Journal of Clinical Medicine

3594 KiB

Open AccessFeature PaperReview

The Role of Interleukin-18, Oxidative Stress and Metabolic Syndrome in Alzheimer’s Disease

by Johanna O. Ojala and Elina M. Sutinen

J. Clin. Med. 2017, 6(5), 55; https://doi.org/10.3390/jcm6050055 - 21 May 2017

Cited by 43 | Viewed by 12216

The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer’s disease (AD), requires further clarification. In addition to neuropathological hallmarks—extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss—chronic inflammation, as well as [...] Read more.

The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer’s disease (AD), requires further clarification. In addition to neuropathological hallmarks—extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss—chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation. The brain is particularly sensitive to OS, due to the richness of its peroxidation-sensitive fatty acids, coupled with its high oxygen demand. At the same time, the brain lack robust antioxidant systems. Among the multiple mechanisms and triggers by which OS can accumulate, inflammatory cytokines can sustain oxidative and nitrosative stress, leading eventually to cellular damage. Understanding the consequences of inflammation and OS may clarify the initial events underlying AD, including in interaction with genetic factors. Inflammatory cytokines are potential inducers of aberrant gene expression through transcription factors. Susceptibility disorders for AD, including obesity, type-2 diabetes, cardiovascular diseases and metabolic syndrome have been linked to increases in the proinflammatory cytokine, IL-18, which also regulates multiple AD related proteins. The association of IL-18 with AD and AD-linked medical conditions are reviewed in the article. Such data indicates that an active lifestyle, coupled to a healthy diet can ameliorate inflammation and reduce the risk of sporadic AD. Full article

(This article belongs to the Special Issue The Role of Oxidant Stress in Disease)

► Show Figures

Figure 1

239 KiB

Open AccessFeature PaperReview

Hemophilia Care in the Pediatric Age

by Marta Bertamino, Francesca Riccardi, Laura Banov, Johanna Svahn and Angelo Claudio Molinari

J. Clin. Med. 2017, 6(5), 54; https://doi.org/10.3390/jcm6050054 - 19 May 2017

Cited by 41 | Viewed by 15204

Abstract

Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should [...] Read more.

Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures—for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care. Full article

(This article belongs to the Special Issue Outstanding Advances in Hemophilia Therapies)

2245 KiB

Open AccessReview

The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart

by Kate M. Herum, Ida G. Lunde, Andrew D. McCulloch and Geir Christensen

J. Clin. Med. 2017, 6(5), 53; https://doi.org/10.3390/jcm6050053 - 19 May 2017

Cited by 131 | Viewed by 24309

Abstract

Cardiac fibrosis, the excessive accumulation of extracellular matrix (ECM), remains an unresolved problem in most forms of heart disease. In order to be successful in preventing, attenuating or reversing cardiac fibrosis, it is essential to understand the processes leading to ECM production and [...] Read more.

Cardiac fibrosis, the excessive accumulation of extracellular matrix (ECM), remains an unresolved problem in most forms of heart disease. In order to be successful in preventing, attenuating or reversing cardiac fibrosis, it is essential to understand the processes leading to ECM production and accumulation. Cardiac fibroblasts are the main producers of cardiac ECM, and harbor great phenotypic plasticity. They are activated by the disease-associated changes in mechanical properties of the heart, including stretch and increased tissue stiffness. Despite much remaining unknown, an interesting body of evidence exists on how mechanical forces are translated into transcriptional responses important for determination of fibroblast phenotype and production of ECM constituents. Such mechanotransduction can occur at multiple cellular locations including the plasma membrane, cytoskeleton and nucleus. Moreover, the ECM functions as a reservoir of pro-fibrotic signaling molecules that can be released upon mechanical stress. We here review the current status of knowledge of mechanotransduction signaling pathways in cardiac fibroblasts that culminate in pro-fibrotic gene expression. Full article

(This article belongs to the Special Issue Signaling Pathways in Organ Fibrosis)

► Show Figures

Graphical abstract

1593 KiB

Open AccessFeature PaperReview

Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases

by Tamilarasan Udhayabanu, Andreea Manole, Mohan Rajeshwari, Perumal Varalakshmi, Henry Houlden and Balasubramaniem Ashokkumar

J. Clin. Med. 2017, 6(5), 52; https://doi.org/10.3390/jcm6050052 - 5 May 2017

Cited by 83 | Viewed by 16073

Abstract

Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on [...] Read more.

Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin. Riboflavin regulates the structure and function of flavoenzymes through its cofactors FMN and FAD and, thus, protects the cells from oxidative stress and apoptosis. Hence, it is not surprising that any disturbance in riboflavin metabolism and absorption of this vitamin may have consequences on cellular FAD and FMN levels, resulting in mitochondrial dysfunction by reduced energy levels, leading to riboflavin associated disorders, like cataracts, neurodegenerative and cardiovascular diseases, etc. Furthermore, mutations in either nuclear or mitochondrial DNA encoding for flavoenzymes and flavin transporters significantly contribute to the development of various neurological disorders. Moreover, recent studies have evidenced that riboflavin supplementation remarkably improved the clinical symptoms, as well as the biochemical abnormalities, in patients with neuronopathies, like Brown-Vialetto-Van-Laere syndrome (BVVLS) and Fazio-Londe disease. This review presents an updated outlook on the cellular and molecular mechanisms of neurodegenerative disorders in which riboflavin deficiency leads to dysfunction in mitochondrial energy metabolism, and also highlights the significance of riboflavin supplementation in aforementioned disease conditions. Thus, the outcome of this critical assessment may exemplify a new avenue to enhance the understanding of possible mechanisms in the progression of neurodegenerative diseases and may provide new rational approaches of disease surveillance and treatment. Full article

(This article belongs to the Special Issue Current Strategies for the Biochemical Diagnosis and Monitoring of Mitochondrial Disease)

► Show Figures

Figure 1

476 KiB

Open AccessFeature PaperReview

Role of Autoantibodies in the Diagnosis of Connective-Tissue Disease ILD (CTD-ILD) and Interstitial Pneumonia with Autoimmune Features (IPAF)

by Adelle S. Jee, Stephen Adelstein, Jane Bleasel, Gregory J. Keir, MaiAnh Nguyen, Joanne Sahhar, Peter Youssef and Tamera J. Corte

J. Clin. Med. 2017, 6(5), 51; https://doi.org/10.3390/jcm6050051 - 4 May 2017

Cited by 60 | Viewed by 13582

Abstract

The diagnosis of interstitial lung disease (ILD) requires meticulous evaluation for an underlying connective tissue disease (CTD), with major implications for prognosis and management. CTD associated ILD (CTD-ILD) occurs most commonly in the context of an established CTD, but can be the first [...] Read more.

The diagnosis of interstitial lung disease (ILD) requires meticulous evaluation for an underlying connective tissue disease (CTD), with major implications for prognosis and management. CTD associated ILD (CTD-ILD) occurs most commonly in the context of an established CTD, but can be the first and/or only manifestation of an occult CTD or occur in patients who have features suggestive of an autoimmune process, but not meeting diagnostic criteria for a defined CTD—recently defined as “interstitial pneumonia with autoimmune features” (IPAF). The detection of specific autoantibodies serves a critical role in the diagnosis of CTD-ILD, but there remains a lack of data to guide clinical practice including which autoantibodies should be tested on initial assessment and when or in whom serial testing should be performed. The implications of detecting autoantibodies in patients with IPAF on disease behaviour and management remain unknown. The evaluation of CTD-ILD is challenging due to the heterogeneity of presentations and types of CTD and ILD that may be encountered, and thus it is imperative that immunologic tests are interpreted in conjunction with a detailed rheumatologic history and examination and multidisciplinary collaboration between respiratory physicians, rheumatologists, immunologists, radiologists and pathologists. Full article

(This article belongs to the Special Issue Chronic Respiratory Diseases)

► Show Figures

Figure 1

250 KiB

Open AccessReview

Glutathione as a Redox Biomarker in Mitochondrial Disease—Implications for Therapy

by Gregory M. Enns and Tina M. Cowan

J. Clin. Med. 2017, 6(5), 50; https://doi.org/10.3390/jcm6050050 - 3 May 2017

Cited by 67 | Viewed by 9225

Abstract

Technical advances in the ability to measure mitochondrial dysfunction are providing new insights into mitochondrial disease pathogenesis, along with new tools to objectively evaluate the clinical status of mitochondrial disease patients. Glutathione (l-ϒ-glutamyl-l-cysteinylglycine) is the most abundant intracellular thiol, [...] Read more.

