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1.
Am J Emerg Med ; 85: 166-171, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39276687

RESUMEN

BACKGROUND: Limited data are available on locations of public access defibrillation programs across communities in the United States, despite their widespread presence. Our goal was to determine publicly available AED locations of large businesses in a mixed urban-rural county. We then compared our survey results to a NC state-mandated AED registry and the county's emergency medical dispatch center AED registry. METHODS: We conducted structured phone surveys of all large businesses (>19 employees) and select small businesses (healthcare, government, childcare, educational, and religious organizations with 1-19 employees) in Forsyth County, NC (n = 1702) to determine AED ownership and location. In addition, AED lists were elicited from multi-building organizations (e.g., health systems, universities, and local government), the NC Office of Emergency Medical Services (OEMS), and the Forsyth County emergency medical dispatch center. RESULTS: Our survey yielded a response rate of 79.1 % and identified 411 businesses with ≥ 1 AEDs. An additional 162 AED locations were contained in AED lists from multi-building organizations and registries. In total, our canvas identified 963 AEDs at 573 unique locations. The majority of AEDs (65.1 % [627/963]) were not previously registered in the NC OEMS AED registry. Few identified AEDs (11.8 % [114/963]) were listed in the county emergency medical dispatch center registry.

2.
Int J Mol Sci ; 25(17)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39273400

RESUMEN

Zika virus (ZIKV), transmitted by Aedes mosquitoes, has been a global health concern since 2007. It primarily causes fetal microcephaly and neuronal defects through maternal transmission and induces neurological complications in adults. Recent studies report elevated proinflammatory cytokines and persistent neurological alterations post recovery, but the in vivo mechanisms remain unclear. In our study, viral RNA loads in the brains of mice infected with ZIKV peaked at 7 days post infection and returned to baseline by day 21, indicating recovery. RNA sequencing of the cerebral cortex at 7 and 21 days revealed upregulated genes related to neuroinflammation and microglial activation. Histological analyses indicated neuronal cell death and altered neurite morphology owing to severe neuroinflammation. Additionally, sustained microglial activation was associated with increased phospho-Tau levels, constituting a marker of neurodegeneration. These findings highlight how persistent microglial activation leads to neuronal dysfunction post ZIKV recovery, providing insights into the molecular pathogenesis of ZIKV-induced brain abnormalities.


Asunto(s)
Microglía , Neuronas , Infección por el Virus Zika , Virus Zika , Animales , Infección por el Virus Zika/virología , Infección por el Virus Zika/patología , Infección por el Virus Zika/metabolismo , Microglía/virología , Microglía/metabolismo , Microglía/patología , Ratones , Virus Zika/fisiología , Virus Zika/patogenicidad , Neuronas/virología , Neuronas/metabolismo , Neuronas/patología , Sinapsis/patología , Sinapsis/metabolismo , Encéfalo/virología , Encéfalo/patología , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Femenino , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/virología , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/metabolismo , Carga Viral
3.
Anim Biotechnol ; 31(1): 32-41, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30570378

RESUMEN

PERV is a major virus concerning xenotransplantation study. However, the interesting part is that PERV is present in all kinds of pigs without pathogenicity and immune response. Furthermore, since pig cells have receptors for PERV, the gene delivery system using PERV envelope is highly likely to develop into an excellent viral vector in pigs. We developed a recombinant baculovirus with a modified surface for expressing the porcine endogenous retrovirus (PERV) envelope. Porcine reproductive and respiratory syndrome virus (PRRSV) infection is a severe concern in the porcine industry due to reproduction failure and respiratory symptoms. GP5 and M proteins are major immunogenic proteins of PRRSV. Using PERV-modified baculovirus (Ac mPERV) as a delivery vector, we constructed a dual antigen (GP5 and M)-encoding DNA vaccine system, Ac mPERV-C5/C6. Intramuscular immunization in mice and pigs, Ac mPERV-C5/C6 induced comparative high humoral and cellular immune responses. Our results support further development of Ac mPERV-C5/C6 as a potential PRRSV vaccine in the porcine industry. In addition, the Ac mPERV system may be applied to the generation of other effective DNA vaccines against porcine viral diseases.


