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We describe the case of a 52-year-old male who presented with two episodes of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) during work, while suspending live chickens for slaughter. The patient was exposed to high levels of bioaerosols, including endotoxins and microorganisms. Endotoxins can induce bronchoconstriction and airway inflammation, and COPD patients are more vulnerable to airway infections caused by microorganisms inhaled with bioaerosols. This study suggests that a high level of bioaerosols may induce airway infections, resulting in acute exacerbations of COPD.
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Matadouros , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Animais , Galinhas , Doença Pulmonar Obstrutiva Crônica/complicações , Progressão da DoençaRESUMO
OBJECTIVE: Theoretical predicting cytotoxic T lymphocyte (CTL) epitopes are an important tool in vaccine design and CTL therapy for enhancing our understanding of the cellular immune system. We would like to identify available CTL epitopes against HIV-1 Korean clade B. CTL activity was assessed in freshly isolated peripheral blood mononuclear cells from Korean HIV patients in order to assess whether these CTL epitopes induce a cell-mediated immune response (CMI). METHODS: NetCTLpan1.1 software, which is the most popular prediction computer software package, and full atom-based simulation (FABS), which is a 3D modelling system for binding activity between epitopes and human leucocyte antigen (HLA) molecules, were used to predict the peptide-spanning Env region binding to HLA-A*24:02, HLA-A*02:01 and HLA-B*15:01, which are frequently found in the Korean population. Granzyme B and interferon-γ ELISPOT assays were used to determine whether identified CTL epitopes induce CMI. RESULTS: Three HIV-1 Korean clade B-specific Env CTL epitopes were identified: Gp41-RYL and Gp41-RQG are localized within gp41, and Gp120-LLQ within gp120. In in vitro assays using granzyme B ELISPOT, Gp120-LLQ and Gp41-RQG induced epitope-specific CTL responses in HLA-restricted cells. In ex vivo assay using IFN-γ ELISPOT, cell-mediated immune responses to Gp41-RYL were present in 50% of HLA-matched patients, and responses to Gp120-LLQ and Gp41-RQG were found in 33% of HLA-matched patients. CONCLUSION: In this study, we found that a prediction pipeline for CTL epitopes might be based on the most popular computer prediction software and FABS methods. Our results suggest that these CTL epitopes may provide useful tools and information for the development of a therapeutic vaccine against HIV-1 Korean clade B.
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Biologia Computacional/métodos , Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos Virais/metabolismo , ELISPOT , Genótipo , Granzimas/análise , Infecções por HIV/virologia , HIV-1/genética , Antígenos HLA-A/metabolismo , Antígenos HLA-B/metabolismo , Humanos , Interferon gama/análise , Ligação Proteica , República da CoreiaRESUMO
BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC), and is correlated with poor prognosis, making it an attractive target for monoclonal antibody (mAb) therapy. A component of the therapeutic efficacy of IgG1 mAbs is their stimulation of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells bearing the CD16 receptor. As NK cells are functionally impaired in cancer patients and may be further compromised upon chemotherapy, it is crucial to assess whether immunotherapeutic strategies aimed at further enhancing ADCC are viable. METHODS: CRC patients before, during and after chemotherapy were immunophenotyped by flow cytometry for major white blood cell populations. ADCC-independent NK cell functionality was assessed in cytotoxicity assays against K562 cells. ADCC-dependent killing of EGFR(+) A431 cancer cells by NK cells was measured with a degranulation assay where ADCC was induced by GA201, an anti-EGFR mAb glyco-engineered to enhance ADCC. RESULTS: Here, we confirm the observation that NK cells in cancer patients are dysfunctional. However, GA201 was able to induce robust NK cell-dependent cytotoxicity in CRC patient NK cells, effectively overcoming their impairment. CONCLUSIONS: These findings support the evaluation of the therapeutic potential of GA201 in combination with chemotherapy in CRC patients.
