Chronic Nonbacterial Osteomyelitis: Pathophysiological Concepts and Current Treatment Strategies

2016 ◽  
Vol 43 (11) ◽  
pp. 1956-1964 ◽  
Author(s):  
Sigrun R. Hofmann ◽  
Anja Schnabel ◽  
Angela Rösen-Wolff ◽  
Henner Morbach ◽  
Hermann J. Girschick ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Chronic Recurrent Multifocal Osteomyelitis ◽  
Current Treatment ◽  
Multifocal Osteomyelitis ◽  
The One ◽  
Molecular Pathophysiology ◽  
Bone Inflammation ◽  
Chronic Nonbacterial Osteomyelitis

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, covering a clinical spectrum with asymptomatic inflammation of single bones at the one end, and chronic recurrent multifocal osteomyelitis (CRMO) at the other end. The exact molecular pathophysiology of CNO remains largely unknown. Provided familial clusters and the association with inflammatory disorders of the skin and intestine suggest a genetic predisposition. Recently, profound dysregulation of cytokine responses was demonstrated in CRMO. Failure to produce antiinflammatory cytokines interleukin (IL)-10 and IL-19 contributes to activation of inflammasomes and subsequent IL-1β release. In IL-10–deficient and in CNO-prone chronic multifocal osteomyelitis mice, IL-1β was linked to bone inflammation. Further, alterations to the gut microbiome were suggested in contributing to IL-1β release from innate immune cells in mice, offering an interesting target in the search for molecular mechanisms in CNO. Here, we summarize clinical presentation and treatment options in CNO/CRMO, current pathophysiological concepts, available mouse models, and promising future scientific directions.

scholarly journals Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1548
Author(s):  
Mustafa N. Mithaiwala ◽  
Danielle Santana-Coelho ◽  
Grace A. Porter ◽  
Jason C. O’Connor
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Kynurenine Pathway ◽  
Economic Problem ◽  
Cns Disease ◽  
Therapeutic Implications ◽  
Efficacious Treatment ◽  
The Central Nervous System ◽  
Significant Health

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

scholarly journals Pharmacological Interventions for Pulmonary Involvement in Rheumatic Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 251 ◽  
Author(s):  
Eun Ha Kang ◽  
Yeong Wook Song
Keyword(s):  
Rheumatic Diseases ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Pulmonary Involvement ◽  
Current Treatment ◽  
Targeted Agents ◽  
Pharmacological Interventions ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Epidemiologic Features

Among the diverse forms of lung involvement, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are two important conditions in patients with rheumatic diseases that are associated with significant morbidity and mortality. The management of ILD and PAH is challenging because the current treatment often provides only limited patient survival benefits. Such challenges derive from their common pathogenic mechanisms, where not only the inflammatory processes of immune cells but also the fibrotic and proliferative processes of nonimmune cells play critical roles in disease progression, making immunosuppressive therapy less effective. Recently, updated treatment strategies adopting targeted agents have been introduced with promising results in clinical trials for ILD ad PAH. This review discusses the epidemiologic features of ILD and PAH among patients with rheumatic diseases (rheumatoid arthritis, myositis, and systemic sclerosis) and the state-of-the-art treatment options, focusing on targeted agents including biologics, antifibrotic agents, and vasodilatory drugs.

scholarly journals Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 202 ◽  
Author(s):  
Sonia Vallet ◽  
Julia-Marie Filzmoser ◽  
Martin Pecherstorfer ◽  
Klaus Podar
Keyword(s):  
Bone Disease ◽  
Molecular Mechanisms ◽  
Bone Fractures ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Nf Kappa B ◽  
Skeletal Involvement ◽  
Myeloma Bone Disease ◽  
Skeletal Related Events ◽  
Novel Treatment Strategies

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients’ quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the mainstay to prevent skeletal-related events in MM for almost two decades. Excitingly, the most recent approval of the receptor activator of NF-kappa B ligand (RANKL) inhibitor, denosumab, expanded treatment options for MBD, for patients with compromised renal function, in particular. In addition, several other bone-targeting agents, including bone anabolic drugs, are currently in preclinical and early clinical assessment. This review summarizes our up-to-date knowledge on the pathogenesis of MBD and discusses novel state-of-the-art treatment strategies that are likely to enter clinical practice in the near future.

scholarly journals Cannabis and epilepsy

2018 ◽  
Vol 18 (6) ◽  
pp. 465-471 ◽  
Author(s):  
Rhys H Thomas ◽  
Mark O Cunningham
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
High Profile ◽  
High Street ◽  
The Usa ◽  
The Difference ◽  
The One ◽  
The Uk ◽  
Genetic Epilepsies ◽  
Trial Evidence

Click here to listen to the PodcastThe one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics. The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis. It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence. In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.

scholarly journals Vulpinic Acid as a Natural Compound Inhibits the Proliferation of Metastatic Prostate Cancer Cell by Inducing Apoptosis

2021 ◽  
Author(s):  
Demet Cansaran Duman ◽  
Gamze Guney Eskiler ◽  
Betül Çolak ◽  
Elif Sozen Kucukkara
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Annexin V ◽  
Current Treatment ◽  
Pcr Analysis ◽  
G1 Arrest ◽  
Advanced Analysis ◽  
Induced Apoptosis

Abstract Lichen secondary metabolites have drawn considerable attention in recent years due to limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. After identification of the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effect through G0/G1 arrest, nuclear bleebing and the activation of particularly initiator caspases. Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further performed.

Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Dopamine Metabolism ◽  
Dopaminergic Agonists ◽  
Alternative Drug ◽  
Synthetic Agents ◽  
Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

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