Asunto(s)
Síndrome Respiratorio y de la Reproducción Porcina/prevención & control , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Proteínas del Envoltorio Viral/inmunología , Proteínas de la Matriz Viral/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/inmunología , Baculoviridae/genética , Retrovirus Endógenos/genética , Inmunidad Humoral , Ratones , Ratones Endogámicos BALB C , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Proteínas Recombinantes , Organismos Libres de Patógenos Específicos , Spodoptera , Porcinos , Vacunas de ADN/genética , Vacunas de ADN/inmunología , Proteínas del Envoltorio Viral/genética , Proteínas de la Matriz Viral/genética , Vacunas Virales/genética
4.
Biochem Biophys Res Commun ; 505(4): 1010-1014, 2018 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-30309651

RESUMEN

Zika virus (ZIKV), a mosquito-borne flavivirus that has recently emerged globally, poses a major threat to public health. To control this emerging disease, accurate diagnostics are required for monitoring current ZIKV outbreaks. Owing to the high nucleotide sequence similarity and cross-reactivity of ZIKV with other members of the Flaviviridae family, discrimination from other flavivirus infections is often difficult in endemic areas. ZIKV NS1 induces major virus-specific antibodies and is therefore utilized as a serological marker for ZIKV diagnosis. To identify ZIKV specific epitopes for clinical application, 33 NS1 peptides that are 15-30 amino acid in length covering whole NS1 were synthesized and analyzed linear B-cell epitopes with 38 human serum samples (20 ZIKV-positive and 18 ZIKV-negative). As a result of screening, eight epitope regions were identified. In particular, the Z8 and Z14 peptides located in the ß-ladder surface region showed higher levels of binding activity in ZIKV-positive sera without cross-reactivity to other flaviviruses. These identified sensitive and specific epitopes provide a tool for design of diagnostics and structure-based vaccine antigens for ZIKV infection.


Asunto(s)
Epítopos de Linfocito B/química , Péptidos/análisis , Virus Zika/química , Epítopos de Linfocito B/sangre , Humanos , Modelos Moleculares , Péptidos/síntesis química
5.
Heart Vessels ; 29(5): 578-83, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23974943

RESUMEN

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.


Asunto(s)
Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Ticlopidina/análogos & derivados , Warfarina/uso terapéutico , Anciano , Anticoagulantes/efectos adversos , Pueblo Asiatico , Aspirina/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etnología , Fibrilación Atrial/mortalidad , Coagulación Sanguínea/efectos de los fármacos , Clopidogrel , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etnología , Enfermedad de la Arteria Coronaria/mortalidad , Trombosis Coronaria/etnología , Trombosis Coronaria/prevención & control , Supervivencia sin Enfermedad , Monitoreo de Drogas/métodos , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Humanos , Relación Normalizada Internacional , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/etnología , Infarto del Miocardio/prevención & control , Oportunidad Relativa , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Modelos de Riesgos Proporcionales , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etnología , Accidente Cerebrovascular/prevención & control , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Warfarina/efectos adversos
6.
J Microbiol ; 61(7): 703-711, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37358709

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence in 2019 led to global health crises and the persistent risk of viral mutations. To combat SARS-CoV-2 variants, researchers have explored new approaches to identifying potential targets for coronaviruses. This study aimed to identify SARS-CoV-2 inhibitors using drug repurposing. In silico studies and network pharmacology were conducted to validate targets and coronavirus-associated diseases to select potential candidates, and in vitro assays were performed to evaluate the antiviral effects of the candidate drugs to elucidate the mechanisms of the viruses at the molecular level and determine the effective antiviral drugs for them. Plaque and cytopathic effect reduction were evaluated, and real-time quantitative reverse transcription was used to evaluate the antiviral activity of the candidate drugs against SARS-CoV-2 variants in vitro. Finally, a comparison was made between the molecular docking binding affinities of fenofibrate and remdesivir (positive control) to conventional and identified targets validated from protein-protein interaction (PPI). Seven candidate drugs were obtained based on the biological targets of the coronavirus, and potential targets were identified by constructing complex disease targets and PPI networks. Among the candidates, fenofibrate exhibited the strongest inhibition effect 1 h after Vero E6 cell infection with SARS-CoV-2 variants. This study identified potential targets for coronavirus disease (COVID-19) and SARS-CoV-2 and suggested fenofibrate as a potential therapy for COVID-19.


