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1.
Ocul Immunol Inflamm ; : 1-7, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793360

RESUMO

PURPOSE: To establish diagnostic criteria for vitreoretinal lymphoma (VRL) using cytology and laboratory tests from vitreous samples: interleukin (IL)-10/IL-6 ratio, immunoglobulin (Ig) H gene rearrangement, and clonal B-cells on flow cytometry. METHODS: Fifty-six patients with and 39 without VRL were included. We assessed the sensitivity and specificity of each test and those of diagnostic criteria based on combinations of these tests. RESULTS: The sensitivity values for malignant cytology, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry were 0.554, 0.821, 0.732, and 0.625 with specificity of 1.000, 1.000, 0.846, and 0.974, respectively. When the diagnostic criteria were set at malignant cytology or at two or more of of four tests (atypical cells, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry), the sensitivity and specificity values for accurate diagnosis were 0.929 and 1.00, respectively. CONCLUSION: Malignant cytology or positive results for two or more of four tests may be adequate for VRL diagnosis.

2.
PLoS One ; 16(3): e0247711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661990

RESUMO

PCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The repeatability and within-laboratory precision were obviously good in validations, following to the CLSI document EP15-A3. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this new automated method for detecting antibody against both N and S proteins of SARS-CoV-2 is sufficient for use in laboratory testing.


Assuntos
Anticorpos Antivirais/sangue , /diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , /isolamento & purificação , Anticorpos Antivirais/imunologia , /epidemiologia , /imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Japão/epidemiologia , Medições Luminescentes/métodos , Fosfoproteínas/imunologia , Fosfoproteínas/isolamento & purificação , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/isolamento & purificação
3.
J Gastroenterol Hepatol ; 36(3): 551-560, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33709610

RESUMO

Despite recent improvements in therapeutic interventions, hepatocellular carcinoma is still associated with a poor prognosis in patients with an advanced disease at diagnosis. Recently, significant progress has been made in image recognition through advances in the field of artificial intelligence (AI) (or machine learning), especially deep learning. AI is a multidisciplinary field that draws on the fields of computer science and mathematics for developing and implementing computer algorithms capable of maximizing the predictive accuracy from static or dynamic data sources using analytic or probabilistic models. Because of the multifactorial and complex nature of liver diseases, the machine learning approach to integrate multiple factors would appear to be an advantageous approach to improve the likelihood of making a precise diagnosis and predicting the response of treatment and prognosis of liver diseases. In this review, we attempted to summarize the potential use of AI in the diagnosis and management of liver diseases, especially hepatocellular carcinoma.

4.
Sci Rep ; 11(1): 5190, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664450

RESUMO

In Coronavirus disease 2019 (COVID-19) subjects, recent evidence suggests the presence of unique coagulation abnormalities. In this study, we performed clot waveform analyses to investigate whether specific modulations are observed in COVID-19 subjects. We analyzed the second derivative of the absorbance in routine APTT tests performed using an ACL-TOP system. We observed high frequencies of abnormal patterns in APTT second-derivative curves that could be classified into an early shoulder type, a late shoulder type, or a biphasic type, high maximum first-derivative and second-derivative peak levels, and a low minimum second-derivative peak level in COVID-19 subjects. These modulations were not observed in subjects with disseminated intravascular coagulation. These abnormal patterns are also observed in patients with lupus anticoagulant, hemophilia, or factor IX deficiency. The plasma fibrinogen levels might also be involved in the abnormal APTT waveforms, especially the high maximum first-derivative and second-derivative peak levels. The abnormal patterns in the APTT second-derivative curves appear with highest frequency at around 2 weeks after the onset of COVID-19 and were not associated with the severity of COVID-19. These results suggest the possible presence of a specific abnormal coagulopathy in COVID-19.


Assuntos
Coagulação Sanguínea , /sangue , Idoso , Testes de Coagulação Sanguínea , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Triazóis
5.
Int J Lab Hematol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586915

RESUMO

INTRODUCTION: While white blood cell (WBC) parameters have been suggested to depend on ethnicity and gender, reference intervals in healthy Asian populations are limited. The present study established reference intervals of WBC parameters for healthy adults in Japan. METHODS: A total of 750 healthy adults (447 women and 303 men; 18-67 years old, median 40 years old) at 7 Japanese centers who participated in regular medical checkups entered this study. The WBC parameters were measured using automated hematocytometers and blood film reviews by a manual microscopic examination. RESULTS: The reference intervals of the WBC parameters according to gender in healthy adults were determined. Age-specific decreases in WBC counts of both gender groups and in neutrophil counts of women were noted. Favorable correlations between the hematocytometer and microscopic methods were found in neutrophils, lymphocytes, and eosinophils but not in monocytes or basophils. CONCLUSION: This study suggests the need to consider gender and age in the clinical use of reference intervals of WBC parameters.

