scholarly journals Assessment of Glial Activation Response in the Progress of Natural Scrapie after Chronic Dexamethasone Treatment

2020 ◽  
Vol 21 (9) ◽  
pp. 3231 ◽  
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  

Neuroinflammation has been correlated with the progress of neurodegeneration in many neuropathologies. Although glial cells have traditionally been considered to be protective, the concept of them as neurotoxic cells has recently emerged. Thus, a major unsolved question is the exact role of astroglia and microglia in neurodegenerative disorders. On the other hand, it is well known that glucocorticoids are the first choice to regulate inflammation and, consequently, neuroglial inflammatory activity. The objective of this study was to determine how chronic dexamethasone treatment influences the host immune response and to characterize the beneficial or detrimental role of glial cells. To date, this has not been examined using a natural neurodegenerative model of scrapie. With this aim, immunohistochemical expression of glial markers, prion protein accumulation, histopathological lesions and clinical evolution were compared with those in a control group. The results demonstrated how the complex interaction between glial populations failed to compensate for brain damage in natural conditions, emphasizing the need for using natural models. Additionally, the data showed that modulation of neuroinflammation by anti-inflammatory drugs might become a research focus as a potential therapeutic target for prion diseases, similar to that considered previously for other neurodegenerative disorders classified as prion-like diseases.

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.


2020 ◽  
Vol 21 (3) ◽  
pp. 914 ◽  
Author(s):  
Natalia Starodubtseva ◽  
Natalia Nizyaeva ◽  
Oleg Baev ◽  
Anna Bugrova ◽  
Masara Gapaeva ◽  
...  

Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitrypsin) in urine remain one of the most promising peptide markers of PE. In this study the diagnostic potential of urinary α1-antitrypsin peptides in PE was evaluated. The urinary peptidome composition of 79 pregnant women with preeclampsia (PE), chronic arterial hypertension (CAH), and a control group was investigated. Mann–Whitney U-test (p < 0.05) revealed seven PE specific SERPINA1 peptides demonstrating 52% sensitivity and 100% specificity. SERPINA1 in urine has been associated with the most severe forms of preeclampsia (p = 0.014), in terms of systolic hypertension (p = 0.01) and proteinuria (p = 0.006). According to Spearman correlation analysis, the normalized intensity of SERPINA1 urinary peptides has a similar diagnostic pattern with known diagnostic PE markers, such as sFLT/PLGF. SERPINA1 peptides were not urinary excreted in superimposed PE (PE with CAH), which is a milder form of PE. An increase in expression of SERPINA1 in the structural elements of the placenta during preeclampsia reflects a protective mechanism against hypoxia. Increased synthesis of SERPINA1 in the trophoblast leads to protein accumulation in fibrinoid deposits. It may block syncytial knots and placenta villi, decreasing trophoblast invasion. Excretion of PE specific SERPINA1 peptides is associated with syncytiotrophoblast membrane destruction degradation and increased SERPINA1 staining. It confirms that the placenta could be the origin of SERPINA1 peptides in urine. Significant correlation (p < 0.05) of SERPINA1 expression in syncytiotrophoblast membrane and cytoplasm with the main clinical parameters of severe PE proves the role of SERPINA1 in PE pathogenesis. Estimation of SERPINA1 peptides in urine can be used as a diagnostic test of the severity of the condition to determine further treatment, particularly the need for urgent surgical delivery.


Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 250-255
Author(s):  
Michael A. Klein ◽  
Adriano Aguzzi

Prion diseases are fatal neurodegenerative disorders of animals and humans. Here we address the role of the immune system in the spread of prions from peripheral sites to the central nervous system and its potential relevance to iatrogenic prion disease.


2020 ◽  
Vol 21 (20) ◽  
pp. 7765
Author(s):  
Caterina Peggion ◽  
Roberto Stella ◽  
Paolo Lorenzon ◽  
Enzo Spisni ◽  
Alessandro Bertoli ◽  
...  

Prion diseases are rare transmissible neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the cellular prion protein (PrPC) in the central nervous system (CNS). Neuropathological hallmarks of prion diseases are neuronal loss, astrogliosis, and enhanced microglial proliferation and activation. As immune cells of the CNS, microglia participate both in the maintenance of the normal brain physiology and in driving the neuroinflammatory response to acute or chronic (e.g., neurodegenerative disorders) insults. Microglia involvement in prion diseases, however, is far from being clearly understood. During this review, we summarize and discuss controversial findings, both in patient and animal models, suggesting a neuroprotective role of microglia in prion disease pathogenesis and progression, or—conversely—a microglia-mediated exacerbation of neurotoxicity in later stages of disease. We also will consider the active participation of PrPC in microglial functions, by discussing previous reports, but also by presenting unpublished results that support a role for PrPC in cytokine secretion by activated primary microglia.


