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1.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1009346

RESUMEN

OBJECTIVE@#To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.@*METHODS@#A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.@*RESULTS@#Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05).@*CONCLUSION@#It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.


Asunto(s)
Embarazo , Femenino , Humanos , Embarazo Gemelar , Diagnóstico Prenatal , Síndrome de Down/genética , Aberraciones Cromosómicas , Aneuploidia , Síndrome de la Trisomía 18/genética , Trisomía
2.
BMC Biol ; 21(1): 235, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880634

RESUMEN

BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.


Asunto(s)
Axones , Neuralgia , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Animales , Ratas , Axones/fisiología , Ganglios Espinales/fisiología , Regeneración Nerviosa/genética , Neuralgia/genética , Neuronas , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Factores Protectores , Ratas Sprague-Dawley , Análisis de Secuencia de ARN
3.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-826489

RESUMEN

OBJECTIVE@#To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations.@*METHODS@#The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out.@*RESULTS@#The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p.@*CONCLUSION@#Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.

4.
Chinese Journal of Traumatology ; (6): 356-362, 2020.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-879658

RESUMEN

PURPOSE@#By comparing the outcomes of total hip arthroplasty with hemiarthroplasty in elderly patients with a femoral neck fracture to investigate the one-year mortality, dislocation, infection, reoperation rate, and thromboembolic event.@*METHODS@#The PubMed, EMBASE databases, and Cochrane library were systematically searched from the inception dates to April 1, 2020 for relevant randomized controlled trials in English language using the keywords: "total hip arthroplasty", "hemiarthroplasty" and "femoral neck fracture" to identify systematic reviews and meta-analyses. Two reviewers independently selected articles, extracted data, assessed the quality evidence and risk bias of included trials using the Cochrane Collaboration' stools, and discussed any disagreements. The third reviewer was consulted for any doubts or uncertainty. We derived risk ratios and 95% confidence intervals. Mortality was defined as the primary outcome. Secondary outcomes were other complications, dislocation, infection, reoperation rate, and thromboembolic event.@*RESULTS@#This meta-analysis included 10 studies with 1419 patients, which indicated that there were no significant differences between hemiarthroplasty and total hip arthroplasty in reoperation, infection rate, and thromboembolic event. However, there was a lower mortality and dislocation rate association with total hip arthroplasty at the one-year follow-up.@*CONCLUSION@#Based on our results, we found that total hip arthroplasty was better than hemiarthroplasty for a hip fracture at one-year follow-up.


Asunto(s)
Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Artroplastia de Reemplazo de Cadera/métodos , Fracturas del Cuello Femoral/cirugía , Estudios de Seguimiento , Hemiartroplastia/métodos , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Infección de la Herida Quirúrgica/epidemiología , Tromboembolia/epidemiología , Factores de Tiempo , Resultado del Tratamiento
5.
Neurosci Bull ; 35(3): 401-418, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30659524

RESUMEN

Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors. Recent studies have indicated the superiority of gait analysis over traditional evaluations (e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here, pain-related gait parameters, whose criteria include (1) alteration in pain models, (2) correlation with nociceptive threshold, and (3) normalization by analgesics, were identified in representative models of neuropathic pain (spared nerve injury: coordination data) and inflammatory pain (intraplantar complete Freund's adjuvant: both coordination and intensity data) in the DigiGait™ and CatWalk™ systems. DigiGait™ had advantages in fixed speed (controlled by treadmill) and dynamic SFI, while CatWalk™ excelled in intrinsic velocity, intensity data, and high-quality 3D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.