6.
Sci Rep ; 11(1): 2776, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531605

RESUMO

The accurate and prompt diagnosis of SARS-CoV-2 infection is required for the control and treatment of the coronavirus infection disease 2019 (COVID-19). In this study, we aimed to investigate the time courses of the anti-severe acute corona respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM and IgG titers and to evaluate the sensitivity and specificity of such tests according to the specific day after the onset of COVID-19 among a patient population in Japan. We measured the titers of SARS-CoV-2 IgM and IgG in sera from 105 subjects, including 26 symptomatic COVID-19 patients, using chemiluminescent immunoassay (CLIA) methods utilizing magnetic beads coated with SARS-CoV-2 nucleocapsid protein and spike protein. The results of a ROC analysis suggested the possibility that the cutoff values in Japan might be lower than the manufacturer's reported cutoff (10 AU/mL): 1  AU/mL for IgM and 5  AU/mL for IgG. The sensitivity of the test before Day 8 after symptom onset was less than 50%; at Days 9-10, however, we obtained a much higher sensitivity of 81.8% for both IgM and IgG. At 15 days or later after symptom onset, the SARS-CoV-2 IgG test had a sensitivity of 100%. These results suggest that if the number of days since disease onset is taken into consideration, these antibody tests could be very useful for the diagnosis of COVID-19 and similar diseases.


Assuntos
Especificidade de Anticorpos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , /imunologia , /virologia , Ensaio de Imunoadsorção Enzimática , Humanos , Japão
7.
Sci Rep ; 11(1): 3984, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597645

RESUMO

Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA1 receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possible potential efficacy of the ATX inhibitor for NP treatment, we used an NP model with compression of DRG (CD model) and investigated LPA dynamics and whether ATX inhibition could ameliorate NP symptoms, using an orally available ATX inhibitor (ONO-8430506) at a dose of 30 mg/kg. In CD model, we observed increased LPC and LPA levels in CSF, and decreased threshold of the pain which were ameliorated by oral administration of the ATX inhibitor with decreased microglia and astrocyte populations at the site of the spinal dorsal horn projecting from injured DRG. These results suggested possible efficacy of ATX inhibitor for the treatment of NP caused by spinal nerve root compression and involvement of the ATX-LPA axis in the mechanism of NP induction.

8.
J Lipid Res ; 62: 100029, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33524376

RESUMO

Lysophosphatidic acid (LPA) is a potent signaling lipid, and state-dependent alterations in plasma LPA make it a promising diagnostic marker for various diseases. However, plasma LPA concentrations vary widely among reports, even under normal conditions. These variations can be attributed, at least in part, to the artificial metabolism of LPA after blood collection. Here, we aimed to develop an optimized plasma preparation method that reflects the concentration of LPA in the circulating blood. The main features of the devised method were suppression of both LPA production and degradation after blood collection by keeping whole blood samples at low temperature followed by the addition of an autotaxin inhibitor to plasma samples. Using this devised method, the LPA level did not change for 30 min after blood collection. Also, human and mouse LPA levels were found to be much lower than those previously reported, ranging from 40 to 50 nM with minimal variation across the individual. Finally, the increased accuracy made it possible to detect circadian rhythms in the levels of certain LPA species in mouse plasma. These results demonstrate the usefulness of the devised plasma preparation method to determine accurate plasma LPA concentrations.

9.
Sci Rep ; 11(1): 747, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436915

RESUMO

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (µLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse µLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. µLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in µLOT may minimize IOP elevation and postoperative fibrosis.

