Mast cells in neuropathic pain: an increasing spectrum of their involvement in pathophysiology

2017 ◽  
Vol 28 (7) ◽  
pp. 759-766 ◽  
Author(s):  
Gunjanpreet Kaur ◽  
Nirmal Singh ◽  
Amteshwar Singh Jaggi
Keyword(s):  
Neuropathic Pain ◽  
Mast Cells ◽  
Critical Role ◽  
Experimental Models ◽  
The Body ◽  
Pathological Conditions ◽  
Dual Action ◽  
Time Of Administration ◽  
Different Parts

AbstractMast cells are immunological cells that are diversely distributed in different parts of the body. Their role in various pathological conditions such as hypersensitivity, atherosclerosis, pulmonary hypertension, and male infertility has been reported by different scientists. Apart from these, a number of studies have shown their important role in pathogenesis of neuropathic pain of diverse aetiology. They have been found to release active mediators, primarily histamine and serotonin on degranulation in response to different stimuli including chemical, nerve damage, toxin or disease-related conditions. The mast cells stabilizer has shown pain attenuating effects by preventing degranulation of mast cells. Similarly, compound 48/80 (first dose 200 μg/100 g and after 6-h interval, second dose of 500 μg/100 g) caused the degranulation of the accumulated endoneurial histamine and 5-HT antagonists have shown pain relieving effects by attenuating the effects of histamine and serotonin, respectively. On the other hand, the mast cell degranulator compound 48/80 has shown dual action depending on its time of administration. The present review discusses the critical role of mast cells in the generation and maintenance of neuropathic pain in experimental models.

scholarly journals Role of eosinophils in the initiation and progression of pancreatitis pathogenesis

2018 ◽  
Vol 314 (2) ◽  
pp. G211-G222 ◽  
Author(s):  
Murli Manohar ◽  
Alok K. Verma ◽  
Sathisha Upparahalli Venkateshaiah ◽  
Anil Mishra
Keyword(s):  
Chronic Pancreatitis ◽  
Mast Cells ◽  
Critical Role ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Human Pancreas ◽  
Protein Levels ◽  
Tissue Sections ◽  
Tissue Eosinophilia

Eosinophilic pancreatitis (EP) is reported in humans; however, the etiology and role of eosinophils in EP pathogenesis are poorly understood and not well explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Accordingly, we performed anti-major basic protein immunostaining, chloroacetate esterase, and Masson’s trichrome analyses to detect eosinophils, mast cells, and collagen in the tissue sections of mouse and human pancreas. Induced eosinophils accumulation and degranulation were observed in the tissue sections of human pancreatitis, compared with no eosinophils in the normal pancreatic tissue sections. Similarly, we observed induced tissue eosinophilia along with mast cells and acinar cells atrophy in cerulein-induced mouse model of chronic pancreatitis. Additionally, qPCR and ELISA analyses detected induced transcript and protein levels of proinflammatory and profibrotic cytokines, chemokines like IL 5, IL-18, eotaxin-1, eotaxin-2, TGF-β1, collagen-1, collagen-3, fibronectin, and α-SMA in experimental pancreatitis. Mechanistically, we show that eosinophil-deficient GATA1 and endogenous IL-5-deficient mice were protected from the induction of proinflammatory and profibrotic cytokines, chemokines, tissue eosinophilia, and mast cells in a cerulein-induced murine model of pancreatitis. These human and experimental data indicate that eosinophil accumulation and degranulation may have a critical role in promoting pancreatitis pathogenesis including fibrosis. Taken together, eosinophil tissue accumulation needs appropriate attention to understand and restrict the progression of pancreatitis pathogenesis in humans.NEW & NOTEWORTHY The present study for the first time shows that eosinophils accumulate in the pancreas and promote disease pathogenesis, including fibrosis in earlier reported cerulein-induced experimental models of pancreatitis. Importantly, we show that GATA-1 and IL-5 deficiency protects mice form the induction of eosinophil active chemokines, and profibrotic cytokines, including accumulation of tissue collagen in an experimental model of pancreatitis. Additionally, we state that cerulein-induced chronic pancreatitis is independent of blood eosinophilia.

scholarly journals The Role of Dll4/Notch Signaling in Normal and Pathological Ocular Angiogenesis: Dll4 Controls Blood Vessel Sprouting and Vessel Remodeling in Normal and Pathological Conditions

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ivan Lobov ◽  
Natalia Mikhailova
Keyword(s):  
Blood Vessel ◽  
Transmembrane Protein ◽  
Mammalian Species ◽  
Vascular Development ◽  
Critical Role ◽  
Notch Pathway ◽  
The Body ◽  
Therapeutic Effects ◽  
Pathological Conditions

Background. Retina is the highest oxygen-demanding and vascularized tissue in the body. Retinal development and function require proper vascularization and blood vessel function and integrity. Dll4 is most prominently expressed in the endothelium of angiogenic blood vessels and in quiescent arteries and capillaries in all tissues and organs of the mammalian species, and it is the key regulator of blood vessel sprouting.Results. Dll4 is a transmembrane protein that acts as a ligand for Notch receptors 1 and 4. Genetic deletion of Dll4 causes severe abnormalities in embryonic and postnatal vascular development. Deletion of even a single Dll4 allele results in almost complete embryonic lethality due to severe vascular abnormalities, the phenomenon called haploinsufficiency indicating the critical role of Dll4/Notch in vascular development. Dll4/Notch pathway interplays at multiple levels with other signaling pathways including VEGF, Wnt/Fzd, and genes controlling vascular toning. Multiple studies of the effects of Dll4 inhibition were performed in the developing retina to elucidate the key functions of Dll4 in normal and pathological angiogenesis. Several genetic approaches and therapeutic molecules were tested to evaluate the biological and therapeutic effects of acute and prolonged Dll4 inhibition in the eye and oncology.Conclusions. All current studies demonstrated that Dll4 controls blood vessel sprouting, growth, and remodeling in normal and pathological conditions as well as arterial-venous differentiation. Genetic and therapeutic Dll4 modulation studies show that Dll4 inhibition can promote blood vessel sprouting and might be useful to stimulate vessel growth in the ischemic retina and Dll4 is the key modulator of the postangiogenic vascular remodeling that ultimately defines vascular patterning.

Updating long-held assumptions about fat stigma: For women, body shape plays a critical role

2020 ◽  
Author(s):  
Jaimie Krems ◽  
Steven L. Neuberg
Keyword(s):  
Body Shape ◽  
Critical Role ◽  
The Body ◽  
Theoretical Assumption ◽  
Obesity Stigma ◽  
Obese Female ◽  
Three Samples ◽  
Female Bodies ◽  
Different Parts ◽  
Fat Stigma

Heavier bodies—particularly female bodies—are stigmatized. Such fat stigma is pervasive, painful to experience, and may even facilitate weight gain, thereby perpetuating the obesity-stigma cycle. Leveraging research on functionally distinct forms of fat (deposited on different parts of the body), we propose that body shape plays an important but largely underappreciated role in fat stigma, above and beyond fat amount. Across three samples varying in participant ethnicity (White and Black Americans) and nation (U.S., India), patterns of fat stigma reveal that, as hypothesized, participants differently stigmatized equally-overweight or -obese female targets as a function of target shape, sometimes even more strongly stigmatizing targets with less rather than more body mass. Such findings suggest value in updating our understanding of fat stigma to include body shape and in querying a predominating, but often implicit, theoretical assumption that people simply view all fat as bad (and more fat as worse).

Extase scopique, sédimentation langagičre et inscription corporelle. Les images dans la civilisation contemporaine

PARADIGMI ◽  
2009 ◽  
pp. 71-83
Author(s):  
Jean-Jacques Wunenburger
Keyword(s):  
Key Words ◽  
The Body ◽  
Pathological Conditions ◽  
Image Informatics

- Linguistic Sedimentation, and Bodily Inscription At present, we are exposed to an excessive offer of images, which raises a problem of assimilation. Subjects are increasingly passive, in ways that can border on pathological conditions. Yet, it is not so much a question of condemning this situation as of finding a way of re-symbolizing images, saving them from mere contemplation and inserting them in a process of contextualisation. Such a process requires an understanding of the role of the body and of the incorporation of images along the lines of Bachelard's intuition of the "resisting" nature of images. This raises the possibility of an education to images suited to the present age.Key words: Alienation, Education, Embodiment, Image, Informatics, Symbolisation.Parole chiave: Alienazione, Educazione, Immagine, Incorporazione, Informatica, Simbolizzazione.

A critical role for central vasopressin in regulation of fever during bacterial infection

1992 ◽  
Vol 263 (6) ◽  
pp. R1235-R1240
Author(s):  
R. A. Cridland ◽  
N. W. Kasting
Keyword(s):  
Body Temperature ◽  
Arginine Vasopressin ◽  
Continuous Measurement ◽  
Critical Role ◽  
Experimental Models ◽  
Bacterial Endotoxins ◽  
Chronic Infusion ◽  
Live Bacteria ◽  
The Brain

Previous investigations on the antipyretic properties of arginine vasopressin have used bacterial endotoxins or pyrogens to induce fever. Because these experimental models of fever fail to mimic all aspects of the responses to infection, we felt it was important to examine the role of endogenously released vasopressin as a neuromodulator in febrile thermoregulation during infection. Therefore the present study examines the effects of chronic infusion of a V1-receptor antagonist or saline (via osmotic minipumps into the ventral septal area of the brain) on a fever induced by injection of live bacteria. Telemetry was used for continuous measurement of body temperature in the awake unhandled rat. Animals infused with the V1-antagonist exhibited fevers that were greater in duration compared with those of saline-infused animals. These results support the hypothesis that vasopressin functions as an antipyretic agent or fever-reducing agent in brain. Importantly, they suggest that endogenously released vasopressin may play a role as a neuromodulator in natural fever.

scholarly journals Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Ryul Lee
Keyword(s):  
Oxidative Stress ◽  
Zinc Deficiency ◽  
Metal Binding ◽  
Inflammatory Responses ◽  
Binding Capacity ◽  
Critical Role ◽  
Cellular Systems ◽  
Oxidative Stresses ◽  
Dual Action

Zinc is recognized as an essential trace metal required for human health; its deficiency is strongly associated with neuronal and immune system defects. Although zinc is a redox-inert metal, it functions as an antioxidant through the catalytic action of copper/zinc-superoxide dismutase, stabilization of membrane structure, protection of the protein sulfhydryl groups, and upregulation of the expression of metallothionein, which possesses a metal-binding capacity and also exhibits antioxidant functions. In addition, zinc suppresses anti-inflammatory responses that would otherwise augment oxidative stress. The actions of zinc are not straightforward owing to its numerous roles in biological systems. It has been shown that zinc deficiency and zinc excess cause cellular oxidative stress. To gain insights into the dual action of zinc, as either an antioxidant or a prooxidant, and the conditions under which each role is performed, the oxidative stresses that occur in zinc deficiency and zinc overload in conjunction with the intracellular regulation of free zinc are summarized. Additionally, the regulatory role of zinc in mitochondrial homeostasis and its impact on oxidative stress are briefly addressed.

scholarly journals The Role of Immune-Related miRNAs in the Pathology of Kidney Transplantation

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1198
Author(s):  
Emanuela Boštjančič ◽  
Željka Večerić-Haler ◽  
Nika Kojc
Keyword(s):  
Immune Response ◽  
Kidney Transplantation ◽  
Kidney Diseases ◽  
Experimental Models ◽  
Regulatory Rna ◽  
Limited Data ◽  
Pathological Conditions ◽  
Monitoring Response ◽  
Disease Specific

MicroRNAs (miRNAs) are members of the non-coding regulatory RNA family that play pivotal roles in physiological and pathological conditions, including immune response. They are particularly interesting as promising therapeutic targets, prognostic and diagnostic markers due to their easy detection in body fluids and stability. There is accumulating evidence that different miRNAs provide disease-specific signatures in liquid samples of distinct kidney injuries. Using experimental models and human samples, there have been numerous suggestions that immune-related miRNAs are also important contributors to the development of different kidney diseases as well as important markers for monitoring response after kidney transplantation. However, there are limited data for understanding their function in the molecular pathways of allograft pathologies. In our review, we focused on microRNAs that are related to different aspects of immune response after kidney transplantation.

Adoption of students' loan schemes: the contingent role of financial knowledge

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Gloria Ocran ◽  
Livingstone Divine Caesar
Keyword(s):  
Critical Role ◽  
Financial Education ◽  
The Body ◽  
Financial Knowledge ◽  
Relative Advantage ◽  
Research Approach ◽  
Content Type ◽  
Four Dimensions ◽  
Behavioural Factors

PurposeDespite the introduction of structural reforms to the students' loan scheme (SLS) in Ghana's higher education sector, patronage is still low. This paper aims to examine the complexity of technological and behavioural factors underpinning the low rate of students' loan adoption in Ghana. It further contributes to the body of knowledge by exploring the moderating role of financial knowledge in the hypothesized relationships.Design/methodology/approachUsing a positivistic research approach, a sample of 700 tertiary students with experience in accessing SLSs were surveyed. An 88% response rate was realized and the data analysed using descriptive statistics, exploratory and confirmatory factor analysis.FindingsFour dimensions of technological factors (relative advantage, trialability, observability and compatibility) and two of behavioural factors (attitude and control behaviour) were positively related to adoption of the SLS. Financial knowledge only moderated the relationship between compatibility, attitude, behavioural control and students' loan adoption.Practical implicationsFinancial knowledge plays a critical role in influencing the investment decisions of people. Management of SLSs needs to offer financial education to targeted parents/students to clear misconceptions. It is also imperative that all other technical challenges are addressed to enhance adoption rates for the SLS. Review of guarantor requirements is needed also.Originality/valueThis paper introduces financial knowledge as a moderating variable to investigate the hypothesized relationships. It offers a developing country insight into how technological/behavioural factors and financial knowledge might be impacting adoption of SLSs.

Cell Delivery and Recirculation

2004 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Tissue Engineering ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Critical Role ◽  
Cell Movement ◽  
The Body ◽  
Associated Proteins ◽  
Adult Organism ◽  
Adenine Deaminase

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.

scholarly journals Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning

2020 ◽  
Vol 31 (1) ◽  
pp. 267-280
Author(s):  
Rossella Breveglieri ◽  
Annalisa Bosco ◽  
Sara Borgomaneri ◽  
Alessia Tessari ◽  
Claudio Galletti ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Parietal Cortex ◽  
Magnetic Stimulation ◽  
Posterior Parietal Cortex ◽  
Critical Role ◽  
The Body ◽  
Visually Guided ◽  
Visually Guided Reaching ◽  
Posterior Parietal

Abstract Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A–hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

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