Asunto(s)
Analgésicos/administración & dosificación , Análisis de la Marcha/métodos , Marcha , Dolor/fisiopatología , Animales , Adyuvante de Freund/administración & dosificación , Marcha/efectos de los fármacos , Procesamiento de Imagen Asistido por Computador , Inflamación/inducido químicamente , Masculino , Neuralgia/fisiopatología , Neuralgia/prevención & control , Dolor/etiología , Dolor/prevención & control , Ratas Sprague-Dawley
6.
Neuroscience Bulletin ; (6): 401-418, 2019.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-775430

RESUMEN

Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors. Recent studies have indicated the superiority of gait analysis over traditional evaluations (e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here, pain-related gait parameters, whose criteria include (1) alteration in pain models, (2) correlation with nociceptive threshold, and (3) normalization by analgesics, were identified in representative models of neuropathic pain (spared nerve injury: coordination data) and inflammatory pain (intraplantar complete Freund's adjuvant: both coordination and intensity data) in the DigiGait™ and CatWalk™ systems. DigiGait™ had advantages in fixed speed (controlled by treadmill) and dynamic SFI, while CatWalk™ excelled in intrinsic velocity, intensity data, and high-quality 3D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.


Asunto(s)
Animales , Masculino , Analgésicos , Adyuvante de Freund , Marcha , Análisis de la Marcha , Métodos , Procesamiento de Imagen Asistido por Computador , Inflamación , Neuralgia , Dolor , Ratas Sprague-Dawley
7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-771981

RESUMEN

OBJECTIVE@#To carry out genetic diagnosis for a pregnant woman and her fetus.@*METHODS@#Chromosome G-banding and microarray analysis were used to analyze the woman featuring dysmorphism and recognition defect and her fetus featuring developmental retardation.@*RESULTS@#The karyotype of the woman was normal, but chromosome microarray analysis showed that she has carried a 1423 kb deletion at 7q11.23 region. Her fetus has carried a 1530 kb deletion at the same region. Both individuals were diagnosed as Williams-Beuren syndrome.@*CONCLUSION@#Familiarity with its clinical features and proper selection of genetic testing methods are crucial for the diagnosis of Williams-Beuren syndrome.


Asunto(s)
Niño , Femenino , Humanos , Embarazo , Bandeo Cromosómico , Cromosomas Humanos Par 7 , Pruebas Genéticas , Cariotipificación , Diagnóstico Prenatal , Síndrome de Williams , Diagnóstico
8.
Oncol Rep ; 40(4): 2171-2182, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30106444

RESUMEN

Mutant KRAS and BRAF are associated with primary EGFR inhibitor resistance in colorectal cancer (CRC). However, other biomarkers that could predict EGFR inhibitor resistance remain elusive. In the present study, immunoblotting and cell proliferation results revealed that yes­associated protein (YAP), a downstream effector of the Hippo pathway, was positively associated with primary cetuximab resistance in CRC cells. YAP knockdown enhanced the cytotoxicity of cetuximab in CRC cells. Simvastatin, a 3­hydroxy­3­methylglutaryl­coenzyme A (HMG­CoA) reductase inhibitor of the mevalonate pathway that inhibits YAP bioactivity through nuclear translocation and total YAP expression, increased the cytotoxicity of EGFR inhibitors (cetuximab and gefitinib) against CRC cells. The combination of simvastatin and EGFR inhibitors inhibited YAP and EGFR signaling more markedly than each agent alone. Adding back geranylgeranyl pyrophosphate (GGPP), a key product of the mevalonate pathway, reversed the YAP bioactivity inhibition induced by simvastatin and the cell proliferation inhibition induced by the combination of simvastatin and EGFR inhibitors. Collectively, these results revealed that YAP may be useful in identifying cetuximab resistance in CRC and indicated that targeting of both YAP and EGFR signals may present a promising therapeutic approach for CRC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos , Fosfoproteínas/antagonistas & inhibidores , Fosfatos de Poliisoprenilo/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Simvastatina/farmacología , Animales , Anticolesterolemiantes/farmacología , Apoptosis , Proliferación Celular , Cetuximab/farmacología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Receptores ErbB/metabolismo , Femenino , Gefitinib , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Quinazolinas/farmacología , Transducción de Señal , Factores de Transcripción , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Señalizadoras YAP
9.
J Neurosci ; 38(7): 1756-1773, 2018 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-29335353

