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1.
Rev. otorrinolaringol. cir. cabeza cuello ; 83(2): 158-165, jun. 2023. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1515474

RESUMO

Introducción: El colesteatoma del conducto auditivo externo (CCAE) es una estructura quística revestida por epitelio escamoso estratificado queratinizado que tiene la capacidad de invadir y erosionar localmente al hueso temporal. Su incidencia es de 0,19 a 0,3/100.000 habitantes siendo 60 veces menos frecuente que el de oído medio. Objetivo: Describir las características epidemiológicas, clínicas, imagenológicas y tratamiento de los pacientes diagnosticados con CCAE en el Servicio de Otorrinolaringología Hospital del Salvador. Material y Método: Se presenta una serie de ocho casos clínicos recopilados durante el período 2017 y 2021. Se realizó revisión de fichas clínicas, biopsias y tomografías computadas de oídos (TC oídos). Se describen los hallazgos y tratamiento efectuado. Resultados: El promedio de edad fue de 65,6 años, correspondiente a 5 mujeres y 3 hombres con presencia de tabaquismo y diabetes en la mitad de los casos. Los síntomas y signos más frecuentes fueron otalgia e hipoacusia seguido de otorrea. 7 pacientes se presentaron con tímpano íntegro y el compromiso de la pared inferior del conducto se evidenció en 6 de 8 pacientes. La TC oídos mostró erosión ósea del conducto, con o sin compromiso de estructuras adyacentes, en todos los casos y el diagnóstico histológico fue efectuado en el 100% de los pacientes. Se privilegió el tratamiento conservador mediante curaciones óticas periódicas asociado a ácido salicílico al 3% y/o antibióticos tópicos en 6/8 pacientes. Conclusiones: El CCAE es una entidad poco frecuente sin signos ni síntomas patognomónicos por lo que el diagnóstico histológico junto con el estudio imagenológico es perentorio. El tratamiento conservador es una alternativa terapéutica válida que ofrece buenos resultados en pacientes con adecuada adherencia al tratamiento y posibilidad de seguimiento estricto.


Introduction: External ear canal cholesteatoma (EECC) is a cystic structure lined by keratinized stratified squamous epithelium that has the ability to locally invade and erode the temporal bone. Its incidence is 0.19 to 0.3 / 100,000 habitants, being 60 times less frequent than that of the middle ear. Aim: To describe the epidemiological, clinical, imaging and treatment characteristics of patients diagnosed with EECC in the Hospital del Salvador ENT department. Material and Methods: A series of eight clinical cases collected during the period 2017 and 2021 is presented. A review of clinical records, biopsies and computed tomography of the ear (ear CT) was carried out. The findings and treatment carried out are described. Results: The average age was 65.6 years corresponding to 5 women and 3 men with the presence of smoking and diabetes in half of the cases. The most frequent symptoms and signs were earache and hearing loss followed by otorrhea. 7 patients presented with an intact eardrum and compromise of the inferior wall of the canal was evidenced in 6 of 8 patients. Ears CT showed bone erosion of the canal with or without compromise of adjacent structures in all cases and the histological diagnosis was made in 100% of the patients. Conservative treatment with periodic ear dressings associated with 3% salicylic acid and / or topical antibiotics was favored in 6/8 patients. Conclusion: EECC is a rare entity without pathognomonic signs or symptoms, therefore the histological diagnosis together with the imaging study is peremptory. Conservative treatment is a valid therapeutic alternative that offers good results in patients with adequate adherence to treatment and the possibility of strict follow-up.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Colesteatoma/diagnóstico , Colesteatoma/epidemiologia , Meato Acústico Externo/diagnóstico por imagem , Tomografia , Chile/epidemiologia , Epidemiologia Descritiva
2.
Eur Rev Med Pharmacol Sci ; 22(16): 5394-5401, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30178867

