Search results for: cardiac inflammation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 973

Search results for: cardiac inflammation

463 Acute Renal Failure Associated Tetanus Infection: A Case Report from Afghanistan

Authors: Shohra Qaderi

Abstract:

Introduction: Tetanus is a severe infection characterized by the spasm of skeletal muscles that often progresses toward respiratory failure. Acute Renal failure (ARF) is an important complication associated Tetanus infection, occurring in 15%-39% of cases. Presentation of cases: A previous healthy 14-year-old boy was admitted to the Tetanus ward of a hospital in Kabul, presenting with severe muscle spasms. On day four of admission, he started having cola-colored urine with decreased urine output. Due to lack of peritoneal dialysis, he went under hemodialysis in view of rapidly raising in blood urea (from baseline 32 mg/dl to 150 mg/dl) and creatinine from (baseline 0.9 mg/dl to 6.2g/dl). Despite all efforts, he had a sudden cardiac arrest and passed away on day 6 of admission. Discussion: ARF is a complication of tetanus, reported to be mild and non-oliguric. Suggested pathological mechanisms include autonomic dysfunction and rhabdomyolysis, owing to uncontrolled muscle spasms. Autonomic dysfunction, most evident in the first two weeks of infection. Conclusion: The prevalence and mortality of tetanus is high in Afghanistan. Physicians and pediatricians need to be aware of this complication of tetanus so as to take appropriate preventive measures and recognize and manage it early.

Keywords: afghanistan, acute renal failure, child, mortality

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462 Effects of β-Glucan on the Release of Nitric Oxide by RAW264.7 Cells Stimulated with Escherichia coli Lipopolysaccharide

Authors: Eun Young Choi, So Hui Choe, Jin Yi Hyeon, Ji Young Jin, Bo Ram Keum, Jong Min Lim, Hyung Rae Cho, Kwang Keun Cho, In Soon Choi

Abstract:

This research analyzed the effect of β-glucan that is expected to alleviate the production of inflammatory mediator in macrophagocyte, which was processed by the lipopolysaccharide (LPS) of Escherichia, a pathogen related to allergy. The incubated layer was used for nitric oxide (NO) analysis. The DNA-binding activation of the small unit of NF-κB was measured using ELISA-based kit. In RAW264.7 cells that were vitalized by E.coli LPS, β-glucan inhibited both the combatant and rendering phases of inducible NO synthase (iNOS)-derived NO. β-glucan increased the expression of heme oxygenase-1 (HO-1) in the cell that was stimulated by E.coli LPS, and HO-1 activation was inhibited by SnPP. This shows that NO production induced by LPS is related to the inhibition effect of β-glucan. The phosphorylation of JNK and p38 induced by LPS were not influenced by β-glucan, and IκB-α decomposition was not influenced either. Instead, β-glucan remarkably inhibited the phosphorylation of STAT1 that was induced by E.coli LPS. Overall, β-glucan inhibited the production of NO in macrophagocyte that was vitalized by E.coli LPS through HO-1 induction and STAT1 pathways inhibition in this research. As the host inflammation reaction control by β-glucan weakens the progress of allergy, β-glucan can be used as an effective treatment method.

Keywords: β-glucan, lipopolysaccharide (LPS), nitric oxide (NO), RAW264.7 cells, STAT1

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461 Evaluation of Collagen Synthesis in Macrophages/Fibroblasts Co-Culture Using Polylactic Acid Particles as Stimulants

Authors: Feng Ju Chuang, Yu Wen Wang, Tai Jung Hsieh, Shyh Ming Kuo

Abstract:

Polylactic acid is a synthetic polymer with good biocompatibility and degradability, is widely used in clinical applications. In this study, we utilized Polylactic acid particles as stimulants for macrophages and the collagen synthesis of co-cultured fibroblasts was evaluated. The results indicated that Polylactic acid particles were nontoxic to cells from 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. No obvious inflammation effect was observed (under the PLLA concentration of 1 mg/mL) after 24-h co-culture of Raw264.7 and NIH3T3 cells (from TNF-α assay). The addition of PLLA particles to the Raw264.7 and NIH3T3 co-cultures increased the synthesis of collagen, the highest collagen synthesis from the fibroblast was the 0.2 mg/mL (approximately 60% increased as compared with without addition Polylactic acid particles). Moreover, a co-axial atomization delivery device was used to percutaneously introduce Polylactic acid particles into the dermis layer and stimulating macrophages to secrete growth factors promoting fibroblasts to produce collagen. The preliminary results demonstrated the synthesis of collagen was increased mildly after the introduction of Polylactic acid particles for 28-d post implantation. The Polylactic acid particles could be successfully introduced into the dermis layer from H&E staining examination, however, the optimum concentration of Polylactic acid particles and the time-period for collagen synthesis still need to be evaluated.