RESUMEN

Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multifunctional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 colocalizes with transient receptor potential ion channel V1 (TRPV1), a critical molecule involved in peripheral sensitization during inflammatory pain. Furthermore, the N-terminal 31-50 fragment of KChIP3 is capable of binding both the intracellular N and C termini of TRPV1, which substantially decreases the surface localization of TRPV1 and the subsequent Ca2+ influx through the channel. Importantly, intrathecal administration of the transmembrane peptide transactivator of transcription (TAT)-31-50 remarkably reduces Ca2+ influx via TRPV1 in DRG neurons and alleviates thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced inflammatory pain model in male rats. Moreover, intraplantar injection of TAT-31-50 attenuated the capsaicin-evoked spontaneous pain behavior and thermal hyperalgesia, which further strengthened the regulatory role of TAT-31-50 on TRPV1 channel. In addition, TAT-31-50 could also alleviate inflammatory thermal hyperalgesia in kcnip3-/- rats generated in our study, suggesting that the analgesic effect mediated by TAT-31-50 is independent of endogenous KChIP3. Our study reveals a novel peripheral mechanism for the analgesic function of KChIP3 and provides a potential analgesic agent, TAT-31-50, for the treatment of inflammatory pain.SIGNIFICANCE STATEMENT Inflammatory pain arising from inflamed or injured tissues significantly compromises the quality of life in patients. This study aims to elucidate the role of peripheral potassium channel interacting protein 3 (KChIP3) in inflammatory pain. Direct interaction of the KChIP3 N-terminal 31-50 fragment with transient receptor potential ion channel V1 (TRPV1) was demonstrated. The KChIP3-TRPV1 interaction reduces the surface localization of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by peripheral inflammation. Furthermore, the transmembrane transactivator of transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory hyperalgesia independently of endogenous KChIP3. This work reveals a novel mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from its classical role as a transcriptional repressor in pain modulation.


Asunto(s)
Hiperalgesia/fisiopatología , Inflamación/fisiopatología , Proteínas de Interacción con los Canales Kv/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Señalización del Calcio , Represión Epigenética , Adyuvante de Freund , Marcha , Ganglios Espinales/efectos de los fármacos , Técnicas de Inactivación de Genes , Hiperalgesia/inducido químicamente , Inflamación/inducido químicamente , Inyecciones Espinales , Proteínas de Interacción con los Canales Kv/genética , Masculino , Dimensión del Dolor/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Unión Proteica , Ratas , Canales Catiónicos TRPV/efectos de los fármacos
10.
J Neurosci ; 38(1): 183-199, 2018 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-29133434

RESUMEN

Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836-871 and phosphorylates it at Ser 869, 871, and 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex. Intriguingly, neuronal activity enhances the interactions between N-cadherin and PKD1, which are critical for the activity-dependent growth of dendritic spines. Accordingly, either disruption the binding between N-cadherin and PKD1 or preventing the phosphorylation of N-cadherin by PKD1 in the hippocampal CA1 region of male rat leads to the reduction in synapse number and impairment of LTP. Together, this study demonstrates a novel mechanism of PKD1 regulating the surface localization of N-cadherin and suggests that the PKD1-N-cadherin interaction is critical for synapse formation and function.SIGNIFICANCE STATEMENT Defects in synapse formation and function lead to various neurological diseases, although the mechanisms underlying the regulation of synapse development are far from clear. Our results suggest that protein kinase D1 (PKD1) functions upstream of N-cadherin, a classical synaptic adhesion molecule, to promote functional synapse formation. Notably, we identified a crucial binding fragment to PKD1 at C terminus of N-cadherin, and this fragment also contains PKD1 phosphorylation sites. Through this interaction, PKD1 enhances the stability of N-cadherin on cell membrane and promotes synapse morphogenesis and synaptic plasticity in an activity-dependent manner. Our study reveals the role of PKD1 and the potential downstream mechanism in synapse development, and contributes to the research for neurodevelopment and the therapy for neurological diseases.