10.
Sci Rep ; 11(1): 1408, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446826

RESUMO

The purpose of this study is to examine if aqueous autotaxin (ATX) and TGF-ß levels could be used for differentiating glaucoma subtypes. This prospective observational study was performed using aqueous humor samples obtained from 281 consecutive patients. Open angle glaucoma patients were classified into three groups: primary open-angle glaucoma (POAG), secondary open-angle glaucoma (SOAG), and exfoliation glaucoma (XFG). Aqueous levels of ATX and TGF-ßs were quantified. The AUC as well as sensitivity and specificity for the classification into normal and glaucoma subtypes using four indicators-ATX, TGF-ß1, TGF-ß2, and TGF-ß3, upon the application of three machine learning methods. ATX, TGF-ß1, and TGF-ß3 were positively correlated with IOP, and ATX was significantly and negatively correlated with the mean deviation. From least absolute shrinkage and selection operator regression analysis, the AUC values to distinguish each subgroup [normal, POAG, SOAG, and XFG] ranged between 0.675 (POAG vs. normal) and 0.966 (XFG vs. normal), when four variables were used. High AUC values were obtained with ATX for discriminating XFG from normal eyes and with TGF-ß3 for discriminating XFG from normal eyes, POAG, or SOAG. Aqueous TGF-ß and ATX exhibited high diagnostic performance in detecting glaucoma subtypes, and could be promising biomarkers for glaucoma.

11.
Biol Pharm Bull ; 44(1): 39-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390548

RESUMO

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder. It often causes weight loss, which is considered a poor prognostic factor. A Japanese herbal Kampo medicine, Hochuekkito (TJ-41), has been reported to prevent systemic inflammation and weight loss in COPD patients, but the underlying biological mechanisms remain unknown. In the present study, we investigated the role of TJ-41 in vivo using a mouse model of lung emphysema. We used lung epithelium-specific Taz conditional knockout mice (Taz CKO mice) as the lung emphysema model mimicking the chronic pulmonary inflammation in COPD. Acute inflammation was induced by intratracheal lipopolysaccharide administration, simulating COPD exacerbation. Mice were fed a diet containing 2% TJ-41 or a control diet. Taz CKO mice showed increased numbers of inflammatory cells in the bronchoalveolar lavage fluid compared to control mice. This effect was reduced by TJ-41 treatment. In the acute exacerbation model, TJ-41 mitigated the increased numbers of inflammatory cells in the bronchoalveolar lavage fluid and attenuated lung inflammation in histopathological studies. Additional in vitro experiments using the human macrophage cell line U-937 demonstrated that lipopolysaccharide-induced tumor necrosis factor-alpha expression was significantly downregulated by TJ-41. These results suggest that TJ-41 has anti-inflammatory effects in lung emphysema both in the chronic phase and during an acute exacerbation. In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients.

12.
Int Heart J ; 62(1): 95-103, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33455980

RESUMO

Enlargement of the mitral valve (MV) has gained attention as a compensatory mechanism for functional mitral regurgitation (FMR). We aimed to determine if MV leaflet area is associated with MV coaptation-zone area and identify the clinical factors associated with MV leaflet size and coaptation-zone area in patients with normal left ventricle (LV) systolic function and size using real-time 3D echocardiography (RT3DE).We performed RT3DE in 135 patients with normal LV size and ejection fraction. MV leaflet and coaptation-zone areas were measured using custom 3D software. The clinical factors associated with MV leaflet and coaptation-zone areas were evaluated using univariate and multivariate linear regression analyses.There was a significant relationship between MV leaflet and coaptation-zone areas (r = 0.499, P < 0.001). MV leaflet area was strongly associated with body surface area (BSA) (r = 0.905, P < 0.001) rather than LV size and age. MV leaflet area/BSA was independently associated with male gender (P = 0.002), lower diastolic blood pressure (P = 0.042), and LV end-diastolic volume (LVEDV) index (P = 0.048); MV coaptation-zone area/BSA was independently associated with lower LVEDV index (P = 0.01).In patients with normal LV systolic function and size, MV leaflet size has a significant impact on competent MV coaptation. MV leaflet area might be intrinsically determined by body size rather than age and LV size, and the MV leaflet area/BSA is relatively constant. On the other hand, some clinical factors might also influence MV leaflet and coaptation-zone area.


Assuntos
Ventrículos do Coração/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/diagnóstico por imagem , Função Ventricular Esquerda/fisiologia , Idoso , Pressão Sanguínea/fisiologia , Ecocardiografia Tridimensional/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Sexuais , Volume Sistólico/fisiologia , Sístole
13.
Trends Biotechnol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33509656

RESUMO

Technological advances in image-based platelet analysis or platelet morphometry are critical for a better understanding of the structure and function of platelets in biological research as well as for the development of better clinical strategies in medical practice. Recently, the advent of high-throughput optical imaging and deep learning has boosted platelet morphometry to the next level by providing a new set of capabilities beyond what is achievable with traditional platelet morphometry, shedding light on the unexplored domain of platelet analysis. This Opinion article introduces emerging opportunities in 'intelligent' platelet morphometry, which are expected to pave the way for a new class of diagnostics, pharmacometrics, and therapeutics.