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Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Receptores ErbB/imunologia , Glicoproteínas/imunologia , Glicoproteínas/farmacologia , Células Matadoras Naturais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Proteínas Ligadas por GPI/imunologia , Humanos , Imunoglobulina G/imunologia , Células K562 , Receptores de IgG/imunologiaRESUMO
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.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Estilbenos/uso terapêutico , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Ativação Enzimática/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipotrópicos/farmacologia , Lipotrópicos/uso terapêutico , Masculino , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Interferência de RNA , Resveratrol , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/química , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Fatores de Transcrição/agonistas , Fatores de Transcrição/metabolismoRESUMO
Renal relapse in patients with lupus nephritis (LN) is a risk factor for poor renal function. Therefore, there is a need to identify clinical and serological risk factors for renal relapse. A total of 108 patients with LN were enrolled in this study. All the subjects had achieved complete remission or partial remission following six months of induction therapy. We retrospectively analyzed their clinical and laboratory indices, final renal function, and kidney biopsy findings. The median follow-up period after LN diagnosis was 81 months. Renal relapse had occurred in 36 patients; it occurred in 38% and 46% of patients within five and 10 years after achievement of renal remission, respectively. There was no difference between the relapsed rate in patients with complete remission and that in those with partial remission. Clinical variables at LN onset and renal biopsy findings in the patients with sustained remission and relapsed patients were also not different. The probability of renal relapse was significantly higher in patients with an earlier age of onset of systemic lupus erythematosus (SLE) (≤ 28 years versus >28 years; HR 7.308, P=0.001), seronegativity for anti-Ro antibody (seronegativity versus seropositivity; HR 3.514, P=0.007), and seropositivity for anti-dsDNA antibody at six months after initiation of induction therapy (HR 8.269, P=0.001). Our study demonstrated that early onset of SLE, seronegativity for anti-Ro antibody and increased anti-dsDNA antibody following six months of induction therapy independently predict renal relapse among the LN patients.
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Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Adulto , Biópsia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Rim/patologia , Testes de Função Renal , Nefrite Lúpica/patologia , Masculino , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: We investigated the effect of combined use of rituximab (RTX) and plasmapheresis (PP) pre-transplant on post-transplant infection. METHODS: A total of 196 patients undergoing living-donor kidney transplantation at Seoul St. Mary's Hospital, all of whom underwent basiliximab induction therapy, were included in the study. They were divided into 3 groups: RTX/PP/intravenous immune globulin (IVIG) (the RPI group; n = 53), RTX monotherapy (the RTX group; n = 14), and control (the CONT group; n = 129). We compared the post-transplant infections in the 3 groups. RESULTS: The overall prevalence of infection was significantly higher, and the infection-free survival rate was lower, in the RPI group compared with the RTX or CONT groups (P < 0.05). A trend toward more severe bacterial infections was seen in the RPI group compared with the other groups, and fungal infections developed only in the RPI group. After anti-rejection therapy, a significantly higher rate of infection developed in the RPI group than in the other groups (P < 0.05). In addition, the RPI group was an independent risk factor for the development of infection. CONCLUSION: Our results show that in the setting of basiliximab induction, the use of combined RTX and PP therapy pre-transplant significantly increases the risk for post-transplant infection.
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Anticorpos Monoclonais Murinos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Transplante de Rim/métodos , Plasmaferese/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Anticorpos Monoclonais/uso terapêutico , Vírus BK , Basiliximab , Terapia Combinada/efeitos adversos , Infecções por Citomegalovirus/etiologia , Intervalo Livre de Doença , Feminino , Rejeição de Enxerto/prevenção & controle , Herpes Zoster/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Pneumopatias Fúngicas/etiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/etiologia , Infecções por Polyomavirus/etiologia , Cuidados Pré-Operatórios/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Rituximab , Infecções Tumorais por Vírus/etiologia , Infecções Urinárias/etiologiaRESUMO
OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.
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Coinfecção , Infecções Comunitárias Adquiridas , Pneumonia por Mycoplasma , Viroses , Vírus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana , Humanos , Macrolídeos/uso terapêutico , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Prescrições , Estudos Prospectivos , Viroses/tratamento farmacológicoRESUMO
Infection with human immunodeficiency virus (HIV) results in a chronic infection that progressively impairs the immune system. Although depletion of CD4(+) T cells is frequently used to explain immunosuppression, chronicity of infection and progressive loss of CD4(+) T cells are not sufficient to fully account for immune dysregulation. Arginase-induced l-arginine deprivation is emerging as a key mechanism for the down-regulation of immune responses. Here, we hypothesized that the level of arginase activity increases with disease severity in HIV-seropositive patients. We determined the levels of arginase activity in peripheral blood mononuclear cells from HIV-seropositive patients and uninfected control participants. Our results show that peripheral blood mononuclear cells from HIV-seropositive patients with low CD4(+) T cell counts expressed statistically significantly higher levels of arginase activity, compared with patients with high CD4(+) T cell counts or uninfected control participants. Furthermore, we found a statistically significant correlation between high level of arginase activity and high viral load in HIV-seropositive patients.