Asunto(s)
Cadherinas/metabolismo , Hipocampo/metabolismo , Sinapsis/fisiología , Canales Catiónicos TRPP/fisiología , Animales , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Espinas Dendríticas/fisiología , Femenino , Hipocampo/citología , Hipocampo/crecimiento & desarrollo , Potenciación a Largo Plazo/fisiología , Masculino , Neuronas/efectos de los fármacos , Fosforilación , Embarazo , Cultivo Primario de Células , Unión Proteica , Ratas , Ratas Sprague-Dawley
11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-687972

RESUMEN

<p><b>OBJECTIVE</b>To assess the accuracy of quantitative fluorescence PCR(QF-PCR) for the detection of fetal chromosomal aneuploidies and its values for prenatal diagnosis.</p><p><b>METHODS</b>QF-PCR and chromosomal karyotyping were used to analyze 6066 amniotic fluid samples derived from 6034 pregnant women.</p><p><b>RESULTS</b>Both QF-PCR and karyotyping analysis have detected 135 cases of fetal aneuploidies involving chromosomes 21, 18, 13, X, and Y. The QF-PCR assay was also successful in 67 cases for which amniotic fluid culture has failed. Furthermore, it has identified maternal cell contamination in 7 cases. By determining the consistency of short tandem repeat (STR) sites, the QF-PCR assay has identified 22 dizygotic twins among 32 twins with double chorions and double amniotic sacs. In 12 cases, it has signaled numerical chromosomal aberration by critical or partial abnormal values for the fluorescence peak area ratio, which were verified by karyotyping analysis as mosaicisms of chromosome aneuploidies.</p><p><b>CONCLUSION</b>The QF-PCR can provide an useful supplement for chromosomal karyotyping and has an important role in rapid prenatal diagnosis.</p>


Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Adulto Joven , Aneuploidia , Fluorescencia , Cariotipificación , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Métodos , Diagnóstico Prenatal , Métodos
13.
China Pharmacy ; (12): 1378-1380, 2016.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-504422

RESUMEN

OBJECTIVE:To strengthen the supervision of drug stocktaking,and to improve drug management. METHODS:The data of drug stocktaking were extracted from our hospital from 2011 to 2014,and was analyzed in respects of accounts coinci-dence rate,drug profit and loss account rate,the entry and exit account between departments and original record,etc. A series of supervision strategies were established,and the data of drug stocktaking was analyzed during Jan.-Jun. in 2015 statistically to evalu-ated supervision effects. RESULTS:The supervision of drug stocktaking was strengthened through limiting the right of drug profit and loss on stocktaking,strengthening original stocktaking record management,establishing Key Drug List,setting up drug stock-taking supervision institutions,etc. During Jan.-Jun. in 2015,there was obvious improvement in the drug supervision skills,in terms of account coincidence rate,profit and loss account,material safety,cash flow rate,staff responsibility and stocktaking dura-tion,etc. More specially,the accounts coincidence rate had rose from about 82.8% to more than 95%;both the key drug accounts coincidence rate and the entry and exit account between departments coincidence rate had reached to 100%;the profit and loss ac-count rate had reduced from about 7.6% to less than 0.3%;the stocktaking time had reduced from 10 h to 3 h. CONCLUSIONS:Strengthening drug stocktaking supervision can not only improve the stocktaking efficiency and quality markedly,but also contrib-utes to the development of other pharmacy work in hospital.

14.
Acta Pharmaceutica Sinica ; (12): 425-2016.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-779187

RESUMEN

Complexes containing cobalt and carbon monoxide ligands, CO releasing molecules (CORMs), have the potential of anti-tumor and anti-inflammatory. In this paper, three hybrid CORMs 1-3 were synthesized and tested for their toxicology in vivo and bioactivities. The results suggest that the complexes have a long half-life in the range of 43-53 min; their oral LD50 to mouse are between 1 500 mg·kg-1 and 5 000 mg·kg-1. After the successive administration, complex 1 exhibited a toxic activity in rats' liver, and induced an injury to liver cells. Complex 1 had a strong growth inhibition activity (IC50 36.20 μmol·L-1 and 39.25 μmol·L-1) in both HeLa cells and HepG2 cells, complex 2 displayed a lower activity in the inhibition of HeLa cells proliferation than the control 5-FU (IC50 114.19 μmol·L-1), but had a higher activity in the inhibition of HepG2 cells than the control 5-FU (IC50 171.34 μmol·L-1). The anti-inflammatory study suggests that all of them reduce intracellular nitrite level, complexes 1 and 2 have a stronger activity than complex 3. Their anti-inflammatory activity attributes to the CO molecules of the CORMs, which was confirmed by comparison with the corresponding ligand.