RESUMO

OBJECTIVE: To explore the effect of PI3K/Nrf2 pathway on acute kidney injury (AKI) induced by endotoxic shock in rats by construction of the endotoxic shock rat model. MATERIALS AND METHODS: A total of 30 Sprague Dawley (SD) rats were randomly assigned into three group, namely the control group (group C), endotoxic shock model group (group L) and wortmannin + endotoxic shock model group (group WL), with 10 rats in each group. Pathological lesions in renal tissues were evaluated by histological score of kidney (HSK). Biochemical indicators including blood urine nitrogen (BUN), creatinine (Cr) and urinary α1-microglobulin (α1-MG) in renal tissues were accessed. Activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by relative commercial kits. Expression levels of Nrf2, Heme oxygenase 1 (HO-1) and Akt in renal tissues were determined by Western blot and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), respectively. RESULTS: HSK, levels of BUN, Cr and α1-MG and activities of SOD and MDA were significantly increased in group L comparing to those in group C (p<0.05). The above-mentioned indicators were also remarkably higher in group WL than those of group L (p<0.05). There were significant differences in expression levels of Nrf2, HO-1 and Akt between group L and group WL (p<0.05). In particular, lower mRNA levels of Nrf2 and HO-1, as well as protein levels of p-Akt, Nrf2 and HO-1 were observed in group WL compared with those in group L (p<0.05). CONCLUSIONS: The present study showed that AKI induced by endotoxic shock in rats was regulated through PI3K/Nrf2 pathway. HO-1 acts as the effector protein, might serve as an essential factor in protecting AKI induced by endotoxic shock.


Assuntos
Injúria Renal Aguda/fisiopatologia , Fator 2 Relacionado a NF-E2/metabolismo , Choque Séptico/complicações , Animais , Creatinina/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Malondialdeído/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Choque Séptico/fisiopatologia , Superóxido Dismutase/metabolismo
3.
Rev. otorrinolaringol. cir. cabeza cuello ; 78(2): 213-220, jun. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-961618

RESUMO

RESUMEN La tos persistente es un síntoma de consulta frecuente, de origen multifactorial, que involucra a diferentes especialidades como la neumología, la gastroenterología y la otorrinolaringología. Sus causas más frecuentes son la descarga nasal posterior, tos como variante del asma y reflujo gastroesofágico/faringolaríngeo. Una vez descartadas dichas causas, cobran importancia los trastornos sensoriales del nervio vago, una entidad relativamente nueva que también es conocida como neuropatía laríngea sensitiva. En la neuropatía laríngea, una injuria a nivel neuronal aferente del reflejo de la tos produce un estado de hipersensibilidad laríngea en la que estímulos normalmente ignorados (que no producen respuesta tusígena) comienzan a gatillar el reflejo. Las características clínicas de la tos y el descarte de las causas más frecuentes permite llegar a este diagnóstico. Su tratamiento tiene como objetivo la modulación de las vías neuronales alteradas basándose en 3 pilares: educación sobre la patología, recomendaciones conductuales (higiene vocal, estrategias de reducción de tos) y los fármacos entre los que se usan los inhibidores de bomba de protones, mucolíticos y neuromoduladores.


ABSTRACT Persistent cough is a common symptom for medical consultation, it is of multifactorial origin and involves different specialties such as pneumology gastroenterology and otorhinolaryngology. The most frequent causes are postnasal drip, cough variant asthma and gastroesophageal/pharyngolaryngeal reflux. Once these causes are discarded the vagus nerve sensory disorder becomes of importance, it is a relatively new entity also known as laryngeal sensitive neuropathy. In the laryngeal neuropathy, an injury in the afferent neuronal pathway of the cough reflex produces laryngeal hypersensitivity in which normally ignored stimulus (i.e. do not cause cough) start to trigger the reflex. The clinical features of the cough and the rule out of the most frequent causes allow the diagnosis. The objective of the treatment is to modulate the altered neuronal pathways based on 3 pillars: education regarding the pathology, behavioral recommendations (vocal hygiene, cough reduction strategies) and drugs among which proton pump inhibitors, mucolytics and neuromodulators are used.


Assuntos
Humanos , Doenças da Laringe , Tosse/diagnóstico , Tosse/fisiopatologia , Doenças do Nervo Vago/fisiopatologia , Tosse/etiologia , Tosse/terapia , Refluxo Laringofaríngeo , Nervos Laríngeos
4.
Clin Microbiol Infect ; 24(11): 1195-1199, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29458157

RESUMO

OBJECTIVES: Clostridium innocuum can cause extraintestinal infection in patients with underlying diseases. The role of C. innocuum in antibiotic-associated diarrhoea (AAD) remains unknown. METHODS: Clinical information of 103 patients from whom C. innocuum was isolated was reviewed. We carried out cellular and animal experiments to examine the pathogenic potential of C. innocuum in AAD. RESULTS: Eighty-eight per cent (91/103) of the 103 patients received antibiotics within 2 weeks of diarrhoea onset. Patients were further classified into two groups, severe colitis and diarrhoea, according to clinical severity level. The mortality rate was 13.6% (14/103) among the patients from whom C. innocuum was isolated. The lowest concentrations at which 90% of the isolates were inhibited for metronidazole and vancomycin were 0.5 and 16 mg/L, respectively. All isolates tested were susceptible to metronidazole but resistant to vancomycin. Nineteen randomly selected isolates (ten from severe colitis group, nine from diarrhoea group) were subjected to further in vitro cellular examinations. The level of cytotoxicity to Vero cells was significantly higher in isolates from the severe colitis group at both 24 and 48 hours after inoculation (24 and 48 hours, p 0.042 and 0.033, respectively). We observed apoptotic changes that subsequently led to cell death in C. innocuum-infected Vero cells. Tissue damages, necrotic changes and oedema were observed in the mouse ileal loop infected by C. innocuum. CONCLUSIONS: Vancomycin-resistant C. innocuum may play a potential role as a causative agent of AAD. The clinical manifestations of AAD caused by C. innocuum were diarrhoea or severe colitis, including pseudomembranous colitis.


Assuntos
Antibacterianos/efeitos adversos , Infecções por Clostridium/microbiologia , Clostridium/classificação , Diarreia/etiologia , Resistência a Vancomicina , Vancomicina/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Clostridium/efeitos dos fármacos , Clostridium/patogenicidade , Infecções por Clostridium/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Rev. otorrinolaringol. cir. cabeza cuello ; 77(3): 239-245, set. 2017. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-902771

RESUMO

Introducción: Los quistes de cuerda vocal son una causa relativamente frecuente de disfonía. Su origen es aún controversial, y su diagnóstico y manejo continúan siendo un desafío clínico. Objetivo: Exponer y analizar las características clínicas de los quistes de cuerda vocal en nuestra serie de pacientes. Material y método: Estudio retrospectivo descriptivo de los pacientes con diagnóstico de quiste de cuerda vocal atendidos en nuestro centro entre junio de 2012 y diciembre de 2015. Resultados: Se atendieron 44 pacientes con diagnóstico de quiste de cuerda vocal, lo que representa el 4,32% de las consultas en nuestro Centro de Voz. La mayoría de los pacientes fueron adultos, y de ellos el 68,29% correspondió a mujeres. El 34,1% de los pacientes fueron sometidos a tratamíento quirúrgico con técnica de microfonocirugía. El 75% de los pacientes operados presentó mejoría en patrón de onda mucosa videolaringoestroboscópica. Todos los pacientes en los que se disponía de encuestas de valoración subjetiva de la voz pre y posoperatorias demostraron mejoría vocal significativa. Conclusión: Los quistes de cuerda vocal son lesiones que afectan a niños y adultos. La videolaringoestroboscopía es clave en el diagnóstico de estas lesiones, y el tratamiento quirúrgico con microfonocirugía es efectiva en cuanto a resultados vocales desde el punto de vista anatómico y funcional.


Introduction: Vocal cord cysts are a relatively frequent cause of dysphonia. Their origin is still controversial, and their diagnosis and management continue to be a clinical challenge. Aim: To describe and analyze the clinical characteristics of vocal cord cysts in our series of patients. Material and method: Descriptive retrospective study of patients with diagnosis of vocal cord cyst attended in our center between June 2012 and December 2015. Results: 44 patients had the diagnosis of vocal cord cyst, which represents 4.32% of the patients that attended our Voice Center during that period. Most of the patients were adults, and among them 68.29% corresponded to women. 34.1% of the patients were submitted to surgical treatment with microphonosurgery technique. 75% of the surgical patients presented an improvement in the pattern of the videolaryngostroboscopic mucosal wave. All the patients in which pre and postsurgical subjective voice assessment polls were available, showed a significant voice improvement. Conclusion: Vocal cord cysts are lesions that affect both children and adults. The videolaryngostroboscopy evaluation is key in the diagnosis of these lesions, and the surgical treatment with microphonosurgery is effective in terms of anatomical and functional vocal results.


Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Prega Vocal/cirurgia , Prega Vocal/patologia , Doenças da Laringe/cirurgia , Doenças da Laringe/patologia , Cistos/cirurgia , Cistos/patologia , Doenças da Laringe/diagnóstico , Estudos Retrospectivos , Cistos/diagnóstico , Estroboscopia , Disfonia/etiologia , Laringoscopia , Microcirurgia/métodos
6.
Rev. otorrinolaringol. cir. cabeza cuello ; 77(1): 35-43, mar. 2017. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: biblio-845644

RESUMO

Introducción: El cáncer de laringe es la segunda causa de muerte en otorrinolaringología. Su tratamiento en estadios avanzados es agresivo y controversial. Objetivo: Reportar los datos de pacientes atendidos en el Complejo Asistencial Doctor Sótero del Río entre los años 2005-2011. Material y método: Análisis retrospectivo descriptivo. Resultados: Total de 38 pacientes, 30 (79%) hombres, mediana de edad 66 años. Los principales motivos de consulta fueron dificultad respiratoria en 18 pacientes (47%) y disfonía en 14 (37%). Se realizó estudio y etapificación con nasofibroscopía y tomografía computarizada. El 71% se presentó en estadio avanzado, de ellos, el 30% recibió quimiorradioterapia exclusiva. La sobrevida global a 2 y 5 años fue de 56% y 42% respectivamente en estadio avanzado y de 100% y 71% respectivamente en estadio precoz. Discusión: El cáncer de laringe es una enfermedad con sobrevida baja a pesar de tratamientos agresivos. Se han planteado alternativas al tratamiento estándar como terapia conservadora con quimiorradioterapia exclusiva o microcirugía láser transoral. Conclusiones: La epidemiología del cáncer laríngeo se ha mantenido relativamente estable y la clasificación TNM sigue siendo fundamental para el tratamiento, especialmente en contexto de nuevas alternativas de manejo de cáncer avanzado. Se espera evaluar estas terapias.


Introduction: Laryngeal cancer is the second cause of death in otolaryngology. Its treatment in advanced stage is aggressive and controversial. Aim: To report data from patients treated in Complejo Asistencial Doctor Sótero del Río in the period between 2005-2011. Material and method: Descriptive retrospective analysis. Results: 38 patients in total, 30 (79%) men, median age 66 years. The main symptoms were breathing difficulty in 18 patients (47%) and dysphonia in 14 (37%). Every patient completed study and disease staging with nasofibroscopy and computed tomography. 71% presented in advanced stage, among them, 30% received exclusive chemoradiotherapy. Overall survival for 2 and 5-year in advanced stage was 56% and 42% respectively; and 100% and 71% in early stage. Discussion: Advanced laryngeal cancer has low survival rate in spite of aggressive treatments. Alternatives to standard care have been proposed, such as conservative therapy with exclusive chemoradiotherapy or transoral laser microsurgery. Conclusions: Laryngeal cancer's epidemiology remains relatively unchanged and TNM classification still remains fundamental for treatment, specially in the context of new therapeutic alternatives for advanced cancer. Evaluation of these therapies is expected.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/cirurgia , Epidemiologia Descritiva , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida
7.
Rev. Hosp. Clin. Univ. Chile ; 27(2): 103-108, dic. 2016. tab
Artigo em Espanhol | LILACS | ID: biblio-869427

RESUMO

It is believed that the greater production of sex hormones during pregnancy cause changes that affect the hearing system, although their specific mechanisms are still under investigation.Physiological changes occur during pregnancy such as the non-pathologic drop of hearing thresholds for low frequencies and diminished hearing tolerance to intense sounds, both ofwhich return to their basal range in the post-partum. Certain diseases, like sudden hearing loss, Ménière´s Disease and otosclerosis can appear for the first time or alter their course during pregnancy. A brief bibliographic revision is made regarding the physiological and pathological hearing changes that occur during pregnancy.


Assuntos
Humanos , Adolescente , Adulto , Feminino , Gravidez , Adulto Jovem , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/fisiopatologia , Perda Auditiva/diagnóstico , Perda Auditiva/patologia
8.
Osteoporos Int ; 26(2): 589-99, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25278298

RESUMO

SUMMARY: Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. INTRODUCTION: Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. METHODS: The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. RESULTS: A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. CONCLUSION: The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Produtos Fermentados do Leite , Fêmur/efeitos dos fármacos , Osteoporose Pós-Menopausa/dietoterapia , Animais , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Peptídeos/efeitos dos fármacos , Peptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
9.
Oncogene ; 34(1): 94-103, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-24317514

RESUMO

Mice in which lung epithelial cells can be induced to express an oncogenic Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis.


Assuntos
Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Iodeto Peroxidase/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/genética , MicroRNAs/metabolismo , Alelos , Animais , Proteínas de Ligação ao Cálcio , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Mapeamento Cromossômico , Feminino , Perfilação da Expressão Gênica , Genes ras/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Iodeto Peroxidase/metabolismo , Perda de Heterozigosidade , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Família Multigênica , Mutação , Polimorfismo de Nucleotídeo Único , RNA/metabolismo , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Regulação para Cima
10.
Cell Death Dis ; 5: e1220, 2014 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-24810056

RESUMO

The survival of prostate cancer (PrCa) patients is associated with the transition to hormone-independent tumor growth and metastasis. Clinically, the dysregulation of androgen action has been associated with the formation of PrCa and the outcome of androgen deprivation therapy in PrCa. CCAAT/enhancer binding protein delta (CEBPD) is a transcription factor that has been reported to act as an oncogene or tumor suppressor, depending on the extra- and intracellular environments following tumorigenesis. We found that androgen can activate CEBPD transcription by direct binding of the androgen receptor (AR) to the CEBPD promoter region. Increases of suppressor of zeste 12 (SUZ12) and enhancer of zeste homolog 2 (EZH2) attenuated the androgen-induced transcription of CEBPD. Importantly, the increases in E2F1, SUZ12 and EZH2 as well as the inactivation of CEBPD were associated with the clinicopathological variables and survival of PrCa patients. We revealed that caspase 8 (CASP8), an apoptotic initiator, is responsive to CEBPD induction. Reporter and in vivo DNA-binding assays revealed that CEBPD directly binds to and activates CASP8 reporter activity. A prodrug system was developed for therapeutic application in AR-independent or androgen-insensitive PrCa to avoid the epigenetic effects on the suppression of CEBPD expression. Our results showed that the combination of a perforin (PF)-CEBPD prodrug (which increases the level of procaspase-8) and a PF-granzyme B prodrug (which activates CASP8 and caspase 3 (CASP3)) showed an additive effect in triggering the apoptotic pathway and enhancing apoptosis in PrCa cells.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proteína delta de Ligação ao Facilitador CCAAT/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Granzimas/farmacologia , Perforina/farmacologia , Pró-Fármacos/farmacologia , Neoplasias da Próstata/enzimologia , Proteínas Recombinantes de Fusão/farmacologia , Animais , Células 3T3 BALB , Sítios de Ligação , Caspase 8/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Masculino , Camundongos , Proteínas de Neoplasias , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Pró-Fármacos/metabolismo , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Fatores de Transcrição , Transfecção
11.
Sci Rep ; 4: 4525, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24717290

RESUMO

Electronic structures of graphene oxide (GO) and hydro-thermally reduced graphene oxides (rGOs) processed at low temperatures (120-180°C) were studied using X-ray absorption near-edge structure (XANES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS). C K-edge XANES spectra of rGOs reveal that thermal reduction restores C = C sp(2) bonds and removes some of the oxygen and hydroxyl groups of GO, which initiates the evolution of carbonaceous species. The combination of C K-edge XANES and Kα XES spectra shows that the overlapping π and π* orbitals in rGOs and GO are similar to that of highly ordered pyrolytic graphite (HOPG), which has no band-gap. C Kα RIXS spectra provide evidence that thermal reduction changes the density of states (DOSs) that is generated in the π-region and/or in the gap between the π and π* levels of the GO and rGOs. Two-dimensional C Kα RIXS mapping of the heavy reduction of rGOs further confirms that the residual oxygen and/or oxygen-containing functional groups modify the π and σ features, which are dispersed by the photon excitation energy. The dispersion behavior near the K point is approximately linear and differs from the parabolic-like dispersion observed in HOPG.

