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Cells Mar 2022Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive... (Review)
Review
Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulate a range of functional processes at the cellular, tissue, and systemic levels in healthy humans. Conversely, excess ROS or RNS activity can disrupt function, impairing the performance of daily activities. This article analyzes the impact of redox mechanisms on extreme task performance. Such activities (a) require complex motor skills, (b) are physically demanding, (c) are performed in an extreme environment, (d) require high-level executive function, and (e) pose an imminent risk of injury or death. The current analysis utilizes race car driving as a representative example. The physiological challenges of this extreme task include physical exertion, g loading, vibration, heat exposure, dehydration, noise, mental demands, and emotional factors. Each of these challenges stimulates ROS signaling, RNS signaling, or both, alters redox homeostasis, and exerts pro-oxidant effects at either the tissue or systemic levels. These redox mechanisms appear to promote physiological stress during race car driving and impair the performance of driver athletes.
Topics: Abnormalities, Multiple; Athletes; Cleft Palate; Exophthalmos; Humans; Microcephaly; Osteosclerosis; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 35269521
DOI: 10.3390/cells11050899 -
The Journal of Allergy and Clinical... May 2023Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several...
BACKGROUND
Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown.
OBJECTIVE
To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis.
METHODS
A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis.
RESULTS
Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1β (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases.
CONCLUSIONS
SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.
Topics: Cytokines; Mastocytosis, Systemic; Bone Remodeling; Bone Resorption; Osteosclerosis; Biomarkers; Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged
PubMed: 36801493
DOI: 10.1016/j.jaip.2023.02.007 -
Genes Oct 2022Osteopetrosis (from the Greek "osteo": bone; "petrosis": stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same... (Review)
Review
Osteopetrosis (from the Greek "osteo": bone; "petrosis": stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: "Marble bone disease". Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO-including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called 'Albers-Schonberg' disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a 'Marble Bone Appearance' especially in the ARO type), different metaphyseal alterations/enlargement including the so-called 'Erlenmeyer flask deformity' (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), 'bone in bone' appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and 'rugger-jersey spine' appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.
Topics: Humans; Osteopetrosis; Genes, Dominant; Inheritance Patterns; Radiology; Calcium Carbonate
PubMed: 36360203
DOI: 10.3390/genes13111965 -
Proceedings of the Royal Society of... Jan 1951
Topics: Bones of Lower Extremity; Humans; Leg; Melorheostosis; Tibia
PubMed: 14808238
DOI: No ID Found -
Journal of Medical Genetics Mar 1988
Topics: Bone Diseases, Developmental; Cranial Nerve Diseases; Diagnosis, Differential; Female; Genes, Recessive; Gigantism; Humans; Intracranial Pressure; Male; Nerve Compression Syndromes; Osteopetrosis; Osteosclerosis; Syndrome
PubMed: 3351908
DOI: 10.1136/jmg.25.3.200 -
Proceedings of the Royal Society of... Aug 1972
Topics: Calcium, Dietary; Child; Diet Therapy; Humans; Infant; Male; Osteopetrosis
PubMed: 5085970
DOI: No ID Found -
Analytical Chemistry Jan 2020Osteosclerosis and myefibrosis are complications of myeloproliferative neoplasms. These disorders result in excess growth of trabecular bone and collagen fibers that...
Osteosclerosis and myefibrosis are complications of myeloproliferative neoplasms. These disorders result in excess growth of trabecular bone and collagen fibers that replace hematopoietic cells, resulting in abnormal bone marrow function. Treatments using imatinib and JAK2 pathway inhibitors can be effective on osteosclerosis and fibrosis; therefore, accurate grading is critical for tracking treatment effectiveness. Current grading standards use a four-class system based on analysis of biopsies stained with three histological stains: hematoxylin and eosin (H&E), Masson's trichrome, and reticulin. However, conventional grading can be subjective and imprecise, impacting the effectiveness of treatment. In this Article, we demonstrate that mid-infrared spectroscopic imaging may serve as a quantitative diagnostic tool for quantitatively tracking disease progression and response to treatment. The proposed approach is label-free and provides automated quantitative analysis of osteosclerosis and collagen fibrosis.
Topics: Biopsy; Bone and Bones; Collagen; Disease Progression; Fibrosis; Humans; Osteosclerosis; Spectroscopy, Fourier Transform Infrared
PubMed: 31793292
DOI: 10.1021/acs.analchem.9b03015 -
Journal of Bone and Mineral Research :... Apr 2021Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of...
Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b ) mice. Although male and female Mpig6b mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b mice developed progressive splenomegaly starting at 8 weeks of age. Micro-computed tomography (μCT) of femurs showed that female Mpig6b mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16 weeks. Ovariectomy of 10-week-old female Mpig6b mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Bone and Bones; Female; Humans; Male; Megakaryocytes; Mice; Osteosclerosis; Ovariectomy; Primary Myelofibrosis; X-Ray Microtomography
PubMed: 33434328
DOI: 10.1002/jbmr.4245 -
Medicina 2023
Topics: Humans; Osteopoikilosis; Incidental Findings; Radiography
PubMed: 38117729
DOI: No ID Found -
Indian Pediatrics Jun 2007
Topics: Child; Diagnosis, Differential; Female; Humans; Melorheostosis
PubMed: 17620703
DOI: No ID Found