Early diabetic nephropathy is largely undetectable before substantial functional changes have occurred. In the present study, we investigated the distribution of electrolytes and urea in the early diabetic kidney in order to explore whether pathophysiological and metabolic changes appear concomitantly with a decreased sodium and urea gradient. By using hyperpolarized 13C urea it was possible to measure the essential intrarenal electrolyte gradients and the acute changes following furosemide treatment. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney.
Magnetic resonance imaging (MRI) is increasingly the method of choice for rapid stroke assessment in patients and for guiding patient selection in clinical trials. The underlying metabolic status during stroke and following treatment is recognized as an important prognostic factor; thus, new methods are required to monitor local biochemistry following cerebral infarction, rapidly and in vivo. Hyperpolarized MRI with the tracer [1-13C]pyruvate enables rapid detection of localized [1-13C]lactate production, which has recently been shown in patients, supporting its translation to assess clinical stroke. Here we show the ability of hyperpolarized 13C MRI to detect the metabolic alterations characteristic of endothelin-1-induced ischemic stroke in rodents. In the region of penumbra, determined via T2-weighted 1H MRI, both [1-13C]pyruvate delivery and [1-13C]pyruvate cellular uptake independently increased. Furthermore, we observed a 33% increase in absolute [1-13C]lactate signal in the penumbra, and we determined that half of this increase was due to increased intracellular [1-13C]pyruvate supply and half was mediated by enhanced lactate dehydrogenase-mediated [1-13C]lactate production. Future work to characterize the kinetics of delivery, uptake, and enzymatic conversions of hyperpolarized tracers following ischemic stroke could position hyperpolarized 13C MRI as an ideal technology for rapid assessment of the penumbra during the critical time window following ischemic stroke in patients.
Coronavirus pandemic is the most important public health event in the world currently. Patients with coronavirus disease 2019 (COVID-19) in a critical state are at risk of progressing rapidly into many serve complications; they require a high level of care from ICU nurses. How to avoid the virus to infect health care worker is also a critical issue. Based on the summarized experience of Chinese health workers, literature review and clinical practice, this article introduced donning and doffing of personal protective equipment (PPE) protocol and some keypoints of nursing critical care in patients with coronavirus disease 2019 (COVID-19): caring of patients requiring intubation and ventilation, venous thromboembolism (VTE) prevention, caring of patients on ECMO, caring for patients requiring enteral nutrition, psychological support and nursing management of COVID-19 ICU. This article introduced a useful protocol of donning and doffing personal protective equipment to protect health care workers, and provided key points for the ICU nurses how to take care of COVID-19 patients.
Spinocerebellar ataxia 3, also known as Machado-Joseph disease (SCA3/MJD), is a rare autosomal-dominant neurodegenerative disease caused by an abnormal expansion of CAG repeats in the
ATXN3
gene. In the present study, we performed a global metabolomic analysis to identify pathogenic biochemical pathways and novel biomarkers implicated in SCA3 patients. Metabolic profiling of serum samples from 13 preclinical SCA3 patients, 13 symptomatic SCA3 patients, and 15 healthy controls were mapped using ultra-high-performance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry techniques. The symptomatic SCA3 patients showed a metabolic profile significantly distinct from those of the preclinical SCA3 patients and healthy controls. The principal differential metabolites were involved in the amino acid (AA) metabolism and fatty acid metabolism pathways. In addition, four candidate serum biomarkers, FFA 16:1 (palmitoleic acid), FFA 18:3 (linolenic acid), L-Proline and L-Tryptophan, were selected to discriminate between symptomatic SCA3 patients and healthy controls by receiver operator curve analysis with an area under the curve of 0.979. Our study demonstrates that symptomatic SCA3 patients present distinct metabolic profiles with perturbed AA metabolism and fatty acid metabolism, and FFA 16:1, FFA 18:3, L-Proline and L-Tryptophan are identified as potential disease biomarkers.
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