scholarly journals Changes in noradrenaline and dopamine levels under oxygen debt conditions in the brain of rats during experimental acute pancreatitis

2022 ◽  
Vol 77 (11) ◽  
pp. 6589-2022
Author(s):  
AGNIESZKA MARKIEWICZ-GOSPODAREK ◽  
IWONA ŁUSZCZEWSKA-SIERAKOWSKA ◽  
PIOTR KUSZTA ◽  
MARCIN KOPIENIAK ◽  
ELŻBIETA RADZIKOWSKA-BÜCHNER
Keyword(s):  
Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Mechanical Damage ◽  
Oxygen Debt ◽  
Research Groups ◽  
Emotional Processes ◽  
The Common ◽  
The Brain

This study’s aim was to assess the level of catecholamines, i.e., noradrenaline and dopamine, under oxygen debt conditions in the brain of experimental animals in which acute pancreatitis was experimentally induced. Catecholamines play the role of neurotransmitters and neuromediators. They are responsible for the regulation of motor and emotional processes, take part in the regulation of hormonal activities, sleep, wakefulness, concentration, attention, and learning processes. The experiment also determined the oxygen tension as an indicator of respiratory failure and the activity of amylase and lipase in the development of the inflammatory process. The animals on which the experiment was conducted were Wistar rats (140 animals) divided into 3 research groups: control (C) animals (n = 30), healthy (H) animals (n = 30), and operated (O) animals (n = 80). The determination of amylase, lipase, oxygen pressure, NA, and DO levels were performed at hours 2, 6, 12, 24, and 48 of the experiment. The animals in group C had an injection needle inserted to investigate only the effects of mechanical damage to the organs. On the other hand, the animals in group O had a 5% solution of sodium taurocholate introduced into the common bile-pancreatic duct. The research conducted shows that the most significant changes in NA and DO levels were observed on the first day of the experiment. The concentrations of the above catecholamines were statistically significantly correlated with the level of amylase in the blood. The peak of dopamine was observed between the 6th and 12th hours of the experiment, while the lowest concentration of noradrenaline was observed at the 6th hour of the experiment.

scholarly journals Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases

2019 ◽  
Vol 20 (12) ◽  
pp. 2982 ◽  
Author(s):  
Gil Yong Park ◽  
Angelo Jamerlan ◽  
Kyu Hwan Shim ◽  
Seong Soo A. An
Keyword(s):  
Cerebrospinal Fluid ◽  
Genetic Mutations ◽  
Hormone Binding ◽  
Wild Type ◽  
Autonomic Motor ◽  
Hormone Binding Protein ◽  
The Brain ◽  
Tetrameric Form

Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented.

scholarly journals Neural Control of Immunity in Hypertension: Council on Hypertension Mid Career Award for Research Excellence, 2019

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 622-628
Author(s):  
Daniela Carnevale
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Neural Control ◽  
Neural Signals ◽  
The Past ◽  
Target Organs ◽  
Long Time ◽  
The Common ◽  
The Brain

The nervous system and the immune system share the common ability to exert gatekeeper roles at the interfaces between internal and external environment. Although interaction between these 2 evolutionarily highly conserved systems has been recognized for long time, the investigation into the pathophysiological mechanisms underlying their crosstalk has been tackled only in recent decades. Recent work of the past years elucidated how the autonomic nervous system controls the splenic immunity recruited by hypertensive challenges. This review will focus on the neural mechanisms regulating the immune response and the role of this neuroimmune crosstalk in hypertension. In this context, the review highlights the components of the brain-spleen axis with a focus on the neuroimmune interface established in the spleen, where neural signals shape the immune response recruited to target organs of high blood pressure.

scholarly journals Genetic approaches to the investigation of serotonergic neuron functions in animals

2019 ◽  
Vol 23 (4) ◽  
pp. 448-455
Author(s):  
U. S. Drozd ◽  
E. V. Shaburova ◽  
N. N. Dygalo
Keyword(s):  
Developmental Stages ◽  
Sensory Information ◽  
Serotonergic System ◽  
Serotonergic Neurons ◽  
Neurotransmitter Systems ◽  
New Therapeutic Approaches ◽  
Serotonin System ◽  
The Brain

