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1.
Zhonghua Nei Ke Za Zhi ; 59(5): 366-371, 2020 May 01.
Article in Zh | MEDLINE | ID: mdl-32370465

ABSTRACT

Objective: To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK). Methods: The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD. Results: Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband's father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline. Conclusions: Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Glucokinase/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/therapy , Female , Follow-Up Studies , Humans , Male , Mutation , Pedigree
2.
Lupus ; 28(1): 19-26, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30458691

ABSTRACT

OBJECTIVE: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. RESULTS: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. CONCLUSIONS: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.


Subject(s)
Lupus Erythematosus, Systemic/complications , Osteomyelitis/epidemiology , Adolescent , Adult , Age Distribution , Aged , Case-Control Studies , Databases, Factual , Female , Humans , Incidence , Lupus Erythematosus, Systemic/mortality , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Assessment , Risk Factors , Sex Distribution , Survival Analysis , Taiwan/epidemiology , Young Adult
3.
Clin Exp Allergy ; 47(7): 937-945, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28294434

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.


Subject(s)
Asthma/immunology , Asthma/metabolism , Fetal Blood/cytology , Immunomodulation , Mesenchymal Stem Cells/metabolism , Ovalbumin/immunology , Allergens/immunology , Animals , Cytokines/metabolism , Disease Models, Animal , Female , Humans , Immunization , Immunoglobulin E/blood , Immunoglobulin E/immunology , Inflammation Mediators/metabolism , Lymph Nodes/immunology , Methacholine Chloride/metabolism , Mice , Spleen/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
4.
Lupus ; 26(11): 1149-1156, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28420053

ABSTRACT

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.


Subject(s)
Endocarditis/epidemiology , Lupus Erythematosus, Systemic/epidemiology , Adolescent , Adult , Comorbidity , Databases, Factual , Endocarditis/diagnosis , Female , Heart Diseases/epidemiology , Humans , Incidence , Kaplan-Meier Estimate , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Multivariate Analysis , Oral Surgical Procedures/adverse effects , Proportional Hazards Models , Pulse Therapy, Drug , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , Risk Factors , Steroids/administration & dosage , Steroids/adverse effects , Taiwan/epidemiology , Time Factors , Young Adult
5.
Clin Exp Allergy ; 46(3): 411-21, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26436720

ABSTRACT

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.


Subject(s)
Asthma/immunology , Asthma/pathology , Enterotoxins/immunology , Eosinophils/immunology , Eosinophils/pathology , Immunoglobulin E/immunology , Staphylococcus aureus/immunology , Adult , Age of Onset , Aged , Aged, 80 and over , Antibody Specificity/immunology , Asthma/diagnosis , Case-Control Studies , Cohort Studies , Female , Humans , Immunoglobulin E/blood , Leukocyte Count , Male , Middle Aged , Respiratory Function Tests , Risk Factors , Severity of Illness Index
6.
Br Poult Sci ; 57(6): 734-739, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27400405

ABSTRACT

The post-mortem proteolysis and tenderisation between male and female duck breast muscles were compared. The results showed that µ-calpain activity, desmin content and shear force decreased more quickly in female than in male samples stored at 5°C. It is suggested that the post-mortem proteolysis and tenderisation are more rapid and extensive in female duck breast muscle.


Subject(s)
Avian Proteins/metabolism , Calpain/metabolism , Desmin/metabolism , Meat/analysis , Proteolysis , Animals , Ducks/metabolism , Female , Food Storage , Male , Muscle Proteins/metabolism , Shear Strength
7.
Allergy ; 70(1): 124-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25280183

ABSTRACT

Google Trends (GT) is a Web-based surveillance tool used to explore the searching trends of specific queries on Google. Recent studies have suggested the utility of GT in predicting outbreaks of influenza and other diseases. However, this utility has not been thoroughly evaluated for allergic diseases. Therefore, we investigated the utility of GT for predicting the epidemiology of allergic rhinitis. In the USA, GT for allergic rhinitis showed repetitive seasonality that peaked in late April and early May and then rapidly decreased, and a second small peak occurred in September. These trends are highly correlated with the searching trends for other queries such as 'pollen count', antihistamines such as loratadine and cetirizine (all r > 0.88 and all P < 0.001), and even the total pollen count collected from 21 pollen counters across the USA (r = 0.928, P < 0.001). Google Trends for allergic rhinitis was similar to the monthly changes in rhinitis symptoms according to the US National Health and Nutrition Examination Survey III, sales for Claritin(®) and all over-the-counter antihistamines, and the number of monthly page views of 'claritin.com'. In conclusion, GT closely reflects the real-world epidemiology of allergic rhinitis in the USA and could potentially be used as a monitoring tool for allergic rhinitis.


