Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
PLOS Glob Public Health ; 3(12): e0002539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38109300

RESUMO

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.

2.
J Microbiol ; 61(7): 703-711, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37358709

RESUMO

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.


Assuntos
COVID-19 , Fenofibrato , Humanos , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/química , Simulação de Acoplamento Molecular , Fenofibrato/farmacologia
3.
Cell Death Discov ; 8(1): 153, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35368019

RESUMO

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.

4.
Pharmaceuticals (Basel) ; 14(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34577580

RESUMO

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.

5.
Vaccines (Basel) ; 9(5)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946611

RESUMO

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.

6.
Perm J ; 252021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33970086

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Hipoglicemiantes/efeitos adversos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
7.
Eur J Pharmacol ; 904: 174144, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33957087

RESUMO

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.


Assuntos
Antivirais/farmacologia , Curcumina/farmacologia , Infecção por Zika virus/tratamento farmacológico , Zika virus/efeitos dos fármacos , Animais , Antivirais/química , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Simulação por Computador , Curcumina/química , Reposicionamento de Medicamentos , Mapas de Interação de Proteínas , Células Vero , Ensaio de Placa Viral , Ligação Viral/efeitos dos fármacos
8.
NPJ Vaccines ; 6(1): 37, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741992

RESUMO

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.

9.
Genes (Basel) ; 11(11)2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158084

RESUMO

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.


Assuntos
Proteínas Recombinantes/efeitos adversos , Transcriptoma/genética , Transgenes/imunologia , Animais , Baculoviridae/genética , Linhagem Celular , Terapia Genética/métodos , Estudo de Associação Genômica Ampla/métodos , Humanos , Insetos/genética , Regiões Promotoras Genéticas/genética , Proteínas Recombinantes/genética , Transcriptoma/imunologia , Transgenes/genética , Replicação Viral/genética
10.
Int J Infect Dis ; 100: 53-58, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32829050

RESUMO

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.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vírus da Encefalite Japonesa (Espécie)/imunologia , Vacinas contra Encefalite Japonesa/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/prevenção & controle , Feminino , Humanos , Programas de Imunização , Memória Imunológica , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Fatores de Tempo , Adulto Jovem
11.
Anim Biotechnol ; 31(1): 32-41, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30570378

RESUMO

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.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas da Matriz Viral/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Baculoviridae/genética , Retrovirus Endógenos/genética , Imunidade Humoral , Camundongos , Camundongos Endogâmicos BALB C , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Proteínas Recombinantes , Organismos Livres de Patógenos Específicos , Spodoptera , Suínos , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética , Proteínas da Matriz Viral/genética , Vacinas Virais/genética
12.
Viruses ; 11(9)2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470671

RESUMO

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.


Assuntos
Retrovirus Endógenos/isolamento & purificação , Xenoenxertos/virologia , Transplante de Rim/efeitos adversos , Transplante Heterólogo/efeitos adversos , Bexiga Urinária/virologia , Animais , Animais Geneticamente Modificados , Quimerismo , Citocromos b/genética , Retrovirus Endógenos/genética , Genes Virais/genética , Xenoenxertos/citologia , Humanos , Macaca mulatta , Suínos , Bexiga Urinária/citologia
13.
Clin Hypertens ; 25: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534782

RESUMO

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.

14.
J Microbiol Biotechnol ; 29(5): 813-819, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30982320

RESUMO

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.


Assuntos
Infecções por Coronavirus/prevenção & controle , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Dobramento de Proteína , Proteínas Recombinantes de Fusão/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Antígenos Virais/genética , Feminino , Imunização , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G , Camundongos , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Testes de Neutralização , Células Sf9 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Virais/genética
15.
Int Urol Nephrol ; 51(1): 53-59, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30387068

RESUMO

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.


Assuntos
Cistite , Gabapentina/farmacologia , Hiperalgesia , Uretra , Analgésicos/farmacologia , Animais , Cistite/tratamento farmacológico , Cistite/fisiopatologia , Modelos Animais de Doenças , Eletromiografia/métodos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Camundongos , Contração Muscular/efeitos dos fármacos , Resultado do Tratamento , Uretra/efeitos dos fármacos , Uretra/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Urodinâmica/efeitos dos fármacos
16.
Biochem Biophys Res Commun ; 505(4): 1010-1014, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30309651

RESUMO

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.