15.
Nat Commun ; 6: 7660, 2015 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-26179626

RESUMEN

The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.


Asunto(s)
Ansiedad/genética , Conducta Animal , Dolor Crónico/genética , Quinasa 5 Dependiente de la Ciclina/genética , Hiperalgesia/genética , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Animales , Ansiedad/metabolismo , Ansiedad/psicología , Dolor Crónico/metabolismo , Dolor Crónico/psicología , Conducta Exploratoria , Técnicas de Silenciamiento del Gen , Hiperalgesia/metabolismo , Hiperalgesia/psicología , Masculino , Ratones , Ratones Endogámicos C57BL , Optogenética , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley
16.
PLoS One ; 10(4): e0123405, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25906284

RESUMEN

BACKGROUND AND AIMS: Prediction of severe clinical outcomes in Clostridium difficile infection (CDI) is important to inform management decisions for optimum patient care. Currently, treatment recommendations for CDI vary based on disease severity but validated methods to predict severe disease are lacking. The aim of the study was to derive and validate a clinical prediction tool for severe outcomes in CDI. METHODS: A cohort totaling 638 patients with CDI was prospectively studied at three tertiary care clinical sites (Boston, Dublin and Houston). The clinical prediction rule (CPR) was developed by multivariate logistic regression analysis using the Boston cohort and the performance of this model was then evaluated in the combined Houston and Dublin cohorts. RESULTS: The CPR included the following three binary variables: age ≥ 65 years, peak serum creatinine ≥ 2 mg/dL and peak peripheral blood leukocyte count of ≥ 20,000 cells/µL. The Clostridium difficile severity score (CDSS) correctly classified 76.5% (95% CI: 70.87-81.31) and 72.5% (95% CI: 67.52-76.91) of patients in the derivation and validation cohorts, respectively. In the validation cohort, CDSS scores of 0, 1, 2 or 3 were associated with severe clinical outcomes of CDI in 4.7%, 13.8%, 33.3% and 40.0% of cases respectively. CONCLUSIONS: We prospectively derived and validated a clinical prediction rule for severe CDI that is simple, reliable and accurate and can be used to identify high-risk patients most likely to benefit from measures to prevent complications of CDI.


Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/diagnóstico , Anciano , Clostridioides difficile/patogenicidad , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/fisiopatología , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad
17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-239498

RESUMEN

<p><b>OBJECTIVE</b>To analyze 81 spontaneous abortion samples with fluorescence in situ hybridization (FISH).</p><p><b>METHODS</b>Chromosome 13, 21, 16, 22, 18, X and Y probes were used to detect the samples.</p><p><b>RESULTS</b>FISH was successful in 80 cases (98.77%). Among these, 35 (43.75%) had an abnormal karyotype, which included 19 autosomal aneuploidies, 6 sex chromosome aneuploidies, 9 triploidies and 1 tetraploidy.</p><p><b>CONCLUSION</b>FISH is a rapid and easy method for detecting chromosomal aneuploidies in spontaneous abortion samples, and has a higher detection rate in early spontaneous abortion samples.</p>


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Adulto Joven , Aborto Espontáneo , Diagnóstico , Genética , Aneuploidia , Aberraciones Cromosómicas , Cromosomas de los Mamíferos , Genética , Enfermedades Fetales , Diagnóstico , Genética , Hibridación Fluorescente in Situ , Diagnóstico Prenatal
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-237278

RESUMEN

<p><b>OBJECTIVE</b>To assess the value of fluorescent in situ hybridization (FISH) for detecting common chromosome aneuploidies in interphase nuclei of amniotic fluid cells.</p><p><b>METHODS</b>Eighty two uncultured amniotic fluid samples and supernatants from 2 successfully and 5 unsuccessfully cultured amniotic fluid samples were analyzed with FISH. Results from standard cytogenetic analysis of 79 uncultured amniotic fluid samples and 2 successfully cultured amniotic fluid samples were compared with FISH results.</p><p><b>RESULTS</b>All of the 89 samples were succeeded analyzed with FISH. Positive findings included 3 cases with trisomy 21, 1 case with 47, XYY and 1 case with 69, XXX, which were consistent with results of karyotype analysis.</p><p><b>CONCLUSION</b>FISH is a rapid and accurate method for prenatal diagnosis, and can also provide a remedy to failed amniotic fluid cells culture.</p>