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Arginase/metabolismo , Infecções por HIV/patologia , Leucócitos Mononucleares/enzimologia , Índice de Gravidade de Doença , Adulto , Contagem de Linfócito CD4 , Células Cultivadas , Feminino , HIV/isolamento & purificação , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
BACKGROUND AND PURPOSE: Nigrostriatal dopaminergic function in patients with Parkinson disease can be assessed using 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan dopamine transporter (123I-FP-CIT) SPECT, and a good correlation has been demonstrated between nigral status on SWI and dopaminergic denervation on 123I-FP-CIT SPECT. Here, we aim to correlate quantified dopamine transporter attenuation on 123I-FP-CIT SPECT with nigrosome-1 status using susceptibility map-weighted imaging (SMWI). MATERIALS AND METHODS: Between May 2017 and January 2018, consecutive patients with idiopathic Parkinson disease (n = 109) and control participants (n = 29) who underwent 123I-FP-CIT SPECT with concurrent 3T SWI were included. SMWI was generated from SWI. Two neuroradiologists evaluated nigral hyperintensity from nigrosome-1 on each side of the substantia nigra. Using consensus reading, we compared the 123I-FP-CIT-specific binding ratio according to nigral hyperintensity status and the 123I-FP-CIT specific binding ratio threshold to confirm the loss of nigral hyperintensity was determined using receiver operating characteristic curve analysis. RESULTS: The concordance rate between SMWI and 123I-FP-CIT SPECT was 65.9%. The 123I-FP-CIT-specific binding ratios in the striatum, caudate nucleus, and putamen were significantly lower when nigral hyperintensity in the ipsilateral substantia nigra was absent than when present (all, P < .001). The 123I-FP-CIT-specific binding ratio threshold values for the determination of nigral hyperintensity loss were 2.56 in the striatum (area under the curve, 0.890), 3.07 in the caudate nucleus (0.830), and 2.36 in the putamen (0.887). CONCLUSIONS: Nigral hyperintensity on SMWI showed high positive predictive value and low negative predictive value with dopaminergic degeneration on 123I-FP-CIT SPECT. In patients with Parkinson disease, the loss of nigral hyperintensity is prominent in patients with lower striatal specific binding ratios.
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Transtornos Parkinsonianos , Substância Negra , Idoso , Idoso de 80 Anos ou mais , Denervação , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The metabolism of the amino acid L-arginine is emerging as a crucial mechanism for the regulation of immune responses. Here, we characterized the impact of L-arginine deprivation on T cell and macrophage (MPhi) effector functions: We show that whereas L-arginine is required unconditionally for T cell activation, MPhi can up-regulate activation markers and produce cytokines and chemokines in the absence of L-arginine. Furthermore, we show that L-arginine deprivation does not affect the capacity of activated MPhi to up-regulate L-arginine-metabolizing enzymes such as inducible NO synthase and arginase 1. Thus, our results show that to exert their effector functions, T cells and MPhi have different requirements for L-arginine.
Assuntos
Arginina/deficiência , Ativação Linfocitária/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Linfócitos T/imunologia , Animais , Arginase/metabolismo , Arginina/farmacologia , Biomarcadores/metabolismo , Proliferação de Células , Citocinas/biossíntese , Feminino , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/enzimologiaRESUMO
The aim of the study was to evaluate the trends of initial CD4+ T-cell counts (CD4+) at HIV diagnoses and to identify the factors influencing the annual changes of CD4+ cell counts in Korea during 1988-2006. As a retrospective study, 2613 individuals (>/=15 years at diagnosis, their CD4+ counts were measured within six months) were selected from all 4580 HIV-infected Koreans diagnosed between 1985 and 2006. The mean CD4+ cell counts in all the selected individuals was 312 cells/mm(3), and this value decreased significantly by 20.3 cells/mm(3)/year over the 19 year study period. Men had lower CD4+ cell count than women by 22.7 cells/mm(3), and age at HIV diagnosis had an inverse relationship with CD4+ cell counts of 23.5 cells/mm(3) lower per 10 years advancing age. Cases diagnosed in hospitals showed CD4+ cell count levels 33.9 cells/mm(3) lower than public institutions by 33.9 cells/mm(3). Gender and age seemed to affect trends of CD4+ count; however the institution where cases were diagnosed had the strongest effect on decreasing CD4+ cell counts. The results suggest that HIV diagnoses in recent years are being made in later stages of HIV infection and that it is imperative to develop more efficient programmes for early HIV diagnosis to prevent transmission.