Keywords: collagen synthesis, macrophage, NIH3T3 cells, polylactic acid particles

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460 Roles of Lysine-63-Linked Ubiquitination in Cell Decision Fate between Cell Proliferation and Apoptosis

Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

Abstract:

K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

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459 Effects of Tiliacora triandra Leaf Water Extract in High-Fat Diet Leaf Water

Authors: Urarat Nanna, Jarinyaporn Naowaboot

Abstract:

Tiliacora triandra (T. triandra) is traditional Southeast Asian medicine and widely used in the cuisines of northeast Thailand and Laos. It has been used as antipyretic, detoxication agent, antiinflammation. But the activity of T. triandra leaf water extract (TTW) in the regulation of metabolic syndrome is still little known. In this study, we evaluated the effects of TTW in high-fat diet (HFD)-induced obese mice. Male ICR mice were induced to be obese by HFD feeding (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with TTW at 250 and 500 mg/kg/day. The biochemical parameters and histology analysis were measured at the end of treatment period. After 6 weeks of TTW treatment, the hyperglycemia, hyperinsulinemia, hyperleptinemia and hyperlipidemia were significantly decreased. Hepatic lipid accumulation and adipocyte hypertrophy were also reduced. Serum adiponectin was increased in TTW-treated obese mice. TTW treatment could reduce the malondialdehyde in serum and liver tissue. Furthermore, the elevated serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 were reduced (MCP-1) by TTW. These results suggest that T. triandra leaf is a beneficial plant in alleviating hyperglycemia, hyperlipidemia, oxidative stress and inflammation in the obese condition induced by HFD.

Keywords: Tiliacora triandra, insulin resistance, hyperlipidemia, oxidative stress

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458 Developing a Methodology to Examine Psychophysiological Responses during Stress Exposure and Relaxation: An Experimental Paradigm

Authors: M. Velana, G. Rinkenauer

Abstract:

Nowadays, nurses are facing unprecedented amounts of pressure due to the ongoing global health demands. Work-related stress can cause a high physical and psychological workload, which can lead, in turn, to burnout. On the physiological level, stress triggers an initial activation of the sympathetic nervous and adrenomedullary systems resulting in increases in cardiac activity. Furthermore, activation of the hypothalamus-pituitary-adrenal axis provokes endocrine and immune changes leading to the release of cortisol and cytokines in an effort to re-establish body balance. Based on the current state of the literature, it has been identified that resilience and mindfulness exercises among nurses can effectively decrease stress and improve mood. However, it is still unknown what relaxation techniques would be suitable for and to what extent would be effective to decrease psychophysiological arousal deriving from either a physiological or a psychological stressor. Moreover, although cardiac activity and cortisol are promising candidates to examine the effectiveness of relaxation to reduce stress, it still remains to shed light on the role of cytokines in this process so as to thoroughly understand the body’s response to stress and to relaxation. Therefore, the main aim of the present study is to develop a comprehensive experimental paradigm and assess different relaxation techniques, namely progressive muscle relaxation and a mindfulness exercise originating from cognitive therapy by means of biofeedback, under highly controlled laboratory conditions. An experimental between-subject design will be employed, where 120 participants will be randomized either to a physiological or a psychological stress-related experiment. Particularly, the cold pressor test refers to a procedure in which the participants have to immerse their non-dominant hands into ice water (2-3 °C) for 3 min. The participants are requested to keep their hands in the water throughout the whole duration. However, they can immediately terminate the test in case it would be barely tolerable. A pre-test anticipation phase and a post-stress period of 3 min, respectively, are planned. The Trier Social Stress Test will be employed to induce psychological stress. During this laboratory stressor, the participants are instructed to give a 5-min speech in front of a committee of communication specialists. Before the main task, there is a 10-min anticipation period. Subsequently, participants are requested to perform an unexpected arithmetic task. After stress exposure, the participants will perform one of the relaxation exercises (treatment condition) or watch a neutral video (control condition). Electrocardiography, salivary samples, and self-report will be collected at different time points. The preliminary results deriving from the pilot study showed that the aforementioned paradigm could effectively induce stress reactions and that relaxation might decrease the impact of stress exposure. It is of utmost importance to assess how the human body responds under different stressors and relaxation exercises so that an evidence-based intervention could be transferred in a clinical setting to improve nurses’ general health. Based on suggestive future laboratory findings, the research group plans to conduct a pilot-level randomized study to decrease stress and promote well-being among nurses who work in the stress-riddled environment of a hospital located in Northern Germany.