Author(s):  
Sujata Basu ◽  
Manisha Singh ◽  
Mansi Verma ◽  
Rachana R.

The glial cells along with cells of hematopoietic origin and microvascular endothelia work together to maintain the normal development and/or functioning of the nervous system. Disruption in functional coordination among these cells interrupts the efficiency of the nervous system, leading to neurodegeneration. Various proteins in the nerve cells maintain the normal signaling mechanism with these cells and throughout the body. Structural/functional disorganization of these proteins causes neurodegenerative disorders. The molecular mechanisms involved in these phenomena are yet to be explored extensively from therapeutic perspectives. Through this chapter, the authors have elaborated on less known protein Bcl-2 associated athanogene 3 (BAG3) involved in neurodegeneration. They have explored BAG3 protein and its role in neurodegeneration, protein homeostasis, its mechanism of action, its uses as a drug target, and its uses as a possible diagnostic marker of neurodegeneration.


Author(s):  
Robert Peter Biney ◽  
Thabisile Mpofana ◽  
Ella Anle Kasanga

Free radicals are intricately woven into the fabric of oxidative stress and are significant in the development of neurodegenerative disorders (NDs). This chapter examines free radicals in the context of neurodegeneration and provides overview of the multiple roles they play in the pathophysiology and clinical progression of varying NDs including Pick's disease (PiD), Parkinson's disease (PD), Alzheimer's disease (AD), prion diseases (PrD), traumatic brain injury, and aging. The molecular mechanisms of degeneration in Huntington's disease (HD) are also examined with respect to free radicals. Different antioxidant systems and their mechanisms of action are briefly reviewed in addition to the role of diet in aging. The effectiveness of selected synthetic drugs and natural products used in oxidative stress is also reviewed. Lastly, the chapter examines challenges associated with the use of antioxidants and how promising future directions like the endocannabinoid system is being pursued in the race to effectively manage NDs.


2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


2012 ◽  
Vol 15 (2) ◽  
pp. 84 ◽  
Author(s):  
Canturk Cakalagaoglu ◽  
Cengiz Koksal ◽  
Ayse Baysal ◽  
Gokhan Alici ◽  
Birol Ozkan ◽  
...  

<p><b>Aim:</b> The goal was to determine the effectiveness of the posterior pericardiotomy technique in preventing the development of early and late pericardial effusions (PEs) and to determine the role of anxiety level for the detection of late pericardial tamponade (PT).</p><p><b>Materials and Methods:</b> We divided 100 patients randomly into 2 groups, the posterior pericardiotomy group (n = 50) and the control group (n = 50). All patients undergoing coronary artery bypass grafting surgery (CABG), valvular heart surgery, or combined valvular and CABG surgeries were included. The posterior pericardiotomy technique was performed in the first group of 50 patients. Evaluations completed preoperatively, postoperatively on day 1, before discharge, and on postoperative days 5 and 30 included electrocardiographic study, chest radiography, echocardiographic study, and evaluation of the patient's anxiety level. Postoperative causes of morbidity and durations of intensive care unit and hospital stays were recorded.</p><p><b>Results:</b> The 2 groups were not significantly different with respect to demographic and operative data (<i>P</i> > .05). Echocardiography evaluations revealed no significant differences between the groups preoperatively; however, before discharge the control group had a significantly higher number of patients with moderate, large, and very large PEs compared with the pericardiotomy group (<i>P</i> < .01). There were 6 cases of late PT in the control group, whereas there were none in the pericardiotomy group (<i>P</i> < .05). Before discharge and on postoperative day 15, the patients in the pericardiotomy group showed significant improvement in anxiety levels (<i>P</i> = .03 and .004, respectively). No differences in postoperative complications were observed between the 2 groups.</p><p><b>Conclusion:</b> Pericardiotomy is a simple, safe, and effective method for reducing the incidence of PE and late PT after cardiac surgery. It also has the potential to provide a better quality of life.</p>


2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.


2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.


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