Background/Aims: Heme oxygenase-1 (HO-1) plays a central role in cellular defense against inflammatory insults, and its induction in macrophages potentiates their efferocytic activity. In this study, we explored the potential role of macrophage HO-1 in the resolution of experimentally induced colitis. Methods: To induce colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in the drinking water for 7 days. To investigate efferocytosis, apoptotic colon epithelial CCD 841 CoN cells were coincubated with bone marrow-derived macrophages (BMDMs). Results: Administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs treated with apoptotic colonic epithelial cells showed significantly elevated expression of HO-1 and its regulator Nrf2. Under the same experimental conditions, the proportion of CD206-expressing macrophages was also enhanced. ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing apoptotic colonic epithelial cells. This result was verified with BMDMs isolated from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, exhibited increased expression of CD86, a marker of M1 macrophages.Coculture of lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris dampened the expression of CD86 as well as the pro-inflammatory cytokines in an HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the scavenger receptor CD36. Conclusions HO-1 plays a key role in the resolution of experimentally induced colitis by modulating the polarization of macrophages.

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.
Allergens ; Anaphylaxis ; Animals ; Cats ; Dander ; Dermatophagoides farinae ; Dermatophagoides pteronyssinus ; Dogs* ; Dust* ; Humans ; Hypersensitivity* ; Immunotherapy* ; Pilot Projects* ; Pollen ; Pyroglyphidae* ; Quality of Life ; Rhinitis ; Rhinitis, Allergic ; Sublingual Immunotherapy ; Treatment Outcome

PURPOSE: The purpose of this study was to evaluate the long-term efficacy of ultrasound (US)-guided steroid injections in patients with piriformis syndrome. METHODS: Between January 2010 and October 2012, 63 patients (23 men and 40 women; average age, 63.2 years; range, 24 to 90 years) were diagnosed with piriformis syndrome based on clinical history, electromyography, and flexion-adduction-internal rotation test results. They were divided into two groups. The first group (37 subjects) received a US-guided steroid injection around the piriformis muscle. The second group (26 subjects) received both piriformis muscle and spinal epidural injections. The therapeutic effect was categorized as improvement, partial improvement, or failure depending on the degree of symptom alleviation one month after injection, based on a review of each patient's medical records. RESULTS: In the first group, 15 patients (40.5%) showed improvement, seven (18.9%) showed partial improvement, and 15 (40.5%) failed to respond to the initial treatment. In the second group, eight patients (30.8%) showed improvement, 11 (42.3%) showed partial improvement, and seven (26.9%) failed to respond to the initial treatment. A second piriformis injection was performed in four cases, after which two patients showed improvement within 3 years, but the other two showed no therapeutic effect. CONCLUSION: US-guided steroid injection may be an effective treatment option for patients with piriformis syndrome.
Electromyography ; Female ; Humans ; Injections, Epidural ; Male ; Medical Records ; Piriformis Muscle Syndrome* ; Steroids ; Ultrasonography

OBJECTIVE: This study aims to compare liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma glutamyl transferase [GGT]) among males who work with lead, organic solvents, or both lead and organic solvents, under the permissible exposure limit (PEL). METHODS: A total of 593 (out of 2,218) male workers who agreed to share their personal health information for medical research were selected for this study. Those excluded were hepatitis B carriers, individuals exposed to occupational risk factors other than lead and organic solvents, and individuals without liver function results. The 593 were divided into five groups: a lead-exposed group, an organic solvent-exposed group exposed to trichloroethylene (TCE co-exposed solvent group), an organic solvent-exposed group not exposed to trichloroethylene (TCE non-exposed solvent group), a lead and organic solvent-exposed group (mixed exposure group), and a non-exposed group (control group). We performed a one way-analysis of variance (one way-ANOVA) test to compare the geometric means of liver function indices among the groups, using a general linear model (GLM) to adjust for age, work duration, body mass index (BMI), smoking, and alcohol intake. In addition, we performed a binary logistic regression analysis to compare the odds ratios among groups with an abnormal liver function index, according to a cut-off value. RESULTS: The ALT and AST of the mixed exposure group were higher than those of the other groups. The GGT of the mixed exposure group was higher than the TCE co-exposed solvent group, but there was no difference among the control group, TCE non-exposed solvent group, lead-exposed group, and mixed exposure group. The same result was evident after adjusting by GLM for age, work duration, BMI, smoking, and alcohol intake, except that ALT from the mixed exposure group showed no difference from the TCE co-exposed solvent group. When the cut-off values of the AST, ALT, and GGT were 40 IU/L, 42 IU/L, and 63 IU/L, respectively, a logistic regression analysis showed no differences in the odds ratios of those who had an abnormal liver function index among the groups. However, if the cut-off values of the AST, ALT, and GGT were 30 IU/L, 30 IU/L, and 40 IU/L, respectively, the odds ratio of the AST in the mixed exposure group was 4.39 (95% CI 1.86-10.40) times higher than the control. CONCLUSION: This study indicates that a mixed exposure to lead and organic solvents is dangerous, even if each single exposure is safe under the permissible exposure limit. Therefore, to ensure occupational health and safety in industry, a continuous efforts to study the effects from exposure to mixed chemicals is needed.
Alanine Transaminase ; Body Mass Index ; Hepatitis B ; Humans ; Linear Models ; Liver Function Tests* ; Liver* ; Logistic Models ; Male ; Occupational Health ; Odds Ratio ; Risk Factors ; Smoke ; Smoking ; Solvents* ; Transferases ; Trichloroethylene