Keywords: nurses, psychophysiology, relaxation, stress

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457 Inflammatory Alleviation on Microglia Cells by an Apoptotic Mimicry

Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

Abstract:

Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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456 The Effects of Maternal Exposure Riboflavin to Prevent Uterus Arsenic Damage in Offspring Rats

Authors: Ali Olfati, Parichehr Nouri

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Objective: In this study, we have investigated for the first time in the literature the efficacy of riboflavin [VB2] in preventing uterus As₂O₃ damage. Methods: Rats received 40 μg LHRHa for estrus synchronization. 48 pregnant Wistar rats were included. Four groups were formed with 7 rats in each group: Sham, 1.5 mg arsenic trioxide (As₂O₃/L) alone or in combination with VB2 [20 and 40 mg/L] in drinking water [for 21 days continuously]. Similar to maternal generation treatment, the F1-female generation was also arranged [for 35 days continuously until puberty]. Results: Data indicated that As₂O₃ reduced body weight and feed intake (p<0.05). Furthermore, the serum malondialdehyde levels in the As₂O₃ group were significantly higher than that of the control group (p<0.05). At the same time, total antioxidative status and the activities of glutathione peroxidase, superoxide dismutase, and catalase were reduced (p<0.05). Meanwhile, As₂O₃ remarkably increased the production of inflammatory markers [interleukin 6 and C-reactive protein](p<0.05). As₂O₃ administration induced uterus apoptosis-related genes by upregulating caspase-3, iNOS, and Bax genes and downregulating Bcl-2 gene of pubertal F1-female rats (p<0.05). Conclusion: Our observation indicated that VB2 therapy is potentially an effective strategy to modifying the detrimental effects of As₂O₃ in pubertal F1-female rats via suppresses oxidative damages.

Keywords: As₂O₃, inflammation, puberty, vitamin B2

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455 Regulation of SHP-2 Activity by Small Molecules for the Treatment of T Cell-Mediated Diseases

Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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454 Automated Heart Sound Classification from Unsegmented Phonocardiogram Signals Using Time Frequency Features

Authors: Nadia Masood Khan, Muhammad Salman Khan, Gul Muhammad Khan

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Cardiologists perform cardiac auscultation to detect abnormalities in heart sounds. Since accurate auscultation is a crucial first step in screening patients with heart diseases, there is a need to develop computer-aided detection/diagnosis (CAD) systems to assist cardiologists in interpreting heart sounds and provide second opinions. In this paper different algorithms are implemented for automated heart sound classification using unsegmented phonocardiogram (PCG) signals. Support vector machine (SVM), artificial neural network (ANN) and cartesian genetic programming evolved artificial neural network (CGPANN) without the application of any segmentation algorithm has been explored in this study. The signals are first pre-processed to remove any unwanted frequencies. Both time and frequency domain features are then extracted for training the different models. The different algorithms are tested in multiple scenarios and their strengths and weaknesses are discussed. Results indicate that SVM outperforms the rest with an accuracy of 73.64%.

Keywords: pattern recognition, machine learning, computer aided diagnosis, heart sound classification, and feature extraction

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453 Sudden Death of a Cocaine Body Packer: An Autopsy Examination Findings

Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

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452 Serum Anti-Oxidation Enzymes Response to L-Carnitine Supplementation

