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1.
BMJ Case Rep ; 17(10)2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357919

RESUMO

Solitary fibrous tumours (SFTs) and chronic myeloid leukaemia (CML) are both uncommon neoplasms with distinct chromosomal aberrations and clinical presentations. Here, we present a case of a male in his late 50s with a history of intracranial SFT who presented 8 years after subtotal resection and adjuvant radiotherapy with splenic infarcts, a white blood cell of 83 000 cells/mL, and liver masses. He was treated with dasatinib for CML and temozolomide/bevacizumab for SFT. This case emphasises the benefits of broad differential diagnoses that include multiple concurrent disease processes when confronted with unusual presentations. It highlights the need for interdisciplinary efforts and personalised approaches when managing patients with multiple primary malignancies.


Assuntos
Neoplasias Encefálicas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Tumores Fibrosos Solitários , Humanos , Masculino , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Neoplasias Encefálicas/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Diagnóstico Diferencial , Dasatinibe/uso terapêutico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Temozolomida/uso terapêutico
2.
Adv Sci (Weinh) ; 11(33): e2400398, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38958553

RESUMO

The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen deprivation or AR antagonist therapy, highlights the need to explore alternative strategies. One strategy involves the use of heterobifunctional degraders, also known as proteolysis-targeting chimeras, which are novel small-molecule therapeutics that inhibit amplified or mutated targets. Here, the study reports a novel cereblon-based AR degrader, UBX-390, and demonstrates its superior activity over established AR degraders, such as ARV-110 or ARCC-4, in prostate cancer cells under short- and long-term treatment conditions. UBX-390 suppresses chromatin binding and gene expression of AR and demonstrates substantial efficacy in the degradation of AR mutants in patients with treatment-resistant prostate cancer. UBX-390 is presented as an optimized AR degrader with remarkable potential for treating castration-resistant prostate cancer.


Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Linhagem Celular Tumoral , Animais , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Camundongos , Modelos Animais de Doenças , Proteólise/efeitos dos fármacos
3.
J Korean Med Sci ; 39(21): e166, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38832476

RESUMO

BACKGROUND: The Korea Expert Committee on Immunization Practices (KECIP) is a key advisory body the government to develop guidelines and provide technical advisory activities on immunization policies in Korea. A recent policy study, inspired by global best practices, aims to enhance KECIP's functionality for providing timely and transparent recommendations in the face of evolving vaccine science and emerging infectious diseases like COVID-19. METHODS: This study reviewed the current status of KECIP and collected expert opinions through surveys and consultations. Among the 40 panel members who were surveyed, 19 responded to a questionnaire specifically designed to assess the potential areas of improvement within KECIP. RESULTS: The majority of respondents favored maintaining the current member count and emphasized the need for a subcommittee. Opinions varied on issues such as the length of KECIP's term, the representation of vaccine manufacturers' perspectives, and the chairperson's role. However, there was a consensus on the importance of expertise, transparency, and fair proceedings within the committee. CONCLUSION: This study underscores the pivotal role of KECIP in shaping national immunization policies, emphasizing the necessity for informed guidance amidst evolving vaccine science and emerging infectious diseases. Furthermore, it stressed the importance of enhancing KECIP's capacity to effectively address evolving public health challenges and maintain successful immunization programs in South Korea.


Assuntos
COVID-19 , Consenso , Humanos , República da Coreia , COVID-19/prevenção & controle , Inquéritos e Questionários , Imunização , Comitês Consultivos , SARS-CoV-2 , Política de Saúde , Vacinas contra COVID-19
4.
Obstet Gynecol Sci ; 66(5): 337-346, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37439085

RESUMO

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality globally. PTB rates have increased in South Korea despite reduction in birth rates. A history of PTB is a strong predictor of subsequent PTB and screening of cervical length between 16 0/7 weeks and 24 0/7 weeks of gestation is recommended in women with a singleton pregnancy and a prior spontaneous PTB. However, the prediction and prevention of spontaneous PTBs in women without a prior PTB remain a matter of debate. The scope of this review article comprises cervical screening and prevention strategies for PTB in asymptomatic women without a prior PTB, based on recent evidence and guidelines.