12.
Cancer Gene Ther ; 20(5): 276-81, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23598434

RESUMO

Extracellular activation of hydrophilic glucuronide prodrugs by ß-glucuronidase (ßG) was examined to increase the therapeutic efficacy of bacteria-directed enzyme prodrug therapy (BDEPT). ßG was expressed on the surface of Escherichia coli by fusion to either the bacterial autotransporter protein Adhesin (membrane ßG (mßG)/AIDA) or the lipoprotein (lpp) outermembrane protein A (mßG/lpp). Both mßG/AIDA and mßG/lpp were expressed on the bacterial surface, but only mßG/AIDA displayed enzymatic activity. The rate of substrate hydrolysis by mßG/AIDA-BL21cells was 2.6-fold greater than by pßG-BL21 cells, which express periplasmic ßG. Human colon cancer HCT116 cells that were incubated with mßG/AIDA-BL21 bacteria were sensitive to a glucuronide prodrug (p-hydroxy aniline mustard ß-D-glucuronide, HAMG) with an half maximal inhibitory concentration (IC50) value of 226.53±45.4 µM, similar to the IC50 value of the active drug (p-hydroxy aniline mustard, pHAM; 70.6±6.75 µM), indicating that mßG/AIDA on BL21 bacteria could rapidly and efficiently convert HAMG to an active anticancer agent. These results suggest that surface display of functional ßG on bacteria can enhance the hydrolysis of glucuronide prodrugs and may increase the effectiveness of BDEPT.


Assuntos
Escherichia coli/enzimologia , Glucuronatos/farmacocinética , Glucuronidase/metabolismo , Glucuronídeos/farmacocinética , Nitrofenóis/farmacocinética , Pró-Fármacos/farmacocinética , Proteínas de Transporte/farmacocinética , Escherichia coli/genética , Glucuronidase/biossíntese , Glucuronidase/genética , Células HCT116 , Humanos , Proteínas Recombinantes , Células Tumorais Cultivadas
14.
Epidemiol Infect ; 137(2): 266-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18474127

RESUMO

Two hundred and four Salmonella enterica serotype Typhi (S. Typhi) isolates were collected from seven Asian countries during 2002-2004. Multidrug-resistant S. Typhi (resistant to > or = 3 antibiotics) was detected in 84 (41.2%) isolates and 142 (69.6%) showed reduced susceptibility to ciprofloxacin (minimum inhibitory concentration=0.125-1.0 mg/l). This study highlights the worsening situation of antimicrobial resistance of S. Typhi in Asia.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/microbiologia , Ásia , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi/isolamento & purificação
15.
Transplant Proc ; 40(7): 2392-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18790244

RESUMO

OBJECTIVE: Renal transplant recipients display an increased risk of malignancy due to long-term immunosuppression. The type and incidence of malignancies vary geographically. Hepatocellular carcinoma (HCC) is a leading cause of malignancy in posttransplantation recipients in Taiwan, which is an endemic area for hepatitis B. We performed a retrospective study to investigate the clinical features of HCC among our renal transplant recipients. METHODS: Between 1988 and 2006, 15 patients of the 554 kidney recipients followed up at our transplantation clinic were diagnosed with HCC. The medical records corresponding to these 15 patients were reviewed for age, gender, initial presentation and symptoms, posttransplant duration, immunosuppressive regimens, graft and patient survival, treatment of HCC, and outcomes. RESULTS: Fifteen recipients developed HCC, (2.7%), of whom 11 were men. Four patients were hepatitis B surface antigen (HBsAg)-positive, 4 were anti-hepatitis C antibody (anti-HCV Ab)-positive, and another 7 were negative for HBsAg and/or anti-HCV Ab. The mean age at the time of HCC diagnosis was 52 +/- 12 years, with a mean posttransplantation duration to HCC of 83 +/- 48.4 months. Over a follow-up period of 59.9 +/- 39.1 months, 8 patients remained alive and 7 died. Among these 7 individuals, 6 had no treatment for HCC and died rapidly (<3 months) and, 1 underwent hepatic lobectomy but died 6 months later due to liver failure. All 8 surviving patients received treatment: 4 underwent transarterial embolization (TAE) and the other 4 underwent surgery. As of July 2006, the average survival was 68 months. Three of these 8 patients had graft failure, including 2 whom have returned to maintenance hemodialysis and 1 who had a successful second graft. CONCLUSION: HCC is a major cancer among renal recipients in Taiwan. In our center the outcomes of treatable patients were good. Our study revealed that either TAE or surgery resulted in excellent survival rates. It is necessary to adjust the immunosuppressive regimen in patients with HCC and to detect a malignancy at an early stage to improve the outcomes.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Transplante de Rim/efeitos adversos , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Transplant Proc ; 40(7): 2409-11, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18790250

