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1.
Neurochem Res ; 49(7): 1879-1901, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38755517

RESUMO

Oxidative stress-induced death of neurons and astrocytes contributes to the pathogenesis of numerous neurodegenerative diseases. While significant progress has been made in identifying neuroprotective molecules against neuronal oxidative damage, little is known about their counterparts for astrocytes. Prolactin (PRL), a hormone known to stimulate astroglial proliferation, viability, and cytokine expression, exhibits antioxidant effects in neurons. However, its role in protecting astrocytes from oxidative stress remains unexplored. Here, we investigated the effect of PRL against hydrogen peroxide (H2O2)-induced oxidative insult in primary cortical astrocyte cultures. Incubation of astrocytes with PRL led to increased enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX), resulting in higher total antioxidant capacity. Concomitantly, PRL prevented H2O2-induced cell death, reactive oxygen species accumulation, and protein and lipid oxidation. The protective effect of PRL upon H2O2-induced cell death can be explained by the activation of both signal transducer and activator of transcription 3 (STAT3) and NFE2 like bZIP transcription factor 2 (NRF2) transduction cascades. We demonstrated that PRL induced nuclear translocation and transcriptional upregulation of Nrf2, concurrently with the transcriptional upregulation of the NRF2-dependent genes heme oxygenase 1, Sod1, Sod2, and Gpx1. Pharmacological blockade of STAT3 suppressed PRL-induced transcriptional upregulation of Nrf2, Sod1 and Gpx1 mRNA, and SOD and GPX activities. Furthermore, genetic ablation of the PRL receptor increased astroglial susceptibility to H2O2-induced cell death and superoxide accumulation, while diminishing their intrinsic antioxidant capacity. Overall, these findings unveil PRL as a potent antioxidant hormone that protects astrocytes from oxidative insult, which may contribute to brain neuroprotection.


Assuntos
Antioxidantes , Astrócitos , Morte Celular , Peróxido de Hidrogênio , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Prolactina , Fator de Transcrição STAT3 , Transdução de Sinais , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Prolactina/farmacologia , Prolactina/metabolismo , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/farmacologia , Células Cultivadas , Camundongos , Ratos
2.
Endocrinology ; 164(12)2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37864848

RESUMO

The close association between rheumatoid arthritis (RA), sex, reproductive state, and stress has long linked prolactin (PRL) to disease progression. PRL has both proinflammatory and anti-inflammatory outcomes in RA, but responsible mechanisms are not understood. Here, we show that PRL modifies in an opposite manner the proinflammatory actions of IL-1ß and TNF-α in mouse synovial fibroblasts in culture. Both IL-1ß and TNF-α upregulated the metabolic activity and the expression of proinflammatory factors (Il1b, Inos, and Il6) via the activation of the nuclear factor-κB (NF-κB) signaling pathway. However, IL-1ß increased and TNF-α decreased the levels of the long PRL receptor isoform in association with dual actions of PRL on synovial fibroblast inflammatory response. PRL reduced the proinflammatory effect and activation of NF-κB by IL-1ß but increased TNF-α-induced inflammation and NF-κB signaling. The double-faceted role of PRL against the 2 cytokines manifested also in vivo. IL-1ß or TNF-α with or without PRL were injected into the knee joints of healthy mice, and joint inflammation was monitored after 24 hours. IL-1ß and TNF-α increased the joint expression of proinflammatory factors and the infiltration of immune cells. PRL prevented the actions of IL-1ß but was either inactive or further increased the proinflammatory effect of TNF-α. We conclude that PRL exerts opposite actions on joint inflammation in males and females that depend on specific proinflammatory cytokines, the level of the PRL receptor, and the activation of NF-κB signaling. Dual actions of PRL may help balance joint inflammation in RA and provide insights for development of new treatments.


Assuntos
Artrite Reumatoide , Citocinas , Masculino , Feminino , Camundongos , Animais , Citocinas/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Prolactina/farmacologia , Prolactina/metabolismo , Membrana Sinovial/metabolismo , Células Cultivadas , Artrite Reumatoide/metabolismo , Inflamação/metabolismo , Fibroblastos/metabolismo
3.
Microorganisms ; 9(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34442851

RESUMO

Exploring differences in clinical outcomes based on race and origin among patients hospitalized for COVID-19 is a controversial issue. The ALC COVID-19 Registry includes all confirmed COVID-19 patients admitted to hospital from 3 March 2020 to 17 December 2020. The data were obtained from electronic health records in order to evaluate the differences in the clinical features and outcomes among European and Latin American patients. The follow-ups occurred after 156 days. A propensity score weighting (PSW) logistic regression model was used to estimate the odds ratio (OR, 95% CI) for Latin American origin and outcome associations. Of the 696 patients included, 46.7% were women, with a median age of 65 (IQR 53-67) years, 614 (88.2%) were European, and 82 (11.8%) were Latin American. Latin American patients were younger, with fewer comorbidities, and a higher incidence of extensive pneumonia. After adjusting for residual confounders, Latin American origin was not associated with an increased risk of death (PSW OR 0.85 (0.23-3.14)) or with the need for invasive mechanical ventilation (PSW OR 0.35 (0.12-1.03)). Latin American origin was associated with a shorter hospital stay, but without differences in how long the patient remained on mechanical ventilation. In a public healthcare system, the rates of death or mechanical ventilation in severe COVID-19 cases were found to be comparable between patients of European and Latin American origins.

4.
Nanotechnology ; 31(27): 275601, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32109905

RESUMO

We report a method for the efficient anchoring of cadmium selenide (CdSe) nanoparticles on the surface of different types of multi-walled carbon nanotubes (purified, N-doped, O-doped and exfoliated). Characterization using different types of electron microscopies (SEM, STEM, and TEM), energy dispersive spectroscopy (EDS) and x-ray diffraction showed well anchored CdSe nanoparticles (NP) on the nanotube surfaces, NP shapes and sizes varied with temperature and other synthesis conditions, and formed with good yields. The method here reported does not require previous activation of the carbon nanotube surface by chemical functionalization, nor the use of organic solvents, and the reaction proceeded in aqueous solutions, making this process simpler and more environmentally friendly than others.

5.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R760-R771, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32048872

RESUMO

Morphological and behavioral evidence suggests that vasoinhibin is present in the central nervous system (CNS), triggering neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin reduces neuronal survival and differentiation of primary sensory neurons of the peripheral nervous system. To address the functional role played by vasoinhibin at the CNS, and to better understand the underlying mechanisms involved in its actions, we treated primary cultured hippocampal neurons obtained from embryonic day 16 (E16) mice with a human recombinant vasoinhibin. We examined the resulting cellular changes, focusing on neuronal cell death, and explored the local generation of vasoinhibin within the hippocampus. Our results show that vasoinhibin significantly reduced neuronal cell density and increased immunoreactive activated caspase-3 and TUNEL-positive staining at 72, 16, and 24 h, respectively. Furthermore, vasoinhibin increased the expression of proapoptotic genes BAX, BAD, BIM, and PUMA and decreased that of the antiapoptotic gene BCL-2 at 24 h, as assessed by quantitative real-time reverse transcription-polymerase chain reaction. Vasoinhibin effects were blocked by coincubation with a vasoinhibin antibody or with prolactin. Immunoreactive bands consistent with vasoinhibin were observed in hippocampal extracts by Western blot analysis, and a prolactin standard was cleaved to vasoinhibin by a hippocampal lysate in a heat- and cathepsin D inhibitor pepstatin A-dependent fashion. Taken together, these data support the notion that vasoinhibin is locally produced by cathepsin D within the embryonic mouse hippocampus, a brain region that plays a critical role in emotional regulation, resulting in decreased neuronal cell viability via the activation of the intrinsic apoptosis pathway.


Assuntos
Apoptose/fisiologia , Hipocampo/metabolismo , Neurônios/fisiologia , Animais , Proteínas de Ciclo Celular/metabolismo , Regulação para Baixo , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/embriologia , Camundongos , Prolactina/metabolismo , Regulação para Cima
6.
Pancreatology ; 18(3): 280-285, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29496438

RESUMO

OBJECTIVE: Whether chronic pancreatitis (CP) may present with dyspepsia is controversial. We aimed at evaluating the frequency and risk factors of changes of CP in patients presenting with epigastric pain syndrome (EPS)-like symptoms. DESIGN: A prospective, observational, cross-sectional study was carried out in patients with EPS-like symptoms. Patients underwent endoscopic ultrasound (EUS) evaluation of the pancreas, and changes of CP were defined as the presence of five or more EUS criteria of the disease. In patients with 3 or 4 EUS criteria, magnetic resonance dynamic evaluation of the pancreas (MRI/sMRCP) and endoscopic pancreatic function test (ePFT) were carried out to confirm or exclude the presence of changes of CP. A multivariate logistic regression analysis was performed to evaluate factors associated with CP findings, and results are shown as odds ratio (OR) and 95% confidence interval (CI). RESULTS: 213 patients were included. Changes of CP were confirmed by EUS (≥5 criteria) in 18 patients (8.4%). Thirty-four patients had 3-4 EUS criteria, and changes of CP were confirmed in 27 of them by MRI/sMRCP and ePFT (12.7%). Morphological and functional findings of CP were then present in 45 patients (21.1%). Male gender (OR 2.97; 95%CI 1.39-6.37) and alcohol and tobacco consumption (OR 6.56; 95%CI 1.97-21.85) were associated with the presence of changes of CP. CONCLUSION: Morphological and functional changes of CP are frequent in patients with EPS-like symptoms. Whether these pancreatic changes explain EPS-like symptoms requires further investigation.


Assuntos
Dispepsia/complicações , Dispepsia/patologia , Pancreatite Crônica/complicações , Pancreatite Crônica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/complicações , Colangiopancreatografia por Ressonância Magnética , Estudos Transversais , Dispepsia/diagnóstico por imagem , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/patologia , Testes de Função Pancreática , Pancreatite Crônica/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Uso de Tabaco/efeitos adversos , Adulto Jovem
7.
Med. clín (Ed. impr.) ; 149(9): 375-382, nov. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-168050

RESUMO

Introducción y objetivo: La inclusión en práctica real de los antivirales de acción directa en pacientes con hepatitis crónica por VHC ha supuesto un hito histórico en Medicina. Pacientes y métodos: Estudio analítico, prospectivo que incluyó 126 pacientes con hepatitis crónica por VHC tratados con antivirales de acción directa. Evaluamos la eficacia y seguridad del tratamiento y factores asociados a fracaso terapéutico. Resultados: Edad 54±10 años. Varón (70%). Cirrosis (60%). Distribución según genotipos: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B y C (n=15). Naïve (56%). Tasa RVS fue (87,3%): Child-A (91%), Child-B (75%) y Child-C (60%). Las mejores tasas de curación se alcanzaron con las combinaciones Combo 3D/2D±ribavirina (RVS=97,4%; n=39) y sofosbuvir/ledipasvir±ribavirina (RVS=93,1%; n=29). Tasas<90% se registraron con: sofosbuvir+simeprevir±ribavirina (RVS=88%; n=25), simeprevir+daclatasvir±ribavirina (RVS=78%; n=18) y sofosbuvir+daclatasvir±ribavirina (RVS=73,3%; n=15). La adicción de ribavirina a estas 3 últimas opciones terapéuticas (n=19) mejoraba las tasas de curación (RVS=94,7%; 18/19) frente a su ausencia (n=39; RVS=77%). Mejoría MELD (40%). Salida lista trasplante (20%). Sustituciones asociadas a resistencias NS3: G1a (posiciones 80K; n=5); G1b y G4 (posición 168 y 36; n=4), mientras para NS5a: G1a (posición 30; n=2) y G1b y G3 (posición 93; n=3). Variables asociadas al fracaso en análisis multivariante (p<0,05): presencia de ascitis, G3 y dosis de ribavirina<600mg/día. Discusión: La presencia de genotipo 3, ascitis o dosis de ribavirina<600mg/día se asoció a mayores tasas de fracasos. Sería recomendable el uso de ribavirina≥600mg/día en cirróticos G1 o G3, que vayan a ser tratados con sofosbuvir+simeprevir o daclatasvir, si no hubiese disponibilidad de un test de resistencia basal (AU)


Introduction and objective: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. Patients and methods: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. Results: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. Discussion: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Administração da Prática Médica/organização & administração , Antivirais/uso terapêutico , Falha de Tratamento , Estudos Prospectivos , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de Intervenções , Análise de Dados , Razão de Chances
8.
ACS Appl Mater Interfaces ; 9(30): 25474-25480, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28701040

RESUMO

We report a scalable method to obtain a new material where large graphene sheets form webs linking carbon fibers. Film-fiber hybrid nonwoven mats are formed during fiber processing and converted to carbon structures after a simple thermal treatment. This contrasts with multistep methods that attempt to mix previously prepared graphene and fibers, or require complicated and costly processes for deposition of graphene over carbon fibers. The developed graphene-fiber hybrid structures have seamless connections between graphene and fibers, and in fact the graphene "veils" extend directly from one fiber into another forming a continuous surface. The graphene-fiber hybrid structures are produced in situ from aqueous poly(vinyl alcohol) solutions. The solutions were subjected to centrifugal spinning to produce fine nanofiber mats. The addition of salt to the polymer solution stimulated a capillarity effect that promoted the formation of thin veils, which become graphene sheets upon dehydration by sulfuric acid vapor followed by carbonization (at relatively low temperatures, below 800 °C). These veils extend over several micrometers within the pores of the fiber network, and consist of crystalline graphene layers that cross-link the fibers to form a highly interconnected hybrid network. The surface area and pore diameter of the hybrid structures were measured to be 521 m2g-1 and 10 nm, respectively. The resulting structure shows high electrical conductivity, 550 S/m, and promising shielding of electromagnetic interference, making it an attractive system for a broad range of electronic applications.

9.
Med Clin (Barc) ; 149(9): 375-382, 2017 Nov 09.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28416232

RESUMO

INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. RESULTS: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Viremia/tratamento farmacológico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
10.
Med. clín (Ed. impr.) ; 144(12): 536-543, jun. 2015. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-141028

RESUMO

Fundamento y objetivo: Valorar el metabolismo basal y cinético de las lipoproteínas durante el primer mes de biterapia en pacientes con hepatitis crónica C genotipo 1 (HCC-1). Pacientes y métodos: Estudio longitudinal, prospectivo, que incluyó 99 pacientes HCC-1 naive, biopsiados y tratados con biterapia. Clasificamos a nuestros pacientes en 5 niveles de exigencia lipídica, según el grado de fibrosis hepática, carga viral basal y ratio de infectividad (cociente entre concentraciones medias de triglicéridos y colesterol unido a lipoproteínas de alta densidad durante el primer mes), estableciendo para cada uno de ellos, durante este período, una concentración media mínima necesaria de colesterol unido a lipoproteínas de baja densidad (colesterol LDL) para que el paciente alcanzara un «metabolismo lipídico favorable» (MLF), y valoramos su relación con las tasas de curación. Resultados: Alcanzaron mayores tasas de curación aquellos pacientes con fibrosis F3-F4 que presentaron mayores concentraciones basales de colesterol LDL, así como aquellos que consiguieron mantener durante el primer mes de biterapia una ratio de infectividad menor de 3,2 y mayores concentraciones medias de colesterol LDL: media (DE) de 100 (23) mg/dl en «curados» frente a 89 (28) mg/dl en «no curados»,odds ratio 1,1, intervalo de confianza del 95% (1,0-1,2) (p < 0,05), siendo más significativas estas diferencias en los genotipos IL-28B-CC (p = 0,013). Aquellos que alcanzaron la respuesta virológica sostenida presentaron mayores tasas de MLF. Conclusiones: No todos los pacientes con HCC-1 van a presentar durante el primer mes de tratamiento una cinética lipídica favorable, siendo necesario para curarse y/o alcanzar un MLF mantener durante este período unas concentraciones plasmáticas medias de colesterol LDL mayores. Aquellos con ausencia de un MLF podrían beneficiarse del uso de estatinas (AU)


Background and objective: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). Patients and methods: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different “degrees of lipid requirement” that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve 'a favorable lipid metabolism' (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. Results: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P < .05, these differences being more significant for genotype IL-28B-CC (P = .013). Patients with sustained virological response had higher rates of FLM. Conclusions: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins (AU)


Assuntos
Feminino , Humanos , Masculino , Cinética , Mobilização Lipídica/genética , Hepatite C/sangue , Hepatite C/metabolismo , Polimorfismo Genético/genética , Lipoproteínas/administração & dosagem , Lipoproteínas , Cirrose Hepática/patologia , Reação em Cadeia da Polimerase/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/instrumentação , Mobilização Lipídica/fisiologia , Hepatite C/diagnóstico , Hepatite C/patologia , Polimorfismo Genético/fisiologia , Lipoproteínas/deficiência , Lipoproteínas/farmacologia , Cirrose Hepática/metabolismo , Reação em Cadeia da Polimerase/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
11.
Med Clin (Barc) ; 144(12): 536-43, 2015 Jun 22.
Artigo em Espanhol | MEDLINE | ID: mdl-24726260

RESUMO

BACKGROUND AND OBJECTIVE: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). PATIENTS AND METHODS: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different "degrees of lipid requirement" that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve "a favorable lipid metabolism" (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. RESULTS: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P<.05, these differences being more significant for genotype IL-28B-CC (P=.013). Patients with sustained virological response had higher rates of FLM. CONCLUSIONS: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Lipídeos/sangue , Lipoproteínas/sangue , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Antivirais/farmacologia , Quimiocina CXCL10/sangue , Colesterol/sangue , Quimioterapia Combinada , Reações Falso-Positivas , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Feminino , Seguimentos , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/induzido quimicamente , Interferon-alfa/efeitos adversos , Interferon-alfa/farmacologia , Interferons , Interleucinas/genética , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacologia , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Curva ROC , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Ribavirina/farmacologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral , Viremia/sangue
12.
Wilderness Environ Med ; 25(2): 210-3, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24507436

RESUMO

OBJECTIVE: The purpose of this institutional review board-approved, cross-sectional study was to identify residual symptoms and signs of envenomation reported by snakebite survivors via a telephone survey. METHODS: Victims of rattlesnake bite who were treated at a single hospital center during a 10-year period were contacted through a telephone survey. Study subjects were included through a diagnosis-based retrospective chart review of snakebite victims, and excluded if they did not receive rattlesnake antivenom. Data collection was done using a standardized form that included sections about residual, recurrent, or new pain, weakness, paresthesias, or other limitations of the bitten limb. RESULTS: We identified 46 snakebite cases including 5 of 46 "dry" bites. The remaining cases (41 of 46) all received Crofab. Interviews were completed for 31% of these patients (13 of 41), and the remainder were lost to follow-up. Most bites occurred in men (12 cases, 92% males) and on the arms (9 cases, 69%). Six of the 13 respondents (46%) reported residual symptoms from the bite. Persistent symptoms described included localized pain at the bite site (3 cases), numbness or paresthesias (2 cases), abnormal skin peeling and discoloration at the bite site (2 cases), and persistent weakness of the bitten extremity (1 case). Among patients reporting persistent symptoms, the bite-to-survey interval ranged from 7 months to 12 years, with a median interval of 4 years. CONCLUSIONS: Our study population demonstrated a notable incidence (43%) of self-reported persistent symptoms related to their rattlesnake bites, although the overall level of disability from these injuries seems low.


Assuntos
Mordeduras de Serpentes/complicações , Adolescente , Adulto , Animais , Antivenenos/uso terapêutico , California/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Crotalus , Feminino , Inquéritos Epidemiológicos , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Masculino , Dor/etiologia , Estudos Retrospectivos , Mordeduras de Serpentes/tratamento farmacológico , Telefone
13.
Toxicon ; 69: 38-41, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23200707

RESUMO

OBJECTIVE: We investigated clinical patterns of crotaline envenomation presenting to a tertiary-care academic hospital in Central California over a 10-year period. METHODS: An IRB-approved, retrospective chart review was conducted on all patients diagnosed with snakebite from December 2000 to December 2010. Data abstracted: demographics, anatomic location of bite, comorbid conditions and intoxicants, length of stay, antivenom dose, laboratory results, and complications or procedures. RESULTS: There were 46 snakebite cases admitted over the study period. Five were "dry bites"; the remaining cases (41/46) received antivenom. There was a male predominance (83% male victims). Upper extremity bites were more common (32/41 upper vs 10/42 lower extremity). One victim sustained bilateral bites to the hands. Thirty-five patients (85%) were admitted, with an average length of stay 2.12 days. The longest hospitalization was 15 days. There were no fatalities. The average time from bite to ED presentation was 2 h 44 min. Bites occurred during every month except November, with the majority occurring during spring and summer months and peaking in June (12/42 cases). Most bites occurred in the hours between noon and 8 pm. The amount of antivenom given ranged from 2 to 35 vials (average, 9 vials). Interfacility transfers were common in our study population: thirteen (32%) patients were transferred into our emergency department for a higher level of care, and 3 (7%) were transferred out (two because of insurance requirements, and one for higher level of Pediatric ICU care). There were no surgical interventions in our study group. Intoxication did not appear to play a major role in this population as only 3 patients (7%) were found to be acutely intoxicated: one with cannabis and amphetamines, 1 with alcohol, and 1 with opioids. CONCLUSIONS: In Central California, crotaline envenomations occurred mainly in adult males. Dry bites, or bites not requiring antivenom administration, were uncommon, comprising only 10% of bites in this study population. Contrary to popular and clinical beliefs, substance abuse and/or alcohol intoxication did not appear to play a role in the majority of patients in this study. Care providers and snakebite specialists should be aware that snakebite patients are often transferred between facilities, a finding that may be useful in designing future first aid protocols and research. We hope these findings add concrete data and help correct some common misconceptions about snakebites in Central California.


Assuntos
Mordeduras de Serpentes/epidemiologia , Sobreviventes , Adolescente , Adulto , Animais , Antivenenos/uso terapêutico , California/epidemiologia , Criança , Pré-Escolar , Crotalus , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Estações do Ano , Mordeduras de Serpentes/diagnóstico , Mordeduras de Serpentes/tratamento farmacológico , Resultado do Tratamento
14.
Nano Lett ; 9(4): 1527-33, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19260705

RESUMO

We found that multiwalled carbon nanotubes (MWNTs) can be opened longitudinally by intercalation of lithium and ammonia followed by exfoliation. Intercalation of open-ended tubes and exfoliation with acid treatment and abrupt heating provided the best results. The resulting material consists of: (i) multilayered flat graphitic structures (nanoribbons), (ii) partially open MWNTs, and (iii) graphene flakes. We called the completely unwrapped nanotubes ex-MWNTs, and their large number of edge atoms makes them attractive for many applications.

15.
Rev. Asoc. Argent. Traumatol. Deporte ; 14(2): 26-7, 2007. ilus
Artigo em Espanhol | BINACIS | ID: bin-120633

RESUMO

El objetivo del trabajo es presentar nuestra experiencia en el tratamiento del Síndrome de fricción de la banda iliotibial (SFBIT). El SFBIT es una lesión por sobreuso, producida por la fricción en exceso entre la banda iliotibial (BIT) y el epicóndilo femoral externo.Fueron tratados 16 pacientes, 5 de los cuales demandaron tratamiento quirúrgico. En todos los casos realizamos el aplanamiento del epicóndilo externo con resultados satisfactorios y sin recurrencias en la patología


Assuntos
Adulto , Transtornos Traumáticos Cumulativos/diagnóstico , Transtornos Traumáticos Cumulativos/terapia , Transtornos Traumáticos Cumulativos/cirurgia , Traumatismos em Atletas/diagnóstico , Joelho/patologia , Dor , Fricção , Síndrome , Diagnóstico Diferencial , Futebol/lesões , Corrida/lesões
16.
Rev. Asoc. Argent. Traumatol. Deporte ; 14(2): 26-27, 2007. ilus
Artigo em Espanhol | LILACS | ID: lil-490466

RESUMO

El objetivo del trabajo es presentar nuestra experiencia en el tratamiento del Síndrome de fricción de la banda iliotibial (SFBIT). El SFBIT es una lesión por sobreuso, producida por la fricción en exceso entre la banda iliotibial (BIT) y el epicóndilo femoral externo.Fueron tratados 16 pacientes, 5 de los cuales demandaron tratamiento quirúrgico. En todos los casos realizamos el aplanamiento del epicóndilo externo con resultados satisfactorios y sin recurrencias en la patología.


Assuntos
Dor , Joelho/patologia , Transtornos Traumáticos Cumulativos/cirurgia , Transtornos Traumáticos Cumulativos/diagnóstico , Transtornos Traumáticos Cumulativos/terapia , Traumatismos em Atletas/diagnóstico , Diagnóstico Diferencial , Futebol/lesões , Síndrome
17.
Rev. Asoc. Argent. Traumatol. Deporte ; 14(2): 26-27, 2007. ilus
Artigo em Espanhol | BINACIS | ID: bin-122923

RESUMO

El objetivo del trabajo es presentar nuestra experiencia en el tratamiento del Síndrome de fricción de la banda iliotibial (SFBIT). El SFBIT es una lesión por sobreuso, producida por la fricción en exceso entre la banda iliotibial (BIT) y el epicóndilo femoral externo.Fueron tratados 16 pacientes, 5 de los cuales demandaron tratamiento quirúrgico. En todos los casos realizamos el aplanamiento del epicóndilo externo con resultados satisfactorios y sin recurrencias en la patología.(AU)


Assuntos
Transtornos Traumáticos Cumulativos/diagnóstico , Transtornos Traumáticos Cumulativos/terapia , Transtornos Traumáticos Cumulativos/cirurgia , Traumatismos em Atletas/diagnóstico , Joelho/patologia , Dor , Síndrome , Diagnóstico Diferencial , Futebol/lesões
18.
Dev Neurosci ; 28(6): 488-98, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17028426

RESUMO

Wild-type and myelin-deficient rats received a single intraparenchymal injection of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus callosum at postnatal day 4. The fate of endogenous stem cells in the brain was examined by the expression of the stem cell marker nestin, together with Tf, neurofilaments and glial fibrillary acidic protein from 2 to 14 days after injection. Treated mutants lacked nestin expression in the ventricular wall and had an increase in nestin-labeled radial cell processes in the subventricular regions, and extended into the parenchyma. The subventricular zone was populated by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells originated by proliferation and were identified as OLs based upon Tf expression. Thus, TS1 is an effective treatment to promote endogenous subventricular zone progenitor proliferation, migration and OL lineage specification. This strategy offers for the first time the possibility of myelin restoration to treat myelin disorders.


Assuntos
Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/crescimento & desenvolvimento , Doenças Desmielinizantes/metabolismo , Oligodendroglia/metabolismo , Células-Tronco/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/metabolismo , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/fisiopatologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas de Filamentos Intermediários/metabolismo , Ventrículos Laterais , Masculino , Proteínas do Tecido Nervoso/metabolismo , Nestina , Proteínas de Neurofilamentos/metabolismo , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Mutantes , Ratos Wistar , Células-Tronco/efeitos dos fármacos , Telencéfalo/efeitos dos fármacos , Telencéfalo/crescimento & desenvolvimento , Telencéfalo/metabolismo , Transferrina/farmacologia
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