5.
Life (Basel) ; 13(6)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37374113

RESUMO

This study aimed to develop an early pregnancy risk scoring model for pregnancy-associated hypertension (PAH) based on maternal pre-pregnancy characteristics, such as mean arterial pressure (MAP), pregnancy-associated plasma protein-A (PAPP-A) or neither. The perinatal databases of seven hospitals from January 2009 to December 2020 were randomly divided into a training set and a test set at a ratio of 70:30. The data of a total pregnant restricted population (women not taking aspirin during pregnancy) were analyzed separately. Three models (model 1, pre-pregnancy factors only; model 2, adding MAP; model 3, adding MAP and PAPP-A) and the American College of Obstetricians and Gynecologists (ACOG) risk factors model were compared. A total of 2840 (8.11%) and 1550 (3.3%) women subsequently developed PAH and preterm PAH, respectively. Performances of models 2 and 3 with areas under the curve (AUC) over 0.82 in both total population and restricted population were superior to those of model 1 (with AUCs of 0.75 and 0.748, respectively) and the ACOG risk model (with AUCs of 0.66 and 0.66) for predicting PAH and preterm PAH. The final scoring system with model 2 for predicting PAH and preterm PAH showed moderate to good performance (AUCs of 0.78 and 0.79, respectively) in the test set. "A risk scoring model for PAH and preterm PAH with pre-pregnancy factors and MAP showed moderate to high performances. Further prospective studies for validating this scoring model with biomarkers and uterine artery Doppler or without them might be required".

6.
J Clin Med ; 12(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240542

RESUMO

This study aimed to investigate the clinical features and risk factors of uveitis in Korean children with juvenile idiopathic arthritis (JIA). The medical records of JIA patients diagnosed between 2006 and 2019 and followed up for ≥1 year were retrospectively reviewed, and various factors including laboratory findings were analyzed for the risk of developing uveitis. JIA-associated uveitis (JIA-U) developed in 30 (9.8%) of 306 JIA patients. The mean age at the first uveitis development was 12.4 ± 5.7 years, which was 5.6 ± 3.7 years after the JIA diagnosis. The common JIA subtypes in the uveitis group were oligoarthritis-persistent (33.3%) and enthesitis-related arthritis (30.0%). The uveitis group had more baseline knee joint involvement (76.7% vs. 51.4%), which increased the risk of JIA-U during follow-up (p = 0.008). Patients with the oligoarthritis-persistent subtype developed JIA-U more frequently than those without it (20.0% vs. 7.8%; p = 0.016). The final visual acuity of JIA-U was tolerable (0.041 ± 0.103 logMAR). In Korean children with JIA, JIA-U may be associated with the oligoarthritis-persistent subtype and knee joint involvement.

7.
Blood Adv ; 7(1): 92-105, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36269842

RESUMO

Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade. BCR activation can contribute to the growth and survival of B-cell lymphoma or leukemia. The inhibition of the BCR signaling pathway is critical for blocking downstream events and treating B-cell lymphomas. Herein, we report potent and orally available proteolysis-targeting chimeras (PROTACs) that target BTK to inactivate BCR signaling. Of the PROTACs tested, UBX-382 showed superior degradation activity for wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of half-maximal degradation concentration in diffuse large B-cell lymphoma cell line. UBX-382 was effective on 7 out of 8 known BTK mutants in in vitro experiments and was highly effective in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells over ibrutinib, ARQ-531, and MT-802. Remarkably, oral dosing of UBX-382 for <2 weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. UBX-382 also provoked the cell type-dependent and selective degradation of cereblon neosubstrates in various hematological cancer cells. These results suggest that UBX-382 treatment is a promising therapeutic strategy for B-cell-related blood cancers with improved efficacy and diverse applicability.


Assuntos
Linfoma Difuso de Grandes Células B , Pirimidinas , Humanos , Animais , Camundongos , Tirosina Quinase da Agamaglobulinemia , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Transdução de Sinais , Modelos Animais de Doenças , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética
8.
Vaccines (Basel) ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36366321

RESUMO

Although there have been several studies regarding the immunogenicity of one or two booster doses of the measles−mumps−rubella (MMR) vaccine in measles-seronegative young adults, limited data are available about how long the immune response is sustained compared with natural infection. This study included seronegative healthcare workers (HCWs) (aged 21−38 years) who received one or two doses of the measles−mumps−rubella (MMR) vaccine and HCWs with laboratory-confirmed measles infection during an outbreak in 2019. We compared neutralizing antibody titers measured using the plaque reduction neutralization (PRN) test and measles-specific immunoglobulin G (IgG) using chemiluminescent immunoassays 2 years after vaccination or infection. Among 107 HCWs with seronegative measles IgGs, the overall seroconversion rate of measles IgGs remained 82.2% (88/107), and 45.8% (49/107) of the participants had a medium (121−900) or high (>900) PRN titer after 2 years from one or two booster doses. The measles-neutralizing antibody titers of both PRN titer (ND50) and geometric mean concentration 2 years after natural infection were significantly higher than those of one or two booster doses of the MMR vaccine (p < 0.001 and p < 0.001, respectively). Our results suggest that serologic screening followed by appropriate postexposure prophylaxis can be beneficial for young HCWs without a history of natural infection especially in a measles outbreak setting, because of possible susceptibility to measles despite booster MMR vaccination 2 years ago. Long-term data about sustainable humoral immunity after one or two booster vaccination are needed based on the exact vaccination history.

