RESUMEN

OBJECTIVE: To investigate the influence of restrictive and liberal red blood cell suspension (RBCs) transfusions on the prognosis of premature infants and to analyze the influencing factors to provide a reference for the transfusion strategy of preterm infants. METHODS: Retrospective analysis was conducted on 85 cases of anemic premature infants treated in our center, including 63 cases in the restrictive transfusion group and 22 in the liberal transfusion group. RESULTS: RBCs transfusions were effective in both groups, and there were no statistically significant differences in post-transfusion hemoglobin and hematocrit between the two groups (P > 0.05). The outcome events: the duration of ventilatory support was statistically prolonger in the restrictive group compared with the liberal group (P < 0.001); however, the differences in mortality, the increased weight before discharge, and length of stay in the hospital within the two groups were not statistically significant (P = 0.237, 0.36 and 0.771, respectively). Univariate survival analysis showed that age, birth weight, Apgar 1 min and Apgar 10 min scores were the influencing factors for death, with P values of 0.035, 0.004, <0.001, and 0.013, respectively; COX regression analysis showed that Apgar 1 min score was an independent factor of the survival time of preterm infants (P = 0.002). CONCLUSION: Compared with the restrictive transfusion group, liberal transfusion patients presented a shorter duration of ventilatory support, which is more beneficial to the prognosis of premature infants.

Asunto(s)

Transfusión de Eritrocitos , Recien Nacido Prematuro , Lactante , Humanos , Recién Nacido , Estudios Retrospectivos , Hemoglobinas/análisis , Pronóstico , Eritrocitos/química

Asunto(s)

Infecciones por Virus de Epstein-Barr/virología , Fiebre/virología , Herpesvirus Humano 4/patogenicidad , Hipertensión Intracraneal/virología , Meningitis/virología , Aciclovir/uso terapéutico , Adulto , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Infecciones por Virus de Epstein-Barr/diagnóstico por imagen , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Fiebre/diagnóstico por imagen , Fiebre/tratamiento farmacológico , Fiebre/inmunología , Glucosa/líquido cefalorraquídeo , Herpesvirus Humano 4/inmunología , Humanos , Inmunocompetencia , Hipertensión Intracraneal/diagnóstico por imagen , Hipertensión Intracraneal/tratamiento farmacológico , Hipertensión Intracraneal/inmunología , Meningitis/diagnóstico por imagen , Meningitis/tratamiento farmacológico , Meningitis/inmunología , Monocitos/patología , Monocitos/virología , Cráneo/diagnóstico por imagen , Cráneo/efectos de los fármacos , Cráneo/inmunología , Cráneo/virología

RESUMEN

BACKGROUND/AIMS: The objective of this study was to determine whether treatment with acetylcholinesterase inhibitors would provide cognitive benefit for patients with vascular dementia. METHODS: Studies in patients with vascular dementia, who had not taken acetylcholinesterase inhibitors or memantine for at least 6 weeks, were included. RESULTS: Twelve studies were included in the final analysis. Donepezil showed significant improvement in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) as compared to placebo, at the doses tested, that is, 5 and 10 mg/day (difference in means -1.389 and -1.680, respectively, p ≤ 0.008), but not on the Mini Mental State Examination (MMSE) (p ≥ 0.259). Galantamine also improved the ADAS-cog in comparison to the placebo (difference in means -2.191, p < 0.001), whereas, rivastigmine did not show any benefit on ADAS-cog. However, the findings with rivastigmine are difficult to interpret, given there were only 2 studies. Treatment with cholinesterase inhibitors was associated with a twofold increase in the odds of discontinuation, due to adverse events (pooled OR 1.966, 95% CI 1.630-2.371, p < 0.001). CONCLUSION: The present results reveal the therapeutic benefits of donepezil and galantamine in patients with vascular dementia. Interestingly, the ADAS-cog and MMSE varied considerably in detecting cognitive improvement.

Asunto(s)

Inhibidores de la Colinesterasa/uso terapéutico , Demencia Vascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Donepezilo , Femenino , Galantamina/uso terapéutico , Humanos , Indanos/uso terapéutico , Pruebas Neuropsicológicas , Piperidinas/uso terapéutico , Rivastigmina/uso terapéutico

RESUMEN

Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX­induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX­induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX­induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N­acetyl­L­cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX­induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-γ-lyase were examined by western blotting.

Asunto(s)

Cardiotoxicidad/metabolismo , Doxorrubicina/toxicidad , Sulfuro de Hidrógeno/farmacología , Miocitos Cardíacos/metabolismo , Peroxiredoxina III/metabolismo , Acetilcisteína/farmacología , Animales , Cardiotónicos/farmacología , Cardiotoxicidad/patología , Muerte Celular/efectos de los fármacos , Cistationina gamma-Liasa/metabolismo , Citoprotección/efectos de los fármacos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Factores de Tiempo

RESUMEN

Resveratrol is a polyphenolic compound found in wine, which is mainly produced by the grapevine and exerts chemopreventive effects against hepatocellular carcinoma. However, the underlying molecular mechanisms have remained to be fully elucidated. The present study assessed whether resveratrol-induced apoptosis was mediated via the activation of the forkhead box O3a (FoxO3a) transcription factor. It was demonstrated that resveratrol treatment induced apoptosis in HepG2 cells, and that this pro-apoptotic effect was accompanied with increases in the expression of apoptotic protein Bim. Following resveratrol treatment, Akt-mediated phosphorylation of FoxO3a was observed to be diminished in HepG2 cells. Furthermore, resveratrol enhanced the nuclear levels of FoxO3a and mediated neuronal death via Bim. The present study demonstrated that resveratrol induced apoptosis in HepG2 cells through activation of the transcription factor FoxO3a and increasing the expression of Bim protein.

Asunto(s)

Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Factores de Transcripción Forkhead/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal/efectos de los fármacos , Estilbenos/farmacología , Proteína 11 Similar a Bcl2 , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Proteína Forkhead Box O3 , Células Hep G2 , Humanos , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Resveratrol

RESUMEN

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 µM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration amplified P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX-induced apoptosis via the AMPK/P53 pathway.

Asunto(s)

Proteínas Quinasas Activadas por AMP/genética , Apoptosis/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Línea Celular , Doxorrubicina/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ratas , Resveratrol , Transducción de Señal/efectos de los fármacos , Estilbenos/administración & dosificación , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/biosíntesis , Proteína X Asociada a bcl-2/genética

RESUMEN

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it produces reactive oxygen species (ROS) that induce severe cytotoxicity, limiting its clinical application. The aim of the present study was to investigate the role of peroxiredoxin III (Prx III) in DOX-induced H9c2 cell injuries. Following DOX treatment, the expression of phosphorylated-FoxO3a (p-FoxO3a) was decreased and Prx III expression was increased in H9c2 cells. In order to detect whether oxidative stress was involved in the induction of Prx III expression by FoxO3a, exogenous H2O2 was used to induce oxidative stress in the H9c2 cells. Apoptosis of H9c2 cardiomyocytes was assessed using methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and p-FoxO3a were evaluated using western blot analysis. As expected, H2O2 was found to mimic the effect of DOX, decreasing the expression of p-FoxO3a and increasing the expression of Prx III. In addition, the study evaluated whether the transcription factor FoxO3a was essential for the expression of Prx III. Pretreatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to exposure to DOX dramatically increased the phosphorylation of FoxO3a and led to a marked reduction in Prx III expression in the H9c2 cells. In conclusion, the results of the current study suggest that FoxO3a mediates the expression of Prx III in DOX-induced injuries.

RESUMEN

MicroRNA (miR)-146a is a negative regulator of nuclear factor-κB (NF-κB) signaling that affects tumor growth and survival. The present study was undertaken to determine whether the cytotoxicity of curcumin (diferuloylmethane), a natural polyphenolic compound isolated from turmeric (Curcuma longa Linn), in glioblastoma cells is mediated through upregulation of miR­146a. Human U­87 MG glioblastoma cells were treated with curcumin and temozolomide (TMZ) alone or in combination, and cell proliferation and apoptosis were assessed. The involvement of miR­146a and NF­κB signaling in curcumin­mediated chemosensitization was explored. Curcumin exposure led to upregulation of miR­146a in U­87 MG cells. Combined curcumin and TMZ treatment significantly (P<0.05) inhibited U­87 MG cell proliferation and induced apoptotic death, compared with each alone. Notably, curcumin­mediated enhancement of TMZ­induced apoptosis was blocked by depletion of miR­146a. By contrast, miR­146a overexpression enhanced apoptosis and suppressed NF­κB activation in TMZ­treated cells. Additionally, pharmacological inhibition of NF­κB signaling significantly increased TMZ­induced apoptosis. To the best of our knowledge, the present study provides the first evidence that upregulation of miR­146a and inactivation of NF­κB signaling mediates the sensitization of human glioblastoma cells to TMZ-induced apoptosis by curcumin.

Asunto(s)

Antineoplásicos/farmacología , Neoplasias Encefálicas/genética , Curcumina/farmacología , Dacarbazina/análogos & derivados , Resistencia a Antineoplásicos , Glioblastoma/genética , MicroARNs/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dacarbazina/farmacología , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/metabolismo , Humanos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Temozolomida

RESUMEN

Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX­induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N­acetyl­L­cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX­induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells.

Asunto(s)

Antineoplásicos/farmacología , Calreticulina/genética , Doxorrubicina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Antineoplásicos/efectos adversos , Apoptosis/efectos de los fármacos , Apoptosis/genética , Cardiotoxicidad , Línea Celular , Doxorrubicina/efectos adversos , Humanos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo

RESUMEN

Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.

Asunto(s)

Factores de Transcripción Forkhead/metabolismo , Glucosa/toxicidad , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Neurotoxinas/toxicidad , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estilbenos/farmacología , Acetilcisteína/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 11 Similar a Bcl2 , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Cromonas/farmacología , Regulación hacia Abajo/efectos de los fármacos , Proteína Forkhead Box O3 , Proteínas de la Membrana/metabolismo , Morfolinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Transducción de Señal/efectos de los fármacos

RESUMEN

BACKGROUND: Recent studies have linked chemotherapy resistance to the altered expression of microRNAs (miRNAs). Thus, miRNA-based approaches to modulating sensitivity to temozolomide (TMZ) may overcome chemoresistance. The aim of the present study was to investigate whether miR-136 could modulates glioma cell sensitivity to TMZ. METHODS: The proliferation of glioma U251 cell line was evaluated by MTT assay. The expression of astrocyte elevated gene-1 (AEG-1)was detected by real­time polymerase chain reaction (RT-PCR)and Western blot. The luciferase reporter gene was used to test whether AEG-1 was the target of the miR-136. RESULTS: The MTT assay showed that U251 cells with miR-136 overexpression were significantly more sensitive to the therapy of TMZ than control cells. Luciferase assays revealed that miR-136 directly targeted the 3'UTR of AEG-1. qRT-PCR and western blotting analysis found that AEG-1 expression at the mRNA and protein levels decreased in the miR-136 mimic-treatment group relative to control group. Downregulation of AEG-1 expression by siRNAs, U251 cells became more sensitive to the therapy of TMZ. In addition, the enhanced growth-inhibitory effect by the miR-136 mimics transfection was enhanced after the addition of AEG-1 siRNA. CONCLUSIONS: The present study provides the first evidence that miR-136 plays a key role in TMZ resistance by targeting the AEG-1 protein in glioma cell line, suggesting that miR-136 can be used to predict a patient's response to TMZ therapy as well as serve as a novel potential maker for glioma therapy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_173.

Asunto(s)

Antineoplásicos Alquilantes/uso terapéutico , Moléculas de Adhesión Celular/genética , Dacarbazina/análogos & derivados , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/genética , MicroARNs/genética , Astrocitos , Línea Celular Tumoral , Proliferación Celular , Dacarbazina/uso terapéutico , Regulación hacia Abajo , Glioma/tratamiento farmacológico , Humanos , Proteínas de la Membrana , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Temozolomida , Transfección

RESUMEN

BACKGROUND/AIMS: Post-stroke complications may influence prognosis, and may even become potentially life-threatening. The aim of this prospective study was to examine the frequency and timing of medical complications during the acute stage of critical ischemic stroke in patients treated in a neurological intensive care unit. METHODS: Seventy acute ischemic stroke patients in a critical condition with morbid changes in organs other than the brain or with severe complications were admitted to a neurological intensive care unit and followed up with assessments of 15 specified complications during the first 2 weeks on days 2, 4, 7, and 14. RESULTS: The most common complications within 2 weeks of onset were chest infection (90%), fever (64%), hypoalbuminemia (56%), arrhythmia (46%), irritable ulcer (44%), gastrointestinal dysfunction (39%), progression or recurrence of stroke (33%), and urinary tract infection (30%). The incidence of progression or recurrence of stroke and urinary tract infection peaked at day 2, and the incidence of arrhythmia, fever, chest infection, irritable ulcer, gastrointestinal dysfunction, and malnutrition peaked from 1 to 2 weeks. CONCLUSION: Progression or recurrence of stroke, fever, and chest infection are common complications in the acute stage of critical ischemic stroke.

Asunto(s)

Fiebre/etiología , Enfermedades Pulmonares/etiología , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/etiología , Isquemia Encefálica/complicaciones , Progresión de la Enfermedad , Femenino , Enfermedades Gastrointestinales/etiología , Humanos , Hipoalbuminemia/etiología , Incidencia , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/etiología , Factores de Tiempo , Infecciones Urinarias/etiología

RESUMEN

A national screening and referral program of short school children was launched in Taiwan in 2000. We analyzed 655 referrals (boys 303, girls 352) from this program whose heights were below--2 standard deviation score (SDS) for age and gender. Evaluation included: detailed medical history, physical examination and laboratory tests such as blood count, thyroid function, growth hormone screening, bone age and chromosome tests. The results were compared with worldwide data. Normal variations accounted for 64.9% of all etiologies for reasons such as constitutional delay 37.4%, familial short stature 16.5%, and a combination of above two 11.0%. The rest were of pathological short stature for reasons such as: idiopathic short stature 7.9%, growth hormone deficiency 7.9%, precocity 3.2%, skeletal dysplasia 2.3%, intrauterine growth retardation 1.4%, Turner syndrome 1.4%, other chromosomal anomaly 0.8%, and others 5.0%. We conclude that the majority of short stature in Taiwanese children is due to normal variation although potentially treatable causes account for at least 12.8% of cases, such as GHD, Turner syndrome, hypothyroidism and precocity. The inexpensive screening program therefore seems to be beneficial in identifying children with short stature of potentially treatable etiology.

Asunto(s)

Trastornos del Crecimiento/etiología , Adolescente , Niño , Femenino , Hormona del Crecimiento/deficiencia , Humanos , Masculino , Tamizaje Masivo , Examen Físico , Instituciones Académicas , Taiwán