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2.
Am J Otolaryngol ; 44(6): 103970, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37467676

RESUMO

PURPOSE: The term "breakthrough infection" of COVID-19 indicates that subjects who previously received COVID-19 vaccination became infected with COVID-19. This study compared the recurrence of audio-vestibular disorders following breakthrough infection of COVID-19 vs. those following vaccine administration. PATIENTS AND METHODS: Fifty patients with previous known audio-vestibular disorders visited our clinic due to recurrence of inner ear symptoms following breakthrough infection of COVID-19 and were assigned to Group A. Another 50 patients who had recurrent inner ear symptoms following COVID-19 vaccination were assigned to Group B for comparison. The post-breakthrough infection interval is defined from date of breakthrough infection to the onset of inner ear symptoms, while the post-vaccination interval means the time from date of vaccination to the onset of inner ear symptoms. These two intervals were calculated and then compared. RESULTS: The time from latest vaccination to the breakthrough infection of COVID-19 was 4 m (median), likely due to waning of IgG response. To the onset of inner ear symptoms, the post-breakthrough infection interval was 40d (median) for Group A, which was significantly longer than 10d (median) of the post-vaccination interval for Group B. CONCLUSION: The post-breakthrough infection interval (median, 40d) is significantly longer than the post-vaccination interval (median, 10d) to exacerbate pre-existing audio-vestibular disorders. The reason is probably because an interval of 40d is related to IgG peak response following COVID-19 breakthrough infection, while that of 10d is responsible for IgG production after COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Doenças Vestibulares , Vestíbulo do Labirinto , Humanos , Anticorpos Antivirais , Infecções Irruptivas , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Imunoglobulina G , Vacinação , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/etiologia
3.
Pharmaceutics ; 14(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36145605

RESUMO

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

5.
Audiol Neurootol ; 27(1): 40-47, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34038909

RESUMO

BACKGROUND: Video gaming (VG) has since the 1980s become increasingly ubiquitous entertainment among the adolescents and young adults. Many young people expe-rienced dizzy spells, but not vertiginous episodes, after playing VG. OBJECTIVES: This study performed ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests in subjects before and after engaging on VG to investigate the effect of VG on the otolithic reflex system. METHODS: Twenty subjects who frequently played VG (>3 days per week) for more than 10 years were assigned to the long-term group. Another 20 subjects with engaging on VG <3 days per week or <10 years were assigned to the short-term group. Each subject underwent baseline oVEMP and cVEMP tests first, followed by playing VG for 1 h. Then, all subjects underwent the same paradigm. The "VG-year" is defined as frequency of VG playing within 1 week (day/week) multiplied by total length of VG engagement (year). RESULTS: Engagement on VG rarely affected the oVEMP responses for either short- or long-term players. In contrast, the response rates of cVEMP significantly declined from pre-VG period (80%) to post-VG period (58%) in the short-term group, but not in the long-term group. The cutoff value for predicting absent cVEMP in VG engagement is 21 VG-year. CONCLUSION: Short-term engagement on VG may result in temporary cVEMP loss, while permanent cVEMP loss could be identified in long-term VG players. The cutoff value for predicting absent cVEMP in VG engagement is 21 VG-year, indicating that damage to the sacculo-collic reflex system could be anticipated in a subject who has played VG at least 1 h per session, 7 days weekly for 3 years.


Assuntos
Potenciais Evocados Miogênicos Vestibulares , Jogos de Vídeo , Adolescente , Tontura , Humanos , Membrana dos Otólitos , Reflexo , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adulto Jovem
6.
Front Endocrinol (Lausanne) ; 12: 752995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867797

RESUMO

Background and Aims: The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM). Methods: We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied. Results: There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history. Conclusions: Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.


Assuntos
Índice Tornozelo-Braço , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/complicações , Pé Diabético/complicações , Fatores Etários , Idoso , Povo Asiático , Estatura , Peso Corporal , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Pé Diabético/epidemiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia , Circunferência da Cintura
7.
Endocr Pract ; 26(8): 818-829, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33471673

RESUMO

OBJECTIVE: The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS. METHODS: A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke. RESULTS: The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively). CONCLUSION: Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke. ABBREVIATIONS: ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.


Assuntos
Isquemia Encefálica , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Insulina Detemir/efeitos adversos , Insulina Glargina/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Taiwan/epidemiologia , Resultado do Tratamento
8.
World J Clin Cases ; 7(19): 2942-2952, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31624742

RESUMO

BACKGROUND: Stiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases. AIM: To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects. METHODS: This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively. RESULTS: The median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases. CONCLUSION: While typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

9.
PLoS One ; 14(8): e0221199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415655

RESUMO

BACKGROUND: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. METHODS: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. RESULTS: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of ß cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. CONCLUSIONS: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and ß-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.


