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Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alterna-tives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
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Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.
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The continuous glucose monitoring system (CGMS) has been clinically applied to monitor the dynamic change of the subcutaneous interstitial glucose concentration which is a function of the blood glucose level by glucose sensors. It can track blood glucose levels all day along, and thus provide comprehensive and reliable information about blood glucose dynamics. The clinical application of CGMS enables monitoring of blood glucose fluctuations and the discovery of hidden hyperglycemia and hypoglycemia that are difficult to be detected by traditional methods. As a CGMS needs to work subcutaneously for a long time, a series of factors such as biocompatibility, enzyme inactivation, oxygen deficiency, foreign body reaction, implant size, electrode flexibility, error correction, comfort, device toxicity, electrical safety, et al. should be considered beforehand. The study focused on the difficulties in the technology, and compared the products of Abbott, Medtronic and DexCom, then summarized their cutting-edge. Finally, this study expounded some key technologies in dynamic blood glucose monitoring and therefore can be utilized as a reference for the development of CGMS.
Subject(s)
Humans , Blood Glucose , Blood Glucose Self-Monitoring/methods , Hyperglycemia , Hypoglycemia , Monitoring, Ambulatory/methods , Monitoring, PhysiologicABSTRACT
Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a "slit-shaped" porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical "gel pump" is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.
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The defensive function of defensive
Subject(s)
Humans , Medicine, Chinese Traditional , Meridians , QiABSTRACT
Objective To study the effect of the reinforcing and reducing method of acupuncture reported in first Chapter the Nine Needles and Twelve Yuan of the Miraculous Pivot on interstitial fluid pressure (IFP) in subcutaneous tissue of minipig, and to investigate its biomechanical mechanism of regulating the interstitial fluid. Methods Nine healthy minipigs were randomly selected for reinforcing method (pull or press) and reducing method (wave a big pinhole), and tested on soft skin tissues of the abdomen. The IFP in the normal state (NS), the low volume (LV) state (by extracting interstitial fluid) and the high volume (HV) state (by injecting saline solution) was measured before and after acupuncture. Results In the normal state, pulling and pressing the needle could obviously increase IFP, while reducing method could significantly decrease IFP, leading to a rapid decrease in 5 min after acupuncture. In the LV state, pulling and pressing the needle could increase IFP. However, in 10 min after acupuncture, the descend rates of IFP were relatively slower. In the HV state, the reducing method could significantly decrease IFP, and the changing trend in 5 min after acupuncture was different from that of the control group. Conclusions The reinforcing and reducing method of acupuncture could increase or decrease IFP, which proved that the acupuncture method could regulate IFP in the opposite direction. The research findings provide a new scientific basis for using reinforcing and reducing method of acupuncture in clinic.
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Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM), which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.
Subject(s)
Humans , Acupuncture Points , Connective Tissue , Physiology , Extracellular Fluid , Physiology , Extracellular Space , Physiology , Meridians , Qi , WaterABSTRACT
Objective To compare the consistency between interstitial fluid glucose and arterial blood glucose in septic shock patients with different tissue perfusion levels.Methods A prospective investigative study was conducted. Sixty-one septic shock patients with ages above 18 years old admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from April 2013 to December 2013 were enrolled. The real-time continuous glucose monitoring system (RTCGMS) and arterial blood gas analyzer were used to measure the patients' interstitial fluid glucose and arterial blood glucose, and according to the criteria of International Organization for Standardization (ISO) and the median of relative absolute difference (Median RAD), the consistency between interstitial fluid glucose and arterial blood glucose was calculated. Based on the lactate (Lac) level and pulse oxygen perfusion index (PI), the septic shock patients were divided into groups with different degrees of tissue perfusion, the consistency between the interstitial fluid glucose and arterial blood glucose among septic shock patients with different degrees of tissue perfusion was compared by using Bootstrap re-sampling technique.Results Negative correlation existed between PI and Lac (r= -0.272,P 8 mmol/L, their consistency between interstitial fluid glucose and arterial blood glucose was better than that in those with Lac > 2-4 mmol/L, and the 95% credibility intervals (CI) of ISO standardized deviation value was 0.026-38.710 (P 0.7%-1.4%, the 95%CI of median RAD difference value was 0.002-0.076, and the 95%CI of ISO standardized deviation value was -27.000 to -0.583 (allP 3.0%, their consistency between interstitial fluid glucose and arterial glucose was better than that in those with PI ≤ 0.7%, PI > 0.7%-1.4% and PI > 1.4%-3.0%, and the 95%CI of ISO standardized deviation values were 3.322-28.302, 11.988-40.265 and 5.170-33.333 respectively (allP 8 mmol/L or PI ≤ 0.7%), the worse the tissue perfusion, the better the consistency between interstitial fluid glucose and arterial blood glucose; when septic shock patients were under normal local tissue perfusion (PI > 3.0%), the better the local tissue perfusion, the better the consistency between interstitial fluid glucose and arterial blood glucose.