Subject(s)
Population Surveillance , Rhinitis, Allergic/epidemiology , Social Media , Australia/epidemiology , Humans , Population Surveillance/methods , United Kingdom/epidemiology , United States/epidemiology
8.
Allergy ; 70(6): 625-37, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25649510

ABSTRACT

BACKGROUND: Patients with a previous history of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) are at high risk of the development of HSR to ICM. Many studies have tried to evaluate the diagnostic potential of skin tests in this population but have not yet reached a common conclusion. We investigated the role of skin tests in patients with HSR to ICM in terms of positive rate, cross-reactivity rate, and tolerability to skin test-negative ICM according to the type of HSR. METHODS: We performed literature searches of the MEDLINE and EMBASE databases and included studies where skin tests were performed in patients with HSR to ICM, with extractable outcomes. Outcomes were pooled using a random-effects model. RESULTS: Twenty-one studies were included. Pooled per-patient positive rates of skin tests were 17% (95% CI, 10-26%) in patients with immediate HSR, and up to 52% (95% CI, 31-72%) when confined to severe immediate HSR. Among patients with nonimmediate HSR, the positive rate was 26% (95% CI, 15-41%). The pooled per-patient cross-reactivity rate was higher in nonimmediate HSR (68%; 95% CI, 48-83%) than that in immediate HSR (39%; 95% CI, 29-50%). Median per-test cross-reactivity rates between pairs of ICM were 7% (IQR, 6-9%) in immediate HSR and 38% (IQR, 22-51%) in nonimmediate HSR. Pooled per-patient recurrence rates of HSR to skin test-negative ICM were 7% (95% CI, 4-14%) in immediate HSR and 35% (95% CI, 19-55%) in nonimmediate HSR. CONCLUSION: Skin tests may be helpful in diagnosing and managing patients with HSR to ICM, especially in patients with severe immediate HSR.


Subject(s)
Contrast Media/adverse effects , Drug Hypersensitivity/diagnosis , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Immediate/diagnosis , Iodine Compounds/adverse effects , Cross Reactions , Drug Hypersensitivity/etiology , Humans , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Immediate/chemically induced , Skin Tests
9.
Minerva Pediatr ; 67(6): 489-94, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26530491

ABSTRACT

AIM: Intranasal corticosteroids (INS) have been proven effective in controlling postnasal drip, decreasing inflammatory response, reducing nasal swelling, and increasing aeration of the sinuses such that INS are recommended as treatment of sinusitis. METHODS: Fifty children with acute rhinosinusitis, 50 children with acute rhiniosinusitis and allergic rhinitis (AR), and 20 rhiniosinusitis children as control were selected for investigation. Each group had a single-blind treatment of three types: with coamoxiclav only, with coamoxiclav plus INS, and with matched placebo (without antibiotics and INS) for two weeks. Nasal symptoms were then evaluated. The outcome was measured by using major symptom score (MSS) after treatment for 14 days. RESULTS: Therapeutic effectiveness was 92% in rhinosinusitis patients treated with co-amoxiclav and 84% in those treated with co-amoxiclav plus INS. Among patients with sinusitis combined with AR, therapeutic efficacy was 88% for those treated with co-amoxiclav and 96% for those treated with co-amoxiclav plus INS. Only 30% of the symptoms were reduced in the placebo group. CONCLUSION: There are no statistical differences in the acute sinusitis group treated with co-amoxiclav with or without INS. In the sinusitis with AR group, the efficacy of co-amoxiclav with INS is higher than in children treated with co-amoxiclav alone.


Subject(s)
Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Fluticasone/therapeutic use , Rhinitis/drug therapy , Sinusitis/drug therapy , Acute Disease , Administration, Intranasal , Adolescent , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Female , Fluticasone/administration & dosage , Humans , Male , Rhinitis, Allergic/drug therapy , Single-Blind Method , Treatment Outcome
10.
Clin Exp Allergy ; 44(4): 553-62, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24444125

ABSTRACT

BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. METHODS: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.


