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1.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37628954

RESUMEN

This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment.


Asunto(s)
Peróxido de Hidrógeno , Infertilidad , Humanos , Femenino , Embarazo , Masculino , Nacimiento Vivo , Semen , Espermatozoides , Infertilidad/terapia , Inseminación , Proteína SUMO-1
2.
J Obstet Gynaecol Res ; 48(7): 1968-1977, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35474372

RESUMEN

AIM: The percentage of medicine graduates opting for residency in obstetrics and gynecology (OB/GYN) has been decreasing in developed countries, including in Taiwan, Japan, and Korea. This multicountry study surveyed the OB/GYN residents affiliated with the Taiwan Association of Obstetrics and Gynecology (TAOG), the Japanese Society of Obstetrics and Gynecology (JSOG), and the Korean Society of Obstetrics and Gynecology (KSOG) to evaluate the factors affecting the choice of pursing OB/GYN. METHODS: A 17-item questionnaire surveying the factors influencing the choice of pursuing a major medical specialty was translated into Japanese, Korean, and Chinese and administered to postgraduate OB/GYN residents between July 1, 2020, and August 31, 2020. Data on the participants' sex, age, and level of residency were collected. Responses were compared between countries and sexes. RESULTS: Residents of all three countries chose OB/GYN based on personal interest, and a sense of accomplishment in saving people's life. Other positive factors include improved quality of life; higher salaries; and more opportunity for new techniques, research, and promotion. The negative factors included medical litigations, longer work hours, and unsafe working environments. Korean residents had lower ratings in several items, including "support from family," "safety of working environment," and "effectiveness of the alternative dispute resolution system," which, unlike Japan and Taiwan, is not a no-fault compensation system for childbirth accidents. CONCLUSIONS: The study findings can guide strategy making, such as decreasing workload and yet maintain training quality, to increase the number of medical students pursuing OB/GYN residency.


Asunto(s)
Ginecología , Internado y Residencia , Obstetricia , Femenino , Humanos , Japón , Embarazo , Calidad de Vida , República de Corea , Encuestas y Cuestionarios , Taiwán
3.
Molecules ; 24(10)2019 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-31100896

RESUMEN

The main causes of dysfunction after a spinal cord injury (SCI) include primary and secondary injuries that occur during the first minutes, hours, to days after injury. This treatable secondary cascade provides a window of opportunity for delivering therapeutic interventions. An S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) has anti-inflammatory, cytoprotective, and anticarcinogenic effects in liver or neurodegenerative diseases. The present work examined the effect of S/B on injured spinal cord neurons in cultures and in vivo. S/B effectively reduced peroxide toxicity and lipopolysaccharide stimulation in both spinal cord neuron/glial and microglial cultures with the involvement of PKC and HSP70. The effect of S/B was further conducted in contusive SCI rats. Intraperitoneal injections of S/B to SCI rats preserved spinal cord tissues and effectively attenuated microglial activation. Consistently, S/B treatment significantly improved hindlimb functions of SCI rats. In the acute stage of injury, S/B treatment markedly reduced the levels of ED1 expression and lactate and had a tendency to decrease lipid peroxidation. Taken together, we demonstrated long-term hindlimb restoration alongside histological improvements with systemic S/B remedy treatment in a clinically relevant model of contusive SCI. Our findings highlight the potential of an S/B remedy for acute therapeutic intervention after SCI.


Asunto(s)
Bupleurum/química , Medicamentos Herbarios Chinos/farmacología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Scutellaria baicalensis/química , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Biomarcadores , Células Cultivadas , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Inmunohistoquímica , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/metabolismo
4.
J Biomed Sci ; 24(1): 34, 2017 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-28545516

RESUMEN

BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent. RESULTS: Cultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10-12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40-60% of AdPGIS-OEC transplanted SCI rats. CONCLUSIONS: Enhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.


Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Expresión Génica , Oxidorreductasas Intramoleculares/genética , Neuroglía/fisiología , Nervio Olfatorio/fisiología , Regeneración de la Medula Espinal , Animales , Células Cultivadas , Sistema Enzimático del Citocromo P-450/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Ratas , Ratas Sprague-Dawley , Recuperación de la Función
5.
J Biomed Sci ; 21: 5, 2014 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-24447306

RESUMEN

BACKGROUND: Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model. RESULTS: Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains. CONCLUSIONS: Our data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.


Asunto(s)
Isquemia Encefálica/terapia , Medios de Cultivo Condicionados/farmacología , Trasplante de Células Madre Mesenquimatosas , Accidente Cerebrovascular/terapia , Animales , Células de la Médula Ósea/citología , Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatología , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Células Madre Mesenquimatosas/citología , Ratas , Accidente Cerebrovascular/fisiopatología
6.
Taiwan J Obstet Gynecol ; 63(3): 402-404, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38802207

RESUMEN

OBJECTIVE: To discuss several techniques of hysteroscopic surgery for complete septate uterus. CASE REPORT: A 40-year-old female with unexplained primary infertility was diagnosed with complete septate uterus with septate cervix. Hysteroscopic incision of complete septate uterus was performed by using ballooning technique. The patient conceived naturally shortly after the operation and delivered a healthy, term infant. CONCLUSION: Hysteroscopic incision of complete septate uterus is a safe and prompt way of metroplasty. With the knowledge obtained from a pre-operative MRI, it can be completed without laparoscopy and the need for hospitalization.


Asunto(s)
Cuello del Útero , Histeroscopía , Útero , Humanos , Femenino , Adulto , Histeroscopía/métodos , Embarazo , Cuello del Útero/anomalías , Cuello del Útero/cirugía , Útero/anomalías , Útero/cirugía , Infertilidad Femenina/cirugía , Infertilidad Femenina/etiología , Nacimiento a Término , Anomalías Urogenitales/cirugía , Anomalías Urogenitales/diagnóstico por imagen , Útero Septado
7.
J Neurosci ; 31(11): 4137-47, 2011 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-21411654

RESUMEN

Spinal cord injury elicits an inflammatory response that recruits macrophages to the injured spinal cord. Quantitative real-time PCR results have shown that a repair strategy combining peripheral nerve grafts with acidic fibroblast growth factor (aFGF) induced higher interleukin-4 (IL-4), IL-10, and IL-13 levels in the graft areas of rat spinal cords compared with transected spinal cords at 10 and 14 d. This led to higher arginase I-positive alternatively activated macrophage (M2 macrophage) responses. The gene expression of several enzymes involved in polyamine biosynthesis pathways was also upregulated in the graft areas of repaired spinal cords. The treatment induced a twofold upregulation of polyamine levels at 14 d, as confirmed by HPLC. Polyamines are important for the repair process, as demonstrated by the observation that treatment with inhibitors of arginase I and ornithine decarboxylase attenuates the functional recoveries of repaired rats. After 14 d, the treatment also induced the expression of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as M2 macrophages within grafted nerves expressing BDNF. IL-4 was upregulated in the injury sites of transected rats that received aFGF alone compared with those that received nerve grafts alone at 10 d. Conversely, nerve graft treatment induced NGF and BDNF expression at 14 d. Macrophages expressing polyamines and BDNF may benefit axonal regeneration at 14 d. These results indicate that aFGF and nerve grafts regulate different macrophage responses, and M2 macrophages may play an important role in axonal regeneration after spinal cord injury in rats.


