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ACS Chemical Neuroscience Apr 2019Epilepsy is a common neurological disease characterized by recurrent unpredictable seizures. For the last 30 years, microdialysis sampling has been used to measure... (Review)
Review
Epilepsy is a common neurological disease characterized by recurrent unpredictable seizures. For the last 30 years, microdialysis sampling has been used to measure changes in excitatory and inhibitory neurotransmitter concentrations before, during, and after seizures. These advances have fostered breakthroughs in epilepsy research by identifying neurochemical changes associated with seizures and correlating them to electrophysiological data. Recent advances in methodology may be useful in further delineating the chemical underpinnings of seizures. A new model of ictogenesis has been developed that allows greater control over the timing of seizures that are similar to spontaneous seizures. This model will facilitate making chemical measurements before and during a seizure. Recent advancements in microdialysis sampling, including the use of segmented flow, "fast" liquid chromatography (LC), and capillary electrophoresis with laser-induced fluorescence (CE-LIF) have significantly improved temporal resolution to better than 1 min, which could be used to measure transient, spontaneous neurochemical changes associated with seizures. Microfabricated sampling probes that are markedly smaller than conventional probes and allow for a much greater spatial resolution have been developed. They may allow the targeting of specific brain regions important to epilepsy studies. Coupling microdialysis sampling to optogenetics and light-stimulated release of neurotransmitters may also prove useful for studying epileptic seizures.
Topics: Animals; Brain; Chromatography, Liquid; Electrophoresis, Capillary; Epilepsy; Forecasting; Glutamic Acid; Histamine; Humans; Microdialysis; Neurotransmitter Agents; Spectrometry, Fluorescence; gamma-Aminobutyric Acid
PubMed: 30001105
DOI: 10.1021/acschemneuro.8b00271 -
Acta Crystallographica. Section F,... Jan 2014Protein crystallization was discovered by chance about 150 years ago and was developed in the late 19th century as a powerful purification tool and as a demonstration of... (Review)
Review
Protein crystallization was discovered by chance about 150 years ago and was developed in the late 19th century as a powerful purification tool and as a demonstration of chemical purity. The crystallization of proteins, nucleic acids and large biological complexes, such as viruses, depends on the creation of a solution that is supersaturated in the macromolecule but exhibits conditions that do not significantly perturb its natural state. Supersaturation is produced through the addition of mild precipitating agents such as neutral salts or polymers, and by the manipulation of various parameters that include temperature, ionic strength and pH. Also important in the crystallization process are factors that can affect the structural state of the macromolecule, such as metal ions, inhibitors, cofactors or other conventional small molecules. A variety of approaches have been developed that combine the spectrum of factors that effect and promote crystallization, and among the most widely used are vapor diffusion, dialysis, batch and liquid-liquid diffusion. Successes in macromolecular crystallization have multiplied rapidly in recent years owing to the advent of practical, easy-to-use screening kits and the application of laboratory robotics. A brief review will be given here of the most popular methods, some guiding principles and an overview of current technologies.
Topics: Chemical Precipitation; Crystallization; Data Mining; Microdialysis; Proteins; Robotics
PubMed: 24419610
DOI: 10.1107/S2053230X13033141 -
Esophagus : Official Journal of the... Oct 2021Esophagectomy is the cornerstone in curative treatment for esophageal and gastroesophageal junctional cancer. Esophageal resection is an advanced procedure with many...
BACKGROUND
Esophagectomy is the cornerstone in curative treatment for esophageal and gastroesophageal junctional cancer. Esophageal resection is an advanced procedure with many complications, whereof anastomotic leak is the most dreaded. This study aimed to monitor the microcirculation with microdialysis analysis of local lactate levels in real-time on both sides of the esophagogastric anastomosis in totally minimally invasive Ivor-Lewis esophagectomy.
MATERIALS AND METHODS
Twenty-five patients planned for esophageal resection with gastric conduit reconstruction and intrathoracic anastomosis were recruited. A sampling device, the OnZurf Probe, along with the CliniSenz Analyser (Senzime AB, Uppsala Sweden) was utilized for measurements. Lactate levels from both sides of the anastomosis were analysed in real time, on site, by a transportable analyser device. Measurements were made every 30 min during the first 24 h, and thereafter every 2 hours for up to 4 days.
RESULTS
All probes could be positioned as planned and on the third postoperative day 19/25 and 15/25 of the esophageal and gastric probes, respectively, continued to deliver measurements. In total, 89.6% (1539/1718) and 72.4% (1098/1516) of the measurements were deemed successful. The average lactate level on the esophageal side of the anastomosis and the gastric conduit ranged between 1.1-11.5 and 0.8-7.0 mM, respectively. Two anastomotic leaks occurred, one of which had persisting high lactate levels on the gastric side of the anastomosis.
