Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Publication year range
1.
Nat Commun ; 13(1): 2253, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35474069

ABSTRACT

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.


Subject(s)
Electrophysiological Phenomena , Myocytes, Cardiac , Action Potentials/physiology , Electrodes , Electroporation , Myocytes, Cardiac/physiology
2.
Cancer Res ; 73(1): 119-27, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23108141

ABSTRACT

Dose-dense (DD) regimens of combination chemotherapy may produce superior clinical outcomes, but the basis for these effects are not completely clear. In this study, we assessed whether a DD combinatorial regimen of low-dose cisplatin and paclitaxel produces superior immune-mediated efficacy when compared with a maximum tolerated dose (MTD) regimen in treating platinum-resistant ovarian cancer as modeled in mice. Immune responses generated by the DD regimen were identified with regard to the immune cell subset responsible for the antitumor effects observed. The DD regimen was less toxic to the immune system, reduced immunosuppression by the tumor microenvironment, and triggered recruitment of macrophages and tumor-specific CD8(+) T-cell responses to tumors [as determined by interleukin (IL)-2 and IFN-γ secretion]. In this model, we found that the DD regimen exerted greater therapeutic effects than the MTD regimen, justifying its further clinical investigation. Fourteen patients with platinum-resistant relapse of ovarian cancer received DD chemotherapy consisting of weekly carboplatin (AUC2) and paclitaxel (60-80 mg/m(2)) as the third- or fourth-line treatment. Serum was collected over the course of treatment, and serial IFN-γ and IL-2 levels were used to determine CD8(+) T-cell activation. Of the four patients with disease control, three had serum levels of IL-2 and IFN-γ associated with cytotoxic CD8(+) T-cell activity. The therapeutic effect of the DD chemotherapy relied on the preservation of the immune system and the treatment-mediated promotion of tumor-specific immunity, especially the antitumor CD8(+) T-cell response. Because the DD regimen controlled drug-resistant disease through a novel immune mechanism, it may offer a fine strategy for salvage treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cytokines/biosynthesis , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/immunology , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Flow Cytometry , Humans , Immunoassay , Maximum Tolerated Dose , Mice , Mice, Inbred C57BL , Mice, Nude , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/immunology , Paclitaxel/administration & dosage
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-295453

ABSTRACT

<p><b>OBJECTIVE</b>To comparing two kinds habitat adaptive division of Chinese material medica with different models.</p><p><b>METHOD</b>The habitat adaptive divisions of A. lancea according essential oil accumulation with two kinds pattern, model pattern and template pattern were carrid and compared.</p><p><b>RESULT</b>Two habitat adaptive divisions of A. lancea maps according essential oil accumulation were gotten.</p><p><b>CONCLUSION</b>Both model pattern and template pattern were efficient on habitat adaptive division of Chinese material medica, but they shoud bu used with different processesd and based different background [corrected]</p>


Subject(s)
Atractylodes , Metabolism , Ecosystem , Materia Medica , Medicine, Chinese Traditional , Methods , Oils, Volatile , Metabolism
4.
Am J Perinatol ; 23(5): 265-71, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16685609

ABSTRACT

This one-group pre-post test design was to evaluate sound distribution and sudden peak noise frequencies (SPNs) and the associated events after using a noise-sensor light alarm in a tertiary neonatal intensive care unit (NICU). The alarm is activated as the sound level reaches>or=65 A-weighted decibel (dBA). The environmental sound level was monitored continuously for a period of 1 week before and 1 month after using the alarm. The mean sound level in the incubator of patients receiving ventilator support before and after using the device were 58.0+/-0.6 and 56.4+/-0.7 dBA (t=8.619; p<0.001), whereas those at the radiant heated bed were 58.0+/-2.4 and 58.1+/-2.0 dBA (t=0.715; p=0.476). The percentage of observation time of sound levels<58 dBA increased by 28% in the incubator and 4% at the radiant heated bed (p<0.001). Episodes of SPN decreased from 630 to 185 times/d in the incubator and from 2069 to 748 times/d at the radiant heated bed after using the device. The noise-sensor light alarm effectively reduces sound level and episodes of SPN in the NICU. This may alleviate stress of noise for newborns with critical illness.


Subject(s)
Intensive Care Units, Neonatal , Noise , Environmental Exposure , Hot Temperature , Humans , Incubators, Infant , Infant, Newborn , Noise/prevention & control , Ventilators, Mechanical
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-635193

ABSTRACT

Objective To analyse the cause of misdiagnosis of tuberculosis peritonitis and discuss feasibility for diagnosis of tuberculosis peritonitis by laparoscopy. Methods 12 patients misdiagnosed as tuberculosis peritonitis were retrospectively analysed. Results Tuberculosis peritonitis wrongly diagnosed because of atypical clinical behaviors in spite of specific laboratory examination. However, laparoscopy could diagnose tuberculosis peritonitis exactly and quickly. Conclusion Laparoscopy is an effective method of diagnosis for tuberculosis peritonitis.

SELECTION OF CITATIONS
SEARCH DETAIL
...