Asunto(s)
Factor 1 de Crecimiento de Fibroblastos/metabolismo , Interleucinas/metabolismo , Macrófagos/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Nervios Periféricos/trasplante , Poliaminas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Animales , Arginasa/antagonistas & inhibidores , Cromatografía Líquida de Alta Presión , Femenino , Adhesivo de Tejido de Fibrina , Inmunohistoquímica , Actividad Motora/fisiología , Inhibidores de la Ornitina Descarboxilasa , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Médula Espinal/metabolismo , Regeneración de la Medula Espinal , Factores de Tiempo , Regulación hacia Arriba/fisiología
8.
Taiwan J Obstet Gynecol ; 61(1): 102-109, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35181016

RESUMEN

OBJECTIVE: Increasing obstetric medical litigations had great impacts in health care system resulted in lower recruitment of residents and higher medical cost of defensive medicine in Taiwan. In order to reduce medical litigation, the "Childbirth Accident Emergency Relief Act" was implemented in June 2016. This study presented five-year results of a novel childbirth accident compensation system. MATERIALS AND METHODS: The purpose of the Relief Act was to establish a national relief system to ensure timely relief, reduce medical disputes, promote the partnership between patient and medical personnel. The compensations included maximal 2 million NTD for maternal death, maximal 0.3 million NTD for neonatal and fetal deaths, and 3, 2, and 1.5 million NTD for maternal or neonatal profound, severe, and moderate disabilities, respectively. Puerperal hysterectomy was included with maximal 0.8 million NTD compensation. RESULTS: Since June 30, 2016 to June 30, 2021, there were 1340 applications reviewed by Committee and 1258 were approved with total relief of 744.7 million NTD (26.6 million USD) with approve rate of 93.9%. It took an average of 109.8 days to start application from childbirth and 102.4 days to get compensation from application. 66.1% of accident victims agreed this system can restore doctor-patient relationship by immediate care and assistance from medical institutions. CONCLUSION: The Relief Act is the first government leading compensation system to establish a national relief system. It was enacted to reduce medical disputes, promote the partnership between patient and medical personnel, and enhance health and safety of women during childbirth. A no-fault compensation would be an efficient alternative disputes resolution to childbirth accidents.


Asunto(s)
Traumatismos del Nacimiento , Compensación y Reparación/legislación & jurisprudencia , Disentimientos y Disputas , Mala Praxis/legislación & jurisprudencia , Errores Médicos/legislación & jurisprudencia , Relaciones Médico-Paciente , Traumatismos del Nacimiento/epidemiología , Traumatismos del Nacimiento/etiología , Parto Obstétrico , Femenino , Humanos , Recién Nacido , Seguro de Responsabilidad Civil , Responsabilidad Legal , Embarazo , Taiwán/epidemiología
9.
Taiwan J Obstet Gynecol ; 61(5): 794-799, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36088046

RESUMEN

OBJECTIVE: The purpose of this study was to establish a new reference chart and growth standards for fetal biometry in Taiwan. MATERIALS AND METHODS: 2047 singleton pregnancies were enrolled in this study with 15,813 fetal scans between 18 and 40 gestational weeks. A reference chart and normal range for fetal biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) was established by longitudinal quantile regression model. 330 women with comorbidities including gestational hypertension, preeclampsia and gestational diabetes were excluded and 1717 pregnant women were enrolled for the growth standard. RESULTS: The new reference values were significantly larger across all gestational ages compared with the prior National Taiwan University reference chart in 1983. Compared with Intergrowth-21st, the BPD was larger at 18-23 weeks, the AC was larger at 18-24 weeks and the FL was larger at 18-36 weeks whereas they were all smaller at 29-40 weeks for the BPD, at 32-40 weeks for the AC and at 38-40 weeks for the FL. A quantile regression equation of biometry was established. BPD, AC, and FL had weekly growth of 2.5, 9.87 and 2.15 mm. Prepregnancy body weight, height, age, and gestational diabetes increased fetal size. Both gestational and chronic hypertension decreased fetal size. CONCLUSION: To promote maternal-fetal safety, a new reference chart and growth standard for fetal biometry is necessary to measure fetal growth.


