• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3747-3752
• /
• 2014

Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD), $10.4{\pm}3.02$ and $8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$, p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD.

• Medical Lasers
• /
• v.8 no.2
• /
• pp.64-73
• /
• 2019

Background and Objectives The effectiveness of many physiotherapy modalities in reducing subcutaneous fat has been investigated in numerous previous studies. However, to the best of our knowledge, there have been no attempts to determine the effectiveness of physiotherapy modalities in body contouring. The present report determined the effect of 448-kHz capacitive resistive monopolar radiofrequency (CRMRF) in a porcine model. Materials and Methods This study investigated the effect of selective destruction of the subcutaneous fat layer in abdominal fat tissue using CRMRF. The effects of two types of CRMRF (capacitive electric transfer (CET) and resistive electric transfer (RET)) treatment were evaluated using regular digital photography in addition to thermal imaging evaluation, ultrasound measurement, hematological evaluation, and histologic analyses (H&E (hematoxylin and eosin), Oil red O, and immunohistochemistry staining). Results Preclinical evaluation was performed to obtain the data for comparison of the safety and efficacy of the subcutaneous fat reduction after applying CRMRF using CET and RET. After treatment, the thermal transmission was effective, and a 42-47℃ temperature change was observed in the fat layer while an approximately temperature of 42℃ was confirmed on the skin surface. Moreover, after the application of both types of CRMRF treatment, fibrotic septa were observed in the adipose tissue induced by heat at the treatment sites. TUNEL staining was also performed to confirm the process of apoptosis in the adipocytes. Conclusion These results suggest that both CET and RET for CRMRF treatment are safe and effective for subcutaneous fat reduction in a porcine model.

• YAKHAK HOEJI
• /
• v.49 no.5
• /
• pp.422-427
• /
• 2005

Our previous data showed the protein isolated from Coptidis Rhizoma (CRP) had antifungal activity. In present study, we examined mode of action of the CRP and its activity against subcutaneous candidiasis due to C. albicans yeast cells. Results showed that the CRP blocked hyphal production from yeast form of C. albicans. The CRP also activated RAW 264.7 monocyte/macrophage cell line, which resulted in nitiric oxide (NO) production from the cells. This activation seemed to increase macrophage phagocytosis to destroy the invaders. Like other antimicrobial peptides, CRP was influenced by ionic strength, thus resulting in a decrease of antifungal activity. In murine model of a subcutaneous candidiasis, the sizes of infected areas of the nude mice given the CRP after subcutaneous injection of C. albicans yeast cells to the dorsal skin were $90\%$ less than those of the nude mice groups that received DPBS instead of the CRP. All data indicate that the CRP, which appeared to act like an antimicrobial peptide and to inhibit the morphological transition from blastoconidia, was effec­tive against the subcutaneous disease.

• Journal of Veterinary Science
• /
• v.22 no.5
• /
• pp.47.1-47.10
• /
• 2021

Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.2
• /
• pp.153-160
• /
• 2017

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

• IMMUNE NETWORK
• /
• v.15 no.2
• /
• pp.83-90
• /
• 2015

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

• Journal of Acupuncture Research
• /
• v.24 no.4
• /
• pp.115-124
• /
• 2007

Objective: To evaluate the effect of acupuncture on streptozotocin(STZ)-treated rats by subcutaneous implantation of osmotic pump. Methods: STZ was administered to rats at a low dose with osmotic pump to induce beta cell death and diabetes (STZ osmotic pump model), The experimental animals were divided into 4 groups: 1. The control group which was not treated in the STZ osmotic pump model 2. The sham group which was acupunctured at an arbitrary point in the STZ osmotic pump model 3. The sample A group which was acupunctured at the Chung-wan($CV_{12}$) in the STZ osmotic pump model 4. The sample B group which was acupunctured at the Chok-samni($ST_{36}$) in the STZ osmotic pump model. The effect of acupuncture in the STZ osmotic pump model was observed by measuring the serum glucose level and immunostaining of pancreatic tissue of the rats. Results : STZ injection by subcutaneous implantation of osmotic pump caused hyperglycemia by destroying the pancreatic beta cell selectively. Acupuncture at the Chung-wan acupuncture point($CV_{12}$) and Jhok-samni acupuncture point ($ST_{36}$) in the STZ osmotic pump model separately resulted in a decrease of the serum glucose level. In addition, the cyto-protective effect of the pancreatic beta-cell was detected in the STZ osmotic pump model by acupuncture. And there were few differences between the effects of acupuncture at the CV12 and $ST_{36}$. Conclusion : Acupuncture at the CV12 and ST36 had beneficial effects on Type II diabetes mellitus, and action mechanism of the effect was thought to be concerned with secretion of endogenous beta-endorphin.

