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1.
Reg Anesth Pain Med ; 49(3): 168-173, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-37353356

ABSTRACT

INTRODUCTION: Fluoroscopy can improve the success rate of thoracic epidural catheter placement (TECP). Real-time ultrasound (US)-guided TECP was recently introduced and showed a high first-pass success rate. We tested whether real-time US-guided TECP results in a non-inferior first-pass success rate compared with that of fluoroscopy-guided TECP. METHODS: In this single-center, non-inferiority, randomized trial, the primary outcome was the comparison of the first-pass success rate of TECP between real-time US guidance (US group) and fluoroscopic guidance (fluoroscopy group). Secondary outcomes included time to identifying epidural space, procedure time, total number of needle passes, number of skin punctures, final success, and cross-over success. RESULTS: We randomly assigned 132 patients to the allocated groups. The difference in the first-pass success rate between the groups did not exceed the non-inferiority margin of 15% (US group: 66.7% vs fluoroscopy group: 68.2%; difference -1.5%, 95% exact CI: -14.9% to 11.9%). The difference in the final success rate also did not differ between the groups (98.5% vs 100.0%; difference -1.5%, 95% exact CI: -4.0% to 1.0%). The time to identifying epidural space (45.6 (34-62) vs 59.0 (42-77) s, p=0.004) and procedure time (39.5 (28-78) vs 112.5 (93-166) s, p<0.001) were significantly shorter in the US group. CONCLUSIONS: Real-time US guidance provided a non-inferior success rate and shorter time spent on preparation and procedure compared with fluoroscopic guidance in TECP. TRIAL REGISTRATION NUMBER: KCT0006521.


Subject(s)
Epidural Space , Ultrasonography, Interventional , Humans , Catheters , Epidural Space/diagnostic imaging , Fluoroscopy/methods , Ultrasonography , Ultrasonography, Interventional/methods
2.
Nat Commun ; 14(1): 5869, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37737221

ABSTRACT

Graft-versus-host disease (GvHD) is a severe complication of hematopoietic stem cell transplantation driven by activated allogeneic T cells. Here, we identify a distinct subset of T cell factor-1 (TCF1)+ CD8+ T cells in mouse allogeneic and xenogeneic transplant models of acute GvHD. These TCF1+ cells exhibit distinct characteristics compared to TCF1- cells, including lower expression of inhibitory receptors and higher expression of costimulatory molecules. Notably, the TCF1+ subset displays exclusive proliferative potential and could differentiate into TCF1- effector cells upon antigenic stimulation. Pathway analyses support the role of TCF1+ and TCF1- subsets as resource cells and effector cells, respectively. Furthermore, the TCF1+ CD8+ T cell subset is primarily present in the spleen and exhibits a resident phenotype. These findings provide insight into the differentiation of allogeneic and xenogeneic CD8+ T cells and have implications for the development of immunotherapeutic strategies targeting acute GvHD.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Animals , Mice , CD8-Positive T-Lymphocytes , Cell Differentiation , Hematopoietic Stem Cell Transplantation/adverse effects , Phenotype , Humans
3.
Front Immunol ; 14: 1117092, 2023.
Article in English | MEDLINE | ID: mdl-37409128