Asunto(s)
COVID-19 , Fenofibrato , Humanos , SARS-CoV-2 , Antivirales/farmacología , Antivirales/química , Simulación del Acoplamiento Molecular , Fenofibrato/farmacología
7.
PLOS Glob Public Health ; 3(12): e0002539, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38109300

RESUMEN

Despite prevalent preventative methods of human papillomavirus (HPV), cervical cancer remains the foremost cause of cancer-related death among women of reproductive age in Western Kenya. HPV self-sampling is a preventative measure that can improve accessibility and availability to cervical cancer screening. Correct education about HPV is crucial to combating stigma and increasing HPV screening uptake. In this study, we evaluated the workflow impact of a video-assisted HPV education to promote self-sampling in clinical settings in Kisumu, Kenya. We conducted a descriptive workflow study nested in a two-part cluster-randomized control trial in six government-supported health clinics in Kisumu County. We observed the workflow of HPV screening video-assisted and standard health educations. and evaluated community and clinic health assistant facilitation (CCHA), duration, and feasibility of the intervention. Thirty HPV screening-eligible women who participated in the video intervention were recruited for three focus group discussions (FGDs). The FGDs aimed to better understand women's experience with the video screening, their impressions on the content, and feedback about intervention logistics. Across 33 observations, 16.5 women per day watched the educational video at intervention clinics, and 14 women per day heard standard Ministry of Health cervical cancer prevention education talks at control clinics. Sixty-three percent of women participated in HPV self-sampling in the intervention sites, compared to forty-six percent who screened after standard health talks at control sites. The workflow observations identified variable video projection and viewing space, access to power supply, and CCHA availability and ability to utilize the projector as major factors impacting education workflow. Women in FGDs appreciated the video modality, length of video, and education location. HPV video education is a suitable intervention, with further research recommended to determine the viability of sustainably implementing the intervention in a clinic environment. This research is fully funded by the Duke University Global Health Institute.

8.
Cell Death Discov ; 8(1): 153, 2022 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-35368019

RESUMEN

Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by ß-amyloid (Aß) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigger AD pathological features, including Aß and p-Tau expression. AD-related phenotypes in brain organoids were upregulated via endoplasmic reticulum (ER) stress and unfolded protein response (UPR) after ZIKV infection in brain organoids. Under persistent ER stress, activated-double stranded RNA-dependent protein kinase-like ER-resident (PERK) triggered the phosphorylation of Eukaryotic initiation factor 2 (eIF2α) and then BACE, and GSK3α/ß related to AD. Furthermore, we demonstrated that pharmacological inhibitors of PERK attenuated Aß and p-Tau in brain organoids after ZIKV infection.

9.
Eur J Pharmacol ; 904: 174144, 2021 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-33957087

RESUMEN

Zika virus (ZIKV) is a mosquito-borne flavivirus, that could cause congenital Zika syndrome (CZS), characterized by microcephaly, neurological complications and fetal deaths. No specific treatments for ZIKV are currently available, highlighting the urgent global need to identify and develop therapeutic agents. Drug repositioning of approved natural compounds can provide effective alternative solutions for novel antiviral development. The current study focused on curcumin, a component of turmeric known to exert diverse antiviral effects. We integrated in silico information from publicly available databases to predict interactions between curcumin and potential targets of ZIKV. In our network analysis, we identified four targets, TP53, AKT1, PTEN, and TNF, which were identified as potential targets associated with ZIKV. Based on retrieved targets, we performed molecular docking study and identified curcumin-TNF showed the strongest binding among four targets. The anti-Zika effects of curcumin were validated in vitro with the aid of antiviral and plaque reduction assay. Curcumin at concentrations ranging from 12.5 to 50 µM displayed significant antiviral activity in a dose-dependent manner (p < 0.05). In view of its natural abundance and prevalence in the human diet, curcumin holds significant promise for treatment of ZIKV infections.


Asunto(s)
Antivirales/farmacología , Curcumina/farmacología , Infección por el Virus Zika/tratamiento farmacológico , Virus Zika/efectos de los fármacos , Animales , Antivirales/química , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Simulación por Computador , Curcumina/química , Reposicionamiento de Medicamentos , Mapas de Interacción de Proteínas , Células Vero , Ensayo de Placa Viral , Acoplamiento Viral/efectos de los fármacos
10.
Perm J ; 252021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33970086

RESUMEN

BACKGROUND: The renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2) are now well established, and these agents are recommended by the American Diabetes Association and Kidney Disease: Improving Global Outcomes guidelines for patients with type 2 diabetes and chronic kidney disease. However, the safety profile of SGLT2 inhibitors in chronic kidney disease is not as clear. We describe the adverse event rates of SGLT2 inhibitors, primarily empagliflozin, in Kaiser Permanente Southern California members with diabetic kidney disease. METHODS: This study was a multicenter retrospective descriptive analysis evaluating Kaiser Permanente Southern California members with type 2 diabetes and chronic kidney disease 1, 2, or 3 who first filled an SGLT2 inhibitor prescription in 2018, with follow-up through 2019. Primary outcomes were event rates of diabetic ketoacidosis, bone fracture, amputation, urinary tract infection, genital mycotic infection, hyperkalemia, and acute kidney injury. Secondary outcomes were mean changes in estimated glomerular filtration rates, serum creatine levels, urine albumin-to-creatinine ratios, and hemoglobin A1c percentages during the follow-up period. RESULTS: Of 213 patients, 39 experienced at least 1 adverse event, for a total of 50 adverse events. Urinary tract infection had the highest incidence (62.1 events/1000 person-years), followed by genital mycotic infection (58.0 events/1000 person-years). Favorable changes were observed during the follow-up period for urine albumin-to-creatinine ratios and hemoglobin A1c percentages, with mean decreases of 81.8 mg/g and 0.7%, respectively. SGLT2 inhibitors were discontinued in 47.4% of patients, with the top reasons including increase in serum creatinine (8%) and urinary or genital side effects (5.6%). CONCLUSION: Although most patients did not experience adverse events, urinary tract infections and genital mycotic infections were more common. Our detection of rates and types of adverse effects replicated most results reported in clinical trials. Discontinuations were largely attributed to reasons other than adverse events.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Humanos , Hipoglucemiantes/efectos adversos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos
11.
Pharmaceuticals (Basel) ; 14(9)2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34577580

RESUMEN

The influenza virus is a constantly evolving pathogen that challenges medical and public health systems. Traditionally, curcumin has been used to treat airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate common targets of curcumin and influenza infection and underlying mechanisms, we employed network pharmacology and molecular docking approaches and confirmed results using in vitro experiments. Biological targets of curcumin and influenza were collected, and potential targets were identified by constructing compound-disease target (C-D) and protein-protein interaction (PPI) networks. The ligand-target interaction was determined using the molecular docking method, and in vitro antiviral experiments and target confirmation were conducted to evaluate curcumin's effects on influenza. Our network and pathway analyses implicated the four targets of AKT1, RELA, MAPK1, and TP53 that could be involved in the inhibitory effects of curcumin on influenza. The binding energy calculations of each ligand-target interaction in the molecular docking showed that curcumin bound to AKT1 with the highest affinity among the four targets. In vitro experiments, in which influenza virus-infected MDCK cells were pre-, co-, or post-treated with curcumin, confirmed curcumin's prophylactic and therapeutic effects. Influenza virus induction increased the level of mRNA expression of AKT in MDCK cells, and the level was attenuated by curcumin treatment. Collectively, our findings identified potential targets of curcumin against influenza and suggest curcumin as a potential therapy for influenza infection.

