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Hyo-Rim Jo,1 Yong-Gyun Kim,2 Won-Suk Sung,1 Kyoung Sun Park,3 Yoon Jae Lee,4 Sun Young Cho,5 Byung-Kwan Seo,6 Young-Ee Kwon,2 Eun-Jung Kim1 1Department of Acupuncture & Moxibustion, Dongguk University Bundang Oriental Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea; 2Central Research Institute, Samik Pharmaceutical Company LTD., Incheon, Republic of Korea; 3Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 4Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Korea; 5IntegroMedLab Company Ltd., Seoul, Republic of Korea; 6Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Seoul, Republic of KoreaCorrespondence: Eun-Jung Kim, Department of Acupuncture & Moxibustion, Dongguk University Bundang Oriental Hospital, 268, Buljeong-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea, Tel +82-31-710-3719, Fax +82-31-710-3780, Email hanijjung@naver.comPurpose: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, associated with poor quality of life and increased patient and healthcare resource expenditure. This randomized controlled trial aims to evaluate the efficacy and safety of SIKD1977 (Sogeonjungtang) in combination with standard treatment and estimate an effective dose for treating PHN.Patients and Methods: This is a protocol for a randomized, placebo-controlled, double-blind, multicenter trial. A total of 90 eligible participants with PHN will be recruited from three hospitals and randomly allocated to high-dose group, low-dose group, or placebo group in a 1:1:1 ratio. The trial will involve a 6-week oral administration of SIKD1977/placebo, and a 1-week follow-up period. The primary outcome will be the weekly average change in average daily pain score (ADPS) from baseline to the end of treatment. The secondary outcomes will include the weekly average changes in ADPS from baseline to week 2, 4, and 7, differences in Short-Form McGill Pain Questionnaire, Visual analogue scale, 5-level EuroQol-5 dimensions, Patient Global Impression of Change, and consumption of rescue drugs. All adverse events will be assessed during the trial.Conclusion: This study will provide evidence for the efficacy and safety of SIKD1977, and an effective dose for PHN.Trial Registration: This protocol has been registered in the Clinical Research Information Service with the identification code KCT0007939.Keywords: postherpetic neuralgia, herbal medicine, SIKD1977, Sogeonjungtang, randomized controlled trial, protocol

Seung-Jun Seo,1,* Chung Wung Bark,2,* Jae-Hong Lim,1 Yong-Gun Kim3 1Industrial Technology Convergence Center, Pohang Accelerator Laboratory, POSTECH, Pohang, Gyeongbuk, 2Department of Electrical Engineering, Gachon University, Seongnam, 3Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea *These authors contributed equally to this work Objective: Maxillary sinus floor augmentation has been shown to be the most predictable surgical technique for enhancing the bone volume in the posterior area of the maxilla. The purpose of this study was to analyze the serial slice image segmentation of newly formed bone and bone substitutes after sinus floor elevation using synchrotron radiation X-ray micro-computed tomography (SR-µCT).Materials and methods: Bone biopsy specimens were collected after 6 months of sinus floor augmentation. From the six bone biopsy specimens, the cross-sectional images at every 8 µm along the apical direction from the inferior border using serial segmentation from three-dimensional reconstructed X-ray images were analyzed. The amount of new bone and bone substitutes were measured at each slicing image (300–430 images per specimen).Results: The bone dynamics between the new bone and bone substitutes along the inferior–superior direction in humans after maxillary sinus floor elevation (MSFE) were analyzed using the whole sample region. Although these observations suggest that the specimens are structurally inhomogeneous, sinus floor elevation was confirmed to be a reliable surgical procedure for increasing the amount of bone.Conclusion: SR-µCT is highly effective for obtaining high-resolution images. An analysis of biological specimens using SR-µCT is quite reliable and this technique will be an important tool in the wide field of tissue engineering. Keywords: maxillary sinus floor elevation, synchrotron radiation, micro-computed tomography, serial segmentation, new bone formation

Hyunjeong Baek,1,* Seunghoon Han,2,3,* Dong-Seok Yim,2,3 Sung Joo Kim,4 Soo-Youn Lee,5 Hye Ryoun Jang,6 Jung Eun Lee,6 Dae Joong Kim,6 Yoon-Goo Kim,6 Ha Young Oh,6 Wooseong Huh6 1Department of Medicine, Kangwon National University School of Medicine, Chuncheon, Republic of Korea; 2Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 3PIPET (Pharmacometrics Institute for Practical Education and Training), Seoul, Republic of Korea; 4Department of Surgery, 5Department of Laboratory Medicine and Genetics, 6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea *These authors equally contributed to this work Abstract: This study aimed to evaluate the change in the pharmacokinetics (PK) of cyclosporine in the non-steady-state period in the first week after renal transplantation; the factors influencing this change, including genetic variability; and the time point concentration that correlated best with drug exposure. Data were obtained from 69 patients, and PK studies were conducted on postoperative days (PODs) 2, 3, and 7. Samples were taken pre-dose and at 1, 2, 3, 4, 6, 8, and 12 hours after drug administration. MDR1, CYP3A4, and CYP3A5 were genotyped. A population PK analysis and correlational analysis between the concentration at each time point and the area under the time–concentration curve were performed. A two-compartment model with first-order absorption was chosen. The rate and extent of drug absorption showed a significant increase on POD3, followed by a slight decrease on POD7. Until POD3, 8 hours post-dose was the single time point concentration that correlated best with drug exposure and 3 hours was the best time point on POD7. In both analyses, the MDR1 genotype showed potential as a factor influencing PK change. We conclude that oral administration of cyclosporine and dose adjustment based on a single concentration measurement might result in unexpected drug exposure during this early posttransplantation period. Keywords: renal transplantation, multidrug resistance 1 (MDR1) gene, cytochrome P450