ABSTRACT

In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give rise to Tim-3+PD-1+ terminally differentiated CD8 T cells that retain their effector functions. Tpex cells are thus essential to maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation, and only they respond to PD-1-targeted therapy. Despite their potential as a crucial therapeutic target for immune interventions, the mechanisms controlling the maintenance of virus-specific Tpex cells remain to be determined. We observed approximately 10-fold fewer Tpex cells in the spleens of mice chronically infected with lymphocytic choriomeningitis virus (LCMV) one-year post-infection (p.i.) than at three months p.i. Similar to memory CD8 T cells, Tpex cells have been found to undergo self-renewal in the lymphoid organs, prominently the bone marrow, during chronic LCMV infection. Furthermore, ex vivo treatment with IL-15 preferentially induced the proliferation of Tpex cells rather than the terminally differentiated subsets. Interestingly, single-cell RNA sequencing analysis of LCMV-specific exhausted CD8 T cells after ex vivo IL-15 treatment compared with those before treatment revealed increased expression of ribosome-related genes and decreased expression of genes associated with the TCR signaling pathway and apoptosis in both Tpex and Ttex subsets. The exogenous administration of IL-15 to chronically LCMV-infected mice also significantly increased self-renewal of Tpex cells in the spleen and bone marrow. In addition, we assessed the responsiveness of CD8 tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma patients to IL-15. Similar to the data we obtained from chronic viral infection in mice, the expansion of the Tpex subset of PD-1+ CD8 TILs upon ex vivo IL-15 treatment was significantly higher than that of the terminally differentiated subset. These results show that IL-15 could promote self-renewal of Tpex cells, which has important therapeutic implications.


Subject(s)
Interleukin-15 , Lymphocytic Choriomeningitis , Programmed Cell Death 1 Receptor , Animals , Mice , CD8-Positive T-Lymphocytes , Interleukin-15/pharmacology , Lymphocytic choriomeningitis virus , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction
4.
Medicina (Kaunas) ; 59(5)2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37241078

ABSTRACT

Background and Objectives: With the aging population, the incidence of degenerative lumbar spinal stenosis (LSS) is increasing. Sarcopenia is an age-related muscular decrease. Although epidural balloon neuroplasty is effective in patients with LSS refractory to conventional treatments, its effect has not been assessed in patients with sarcopenia. Therefore, this study evaluated the effect of epidural balloon neuroplasty in patients with LSS and sarcopenia. Materials and Methods: This retrospective study reviewed the following details from the electronic medical records: patient characteristics, including sex, age, body mass index, diabetes, hypertension, stenosis grading, pain duration, location, pain intensity, and medications. Back and leg pain intensity was evaluated before and after the procedure at one, three, and six months during the follow-up period. A generalized estimating equations model was used at six months follow-up. Patients were divided into sarcopenia and non-sarcopenia groups using the cross-sectional area of the psoas muscle at the level of L3 on magnetic resonance imaging. Results: A total of 477 patients were included (sarcopenia group: 314 patients, 65.8%; non-sarcopenia group: 163 patients, 34.2%). Age, sex, body mass index, and medication quantification scale III were statistically different between both groups. The generalized estimating equations analyses-with unadjusted and adjusted estimation-revealed a significantly reduced pain intensity after the procedure compared to the baseline in both groups. The difference in pain intensity between both groups was not statistically different. Conclusions: Percutaneous epidural balloon neuroplasty may be considered for patients with chronic lumbar LSS regardless of accompanying sarcopenia.


Subject(s)
Spinal Stenosis , Humans , Aged , Spinal Stenosis/complications , Spinal Stenosis/surgery , Retrospective Studies , Lumbar Vertebrae/surgery , Lumbar Vertebrae/pathology , Catheters , Constriction, Pathologic , Treatment Outcome
5.
Pain Res Manag ; 2019: 7513617, 2019.
Article in English | MEDLINE | ID: mdl-31065303

ABSTRACT

Background: Although fluoroscopic guidance is recommended highly for more accurate lumbar interlaminar epidural steroid injection (L-ESI), many physicians still use a nonimage-guided approach for L-ESIs. However, because of its associated risk of radiation and increased medical expense, the cost-effectiveness and safety of fluoroscopy-guided ESI have been called into question. The goal of this retrospective matched paired analysis in the same individuals was to assess the effectiveness and prevalence of complications of nonimage-guided L-ESI compared to those of fluoroscopy-guided L-ESI. Methods. Between 2015 and 2016, 94 patients who received both nonimage- and fluoroscopy-guided L-ESIs were analyzed retrospectively. The changes of the numeric rating scale (NRS) in pain intensity and functional outcome and the differences in the number of complications between blind and fluoroscopy-guided L-ESIs in the same individuals were evaluated by a matched paired analysis. Results: Of the 94 patients, the differences in NRS before and after the procedure were 1.29 (95% confidence interval (CI) = 0.94-1.65) for the nonimage-guided group and 1.64 (95% CI = 1.28-2.01) for the fluoroscopy-guided group (p=0.16). More subjective functional improvement was observed in fluoroscopy-guided L-ESI (57, 60.6%) than in nonimage-guided L-ESI (47, 50.0%) without statistical significance (p=0.16). Nine (9.6%) patients in the nonimage-guided group experienced complications related to the procedure overall compared to 4 (4.3%) in the fluoroscopy-guided group (p=0.27). Conclusions: In this study, both blind and image-guided L-ESI techniques included similar extents of postprocedural outcomes and complications. Physicians should consider the risks associated with the two different techniques overall and develop ways to individualize the procedure to decrease the risk of complications and improve the positive outcomes of lumbar epidural steroid injections.


Subject(s)
Epidural Space/diagnostic imaging , Injections, Epidural/methods , Radiography, Interventional/methods , Adult , Epidural Space/surgery , Female , Fluoroscopy/adverse effects , Fluoroscopy/methods , Humans , Injections, Epidural/adverse effects , Lumbosacral Region , Male , Middle Aged , Radiography, Interventional/adverse effects , Retrospective Studies , Steroids/administration & dosage
6.
Blood Adv ; 2(3): 210-223, 2018 02 13.
Article in English | MEDLINE | ID: mdl-29386194

ABSTRACT

Adoptive therapy with ex vivo-expanded genetically modified antigen-specific T cells can induce remissions in patients with relapsed/refractory cancer. The clinical success of this therapy depends upon efficient transduction and expansion of T cells ex vivo and their homing, persistence and cytotoxicity following reinfusion. Lower rates of ex vivo expansion and clinical response using anti-CD19 chimeric antigen receptor (CAR) T cells have been seen in heavily pretreated lymphoma patients compared with B-cell acute lymphoblastic leukemia patients and motivate the development of novel strategies to enhance ex vivo T cell expansion and their persistence in vivo. We demonstrate that inhibition of phosphatidylinositol 3-kinase δ (PI3Kδ) and antagonism of vasoactive intestinal peptide (VIP) signaling partially inhibits the terminal differentiation of T cells during anti-CD3/CD28 bead-mediated expansion (mean, 54.4% CD27+CD28+ T cells vs 27.4% in control cultures; P < .05). This strategy results in a mean of 83.7% more T cells cultured from lymphoma patients in the presence of PI3Kδ and VIP antagonists, increased survival of human T cells from a lymphoma patient in a murine xenograft model, enhanced cytotoxic activity of antigen-specific human CAR T cells and murine T cells against lymphoma, and increased transduction and expansion of anti-CD5 human CAR T cells. PI3Kδ and VIP antagonist-expanded T cells from lymphoma patients show reduced terminal differentiation, enhanced polyfunctional cytokine expression, and preservation of costimulatory molecule expression. Taken together, synergistic blockade of these pathways is an attractive strategy to enhance the expansion and functional capacity of ex vivo-expanded cancer-specific T cells.


Subject(s)
Cell Culture Techniques/methods , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Immunotherapy, Adoptive/methods , T-Lymphocytes/cytology , Vasoactive Intestinal Peptide/antagonists & inhibitors , Adult , Aged , Animals , Cellular Senescence/drug effects , Female , Heterografts , Humans , Lymphoma/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Mice , Middle Aged , Neurotensin/pharmacology , Purines/pharmacology , Quinazolinones/pharmacology , Recombinant Fusion Proteins/pharmacology , T-Lymphocytes/drug effects , Vasoactive Intestinal Peptide/pharmacology
7.
Pain Physician ; 20(6): E841-E848, 2017 09.
Article in English | MEDLINE | ID: mdl-28934790