Technical advances in the ability to measure mitochondrial dysfunction are providing new insights into mitochondrial disease pathogenesis, along with new tools to objectively evaluate the clinical status of mitochondrial disease patients. Glutathione (l-ϒ-glutamyl-l-cysteinylglycine) is the most abundant intracellular thiol, and the intracellular redox state, as reflected by levels of oxidized (GSSG) and reduced (GSH) glutathione, as well as the GSH/GSSG ratio, is considered to be an important indication of cellular health. The ability to quantify mitochondrial dysfunction in an affected patient will not only help with routine care, but also improve rational clinical trial design aimed at developing new therapies. Indeed, because multiple disorders have been associated with either primary or secondary deficiency of the mitochondrial electron transport chain and redox imbalance, developing mitochondrial therapies that have the potential to improve the intracellular glutathione status has been a focus of several clinical trials over the past few years. This review will also discuss potential therapies to increase intracellular glutathione with a focus on EPI-743 (α-tocotrienol quinone), a compound that appears to have the ability to modulate the activity of oxidoreductases, in particular NAD(P)H:quinone oxidoreductase 1. Full article

(This article belongs to the Special Issue Current Strategies for the Biochemical Diagnosis and Monitoring of Mitochondrial Disease)

224 KiB

Open AccessArticle

Serum Profiles of Cytokines in Behcet’s Disease

by Alireza Sadeghi, Fereydoun Davatchi, Farhad Shahram, Arezoo Karimimoghadam, Majid Alikhani, Aiyoub Pezeshgi, Saeideh Mazloomzadeh, Bahar Sadeghi-Abdollahi and Masoud Asadi-Khiavi

J. Clin. Med. 2017, 6(5), 49; https://doi.org/10.3390/jcm6050049 - 2 May 2017

Cited by 17 | Viewed by 4948

Abstract

Introduction: Behcet’s disease (BD) is a chronic systemic autoinflammatory vasculitis which is handled by the variety of proteins like cytokines. Therefore, cytokines are considered as one of the prototypic factors during inflammatory responses of BD. Consequently, the present study was designed for evaluation [...] Read more.

Introduction: Behcet’s disease (BD) is a chronic systemic autoinflammatory vasculitis which is handled by the variety of proteins like cytokines. Therefore, cytokines are considered as one of the prototypic factors during inflammatory responses of BD. Consequently, the present study was designed for evaluation of cytokine profiles in Iranian BD cases, including those with and without uveitis. Materials and Method: All cases were divided into three groups based on ophthalmologic exam results: BD with uveitis, BD without uveitis, and recovered uveitis BD. Cases with a history of BD recovery were placed in the group of recovered uveitis. The patients with infectious uveitis as well as other collagen vascular diseases and patients who have used biologics to treat ocular immune-mediated diseases were excluded. Finally, after venous blood sampling, levels of cytokines were quantified and statistical approaches were performed for measurements. Results: Enrolled cases were divided to 26 patients with active uveitis, 25 patients with recovered uveitis and 24 patients without uveitis and interestingly, just IL-2 was the only cytokine that showed statistical difference in patients with BD uveitis in comparison with other groups (p_value = 0.02). The pair wise comparison showed a significant difference between the patients with and without uveitis groups (p_value = 0.004) as well as patients with uveitis and recovered uveitis groups (p_value = 0.002). Discussion: Significant elevation of IL-2 in patients with uveitis (in comparison with recovered or without uveitis cases) demonstrates that it may be one of the main proteins that enroll in the pathophysiology of BD uveitis and may be considered as a new target for refractory disease therapies. Studies with larger samples can help to obtain more accurate conclusions. Full article

345 KiB

Open AccessReview

Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension

by Kazufumi Nakamura, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Norifumi Kawakita, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Nobuhiro Nishii and Hiroshi Ito

J. Clin. Med. 2017, 6(5), 48; https://doi.org/10.3390/jcm6050048 - 29 Apr 2017

Cited by 24 | Viewed by 6603

Abstract

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor [...] Read more.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor tyrosine kinase inhibitor) -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of pulmonary arterial hypertension (PAH) and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for the treatment of PAH. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Clin. Med., Volume 6, Issue 5 (May 2017) – 8 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI