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Mitochondrion May 2014The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical,... (Review)
Review
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.
Topics: Brain; Disease; Energy Metabolism; Health; Homeostasis; Humans; Metabolic Networks and Pathways; Mitochondria; Stress, Physiological
PubMed: 23981537
DOI: 10.1016/j.mito.2013.08.006 -
Journal of Clinical Periodontology May 2002Periodontal diseases are among the most frequent diseases affecting children and adolescents. These include gingivitis, localized or generalized aggressive periodontitis... (Review)
Review
BACKGROUND
Periodontal diseases are among the most frequent diseases affecting children and adolescents. These include gingivitis, localized or generalized aggressive periodontitis (a.k.a., early onset periodontitis which includes generalized or localized prepubertal periodontitis and juvenile periodontitis) and periodontal diseases associated with systemic disorders. The best approach to managing periodontal diseases is prevention, followed by early detection and treatment.
METHODS
This paper reviews the current literature concerning the most common periodontal diseases affecting children: chronic gingivitis (or dental plaque-induced gingival diseases) and early onset periodontitis (or aggressive periodontitis), including prepubertal and juvenile periodontitis. In addition, systemic diseases that affect the periodontium and oral lesions commonly found in young children are addressed. The prevalence, diagnostic characteristics, microbiology, host-related factors, and therapeutic management of each of these disease entities are thoroughly discussed.
Topics: Adolescent; Age Factors; Aggressive Periodontitis; Candidiasis, Oral; Cheilitis; Child; Child, Preschool; Chronic Disease; Dental Plaque; Diabetes Mellitus, Type 1; Disease; Gingival Overgrowth; Gingivitis; Glossitis, Benign Migratory; HIV Infections; Humans; Hypophosphatasia; Periodontal Diseases; Puberty; Stomatitis, Aphthous; Stomatitis, Herpetic
PubMed: 12060422
DOI: 10.1034/j.1600-051x.2002.290504.x -
Clinical Medicine (London, England) May 2023Catatonia is a severe neuropsychiatric syndrome that affects emotion, speech, movement and complex behaviour. It can occur in a wide range of psychiatric and...
Catatonia is a severe neuropsychiatric syndrome that affects emotion, speech, movement and complex behaviour. It can occur in a wide range of psychiatric and neurological conditions, including depression, mania, schizophrenia, autism, autoimmune encephalitis (particularly NMDAR encephalitis), systemic lupus erythematosus, thyroid disease, epilepsy and medication-induced and -withdrawal states. This concise guideline highlights key recommendations from the British Association for Psychopharmacology (BAP) Catatonia Guideline, published in April 2023. Important investigations may include neuroimaging, electroencephalography and assessment for neuronal autoantibodies in serum and cerebrospinal fluid. First-line treatment comprises benzodiazepines and/or electroconvulsive therapy. The benzodiazepine of choice is lorazepam, which is sometimes used in very high doses. Multidisciplinary working between psychiatrists and physicians is often essential. The main limitation of the guidelines is the low quality of the underlying evidence, comprising mainly small observational studies and case reports or series.
Topics: Humans; Benzodiazepines; Catatonia; Electroconvulsive Therapy; Nervous System Diseases; Syndrome
PubMed: 37236789
DOI: 10.7861/clinmed.2023-0113 -
Nature Reviews. Neuroscience Jan 2008In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the... (Review)
Review
In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
Topics: Animals; Brain; Cytokines; Depression; Disease; Humans; Immune System; Inflammation
PubMed: 18073775
DOI: 10.1038/nrn2297 -
Medical Science Monitor : International... Aug 2012Ocular ischemic syndrome is a rare condition, which is caused by ocular hypoperfusion due to stenosis or occlusion of the common or internal carotid arteries.... (Review)
Review
Ocular ischemic syndrome is a rare condition, which is caused by ocular hypoperfusion due to stenosis or occlusion of the common or internal carotid arteries. Atherosclerosis is the major cause of changes in the carotid arteries. Ocular ischemic syndrome is manifested as visual loss, orbital pain and, frequently, changes of the visual field, and various anterior and posterior segment signs. Anterior segment signs include iris neovascularization and secondary neovascular glaucoma, iridocyclitis, asymmetric cataract, iris atrophy and sluggish reaction to light. Posterior eye segment changes are the most characteristic, such as narrowed retinal arteries, perifoveal telangiectasias, dilated retinal veins, mid-peripheral retinal hemorrhages, microaneurysms, neovascularization at the optic disk and in the retina, a cherry-red spot, cotton-wool spots, vitreous hemorrhage and normal-tension glaucoma. Differential diagnosis of ocular ischemic syndrome includes diabetic retinopathy and moderate central retinal vein occlusion. Carotid artery imaging and fundus fluorescein angiography help to establish the diagnosis of ocular ischemic syndrome. The treatment can be local, for example, ocular (conservative, laser and surgical) or systemic (conservative and surgical treatment of the carotid artery). Since the condition does not affect the eyes alone, patients with ocular ischemic syndrome should be referred for consultation to the neurologist, vascular surgeon and cardiologist.