Yu Seob Shin,1 Li Tao Zhang,1 Chen Zhao,2 Young Gon Kim,1 Jong Kwan Park1 1Department of Urology, Chonbuk National University Medical School, and Institute for Medical Sciences, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; 2Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, People’s Republic of China Purpose: The effects of an anticholinergic or antidiuretic agent as add-on therapy to an ­alpha-blocker for lower urinary tract symptoms (LUTS) according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS.Subjects and methods: Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC), or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS), IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks.Results: A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B, the number of episodes of nocturia in 3 days, nocturnal urine volume, and nocturnal index were significantly decreased using an alpha-blocker plus an antidiuretic agent. In the decreased NBC subgroup of Groups A and B, IPSS storage sub-score, Overactive Bladder Symptom Score, number of episodes of nocturia in 3 days, number of episodes of urgency in 3 days, and NBC index were all significantly decreased using an alpha-blocker plus an anticholinergic agent.Conclusion: An anticholinergic agent or antidiuretic agent as an add-on therapy in men previously treated with an alpha-blocker improves nocturia including LUTS. Keywords: LUTS, nocturia, nocturnal bladder capacity, benign prostatic hyperplasia

Objectives Many chronic kidney disease (CKD) patients have persistent overt proteinuria despite angiotensin receptor blocker (ARB) treatment. This study investigated whether the initial difference in intrarenal renin-angiotensin system activity measured with urinary angiotensinogen would affect the antiproteinuric effects of ARB. Methods Between September 2005 and September 2008, in 50 non-diabetic proteinuric CKD patients not taking renin-angiotensin system inhibitors, the urinary protein/creatinine ratio (P/Cr), angiotensinogen/creatinine ratio (AGT/Cr), plasma renin and aldosterone were measured before starting valsartan, and were followed for 18 months. Results Patients were divided into three groups according to their initial urinary AGT/Cr. The urinary P/Cr was lower in the low angiotensinogen group, but similar in the high and extremely high angiotensinogen groups (1.3±0.38 vs 2.0±0.92 vs 2.2±0.78). In all groups, the urinary P/Cr was decreased most for the first 6 months. The urinary P/Cr reduction at 6 months was greatest in the high angiotensinogen group (-24.2% vs -46.2% vs -16.4%). The urinary AGT/Cr was decreased most in the high angiotensinogen group. Renal functional deterioration was attenuated in the high angiotensinogen group compared with the extremely high angiotensinogen group. Conclusions The antiproteinuric effects of ARB were different according to the initial urinary angiotensinogen levels. These results suggest the potential value of the initial urinary AGT/Cr for predicting the therapeutic effect of ARB in proteinuric non-diabetic CKD patients. [ABSTRACT FROM AUTHOR]

Purpose Activation of the rennin-angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria. Study design Thirty-two patients with non-nephrotic-range proteinuria (0.045-0.23g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50mg/day, and the doses were titrated up to 100mg/day after 6weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24months. Results Baseline characteristics in the two groups were similar. After 24months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group. Conclusion Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD. [ABSTRACT FROM AUTHOR]