Subject(s)
Asthma/epidemiology , Asthma/immunology , Enterotoxins/immunology , Staphylococcus aureus/immunology , Adult , Age of Onset , Aged , Aged, 80 and over , Allergens/immunology , Antibody Specificity/immunology , Cross-Sectional Studies , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Middle Aged , Population Surveillance , Prevalence , Risk Factors , Young Adult
11.
Lupus ; 23(7): 665-71, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24554710

ABSTRACT

OBJECTIVE: The objective of our study was to determine the incidence rates and risk factors of aortic aneurysm and aortic dissection among patients with systemic lupus erythematosus (SLE) using a nationwide population-based data set. METHODS: We conducted a retrospective cohort study using data from the Taiwan National Health Insurance database. Patients with SLE and age-, sex- and comorbidity-matched control patients without SLE were identified. The primary endpoint was the first occurrence of aortic aneurysm or aortic dissection. The incidence rate ratios (IRRs) were calculated based on a 95% confidence interval (CI). A Cox proportional-hazards model was used to evaluate the risk factors for aortic aneurysm and aortic dissection in the SLE cohort. RESULTS: Among the 15,209 patients with SLE (89.9% women and mean age of 38.3 years), 20 developed aortic aneurysm and 13 developed aortic dissection (overall incidence rate, 4.26 per 10,000 person-years). Compared with the control patients, the overall IRR for developing aortic aneurysm or aortic dissection was 3.34 (95% CI, 1.71-6.91; p < 0.001). The IRRs for aortic aneurysm or aortic dissection were 2.98 (95% CI, 1.41-6.70, p = 0.018) for women and 5.50 (95% CI, 1.10-53.15, p = 0.020) for men. Multivariate Cox regression analysis showed that age, male sex, an SLE diagnosis greater than three years prior and hypertension were associated with aortic aneurysm and aortic dissection. CONCLUSION: Aortic aneurysm and aortic dissection occur at higher rates in SLE patients than in people without SLE and a longer disease duration is associated with a higher risk of these rare vascular complications.


Subject(s)
Aortic Aneurysm/epidemiology , Aortic Aneurysm/etiology , Aortic Dissection/epidemiology , Aortic Dissection/etiology , Lupus Erythematosus, Systemic/complications , Adult , Cohort Studies , Female , Humans , Incidence , Male , Retrospective Studies , Risk Assessment , Taiwan/epidemiology
12.
J Appl Microbiol ; 116(3): 542-53, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24279899

ABSTRACT

AIMS: To demonstrate the biodegradation of dibenzofuran (DF) and its structural analogs by a newly isolated Agrobacterium sp. PH-08. METHODS AND RESULTS: To assess the biodegradation potential of newly isolated Agrobacterium sp. PH-08, various substrates were evaluated as sole carbon sources in growth and biotransformation experiments. ESI LC-MS/MS analysis revealed the presence of angular degrading by-products as well as lateral dioxygenation metabolites in the upper pathway. The metabolites in the lower pathway also were detected. In addition, the cometabolically degraded daughter compounds of DF-related compounds such as BP and dibenzothiophene (DBT) in dual substrate degradation were observed. Strain PH-08 exhibited the evidence of meta-cleavage pathway as confirmed by the activity and gene expression of catechol-2,3-dioxygenase. CONCLUSIONS: Newly isolated bacterial strain, Agrobacterium sp. PH-08, grew well with and degraded DF via both angular and lateral dioxygenation as demonstrated by metabolites identified through ESI LC-MS/MS and GC-MS analyses. The other heterocyclic pollutants were also cometabolically degraded. SIGNIFICANCE AND IMPACT OF THE STUDY: Few reports have described the complete degradation of DF by a cometabolic lateral pathway. Our study demonstrates the novel results that the newly isolated strain utilized the DF as a sole carbon source and mineralized it via multiple dioxygenation.


Subject(s)
Agrobacterium/enzymology , Benzofurans/metabolism , Catechol 2,3-Dioxygenase/metabolism , Agrobacterium/genetics , Agrobacterium/isolation & purification , Biodegradation, Environmental , Catechol 2,3-Dioxygenase/genetics , Tandem Mass Spectrometry , Thiophenes/metabolism
13.
Diabetologia ; 56(1): 204-17, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23090186