Asunto(s)
Diabetes Gestacional , Ultrasonografía Prenatal , Biometría , Femenino , Feto , Edad Gestacional , Humanos , Embarazo
10.
J Gene Med ; 13(5): 283-9, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21557400

RESUMEN

BACKGROUND: Following spinal cord injury, the delivery of neurotrophic factors to the injured spinal cord has been shown to promote axonal regeneration and functional recovery. In previous studies, we showed that acidic fibroblast growth factor (aFGF) is a potent neurotrophic factor that promotes the regeneration of axotomized spinal cord or dorsal root ganglion neurones. METHODS: We constructed a recombinant adeno-associated virus (AAV) vector to express human aFGF and evaluated aFGF expression and function in AAV-aFGF-infected PC12 cells. We analyzed AAV-green fluorescent protein (GFP) tropism and AAV-mediated aFGF expression in contused spinal cords. Animals received behavioural testing to evaluate the functional recovery. RESULTS: Overexpression of aFGF was shown in AAV-aFGF-infected PC12 cells in a dose-dependent manner. Concurrently, neurite extension and cell number were significantly increased in AAV-aFGF infected cells. AAV-mediated GFP expression persisted for at least 5 weeks in contused spinal cords, and the most prominently transduced cells were neurones. Contusive injury reduced endogenous aFGF expression in spinal cords. Overexpression of aFGF was demonstrated in AAV-aFGF transduced spinal cords compared to AAV-GFP transduced spinal cords at 3 and 14 days post-injury. Evaluation of motor function revealed that the improvement of AAV-aFGF-treated rats was prominent. Both AAV-aFGF- and recombinant human aFGF-treated rats revealed significantly better recovery at 5 weeks post-injury, compared to vehicle- and AAV-GFP-treated rats. CONCLUSIONS: These data suggest that supplement of aFGF improve the functional recovery of spinal cord-contused rats and that AAV-aFGF-mediated gene transfer could be a clinically feasible therapeutic approach for patients after nervous system injuries.


Asunto(s)
Dependovirus/genética , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Vectores Genéticos/genética , Recuperación de la Función/genética , Traumatismos de la Médula Espinal/terapia , Animales , Astrocitos/metabolismo , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos/administración & dosificación , Células HEK293 , Humanos , Neuronas/metabolismo , Células PC12 , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/metabolismo , Transducción Genética , Transgenes/genética
11.
J Neurosci Res ; 89(2): 199-211, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21162127

RESUMEN

Chemokines can be produced by gliomas, which mediate the infiltration of microglia, a characteristic feature of glioma-associated neuropathogenesis. ATP that is released at a high level from glioma has been reported to play a regulatory role in chemokine production in cultured glioma cells. The objective of this study was to define the potential role of extracellular ATP in the regulation of macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein-1(MCP-1) expression in glioma-associated microglia/macrophages. The results showed that Iba1(+) and ED1(+) microglia existed in the tumor at 3 and 7 day after injection of C6 glioma cells into the rat cerebral cortex (dpi). ED1(+) microglia/macrophages or Iba1(+) microglia in the glioma were also colocalized to MIP-1α- and MCP-1-expressing cells. In vitro study indicated that treatment with ATP and BzATP (an agonist for ATP ionotropic receptor P2X7R) caused an increase in the intracellular levels of microglial MIP-1α and MCP-1. By using an extracellular Ca(2+) chelator (EGTA) and P2X7R antagonists, oxidized ATP (oxATP) and brilliant blue G (BBG), we demonstrated that BzATP-induced production of MIP-1α and MCP-1 levels was due to P2X7R activation and Ca(2+) -dependent regulation. Coadministration of C6 glioma cells and oxATP into the rat cerebral cortex resulted in a reduction of MIP-1α- and MCP-1-expressing microglia/macrophages. We suggest, based on the results from in vivo and in vitro studies, that a massive amount of ATP molecules released in the glioma tumor site may act as the regulator with P2X7R signaling that increases MIP-1α and MCP-1 expression in tumor-infiltrating microglia/macrophages.


