Pathophysiology, Live

PEDIATRICS ◽  
1982 ◽  
Vol 70 (4) ◽  
pp. 650-652
Author(s):  
Ruthmary K. Deuel
Keyword(s):  
The Body ◽  
Energy Substrates ◽  
Resonance Technique ◽  
Magnetic Resonance Technique ◽  
The Status ◽  
Sugar Phosphates ◽  
The Brain ◽  
Ischemic Events ◽  
Metabolic Information

In the August issue of Pediatrics, Delpy et al1 provided a detailed description of changes in intracerebral, intracellular constituents before, during, and after severe ischemic events in rabbits using a nuclear magnetic resonance technique. The constituents, ATP, phosphocreatine (PCr), and sugar phosphates, are the basic energy substrates of the body. Intracellular pH was also monitored throughout. As the authors correctly point out, such noninvasive, in vivo biochemistry would be invaluable to the pediatric clinician, not only to gather direct metabolic information on the status of the brain, but also to increase knowledge about muscle.2 In fact, applications of this technique to other organs such as the liver,3 the kidney,4 and the heart5 are likely to be made soon.

scholarly journals A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Specific Activity ◽  
High Accumulation ◽  
Metabolic Kinetics ◽  
Thiamine Metabolism ◽  
Pet Tracer ◽  
The Status ◽  
The Brain

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

scholarly journals Regional distribution of SGLT activity in rat brain in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. C240-C247 ◽  
Author(s):  
Amy S. Yu ◽  
Bruce A. Hirayama ◽  
Gerald Timbol ◽  
Jie Liu ◽  
Ana Diez-Sampedro ◽  
...  
Keyword(s):  
Rat Brain ◽  
Ex Vivo ◽  
Osmotic Shock ◽  
Regional Distribution ◽  
The Body ◽  
Specific Substrate ◽  
Ex Vivo Autoradiography ◽  
Molecular Imaging Probe ◽  
The Brain

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.

scholarly journals Analysis of In vivo Redox Status with Magnetic Resonance Technique

2009 ◽  
Vol 129 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Kazuhiro ICHIKAWA ◽  
Ken-ichi YAMADA ◽  
Keiji YASUKAWA ◽  
Hideo UTSUMI
Keyword(s):  
Magnetic Resonance ◽  
Redox Status ◽  
Resonance Technique ◽  
Magnetic Resonance Technique

scholarly journals In vivo tracking of intravenously injected mesenchymal stem cells in an Alzheimer’s animal model

2018 ◽  
Vol 27 (8) ◽  
pp. 1203-1209
Author(s):  
Bok-Nam Park ◽  
Tae Sung Lim ◽  
Joon-Kee Yoon ◽  
Young-Sil An
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Gamma Camera ◽  
The Body ◽  
Control Group ◽  
Indium 111 ◽  
The Brain

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer’s disease (AD) animal model. Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.

scholarly journals Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

2019 ◽  
Vol 94 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Sam Kacew ◽  
A. Wallace Hayes
Keyword(s):  
Flame Retardant ◽  
Parent Compound ◽  
Consumer Products ◽  
The Body ◽  
Tetrabromobisphenol A ◽  
Human Breast Milk ◽  
Target Tissue ◽  
Brominated Flame Retardant ◽  
The Brain

AbstractTetrabromobisphenol A (2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol, CAS no. 79-94-7) (TBBPA) is an effective brominated flame retardant present in many consumer products whose effectiveness is attributable to its ability to retard flames and consequently save human lives. Toxicokinetic studies revealed that TBBPA when absorbed via the gastrointestinal tract is rapidly metabolized to glucuronide or sulfate metabolites which are rapidly eliminated by the kidney. TBBPA does not accumulate in the body and there is no evidence that the parent compound is present in the brain. Although this brominated flame retardant was detected in human breast milk and serum, there was no evidence that TBBPA reached the brain in in vivo animal studies as reflected by the absence of neuropathological, neurotoxic, or behavioral alterations indicating that the central nervous system is not a target tissue. These animal investigations were further supported by use of the larval/embryo observations that TBBPA did not produce behavioral changes in a larval/embryo zebrafish a model of chemical-induced neurotoxicity. Although some protein expressions were increased, deceased or not affected in the blood–brain barrier indicating no evidence that TBBPA entered the brain, the changes were contradictory, or gender related, and behavior was not affected supporting that this compound was not neurotoxic. Taken together, TBBPA does not appear to target the brain and is not considered as a neurotoxicant.

scholarly journals A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

2020 ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Specific Activity ◽  
High Accumulation ◽  
Metabolic Kinetics ◽  
Thiamine Metabolism ◽  
Pet Tracer ◽  
The Status ◽  
The Brain

Abstract Background: Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff-Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods: A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity, radiochemical purity, radiochemical concentration, were evaluated by high performance liquid chromatography (HPLC). Metabolic kinetics and brain level of 18F-deoxy-thiamine in mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 minutes after injection as represented by the area under the curve (AUC) and blood thiamine levels were investigated. Results: The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61±0.53 in the liver within 1 minute, 18.67±7.04 in the kidney within half a minute. The SUV dropped to 0.72±0.05 and 0.77±0.35 after 60 minutes of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 minutes after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency by thiamine-deprived diet (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 minutes was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = -0.985, p = 0.015).Conclusion: The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

