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Dermatologie (Heidelberg, Germany) Jul 2023
Topics: Humans; Pellagra; Skin Diseases; Skin; Mental Disorders
PubMed: 37166459
DOI: 10.1007/s00105-023-05157-y -
Neurotherapeutics : the Journal of the... Jul 2023Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence... (Review)
Review
Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.
Topics: Humans; Niacin; Amyloid beta-Peptides; Pellagra; Nervous System Diseases; Alzheimer Disease; Neurology
PubMed: 37084148
DOI: 10.1007/s13311-023-01376-2 -
Annals of Medicine and Surgery (2012) Feb 2023The concept of supernatural forces has always been part of medicine and allied science. These beliefs play a pivotal role in the patient-healthcare bond and disease...
The concept of supernatural forces has always been part of medicine and allied science. These beliefs play a pivotal role in the patient-healthcare bond and disease awareness. Traditionally it was believed that psychiatric illnesses are mostly linked with mythologies and paranormal beings since most mental diseases appear to be lunatic and have no rational ground. Paradoxical to this conventional belief we discovered that mythological beliefs have penetrated all fields of medicine. Porphyria, hepatomegaly presenting with photosensitivity, are associated with "vampirism." Similarly, holoprosencephaly, a congenital anomaly presenting facial deformity is thought to be cyclops folktales. Epilepsy though is simply a neurologic illness believed to be "demonic possession." Patients of pellagra, a deficiency of vitamin B3 are thought to be werewolves. Thus, we found the presence of mythological association in all types of illnesses. We expect our healthcare infrastructure to not limit their management to counseling patients suffering from psychiatric illnesses only.
PubMed: 36845757
DOI: 10.1097/MS9.0000000000000108 -
Cells Feb 2023Research into the functions of nicotinamide adenine dinucleotide (NAD) has intensified in recent years due to the insight that abnormally low levels of NAD are involved... (Review)
Review
Research into the functions of nicotinamide adenine dinucleotide (NAD) has intensified in recent years due to the insight that abnormally low levels of NAD are involved in many human pathologies including metabolic disorders, neurodegeneration, reproductive dysfunction, cancer, and aging. Consequently, the development and validation of novel NAD-boosting strategies has been of central interest, along with the development of models that accurately represent the complexity of human NAD dynamics and deficiency levels. In this review, we discuss pioneering research and show how modern researchers have long since moved past believing that pellagra is the overt and most dramatic clinical presentation of NAD deficiency. The current research is centered on common human health conditions associated with moderate, but clinically relevant, NAD deficiency. In vitro and in vivo research models that have been developed specifically to study NAD deficiency are reviewed here, along with emerging strategies to increase the intracellular NAD concentrations.
Topics: Humans; NAD; Pellagra; Clinical Relevance; Neoplasms; Aging
PubMed: 36766842
DOI: 10.3390/cells12030500 -
European Journal of Case Reports in... 2022Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae....
UNLABELLED
Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae. Deficiencies of vitamin C, vitamin B3 (niacin) and zinc levels contribute to reduced bone density. Vitamin C associated vertebral fractures, although rare in adults, are still treatable if diagnosed early with a thorough clinical and nutritional history, and early supplementation. Radiological clues suggestive of scurvy-induced vertebral fractures can be diagnosed on plain X-ray and MRI spine imaging.
LEARNING POINTS
Although nutritional deficits like scurvy, pellagra and zinc deficiency are rare, early recognition and prompt treatment can prevent critical neurological sequelae.Clinical history including nutritional intake and associated patient symptoms are vital to diagnose scurvy-related vertebral fractures, which are treatable.It is important to note that scurvy can also present in an adult population.
PubMed: 36506738
DOI: 10.12890/2022_003359 -
Epidemiologia (Basel, Switzerland) Apr 2022This paper argues that the public health conceptual framework of epidemiologist Geoffrey Rose, first published as "Sick Individuals and Sick Populations" in 1985,... (Review)
Review
This paper argues that the public health conceptual framework of epidemiologist Geoffrey Rose, first published as "Sick Individuals and Sick Populations" in 1985, provides a useful way to critically analyze prevention and control options for modern non-communicable diseases (NCD) and their forerunner, obesity, a pandemic now engulfing Lower-and-Middle-Income-Countries. That framework is based on the notions of primordial, primary, secondary and tertiary prevention-the full spectrum of "more upstream and more downstream" approaches, each with its pros and cons. These are illustrated using the pellagra epidemic in the southeastern USA from 1900 to the 1940s, which still has much to teach us about these same basic policy options for controlling the modern NCD pandemic. In particular, Rose's dictum, "Seek the causes of (population) incidence, not of (individual) cases", points up the compelling advantages of upstream prevention for controlling both epidemics.
