Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoriasis is a skin disease typically presenting with sharply demarcated, inflammatory, erythematous plaques with characteristic silver-white scaling due to epidermal hyperproliferation and parakeratosis secondary to the inflammation. The name derives from pisigmaomicronrhoalpha (mange or scabies), and in ancient times the disease was confused with leprosy resulting in expulsion from society. Hence, both itching and social stigmatization are major problems affecting patients with psoriasis. Today, psoriasis is recognized as a genetically determined, autoimmune, T cell mediated systemic disease manifesting on the skin, nails and joints and associated with a number of co-morbidities. Accordingly, therapeutic strategies are antiinflammatory, antiproliferative and keratolytic. The extent and severity of disease (PASI), impairment of life quality (DLQI), and affected anatomic regions (inverse, palmoplantar, nails) as well as co-morbidities (arthritis, metabolic syndrome, cardiovascular disease, depression) determine the therapy. In 80 % of cases psoriasis is mild or moderate and sufficiently treated with topical corticosteroids, vitamin D-analogues, and phototherapy. 20 % of patients suffer from severe psoriasis, necessitating systemic drugs such as acitretin, methotrexate, ciclosporin A or the newer biologic agents. Especially in severe psoriasis, psychological strain, co-morbidities, and medico-economic aspects must be taken into account.
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PMID:[Psoriasis]. 2033 15

This paper describes a case of pruritus caused by dysmetabolic hyperferritinemia treated by multiple phlebotomies. A 63-year-old man was followed for generalized pruritus, which was resistant to the usual treatments. He presented with metabolic syndrome. Physical examination showed only excoriations and lichenification on the skin. The serum ferritin was high at 1043 ng/ml, with transferrin saturation at 67%. The other biological investigations and genetic tests for hemochromatosis were negative. In spite of the dietary measures, the ferritin level was still high (853 ng/ml). Magnetic resonance imaging confirmed hepatic iron overload.The association of hyperferritinemia, hepatic iron overload, and metabolic syndrome led to the diagnosis of dysmetabolic hyperferritinemia. Phlebotomies are an unusual treatment, but because the pruritus and hyperferritinemia were still present, phlebotomy was initiated. After 19 months, the patient reported improvement of his pruritus and normalization of ferritin levels.
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PMID:Generalized pruritus in dysmetabolic hyperferritinemia treated by phlebotomy. 2643 95

Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic lesions, and psoriatic arthritis (PsA) in about 30% of cases. Psoriasis is associated with multiple comorbidities including metabolic syndrome, hypertension, diabetes, cardiovascular events, obesity and psychiatric disorders, which can all affect the course of sleep disorders. A systematic review of the literature on the relationship between psoriasis, PsA, and formal sleep disorders identified 33 studies. There is an increased prevalence of obstructive sleep apnea (OSA) with 36%-81.8% prevalence in psoriasis versus 2%-4% in the general population. There was also an increase in the prevalence of restless legs syndrome of 15.1%-18% in psoriasis versus 5%-10% in European and North American samples. The wide variety of insomnia criteria used in studies resulted in an insomnia prevalence of 5.9%-44.8% in psoriasis, which is insufficient to show an elevated prevalence when the general population has a 10% prevalence of chronic insomnia and 30-35% prevalence of transient insomnia. There is evidence that symptoms of insomnia in psoriasis are directly mediated by pruritus and pain. Treatments that decrease the cutaneous symptoms in psoriasis were successful in mitigating insomnia, but did not show improvements in OSA where the relationship with psoriasis is multifactorial.
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PMID:Psoriasis and sleep disorders: A systematic review. 2662 28

Dietary sphingolipids such as glucosylceramide (GlcCer) are potential nutritional factors associated with prevention of metabolic syndrome. Our current understanding is that dietary GlcCer is degraded to ceramide and further metabolized to sphingoid bases in the intestine. However, ceramide is only found in trace amounts in food plants and thus is frequently taken as GlcCer in a health supplement. In the present study, we successfully prepared konjac ceramide (kCer) using endoglycoceramidase I (EGCase I). Konjac, a plant tuber, is an enriched source of GlcCer (kGlcCer), and has been commercialized as a dietary supplement to improve dry skin and itching that are caused by a deficiency of epidermal ceramide. Nerve growth factor (NGF) produced by skin cells is one of the itch factors in the stratum corneum of the skin. Semaphorin 3A (Sema 3A) has been known to inhibit NGF-induced neurite outgrowth of epidermal nerve fibers. It is well known that the itch sensation is regulated by the balance between NGF and Sema 3A. In the present study, while kGlcCer did not show an in vitro inhibitory effect on NGF-induced neurite outgrowth of PC12 cells, kCer was demonstrated to inhibit a remarkable neurite outgrowth. In addition, the effect of kCer was similar to that of Sema 3A in cell morphological changes and neurite retractions, but different from C2-Ceramide. kCer showed a Sema 3A-like action, causing CRMP2 phosphorylation, which results in a collapse of neurite growth cones. Thus, it is expected that kCer is an advanced konjac ceramide material that may have neurite outgrowth-specific action to relieve uncontrolled and serious itching, in particular, from atopic eczema.
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PMID:Chemoenzymatically prepared konjac ceramide inhibits NGF-induced neurite outgrowth by a semaphorin 3A-like action. 2895 19

Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC). LPA has diverse pleiotropic effects in the central nervous system (CNS) and other tissues via the activation of a family of six cognate G protein-coupled receptors. These LPA receptors (LPARs) are expressed in some combination in all known cell types in the CNS where they mediate such fundamental cellular processes as proliferation, differentiation, migration, chronic inflammation, and cytoskeletal organization. As a result, dysregulation of LPA content may contribute to many CNS and PNS disorders such as chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer's disease, metabolic syndrome-induced brain damage, traumatic brain injury, hepatic encephalopathy-induced cerebral edema, macular edema, major depressive disorder, stress-induced psychiatric disorder, alcohol-induced brain damage, HIV-induced brain injury, pruritus, and peripheral nerve injury. ATX activity is now known to be the primary biological source of this bioactive signaling lipid, and as such, represents a potentially high-value drug target. There is currently one ATX inhibitor entering phase III clinical trials, with several additional preclinical compounds under investigation. This review discusses the physiological and pathological significance of the ATX-LPA-LPA receptor signaling axis and summarizes the evidence for targeting this pathway for the treatment of CNS diseases.
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PMID:Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. 3136 25

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients' quality of life. It is characterized by recurrent painful nodules, abscesses and draining sinus tracts in primarily intertriginous areas. We aimed to review the most up-to-date information regarding the epidemiology, clinical presentation, diagnostic studies, pathogenesis, comorbidities and quality of life of patients with hidradenitis suppurativa. We performed a systematic search of Medline, Embase database (from inception to September 2019) and review of bibliographies without restrictions on year or language. HS has an estimated global prevalence of 0.00033-4.1% (but most likely 0.7-1.2% in the European-US population). Patients still experience a significant diagnostic delay, up to several years. In the absence of pathognomonic tests, the diagnosis of HS is made from clinical observation and the disease narrative. Phenotypic variation renders diagnosis and severity assessment difficult. Ultrasound imaging is an emerging assessment tool for deep-seated lesions. The Hurley Staging System is still widely used in severity rating. Follicular hyperkeratosis and dilatation, follicular rupture and chronic inflammation with architectural tissue changes have been implicated in the pathogenesis of HS. HS has been associated with metabolic syndrome and other risk factors for cardiovascular disease, diabetes mellitus type II, polycystic ovarian syndrome, depression, suicide and substance use disorders. It has been linked to other immune-mediated diseases such as inflammatory bowel disease and spondyloarthropathy. Pain, pruritus, malodour, low self-esteem, sleep and sexual dysfunctions, and poor mental health are chronic symptoms or consequences of uncontrolled disease. HS is an under-diagnosed and under-treated disease with a profound negative impact on patients' quality of life. In the light of its associated comorbidities, an interdisciplinary management approach may be needed to ensure the best outcomes.
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PMID:Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life. 3246 Mar 74