PURPOSE: The environmental factors human rhinoviruses (HRVs) and house dust mites (HDMs) are the most common causes of acute exacerbations of asthma. The aim of this study was to compare the chemokine production induced by HRVs in airway epithelial cells with that induced by other respiratory viruses, and to investigate synergistic interactions between HRVs and HDMs on the induction of inflammatory chemokines in vitro. METHODS: A549 human airway epithelial cells were infected with either rhinovirus serotype 7, respiratory syncytial virus (RSV)-A2 strain, or adenovirus serotype 3 and analyzed for interleukin (IL)-8 and regulated on activation, normal T-cell expressed and secreted (RANTES) release and mRNA expression. Additionally, activation of nuclear factor (NF)-kappaB and activator protein (AP)-1 were evaluated. The release of IL-8 and RANTES was also measured in cells stimulated simultaneously with a virus and the HDM allergen, Der f1. RESULTS: HRV caused greater IL-8 and RANTES release and mRNA expression compared with either RSV or adenovirus. NF-kappaB and AP-1 were activated in these processes. Cells incubated with a virus and Der f1 showed an increased IL-8 release. However, compared with cells incubated with virus alone as the stimulator, only HRV with Der f1 showed a statistically significant increase. CONCLUSIONS: IL-8 and RANTES were induced to a greater extent by HRV compared with other viruses, and only HRV with Der f1 acted synergistically to induce bronchial epithelial IL-8 release. These findings may correspond with the fact that rhinoviruses are identified more frequently than other viruses in cases of acute exacerbation of asthma.
Adenoviridae ; Antigens, Dermatophagoides ; Arthropod Proteins ; Asthma ; Chemokine CCL5 ; Chemokines ; Cysteine Endopeptidases ; Epithelial Cells ; Humans ; Interleukin-8 ; Interleukins ; NF-kappa B ; Pyroglyphidae ; Respiratory Syncytial Viruses ; Rhinovirus ; RNA, Messenger ; Sprains and Strains ; T-Lymphocytes ; Transcription Factor AP-1 ; Viruses

PURPOSE: To evaluate the incidence and clinical features of age-related macular degeneration (AMD) in Korea. METHODS: Web-based (www.armd-nova.or.kr) registration was conducted for AMD patients aged 50 or more who were newly diagnosed by retinal specialists in Korea from August 20, 2005 to August 20, 2006. Patient data including ophthalmologic examination, fundus photography, fluorescein angiogram and/or indocyanin green angiogram (ICG), past medical history, behavioral habit, combined systemic diseases were up-loaded. RESULTS: Among finally enrolled 1,141 newly diagnosed AMD patients, 690 patients (60.5%) were male and 451 patients (39.5%) were female. The average age of AMD patients was 69.7+/-8.0. Early AMD was observed in 190 patients and 951 patients had late AMD. Classic choroidal neovascular membrane (CNVM) was observed in 18.6% of exudative AMD patients and 63.4 % had occult CNVM. Subfoveal CNVM was observed in 80.4% of the patients with CNVM. Among the 580 exudative AMD eyes that performed indocyanin green angiography (ICG), 184 eyes (31.7%) had polypoidal choroidal vasculopathy (PCV) and 36 eyes (6.2%) showed retinal angiomatous proliferation (RAP). Age, male gender, smoking, diabetes and hypertension significantly increased the risk of the AMD among Koreans. CONCLUSIONS: Because of the low rate of participation by retinal specialists, definite incidence of AMD was not obtainable. However, the estimated 1-year AMD incidence in the Pusan area of Korea is at least 0.4%. In contrast to Western people, 31.7% of exudative AMD cases were revealed to be PCV and 6.2% were revealed to be RAP. This discrepancy between ethnic groups should be considered in the diagnosis and treatment modality selection of Korean AMD patients.
Aged ; Angiography ; Choroid ; Ethnic Groups ; Eye ; Female ; Fluorescein ; Humans ; Hypertension ; Incidence ; Korea ; Macular Degeneration ; Male ; Membranes ; Photography ; Retinaldehyde ; Smoke ; Smoking ; Specialization