CONCLUSION
Application and use of the novel CliniSenz analyser system, in combination with the OnZurf Probe was feasible and safe. Continuous monitoring of analytes from the perianastomotic area has the potential to improve care after esophageal resection.
Topics: Anastomosis, Surgical; Esophagectomy; Humans; Lactic Acid; Microdialysis; Postoperative Complications
PubMed: 34052933
DOI: 10.1007/s10388-021-00846-w -
Journal of Neuroscience Methods Nov 2021Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This...
BACKGROUND
Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This technique has also been applied to evaluate tumor metabolism and identify pharmacodynamic biomarkers of drug activity. Despite the potential utility of microdialysis for therapeutic discovery, variability in tumor size and location hamper routine use of microdialysis as a preclinical tool. Quantitative validation of microdialysis membrane location relative to radiographically evident tumor regions could facilitate rigorous preclinical studies. However, a widely accessible standardized workflow for preclinical catheter placement and validation is needed.
NEW METHOD
We provide methods for a workflow to yield tailored placement of microdialysis probes within a murine intracranial tumor and illustrate in an IDH1-mutant patient-derived xenograft (PDX) model. This detailed workflow uses a freely available on-line tool built within 3D-slicer freeware to target microdialysis probe placement within the tumor core and validate probe placement fully within the tumor.
RESULTS
We illustrate use of this workflow to validate microdialysis probe location relative to implanted IDH1-mutant PDXs, using the microdialysis probes to quantify levels of extracellular onco-metabolite D-2 hydroxyglutarate.
COMPARISON WITH EXISTING METHODS
Previous methods have used 3D slicer to reliably measure tumor volumes. Prior microdialysis studies have targeted expected tumor locations without validation.
CONCLUSIONS
The new method offers a streamlined and freely available workflow in 3D slicer to optimize and validate microdialysis probe placement within a murine brain tumor.
Topics: Animals; Brain Neoplasms; Central Nervous System; Humans; Mice; Microdialysis
PubMed: 34390758
DOI: 10.1016/j.jneumeth.2021.109321 -
Intensive Care Medicine Sep 2015Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our...
Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
Topics: Humans; Microdialysis; Practice Guidelines as Topic
PubMed: 26194024
DOI: 10.1007/s00134-015-3930-y -
Journal of Neurochemistry Feb 2020Behavioral neuroscience has taken a long time to finally recognize that the largely distinct behavioral repertoires of males and females may arise from differences in...
Everything you always wanted to know about sex and dopamine, but were afraid to ask: An Editorial for 'No basal or drug-induced sex differences in striatal dopaminergic levels: a cluster and metaanalysis of rat microdialysis studies' on page 482.
Behavioral neuroscience has taken a long time to finally recognize that the largely distinct behavioral repertoires of males and females may arise from differences in brain function. This may in particular apply for the neurochemistry of the dopamine systems and their roles in the organization of emotion, learning, and reinforcement in health and in pathological conditions. The current Editorial highlights a study by Egenrieder and colleagues published in the current issue of the Journal of Neurochemistry, in which the authors have analyzed extracellular dopamine neurochemistry from females and males in a meta-analysis. Largely surprising, they report that after detailed control of methodological differences between studies, no major differences in basal or drug-induced extracellular dopamine activity emerged between sexes in rodents. The locally dissociating effects of ovariectomy in females reported in the Egenrieder et al. study, may furthermore suggest that there may be different sex effects in the distinct dopaminergic projections of the mesolimbic and nigrostriatal dopamine system. However, this may only be the beginning of a system's analysis of dopaminergic sex differences that calls for further meta-analyses of the existing studies.
Topics: Animals; Brain; Corpus Striatum; Dopamine; Female; Male; Microdialysis; Rats; Sex Characteristics
PubMed: 31792978
DOI: 10.1111/jnc.14916 -
European Journal of Pharmaceutical... Jul 2022Many new drug entities are poorly water-soluble and thus require solubility-enhancing formulations to ensure sufficient bioavailability. On the other hand, it is more...
Microdialysis and nanofiltration allow to distinguish molecularly dissolved from colloid-associated drug concentrations during biomimetic dissolution testing of supersaturating formulations.