Authors: Farah Nameni, Hamidreza Poursadra, Maasumeh Nurani Pilehrud

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Exercise training induced Inflammation and stress. Antioxidant, for example L- Carnitine has beneficial effects in immune system and increased antioxidant enzymes activity. L- Carnitine protects the tissue against the oxidative side effect and helps the body to protect against stress during and after acute exercise. The aim of this study was to determine the effect of L-Carnitine on the blood enzymes: GPX SOD, CAT and GR response. In this study, 20 basketball players girls participated. Subjects were randomly assigned into two groups; placebo and supplementation. Antioxidadision enzymes (Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase) evaluated. L-Carnitine supplement group orally daily received 3000 mg powder for 14 dys. Then all participates trained basketball exercise acute. Blood samples were drawn vein before and immediately after exercise. Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase were measured, and data was analyzed using repeated measure ANOVA, Bonferroni and t-test. Our results showed: SOD, GPX and GPX (P < 0.05) have a significant increase. These results suggest L-Carnitine supplementation may increase GPX SOD, CAT, and basal anti oxidative capacity. L-Carnitine can modulate the alterations of exercise oxidative damage in girl basketball players.

Keywords: l-carnitine, GPX, SOD, CAT, exercise, GR, anti-oxidant

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451 Carvacrol Attenuates Lung Injury in Rats with Severe Acute Pancreatitis

Authors: Salim Cerig, Fatime Geyikoglu, Pınar Akpulat, Suat Colak, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Kubra Koc

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This study was designed to evaluate whether carvacrol (CAR) could provide protection against lung injury by acute pancreatitis development. The rats were randomized into groups to receive (I) no therapy; (II) 50 μg/kg cerulein at 1h intervals by four intraperitoneal injections (i.p.); (III) 50, 100 and 200 mg/kg CAR by one i.p.; and (IV) cerulein+CAR after 2h of cerulein injection. 12h later, serum samples were obtained to assess pancreatic function the lipase and amylase values. The animals were euthanized and lung samples were excised. The specimens were stained with hematoxylin-eosin (H&E), periodic acid–Schif (PAS), Mallory's trichrome and amyloid. Additionally, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The results showed that the serum activity of lipase and amylase in AP rats were significantly reduced after the therapy (p<0.05). We also found that the 100 mg/kg dose of CAR significantly decreased 8-OH-dG levels. Moreover, the severe pathological findings in the lung such as necrosis, inflammation, congestion, fibrosis, and thickened alveolar septum were attenuated in the AP+CAR groups when compared with AP group. Finally, the magnitude of the protective effect on lung is certain, and CAR is an effective therapy for lung injury caused by AP.

Keywords: antioxidant activity, acute pancreatitis, carvacrol, experimental, lung injury, oxidative DNA damage

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450 Gut-Microbiota-Brain-Axis, Leaky Gut, Leaky Brain: Pathophysiology of Second Brain Aging and Alzheimer’s Disease- A Neuroscientific Riddle

Authors: Bilal Ahmad

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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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449 Grape Seed Extract and Zinc Containing Multivitamin-Mineral Nutritional Food Supplement Protects Heart against Myocardial Ischemic-Reperfusion Injury in Wistar Rats

Authors: S. M. Satyam, K. L. Bairy, R. Pirasanthan, R. L. Vaishnav

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Zincovit tablets have been used as nutritional food supplement over a prolonged period of time. The aim of the present study was to investigate the cardio-protective effect of combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg) using a Langendorff model of ischemia-reperfusion in Wistar rats. Following 21 days of pre-treatment, combined formulation of grape seed extract and Zincovit tablets significantly attenuated ischemia-reperfusion induced cardiac injury in terms of increased coronary flow rate (p < 0.01), decreased creatine kinase activity in coronary effluent (p < 0.05), decreased MDA (p < 0.001), 4-HNE (p < 0.001) and increased protein thiol content (p < 0.01) in comparison with the untreated (control) group. This study opens an avenue to clinical studies to demonstrate the validity of this paradigm as a nutritional food supplement, which could improve the clinical outcome of patients subjected to percutaneous angioplasty.

Keywords: grape seed extract, myocardial ischemia-reperfusion injury, oxidative stress, Zincovit tablets

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448 THRAP2 Gene Identified as a Candidate Susceptibility Gene of Thyroid Autoimmune Diseases Pedigree in Tunisian Population

Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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447 MMP-2 Gene Polymorphism and Its Influence on Serum MMP-2 Levels in Pre-Eclampsia in Indian Population