ABSTRACT

AIMS/HYPOTHESIS: Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. RESULTS: The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. CONCLUSIONS/INTERPRETATION: The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/prevention & control , Kidney/drug effects , Mesangial Cells/drug effects , Protective Agents/therapeutic use , Signal Transduction/drug effects , Stilbenes/therapeutic use , AMP-Activated Protein Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/chemistry , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Cells, Cultured , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Enzyme Activation/drug effects , Kidney/metabolism , Kidney/pathology , Kidney/physiopathology , Lipid Metabolism/drug effects , Lipotropic Agents/pharmacology , Lipotropic Agents/therapeutic use , Male , Mesangial Cells/metabolism , Mesangial Cells/pathology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Oxidative Stress/drug effects , Protective Agents/pharmacology , Protein Processing, Post-Translational/drug effects , RNA Interference , Resveratrol , Sirtuin 1/antagonists & inhibitors , Sirtuin 1/chemistry , Sirtuin 1/genetics , Sirtuin 1/metabolism , Stilbenes/pharmacology , Transcription Factors/agonists , Transcription Factors/metabolism
14.
Biochemistry (Mosc) ; 78(11): 1254-62, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24460939

ABSTRACT

Protein kinase inhibitors have been developed and applied as antitumor drugs. The majority of these inhibitors are derived from ATP analogs with limited specificity towards the kinase target. Here we present our proof-of-principle study on peptide inhibitors for kinases. Two peptides were selected by phage display against double-stranded RNA-dependent protein kinase (PKR). In vitro assay revealed that these peptides exhibit an inhibitory effect on PKR-catalyzed phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2α). The peptides also interrupt PKR activity in cells infected by viruses, as PKR activation is one of the hallmarks of host response to viral infection. Kinetic study revealed that one of the peptides, named P1, is a competitive inhibitor for PKR, while the other, named P2, exhibits a more complicated pattern of inhibition on PKR activity. Fragment-based docking of the PKR-peptide complex suggests that P1 occupies the substrate pocket of PKR and thus inhibits the binding between PKR and eIF2α, whereas P2 sits near the substrate pocket. The computational model of PKR-peptide complex agrees with their kinetic behavior. We surmise that peptide inhibitors for kinases have higher specificity than ATP analogs, and that they provide promising leads for the optimization of kinase inhibitors.


Subject(s)
Peptides/metabolism , Protein Kinase Inhibitors/metabolism , eIF-2 Kinase/antagonists & inhibitors , Amino Acid Sequence , Binding Sites , Cell Surface Display Techniques , Eukaryotic Initiation Factor-2/genetics , Eukaryotic Initiation Factor-2/metabolism , HeLa Cells , Humans , Molecular Docking Simulation , Peptides/chemistry , Phosphorylation , Protein Binding , Protein Kinase Inhibitors/chemistry , Protein Structure, Tertiary , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , eIF-2 Kinase/genetics , eIF-2 Kinase/metabolism
15.
Lupus ; 21(11): 1237-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22627066

ABSTRACT

Protein-losing enteropathy (PLE) and autoimmune oophoritis are unusual manifestations of systemic lupus erythematosus (SLE). Autoimmune oophoritis may result in menstrual disturbance and spontaneous premature ovarian failure. However, there is no validated examination to confirm the diagnosis and it is easily neglected in patients with ovarian insufficiency. A 31-year-old woman with SLE presented with PLE and autoimmune oophoritis during the long course of flares and remissions in her lupus activity. The synchronism implied the association between the two. Moreover, both conditions simultaneously had a good response to cyclosporine A (CsA) therapy.


Subject(s)
Lupus Erythematosus, Systemic/complications , Oophoritis/etiology , Polyendocrinopathies, Autoimmune/etiology , Protein-Losing Enteropathies/etiology , Adult , Cyclosporine/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/physiopathology , Oophoritis/diagnosis , Polyendocrinopathies, Autoimmune/diagnosis , Primary Ovarian Insufficiency/drug therapy , Primary Ovarian Insufficiency/etiology , Protein-Losing Enteropathies/drug therapy , Treatment Outcome
16.
Eur J Neurol ; 19(5): 746-51, 2012 May.
Article in English | MEDLINE | ID: mdl-22221515