Background and Purpose: Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in primary sensory neurons and skin keratinocytes play a crucial role as peripheral pain detectors. Many natural and synthetic ligands have been found to act on thermoTRPs, but little is known about endogenous compounds that inhibit these TRPs. Here, we asked whether resolvin D1 (RvD1), a naturally occurring anti-inflammatory and pro-resolving lipid molecule is able to affect the TRP channel activation.Experimental Approach: We examined the effect of RvD1 on the six thermoTRPs using Ca(2+) imaging and whole cell electrophysiology experiments using the HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. We also checked changes in agonist-specific acute licking/flicking or flinching behaviours and TRP-related mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems with or without inflammation.Key Results: RvD1 inhibited the activities of TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent attenuations in agonist-specific acute pain behaviours by immediate peripheral administration with RvD1 were also observed. Furthermore, local pretreatment with RvD1 significantly reversed mechanical and thermal hypersensitivity in inflamed tissues.Conclusions and Implications: RvD1 was a novel endogenous inhibitor for several sensory TRPs. The results of our behavioural studies suggest that RvD1 has an analgesic potential via these TRP-related mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Interleukin-32 (IL-32) induces various inflammatory molecules in human monocytes and differentiation of monocytes into macrophage-like cells. This study was undertaken to evaluate the effects of IL-32gamma, the most biologically active isoform, on the differentiation and activation of osteoclasts. METHODS: CD14+ monocytes were obtained from healthy volunteers, and samples of synovial tissue and synovial fluid were obtained from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). The concentration and expression levels of IL-32gamma in RA and OA samples were evaluated by enzyme-linked immunosorbent assay and immunoblotting, respectively. To examine the osteoclastogenic effects and functional activities, isolated monocytes were treated with either IL-32gamma or IL-17 in the presence or absence of soluble RANKL (sRANKL) on a culture system and on Osteologic disks. The expression of RANKL and osteoprotegerin (OPG) messenger RNA (mRNA) in RA fibroblast-like synoviocytes (FLS) was measured using reverse transcription-polymerase chain reaction (PCR) and real-time PCR. RESULTS: The concentration and expression levels of IL-32gamma were higher in the RA samples than in the OA samples. Upon costimulation with sRANKL, the osteoclast count and resorbed area increased more significantly in the IL-32gamma-stimulated cultures than in those stimulated with IL-17. In the IL-32gamma-treated group without sRANKL stimulation, osteoclasts were differentiated, but the cells displayed low resorption activity. In RA FLS, RANKL mRNA expression increased in the presence of both IL-32gamma and IL-17. However, transcription of OPG decreased following IL-32gamma stimulation, resulting in a significant increase in the RANKL:OPG ratio. CONCLUSION: Our results suggest that IL-32gamma is a potent mediator of active osteoclast generation in the presence of sRANKL. Moreover, this novel cytokine creates more favorable conditions for osteoclastogenesis in the RA joint by increasing the RANKL:OPG ratio in FLS. [ABSTRACT FROM AUTHOR]

Background: Unstable intertrochanteric fractures in elderly patients are associated with a high rate of complications. The purpose of this investigation was to compare the results of long-stem cementless calcar-replacement hemiarthroplasty with those of treatment with a proximal femoral nail for unstable intertrochanteric fractures in elderly patients.Methods: Fifty-eight elderly patients with an AO/OTA type 31-A2 intertrochanteric fracture of the femur were randomized into two treatment groups and were followed for a minimum of two years. The twenty-nine patients in Group I were treated with a long-stem cementless calcar-replacement prosthesis, and the twenty-nine patients in Group II were treated with a proximal femoral nail. The two treatment groups were comparable with regard to demographic and injury variables.Results: There were no significant differences between the groups in terms of functional outcomes, hospital stay, time to weight-bearing, or general complications. Patients treated with a proximal femoral nail had a shorter operative time, less blood loss, fewer units of blood transfused, a lower mortality rate, and lower hospital costs compared with those treated with the long-stem cementless calcar-replacement prosthesis.Conclusions: In elderly patients with an unstable intertrochanteric femoral fracture, a proximal femoral nail provides superior clinical outcomes but no advantage with regard to functional outcome when compared with a long-stem cementless calcar-replacement arthroplasty.Level Of Evidence: Therapeutic Level I. [ABSTRACT FROM AUTHOR]

Background: Many authors have reported good results with the use of vascularized fibular grafts to treat large osteonecrotic lesions of the femoral head. To our knowledge, there have been no prospective case-controlled studies comparing the effectiveness of vascularized fibular grafting with that of nonvascularized fibular grafting for the prevention of progression and collapse of the lesion.Methods: Nineteen patients (twenty-three hips) with a large osteonecrotic lesion of the femoral head (Stage IIC in ten hips, Stage IIIC in two, and Stage IVC in eleven, according to the classification system of Steinberg et al.) underwent vascularized fibular grafting. This group was retrospectively matched according to the etiology, stage, and size of the lesion to a group of nineteen patients (twenty-three hips) who underwent nonvascularized fibular grafting during the same time period. A prospective case-controlled study of the two groups, with a mean duration of follow-up of four years, was then performed.Results: The mean Harris hip score improved for 70% of the hips treated with a vascularized graft and 35% of the hips treated with a nonvascularized graft (p < 0.05). At the time of the final follow-up, nine of the ten hips with a Stage-IIC lesion treated with a vascularized fibular graft had not collapsed whereas seven of the thirteen hips with a larger lesion (Stage IIIC or IVC) had collapsed. Three hips (13%) were converted to a total hip replacement. The mean dome depression measured 2.8 mm. In the group treated with a nonvascularized graft, five of the ten Stage-IIC hips had not collapsed and eleven of the thirteen hips with a larger lesion had collapsed. Five (22%) of the hips were converted to a total hip replacement. The mean dome depression measured 4.3 mm. The rates of radiographic progression and collapse were significantly lower and the mean dome depression was significantly less in the group treated with a vascularized fibular graft (p < 0.05).Conclusions: Vascularized fibular grafting was associated with better clinical results and was more effective than nonvascularized fibular grafting for the prevention of collapse of the femoral head in a matched population with a Steinberg Stage-IIC or larger osteonecrotic lesion. The results of vascularized grafting were best when the procedure was used to treat precollapse lesions (Steinberg Stage IIC). [ABSTRACT FROM AUTHOR]