ABSTRACT

BACKGROUND: Recently, transforaminal balloon adhesiolysis was introduced to manage patients with chronic radicular pain occurring with or without low back pain. However, the factors associated with successful responses to transforaminal balloon adhesiolysis are not known. OBJECTIVE: To evaluate the factors associated with successful responses to transforaminal balloon adhesiolysis for chronic lumbar spinal stenosis. STUDY DESIGN: This is a retrospective observational study. SETTING: A single pain clinic of tertiary medical center in Seoul, Republic of Korea. METHODS: From January 2013 to December 2014, a retrospective review of 199 patients with chronic lumbar foraminal stenosis, who were scheduled for transforaminal balloon adhesiolysis, was performed. Patients were considered successful responders if they showed either of the following: 1) a decrease of more than 50% on the numerical rating scale or 2) a decrease of more than 30% on the numerical rating scale and improved functional status 3 months after transforaminal balloon adhesiolysis. Logistic regression analysis was performed to determine the factors associated with successful responses to this surgical procedure. RESULTS: Three months after the transforaminal balloon adhesiolysis, 49.4% of patients were considered successful responders. Multivariate logistic regression analysis showed that factors other than degenerative disc herniation were independently associated with successful responses 3 months after this surgical procedure (odds ratio = 0.327; 95% confidence interval = 0.129 - 0.827; P = 0.018). LIMITATIONS: The definition of successful response used in this study differed from the ones used in previous studies; a different definition may have led to different results. Further, the effects of other factors (ballooning, drugs, and saline washes) could not be excluded from our study. In addition, the correct method of assessing functional status, the Oswestry Disability Index, could not be used in this study; hence, the final results may have been affected. CONCLUSION: These results suggest that transforaminal balloon adhesiolysis can successfully lead to improvement of symptoms in patients with chronic lumbar foraminal stenosis caused primarily by degenerative disc herniation.Institutional Review Board (IRB) approval number: 2016-0228.Key words: Balloon, epidural adhesiolysis, chronic pain, radicular pain, lumbar spine, foraminal stenosis, degenerative disc.


Subject(s)
Catheterization/methods , Chronic Pain/surgery , Intervertebral Disc Degeneration/surgery , Low Back Pain/surgery , Lumbar Vertebrae/surgery , Spinal Stenosis/surgery , Adult , Aged , Chronic Pain/diagnostic imaging , Chronic Pain/etiology , Epidural Space/diagnostic imaging , Epidural Space/surgery , Female , Humans , Intervertebral Disc Degeneration/complications , Intervertebral Disc Degeneration/diagnostic imaging , Low Back Pain/diagnostic imaging , Low Back Pain/etiology , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Spinal Stenosis/complications , Spinal Stenosis/diagnostic imaging , Treatment Outcome
8.
Clin J Pain ; 33(10): 905-911, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28118255

ABSTRACT

OBJECTIVES: Although nicotine has an analgesic effect, the incidence and severity of chronic pain is higher in smokers than nonsmokers. Acute pain is more intense in smokers during the perioperative period. This study evaluated whether smokers require higher doses of opioid to reduce pain when they undergo surgery. METHODS: A retrospective review of 236 patients who had intravenous patient-controlled analgesia after distal gastrectomy with gastroduodenostomy between October 2013 and September 2014 was performed to analyze the difference in postoperative opioid requirements between smokers and nonsmokers. Total opioid consumption was observed from the day of operation to postoperative day 2. Patients were grouped into smokers (N=117) and nonsmokers (N=119) for comparison. Simple and multiple regression analyses were performed to identify predictors of postoperative opioid requirements. RESULTS: Opioid consumption by male smokers was higher than nonsmokers. Multiple regression analysis showed that age, smoking, and amount of intraoperative remifentanil were the only significant factors for postoperative opioid requirements. DISCUSSION: Our results suggest that smokers undergoing distal gastrectomy with gastroduodenostomy required more opioid than nonsmokers for postoperative pain. Old age, smoking status, and increment of remifentanil use seemed to be predictors of postoperative opioid consumption.


