Parkinson’s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage.Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination with L-dopa, an amelioration in both motor and non-motor symptoms such as depressionlike behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment of 6-shogaol with L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra.Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs.2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Parkinson’s disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus Mirabilis(P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

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/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Abeta) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Abeta-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Abeta-induced neurotoxicity. In mice with Abeta-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Abeta-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 microg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.
Acetylcholinesterase ; Alzheimer Disease ; Amyloid ; Animals ; Calcium ; Cholinergic Antagonists ; Dementia ; Herbal Medicine ; Hippocampus ; Homeostasis ; Houttuynia* ; Inhibitory Concentration 50 ; Memory ; Mice ; Neurons ; Phosphorylation ; Rats ; Tauopathies ; Water

The congenital complete atrioventricular block(CCAVB) is a rare disease, which is the most serious complication of neonatal lupus erythematosus. Newborn with CCAVB are at risk of diminished cardiac output and the subsequent development of congestive heart failure. Transplacental steroid and beta-adrenergic agonist therapies are useful for the first and second degree atrioventricular block. But those therapies are usually not effective for complete atrioventricular block. If the fetus has a complete atrioventricular block, delivery should be considered unless other delivery contraindications. In this situation, early pacemaker implantation surgery can improve the survival rate of patients. We report one case of premature newborn with congenital complete atrioventricular block who is successfully recovered by pacemaker implantation.
Adrenergic beta-Agonists ; Atrioventricular Block ; Cardiac Output ; Fetus ; Heart Failure ; Humans ; Infant, Newborn ; Lupus Erythematosus, Systemic ; Rare Diseases ; Survival Rate

In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-beta-lactamase nonproducers.
Bacterial Proteins/*genetics/metabolism ; DNA Primers/metabolism ; Databases, Genetic ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/genetics/isolation & purification/metabolism ; *Multiplex Polymerase Chain Reaction ; beta-Lactamases/*genetics/metabolism

BACKGROUND: The purpose of the present study was to investigate the clinico-hematological findings of bone marrow (BM) involvement and leukemic phase in Korean patients with non-Hodgkin lymphoma (NHL). METHODS: We included 791 patients with NHL that were classified with the WHO (2008) criteria. Laboratory data, bone marrow histomorphologic features and medical records were reviewed. Leukemic phase was defined as when the proportion of neoplastic lymphoid cells comprised more than 10% of leukocytes in the peripheral blood or more than 25% of nucleated cells in the BM. RESULTS: We found that 21.7% (172/791) of the patients had BM involvement, and 6.2% (49/791) developed leukemic phase of the disease. NHL subtypes showing high frequencies of leukemic phase development were mantle cell lymphoma (40%), angioimmunoblastic T cell lymphoma (40%), lymphoblastic lymphoma (36.4%), and Burkitt lymphoma (26.1%). Compared to B-cell type, T-cell type of NHL showed significantly higher frequencies of BM involvement (18.6% vs 30.9%; P=0.0004) and leukemic phase development (4.8% vs 10.3%, P=0.008). Complete remission rate was significantly lower in leukemic (55.6%) than in non-leukemic (85.9%) group of patients (P=0.0002), whereas relapse rate was not different between the two groups. Death rate was higher in leukemic (46.9%) than in non-leukemic (30.1%) group of patients, and the 5-yr overall survival probability was significantly lower in leukemic group (P=0.02). CONCLUSIONS: The incidence of leukemic phase development in NHL was lower in Korean patients than that reported for Western populations and higher in T-cell lymphoma. We confirmed that the presence of leukemic phase in NHL patients is associated with a poor prognosis.
B-Lymphocytes ; Bone Marrow ; Burkitt Lymphoma ; Humans ; Incidence ; Leukocytes ; Lymphocytes ; Lymphoma, Mantle-Cell ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; T-Lymphocytes

BACKGROUND: The Korean Red Cross blood laboratory centers have been performing comparative tests for NAT reactive specimens since February 2005. However, five discrepant specimens were found in HCV-diluted specimens between 2007 and 2008 and the reasons for this has been investigated. METHODS: For the five discrepant specimens, the HCV RNA concentration was measured in 5 tubes for each speciment. Subsequently, in order to compare the sensitivity of the low titer specimens measured by RT-PCR and TMA, comparative tests of diluted samples were examined six times per sample. Finally, the genotype was tested in order to determine the characteristics of the discrepant samples. RESULTS: Result of the quantitative tests for HCV RNA demonstrated that aliquots of the plasma bag were homogenous in term of viral load quantitation. As a result of the comparative test, all samples were found to contain over 1.0x10(1) IU/mL as detected by the two analytical systems. In contrast, those less than 1.0x10(1) IU/mL were not entirely detected by the two systems. CONCLUSION: It was impossible to completely detect using the two NAT system and the detection rates for both systems were equivalent for the samples examined. In particular, with respect to HCV, it may be undetectable on the NAT test because viral load decreases rapidly before and after sero-conversion. This result indicates that anti-HCV and NAT should be performed together as an HCV screening test prior to blood donation.
Blood Donors ; Genotype ; Humans ; Mass Screening ; Plasma ; Red Cross ; RNA ; Uronic Acids ; Viral Load