Assuntos
Araceae/química , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas/administração & dosagem , Obesidade , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/tratamento farmacológico , Projetos Piloto , Extratos Vegetais/química
10.
J Clin Nurs ; 28(11-12): 2253-2264, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30791155

RESUMO

AIMS AND OBJECTIVES: To determine prehospitalised diabetes-related foot ulcer (DFU) self-management behaviours and explore the factors associated with these behaviours. BACKGROUND: Although there are many studies that explore DFU prevention and treatment, to our knowledge, there are no quantitative studies of DFU self-management behaviours. DESIGN: Cross-sectional design. METHODS: From June 2015-June 2016, 199 hospitalised patients with DFU were given a survey questionnaire at a medical centre in northern Taiwan. DFU self-management behaviours, diabetes foot self-care behaviours, beliefs in regard to barriers to DFU self-management behaviours, and knowledge regarding warning signs of DFU deterioration were assessed by well-designed measurement tools. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used to ensure quality reporting during this observational study (see Supporting Information Appendix S1). RESULTS: The results revealed that 62.8% of participants never monitored their blood glucose level when they had foot ulcers, and 63.8% never sought treatment for their wounds when their wounds were not painful. After controlling for demographic and medical variables, stepwise multiple regression analysis revealed that the following eight significant variables were associated with DFU self-management behaviours: two DFU self-management barrier beliefs, foot self-care behaviour, no treatment for diabetes, poor financial status, employment, knowledge regarding the warning signs of DFU deterioration, and number of DFU hospitalisations. CONCLUSIONS: Diabetes-related foot ulcer self-management behaviours were insufficient. Some modifiable factors and high-risk groups for insufficient DFU self-management behaviour were identified. RELEVANCE TO CLINICAL PRACTICE: Diabetes-related foot ulcer self-management behaviours should be promoted. Interventions that modify the risk factors that were identified in this study can be designed to promote the performance of DFU self-management behaviours.


Assuntos
Pé Diabético/terapia , Conhecimentos, Atitudes e Prática em Saúde , Autogestão/métodos , Adulto , Estudos Transversais , Pé Diabético/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Taiwan
11.
Ultrasound Med Biol ; 45(1): 108-121, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30336966

RESUMO

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p < 0.05). Nevertheless, combined CAD and positron emission tomography/computed tomography scores and a discrimination point of 4 resulted in a sensitivity of 75% and a specificity of 80% in prediction of incidentaloma benignity.


Assuntos
Diagnóstico por Computador/métodos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia
12.
PLoS One ; 11(4): e0154327, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27104649

RESUMO

ß-amyloid peptide (Aß) aggregation has been thought to be associated with the pathogenesis of Alzheimer's disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aß40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aß40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/ß-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aß40. These results provide a structural basis to link the α-helicity of the α/ß-discordant segment with the conformational conversion propensity of Aß.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Alanina/química , Dicroísmo Circular , Humanos , Isótopos/química , Espectroscopia de Ressonância Magnética , Mutação , Estrutura Secundária de Proteína
13.
Can J Diabetes ; 39(3): 183-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25732759

RESUMO

OBJECTIVE: Diabetic foot ulcer (DFU) is a major complication in patients with diabetes mellitus and the leading cause of non-traumatic amputation in adults. Patients with DFU are usually fragile due to chronic diabetic comorbidities; therefore, tedious debridement and intervention procedures may not be well tolerated in patients with DFU. This study aimed to identify a casual relationship between in-hospital complications and treatment for limb-threatening DFUs. METHODS: From 2009 to 2011, 1130 consecutive patients who were admitted to the Diabetic Foot Care Center in Chang Gung Medical Center were surveyed. Rates of in-hospital mortality or events that lead to transfer to the intensive care unit (ICU) for various severe complications were retrospectively analyzed. RESULTS: Forty-seven patients (4.2%) experienced in-hospital complications (28 patients died). Major adverse cardiac events (MACE) (n=21, 44.7%) were the most common complications, followed by nosocomial infection (n=18, 38.3%). Previous myocardial infarction was a risk factor for MACE. The presentation of MACE was fulminant (eg, acute pulmonary edema, cardiogenic shock,cardiac arrest), and occurred within 10 days of admission or within 10 days following a major procedure in most cases. ST-T segment abnormality at rest was the most common presentation of electrocardiography for MACE. CONCLUSION: MACE should be prevented during treatment for limb-threatening DFU in high-risk patients. Acute stress might have caused MACE during the first 10 days after admission or a major procedure.