Asunto(s)
Adulto , Femenino , Humanos , Embarazo , Líquido Amniótico , Biología Celular , Técnicas de Cultivo de Célula , Hibridación Fluorescente in Situ , Métodos , Cariotipificación
19.
Chinese Pharmaceutical Journal ; (24): 1307-1312, 2012.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-860647

RESUMEN

OBJECTIVE: To prepare amphiphilic long-circulating hydroxycamptothecin nanoparticles and investigate its physicochemical properties and pharmacokinetic characteristics in rats. METHODS: Polyethyleneglycol-polycaprolactone (PEG-PCL) was synthesized. HCPT-PEG-PCL-NPs were prepared by solvent-diffusion method using PEG-PCL block copolymer as the matrix. The obtained NPs were evaluated, and the physical stabilities of both suspl and freeze-dried powder were investigated. High-performance liquid chromatography (HPLC) was used to determine and compare the pharmacokinetic parameters of HCPT injection and HCPT-PEG-PCL-NPs prepared with different copolymers in rats. RESULTS: When using PEG4000-PCL1250, PEG4000-PCL2000, PEG2000-PCL1250, PEG2000-PCL2000 as the carrier materials, the average particle sizes of NPs were 110.0, 116.1, 99.1 and 119.9 nm; the Zeta potentials were -16.9, -22.4, -28.8 and -33.5 mV; the entrapment efficiency were 83.10%, 88.29%, 77.46% and 80.67%; and the drug loading percentages were 2.56%, 2.96%, 2.14% and 2.31%, respectively. The physical stability of the freeze-dried powder was better, and hot environment seemed to be bad for the stability. The t1/2s of HCPT-PEG4000-PCL1250-NPs, HCPT-PEG2000-PCL1250-NPs, HCPT-PEG4000-PCL2000-NPs and HCPT-PEG2000-PCL2000-NPs were 18.07, 9.08, 5.25 and 5.14 times longer than that of HCPT injection which was 0.1418 h. CONCLUSION: The HCPT-PEG-PCL-NPs show sustained-release effect and long-circulation property compared with HCPT injection. Copyright 2012 by the Chinese Pharmaceutical Association.

20.
J Clin Gastroenterol ; 45 Suppl: S154-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21992956

RESUMEN

Clostridium difficile infection (CDI) is one of the most prevalent nosocomial infections. A dramatic increase in the incidence and severity of CDI has been noted in the past decade. Current recommendations suggest metronidazole as first-line therapy in mild to moderately severe CDI and oral vancomycin in individuals with severe CDI, or when metronidazole fails or is contradicted. Alterations of the colonic microbiota, usually caused by antimicrobial therapy, seem to play a critical role in CDI pathogenesis. Probiotics are live microorganisms that confer a health benefit to the host, and have been used in CDI. Although a wide variety of probiotics have been studied, the exact role of probiotics in preventing and treating CDI is not clear. In this study, we reviewed the current literature and recommendations on the most commonly studied protiotic agents (Saccharomyces boulardii, Lactobacillus species, and probiotic mixtures) used to prevent or treat CDI. Lactobacillus-containing probiotic mixtures and S. boulardii may be effective in the prevention of CDI in high-risk antibiotic recipients but this finding is based on small, individual studies, and further, larger, well-controlled studies are needed to confirm preliminary positive findings and to better delineate the efficacy of probiotics in CDI prevention or treatment.


Asunto(s)
Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/terapia , Lactobacillus , Probióticos/uso terapéutico , Saccharomyces , Adulto , Niño , Infección Hospitalaria/prevención & control , Infección Hospitalaria/terapia , Enterocolitis Seudomembranosa/prevención & control , Enterocolitis Seudomembranosa/terapia , Humanos , Lactobacillus/crecimiento & desarrollo , Probióticos/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Saccharomyces/crecimiento & desarrollo , Resultado del Tratamiento
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