9.
Viruses ; 14(11)2022 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-36366556

RESUMO

In this study, we aimed to determine the effect of COVID-19 vaccination on 3-month immune response and durability after natural infection by the Omicron variant and to assess the immune response to a fourth dose of COVID-19 vaccination in patients with prior natural infection with the Omicron variant. Overall, 86 patients aged ≥60 years with different vaccination histories and 39 health care workers (HCWs) vaccinated thrice before Omicron infection were enrolled. The sVNT50 titer was significantly lower in patients with incomplete vaccination before SARS-CoV-2 infection with the S clade (p < 0.001), Delta variant (p < 0.001), or Omicron variant (p = 0.003) than in those vaccinated thrice. The sVNT results against the Omicron variant did not differ significantly in patients aged ≥60 years (p = 0.49) and HCWs (p = 0.17), regardless of the recipient receiving the fourth dose 2 months after COVID-19. Incomplete COVID-19 vaccination before Omicron infection for individuals aged ≥60 years conferred limited protection against homologous and heterologous virus strains, whereas two or three doses of the vaccine provided cross-variant humoral immunity against Omicron infection for at least 3 months. However, a fourth dose 2 months after Omicron infection did not enhance immunity against the homologous strain. A future strategy using the bivalent Omicron-containing booster vaccine with appropriate timing will be crucial.


Assuntos
COVID-19 , Vacinas Virais , Humanos , Imunidade Humoral , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Vacinação , Anticorpos Antivirais
10.
Vaccines (Basel) ; 10(8)2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36016153

RESUMO

The vaccination of immunocompromised children against coronavirus disease 2019 is an important public health issue. We evaluated the serological response, safety, and efficacy of the BNT162b2 vaccine in children with and without inflammatory bowel disease (IBD). A prospective, multicenter, case-control study was conducted in a pediatric population, including patients with IBD, aged 12-18 years. Clinical characteristics, safety profile, and serum samples for surrogate virus-neutralizing antibody testing pre- and post-BNT162b2 vaccination were assessed. The breakthrough infection rate during the Omicron outbreak was calculated to evaluate efficacy. Fifteen controls and twenty-three patients with IBD were enrolled. After two vaccine doses, the median level of percentage inhibition was highly increased, without significant differences between the groups (control 96.9 and IBD 96.3). However, it was significantly reduced in IBD patients receiving combination therapy (anti-tumor necrosis factor-α + immunomodulators) relative to those in other therapies and controls. Serious adverse events were not observed. The breakthrough infection rate was 42.1%, without statistical differences between the groups. Immunization with BNT162b2 in patients with IBD was comparable with that in healthy adolescents in terms of immunogenicity and safety. Nevertheless, the efficacy of BNT162b2 in preventing infection caused by the Omicron variant in the pediatric population was insufficient.

11.
Immune Netw ; 22(2): e16, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35573152

RESUMO

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103+CD11b- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103+CD11b- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-ß2 and Aldh1a2 expression in CD103+CD11b- DCs in mice infected with LM might affect to increase of Foxp3+ regulatory T cells. Changes of major subset of DCs from CD103+ to CD103- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

12.
Eur J Clin Microbiol Infect Dis ; 41(3): 455-466, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34999974

RESUMO

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.


Assuntos
Infecção Hospitalar , Sarampo , Adolescente , Adulto , Anticorpos Antivirais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Hospitais , Humanos , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola , República da Coreia/epidemiologia , Vacinação , Adulto Jovem
13.
Children (Basel) ; 8(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34682110