Asunto(s)
Adenosina Trifosfato/metabolismo , Quimiocina CCL2/biosíntesis , Quimiocina CCL3/biosíntesis , Glioma/metabolismo , Microglía/metabolismo , Receptores Purinérgicos P2X/metabolismo , Animales , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Expresión Génica , Regulación de la Expresión Génica , Glioma/inmunología , Inmunohistoquímica , Ratas , Ratas Sprague-Dawley
12.
Taiwan J Obstet Gynecol ; 60(4): 628-633, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34247799

RESUMEN

OBJECTIVE: The recruitment of obstetrics and gynecology residents has been challenging in Taiwan since 2000. There are a lots factors influencing applying, including career interest and prospects, lifestyle, salary, litigation, stress level, time demands of specialty work and gender consideration. The purpose of this study was to evaluate the factors influencing the career choice of current OB/GYN residents and identify the important factors influencing recruitment. MATERIALS AND METHODS: A cross-sectional questionnaire of career-decision factors was sent to all 280 residents during December, 2019. Total 16 factors were rated on a 5-point Likert and were ranking by their average score on the scale. Gender of residents was analyzed for their association with the scores by a two-sample test and two-tailed t test. RESULTS: 91 (32.5%) residents responded and 61 were female and 30 were male. The top influencing factor was being interested in clinical expertise with an average score of 4.32. The second factor was having a great sense of accomplishment in saving people with an average score of 3.82, followed by it being easier to become a medical practitioner at 3.77. The lowest scoring factor was fewer hours of work, with an average score of 1.77 and a safer working environment with a score of 2.33 was the second lowest factor. Female residents agreed that it was easier to get specialist certification with a score of 3.0. This score was significantly higher than male doctors at 2.63 with p value of 0.017. CONCLUSION: Career interest and prospects were key influencing factors for applying OB/GYN residents. Minimizing the influence of detracting factors like heavy workload and medical litigation was also effective. Enrolling new residents is key to maintaining adequate staffing in specialties in healthcare. Establishing a safer work environment and determining the optimal workload will be the next reforms in the future.


Asunto(s)
Selección de Profesión , Ginecología/educación , Internado y Residencia , Obstetricia/educación , Estudiantes de Medicina/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Embarazo , Encuestas y Cuestionarios , Taiwán
13.
J Tissue Eng Regen Med ; 15(3): 279-292, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33470523

RESUMEN

Several lines of evidence show that a conditioned medium of bone marrow mesenchymal stem cells (BM-MSCcm) improve functional recovery after ischemic stroke but do not reduce ischemic lesions. It is important to develop a treatment strategy that can exhibit a synergistic effect with BM-MSCcm against ischemic stroke. In this study, the effect of BM-MSCcm and/or minocycline was examined in culture and in a middle cerebral artery occlusion (MCAo) animal model. In neuron-glial cultures, BM-MSCcm and combined treatment, but not minocycline, effectively increased neuronal connection and oligodendroglial survival. In contrast, minocycline and combined treatment, but not BM-MSCcm, reduced toxin-induced free radical production in cultures. Either minocycline or BM-MSCcm, or in combination, conferred protective effects against oxygen glucose deprivation-induced cell damage. In an in vivo study, BM-MSCcm and minocycline were administered to rats 2 h after MCAo. Monotherapy with BM-MSCcm or minocycline after ischemic stroke resulted in 9.4% or 17.5% reduction in infarction volume, respectively, but there was no significant difference. Interestingly, there was a 33.9% significant reduction in infarction volume by combined treatment with BM-MSCcm and minocycline in an in vivo study. The combined therapy also significantly improved grasping power, which was not altered by monotherapy. Furthermore, combined therapy increased the expression of neuronal nuclei in the peri-infarct area and hippocampus, and concurrently decreased the expression of ED1 in rat brain and the peri-infarct zone. Our data suggest that minocycline exhibits a synergistic effect with BM-MSCcm against ischemic stroke not only to improve neurological functional outcome but also to reduce cerebral infarction.