Topics: Animals; Diagnosis, Differential; Eye; Eye Diseases; Humans; Ischemia; Syndrome
PubMed: 22847215
DOI: 10.12659/msm.883260 -
Drugs & Aging Oct 2019Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a... (Review)
Review
Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a result of the loss of sex steroids that occurs with menopause. It is a progressive condition that does not resolve without treatment and can adversely affect a woman's quality of life. For a variety of reasons, many symptomatic women do not seek treatment and, of those who do, many are unhappy with their options. Additionally, many healthcare providers do not actively screen their menopausal patients for the symptoms of genitourinary syndrome of menopause. In this review, we discuss the clinical presentation of genitourinary syndrome of menopause as well as the treatment guidelines recommended by the major societies engaged in women's health. This is followed by a review of available treatment options that includes both hormonal and non-hormonal therapies. We discuss both the systemic and vaginal estrogen products that have been available for decades and remain important treatment options for patients; however, a major intent of the review is to provide information on the newer, non-estrogen pharmacologic treatment options, in particular oral ospemifene and vaginal prasterone. A discussion of adjunctive therapies such as moisturizers, lubricants, physical therapy/dilators, hyaluronic acid, and laser therapy is included. We also address some of the available data on both the patient and healthcare providers perspectives on treatment, including cost, and touch briefly on the topic of treating women with a history of, or at high risk for, breast cancer.
Topics: Estrogen Replacement Therapy; Female; Female Urogenital Diseases; Humans; Menopause; Quality of Life; Randomized Controlled Trials as Topic; Syndrome; Women's Health
PubMed: 31452067
DOI: 10.1007/s40266-019-00700-w -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2014The aim of this study was to review the current scientific literature in order to analyse the indications and contraindications of dental implants in medically... (Review)
Review
The aim of this study was to review the current scientific literature in order to analyse the indications and contraindications of dental implants in medically compromised patients. A reference research was carried out on PubMed using the key words "implant" AND (oral OR dental) AND (systemic disease OR medically compromised), in articles published between 1993 and 2013. The inclusion criteria were the following: clinical studies in which, at least, 10 patients were treated, consensus articles, reviewed articles and meta-analysis performed in humans treated with dental implants, and which included the disease diagnosis. A total of 64 articles were found, from which 16 met the inclusion criteria. Cardiac systemic diseases, diabetic endocrine pathologies or controlled metabolic disorders do not seem to be a total or partial contraindication to the placement of dental implants. Tobacco addiction, and head and neck radiotherapy are correlated to a higher loss of dental implants. Patients suffering from osteoporosis undergoing biphosphonates therapy show an increased risk of developing bone necrosis after an oral surgery, especially if the drugs are administered intravenously or they are associated to certain concomitant medication.
Topics: Contraindications; Dental Implants; Disease; Humans; Risk Factors
PubMed: 24608222
DOI: 10.4317/medoral.19565 -
Frontiers in Immunology 2023Sepsis is a hyper-heterogeneous syndrome in which the systemic inflammatory response persists throughout the course of the disease and the inflammatory and immune... (Review)
Review
Sepsis is a hyper-heterogeneous syndrome in which the systemic inflammatory response persists throughout the course of the disease and the inflammatory and immune responses are dynamically altered at different pathogenic stages. Gasdermins (GSDMs) proteins are pore-forming executors in the membrane, subsequently mediating the release of pro-inflammatory mediators and inflammatory cell death. With the increasing research on GSDMs proteins and sepsis, it is believed that GSDMs protein are one of the most promising therapeutic targets in sepsis in the future. A more comprehensive and in-depth understanding of the functions of GSDMs proteins in sepsis is important to alleviate the multi-organ dysfunction and reduce sepsis-induced mortality. In this review, we focus on the function of GSDMs proteins, the molecular mechanism of GSDMs involved in sepsis, and the regulatory mechanism of GSDMs-mediated signaling pathways, aiming to provide novel ideas and therapeutic strategies for the diagnosis and treatment of sepsis.
Topics: Humans; Gasdermins; Sepsis; Cell Death; Inflammation Mediators; Syndrome
PubMed: 38022612
DOI: 10.3389/fimmu.2023.1203687 -
Developmental Biology Sep 2017DNA degradation is critical to healthy organism development and survival. Two nuclease families that play key roles in development and in disease are the Dnase1 and... (Review)
Review
DNA degradation is critical to healthy organism development and survival. Two nuclease families that play key roles in development and in disease are the Dnase1 and Dnase2 families. While these two families were initially characterized by biochemical function, it is now clear that multiple enzymes in each family perform similar, non-redundant roles in many different tissues. Most Dnase1 and Dnase2 family members are poorly characterized, yet their elimination can lead to a wide range of diseases, including lethal anemia, parakeratosis, cataracts and systemic lupus erythematosus. Therefore, understanding these enzyme families represents a critical field of emerging research. This review explores what is currently known about Dnase1 and Dnase2 family members, highlighting important questions about the structure and function of family members, and how their absence translates to disease.
Topics: Animals; Deoxyribonucleases; Disease; Health; Humans; Organ Specificity
PubMed: 28666955
DOI: 10.1016/j.ydbio.2017.06.028 -
Microbiome Oct 2020Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal...
BACKGROUND
Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.
RESULTS
This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features.
CONCLUSIONS
These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Video Abstract.
Topics: Adult; Aged; Animals; Case-Control Studies; Disease; Female; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lupus Erythematosus, Systemic; Male; Middle Aged
PubMed: 33032658
DOI: 10.1186/s40168-020-00923-9