPH) (digital rectal examination (DRE) not showing any abnormally hard areas and normal age adjusted PSA values). Patients with elevated PSA, abnormal DRE, documented urinary tract infection and proved adenocarcinoma prostate (CaP) were excluded from the study. The total weight of prostatectomy specimen, occurrence of carcinoma prostate in the chips, percentage of total tissue resected showing malignancy and Gleason's scores were recorded. Results: A total of 597 patients belonging to the inclusion criteria were studied. The incidence of occult CaP in the study group was 5.2 % (31/597). Out of these, 8 belonged to T1a and 23 belonged to T1b stages. The age group 70 - 79 years had the maximum incidence of occult CaP. It was observed that the clinical grading of prostate did not have a bearing on the incidence of occult CaP whereas the weight of resected specimen correlated with the incidence of CaP. The incidence of occult CaP was greater with low volume prostates (<20 g). (P=0.15). Conclusions: The rate of incidentally detected adenocarcinoma prostate in patients undergoing TURP for clinically diagnosed BPH was found to be only 5.2 % in our study which is low when compared with similar studies done elsewhere. The age of the patient and weight of the resected specimen correlated with incidence of occult prostate cancer. The clinical grading of prostate by DRE however, demonstrated no correlation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3437-3445
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• 2016

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.

• 대한중풍순환신경학회지
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• 제15권1호
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• pp.57-65
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• 2014

■ Objectives The purpose of this case report is to show an effect of korean medicine for patient with bilateral abducens nerve palsy. ■ Methods This patient was 58 year-old man who was diagnosed with bilateral abducens nerve palsy. The patient had Diabetes Mellitus, hypertension, benign prostatic hyperplasia and dyslipidemia as underlying diseases. The patient had symptoms of limited eye movement to lateral, diplopia, dizziness and mild headache. He was treated by korean medicine, containing electroacupuncture, pharmacoacupuncture, moxibustion and herb medicines during 13 days of hospitalization and following outpatient department. His eye movement was evaluated by the method of Scott and kraft and discomfort from his symptoms was scored by the Numerous Rating Scale. And other general conditions were measured. ■ Results After that period, patient's abduction deficit was improved and subjective discomfort from his symptoms was getting better. His other conditions were also better, compared with his admission. ■ Conclusion This study suggests that Korean medicine could have a therapeutic effect for bilateral abducens nerve palsy. So, It could help to relieve patient's symptoms and make general conditions better.