12.
Vaccines (Basel) ; 9(5)2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33946611

RESUMEN

The Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family of enveloped RNA viruses. The correlation between viral infection and fetal microcephaly was revealed in 2015, yet we still lack a vaccine against ZIKV. Here, we present a genetic vaccine that delivers the premembrane (prM) and envelope (E) genes of ZIKV using a recombinant baculovirus vector that expresses a human endogenous retrovirus (HERV) envelope on its surface to enhance gene delivery. We observed that baculoviruses with HERV envelopes (AcHERV) exhibited specifically higher gene transfer efficiency in human cells compared to the wild-type baculovirus vector. Using the AcHERV baculovirus vector, we constructed a recombinant baculovirus vaccine encoding ZIKV prM/E genes (AcHERV-ZIKV), which are major targets of neutralizing antibodies. Mice immunized twice with AcHERV-ZIKV exhibited high levels of IgG, neutralizing antibodies, and IFN-γ. In challenge tests in IFN knock-out mice (A129), AcHERV-ZIKV showed complete protection in both challenge and pregnancy tests. These results suggest that AcHERV-ZIKV could be a potential vaccine candidate for human application.

13.
NPJ Vaccines ; 6(1): 37, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741992

RESUMEN

Here we report a recombinant baculoviral vector-based DNA vaccine system against Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). A non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) was constructed as a DNA vaccine vector for gene delivery into human cells. For MERS-CoV vaccine construction, DNA encoding MERS-CoV S-full, S1 subunit, or receptor-binding domain (RBD) was inserted into the genome of AcHERV. For COVID19 vaccine construction, DNA encoding SARS-CoV2 S-full or S1 or a MERS-CoV NTD domain-fused SARS-CoV2 RBD was inserted into the genome of AcHERV. AcHERV-DNA vaccines induce high humoral and cell-mediated immunity in animal models. In challenge tests, twice immunized AcHERV-MERS-S1 and AcHERV-COVID19-S showed complete protection against MERS-CoV and SARS-CoV2, respectively. Unlike AcHERV-MERS vaccines, AcHERV-COVID19-S provided the greatest protection against SARS-CoV2 challenge. These results support the feasibility of AcHERV-MERS or AcHERV-COVID19 vaccines in preventing pandemic spreads of viral infections.

14.
Genes (Basel) ; 11(11)2020 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-33158084

RESUMEN

Baculovirus expression systems have been widely used to produce recombinant mammalian proteins owing to the lack of viral replication in vertebrates. Although several lines of evidence have demonstrated impacts of baculovirus infection in mammalian hosts, genome-wide effects have not been fully elucidated. Here, we provide comparative transcriptome profiles of baculovirus and host-immune response genes in recombinant baculovirus-infected mammalian and insect cells. Specifically, to decipher the impacts of baculovirus infection in mammalian cells, we conducted total RNA-seq on human 293TT cells and insect Sf9 cells infected with recombinant baculovirus. We found that baculovirus genes were rarely expressed under the control of baculoviral promoters in 293TT cells. Although some baculovirus early genes, such as PE38 and IE-01, showed limited expression in 293TT cells, baculoviral late genes were mostly silent. We also found modest induction of a small number of mammalian immune response genes associated with Toll-like receptors, cytokine signaling, and complement in baculovirus-infected 293TT cells. These comprehensive transcriptome data will contribute to improving recombinant baculovirus as tools for gene delivery, gene therapy, and vaccine development.


Asunto(s)
Proteínas Recombinantes/efectos adversos , Transcriptoma/genética , Transgenes/inmunología , Animales , Baculoviridae/genética , Línea Celular , Terapia Genética/métodos , Estudio de Asociación del Genoma Completo/métodos , Humanos , Insectos/genética , Regiones Promotoras Genéticas/genética , Proteínas Recombinantes/genética , Transcriptoma/inmunología , Transgenes/genética , Replicación Viral/genética
15.
Int J Infect Dis ; 100: 53-58, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32829050