Authors: Ankush Kalra, Mirza Masroor, Usha Manaktala, B. C. Koner, T. K. Mishra

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Introduction: Pre-eclampsia affects 3-5% of pregnancies worldwide and increases maternal-fetal morbidity and mortality. Reduced placental perfusion induces the release of biomolecules by the placenta into maternal circulation causing endothelial dysfunction. Zinc dependent matrix metalloproteinase-2 (MMP-2) may be up-regulated and interact with circulating factors of oxidative stress and inflammation to produce endothelial dysfunction in pre-eclampsia. Aim: To study the functional genetic polymorphism of MMP-2 gene (g-1306 C>T) in pre-eclampsia and its effect on serum MMP-2 levels in these patients. Method: Hundred pre-eclampsia patients and hundred age and gestation period matched healthy pregnant women with their consent were recruited in the study. Serum MMP-2 levels in all subjects were estimated using standard ELISA kits. MMP-2 gene (g.- 1306 C>T) SNPs were genotyped using whole blood by ASO-PCR. Result: The pre-eclampsia patients had higher serum levels of MMP-2 compared to the healthy pregnant (p < 0.05). Also the MMP-2 genotype was associated with significant alteration in the serum MMP-2 concentration in these patients (p < 0.05). Conclusion: This study results suggest an association of MMP-2 genetic polymorphism and serum levels of MMP-2 to the path physiology of hypertensive disorder of pregnancy.

Keywords: allele specific oligonucleotide polymerase chain reaction (ASO-PCR), enzyme linked immunosorbent assay (ELISA), matrix metalloproteinase-2 (MMP-2), pre-eclampsia

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446 Arteriosclerosis and Periodontitis: Correlation Expressed in the Amount of Fibrinogen in Blood

Authors: Nevila Alliu, Saimir Heta, Ilma Robo, Vera Ostreni

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Periodontitis as an oral pathology caused by specific bacterial flora functions as a focal infection for the onset and aggravation of arteriosclerosis. These two distant pathologies, since they affect organs at a distance from each other, communicate with each other with correlation at the level of markers of inflammation in the blood. Fluctuations in the level of fibrinogen in the blood, depending on the active or passive phase of the existing periodontitis, affect the promotion of arteriosclerosis. The study is of the review type to analyze the effect of non-surgical periodontal treatment on fluctuations in the level of fibrinogen in the blood. The reduction of fibrinogen levels in the blood after non-surgical periodontal treatment of periodontitis in the patient's cavity is visible data and supported by literature sources. Also, the influence of a high amount of fibrinogen in the blood on the occurrence of arteriosclerosis is also another important data that again relies on many sources of literature. Conclusions: Thromboembolism and arteriosclerosis, as risk factors expressed in clinical data, have temporary bacteremia in the blood, which can occur significantly and often between phases of non-surgical periodontal treatment of periodontitis, treatments performed with treatment phases and protocols of predetermined treatment. Arterial thromboembolism has a significant factor, such as high levels of fibrinogen in the blood, which are significantly reduced during the period of non-surgical periodontal treatment.

Keywords: fibrinogen, refractory periodontitis, atherosclerosis, non-surgical, periodontal treatment

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445 Peripheral Inflammation and Neurodegeneration; A Potential for Therapeutic Intervention in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Authors: Lourdes Hanna, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan, Grace Imaguezegie

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Background: Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments. Main body: Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neu-ronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not the same finding. Conclusion: Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.

Keywords: intervention, central nervous system, neurodegeneration, neuroinflammation

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444 Novel Molecular Mechanisms Involved in Macrophage Phenotypic Polarization

Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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443 Anti-Implantation Activity of Kepel (Stelechocarpus burahol) Pulp Ethanol Extract in Female Mice

Authors: Suparmi, Israhnanto Isradji, Dina Fatmawati, Iwang Yusuf

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Kepel (Stelechocarpus burahol) is one of the traditional plants originating from Indonesia that can be used to prevent pregnancy, launched urine and kidney inflammation. Kepel pulp has compounds alkaloid, triterpenoid, tannin, saponin, and flavonoid, when used will give the hormonal and cytotoxic effect. This study was aimed at evaluating ethanol extract of kepel in vivo for anti-implantation activities. In this experimental study with post test only control group design, 20 female mice were randomly divided into 4 groups. It was divided into the control, the 0,65 mg dose, 1,3 mg dose, and 3,6 mg dose of kepel pulp extract group. The extract soluted in DMSO’s solution and was given 1 ml per mice. The extract was given 10 days before copulation until 18 days of pregnancy. Then, the number of implantation, presence of fetus, and embrio resorbtion were recorded and used to calculate the percentage anti-implantation effect. The results were tested by One-way ANOVA. The mean number of implantation in group control, 0,65 mg;1,3 mg; and 2,6 mg were 5,60±1,14; 6,20± 1,64; 7,60±1,51; 8,00± 1,58, respectively. One way Annova test showed that there is no significant difference in the number of implantation between the group (p > 0,05). The administration of kepel pulp ethanol extract had no effect on the percentage anti-implantation effect and the number of and embrio resorbtion.