• Journal of Preventive Medicine and Public Health
• /
• v.53 no.4
• /
• pp.256-265
• /
• 2020

Objectives: We compared the associations of 3 computed tomography (CT)-based abdominal adiposity indexes with non-alcoholic fatty liver disease (NAFLD) among middle-aged Korean men and women. Methods: The participants were 1366 men and 2480 women community-dwellers aged 30-64 years. Three abdominal adiposity indexes-visceral fat area (VFA), subcutaneous fat area (SFA), and visceral-to-subcutaneous fat ratio (VSR)-were calculated from abdominal CT scans. NAFLD was determined by calculating the Liver Fat Score from comorbidities and blood tests. An NAFLD prediction model that included waist circumference (WC) as a measure of abdominal adiposity was designated as the base model, to which VFA, SFA, and VSR were added in turn. The area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated to quantify the additional predictive value of VFA, SFA, and VSR relative to WC. Results: VFA and VSR were positively associated with NAFLD in both genders. SFA was not significantly associated with NAFLD in men, but it was negatively associated in women. When VFA, SFA, and VSR were added to the WC-based NAFLD prediction model, the AUC improved by 0.013 (p<0.001), 0.001 (p=0.434), and 0.009 (p=0.007) in men and by 0.044 (p<0.001), 0.017 (p<0.001), and 0.046 (p<0.001) in women, respectively. The IDI and NRI were increased the most by VFA in men and VSR in women. Conclusions: Using CT-based abdominal adiposity indexes in addition to WC may improve the detection of NAFLD. The best predictive indicators were VFA in men and VSR in women.

• Clinical and Experimental Pediatrics
• /
• v.56 no.3
• /
• pp.116-124
• /
• 2013

Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

• Korean Journal of Clinical Pharmacy
• /
• v.26 no.1
• /
• pp.59-69
• /
• 2016

Background: The subcutaneous formulation of biologic disease-modifying antirheumatic drugs (DMARDs) was preferred due to favored self-administration and would be an economical treatment option for patients with rheumatoid arthritis. This study was to compare the economic impact of biologic DMARDs administered by subcutaneous injection in patients with rheumatoid arthritis who had inadequate response to conventional DMARDs. Methods: The cost-minimization analysis was conducted to estimate the lifetime health care costs of treatment sequences with subcutaneous biologic DMARDs as first-line therapy from a health care system perspective. The Markov model was developed to represent the transitions through treatment sequences based on American College of Rheumatology response rate and discontinuation rate. The health care costs comprised the cost of medications, administration, dispensing, outpatient visits, test/diagnostic examination, palliative therapy and treatment of serious infection. All costs were expressed in 2016 Korean Won (KRW) and discounted at 5%. Results: The mean lifetime health care cost per patient was lowest in the etanercept sequence, which was estimated at KRW 63,441,679. The incremental costs of the treatment sequence started with adalimumab, golimumab, abatacept, and tocilizumab were KRW 7,985,730, KRW 4,064,669, KRW 2,869,947, and KRW 4,282,833, respectively, relative to etanercept sequence. These differences in costs mainly were attributable to medication costs. One-way and probabilistic sensitivity analyses confirmed that etanercept represented the option with the lowest cost compared with comparators. Conclusion: This study found that etanercept is likely a cost-saving treatment option among subcutaneous biologic DMARDs in patients with rheumatoid arthritis.