RESUMEN

BACKGROUND: The incidence of Japanese encephalitis (JE) has markedly decreased after the national immunization program in Korea, but still reported intermittently in adults. Prospective studies are required to determine whether JE virus (JEV)-neutralizing antibody (NAb) levels decline with age after the final JE vaccination. In this study, we evaluated the titers of NAbs against JEV in Korean adolescents and adults. METHODS: Specimens were collected from normal, healthy individuals aged 1 to >70 years (a total of 1,605 cases) from five regional hospitals in Korea. Neutralizing antibody (NAb) titers were determined using a pseudotyped JEV NAb assay. RESULTS: The JEV NAb-positive population was >95% in the 15-29 year age group, 89.42% in the 30-44 year age group, 75.24% in the 55-59 years age group, and 59.77% in the ≥70 year age group. NAb titers from the 20 to 70 year age groups showed a progressive decrease in proportion to age (P < 0.0001). CONCLUSIONS: The retention of NAbs after the final JE vaccination in childhood is a key indicator of the vaccination program and will have a significant impact on future JE prevention strategies.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Virus de la Encefalitis Japonesa (Especie)/inmunología , Vacunas contra la Encefalitis Japonesa/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/inmunología , Encefalitis Japonesa/prevención & control , Femenino , Humanos , Programas de Inmunización , Memoria Inmunológica , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea , Factores de Tiempo , Adulto Joven
16.
Int Urol Nephrol ; 51(1): 53-59, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30387068

RESUMEN

PURPOSE: This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography (EMG) of external urethral sphincter (EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice. METHODS: Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200 mg/kg of cyclophosphamide (CYP) 48 h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50 mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension. RESULTS: Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50 mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4 h. VMR was significantly reduced by gabapentin. CONCLUSIONS: The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUS EMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.


Asunto(s)
Cistitis , Gabapentina/farmacología , Hiperalgesia , Uretra , Analgésicos/farmacología , Animales , Cistitis/tratamiento farmacológico , Cistitis/fisiopatología , Modelos Animales de Enfermedad , Electromiografía/métodos , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Ratones , Contracción Muscular/efectos de los fármacos , Resultado del Tratamiento , Uretra/efectos de los fármacos , Uretra/fisiopatología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiopatología , Urodinámica/efectos de los fármacos
17.
J Microbiol Biotechnol ; 29(5): 813-819, 2019 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-30982320

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Inmunogenicidad Vacunal , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Pliegue de Proteína , Proteínas Recombinantes de Fusión/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Antígenos Virales/genética , Femenino , Inmunización , Fragmentos Fc de Inmunoglobulinas/inmunología , Inmunoglobulina G , Ratones , Ratones Endogámicos BALB C , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Pruebas de Neutralización , Células Sf9 , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación , Vacunas de Subunidad/inmunología , Vacunas Virales/genética
18.
Clin Hypertens ; 25: 21, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31534782

RESUMEN

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, chronic disease without curative treatment. Large registry data of these patient populations have been published, although, phenotypic variants within each subtype of PAH have not been elucidated. As interest towards personalized medicine grows, the need for a PAH cohort with a comprehensive understanding of patient phenotypes through multiomics approaches, called deep phenotyping, is on the rise. The PAH Platform for Deep Phenotyping in Korean Subjects (PHOENIKS) cohort is designed to collect clinical data as well as biological specimens for deep phenotyping in patients with idiopathic PAH (IPAH) and heritable PAH (HPAH) in Korea. METHODS: A total of 17 regional hospitals are currently working on enrolling up to 100 consecutive IPAH/HPAH patients for obtaining clinical data and biological specimens across Korea. The diagnosis of PAH is based on right heart catheterization. All clinical data is stored in a government-based online database. Each participating hospitals collect a whole blood sample from each patient, through which DNA, RNA, serum, plasma, and peripheral blood mononuclear cells will be extracted from the buffy coat layer for further multiomics analysis. RESULTS: Not applicable. CONCLUSIONS: The PHOENIKS cohort is enrolling IPAH and HPAH patients across Korea to determine the prognosis and drug response in different phenotypic variant. The data generated by this cohort are expected to open new doors for personalized medicine in PAH patients of South Korea. TRIAL REGISTRATION: ClinicalTrials.gov NCT03933579. Registered on May 1st, 2019.