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Contagem de Linfócito CD4/tendências , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Adulto , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Transoral robotic surgery is an emerging strategy for treating human papillomavirus-positive cancers, but the role of MR imaging in predicting the surgical outcome has not been established. We aimed to identify preoperative MR imaging characteristics that predispose the outcome of transoral robotic surgery toward an insecure (positive or close) surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma. MATERIALS AND METHODS: Between December 2012 and May 2019, sixty-nine patients underwent transoral robotic surgery at our institution. Among these, 29 who were diagnosed with human papillomavirus-positive tonsillar squamous cell carcinoma, did not receive neoadjuvant treatment, underwent preoperative 3T MR imaging, and had postoperative pathologic reports and were included in this retrospective study. Two neuroradiologists evaluated the preoperative MR imaging scans to determine the tumor spread through the pharyngeal constrictor muscle using a 5-point scale: 1, normal constrictor; 2, bulging constrictor; 3, thinning constrictor; 4, obscured constrictor; and 5, tumor protrusion into the parapharyngeal fat. The risk of an insecure surgical margin (involved or <1 mm) according to the MR imaging scores was predicted using logistic regression with the Firth correction. RESULTS: The interobserver agreement for the MR imaging scores was excellent (κ = 0.955, P < .001). A score of ≥4 could predict an insecure margin with 87.5% sensitivity and 92.3% specificity (area under the curve = 0.899) and was the only significant factor associated with an insecure margin in the multivariable analysis (OR, 6.59; 95% CI, 3.11-22.28; P < .001). CONCLUSIONS: The pre-transoral robotic surgery MR imaging scoring system for the pharyngeal constrictor muscle is a promising predictor of the surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Margens de Excisão , Neoplasias Tonsilares/diagnóstico por imagem , Neoplasias Tonsilares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos/diagnóstico por imagem , Músculos/patologia , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Assistida por Computador/métodos , Neoplasias Tonsilares/virologia , Resultado do TratamentoRESUMO
Experimental leishmaniasis is widely used to study the effector functions of T helper cell subsets in vivo. Healing and nonhealing Leishmania major infections have been correlated with T helper 1 and T helper 2 responses, respectively. In the present study, we determined T cell effector functions ex vivo, without any further restimulation and compared them to those obtained following antigen-specific restimulation in vitro. Our results show that T helper cell responses are significantly less polarized when determined ex vivo as compared to those measured after restimulation in vitro. Moreover, the differences in CD4(+) T cell proliferation observed between healer and nonhealer strains of mice differed ex vivo and in vitro. Our results suggest that determination of both ex vivo as well as in vitro T cell responses is crucial to characterize immune responses during experimental leishmaniasis.
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Linfócitos T CD4-Positivos/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/fisiopatologia , Regeneração/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Feminino , Interferon gama/biossíntese , Interleucina-10/biossíntese , Interleucina-4/biossíntese , Leishmaniose Cutânea/patologia , Linfonodos/imunologia , Linfonodos/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBARESUMO
Polyphenols are nonessential phytonutrients abundantly found in fruits and vegetables. A wealth of data from preclinical models and clinical trials consistently supports cardiometabolic benefits associated with dietary polyphenols in murine models and humans. Furthermore, a growing number of studies have shown that specific classes of polyphenols, such as proanthocyanidins (PACs) and ellagitannins, as well as the stilbenoid resveratrol, can alleviate several features of the metabolic syndrome. Moreover, mounting evidence points to the gut microbiota as a key mediator of the health benefits of polyphenols. In this review we summarize recent findings supporting the beneficial potential of polyphenols against cardiometabolic diseases, with a focus on the role of host-microbe interactions.