Assuntos
Pé Diabético/psicologia , Pé Diabético/terapia , Parada Cardíaca/complicações , Edema Pulmonar/complicações , Choque Cardiogênico/complicações , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/complicações , Infecção Hospitalar/mortalidade , Desbridamento/métodos , Feminino , Parada Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/mortalidade , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/mortalidade , Estresse Psicológico/complicações , Taiwan , Resultado do Tratamento
14.
Amyloid ; 22(1): 8-18, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25376379

RESUMO

Mutations within the ß-amyloid peptide (Aß) sequence that cause early onset familial Alzheimer's disease (FAD) have been shown to promote Aß aggregation. How these FAD-related mutants increase the aggregative ability of Aß is not fully understood. Here, we characterized the effect of the Arctic variant (E22G) on the conformational stability of Aß using various forms of spectroscopy and kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The E22G mutation in the Arctic variant reduced the α-helical propensity and conformational stability of Aß on residues 15-25. This mutation also caused an increase in both α-helix-to-ß-strand conversion and fibril nucleation rates. Our results suggest that the α-helical propensity of residues 15-25 may play a determinant role in the aggregative ability of Aß. This may provide a structural basis for understanding the molecular mechanism of Aß aggregation.


Assuntos
Peptídeos beta-Amiloides/química , Fragmentos de Peptídeos/química , Dodecilsulfato de Sódio/química , Tensoativos/química , Sequência de Aminoácidos , Peptídeos beta-Amiloides/genética , Humanos , Cinética , Mutação de Sentido Incorreto , Fragmentos de Peptídeos/genética , Agregação Patológica de Proteínas/genética , Estrutura Secundária de Proteína
15.
PLoS One ; 8(4): e61874, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23634215

RESUMO

Alzheimer's disease is the most common form of neurodegenerative disease. Beta-amyloid peptides (Aß) are responsible for neuronal death both in vitro and in vivo. Previously, L17 and F19 residues were identified as playing key roles in the stabilization of the Aß40 conformation and in the reduction of its neurotoxicity. In this study, the effects of L17A/F19A mutations on the neurotoxicity of Aß genetic mutant Arctic-type Aß40(E22G) were tested. The results showed that compared to Aß40(E22G), Aß40(L17A/F19A/E22G) reduced the rate of conformation conversion, aggregation, and cytotoxicity, suggesting that L17 and F19 are critical residues responsible for conformational changes which may trigger the neurotoxic cascade of Aß. Aß40(L17A/F19A/E22G) also had decreased damage due to reactive oxygen species. The results are consistent with the discordant helix hypothesis, and confirm that residues 17-25 are in the discordant helix region. Compared to Aß40(L17A/F19A), reduction in aggregation of Aß40(L17A/F19A/E22G) was less significantly decreased. This observation provides an explanation based on the discordant helix hypothesis that the mutation of E22 to G22 of Aß40(E22G) alters the propensity of the discordant helix. Arctic-type Aß40(E22G) aggregates more severely than wild-type Aß40, with a consequential increase in toxicity.


Assuntos
Alanina , Substituição de Aminoácidos , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Neurotoxinas/química , Neurotoxinas/toxicidade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Multimerização Proteica , Peptídeos beta-Amiloides/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Cinética , Mutação , Neurotoxinas/genética , Fragmentos de Peptídeos/genética , Estabilidade Proteica , Estrutura Secundária de Proteína/genética , Espécies Reativas de Oxigênio/metabolismo
16.
J Biomol Struct Dyn ; 30(2): 160-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22702727

RESUMO

ß-Amyloid peptide (1) (Aß) aggregates are toxic to neuron and the main cause of Alzheimer's disease (AD). The role of congo red (CR) on Aß aggregation is controversial in aqueous solution. Both prevention and promotion of Aß aggregation have been proposed, suggesting that CR may interact with Aß of different structural conformations resulting in different effects on Aß aggregation behavior. CR with these characteristics can be applied to probe the molecular mechanism of Aß aggregation. Therefore, in the present study, we used CR as a probe to study the Aß aggregation behavior in sodium dodecyl sulfate (SDS) condition. Our results show that Aß(40) adopts two short helices at Q15-S26 and K28-L34 in the SDS environment. CR can interact with the helical form of Aß(40), and the main interaction site is located at the first helical and hydrophobic core region, residues 17-25, which is assigned as a discordant helix region. Furthermore, CR may prevent Aß(40) undergoing α-helix to ß-strand conversion, and therefore aggregation through stabilizing the helical conformation of discordant helix in SDS environment, suggesting that the discordant helix plays a key role on the conformational stabilization of Aß. Our present study implies that any factors or molecules that can stabilize the discordant helical conformation may also prevent the Aß aggregation in membrane associated state. This leads to a new therapeutic strategy for the development of lead compounds to AD.