Assuntos
Epitopos de Linfócito B/química , Peptídeos/análise , Zika virus/química , Epitopos de Linfócito B/sangue , Humanos , Modelos Moleculares , Peptídeos/síntese química
17.
J Microbiol ; 56(8): 586-592, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30047088

RESUMO

The emergence of oseltamivir-resistant variants of influenza virus has highlighted the necessity for the development of more effective novel antiviral drugs. To date, numerous researchers have focused on developing antiviral drugs using natural resources, such as traditional herbal medicines. Poncirus trifoliata is widely used in oriental medicine as a remedy for gastritis, dysentery, inflammation and digestive ulcers. In this study, we investigated the potential antiviral effect of the Poncirus trifoliata orange seed extract against influenza virus. An ethanol extract of Poncirus trifoliata seeds (PTex) inhibited the activity of influenza viruses, in particular, oseltamivir- resistant strains, in Madin-Darby canine kidney cells. In contrast to oseltamivir, PTex exerted a significant inhibitory effect on the cellular penetration pathway of the virus rather than HA receptor binding. The potent antiviral effect and novel working mechanism of PTex support its further development as an effective natural antiviral drug with a wide spectrum of activity against influenza and oseltamivir-resistant viruses.


Assuntos
Antivirais/farmacologia , Orthomyxoviridae/efeitos dos fármacos , Extratos Vegetais/farmacologia , Poncirus/química , Animais , Antivirais/isolamento & purificação , Cães , Células Madin Darby de Rim Canino , Orthomyxoviridae/fisiologia , Extratos Vegetais/isolamento & purificação , Sementes/química , Internalização do Vírus/efeitos dos fármacos
18.
Case Rep Cardiol ; 2018: 5980380, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854472

RESUMO

A 52-year-old male with Brugada syndrome presented with repeated and appropriate shock from an implantable cardioverter defibrillator (ICD). Catheter ablation for substrate elimination targeting low-voltage, complex, and fractionated electrocardiograms and late potentials in the epicardial right ventricular outflow tract was successfully performed. Brugada phenotype in the right precordial leads from the third intercostal space disappeared in the early stage after catheter ablation and that from the standard fourth intercostal space disappeared later. He remained free from ventricular fibrillation over the next fourteen months. We suggest that this novel ablation strategy is effective in Brugada syndrome patients with ICD, and early response after catheter ablation can be predicted by high precordial leads.

19.
J Surg Educ ; 75(6): 1673-1678, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29730182

RESUMO

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.


Assuntos
Endoscopia/educação , Treinamento por Simulação , Incontinência Urinária por Estresse/terapia , Animais , Materiais Biocompatíveis/administração & dosagem , Endoscopia/instrumentação , Feminino , Injeções , Agulhas , Autorrelato , Suínos , Uretra
20.
JACC Cardiovasc Interv ; 9(21): 2220-2228, 2016 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-27832848

RESUMO

OBJECTIVES: This study sought to evaluate the determinants and prognostic implications of periprocedural myocardial injury (PMI) in successful percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). BACKGROUND: There are limited studies addressing the risk factors and clinical implication of PMI in patients undergoing CTO-PCI. METHODS: We examined 1,058 consecutive CTO patients who underwent successful drug-eluting stent implantation and serial measurements of creatine kinase-myocardial band (CK-MB) values between March 2003 and August 2014. PMI was defined as elevations of CK-MB >3 times the upper reference limit (URL). RESULTS: PMI occurred in 121 patients (11.4%). Multivariable analysis revealed that the presence of renal failure (odds ratio [OR]: 4.25; 95% confidence interval [CI]: 1.59 to 11.35; p = 0.004), attempted retrograde approach (OR: 2.27; 95% CI: 1.34 to 3.84; p = 0.002), concomitant non-target lesion intervention (OR: 1.74; 95% CI: 1.17 to 2.59; p = 0.006), and stent number (OR: 1.38; 95% CI: 1.08 to 1.77; p = 0.011) were predictors associated with PMI. During a median follow-up of 4.4 years, PMI was associated with an increased risk of mortality (adjusted hazard ratio: 1.86; 95% CI: 1.09 to 3.17; p = 0.02). These findings were also consistent when higher CK-MB cutoff was used to define PMI. Although there was a trend toward higher all-cause mortality with increasing peak CK-MB levels, in multivariable analyses, this association was statistically significant only for peak CK-MB levels of >10 times the URL. CONCLUSIONS: PMI was associated with an increased risk of long-term mortality after successful CTO-PCI. Patients with renal insufficiency, those who require more stents, multiple lesion treatment, and retrograde approach have a higher likelihood of having PMI.


Assuntos
Oclusão Coronária/terapia , Cardiopatias/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/mortalidade , Creatina Quinase Forma MB/sangue , Bases de Dados Factuais , Stents Farmacológicos , Feminino , Cardiopatias/sangue , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...