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Biochimica Et Biophysica Acta.... Nov 2018Ca signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca-signaling... (Review)
Review
Ca signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca-signaling network is the inositol 1,4,5-trisphosphate (IP) receptor (IPR), a tetrameric channel that mediates Ca release from the endoplasmic reticulum (ER) in response to IP. IPR function is controlled by a myriad of factors, such as Ca, ATP, kinases and phosphatases and a plethora of accessory and regulatory proteins. Further complexity in IPR-mediated Ca signaling is the result of the existence of three main isoforms (IPR1, IPR2 and IPR3) that display distinct functional characteristics and properties. Despite their abundant and overlapping expression profiles, IPR1 is highly expressed in neurons, IPR2 in cardiomyocytes and hepatocytes and IPR3 in rapidly proliferating cells as e.g. epithelial cells. As a consequence, dysfunction and/or dysregulation of IPR isoforms will have distinct pathophysiological outcomes, ranging from neurological disorders for IPR1 to dysfunctional exocrine tissues and autoimmune diseases for IPR2 and -3. Over the past years, several IPR mutations have surfaced in the sequence analysis of patient-derived samples. Here, we aimed to provide an integrative overview of the clinically most relevant mutations for each IPR isoform and the subsequent molecular mechanisms underlying the etiology of the disease.
Topics: Animals; Calcium; Calcium Signaling; Disease Susceptibility; Gene Expression Regulation; Humans; Inositol 1,4,5-Trisphosphate Receptors; Mutation; Protein Isoforms
PubMed: 29906486
DOI: 10.1016/j.bbamcr.2018.06.004 -
Animals : An Open Access Journal From... Nov 2021Macrolide drugs are the treatment of choice for infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to...
Macrolide drugs are the treatment of choice for infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration-pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin induced anhidrosis episode. After Bonferroni correction for multiple testing, 132 gene transcripts were significantly differentially expressed during the anhidrotic timepoint. Gene ontology analysis of the full differentially expressed gene set identified over-represented biological functions for ubiquitination and ion-channel function, both biologically relevant to sweat production. These same mechanisms were previously implicated in heritable equine idiopathic anhidrosis and sweat gland function and their involvement in macrolide-induced temporary anhidrosis warrants further investigation.
PubMed: 34944156
DOI: 10.3390/ani11123379 -
Neurology India Mar 2024
Topics: Humans; Hypohidrosis; Autonomic Nervous System Diseases; Flushing; Male; Female; Adult
PubMed: 38817189
DOI: 10.4103/neurol-india.Neurol-India-D-24-00157 -
Ugeskrift For Laeger May 2016
Topics: Autonomic Nervous System Diseases; Female; Flushing; Humans; Hypohidrosis; Middle Aged
PubMed: 27188995
DOI: No ID Found -
International Journal of Molecular... Aug 2021Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or... (Review)
Review
Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or neurological disorder. Most cases of AIGA have been reported in Asia, especially in Japan, but there have been only a few reports in Europe and the United States. Severe AIGA may result in heatstroke and can reduce quality of life due to restriction of exercise and outdoor works. AIGA is often accompanied by cholinergic urticaria (CholU), and it is thought that AIGA and CholU with anhidrosis/hypohidrosis belong to the same spectrum of the disease. However, the pathophysiology of AIGA has not yet been clarified. Decreased expression of cholinergic receptor M3 on the epithelial cells of eccrine sweat glands is often accompanied by T cell infiltration around eccrine apparatus, suggesting an immunological mechanism of disordered perspiration. AIGA is occasionally associated with various complications indicative of autoimmune disorders. The association of autoimmune complications further suggests that AIGA is an autoimmune disorder. Studies on complications may lead to a better understanding of the pathophysiology of AIGA.
Topics: Animals; Autoimmune Diseases; Humans; Hypohidrosis; Receptor, Muscarinic M3; Receptors, Cholinergic; Urticaria
PubMed: 34445091
DOI: 10.3390/ijms22168389 -
International Journal of Molecular... Oct 2019Claudins are key components of the tight junction, sealing the paracellular cleft or composing size-, charge- and water-selective paracellular channels. Claudin-10... (Review)
Review
Claudins are key components of the tight junction, sealing the paracellular cleft or composing size-, charge- and water-selective paracellular channels. Claudin-10 occurs in two major isoforms, claudin-10a and claudin-10b, which constitute paracellular anion or cation channels, respectively. For several years after the discovery of claudin-10, its functional relevance in men has remained elusive. Within the past two years, several studies appeared, describing patients with different pathogenic variants of the gene. Patients presented with dysfunction of kidney, exocrine glands and skin. This review summarizes and compares the recently published studies reporting on a novel autosomal-recessive disorder based on claudin-10 mutations.
Topics: Claudins; Genetic Predisposition to Disease; Humans; Hypohidrosis; Ichthyosis; Kidney Diseases; Lacrimal Apparatus Diseases; Mutation; Protein Domains; Xerostomia
PubMed: 31671507
DOI: 10.3390/ijms20215396 -
Allergology International : Official... Dec 2012Cholinergic urticaria (CU) has clinically characteristic features, and has been frequently described in the literature. However, despite its comparatively old history,... (Review)
Review
Cholinergic urticaria (CU) has clinically characteristic features, and has been frequently described in the literature. However, despite its comparatively old history, the pathogenesis and classification remains to be clarified. CU patients are occasionally complicated by anhidrosis and/or hypohidrosis. This reduced-sweat type should be included in the classification because the therapeutic approaches are different from the ordinary CU. It is also well-known that autologous sweat is involved in the occurrence of CU. More than half of CU patients may have sweat hypersensitivity. We attempt to classify CU and address the underlying mechanisms of CU based on the published data and our findings. The first step for classification of CU seems to discriminate the presence or absence of hypersensitivity to autologous sweat. The second step is proposed to determine whether the patients can sweat normally or not. With these data, the patients could be categorized into three subtypes: (1) CU with sweat hypersensitivity; (2) CU with acquired anhidrosis and/or hypohidrosis; (3) idiopathic CU. The pathogenesis of each subtype is also discussed in this review.
Topics: Acetylcholine; Humans; Hypohidrosis; Sweat; Sweating; Urticaria
PubMed: 23093795
DOI: 10.2332/allergolint.12-RAI-0485 -
Anais Brasileiros de Dermatologia 2016Ross syndrome is a rare disease characterized by peripheral nervous system dysautonomia with selective degeneration of cholinergic fibers. It is composed by the triad of...
Ross syndrome is a rare disease characterized by peripheral nervous system dysautonomia with selective degeneration of cholinergic fibers. It is composed by the triad of unilateral or bilateral segmental anhidrosis, deep hyporeflexia and Holmes-Adie's tonic pupil. The presence of compensatory sweating is frequent, usually the symptom that most afflicts patients. The aspects of the syndrome are put to discussion due to the case of a male patient, caucasian, 47 years old, with clinical onset of 25 years.
Topics: Cholinergic Fibers; Humans; Hyperhidrosis; Hypohidrosis; Male; Middle Aged; Nerve Degeneration; Peripheral Nervous System Diseases; Primary Dysautonomias; Syndrome
PubMed: 26982793
DOI: 10.1590/abd1806-4841.20163918 -
Journal of Neurology Oct 2021Ross syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and segmental anhidrosis. We sought to characterize the clinical presentation, associated...
BACKGROUND
Ross syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and segmental anhidrosis. We sought to characterize the clinical presentation, associated autoimmune disorders, and autonomic profile in patients with Ross syndrome to further elucidate its pathophysiology.
METHODS
We performed a retrospective chart review of all patients who underwent a thermoregulatory sweat test (TST) between 1998 and 2020 and had confirmation of the diagnosis of Ross syndrome by an autonomic disorders specialist. Standardized autonomic reflex testing was reviewed when available.
RESULTS
Twenty-six patients with Ross syndrome were identified. The most common initial reported manifestation was an abnormal segmental sweating response in 16 patients (described as hyperhidrosis in 12 patients and anhidrosis in 4 patients) while a tonic pupil was the initial manifestation in 10 patients. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency. An associated autoimmune disorder was identified in one patient. Positive autoantibodies were found in a minority of patients often with unclear clinical significance. Distributions of anhidrosis encountered were segmental (n = 15), widespread (n = 7), and global (n = 4). Well-circumscribed small areas of preserved sweating within areas of anhidrosis were observed in the majority of patients (88.5%). Anhidrosis progressed slowly over time and sudomotor dysfunction was predominantly (post)ganglionic. Cardiovagal and adrenergic functions were preserved in most patients.
CONCLUSIONS
The pattern of autonomic dysfunction in Ross syndrome is suggestive of a limited autonomic ganglioneuropathy. Sudomotor impairment is prominent and should be the focus of symptomatic management; however, clinicians should be aware of symptoms beyond the classic triad.
Topics: Autonomic Nervous System Diseases; Humans; Hypohidrosis; Retrospective Studies; Syndrome; Tonic Pupil
PubMed: 33813643
DOI: 10.1007/s00415-021-10531-8