Embodiment and Personal Identity in Dementia

2021 ◽  
pp. 196-216
Author(s):  
Thomas Fuchs
Keyword(s):  
Personal Identity ◽  
John Locke ◽  
The Body ◽  
Self Awareness ◽  
Severe Dementia ◽  
Psychological Continuity ◽  
Body Memory ◽  
The Status ◽  
Rational Choices ◽  
The Brain

Theories of personal identity in the tradition of John Locke emphasize the importance of psychological continuity and the abilities to think, to remember and to make rational choices as basic criteria for personhood. As a consequence, persons with severe dementia are threatened to lose the status of persons. Such concepts, however, are situated within a dualistic framework, in which the body is regarded as a mere vehicle of the brain as the organ of mental faculties. The chapter elaborates a different approach to personal identity: according to this, selfhood is primarily constituted by pre-reflective self-awareness and the body memory. Dementia is then characterized as a loss of reflexivity and meta-perspective, which is contrasted with the preservation of individual forms of body memory even in the later stages of the illness. The ethical consequences of such an embodied approach to dementia are outlined.

Neurobiology of anxiety disorders

2011 ◽  
Vol 26 (S2) ◽  
pp. 2096-2096
Author(s):  
J. Den Boer
Keyword(s):  
Anxiety Disorders ◽  
Life Events ◽  
Stressful Life Events ◽  
Cognitive Disorders ◽  
Cognitive Appraisals ◽  
The Body ◽  
Therapeutic Interventions ◽  
Cognitive Approach ◽  
The Brain

In many psychotherapeutic theories the aim of therapeutic interventions is a restructuring of cognitive appraisals of past and current situations. The question is whether such a ‘dry’ and formal cognitive approach does not unjustly leave out the body. Especially in anxiety disorders brain/bodily changes appear to play an important role in the etiopathogenesis.There is now a great deal of experimental evidence that the brain does not only store mental representations, but that the brain/body is actively involved in mental operations. As an example of this I will discuss recent evidence indicating that early adverse life events not only lead to psychological (cognitive) disorders, but also leads to abnormal functioning of brain mechanisms and bodily functions.These changes occur on different levels of organization. Children who have been neglected or abused have smaller brains and a reduced complexity of neuronal dendrites, and also exhibit dysfunctions in neurotransmitter systems and the immune system.I will specifically discuss recent investigations conducted in our centre in which severely traumatized patients were studied using positron emission tomography, one of the neuroimaging techniques which yields information about brain functioning in vivo.As a final point I will discuss genetic differences that may explain differences in sensitivity for stressful life events, which may lead to the deveopment of a spectrum of anxiety disorders.

scholarly journals Potential Roles and Functions of Listerial Virulence Factors during Brain Entry

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 297
Author(s):  
Franjo Banović ◽  
Horst Schroten ◽  
Christian Schwerk
Keyword(s):  
Virulence Factors ◽  
Current Knowledge ◽  
Cellular Adhesion ◽  
The Body ◽  
Listeriolysin O ◽  
The Brain ◽  
Adhesion And Invasion

Although it rarely induces disease in humans, Listeria monocytogenes (Lm) is important due to the frequency of serious pathological conditions—such as sepsis and meningitis—it causes in those few people that do get infected. Virulence factors (VF) of Lm—especially those involved in the passage through multiple cellular barriers of the body, including internalin (Inl) family members and listeriolysin O (LLO)—have been investigated both in vitro and in vivo, but the majority of work was focused on the mechanisms utilized during penetration of the gut and fetoplacental barriers. The role of listerial VF during entry into other organs remain as only partially solved puzzles. Here, we review the current knowledge on the entry of Lm into one of its more significant destinations, the brain, with a specific focus on the role of various VF in cellular adhesion and invasion.

scholarly journals Glucocorticoids reset circadian clock in choroid plexus via period genes

2020 ◽  
Author(s):  
Karolína Liška ◽  
Martin Sládek ◽  
Vendula Čečmanová ◽  
Alena Sumová
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Glucocorticoid Receptors ◽  
Clock Gene ◽  
Time Of Day ◽  
The Body ◽  
Surgical Removal ◽  
The Brain

The epithelial cells of choroid plexus (CP) in brain ventricles produce cerebrospinal fluid and act as the blood-cerebrospinal fluid barrier. In this study, we confirmed that CP in the 4th ventricle is composed of cellular oscillators that all harbor glucocorticoid receptors and are mutually synchronized to produce a robust clock gene expression rhythm detectable at the tissue level in vivo and in vitro. Animals lacking glucocorticoids (GCs) due to surgical removal of adrenal glands had Per1, Per2, Nr1d1 and Bmal1 clock gene rhythmicity in their CP significantly dampened, whereas subjecting them to daily bouts of synthetic GC analog, dexamethasone (DEX), reinforced those rhythms. We verified these in vivo effects using an in vitro model of organotypic CP explants; depending on time of its application, DEX significantly increased the amplitude and efficiently reset the phase of the CP clock. The results are the first description of a PRC for a non-neuronal clock in the brain, demonstrating that CP clock shares some properties with the non-neuronal clocks elsewhere in the body. Finally, we found that DEX exhibited multiple synergic effects on the CP clock, including acute activation of Per1 expression and change of PER2 protein turnover rate. The DEX-induced shifts of the CP clock were partially mediated via PKA-ERK1/2 pathway. The results provide first evidence that the GC rhythm strengthens and entrains the clock in the CP helping thus fine-tune the brain environment according to time of day.

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