ABSTRACT

BACKGROUND AND PURPOSE: The relationship between myasthenia gravis (MG) and extrathymic malignancies has not been determined. This study aimed to explore the risk of extrathymic malignancy in patients with MG based on a nationwide population-based dataset. METHODS: We identified 2614 patients with MG from the Taiwan National Health Insurance database between 1997 and 2005 and compared the incidence rates of extrathymic malignancies with 15, 684 randomly selected age-, sex-, and comorbidity-matched subjects without MG. Both cohorts were followed until the end of 2009. Cox proportional hazard model was used to evaluate the predictors of extrathymic malignancy in the MG cohort, including age, sex, comorbidities, and prescription drugs. RESULTS: After an average follow-up of 8 years, the MG cohort had a higher risk of extrathymic cancers with an incidence rate ratio (IRR) of 1.38 (95% CI 1.12-1.68, P = 0.002) than the control cohort. Although breast cancer was the most common cancer found, no statistically significant relationship between MG and any specific malignancy was observed. Cox multivariate proportional hazards analysis showed that only age (HR = 1.05, 95% CI 1.04-1.06, P < 0.001) and liver cirrhosis (IRR = 3.85, 95% CI 1.22-12.14, P = 0.021) were predictors of extrathymic cancers in the MG cohort. CONCLUSIONS: Our study showed that patients with MG had an increased risk of extrathymic malignancy in a follow-up of 8 years, but no specific susceptibility to certain malignancies was found.


Subject(s)
Brain Neoplasms/epidemiology , Myasthenia Gravis/epidemiology , Thalamus/pathology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Cohort Studies , Community Health Planning , Female , Health Surveys , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Taiwan/epidemiology , Young Adult
17.
Transpl Infect Dis ; 14(5): 502-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22571347

ABSTRACT

BACKGROUND: Tuberculosis (TB) has been reported to increase morbidity after kidney transplantation and pose a therapeutic challenge. However, population-based research, specifically focused on the association between kidney transplantation and subsequent pulmonary or extrapulmonary TB, is lacking. METHODS: A nationwide population-based study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data belonging to kidney transplant recipients during 1997-2006. Multivariate analysis was used to identify independent risk factors for TB after kidney transplantation. Kaplan-Meier survival analysis was used to assess the outcome of patients with TB. RESULTS: Among 4554 kidney transplant recipients over the 10-year period, 109 (2.4%) patients with newly diagnosed TB were identified: 75 patients with only pulmonary involvement, and 34 with extrapulmonary spread. The incidence of kidney transplant recipients developing TB was 638 per 100,000 person-years. The independent risk factors for post-transplant TB included cyclosporine-based immunosuppressant agents during the first year after kidney transplantation (odds ratio [OR]: 1.98, P = 0.001), hepatitis C infection (OR: 1.79, P = 0.024), and chronic obstructive pulmonary disease (OR: 1.50, P = 0.041). Kidney transplant recipients who developed TB had a lower 5-year survival rate than those who did not (78.6% vs. 93.4%, P = 0.001). CONCLUSIONS: Kidney transplant recipients in Taiwan did have a high risk of TB infection, with high proportion of extrapulmonary spread. Physicians need to be vigilant in surveying for TB in kidney transplantation, especially in high-risk patients.


Subject(s)
Kidney Transplantation/adverse effects , Tuberculosis, Pulmonary/mortality , Tuberculosis/mortality , Adult , Cyclosporine/administration & dosage , Female , Humans , Immunosuppressive Agents/administration & dosage , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Factors , Survival Rate , Taiwan/epidemiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology
18.
Plant Dis ; 96(4): 593, 2012 Apr.
Article in English | MEDLINE | ID: mdl-30727436

ABSTRACT

Desert rose (Adenium obesum (Forssk.) Roem. & Schult, family Apocynaceae) is native to southeastern Africa, and is a perennial potted ornamental with colorful flowers that are popular in Taiwan. Symptoms of mosaic and chlorotic ringspots and line patterns on leaves were observed in July 2010, on all eight plants in a private garden in Potzu, Chiayi, Taiwan. Spherical virus particles with a diameter of approximately 28 nm were observed in crude sap prepared from symptomatic leaves. Virus culture was established by successive local lesion isolation in Chenopodium quinoa and was maintained in the systemic host Nicotiana tabacum van Hicks. The virus was mechanically transmissible to indicator plants and induced symptoms similar to those incited by Cucumber mosaic virus (CMV). Observed symptoms included local lesions on inoculated leaves of C. amaranticolor and systemic mosaic in Cucumis sativus, Lycopersicon esculentum, N. benthamiana, N. glutinosa, and N. rustica. On N. tabacum, necrotic ringspots developed on inoculated leaves followed by systemic mosaic. Serological tests using ELISA assays and western blotting indicated that the virus reacted positively to a rabbit antiserum prepared to CMV (4). Amplicons of an expected size (1.1 kb) were obtained in reverse transcription-PCR with primers specific to the 3'-half of CMV RNA 3 (3) using total RNA extracted from infected desert rose and N. tabacum. The amplified cDNA fragment was cloned and sequenced (GenBank Accession No. AB667971). Nucleotide sequences of the coat protein open reading frame (CP ORF) (657 nt) had 92 to 96% and 76 to 77% sequence identity to those of CMV in subgroups I (GenBank Accession Nos. NC_001440, D00385, M57602, D28780, and AB008777) and II (GenBank Accession Nos. L15336, AF127976, AF198103, and M21464), respectively. Desert roses infected by Tomato spotted wilt virus (TSWV) (1) and CMV (2) have been reported previously. In spite of the plants showing mosaic symptoms similar to that caused by CMV (2) and chlorotic ringspots and line patterns caused by TSWV (1), only CMV was detected in and isolated from these infected desert roses. However, the possibility of mixed infection of CMV and other viruses were not excluded in this research. To our knowledge, this is the first report of CMV infection in desert rose plants occurring in Taiwan. References: (1) S. Adkins and C. A. Baker. Plant Dis. 89:526, 2005. (2) C. A. Baker et al. Plant Dis. 87:1007, 2003. (3) Y. K. Chen et al. Arch. Virol. 146:1631, 2001. (4) Y. K. Chen and C. C. Yang. Plant Dis. 89:529, 2005.