14.
Int J Rheum Dis ; 24(2): 231-239, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33314787

RESUMO

BACKGROUND: Recent studies revealed that lysophospholipids (LPLs) and related molecules, such as autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1 ), are candidates for novel biomarkers in melanoma, glaucoma and diabetic nephropathy. However, it is not clear whether serum levels of ATX/ PS-PLA1 would be associated with pathological and clinical findings of lupus nephritis (LN). METHODS: In this retrospective cohort study, serum samples were collected from 39 patients with LN and 37 patients with other glomerular diseases. The serum levels of ATX and PS-PLA1 were evaluated for an association with renal pathology and clinical phenotypes of LN. RESULTS: The serum levels of ATX and PS-PLA1 were higher in the patients with LN as compared to those with other glomerular diseases. Among the classes of LN, the patients with class IV showed the trend of lower serum levels of ATX. Moreover, the patients with lower levels of ATX exhibited higher scores of activity index (AI) and chronicity index (CI). The level of ATX tended to be negatively correlated with AI and CI. These results might be explained by the effect of treatment, because the serum levels of ATX and PS-PLA1 were inversely correlated with the daily amount of oral prednisolone. Moreover, they did not reflect the level of proteinuria or kidney survival in LN patients. CONCLUSION: Although the serum levels of ATX and PS-PLA1 were affected by the treatment, these levels were higher in the patients with LN. The potential clinical benefits of these markers need to be clarified in further studies.

15.
Sex Transm Infect ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208510

RESUMO

OBJECTIVES: Biologically false positive (BFP) reactions are well described in early literature. However, only a few recent reports described the incidence and clinical characteristics of patients with BFP reactions. We reviewed the serological test results of patients tested for syphilis in our hospital in the past decade and described the clinical characteristics of patients with BFP reactions. METHODS: This is a retrospective study of patients tested for syphilis in a tertiary academic hospital. All serological results were retrieved from the clinical laboratory database. We calculated the incidence of BFP reactions. Clinical characteristics and laboratory data of patients with BFP reactions were reviewed manually. RESULTS: Among 94 462 subjects, 588 patients had BFP reactions (0.62%). Most BFP reactions were observed in patients aged over 60 years, with a history of malignancy and autoimmune diseases. Eighty-five per cent of patients had low rapid plasma reagin (RPR) titre (≤1:4), but two patients had extremely high RPR titre (≥1:256). BFP reactions were more likely to persist beyond 6 months among patients with RPR titre of ≥1:8. There was no statistically significant correlation between RPR titre and total protein albumin gap, surrogate of immunoglobulin levels among patients with BFP reactions. CONCLUSION: There was a low incidence of BFP reactions in the last decade. A minority of BFP reactions had high non-treponemal antibody titre and persisted longer than 6 months. In the era of re-emergence of syphilis, this information could help clinicians interpret the results of well-established diagnostic tests for syphilis.

16.
J Atheroscler Thromb ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32999208

RESUMO

AIM: Recently, it has been established that most of the pleiotropic effects of high-density lipoprotein (HDL) are attributed to sphingosine 1-phosphate (S1P), which rides on HDL via apolipoprotein M (ApoM). In subjects with diabetes mellitus, both the pleiotropic effects of HDL and its role in reverse cholesterol transport are reported to be impaired. To elucidate the mechanisms underlying the impaired pleiotropic effects of HDL in subjects with diabetes, from the aspects of S1P and ApoM. METHODS: The incubation of HDL in a high-glucose condition resulted in the dimerization of ApoM. Moreover, the treatment of HDL with methylglyoxal resulted in the modulation of the ApoM structure, as suggested by the results of western blot analysis, isoelectric focusing electrophoresis, and two-dimensional gel electrophoresis, which was reversed by treatment with anti-glycation reagents. RESULTS: The glycation of HDL resulted in impaired binding of the glycated HDL to S1P, and the S1P on glycated HDL degraded faster. In the case of human subjects, on the other hand, although both the serum ApoM levels and the ApoM content in HDL were lower in subjects with diabetes, we did not observe the polymerization of ApoM. CONCLUSIONS: Modulation of the quantity and quality of ApoM might explain, at least in part, the impaired functions of HDL in subjects with diabetes mellitus. ApoM might be a useful target for laboratory testing and/or the treatment of diabetes mellitus.