Subject(s)
Analgesics, Opioid/therapeutic use , Pain, Postoperative/complications , Pain, Postoperative/drug therapy , Smoking , Stomach Neoplasms/surgery , Age Factors , Analgesia, Patient-Controlled/statistics & numerical data , Duodenostomy , Female , Gastrectomy , Gastrostomy , Humans , Male , Middle Aged , Pain, Postoperative/physiopathology , Regression Analysis , Retrospective Studies , Sex Factors , Smoking/physiopathology , Stomach Neoplasms/complications , Stomach Neoplasms/physiopathology
9.
Medicine (Baltimore) ; 95(43): e5206, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27787378

ABSTRACT

There is no study of optimal volume of contrast medium to use in cervical interlaminar epidural injections (CIEIs) for appropriate spread to target lesions. To determine optimal volume of contrast medium to use in CIEIs. We analyzed the records of 80 patients who had undergone CIEIs. Patients were divided into 3 groups according to the amount of contrast: 3, 4.5, and 6 mL. The spread of medium to the target level was analyzed. Numerical rating scale data were also analyzed. The dye had spread to a point above the target level in 15 (78.9%), 22 (84.6%), and 32 (91.4%) patients in groups 1 to 3, respectively. The dye reached both sides in 14 (73.7%), 18 (69.2%), and 23 (65.7%) patients, and reached the ventral epidural space in 15 (78.9%), 22 (84.6%), and 30 (85.7%) patients, respectively. There were no significant differences of contrast spread among the groups. There were no significant differences in the numerical rating scale scores among the groups during the 3 months. When performing CIEIs, 3 mL medication is sufficient volume for the treatment of neck and upper-extremity pain induced by lower cervical degenerative disease.


Subject(s)
Fluoroscopy/methods , Glucocorticoids/administration & dosage , Imaging, Three-Dimensional , Neck Pain/drug therapy , Pain/drug therapy , Spinal Diseases/complications , Arm , Cervical Vertebrae , Female , Follow-Up Studies , Humans , Injections, Epidural , Magnetic Resonance Imaging , Male , Middle Aged , Neck Pain/diagnosis , Neck Pain/etiology , Pain/diagnosis , Pain/etiology , Pain Measurement , Retrospective Studies , Spinal Diseases/diagnosis , Treatment Outcome
10.
J Org Chem ; 81(17): 7432-8, 2016 09 02.
Article in English | MEDLINE | ID: mdl-27482931

ABSTRACT

This paper describes the stereoselective total syntheses of (+)-1-deoxygalactonojirimycin and (-)-1-deoxygulonojirimycin via new chiral building blocks syn,anti,syn-oxazine 11a and syn,syn,anti-oxazine 13a. These were accomplished in four steps in 44.1 and 33.7% overall yields, respectively. These chirons were derived from the stereoselective addition of a nucleophile to the corresponding aldehydes of syn,anti-oxazine 10 and syn,syn-oxazine 12. Furthermore, this paper describes the stereochemical analysis of three types of chiral 1,3-oxazines; anti,syn-, syn,anti-, and syn,syn-oxazines using the NOESY technique.

11.
Int J Neuropsychopharmacol ; 18(1)2014 Oct 31.
Article in English | MEDLINE | ID: mdl-25539504

ABSTRACT

BACKGROUND: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. METHODS: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. RESULTS: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. CONCLUSIONS: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions.


