Long-term administration of levodopa (L-DOPA) to patients with Parkinson’s disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor mani-festations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

PURPOSE: To investigate the current status of adjuvant chemotherapy (AC) regimens in Korea and the difference in efficacy of AC administered by surgical and medical oncologists in patients with stage II or III gastric cancers. MATERIALS AND METHODS: We performed a retrospective observational study among 1,049 patients who underwent curative resection and received AC for stage II and III gastric cancers between February 2012 and December 2013 at 29 tertiary referral university hospitals in Korea. To minimize the influence of potential confounders on selection bias, propensity score matching (PSM) was used based on binary logistic regression analysis. The 3-year disease-free survival (DFS) rates were compared between patients who received AC administered by medical oncologists or surgical oncologists. RESULTS: Between February 2012 and December 2013 in Korea, the most commonly prescribed AC by medical oncologists was tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%) completed AC as planned more often than medical oncologists (75.9%), with statistical significance (P=0.036). No difference in the 3-year DFS rates of stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the medical and surgical oncologist groups. CONCLUSIONS: S-1 monotherapy and XELOX are a main stay of AC, regardless of whether the prescribing physician is a medical or surgical oncologist. The better compliance with AC by surgical oncologists is a valid reason to advocate that surgical oncologists perform the treatment of AC for stage II or III gastric cancers.
Capecitabine ; Chemotherapy, Adjuvant* ; Compliance ; Disease-Free Survival ; Hospitals, University ; Humans ; Korea* ; Logistic Models ; Observational Study ; Propensity Score ; Referral and Consultation ; Retrospective Studies* ; Selection Bias ; Stomach Neoplasms*

PURPOSE: Chitin is a potent adjuvant in the development of immune response to inhaled allergens in the airways. According to other studies, chitin is known as multi-faced adjuvants which can induce Th2 responses. Recently, we found that TNF-α is a key mediator in the development of Th2 cell response to inhaled allergens. Here, we evaluated the immunologic mechanisms in the development of airway hypersensitivity to inhaled allergens, enhanced by house dust mite (HDM)-derived chitin. METHODS: The role of TNF-α and TLRs was evaluated in an airway hypersensitivity mouse model induced by a sensitization with an allergen (ovalbumin, OVA) and HDM-derived chitin using mice with the null mutation of target genes. RESULTS: The present study showed that airway sensitization with HDM-derived chitin plus OVA enhanced OVA-induced airway inflammation v. OVA alone. This phenotype was associated with the increased expression of Th1, Th2, and Th17 cytokines and also with the enhanced production of OVA-specific IgE, IgG1, and IgG2a. As for T cell responses, OVA-specific Th2 cell response, enhanced by chitin, was abolished by the treatment of chitinase, whereas Th1 and Th17 cell responses enhanced by this treatment. Moreover, the null mutation of the TNF-α gene revealed similar effects as the chitinase treatment. In contrast, all the OVA-specific T cell responses, enhanced by chitin, were blocked by the absence of TLR2, but not of TLR1, TLR4, or TLR6. CONCLUSIONS: In conclusion, these data suggest that HDM-derived chitin may enhance airway hypersensitivity to inhaled allergens, via the TLR2-dependent pathway, and that chitin-induced TNF-α can be a key mediator in the development of Th2 cell response to inhaled allergens.
Allergens* ; Animals ; Chitin* ; Chitinase ; Cytokines ; Dust* ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulin G ; Inflammation ; Mice ; Ovum ; Phenotype ; Pyroglyphidae ; Th17 Cells ; Th2 Cells*