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Doenças Cardiovasculares/metabolismo , Polifenóis/metabolismo , Animais , Microbioma Gastrointestinal/fisiologia , Humanos , Taninos Hidrolisáveis/metabolismo , Proantocianidinas/metabolismo , Resveratrol/metabolismoRESUMO
Recent studies have reported that two single nucleotide polymorphisms (SNPs) in the RANTES gene promoter region, -403G/A and -28C/G, are associated with a slower rate of decline in CD4(+) T-cell number, whereas genetic polymorphisms within the CCR5 promoter are linked to acceleration of AIDS progression. In this study, we investigated the distribution of SNPs in the RANTES and CCR5 promoters and the association between these SNPs and HIV-1 disease progression in HIV-infected Koreans. Twenty-seven long-term non-progressors (LTNPs), 29 AIDS patients and 39 HIV-uninfected persons were enrolled in this study. SNPs for the RANTES and CCR5 promoters were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and a direct sequencing method. In the analysis of RANTES promoter polymorphisms, the genotypic and allelic frequencies of the RANTES -28G mutation were significantly lower in HIV-infected patients than in HIV-uninfected persons (P = 0.005 and P = 0.001, respectively). The genotypic frequencies of RANTES -28G and -403A mutations did not differ significantly between LTNPs and AIDS patients. The frequencies of three CCR5 promoter polymorphisms, designated 59029 G/A, 59353T/C, and 59402G/A, did not differ significantly between HIV-uninfected and HIV-infected patients. However, the allelic frequency of CCR559353C was significantly higher in AIDS patients than in LTNPs (P = 0.003). These results suggest that RANTES-28G and CCR5 59353C mutations might be associated with HIV infection or pathogenesis in the Korean population.
Assuntos
Síndrome da Imunodeficiência Adquirida/genética , Quimiocina CCL5/genética , Frequência do Gene , HIV-1 , Polimorfismo de Nucleotídeo Único , Receptores CCR5/genética , Povo Asiático , Feminino , HIV-1/patogenicidade , Humanos , Coreia (Geográfico) , Masculino , Mutação PuntualRESUMO
BACKGROUND AND PURPOSE: DWI of the head and neck can reveal valuable information, but the effects of fat suppression and multishot acquisition on image quality have not been thoroughly investigated. We aimed to comprehensively compare the quality of head and neck DWI at 3T using 2 fat-suppression techniques, STIR, and spectral presaturation with inversion recovery, which were used with both single- and multishot EPI. MATERIALS AND METHODS: Sixty-five study participants underwent 3 DWI sequences of single-shot EPI-STIR, single-shot EPI-spectral presaturation with inversion recovery, and multishot EPI-spectral presaturation with inversion recovery of the head and neck. In multiple anatomic regions, 2 independent readers assessed 5-point visual scores for fat-suppression uniformity and image distortion, and 1 reader measured the contrast-to-noise ratio and ADC. RESULTS: The mean visual score for fat-suppression uniformity was higher in single-shot EPI-STIR than in other sequences (all regions except for the orbital region, P < .05). The mean visual score for image distortion was higher in multishot EPI-spectral presaturation with inversion recovery than in single-shot EPI sequences (all regions, P < .001). Contrast-to-noise ratio was mostly lower in single-shot EPI-STIR than in other sequences (P < .001), and ADC was significantly higher in multishot EPI-spectral presaturation with inversion recovery than in single-shot EPI sequences (P ≤ .001). CONCLUSIONS: Overall, multishot EPI-spectral presaturation with inversion recovery provided the best image quality, with relatively homogeneous fat suppression, less image distortion than single-shot EPI sequences, and higher contrast-to-noise ratio than single-shot EPI-STIR. The measured ADC values can be higher in multishot EPI-spectral presaturation with inversion recovery, which necessitates cautious application of the previously reported ADC values to clinical settings.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Cabeça/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Pescoço/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem Ecoplanar/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.
Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Cádmio/sangue , Cádmio/urina , Cálcio/uso terapêutico , Suplementos Nutricionais , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Osteoporose/tratamento farmacológico , Vitamina D/uso terapêutico , Absorciometria de Fóton , Idoso , Carga Corporal (Radioterapia) , Cobre , Feminino , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Eliminação Renal , República da Coreia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The Solitaire FR can be used not only as a tool for mechanical thrombectomy but also as a detachable permanent stent. Our aim was to assess the feasibility and safety of permanent stent placement with the Solitaire FR compared with other self-expanding stents for intracranial artery recanalization for acute ischemic stroke. MATERIALS AND METHODS: From January 2011 through January 2016, we retrospectively selected 2979 patients with acute ischemic stroke. Among them, 27 patients who underwent permanent stent placement (13 patients with the Solitaire FR [Solitaire group] and 14 patients with other self-expanding stents [other stent group]) were enrolled. The postprocedural modified TICI grade and angiographic and clinical outcomes were assessed. The safety and efficacy of permanent stent placement of the Solitaire FR for acute large-artery occlusion were evaluated. RESULTS: Stent placement was successful in all cases. Modified TICI 2b-3 reperfusion was noted in 84.6% of the Solitaire group and in 78.6% of the other stent group. Procedural time was significantly shorter in the Solitaire group than in the other stent group (P = .022). Shorter procedural time was correlated with favorable outcome (ρ = 0.46, P = .035). No significant differences were found in the modified TICI grade, NIHSS score, mRS, and hemorrhagic transformation rate between the 2 groups. The acute in-stent thrombosis rate at discharge was significantly lower when a glycoprotein IIb/IIIa inhibitor was injected during the procedure (P = .013). CONCLUSIONS: Permanent stent placement with the Solitaire FR compared with other self-expanding stents appears to be feasible and safe as a rescue tool for refractory intra-arterial therapy.