Subject(s)
Brain/drug effects , Central Nervous System Agents/pharmacology , Cocaine-Related Disorders/drug therapy , Drug-Seeking Behavior/drug effects , Oxytocin/pharmacology , Receptors, AMPA/metabolism , Animals , Brain/physiopathology , Cocaine/administration & dosage , Cocaine-Related Disorders/physiopathology , Dietary Sucrose/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Dose-Response Relationship, Drug , Drug-Seeking Behavior/physiology , Extinction, Psychological/drug effects , Extinction, Psychological/physiology , Extracellular Signal-Regulated MAP Kinases/metabolism , Male , Phosphorylation/drug effects , Rats, Sprague-Dawley , Reinforcement Schedule , Self Administration
12.
Lab Anim Res ; 30(4): 151-60, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25628725

ABSTRACT

Red ginseng and its extracts have been used as traditional medicines and functional foods in countries worldwide. The aim of this study was to examine the bioavailability of pectin lyase-modified red ginseng extracts (GS-E3D), and the effects of GS-E3D on adipogenesis of 3T3-L1 adipocytes, as well as on metabolic disorders such as hyperglycemia, dyslipidemia, and fatty liver in high-fat diet fed obese C57BL/6 mice. Mice were divided into 5 groups: normal diet group, high fat diet-vehicle group, high fat diet + 0.1 g/kg GS-E3D (0.1-GS-E3D), high fat diet + 0.3 g/kg (0.3-GS-E3D), high fat diet + 1.0 g/kg (1.0-GS-E3D). Treatment of GS-E3D reduced differentiation of 3T3-L1 adipocytes with low cytotoxicity. In the animal model, compared to the high fat diet control, serum glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TG, and leptin level were reduced in treatment animals in a dose-dependent manner. In addition, we found that GS-E3D could decrease total hepatic lipid droplets. These results suggest that GS-E3D, as a dietary supplement, has beneficial effects on obesity and may have useful effects in health-care products.

13.
Am J Rhinol Allergy ; 27(5): e135-9, 2013.
Article in English | MEDLINE | ID: mdl-24119594

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is often accompanied by multiple ocular symptoms. This study aimed to evaluate the prevalence of ocular symptoms and the impact of ocular symptoms on the quality of life in patients with AR. METHODS: One thousand one hundred seventy-four patients with AR were enrolled from 24 centers in Korea. They were classified into four groups according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guideline and also classified into perennial AR (PAR) and seasonal AR groups. All patients were asked to complete the questionnaire regarding the presence of ocular symptoms, such as eye itching, watery eyes, and red eyes. The correlation between ocular symptoms and the rest of the quality-of-life areas in the Mini-Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) was also asked. RESULTS: Seven hundred nineteen (61.2%) of 1174 patients had ocular symptoms. In detail, the numbers of patients with eye itching, watery eyes, red eyes, and other ocular symptoms were 605 (51.5%), 313 (26.7%), 207 (17.6%), and 66 (5.6%), respectively. Female patients (72.5%) complained of ocular symptoms more commonly than male patients (55.1%). The patients with moderate-severe persistent AR showed the highest prevalence of ocular symptoms. The correlation coefficients between ocular symptoms and the rest of the quality-of-life areas in the Mini-RQLQ were statistically significant (p < 0.05). CONCLUSION: Sixty-one percent of Korean AR patients experienced ocular symptoms. The patients who were women and had PAR and more severe AR showed higher prevalence of ocular symptoms. The ocular symptoms might have a significant impact on the quality of life in patients with AR.


Subject(s)
Eye Diseases/epidemiology , Rhinitis, Allergic, Perennial/epidemiology , Rhinitis, Allergic, Seasonal/epidemiology , Adult , Disease Progression , Eye Diseases/physiopathology , Female , Humans , Korea , Male , Middle Aged , Prevalence , Quality of Life , Rhinitis, Allergic, Perennial/physiopathology , Rhinitis, Allergic, Seasonal/physiopathology , Sex Factors , Surveys and Questionnaires , Young Adult
14.
J Ethnopharmacol ; 133(3): 973-9, 2011 Feb 16.
Article in English | MEDLINE | ID: mdl-20637275