The serotonergic system is one of the most important neurotransmitter systems that take part in the regulation of vital CNS functions. The understanding of its mechanisms will help scientists create new therapeutic approaches to the treatment of mental and neurodegenerative diseases and find out how this neurotransmitter system interacts with other parts of the brain and regulates their activity. Since the serotonergic system anatomy and functionality are heterogeneous and complex, the best tools for studying them are based on manipulation of individual types of neurons without affecting neurons of other neurotransmitter systems. The selective cell control is possible due to the genetic determinism of their functions. Proteins that determine the uniqueness of the cell type are expressed under the regulation of cell-specific promoters. By using promoters that are specific for genes of the serotonin system, one can control the expression of a gene of interest in serotonergic neurons. Here we review approaches based on such promoters. The genetic models to be discussed in the article have already shed the light on the role of the serotonergic system in modulating behavior and processing sensory information. In particular, genetic knockouts of serotonin genes sert, pet1, and tph2 promoted the determination of their contribution to the development and functioning of the brain. In addition, the review describes inducible models that allow gene expression to be controlled at various developmental stages. Finally, the application of these genetic approaches in optogenetics and chemogenetics provided a new resource for studying the functions, discharge activity, and signal transduction of serotonergic neurons. Nevertheless, the advantages and limitations of the discussed genetic approaches should be taken into consideration in the course of creating models of pathological conditions and developing pharmacological treatments for their correction.

scholarly journals Nitric Oxide: The Common Link in Different Forms of Dementia

2021 ◽  
Vol 6 (3) ◽  
pp. 322-326
Author(s):  
Dipak Kumar Dhar
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitrosative Stress ◽  
Keywords Dementia ◽  
Neurotoxic Effects ◽  
The Common ◽  
Cellular Pathogenesis ◽  
The Brain

Dementia broadly refers to a global decline in cognitive and higher functions of the brain. With the gradually increasing number of aging population, the incidence of dementia has been steadily rising and expected to increase further in the coming years. The causes and forms of dementia are wide-ranging and diverse, with Alzheimer’s disease being its best studied form. With increasing knowledge about various effects and mechanisms of nitric oxide, this chemical neurotransmitter appears to be the connecting link in the cellular pathogenesis of dementia. An exhaustive search of research articles, commentaries and books published from 1990s onwards was performed with various words and combinations linked to dementia and nitric oxide. The existing medical literature shows both neuroprotective and neurotoxic effects of nitric oxide. The present article intends to delve into this topic and provide a lucid understanding of the role of nitric oxide in dementia. Keywords: Dementia, Nitric Oxide, Alzheimer’s disease, excitotoxicity, nitrosative stress.

scholarly journals More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones

2019 ◽  
Vol 20 (24) ◽  
pp. 6124 ◽  
Author(s):  
Arnedo ◽  
Latorre-Pellicer ◽  
Lucia-Campos ◽  
Gil-Salvador ◽  
Antoñanzas-Peréz ◽  
...  
Keyword(s):  
Ketone Bodies ◽  
Endoplasmic Reticulum Membrane ◽  
Glucose Levels ◽  
Metabolic Remodeling ◽  
Lyase Activity ◽  
Cytosolic Side ◽  
Leucine Catabolism ◽  
The Common ◽  
The Brain

There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase (HMGCL), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.

Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer’s disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Simone Eggert ◽  
Stefan Kins ◽  
Kristina Endres ◽  
Tanja Brigadski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Death ◽  
Common Features ◽  
Interaction Partners ◽  
The Central Nervous System ◽  
Bdnf Signaling ◽  
The Common ◽  
The Brain

Abstract Brain-derived neurotrophic factor (BDNF) is an important modulator for a variety of functions in the central nervous system (CNS). A wealth of evidence, such as reduced mRNA and protein level in the brain, cerebrospinal fluid (CSF), and blood samples of Alzheimer’s disease (AD) patients implicates a crucial role of BDNF in the progression of this disease. Especially, processing and subcellular localization of BDNF and its receptors TrkB and p75 are critical determinants for survival and death in neuronal cells. Similarly, the amyloid precursor protein (APP), a key player in Alzheimer’s disease, and its cleavage fragments sAPPα and Aβ are known for their respective roles in neuroprotection and neuronal death. Common features of APP- and BDNF-signaling indicate a causal relationship in their mode of action. However, the interconnections of APP- and BDNF-signaling are not well understood. Therefore, we here discuss dimerization properties, localization, processing by α- and γ-secretase, relevance of the common interaction partners TrkB, p75, sorLA, and sortilin as well as shared signaling pathways of BDNF and sAPPα.

scholarly journals KPC-2 β-lactamase Enables Carbapenem Antibiotic Resistance Through Fast Deacylation of the Covalent Intermediate