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Objective To investigate the intervening effect of electroacupuncture on brain interstitial fluid (ISF) and hippocampal soluble Aβ1-42 levels in mice with early Alzheimer's disease.Method Sixteen 5-month-old male APP/PS1 positive transgenic mice were randomized to model and acupuncture groups, 8 mice each in one cage. Isosexual negative transgenic mice constituted a normal control group. Electroacupuncture at Baihui(GV20) and Yongquan(KI1) or binding under the same condition was used as an intervention measure. Mouse hippocampal interstitial fluid was obtained by brain microdialysis. Hippocampal tissue and ISFβ amyloid protein 1-42 levels were measured by ELISA in the three groups of mice at 6, 7, 8 and 9 hrs after intervention to observe the changes. Result Hippocampal tissue and ISF soluble Aβ1-42 levels were significantly higher in the model group than in the normal group (P0.05). The results of sample detection did not show a tendency to change over time (P>0.05). Conclusion Electroacupuncture can decrease hippocampal soluble Aβ1-42 levels in a mouse model of AD.
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Purpose With the progression of brain tissue aging, the transport and drainage characteristics of metabolites and secretory products for neurons in extracellular space occurs irreversible change. This paper aims to investigate and quantify MR tracer diffusion characteristics in cerebral interstitial fluid of elderly SD rats. Materials and Methods MR contrast agent Gd-DTPA was injected into the caudate nucleus of two groups of rats including 8 in experimental group (15-17 month old) and 15 in control group (7-10 month old). MR scan was performed at 0.25 h, 0.5 h, 1 h, 2 h, 3 h and 4 h to observe the dynamic distribution in the caudate and measure the diffusion and clearance rate. Results There was no statistically significant difference in diffusion rate and D* between control group with (3.32±0.70)×10-4 mm2/s and experimental group with (3.25±0.46)×10-4 mm2/s (t=1.739, P>0.05). The clearance rate k' was significantly different between control group (0.62±0.12)×10-4/s and experimental group (0.29±0.08)×10-4/s (t=11.602, P<0.05). Conclusion The degeneration of aging brain tissue changes the composition of extracellular space resulting in decreased speed of ISF clearance. This may cause accumulation of metabolites which eventually triggers a variety of age-related diseases.
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Objective To measure the interstitial fluid pressure (IFP) on low hydraulic resistance channel along meridians and observe the difference and fluctuation. Method Low hydraulic resistance points (LHRP) and non LHRP were measured on anesthetized mini pigs by a scanning hydraulic resistance measuring device. The IFP was then measured by wick in needle method on these two regions. Results The stomach meridian, kidney meridian and conceptual vessel meridian on mini pigs were measured. The IFP were significantly lower than non LHRP region on the above three meridians(P<0.05), the differences of which were 1.06，0.70，3.69 mmHg respectively with the total pressure difference of 1.44 mmHg and pressure gradient of 1.44~2.88 mmHg/cm（1 mmHg=0．133 kPa）. Conclusions Among the peripheral subcutaneous tissues, there exists a difference of IFP toward the meridian which may drive the flow of interstitial fluid toward the meridians.