Keywords: antiimplantation, fetus, Stelechocarpus burahol, flavonoid

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442 Identification of Potential Predictive Biomarkers for Early Diagnosis of Preeclampsia Growth Factors to microRNAs

Authors: Sadia Munir

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Preeclampsia is the contributor to the worldwide maternal mortality of approximately 100,000 deaths a year. It complicates about 10% of all pregnancies and is the first cause of maternal admission to intensive care units. Predicting preeclampsia is a major challenge in obstetrics. More importantly, no major progress has been achieved in the treatment of preeclampsia. As placenta is the main cause of the disease, the only way to treat the disease is to extract placental and deliver the baby. In developed countries, the cost of an average case of preeclampsia is estimated at £9000. Interestingly, preeclampsia may have an impact on the health of mother or infant, beyond the pregnancy. We performed a systematic search of PubMed including the combination of terms such as preeclampsia, biomarkers, treatment, hypoxia, inflammation, oxidative stress, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, microRNAs. In this review, we have summarized current knowledge on the identification of potential biomarkers for the diagnosis of preeclampsia. Although these studies show promising data in early diagnosis of preeclampsia, the current value of these factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Keywords: activin, biomarkers, growth factors, miroRNA

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441 Effects of Local Decongestive Agents at Trachea and Lungs

Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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440 Diagnosis of Gingivitis Based on Correlations of Laser Doppler Data and Gingival Fluid Cytology

Authors: A. V. Belousov, Yakushenko

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One of the main problems of modern dentistry is development a reliable method to detect inflammation in the gums on the stages of diagnosis and assessment of treatment efficacy. We have proposed a method of gingival fluid intake, which successfully combines accessibility, excluding the impact of the annoying and damaging the gingival sulcus factors and provides reliable results (patent of RF№ 2342956 Method of gingival fluid intake). The objects of the study were students - volunteers of Dentistry Faculty numbering 75 people aged 20-21 years. Cellular composition of gingival fluid was studied using microscope "Olympus CX 31" (Japan) with the calculation of epithelial leukocyte index (ELI). Assessment of gingival micro circulation was performed using the apparatus «LAKK–01» (Lazma, Moscow). Cytological investigation noted the highly informative of epithelial leukocyte index (ELI), which demonstrated changes in the mechanisms of protection gums. The increase of ELI occurs during inhibition mechanisms of phagocytosis and activation of epithelial desquamation. The cytological data correlate with micro circulation indicators obtained by laser Doppler flowmetry. We have identified and confirmed the correlations between parameters laser Doppler flowmetry and data cytology gingival fluid in patients with gingivitis.

Keywords: gingivitis, laser doppler flowmetry, gingival fluid cytology, epithelial leukocyte index (ELI)

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439 A General Framework for Knowledge Discovery from Echocardiographic and Natural Images

Authors: S. Nandagopalan, N. Pradeep

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The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, Bayesian, echocardiographic image, feature vector

Procedia PDF Downloads 417
438 The Effect of SIRT1 on NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3) Inflammasome of Osteoarthritis

Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

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The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

Procedia PDF Downloads 173
437 The Role of Vitamin D Supplementation in Augmenting IFN-γ Production in Response to Mycobacterium Tuberculosis Infection: A Randomized Controlled Trial

Authors: Muhammad Imran Hussain, Ramisha Ibtisam, Tayyaba Fatima, Huba Khalid, Ayesha Aziz, Khansa, Adan Sitara, Anam Shahzad, Aymen Jabeen