19.
Viruses ; 11(9)2019 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-31470671

RESUMEN

Pigs are used as potential donor animals for xenotransplantation. However, porcine endogenous retrovirus (PERV), shown to infect both human and non-human primate (NHP) cells in vitro, presents a risk of transmission to humans in xenotransplantation. In this study, we analyzed PERV transmission in various organs after pig-to-NHP xenotransplantation. We utilized pig-to-NHP xenotransplant tissue samples obtained using two types of transgenic pigs from the National Institute of Animal Science (NIAS, Republic of Korea), and examined them for the existence of PERV genes in different organs via PCR and RT-PCR with specific primers. To determine PERV insertion into chromosomes, inverse PCR using PERV long terminal repeat (LTR) region-specific primers was conducted. The PERV gene was not detected in NHP organs in cardiac xenotransplantation but detected in NHP bladders in renal xenotransplantation. The insertion experiment confirmed that PERVs originate from porcine donor cells rather than integrated provirus in the NHP chromosome. We also demonstrate the presence of pig cells in the NHP bladder after renal xenotransplantation using specific-porcine mitochondrial DNA gene PCR. The PERV sequence was detected in the bladder of NHPs after renal xenotransplantation by porcine cell-microchimerism but did not integrate into the NHP chromosome.


Asunto(s)
Retrovirus Endógenos/aislamiento & purificación , Xenoinjertos/virología , Trasplante de Riñón/efectos adversos , Trasplante Heterólogo/efectos adversos , Vejiga Urinaria/virología , Animales , Animales Modificados Genéticamente , Quimerismo , Citocromos b/genética , Retrovirus Endógenos/genética , Genes Virales/genética , Xenoinjertos/citología , Humanos , Macaca mulatta , Porcinos , Vejiga Urinaria/citología
20.
J Surg Educ ; 75(6): 1673-1678, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29730182

RESUMEN

INTRODUCTION AND OBJECTIVES: Endoscopic injection of urethral bulking agents is an office procedure that is used to treat stress urinary incontinence secondary to internal sphincteric deficiency. Validation studies important part of simulator evaluation and is considered important step to establish the effectiveness of simulation-based training. The endoscopic needle injection (ENI) simulator has not been formally validated, although it has been used widely at University of California, Irvine. We aimed to assess the face, content, and construct validity of the UC, Irvine ENI simulator. METHODS: Dissected female porcine bladders were mounted in a modified Hysteroscopy Diagnostic Trainer. Using routine endoscopic equipment for this procedure with video monitoring, 6 urologists (experts group) and 6 urology trainee (novice group) completed urethral bulking agents injections on a total of 12 bladders using ENI simulator. Face and content validities were assessed by using structured quantitative survey which rating the realism. Construct validity was assessed by comparing the performance, time of the procedure, and the occlusive (anatomical and functional) evaluations between the experts and novices. Trainees also completed a postprocedure feedback survey. Effective injections were evaluated by measuring the retrograde urethral opening pressure, visual cystoscopic coaptation, and postprocedure gross anatomic examination. RESULTS: All 12 participants felt the simulator was a good training tool and should be used as essential part of urology training (face validity). ENI simulator showed good face and content validity with average score varies between the experts and the novices was 3.9/5 and 3.8/5, respectively. Content validity evaluation showed that most aspects of the simulator were adequately realistic (mean Likert scores 3.9-3.8/5). However, the bladder does not bleed, and sometimes thin. Experts significantly outperformed novices (p < 001) across all measure of performance therefore establishing construct validity. CONCLUSION: The ENI simulator shows face, content and construct validities, although few aspects of simulator were not very realistic (e.g., bleeding).This study provides a base for the future formal validation for this simulator and for continuing use of this simulator in endourology training.


Asunto(s)
Endoscopía/educación , Entrenamiento Simulado , Incontinencia Urinaria de Esfuerzo/terapia , Animales , Materiales Biocompatibles/administración & dosificación , Endoscopía/instrumentación , Femenino , Inyecciones , Agujas , Autoinforme , Porcinos , Uretra
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