19.
Int Breastfeed J ; 17(1): 58, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35978362

ABSTRACT

BACKGROUND: Women with COVID-19 experienced numerous concerns and doubts about the safety of breastfeeding their babies, and lack of support may have impacted breastfeeding practices. This study aims to compare breastfeeding beliefs, practices, and contact with healthcare professionals regarding the level of postnatal feeding support provided during the COVID-19 pandemic in Brazil, South Korea, Taiwan, Thailand, and the United Kingdom. METHODS: A multi-country cross-sectional study was conducted with postnatal women in five countries. Women up to six months postpartum were invited to complete an online survey concerning the transmission of preventative measures, beliefs toward breastfeeding, infant feeding practices in the last 24 hours and experiences of postnatal infant feeding support between July to November 2021. Bivariate and multivariate analyses were performed to identify the association. RESULTS: Of the 3,253 eligible responses received, 39.5% of children were aged between one and two months, but in Taiwan (36%) and South Korea (42.8%) they were between three and four months. The mean of the belief score was significantly different among countries (p < 0.0001). Women in Brazil and the UK had a higher rate of breastfeeding at the breast (90.7% and 85.4%, respectively) compared to the three Asian countries (p < 0.0001) while feeding with expressed breastmilk in Thailand (59.9%), Taiwan (52.6%), and South Korea (50.4%) was higher than the others (p < 0.0001). Brazil and UK mothers (mean = 16.0 and 14.5 respectively) had a higher mean score for belief toward breastfeeding during the COVID-19 than the others. These results are inversely associated with breastfeeding but positively related to formula feeding practice. Postnatal feeding support during the COVID-19 pandemic was mainly provided by healthcare professionals (67.1%) and peers / family through face-to-face personal contact (51.6%) in all countries. CONCLUSION: Some differences were found in breastfeeding beliefs during the COVID-19 pandemic in Asian countries. A positive breastfeeding belief was associated with the practice of breastfeeding at the breast. Women from all countries received postpartum infant feeding support from health professionals and peers / family through personal contacts. Governments need to emphasize and disseminate the importance of breastfeeding safety, especially in Asian countries.


Subject(s)
Breast Feeding , COVID-19 , Child , Cross-Sectional Studies , Female , Humans , Infant , Mothers , Pandemics
20.
Clin Exp Allergy ; 41(5): 697-705, 2011 May.
Article in English | MEDLINE | ID: mdl-21488996

ABSTRACT

BACKGROUND: Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported. OBJECTIVE: We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis. METHODS: A total of 1116 subjects (males 419, females 697; age range, 30-86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis-specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR). RESULTS: Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199-2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050-2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448-4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis. CONCLUSION AND CLINICAL RELEVANCE: Clonorchiasis was positively associated with atopy in adults in endemic area.


Subject(s)
Clonorchiasis/complications , Clonorchiasis/epidemiology , Endemic Diseases , Hypersensitivity, Immediate/complications , Hypersensitivity, Immediate/epidemiology , Adult , Aged , Aged, 80 and over , Animals , Clonorchiasis/immunology , Clonorchiasis/parasitology , Clonorchis sinensis/immunology , Clonorchis sinensis/isolation & purification , Female , Humans , Hypersensitivity, Immediate/immunology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Middle Aged , Republic of Korea/epidemiology , Skin Tests , Surveys and Questionnaires
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