BACKGROUND: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. METHODS: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. RESULTS: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-gamma synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-kappaB and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-gamma was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. CONCLUSION: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages.
Antimicrobial Cationic Peptides ; Blotting, Western ; Calcitriol ; Humans ; Interferon-gamma ; Interferons ; Macrophages ; Mycobacterium tuberculosis ; Nitric Oxide ; Nitric Oxide Synthase ; RNA, Messenger ; Toll-Like Receptor 2 ; Tuberculosis

PURPOSE: The only curative treatment for gastric carcinoma is surgery and it is still under debate which reconstruction method is better after performing gastrectomy for gastric carcinoma. The typical reconstruction methods after distal gastrectomy are Billroth I, Billroth II and Roux-en Y reconstruction. Yet it is difficult to compare these methods and not so much is known about which reconstruction is better in terms of the physiologic and nutritional function. With this background, we compared two reconstruction methods after distal gastrectomy (Billroth I versus Roux-en Y reconstruction) in terms of the long term physiologic function and nutritional status to create a reference for selecting reconstruction methods after distal gastrectomy. MATERIALS AND METHODS: Between 1999 and 2002, 663 patients who underwent distal gastrectomy for early gastric carcinoma filled out questionnaires every six months after operation, and these questionnaires evaluated the physiologic function. To evaluate their nutritional status, blood tests were performed every six months to check their albumin, protein and hemoglobin levels, and we checked the body weight every 6 months as well. RESULTS: The total score of the 15 questions on the questionnaire concerned with the physiologic function showed no difference between the two groups at every evaluation time, and both groups showed very low total scores, indicating tolerable physiologic function after operation. When comparing each question between two the groups, only symptoms of regurgitation and food passage showed a difference between the two groups, showing that the Roux-en Y group had better function in terms of these two symptoms. The Billroth I group showed a better nutrition status, indicating that the level of albumin, protein and hemoglobin were higher in the Billroth I group, with statistical significance. Body weight loss was severe in the Roux-en Y group. CONCLUSION: The physiologic function is slightly better in the Roux-en Y group in terms of some symptoms such as regurgitation and food passage. However, the nutritional status is better in the Billroth I group. In conclusion, because we cannot definitely ascertain which reconstruction is better when we consider both the physiologic and nutritional functions, it is reasonable that surgeon should choose reconstruction methods according to their experience and preference.
Body Weight ; Gastrectomy* ; Gastric Bypass* ; Gastroenterostomy* ; Hematologic Tests ; Humans ; Nutritional Status* ; Surveys and Questionnaires

BACKGROUND: Neuronal death in acute-phase cerebral ischemic injury is caused by necrosis. However, neuronal injury after reperfusion can be associated with apoptosis. METHODS: We used Sprague-Dawley rats whose brains were reperfused after middle cerebral artery occlusion for either 30 min or 2 h. We examined a relationship between apoptosis and the expression of inducible nitric oxide synthase (iNOS) in the brain tissue from 3 h to 14 days after reperfusion in both groups. RESULTS: TUNEL and iNOS positivity were closely related in both groups. The 2-h ischemia group exhibited increases in the amount of TUNEL and iNOS-positive cells for up to 3 days after reperfusion, at which the TUNEL and iNOS-positive cells decreased. The 30-min ischemia group exhibited peak positivity 24 h after reperfusion, followed by a similar decrease. iNOS mRNA expression peaked 3 h after reperfusion in the 30-min ischemia group, at which time it decreased. In the 2-h ischemia group, iNOS mRNA increased 3 h after reperfusion, peaked 24 h after reperfusion, and then decreased. CONCLUSION: These results indicated the occurrence of delayed apoptosis in transient cerebral ischemia. Increased expression of iNOS is closely associated with this apoptosis, and oxygen free radical-producing materials, such as nitric oxide, may play an important role in the induction of this apoptosis.
Apoptosis* ; Brain ; Brain Ischemia* ; In Situ Nick-End Labeling ; Infarction, Middle Cerebral Artery ; Ischemia ; Ischemic Attack, Transient ; Necrosis ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase Type II* ; Oxygen ; Rats, Sprague-Dawley ; Reperfusion ; RNA, Messenger

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.
Anaphylaxis ; Angioedema ; Anti-Inflammatory Agents, Non-Steroidal ; Basophils ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Incidence ; Korea ; Pharmacovigilance ; Skin ; Spasm ; Urticaria

Background/Aims: Accurate diagnosis and the effects of allergen-specific immunotherapy for pollinosis are greatly dependent on the potency and stability of the extract. This study aimed to examine factors, such as temperature and storage buffer composition, that affect the stability of allergen extracts from pollens of allergenic importance in Korea. Methods: We prepared four pollen allergen extracts from ragweed, mugwort, Japanese hop, and sawtooth oak, which are the most important causes of seasonal rhinitis in Korea. Changes of protein and major allergen concentration were measured over 1 year by Bradford assay, two-site enzyme-linked immunosorbent assay, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reconstitution of the lyophilized allergen extract in various buffers and stored at room temperature (RT, 18°C to 26°C) or refrigerated (4°C). Results: More than 90% of the original protein concentration in all four extracts examined was detected over 1 year when 50% glycerol was added and refrigerated, whereas 57.9% to 94.5% remained in the extracts at RT. The addition of 50% glycerol to the storage buffer was found to prevent protein degradation at RT. Amb a 1, a major allergen of ragweed, was almost completely degraded in 9 weeks at RT when reconstituted in a buffer without 50% glycerol. However, 55.6% to 92.8% of Amb a 1 content was detected after 1 year of incubation at 4°C in all buffer conditions except 0.3% phenol. Conclusions Addition of 50% glycerol as well as refrigeration was found to be important in increasing the shelf-life of allergen extracts from pollens of allergenic importance.

PURPOSE: To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. MATERIALS AND METHODS: Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. RESULTS: There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2.78 mm), but the data was also statistically insignificant. CONCLUSION: Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models.
Animals ; Dogs ; Granulation Tissue ; Hyperplasia* ; Stents* ; Trachea