Assuntos
Peptídeos beta-Amiloides/química , Vermelho Congo/química , Peptídeos beta-Amiloides/metabolismo , Sítios de Ligação , Interações Hidrofóbicas e Hidrofílicas , Cinética , Modelos Moleculares , Conformação Molecular , Fragmentos de Peptídeos/química , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Scand J Infect Dis ; 43(11-12): 877-82, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21867474

RESUMO

BACKGROUND: There are few reports of Pseudomonas aeruginosa liver abscess (PALA) in the literature, and clinical information regarding its risk factors, route of transmission, and clinical course remains limited. METHODS: The medical records of 1076 patients with pyogenic liver abscess treated at Chang Gung Memorial Hospital were reviewed. RESULTS: Twenty of the patients whose records were analyzed had PALA. Mortality was 20%. Five patients with PALA, diagnosed immediately following an intra-abdominal surgical or endoscopic procedure, were classified as group A. The latent phase for the development of PALA in this group was less than 3 weeks. The remaining 15 patients were further subgrouped into group B (n = 8), with a traceable intra-abdominal procedure, and group C (n = 7), with no history of an invasive intra-abdominal procedure. The latent period in patients in group B varied from 6 weeks to 3.7 y. The absence of multidrug resistance in P. aeruginosa isolates from group C suggests the community-acquired nature of the infection in this group. Risk factor analysis showed that the incidence of hepatobiliary co-morbidities was high in all the groups (100%, 88%, and 71% in groups A, B, and C, respectively). The rates of co-infection with human gastrointestinal tract flora were 20%, 50%, and 71% in groups A, B, and C, respectively. CONCLUSIONS: PALA may be found in subjects without conventional risk factors for P. aeruginosa infection. In addition to patients with a preceding contaminated procedure, those with hepatobiliary co-morbidities form another high-risk group for this condition.


Assuntos
Abscesso Hepático Piogênico/patologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/isolamento & purificação , Adulto , Idoso , Doenças Biliares/complicações , Feminino , Humanos , Abscesso Hepático Piogênico/etiologia , Abscesso Hepático Piogênico/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/patogenicidade , Fatores de Risco
18.
Biochem Biophys Res Commun ; 405(1): 91-5, 2011 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-21216230

RESUMO

Aggregated ß-amyloid peptides (Aß) are neurotoxic and responsible for neuronal death both in vitro and in vivo. From the structural point of view, Aß self-aggregation involves a conformational change in the peptide. Here, we investigated the relationship between conformational changes and amino acid residues of Aß(40). Urea unfolding in combination with NMR spectroscopy was applied to probe the stabilization of Aß(40) conformation. L17 and F19 residues were found more sensitive to environmental changes than the other residues. Replacement of these two residues with alanine could stabilize the conformation of Aß(40). Further analysis indicated that the Aß(40)(L17A/F19A) mutant could diminish the aggregation and reduce the neurotoxicity. These results suggest that L17 and F19 are the critical residues responsible for conformational changes which may trigger neurotoxic cascade of Aß(40).


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Alanina/química , Alanina/genética , Substituição de Aminoácidos , Peptídeos beta-Amiloides/genética , Animais , Sobrevivência Celular , Humanos , Leucina/química , Leucina/genética , Mutação , Ressonância Magnética Nuclear Biomolecular , Células PC12 , Fragmentos de Peptídeos/genética , Fenilalanina/química , Fenilalanina/genética , Conformação Proteica , Ratos , Ureia/química
19.
Chang Gung Med J ; 33(5): 532-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20979704

RESUMO

BACKGROUND: Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported. METHODS: This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis. RESULTS: Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum ß-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline). CONCLUSIONS: The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Complicações do Diabetes/microbiologia , Infecções por Klebsiella/etiologia , Klebsiella pneumoniae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia , Infecções Comunitárias Adquiridas/mortalidade , Infecção Hospitalar/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
Pediatr Pulmonol ; 44(1): 93-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19085926

RESUMO

We present a 14-year-old girl whose initial diagnosis was obstructive sleep apnea syndrome (OSAS) with symptoms of habitual snore, sleep breath holding, shortness of breath, and lump in throat. Lingual thyroid was diagnosed by thyroid scan and histology, and was treated by radioactive iodine therapy and endoscopic carbon dioxide laser therapy. Her OSAS completely subsided after lingual thyroid surgery. Physicians should be aware of rare causes of OSAS in children, such as lingual thyroid and certainly if accompanied by difficulties in swallowing and speech problems.


Assuntos
Tireoide Lingual/complicações , Tireoide Lingual/patologia , Apneia Obstrutiva do Sono/etiologia , Adolescente , Feminino , Humanos , Hipertrofia/complicações , Hipertrofia/diagnóstico , Hipertrofia/cirurgia , Tireoide Lingual/cirurgia , Tireoidectomia/métodos
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