RESUMO

Herpes zoster (HZ) is caused by latent varicella-zoster virus (VZV) reactivation when VZV-specific cell-mediated immunity declines. Information on HZ in children is limited. Therefore, we retrospectively investigated HZ's clinical course and complications in children. We extracted the outpatient and hospitalization medical records of pediatric patients (<19 years) primarily diagnosed with HZ (ICD-10 B02 code) between January 2010 and November 2020. HZ was defined as a typical unilateral dermatomal vesicular rash where HZ was the treating physician's primary diagnosis. Recognized HZ complications included combined bacterial skin infection, ophthalmic zoster, zoster oticus without facial paralysis, meningitis, and PHN. We identified 602 HZ cases, among which 54 developed HZ complications and were included in our analysis. The median age was 14.7 years, most patients were aged ≥13 years (42, 79%), and none were aged <4 years. Fifty-three were immunocompetent, and only one had systemic lupus erythematosus. The most frequent complication was zoster ophthalmicus (n = 26, 48%). HZ complications were also observed in immunocompetent or vaccinated children exhibiting a head or neck rash before and after VZV immunization. Current VZV vaccination programs may be insufficient in preventing HZ complications. Therefore, close varicella and HZ burden monitoring and the establishment of effective VZV vaccination programs are imperative.

14.
Vaccine ; 38(51): 8145-8153, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33162203

RESUMO

Pneumococcal conjugate vaccines (PCVs) have been effective in reducing the disease burden caused by Streptococcus pneumoniae. The first licensed PCV (PCV7) was composed of capsular polysaccharides from seven serotypes. This was followed by PCV10, then PCV13, and currently there are a number of higher valency vaccines in development. As part of licensure, new vaccine iterations require assessment of immunogenicity. Since some antibodies can be non-functional, measuring functional antibodies is desirable. To meet this need, opsonophagocytic assays (OPAs) have been developed. Previous studies have shown there can be significant variations in OPA results from different laboratories. We have previously shown that standardizing OPA data using reference serum 007sp can decrease this variation. To extend this approach to additional serotypes, a panel of sera was tested by five laboratories using a multiplexed OPA for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F. Each sample was tested in five runs with 007sp tested three times in each run. Results were analyzed using a mixed effects ANOVA model. Standardization of the results significantly decreased the inter-laboratory variation for some serotypes. For serotypes 2, 8, and 11A, the variability was reduced by 40%, 45%, and 40%, respectively. For serotypes 12F, 17F, and 20B, the reductions were more modest (14%, 19%, and 24%, respectively). Standardization had little effect for the remaining serotypes. In many cases, the impact of normalization was blunted by the results from five sera that were collected after an extended post-vaccination interval. We have previously reported consensus values for 007sp for 13 serotypes, as well as the creation of a calibration serum panel ("Ewha Panel A"). Here, we report consensus values for 11 additional serotypes for 007sp and the creation of a second serum panel ("Ewha Panel B"). These consensus values will facilitate the development of next-generation PCVs.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Anticorpos Antibacterianos , Calibragem , Humanos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Vacinas Conjugadas
15.
Clin Exp Pediatr ; 63(4): 125-132, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32252139

RESUMO

Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

16.
J Korean Med Sci ; 34(23): e169, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31197986

RESUMO

BACKGROUND: After the introduction of the meningococcal ACWY-CRM197 conjugate vaccine (MenACWY-CRM) in 2012 and the meningococcal ACWY-diphtheria toxoid conjugate vaccine (MenACWY-DT) in 2014, immunization was recommended for certain high-risk groups including new military recruits in Korea. However, comparative immunogenicity studies for these vaccines have not been performed in Korea. Here, we compared the immunogenicity of these two vaccines in healthy adults. METHODS: A total of 64 adults, 20-49 years of age, were randomly divided into two groups (1:1) to receive either of the two vaccines. The sera were obtained before and 1 month after vaccination and tested for serogroup-specific serum bactericidal activity using baby rabbit complement. RESULTS: There were no significant differences post-vaccination in the geometric mean indices and the seropositive rate to all serogroups between the vaccines. The proportion of seropositive subjects after vaccination ranged from 88% to 100%. CONCLUSION: Both meningococcal conjugate vaccines showed good immunogenicity in healthy Korean adults without statistically significant differences. Further investigations for serotype distribution of circulating meningococci and the immune interference between other diphtheria toxin-containing vaccines concomitantly used for military recruits are needed to optimize immunization policies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002460.