PubMed: 36417251
DOI: 10.3390/epidemiologia3020015 -
ERJ Open Research Oct 2022Pirfenidone (PFD) is widely used in patients with idiopathic pulmonary fibrosis (IPF) and its adverse effects, such as nausea and photosensitivity, are well known. Many...
BACKGROUND
Pirfenidone (PFD) is widely used in patients with idiopathic pulmonary fibrosis (IPF) and its adverse effects, such as nausea and photosensitivity, are well known. Many patients with IPF have reduced doses or even cessation of PFD because of its side-effects. No solutions have been found for these side-effects because the current mechanistic insights are insufficient.
METHODS
Using the results of real-world data analysis from the US Food and Drug Administration Adverse Events Reporting System, we hypothesised that PFD-related symptoms may be similar to pellagra. Reverse translational experiments using female BALB/c mice were performed to validate and estimate this hypothesis. Niacin and its metabolite responses were compared between patients with IPF treated with PFD and those treated without PFD.
RESULTS
The pellagra hypothesis was translated from real-world data analysis. Pharmacological and comprehensive genetic investigations showed that PFD caused pellagra-related nausea and photosensitivity in a mouse model, which may have been mediated by the actions of nicotinamide methyltransferase (NNMT). Higher NNMT substrate responses were observed in urine from patients and mice with PFD than in those without PFD.
CONCLUSIONS
PFD may cause pellagra or pellagra-like symptoms such as photosensitivity. Further studies are required to investigate whether niacin prevents pellagra-like symptoms caused by PFD in patients with IPF.
PubMed: 36299372
DOI: 10.1183/23120541.00245-2022 -
Frontiers in Allergy 2022Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with... (Review)
Review
Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with drugs. DIP includes phototoxicity and photoallergy. A phototoxic reaction is obtained when topical and systemic drugs or their metabolites absorb light inducing a direct cellular damage, while a photoallergic reaction takes place when the interaction between drugs and ultraviolet radiations causes an immune cutaneous response. Clinically, phototoxicity is immediate and appears as an exaggerated sunburn, whereas photoallergy is a delayed eczematous reaction. DIP may show several clinical subtypes. In this mini-review we report the pathogenetic mechanisms and causative drugs of DIP. We offer a detailed description of DIP clinical features in its classical and unusual subtypes, such as hyperpigmentation/dyschromia, pseudoporphyria, photo-onycolysis, eruptive teleangiectasia, pellagra-like reaction, lichenoid reaction, photodistributed erythema multiforme and subacute/chronic cutaneous lupus erythematosus. We described how physicians may early recognize and manage DIP, including diagnostic tests to rule out similar conditions. We made suggestions on how to improve sun exposure behaviors of patients at risk of DIP by means of an aware use of sunscreens, protective clothing and recent technologic tools. We highlighted the lack of sun safety programs addressed to patients at risk of DIP, who need a formal education about their condition.
PubMed: 36238932
DOI: 10.3389/falgy.2022.876695 -
Frontiers in Molecular Biosciences 2022Tryptophan is an essential amino acid, which is not only a building block for protein synthesis, but also a precursor for the biosynthesis of co-enzymes and... (Review)
Review
Tryptophan is an essential amino acid, which is not only a building block for protein synthesis, but also a precursor for the biosynthesis of co-enzymes and neuromodulators, such as NAD/NADP(H), kynurenic acid, melatonin and serotonin. It also plays a role in immune homeostasis, as local tryptophan catabolism impairs T-lymphocyte mediated immunity. Therefore, tryptophan plasmatic concentration needs to be stable, in spite of large variations in dietary supply. Here, we review the main checkpoints accounting for tryptophan homeostasis, including absorption, transport, metabolism and elimination, and we discuss the physiopathology of disorders associated with their dysfunction. Tryptophan is catabolized along the kynurenine pathway through the action of two enzymes that mediate the first and rate-limiting step of the pathway: indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). While IDO1 expression is restricted to peripheral sites of immune modulation, TDO is massively expressed in the liver and accounts for 90% of tryptophan catabolism. Recent data indicated that the stability of the TDO protein is regulated by tryptophan and that this regulation allows a tight control of tryptophanemia. TDO is stabilized when tryptophan is abundant in the plasma, resulting in rapid degradation of dietary tryptophan. In contrast, when tryptophan is scarce, TDO is degraded by the proteasome to avoid excessive tryptophan catabolism. This is triggered by the unmasking of a degron in a non-catalytic tryptophan-binding site, resulting in TDO ubiquitination by E3 ligase SKP1-CUL1-F-box. Deficiency in TDO or in the hepatic aromatic transporter SLC16A10 leads to severe hypertryptophanemia, which can disturb immune and neurological homeostasis.
PubMed: 36188218
DOI: 10.3389/fmolb.2022.897929