Asunto(s)
Células de la Médula Ósea/metabolismo , Accidente Cerebrovascular Isquémico , Células Madre Mesenquimatosas/metabolismo , Minociclina/farmacología , Animales , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Masculino , Ratas , Ratas Long-Evans
14.
Biol Reprod ; 82(5): 905-13, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20107204

RESUMEN

Reactive oxygen species may cause oxidative damage in the placenta, yet some mechanisms must exist to reduce or prevent such damage. We investigated whether oxidative injury to placental endothelial cells is inhibited by activation of antioxidant enzymes by paracrine factors secreted by human placental multipotent mesenchymal stromal cells (hPMSC). hPMSC-conditioned medium and umbilical endothelial cells were assayed for cytokines and cytokine receptor expression by immunoassay and real-time PCR. Endothelial cell survival was evaluated by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay and caspase 3 activity assay. tert-Butyl hydroperoxide was used to induce oxidative injury in endothelial cells, with fluorescent microscopy and flow cytometry used to detect intracellular peroxides and cell apoptosis. Western blot, real-time PCR, STAT3 DNA-binding activity assay, and STAT3 siRNA were used to assess endothelial cell antioxidant enzymes. hPMSC-conditioned medium supported endothelial cell survival and reduced endothelial cell intracellular peroxides and apoptosis. hPMSCs expressed the transcripts of the interleukin (IL) 6 cytokine family, including IL6 and leukemia-inhibitory factor. hPMSC-conditioned medium activated STAT3 expression in endothelial cells, which was inhibited by neutralizing antibody to interleukin 6 signal transducer (IL6ST) but not to IL6 or leukemia-inhibitory factor. STAT3 siRNA or manganese superoxide dismutase (SOD2) siRNA transfected into endothelial cells inhibited the antiapoptotic effect of conditioned medium. SOD2 was significantly upregulated in endothelial cells by conditioned medium via STAT3 activation that, in turn, was inhibited by IL6ST-neutralizing antibody or STAT3 siRNA. Paracrine factors secreted by hPMSCs support endothelial cell survival. STAT3 activation and SOD2 production protect against oxidative stress-induced endothelial cell damage.


Asunto(s)
Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Multipotentes/metabolismo , Placenta/citología , Factor de Transcripción STAT3/fisiología , Superóxido Dismutasa/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Células Endoteliales/efectos de los fármacos , Femenino , Humanos , Interleucina-6/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Comunicación Paracrina/fisiología , Placenta/metabolismo , Embarazo , Factor de Transcripción STAT3/efectos de los fármacos , Superóxido Dismutasa/efectos de los fármacos
15.
Neurosurgery ; 87(4): 823-832, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-31960049

RESUMEN

BACKGROUND: Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery. OBJECTIVE: To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair. METHODS: First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury. RESULTS: Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance. CONCLUSION: Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.


Asunto(s)
Neuropatías del Plexo Braquial/patología , Inmunosupresores/farmacología , Regeneración Nerviosa/efectos de los fármacos , Recuperación de la Función/efectos de los fármacos , Sirolimus/farmacología , Animales , Axotomía , Plexo Braquial/lesiones , Femenino , Regeneración Nerviosa/fisiología , Neuroprotección , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/fisiología , Raíces Nerviosas Espinales/lesiones
16.
J Neurosurg ; 110(4): 775-85, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19119881