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

Podostroma cornu-damae is a rare species of fungus belonging to the Hyocreaceae family. Its fruit body is highly toxic, as it contains trichothecene mycotoxins. The morphology is similar to that of immature Ganoderma lucidum, making identification difficult for non-experts. We experienced such a case of a 56- year-old male who picked and consumed podostroma cornu-damae, and consumed. Later that day, he developed digestive system symptoms, including nausea, vomiting, and abdominal pain. He presented to the emergency room (ER), there were no abnormal physical findings, symptoms improved after gastric lavage, and the patient voluntarily discharged himself on the same day. The following day, as the symptoms gradually deteriorated, he was admitted via the ER. He was presented with severe pancytopenia, alopecia, desquamation of skin, and acute renal failure. He recovered without any complications after conservative care, antibiotics therapy, and granulocyte colony stimulating factor administration. The most commonly reported complications of podostroma cornu-damae intoxication were reported pancytopenia, infection, disseminated intravascular coagulation, acute renal failure, etc. since Prevention is especially important because its toxicity can be lethal and there is no particular treatment to date, prevention is especially important. Promotion and education for the public are needed.
Abdominal Pain ; Acute Kidney Injury ; Agaricales ; Alopecia ; Anti-Bacterial Agents ; Colony-Stimulating Factors ; Digestive System ; Disseminated Intravascular Coagulation ; Education ; Emergency Service, Hospital ; Fruit ; Fungi ; Gastric Lavage ; Granulocytes* ; Humans ; Male ; Mycotoxins ; Nausea ; Pancytopenia* ; Reishi ; Skin* ; Vomiting

PURPOSE: Persistent pulmonary hypertension (PPHN) is considered an important prognostic factor in meconium aspiration syndrome (MAS). The aim of this study was to determine the comorbid risk factors for PPHN in infants with MAS. METHODS: We retrospectively analyzed 60 infants diagnosed with MAS and admitted to the neonatal intensive care unit of the Sanggye Paik Hospital from January 2007 to April 2013. There were 28 infants (47%) with PPHN and 32 infants (53%) without PPHN. Clinical characteristics, laboratory findings within 24 hours after birth, and initial capillary blood gas analysis results were compared between infants with and without PPHN. RESULTS: Incidence of PPHN was associated with the severity of MAS (P<0.001). The PPHN group had a greater incidence of hypotension and hypoxic-ischemic encephalopathy within 24 hours of birth compared to the non-PPHN group. The PPHN group also had a lower initial pH. However, there was no significant difference for laboratory findings within 24 hours of birth and initial capillary blood gas analysis. In the multivariate analysis, hypotension within 24 hours of birth (P=0.046, odds ratio 11.494, 95% confidence interval 1.048-125.00) was found to be a significant comorbid factor for PPHN in infants with MAS. CONCLUSION: Infants with MAS who develop hypotension within 24 hours of birth should be closely monitored for development of PPHN.
Blood Gas Analysis ; Capillaries ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary* ; Hypotension ; Hypoxia-Ischemia, Brain ; Incidence ; Infant* ; Infant, Newborn* ; Intensive Care, Neonatal ; Meconium Aspiration Syndrome* ; Multivariate Analysis ; Odds Ratio ; Parturition ; Retrospective Studies ; Risk Factors*

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.
Animals ; Aspirin/pharmacology/*therapeutic use ; Cell Polarity/drug effects/immunology ; Feedback, Physiological/*drug effects ; Interferon-gamma/deficiency/metabolism ; Interleukin-17/*metabolism/pharmacology ; Interleukin-6/biosynthesis/*metabolism ; Lipopolysaccharides/pharmacology ; Lung/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Pneumonia/*drug therapy/*immunology/pathology ; Th17 Cells/drug effects/*immunology/pathology ; Transforming Growth Factor beta1/pharmacology

PURPOSE: Ibuprofen and indomethacin has been used in treatment of patent ductus arteriosus (PDA) in Korea. But, there were few reports about oral ibuprofen for the treatment of PDA. We aimed to evaluate the efficacy and safety of oral ibuprofen versus intravenous indomethacin for the treatment of PDA in very low birth weight (VLBW) infants. METHODS: A retrospective study of VLBW infants treated with oral ibuprofen or intravenous indomethacin for symptomatic PDA at Inje University Sanggye Paik Hospital between February 2002 and April 2012 was performed. RESULTS: We identified 43 infants that received oral ibuprofen and 9 infants that received intravenous indomethacin. There were no significant differences in the efficacy and safety between oral ibuprofen group and intravenous indomethacin group. There was no significant difference between the use of oral ibuprofen before 48 hours after birth and after 48 hours the efficacy and safety. CONCLUSION: In our study, oral ibuprofen appears to be as effective as intravenous indomethacin for the treatment of PDA in VLBW infants with similar complication rates.
Ductus Arteriosus, Patent ; Humans ; Ibuprofen ; Indomethacin ; Infant ; Infant, Very Low Birth Weight ; Korea ; Parturition ; Retrospective Studies