ABSTRACT

AIM OF THIS STUDY: Citrus unshiu (Satsuma mandarin, SM) is a citrus fruit the peel of which has been used as a traditional Chinese medicine to treat common cold, relieve exhaustion, and cancer. In this study, we examined how effectively the content and peel extracts of SM can suppress cancer growth. The mechanism underlying cancer-suppressing properties of SM was investigated in tumor-bearing mice with renal carcinoma cell, Renca. MATERIALS AND METHODS: Effectiveness of SM in tumor suppression was evaluated by measuring size of tumor mass in tumor-bearing mice treated with various doses of SM content and peel extracts. Proliferation of tumor cells and splenocytes was determined by MTT assay and [³H]TdR uptake, respectively. Relevant immunological mechanisms were chased by assaying cytokines including TGF-ß, IL-6, IFN-γ, and TNF-α by ELISA. RESULTS: The content and peel extracts of SM inhibited the growth of tumor cells in tumor-bearing mice. Especially, average tumor volume of two groups treated with 3 and 30 mg peel extracts per mouse weight (kg) were significantly decreased to 52.32% (p<0.05) and 68.72% (p<0.01), respectively. To identify tumor regression mechanism, anti-tumor cytokines measured in Con A-activated splenocytes from tumor-bearing mice. IFN-γ was increased in both of the peel extract-treated groups, while TNF-α, which had been decreased by tumor growth, was rescued to the normal level in SM content and peel extracts-treated groups. However, SM content and peel extracts did not inhibit proliferation and tumor-proliferative cytokines including TGF-ß and IL-6 production of tumor cells. CONCLUSION: These results indicate that SM content and peel extracts have anti-tumor properties in the tumor-bearing murine model. The mechanism underlying the anti-tumor effects of SM extracts is strongly suggested to be via boosting cytokines such as IFN-γ and TNF-α, enhancing immune-mediated anti-tumor properties.


Subject(s)
Carcinoma, Renal Cell/pathology , Cell Division/drug effects , Citrus/chemistry , Disease Models, Animal , Kidney Neoplasms/pathology , Plant Extracts/pharmacology , Animals , Carcinoma, Renal Cell/metabolism , Cell Division/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Chromatography, High Pressure Liquid , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Flavonoids/analysis , Kidney Neoplasms/metabolism , Lymphocytes/cytology , Lymphocytes/drug effects , Mice , Mice, Inbred BALB C , Spleen/cytology , Spleen/drug effects
15.
Otolaryngol Head Neck Surg ; 141(1): 91-6, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19559965

ABSTRACT

OBJECTIVE: Chronic rhinosinusitis (CRS) is characterized by persistent inflammation and tissue remodeling of the nasal mucosa. Adenoidectomy is an effective surgical treatment in pediatric CRS. To evaluate the effect of pediatric CRS on the severity and characteristics of adenoid inflammation, the authors evaluated the expressions of inflammatory cell activation markers and tissue remodeling in adenoid tissues associated with cytokines tissue-remodeling-associated cytokines in adenoid tissues. STUDY DESIGN AND SETTING: A prospective controlled study on 40 pediatric patients admitting for adenotonsillectomy. SUBJECTS AND METHODS: Immunoassays were performed on adenoid tissues homogenates from 16 children with CRS and from 24 children without CRS to quantify the levels of inflammatory cell activation markers, such as soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23), IL-6, eosinophilic cationic protein (ECP), and tryptase, and the levels of cytokines associated with tissue remodeling, such as transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitor of metalloproteinase (TIMP)-1. RESULTS: The mean levels (the ratio to albumin level) of sIL-2R, TGF-beta1, MMP-2, MMP-9, and TIMP-1 were significantly higher in adenoid tissues of patients with CRS (27.31+/-30.32, 4894.65+/-2388.77, 500.13+/-604.59, and 23.06+/-10.37, respectively) than those without it (16.27+/-10.93, 2635.51+/-1448.63, 120.87+/-321.50, 16.74+/-11.10, and 7.39+/-3.12, respectively; all P<0.05). Regarding the severity of CRS, ECP level was significantly higher in patients with severe CRS than in those with mild to moderate CRS (P=0.033). CONCLUSIONS: Adenoid tissues in pediatric CRS patients had higher levels of tissue-remodeling-associated cytokines, which may explain the relationship between pediatric CRS and adenoid inflammation.