RESUMEN

OBJECT: In this study, the authors evaluated the efficacy of a new surgical strategy for reconnecting the injured brachial plexus with the spinal cord using fibrin glue containing acidic fibroblast growth factor as an adhesive and neurotrophic agent. METHODS: Eighteen patients with preganglionic brachial plexus injuries, each with varying degrees of upper limb dysfunction, underwent cervical laminectomy with or without sural nerve grafting. The treatment of each avulsed root varied according to the severity of the injury. Some patients also underwent a second-stage operation involving supraclavicular brachial plexus exploration for reconnection with the corresponding segment of cervical spinal cord at the trunk level. Muscle strength was graded both pre- and postoperatively with the British Medical Research Council scale, and the results were analyzed with the Friedman and Wilcoxon signed-rank tests. RESULTS: Muscle strength improvements were observed in 16 of the 18 patients after 24 months of follow-up. Significant improvements in mean muscle strength were observed in patients from all repair method groups at 12 and 24 months postoperatively (p < 0.05). Statistical significance was not reached in the groups with insufficient numbers of cases. CONCLUSIONS: The authors' new surgical strategy yielded clinical improvement in muscle strength after preganglionic brachial plexus injury, such that nerve regeneration may have taken place. Reconnection of the brachial plexus to the cervical spinal cord is possible. Functional motor recovery, observed through increases in Medical Research Council-rated muscle strength in the affected arm, is likewise possible.


Asunto(s)
Plexo Braquial/lesiones , Procedimientos Neuroquirúrgicos/métodos , Radiculopatía/cirugía , Raíces Nerviosas Espinales/cirugía , Nervio Sural/trasplante , Adolescente , Adulto , Fibras Autónomas Preganglionares , Niño , Estudios de Seguimiento , Humanos , Laminectomía , Persona de Mediana Edad , Cuello , Trasplante Autólogo
17.
J Trauma ; 66(5): 1379-84, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19430242

RESUMEN

BACKGROUND: There have been no clinical trials concerning the effect of acidic fibroblast growth factor (aFGF) on human peripheral nerve lesions. Our interest was focused on the question of whether a repair strategy incorporating growth factors could be applied to repair of common peroneal nerve lesions. METHODS: This study involved three groups of patients with common peroneal nerve lesions: group 1 (n = 21) received surgical repair with fibrin glue added with aFGF; group 2 (n = 8) received surgical repair only; group 3 (n = 16) did not receive any surgical intervention. All patients received electrophysiologic examinations and physical examination at baseline, 6 months, and 12 months postsurgically. RESULTS: Group 1 demonstrated significantly increased average muscle strength score by 0.4299 and 0.5045 at 6 and 12 months after the operation (p = 0.0197 and 0.0297, respectively). In groups 2 and 3 patients, however, significant increase of average muscle strength scores was not achieved either at 6 or 12 months postoperatively. During the first follow-up evaluation the average muscle strength score in group 1 (3.06 +/- 1.60) was significantly higher than those in group 2 (1.04 +/- 0.86) and group 3 (1.65 +/- 1.43) (p = 0.005). However, significant difference was not achieved during the second follow-up evaluation. CONCLUSION: This study demonstrated the potential of this innovative repair strategy with aFGF treatment to facilitate nerve regeneration and motor function recovery following peripheral nerve lesions.


Asunto(s)
Factor 1 de Crecimiento de Fibroblastos/uso terapéutico , Fuerza Muscular/efectos de los fármacos , Procedimientos Neuroquirúrgicos/métodos , Neuropatías Peroneas/tratamiento farmacológico , Neuropatías Peroneas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Terapia Combinada , Electromiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Regeneración Nerviosa/efectos de los fármacos , Conducción Nerviosa , Nervio Peroneo/efectos de los fármacos , Nervio Peroneo/fisiopatología , Nervio Peroneo/cirugía , Neuropatías Peroneas/diagnóstico , Probabilidad , Estudios Prospectivos , Recuperación de la Función , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
18.
World Neurosurg ; 122: e773-e782, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30391621