Assuntos
Proteínas de Bactérias/química , Toxoide Diftérico/química , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Vacinas Conjugadas/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Feminino , Humanos , Masculino , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/química , Pessoa de Meia-Idade , Neisseria meningitidis/imunologia , Sorogrupo , Vacinas Conjugadas/química , Adulto Jovem
17.
Int Forum Allergy Rhinol ; 9(7): 724-729, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30907985

RESUMO

BACKGROUND: Staphylococcus pseudintermedius is a Gram-positive bacteria that colonizes the skin and orifices of healthy canines and felines. It has recently been identified as a cause of sinonasal infections in humans. METHODS: This study was a retrospective review of chronic rhinosinusitis (CRS) patients with S pseudintermedius-positive sinonasal cultures and comparison to a prospectively collected control sample of patients who underwent culture for acute exacerbation of CRS. RESULTS: Thirty-three patients with CRS had nasal cultures positive for S pseudintermedius. Of the positive cultures, 82% demonstrated resistance to penicillin, 58% to clindamycin, 45% to trimethoprim-sulfamethoxazole, 33% to doxycycline, and 27% to oxacillin. Ninety-seven percent of patients with S pseudintermedius were dog owners. There was no significant difference in age, gender, recent endoscopic sinus surgery, or immunosuppression or deficiency between S pseudintermedius patients and patients undergoing culture for acute exacerbation of CRS, but S pseudintermedius infection was associated with dog ownership (p < 0.01). S pseudintermedius infection was not associated with behaviors such as a dog sleeping in the bedroom, routinely licking humans, or being diagnosed with a soft tissue infection. CONCLUSION: Although a rare cause of infection in humans, S pseudintermedius should be considered in sinonasal infections refractory to standard medical management, especially if the patient has regular contact with dogs. S pseudintermedius is not readily identified with routine laboratory diagnostic testing and often demonstrates multidrug resistance, making it a pathogen that is commonly misdiagnosed and difficult to treat.


Assuntos
Animais de Estimação/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus , Animais , Antibacterianos/uso terapêutico , Doenças do Gato/transmissão , Gatos , Doença Crônica , Doenças do Cão/transmissão , Cães , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/microbiologia , Rinite/tratamento farmacológico , Fatores de Risco , Sinusite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Zoonoses/transmissão
18.
Acta Biomater ; 90: 362-372, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30922953

RESUMO

Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. STATE OF SIGNIFICANCE: In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Nanopartículas/química , Infecções Pneumocócicas , Vacinas Pneumocócicas , Streptococcus pneumoniae/imunologia , Vacinação , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Administração Intranasal , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/uso terapêutico , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/patologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/farmacologia
19.
Int J Biol Macromol ; 131: 1084-1091, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30914368

RESUMO

Barley is commonly used in many food and health products. We have previously demonstrated the macrophage-stimulating properties of polysaccharides derived from fermented barley. In this study, three polysaccharide fractions (BF-I-III) were purified from fermented barley and their monosaccharide composition was analyzed. Their immune-stimulatory activities and intracellular signaling pathways were also studied in RAW264.7 cells. Among the three fractions, BF-I exhibited enhanced macrophage activation properties, such as inducing the production of IL-6, IL-12, and TNF-α. However, BF-II and BF-III showed moderate effects on RAW 264.7 cells. BF-I treatment led to the phosphorylation of MAPKs, NF-κB, and c-Jun (major component of AP-1 transcription factor) and induced the nuclear translocation of p65 in RAW264.7 cells. In addition, experiments with neutralizing antibodies showed that Dectin-1, toll-like receptor (TLR) 4, scavenge receptor (SR), and CD14 were mainly involved in the stimulation of nitric oxide (NO) production by BF-I which was suppressed by the inhibition of JNK phosphorylation. These findings suggest that BF-I, isolated from fermented barley, has an immune potentiation activity on macrophages, where it activates the JNK signaling pathway via several macrophage receptors including dectin-1, TLR4, SR, and CD14.


Assuntos
Hordeum/química , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Polissacarídeos/imunologia , Transdução de Sinais , Animais , Biomarcadores , Sobrevivência Celular , Fracionamento Químico , Cromatografia , Citocinas/biossíntese , Fermentação , Mediadores da Inflamação/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peso Molecular , NF-kappa B/metabolismo , Fosforilação , Extratos Vegetais , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Açúcares/química
20.
Comput Methods Biomech Biomed Engin ; 22(3): 251-258, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30773916

RESUMO

The purpose of this study is to measure the failure risk of a crown depending on the cusp angle. Three all-ceramic crown models consisting of CH (high incline), CM (middle incline), and CL (low incline) are designed. Stress is applied to the crown with Loading case-1 (top of cusp tip) and Loading case-2 (middle of cusp ridge) with the use of FEA software. In Loading case-1 and case-2, the CH showed the highest Maximum Principal Stress (MPS) while the CL showed the lowest MPS. The cusp angle is an influential factor affecting stress distribution in dental crowns.


Assuntos
Coroas , Planejamento de Prótese Dentária , Análise do Estresse Dentário , Análise de Elementos Finitos , Humanos , Estresse Mecânico
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