Assuntos
Arteriopatias Oclusivas/terapia , Revascularização Cerebral/instrumentação , Procedimentos Endovasculares/instrumentação , Stents , Acidente Vascular Cerebral/terapia , Idoso , Revascularização Cerebral/métodos , Procedimentos Endovasculares/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay is a powerful tool for measuring the frequency of alloantigen-specific T cells, reflecting cellular immunity. We correlated the pretransplant frequencies of donor-specific and third-party-specific IFN-gamma ELISPOT tests, with the posttransplant outcomes of 45 recipients of living donor renal transplantations. The mean frequency of pretransplant donor-specific ELISPOT was significantly greater among patients with acute rejection episodes (ARE) than those without ARE (18.0 [12 to 50] versus 8.8 [5 to 30.4]) spots per 200,000 peripheral blood lymphocytes (PBLs; P=.024). A cutoff level of 12 spots per 200,000 PBLs on the donor-specific ELISPOT identified an ARE-positive patient with a sensitivity of 81.8% and a specificity of 64.7%. The recipients with pretransplant donor-specific ELISPOT+showed higher serum creatinine levels and lower glomerular filtration rate (GFR) at 6 posttransplant months (P<.05). Although the pretransplant third-party-specific ELISPOT results correlated with the donor-specific ELISPOT results (r=.783; P<.001), there was no significant difference in the third-party ELISPOT results between the ARE-positive and ARE-negative recipients. In conclusion, an analysis of pretransplant donor-specific IFN-gamma ELISPOT may identify the posttransplant risk of developing ARE and displaying decreased GFR at 6 months.
Assuntos
Rejeição de Enxerto/patologia , Interferon gama/sangue , Transplante de Rim/patologia , Adulto , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Rejeição de Enxerto/imunologia , Humanos , Isoantígenos/imunologia , Transplante de Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Linfócitos T/imunologiaRESUMO
BACKGROUND AND PURPOSE: Typewriter tinnitus, a symptom characterized by paroxysmal attacks of staccato sounds, has been thought to be caused by neurovascular compression of the cochlear nerve, but the correlation between radiologic evidence of neurovascular compression of the cochlear nerve and symptom presentation has not been thoroughly investigated. The purpose of this study was to examine whether radiologic evidence of neurovascular compression of the cochlear nerve is pathognomonic in typewriter tinnitus. MATERIALS AND METHODS: Fifteen carbamazepine-responding patients with typewriter tinnitus and 8 control subjects were evaluated with a 3D T2-weighted volume isotropic turbo spin-echo acquisition sequence. Groups 1 (16 symptomatic sides), 2 (14 asymptomatic sides), and 3 (16 control sides) were compared with regard to the anatomic relation between the vascular loop and the internal auditory canal and the presence of neurovascular compression of the cochlear nerve with/without angulation/indentation. RESULTS: The anatomic location of the vascular loop was not significantly different among the 3 groups (all, P > .05). Meanwhile, neurovascular compression of the cochlear nerve on MR imaging was significantly higher in group 1 than in group 3 (P = .032). However, considerable false-positive (no symptoms with neurovascular compression of the cochlear nerve on MR imaging) and false-negative (typewriter tinnitus without demonstrable neurovascular compression of the cochlear nerve) findings were also observed. CONCLUSIONS: Neurovascular compression of the cochlear nerve was more frequently detected on the symptomatic side of patients with typewriter tinnitus compared with the asymptomatic side of these patients or on both sides of control subjects on MR imaging. However, considering false-positive and false-negative findings, meticulous history-taking and the response to the initial carbamazepine trial should be regarded as more reliable diagnostic clues than radiologic evidence of neurovascular compression of the cochlear nerve.