RESUMEN

BACKGROUND: Surgery is the first-line therapy for glioblastoma. There is evidence that extent of resection is significantly associated with patient survival. Unfortunately, optimal surgical resection is usually limited because of the difficulty in discriminating tumor-infiltrated region and normal brain tissue. This study aimed to develop a tool to distinguish between infiltration zone and normal tissue in real time during glioma surgery. METHODS: In an in vivo study, C6 glioma cells were implanted into the left cerebral hemispheres of 6 rats to mimic tumorigenesis. A newly designed optical fiber-embedded needle probe was used to measure the autofluorescence of both cerebral hemispheres at various depths 5 days after the implantation. These rats were then sacrificed, and both cerebral hemispheres were removed for histopathologic analysis. RESULTS: Comparative analyses of corresponding areas by histopathology and autofluorescence revealed highly significant (P < 0.001) differences among the normal tissue, infiltration zone, tumors, and the contralateral cerebral hemispheres. The area of the receiver operating characteristic curve was 0.978, and the sensitivity and specificity of tumor delineation were 93.9% and 94.4%, respectively. CONCLUSIONS: The newly designed in vivo fiber-optic probe can distinguish tumor-infiltration zones from normal brain tissue in this in vivo study. Therefore, it may help neurosurgeons to increase extent of resection without damaging normal brain tissue and thus potentially improve the patients' survival and quality of life.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Sistemas de Computación , Glioma/diagnóstico por imagen , Imagen Óptica/métodos , Animales , Encéfalo/patología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Femenino , Tecnología de Fibra Óptica/métodos , Glioma/patología , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Ratas , Ratas Sprague-Dawley
19.
J Cancer ; 10(25): 6191-6198, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31772651

RESUMEN

The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.

20.
Taiwan J Obstet Gynecol ; 58(5): 692-697, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31542095

RESUMEN

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 22 at amniocentesis in a pregnancy with facial cleft, oligohydramnios and intrauterine growth restriction (IUGR), and we review the literature. CASE REPORT: A 37-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+22[9]/46,XX[9]. Array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes showed a result of arr(22) × 3 [0.8]. Prenatal ultrasound revealed fetal median facial cleft, oligohydramnios and IUGR. Repeat amniocentesis at 22 weeks of gestation using uncultured amniocytes revealed an aCGH result of arr 22q11.1q13.33 (17,397,498-51,178,264) × 2.8 compatible with 80% mosaicism for trisomy 22, and a fluorescence in situ hybridization (FISH) result of mosaic trisomy 22 with trisomy 22 in 54/100 interphase cells. The cultured amniocytes at repeat amniocentesis had a karyotype of 47,XX,+22[12]/46,XX[8]. The parental karyotypes were normal. Polymorphic DNA marker analysis confirmed a maternal origin of the extra chromosome 22. The pregnancy was terminated, and a 256-g female fetus was delivered with facial dysmorphism and median facial cleft. Cytogenetic analysis of the skin fibroblasts revealed a karyotype of 47,XX,+22[33]/46,XX[7]. CONCLUSION: Fetuses with high level mosaicism for trisomy 22 at amniocentesis may present IUGR, facial cleft and oligohydramnios on prenatal ultrasound.


Asunto(s)
Amniocentesis/métodos , Trastornos de los Cromosomas/diagnóstico , Retardo del Crecimiento Fetal/diagnóstico , Anomalías Maxilofaciales/diagnóstico , Oligohidramnios/diagnóstico , Trisomía/diagnóstico , Disomía Uniparental/diagnóstico , Aborto Inducido , Adulto , Trastornos de los Cromosomas/embriología , Cromosomas Humanos Par 22 , Hibridación Genómica Comparativa , Femenino , Retardo del Crecimiento Fetal/genética , Humanos , Hibridación Fluorescente in Situ , Anomalías Maxilofaciales/embriología , Anomalías Maxilofaciales/genética , Mosaicismo/embriología , Oligohidramnios/genética , Embarazo , Ultrasonografía Prenatal
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