Subject(s)
Adenoids/immunology , Biomarkers/analysis , Rhinitis/immunology , Sinusitis/immunology , Adolescent , Child , Child, Preschool , Chronic Disease , Eosinophil Cationic Protein/immunology , Female , Humans , Interleukin-6/immunology , Male , Matrix Metalloproteinase 2/immunology , Matrix Metalloproteinase 9/immunology , Prospective Studies , Receptors, IgE/immunology , Receptors, Interleukin-2/immunology , Statistics, Nonparametric , Tissue Inhibitor of Metalloproteinase-1/immunology , Transforming Growth Factor beta1/immunology , Tryptases/immunology
16.
Laryngoscope ; 119(1): 171-5, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19117319

ABSTRACT

OBJECTIVES/HYPOTHESIS: To evaluate local production of staphylococcal superantigen (SAg)-specific IgE in adenoid tissue and to compare its prevalence with that in the tonsil and serum, as well as its relationship with markers of allergic inflammation within adenoid tissue. STUDY DESIGN: Prospective randomized study. METHODS: We recruited 18 atopic children who had rhinitis symptoms and were sensitized to more than one common aeroallergen, and 22 nonatopic children undergoing adenotonsillectomy. Immunoassays were performed using adenoid tissue homogenate to quantify the levels of three staphylococcal SAg-specific IgE (SEA, SEB, and TSST-1), total IgE, eosinophil cationic protein (ECP), mast cell tryptase, and soluble CD23. RESULTS: Three kinds of SAg-specific IgE were detected in the adenoid and tonsil tissues of atopic patients, but not in those of nonatopic patients. In atopic children, the prevalence of SEA-, SEB-, and TSST-1-specific IgE in adenoid tissues (61.1%, 27.8%, 33.3%, respectively) were higher than those in tonsil tissues (38.9%, 5.6%, 11.1%, respectively) and in sera (11.1%, 27.8%, 16.7%, respectively). Subjects with high SEA levels showed significantly higher serum and adenoid total IgE, with higher eosinophilia. Significant correlations were noted between SAg-specific IgE levels and tryptase levels in adenoid tissue. CONCLUSIONS: Local specific IgE response to staphylococcal SAgs, especially SEA may contribute to ongoing allergic inflammation in adenoid tissue from atopic children.


Subject(s)
Adenoids/immunology , Bacterial Toxins/immunology , Enterotoxins/immunology , Eosinophilia/immunology , Immunoglobulin E/immunology , Rhinitis, Allergic, Perennial/immunology , Staphylococcus/immunology , Superantigens/immunology , Adolescent , Child , Child, Preschool , Female , Humans , Male , Palatine Tonsil/immunology , Prospective Studies
17.
Pediatr Allergy Immunol ; 20(2): 134-41, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18657051

ABSTRACT

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non-atopic children. We hypothesized that locally produced total IgE and allergen-specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)-specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non-atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP-specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL-2 receptors (sIL-2R), soluble CD23 (sCD23), and IL-6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non-atopic individuals. Median values of DP-specific IgE and IgA antibodies were significantly higher in atopics than in non-atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP-specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non-atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL-2R, and IL-6 levels. The levels of DP-specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL-2R, sCD23, and IL-6. The presence of total IgE and DP-specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally-produced total IgE and DP-specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.


Subject(s)
Adenoids/metabolism , Antigens, Dermatophagoides/immunology , Dermatophagoides pteronyssinus/immunology , Immunoglobulins/metabolism , Respiratory Hypersensitivity/immunology , Adolescent , Animals , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Eosinophil Cationic Protein/metabolism , Epitopes , Female , Humans , Immunoglobulins/immunology , Interleukin-6/metabolism , Male , Organ Specificity , Receptors, IgE , Receptors, Interleukin-2/metabolism , Respiratory Hypersensitivity/metabolism , Tryptases/metabolism
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