RESUMO

PURPOSE: New-onset diabetes mellitus (PTDM), a major metabolic complication after renal transplantation, examined for incidence and risk factors. METHODS: The records of 358 renal transplant recipients with functioning grafts, from 1986 to 2006, were categorized into two groups according to the usage of tacrolimus (FK): FK-based (n = 120 patients) and non-FK-based (n = 238). Using Kaplan-Meier survival analysis and a Cox regression model, this study analyzed the cumulative incidence of PTDM and risk factors, including gender, age, and presence of hepatitis. RESULTS: Cumulative incidences of PTDM after 1, 3, and 5 years posttransplantation in the FK-based group were 11%, 18%, and 22%, respectively. In the non-FK-based group, the cumulative incidences were 5%, 9%, and 12% (P = .01). Taking into account the risk factors, the cumulative incidence of PTDM was significant among patients 51 years or older (odds ratio, 3.965; P = .005), but not with regard to gender or presence of hepatitis B and/or C. Overall cumulative incidence of PTDM in our series was 15% (54/358), including 44% (24/54) of cases that occurred within 1 year after renal transplantation. CONCLUSION: FK is more diabetogenic than cyclosporine or sirolimus. Older age (> or =51 years) is a significant risk factor, in contrast to hepatitis and gender. About half of these cases of PTDM occurred within 1 year after transplantation. These results suggest that aggressive monitoring of blood sugar is necessary for early detection of PTDM.


Assuntos
Diabetes Mellitus/epidemiologia , Transplante de Rim/efeitos adversos , Adulto , Animais , Intervalo Livre de Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Tacrolimo/uso terapêutico , Fatores de Tempo
17.
Transplant Proc ; 39(10): 3251-6, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18089365

RESUMO

AIM: To report the morbidity and mortality of patients who undergo liver transplantation with or without T-tube implantation after choledochocholedochostomy as well as to discuss management of biliary complications. PATIENTS AND METHODS: We performed a retrospective review of 104 liver transplantations from August 2001 to February 2006, including 51 patients who underwent choledochocholedochostomy with a T-tube (group A) and 53, without a T-tube (group B). We compared the clinical characteristics, operative methods, biliary complications, morbidity, mortality, and management of complications. RESULTS: Between the two groups, there were no significant differences in clinical characteristics, including sex, age, and indication for liver transplantation (hepatitis B virus, hepatitis C virus, alcoholic liver cirrhosis, or hepatocellular carcinoma), Child-Pugh classification, Model for End-stage Liver Disease score, and operative macroscopic/microscopic findings. Additionally, there was no significant difference in biliary complications. Among these 104 patients, 14 (13.5%) developed biliary complications: seven anastomotic strictures, two intrahepatic duct strictures, two anastomotic stricture combined intrahepatic duct stricture, one bile leakage, one bile leakage combined with anastomotic stricture, and one external biliary compression. Nine patients with anastomotic stricture underwent endoscopy with a stent, which was successful only in two patients. The other six patients underwent choledochojejunostomy with excellent results. CONCLUSIONS: This study showed choledochocholedochostomy with or without a T-tube after liver transplantation did not influence the biliary complications. The biliary complications of anastomotic stricture after liver transplantation can be managed by endoscopy with a stent. If endoscopy fails, surgical intervention should be considered immediately.


Assuntos
Doenças Biliares/epidemiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Doenças Biliares/etiologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatite B/complicações , Hepatite B/cirurgia , Hepatite C/complicações , Hepatite C/cirurgia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Rev Esp Enferm Dig ; 99(9): 502-4, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18052644

RESUMO

OBJECTIVE: The purpose of this study was to report our experience in management and clinical result of Spigelian hernia with preperitoneal mesh repair or without mesh repair. EXPERIMENTAL DESIGN: Retrospecitve analysis. SUBJECTS: the medical records of 11 cases of Spigelian hernia with surgical treatment were reviewed. The clinical characteristic, treatment and clinical result were evaluated. RESULTS: of the 11 cases that were evaluated, 7 patients underwent open repair of hernia without extra-peritoneal mesh (group A), the other 4 patients underwent open surgery with extra-peritoneal mesh (group B). There were no significant difference in age, gender, body mass index, underlying diseases, symptoms, duration of symptoms, features of hernia sac and method of approach. No recurrence was found in these two groups. The mean follow-up time was 8.5 +/- 3.2 (years) in group A and 6.7 +/- 2.1 (years) in group B. CONCLUSIONS: whether open repair of spigelian hernia with or without extra-peritoneal mesh gives the same and well result.


Assuntos
Hérnia Ventral/cirurgia , Telas Cirúrgicas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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