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Vitamin D supports the immune system fight TB by inhibiting Interferon-gamma (IFN-γ) and lowering host inflammation. The purpose of the research was to see if giving the vitamin D supplements to TB patients affected their prognosis. A randomized placebo control study of 200 TB patients was performed among which 106 received 400,000 IU of injectable vitamin D3 and 94 received placebo for 2 doses. Assessment was carried out at the end of every month for 3 months. IFN-γ responses to whole blood stimulation generated by the Mycobacterium tuberculosis sonicate (MTBs) antigen and early secreted and T cell activated 6 kDa (ESAT6) were assessed at 0 and 12 weeks. The statistical analysis used descriptive statistics (mean and standard deviation), Friedman's test and Fisher's test. The vitamin D group gained significantly more weight (+3.90 pounds) and had less persistent lung disease on imaging (1.33 zones vs. 1.84 zones). They also had a 50% decrease in cavity size. Additionally, patients with low baseline serum concentrations of 25-(OH)D had a significant increase in MTB-induced IFN-γ production after taking vitamin D supplements. Vitamin D administration in large amounts can hasten the recovery of TB patients. The findings point is a therapeutically useful activity of Vitamin D's in the management for tuberculosis.

Keywords: tuberculosis, vitamin D, interferon gamma, protein, infection

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436 The Correlation Between Epicardial Fat Pad and Coronary Artery Disease

Authors: Behnam Shakerian, Negin Razavi

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The pathogenesis of coronary artery disease is multifactorial. The epicardial fat pad is a localized fat depot lying between the myocardium and the visceral layer of the pericardium. The mechanisms through which epicardial fat pad can cause atherosclerosis are complex. The epicardial fat pad can surround the coronary arteries and contributes to the development and progression of coronary artery disease. Methods: we selected 50 patients who underwent coronary artery angiography for the evaluation of coronary artery disease that results were positive for coronary artery disease. All patients underwent an echocardiographic examination after coronary angiography to measure epicardial fat pad thickness. The epicardial fat pad was defined as an echo-free space between the myocardium's outer wall and the pericardium's visceral layer. Results: The epicardial fat pad was measured on the right ventricle apex in 46 patients. Sixty- five percent of the studied patients were male. The most common vessel with stenosis was the left anterior descending artery. A significant correlation was observed between epicardial fat pad thickness and the severity of coronary artery disease. Discussions: The epicardial fat pad provides a horizon on the pathophysiology of cardiovascular diseases. It directly contributes to the development and progression of coronary artery disease by causing inflammation and endothelial damage. Further investigations are needed to determine whether medical treatment can reduce the mass of epicardial fat pad and can help to improve atherosclerosis. Conclusion: The epicardial fat pad measurement could be used as an indicator of coronary arteries’ atherosclerosis. Therefore, thickness measurement of the epicardial fat pad in the clinical practice could be of assistance in identifying patients at risk and if required, undergoing supplementary diagnosis with coronary angiography.

Keywords: epicardial, fat pad, coronary artery disease, echocardiography

Procedia PDF Downloads 134
435 Ethanol Extract of Potentilla pradoxa Nutt Inhibits LPS-induced Inflammatory Responses via NF-κB and AP-1 Inactivation

Authors: Hae-Jun Lee, Ji-Sun Shin, Kyung-Tae Lee

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Potentilla species (Rosasease) have been used in traditional medicine to treat different ailment, disease or malady. In this study, we investigated the anti-inflammatory effects of ethanol extracts of NUTT (EPP) in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages and septic mice. EPP suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-induced Raw 264.7 macrophages. Consistent with these observations, EPP reduced the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by downregulation of their promoter activities. EPP inhibited tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) at production and mRNA levels. Molecularly, EPP attenuated the LPS-induced transcriptional activity, and DNA-binding activity of nuclear factor-κB (NF-κB), and this was associated with a decrease of translocation and phosphorylation of p65 NF-κB by inhibiting the inhibitory κB-α (IκB-α) degradation and IκB kinase-α/β (IKK-α/β) phosphorylation. Furthermore, EPP suppressed the LPS-induced activation of activator protein-1 (AP-1) by reducing the expression of c-Fos and c-Jun in nuclear. EPP also reduced the phosphorylation of mitogen-activated protein kinase (MAPK), such as p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). In a sepsis model, pretreatment with EPP reduced the LPS-induced lethality. Collectively, these results suggest that the anti-inflammatory effects of EPP were associated with the suppression of NF-κB and AP-1 activation, and support its possible therapeutic role for the treatment of sepsis.

Keywords: anti-inflammation, activator protein-1, nuclear factor κB, Potentilla paradoxa Nutt

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434 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease

Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

Procedia PDF Downloads 188