17.
Oncotarget ; 11(39): 3590-3600, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33062195

RESUMO

Small cell lung cancer (SCLC) is a high-grade malignancy, and treatment strategies have not changed for decades. In this study, we searched for novel targets for antibody-drug conjugate (ADC) therapy for SCLC. We identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1). The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines (SHP77 and NCI-H526). The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines. Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy. Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.

18.
Sci Rep ; 10(1): 17933, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087731

RESUMO

Vasovagal syncope (VVS) is well-known to occur in patients undergoing phlebotomy, however, there have been no large-scale studies of the incidence of VVS in the blood collection room. The aim of our present retrospective study was to investigate the conditions of phlebotomy and determine the incidence/factors predisposing to the development of VVS. We investigated 677,956 phlebotomies performed in outpatients in the blood collection room, to explore factors predisposing to the development of VVS. Our analysis revealed an overall incidence of VVS of 0.004% and suggested that use of more than 5 blood collection tubes and a waiting time of more than 15 min were associated with a higher risk of VVS. The odds ratios of these factors were 8.10 (95% CI 3.76-17.50) and 3.69 (95% CI 0.87-15.60), respectively. This is the large-scale study to analyze factors of the development of VVS in the blood collection room, and according to our results, use of a large number of blood collection tubes and a prolonged waiting time for phlebotomy may be risk factors for the development of VVS.

19.
Echocardiography ; 37(11): 1749-1756, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32959402

RESUMO

BACKGROUND: Increased body mass index (BMI) is a major risk factor for heart failure with preserved ejection fraction (HFpEF), and HFpEF is more prevalent in elderly females than males. We hypothesized that there may be gender differences in the association between BMI and echocardiographic left ventricular (LV) diastolic parameters. METHODS: We enrolled 456 subjects (243 males) without overt cardiac diseases, all of whom underwent a health checkup. Early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), and left atrial (LA) volume index were measured by echocardiography to assess LV diastolic function. To examine gender differences in the association between BMI and LV diastolic function, we analyzed the interaction effects of gender on the association between BMI and echocardiographic LV diastolic parameters. RESULTS: Although there were significant gender differences in the association between BMI and E/A and e' in the crude model (interaction effect 0.037 and 0.173, respectively; P = .006 and .022, respectively), these differences were not statistically significant after adjustment for factors related to LV diastolic function. On the other hand, there were significant associations between BMI and LV diastolic parameters in each gender, even after adjustment. CONCLUSIONS: Our findings suggest there is no gender difference in the association between BMI and echocardiographic LV diastolic parameters. However, the association between BMI and LV diastolic parameters was significant in both genders. Controlling body weight might be beneficial for both women and men to prevent progression of LV diastolic dysfunction and development of HFpEF.

20.
FASEB J ; 34(11): 14655-14670, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918529

RESUMO

Hepatobiliary cholesterol handling, mediated by Niemann-Pick C1-like 1 protein (NPC1L1) and ABCG5/8, is well-known to contribute to the homeostasis of cholesterol. We attempted to elucidate the impact of hepatobiliary cholesterol handling on the homeostasis of sphingolipids and lysophospholipids, especially sphingosine 1-phosphate (S1P). We induced the overexpression of NPC1L1 or ABCG5/8 in the mouse liver. Hepatic NPC1L1 overexpression increased the plasma and hepatic S1P levels, while it decreased the biliary S1P levels, and all of these changes were inhibited by ezetimibe. The ability of HDL to activate Akt in the endothelial cells was augmented by hepatic NPC1L1 overexpression. NPC1L1-mediated S1P transport was confirmed by both in vitro and in vivo studies conducted using C17 S1P, an exogenous S1P analog. Upregulation of apolipoprotein M (apoM) was involved in these modulations, although apoM was not necessary for these modulations. Moreover, the increase in the plasma S1P levels also observed in ABCG5/8-overexpressing mice was dependent on the elevation of the plasma apoM levels. In regard to other sphingolipids and lysophospholipids, ceramides were similarly modulated by NPC1L1 to S1P, while other lipids were differently influenced by NPC1L1 or ABCG5/8 from S1P. Hepatobiliary cholesterol handling might also regulate the functional lipids, such as S1P.

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