Panniculitis generally indicates a group of diseases whose hallmark is fibrous thickening and chronic inflammation of subcutaneous fat. Various factors seem to induce a similar pathological histology, and morphological differences can be found among the patients diagnosed with the same disease. Paraneoplastic causes account for 3~10% of the cases of panniculitis. The commonest causes of cancer associated panniculitis are hematological malignancies and mostly lymphomas. In this case, we confirmed acute myeloid leukemia by a blood test and bone marrow examination, and with considering the clinical aspects and pathological findings of the skin lesion, and we finally diagnosed the patient as having panniculitis, which seems to be related with acute myeloid leukemia. The obvious clinical symptoms or pathophysiological features of this rare type of panniculitis are not yet fully known, and so making the differential diagnosis is needed to distinguish this malady from erythema nodosum, erythema induratum and various connective tissue disorders with accompanying erythematous subcutaneous nodules. We diagnosed this very rare and interesting case of paraneoplastic panniculitis that seemed to be generated from acute myeloid leukemia. We report here on this case and we review the relevant literature.
Bone Marrow Examination ; Connective Tissue ; Diagnosis, Differential ; Erythema Induratum ; Erythema Nodosum ; Hematologic Neoplasms ; Hematologic Tests ; Humans ; Inflammation ; Leukemia, Myeloid, Acute ; Lymphoma ; Panniculitis ; Skin ; Subcutaneous Fat

PURPOSE: Microvascular reconstructive surgery has become an integral part of the treatment of head and neck cancer patients. This review of 121 free flaps for head and neck cancer patients performed over the last 11 years was done to evaluate circulatory crisis, salvage, and secondary reconstruction and to investigate which factors may contribute to these rates. METHOD: Nine emergent explorations among 121 head and neck reconstruction with free flaps were reviewed to analyze detection of vascular crisis, the time interval from detection of circulatory crisis to exploration, operation procedures and results, and secondary reconstructions. Emergent exploration was done with our protocol. RESULT: Nine free flaps exhibited signs of vascular problems between 1 day and 6 days postoperatively. The emergent exploration rate of this series was 7.4% (9/121). The salvage rate was 55.6% (5/9), giving an overall flap viability of 96.7% (117/121). In our study, preoperative radiation therapy, positive smoking history, alcohol consumption history, combined disease such as diabetes mellitus and hypertension, recipient vessels and types of vascular anastomosis were not related to the causes of circulatory crisis. The mean time interval between the onset of clinical recognition of impaired flap perfusion and re-exploration of the salvaged 5 flaps was 3.2 hours, that of failed 4 flaps was 11.25 hours. CONCLUSION: Despite high overall success rate, relatively low salvage rate may be attributed to late detection of circulatory crisis and in long time interval between detection and exploration. We conclude that early detection of circulatory crisis and expeditious re-exploration are a matter of great importance for the success of salvage operation.
Alcohol Drinking ; Diabetes Mellitus ; Free Tissue Flaps ; Head ; Head and Neck Neoplasms ; Humans ; Hypertension ; Neck ; Perfusion ; Smoke ; Smoking

Reconstruction in the head and neck region uses a wide range of surgical flaps for defect closure. The methods range from local, mostly myocutaneous flaps, and skin grafts to free microsurgical flaps. Reconstructive surgery must conserve the appearance and mimic the original function. Moreover, the donor-site defect needs to be reduced, with no resulting functional or aesthetic impairment. To achieve these goals, a thin reliable flap that is close to the face and neck region with a good match of the skin texture and a smooth, hairless skin surface is needed. So we used a flap from the shoulder region which provides an optimum skin texture to match the neck and face. This supraclavicular flap is a fasciocutaneous island flap, which has a vascular pedicle extending from the transverse cervical artery with two accompanying veins. Moreover, the tunneling method improves the donor site by reducing scarring. We hereby introduce the anatomic characteristics and effectiveness of this method.
Arteries ; Cicatrix ; Head* ; Humans ; Myocutaneous Flap ; Neck* ; Shoulder ; Skin ; Surgical Flaps ; Tissue Donors ; Transplants ; Veins

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured