Staphylococcus aureus (S. aureus ) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S.aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis.TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.

PURPOSE: In the present study, factors related to the recurrence of breast ductal carcinoma in situ (DCIS) in Korean patients were identified, and the prognostic factors for each age group were explored.METHODS: The subjects were 226 patients who were diagnosed with DCIS by histopathologic examination, and the effect of representative prognostic factors that are known already, including estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) status, Ki-67 levels, and adjuvant therapy on the recurrence of DCIS was analyzed by using the Cox proportional hazard model.RESULTS: Among the 226 subjects, 11 patients underwent the recurrence of breast cancer. The average follow-up period was 52.7±23.5 months. The average age of the subjects was 50.6±9.3 years. Among the DCIS patients, the recurrence of breast cancer was significantly higher in the ER negative patients and those who have a Ki-67 level over 20%. However, the PR and HER2 status did not significantly affect breast cancer recurrence. The result also showed that only ER negative was a significant factor before the age of 50 years and that only the Ki-67 level over 20% was a significant factor to the patients 50 years of age or older.CONCLUSION: DCIS patients should be appropriately treated and managed depending on their age and clinicopathological factors to prevent the recurrence of DCIS.
Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Estrogens ; Follow-Up Studies ; Humans ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Recurrence

PURPOSE: In Korea, the incidence of breast cancer peaks in the fifth decade, which is younger than that observed in the Western world. We conducted this study to compare the clinical characteristics and prognostic factors of breast cancer in women < 35 and ≥35 years old.METHODS: The medical records of 969 patients treated for breast cancer at the Gil Medical Center from 2008 through 2012 were reviewed. Tumor characteristics, surgical methods, and adjuvant therapies were compared in two groups.RESULTS: Number of childbirths, family history, the proportion of postmenopausal women were lower among those aged < 35 years. However, tumor size, number of metastatic lymph nodes, and surgical procedures were similar in two groups. The rate of triple negative status in younger patients was higher than in older patients. Adjuvant chemotherapy was effective in patients positive for hormone receptors and no lymph nodal invasion, and it was effective in patients negative for hormone receptors and lymph nodal invasion in patients aged >35 years old. Postoperative radiotherapy was statistically effective in patients aged < 35 and ≥35 years old that underwent breast-conserving surgery. Pregnancy were significantly associated with survival in younger patients. While lymph node stage, presence of progesterone receptor, and triple negative status were significantly associated with survival on older patients.CONCLUSION: The prognostic factors of breast cancer in patients younger than 35 years old were pregnancy. Triple negative status rate was higher in younger patients than in older patients. Adjuvant therapy had similar effects in patients aged < 35 or ≥35 years old.
Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; Incidence ; Korea ; Lymph Nodes ; Mastectomy, Segmental ; Medical Records ; Parturition ; Pregnancy ; Prognosis ; Radiotherapy ; Receptors, Progesterone ; Western World ; Young Adult

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH₂)₅[Tyr(Me)²,Dab⁵] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH₂-d(CH₂)₅[DTyr², Thr⁴]OVT, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.
Analgesia* ; Calcium ; Diagnosis-Related Groups ; Electrophysiology ; Fura-2 ; Ganglia, Spinal* ; Humans ; Injections, Intraperitoneal ; Neurons ; Oxytocin* ; Potassium* ; Receptors, Oxytocin ; Receptors, Vasopressin ; Rodentia ; Spinal Nerve Roots*

PURPOSE: There is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin. METHODS: Dermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups). RESULTS: The body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group. CONCLUSIONS: These results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.
Adipokines ; Adiponectin ; Animals ; Body Weight ; Capsaicin ; Dermatitis ; Dermatitis, Atopic* ; Immunoglobulin E ; Leptin ; Litter Size ; Models, Animal* ; Nerve Growth Factor ; Obesity* ; Pediatric Obesity ; Plasma ; Rats ; RNA, Messenger ; Skin

No abstract available.

PURPOSE: Since 1996, the Korean Breast Cancer Society has collected nation-wide breast cancer data and analyzed the data using their online registration program biannually. The purpose of this study was to evaluate the characteristics of Korean breast cancer from 2008 and examine chronological based patterns. METHODS: Data were collected from 38 medical schools (67 hospitals), 20 general hospitals, and 10 private clinics. The data on the total number, gender, and age distribution were collected through a questionnaire as well as other detailed data analyzed via the online registration program. RESULTS: In 2008, there were 13,908 patients who were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 57.3 among 100,000 and the median age was 49 years. The age distribution had not changed since the initial survey; however the proportion of postmenopausal patients had increased and median age was older than the past. In staging distribution, the proportion of early breast cancer (stage 0, I) was 47.2% with, breast-conserving surgery performed in 58% and mastectomy in 39.5%. CONCLUSION: Compared to past data, the incidence of breast cancer in Korea continues to rise. Furthermore, the proportion of those detected by screening and breast conservation surgery has increased remarkably. To understand the patterns of Korean breast cancer, the nation-wide data should continuously investigated.
Age Distribution ; Breast ; Breast Neoplasms ; Female ; Hospitals, General ; Humans ; Incidence ; Korea ; Mass Screening ; Mastectomy ; Mastectomy, Segmental ; Online Systems ; Registries ; Schools, Medical ; Surveys and Questionnaires

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists (1 microgram bicuculline/rat and 5 microgram phaclofen/rat), agonists (1 microgram muscimol/rat and 0.5 microgram baclofen/rat) or GABA transporter (GAT) inhibitors (20 microgram NNC-711/rat and 1 microgram SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.
Animals ; Blotting, Western ; GABA Agonists ; GABA Antagonists ; gamma-Aminobutyric Acid ; Immunohistochemistry ; Negotiating ; Neuralgia ; Peptides ; Peripheral Nerve Injuries ; Polymerase Chain Reaction ; Rats

OBJECTIVE: This study was designed to determine the optimal mixture ratio of gadolinium and iodinated contrast agent for simultaneous direct MR arthrography and CT arthrography. MATERIALS AND METHODS: An in vitro study was performed utilizing mixtures of gadolinium at six different concentrations (0.625, 1.25, 2.5, 5.0, 10 and 20 mmol/L) and iodinated contrast agent at seven different concentrations (0, 12.5, 25, 37.5, 50, 75 and 92-99.9%). These mixtures were placed in tissue culture plates, and were then imaged with CT and MR (with T1-weighted sequences, proton-density sequences and T2-weighted sequences). CT numbers and signal intensities were measured. Pearson's correlation coefficients were used to assess the correlations between the gadolinium/iodinated contrast agent mixtures and the CT numbers/MR signal intensities. Scatter diagrams were plotted for all gadolinium/iodinated contrast agent combinations and two radiologists in consensus identified the mixtures that yielded the optimal CT numbers and MR signal intensities. RESULTS: The CT numbers showed significant correlation with iodinated contrast concentrations (r = 0.976, p < 0.001), whereas the signal intensities as measured on MR images showed a significant correlation with both gadolinium and iodinated contrast agent concentrations (r = -484 to -0.719, p < 0.001). A review of the CT and MR images, graphs, and scatter diagram of 42 combinations of the contrast agent showed that a concentration of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was the best combination for simultaneous CT and MR imaging. CONCLUSION: A mixture of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was found to be optimal for simultaneous direct MR arthrography and CT arthrography.
*Arthrography ; Contrast Media/*administration & dosage ; Gadolinium/administration & dosage/*diagnostic use ; Iohexol/administration & dosage/*analogs & derivatives/diagnostic use ; *Magnetic Resonance Imaging ; Meglumine/administration & dosage/*diagnostic use ; Organometallic Compounds/administration & dosage/*diagnostic use ; Phantoms, Imaging ; *Tomography, X-Ray Computed