2020 ◽  
pp. jbc.RA120.015050
Author(s):  
Shrenik C Mehta ◽  
Ian M Furey ◽  
Orville A Pemberton ◽  
David M Boragine ◽  
Yu Chen ◽  
...  
Keyword(s):  
Active Site ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
The Common ◽  
Covalent Intermediate ◽  
Hydrolysis Of ◽  
Carbapenem Antibiotic ◽  
Enzyme Intermediate

Serine active-site β-lactamases hydrolyze β-lactam antibiotics through formation of a covalent acyl-enzyme intermediate followed by deacylation via an activated water molecule. Carbapenem antibiotics are poorly hydrolyzed by most β-lactamases due to slow hydrolysis of the acyl-enzyme intermediate. However, the emergence of the KPC-2 carbapenemase has resulted in widespread resistance to these drugs, suggesting it operates more efficiently. Here, we investigated the unusual features of KPC-2 that enable this resistance. We show that KPC-2 has a 20,000-fold increased deacylation rate compared to the common TEM-1 β-lactamase. Further, kinetic analysis of active site alanine mutants indicates that carbapenem hydrolysis is a concerted effort involving multiple residues. Substitution of Asn170 greatly decreases the deacylation rate, but this residue is conserved in both KPC-2 and non-carbapenemase β-lactamases, suggesting it promotes carbapenem hydrolysis only in the context of KPC-2. X-ray structure determination of the N170A enzyme in complex with hydrolyzed imipenem suggests Asn170 may prevent the inactivation of the deacylating water by the 6α-hydroxyethyl substituent of carbapenems. In addition, the Thr235 residue, which interacts with the C3 carboxylate of carbapenems, also contributes strongly to the deacylation reaction. In contrast, mutation of the Arg220 and Thr237 residues decreases the acylation rate and, paradoxically, improves binding affinity for carbapenems. Thus, the role of these residues may be ground state destabilization of the enzyme-substrate complex or, alternatively, to ensure proper alignment of the substrate with key catalytic residues to facilitate acylation. These findings suggest modifications of the carbapenem scaffold to avoid hydrolysis by KPC-2 β-lactamase.

The Role of Pancreatic Glucagon in the Pathogenesis of Acute Pancreatitis

1972 ◽  
Vol 43 (5) ◽  
pp. 597-603 ◽  
Author(s):  
J. L. Day ◽  
M. Knight ◽  
J. R. Condon
Keyword(s):  
Acute Pancreatitis ◽  
Cell Function ◽  
Severe Disease ◽  
Normal Subjects ◽  
Specific Method ◽  
Pancreatic Glucagon ◽  
Cell Dysfunction ◽  
Alpha Cell Function

1. A reliable, reproducible and specific method for determination of pancreatic glucagon in plasma by radioimmunoassay is described and plasma glucagon was measured in normal subjects and patients with acute pancreatitis. 2. In patients with acute pancreatitis the normal relationship between glucagon and glucose was impaired and disturbance of alpha-cell function was indicated by relative hyperglucagonaemia in patients with moderately severe disease. 3. In patients with severe pancreatitis glucagon concentrations were low and the possible relationship between hyper- and hypo-glucagonaemia and the pathogenesis of acute pancreatitis is discussed. 4. Insulin values in acute pancreatitis, although increased, were not as high as would be expected for the raised glucose concentrations. 5. It is concluded that both alpha- and beta-cell dysfunction may account for the high incidence of carbohydrate intolerance in acute pancreatitis.

The Role of the Glucocorticoid-Dependent Mechanism in the Progression of Sodium Taurocholate–Induced Acute Pancreatitis in the Rat

Pancreas ◽  
2004 ◽  
Vol 29 (1) ◽  
pp. 75-82 ◽  
Author(s):  
A. Paszt ◽  
T. Takács ◽  
Z. Rakonczay ◽  
J. Kaszaki ◽  
A. Wolfard ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Dependent Mechanism

Possible role of histamine in brain function: neurochemical, physiological, and pharmacological indications

1984 ◽  
Vol 62 (6) ◽  
pp. 709-714 ◽  
Author(s):  
I. M. Mazurkiewicz-Kwilecki
Keyword(s):  
Psychotropic Drugs ◽  
Brain Function ◽  
Hormonal Regulation ◽  
Inhibitory Effects ◽  
Brain Histamine ◽  
Future Studies ◽  
Cyclic Variations ◽  
The Brain

Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine.

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