Many new drug entities are poorly water-soluble and thus require solubility-enhancing formulations to ensure sufficient bioavailability. On the other hand, it is more and more accepted that not all "dissolved" states of a drug contribute equally to enhanced absorption, i.e. an increase in apparent solubility does not necessarily go in parallel with an increase in molecularly dissolved drug, the latter being regarded as the key driving force for absorption. Our study aimed to provide time-resolved information on the dissolution, supersaturation, and precipitation behavior of molecularly dissolved drug as released from an amorphous solid dispersion and a surfactant-containing crystalline suspension of Posaconazole (PCZ), a weakly basic and poorly water-soluble drug. Thereby, we aimed to gain a deeper mechanistic understanding of enabling formulation principles and possibly establish a dynamic biopharmaceutical assessment tool for molecularly dissolved drug released from enabling formulations. A two-staged dissolution test, with media transition from simulated gastric fluid (SGF) to fasted state simulated intestinal fluid (FaSSIF), was performed with three alternative sampling approaches in parallel: the classical bench centrifugation approach was used to assess total dissolved concentrations, while a nanofiltration method and a microdialysis setup were tested for their ability to discriminate molecularly and colloid-associated drug concentrations over time. For comparison, a single-stage dissolution setup was performed, where a marketed PCZ suspension was dispersed in biomimetic media with increasing amounts of solubilizing agents to understand their effect on the concentration of molecularly dissolved drug. It was demonstrated that the microdialysis setup allowed to follow the molecularly dissolved drug concentration in a time-resolved manner during the single-and two-stage dissolution tests with marginal delays. Interestingly, the PCZ concentrations measured by the nanofiltration approach differed from both, the molecularly dissolved (assessed by microdialysis) and apparently dissolved (assessed by centrifuge) PCZ concentrations, indicating that nanofiltration may allow to differentiate between different colloid-associated (apparently) dissolved drug species. Moreover, it was shown that the release of the molecularly dissolved drug from an amorphous solid dispersion did not correlate at all with the results obtained by the centrifugation method: While this conventional sampling revealed a classical spring and parachute concentration/time-profile with a high degree of (apparent) supersaturation, the concentration of molecularly dissolved drug (assessed by the microdialysis setup) indicated an initial short decline of PCZ concentration, followed by a prolonged (moderate) molecular supersaturation. This observation may give rise to a re-thinking of the current mechanistic understanding of how amorphous solid dispersions enhance oral bioavailability. In essence, the current study provides data which indicate a benefit of both the microdialysis sampling and nanofiltration approaches for the in vitro biopharmaceutical assessment of enabling drug formulations.
Topics: Biological Products; Biomimetics; Colloids; Excipients; Microdialysis; Solubility; Water
PubMed: 35283259
DOI: 10.1016/j.ejps.2022.106166 -
Current Protocols in Neuroscience Apr 2009The technique of microdialysis enables sampling and collecting of small-molecular-weight substances from the interstitial space. It is a widely used method in...
The technique of microdialysis enables sampling and collecting of small-molecular-weight substances from the interstitial space. It is a widely used method in neuroscience and is one of the few techniques available that permits quantification of neurotransmitters, peptides, and hormones in the behaving animal. More recently, it has been used in tissue preparations for quantification of neurotransmitter release. This unit provides a brief review of the history of microdialysis and its general application in the neurosciences. The authors review the theoretical principles underlying the microdialysis process, methods available for estimating extracellular concentration from dialysis samples (i.e., relative recovery), the various factors that affect the estimate of in vivo relative recovery, and the importance of determining in vivo relative recovery to data interpretation. Several areas of special note, including impact of tissue trauma on the interpretation of microdialysis results, are discussed. Step-by-step instructions for the planning and execution of conventional and quantitative microdialysis experiments are provided.
Topics: Algorithms; Animals; Brain; Brain Chemistry; Brain Injuries; Humans; Microdialysis; Microelectrodes
PubMed: 19340812
DOI: 10.1002/0471142301.ns0701s47 -
British Journal of Anaesthesia Jul 2006Cerebral microdialysis is a well-established laboratory tool that is increasingly used as a bedside monitor to provide on-line analysis of brain tissue biochemistry... (Review)
Review
Cerebral microdialysis is a well-established laboratory tool that is increasingly used as a bedside monitor to provide on-line analysis of brain tissue biochemistry during neurointensive care. This review describes the principles of cerebral microdialysis and the rationale for its use in the clinical setting, including discussion of the most commonly used microdialysis biomarkers of acute brain injury. Potential clinical applications are reviewed and future research applications identified. Microdialysis has the potential to become an established part of mainstream multi-modality monitoring during the management of acute brain injury but at present should be considered a research tool for use in specialist centres.
Topics: Biomarkers; Brain; Brain Chemistry; Brain Injuries; Critical Care; Humans; Microdialysis; Monitoring, Physiologic
PubMed: 16698861
DOI: 10.1093/bja/ael109 -
BMJ (Clinical Research Ed.) Mar 2002
Review
Topics: Blood Glucose; Brain Ischemia; Drug Monitoring; Humans; Microdialysis; Monitoring, Physiologic
PubMed: 11884326
DOI: 10.1136/bmj.324.7337.588