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Journal of Current Ophthalmology 2023To review the concept of plateau iris and summarize the recent evidence on its diagnosis and management. (Review)
Review
PURPOSE
To review the concept of plateau iris and summarize the recent evidence on its diagnosis and management.
METHODS
This is a narrative review on the plateau iris. A literature review was conducted in PubMed, Google Scholar, and Scopus databases using keywords: angle-closure glaucoma, glaucoma, nonpupillary block glaucoma, plateau iris, and plateau iris management.
RESULTS
This review defined the current knowledge about plateau iris. First of all, the anatomy and epidemiology were discussed. Then, we outlined the available evidence on the diagnosis of plateau iris and its differential diagnosis. Conclusively, the treatment options were mentioned.
CONCLUSIONS
Plateau iris is a condition in which nonpupillary block mechanisms are responsible for intraocular pressure elevation and angle closure attack when a patent peripheral iridotomy has removed the relative pupillary block. An anteriorly positioned ciliary body causes mechanical obstruction of trabecular meshwork in these patients. It is usually seen in younger patients with angle closure and is diagnosed by gonioscopic examination and imaging modalities such as Ultrasound biomicroscopy. Despite the known mechanism of plateau iris, there is no consensus over treatment. Low-dose pilocarpine and Argon laser peripheral iridoplasty are nonsurgical treatments for these patients, but their effects are short-term. Cataract extraction with/without endocyclophotocoagulation (ECP), endocycloplasty, excisional goniotomy, and transscleral cyclophotocoagulation are alternative treatments. Patients should be examined periodically for further progression or recurrence of plateau iris. In cases of glaucoma unresponsive to conventional medical treatments, surgical treatments such as trabeculectomy and drainage devices should be considered.
PubMed: 37680292
DOI: 10.4103/joco.joco_319_22 -
Pharmacological Research Sep 2023Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent...
Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent studies indicate that microglia modulate epilepsy-induced neuronal activities, however, the mechanisms underlying microglia-neuron communication in epilepsy are still unclear. Here we report that epileptic neuronal hyperexcitability activates microglia and drives microglial ATP/ADP hydrolyzing ectoenzyme CD39 (encoded by Entpd1) expression via recruiting the cAMP responsive element binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) from cytoplasm to the nucleus and binding to CREB. Activated microglia in turn suppress epileptic neuronal hyperexcitability in a CD39 dependent manner. Disrupting microglial CREB/CRTC1 signaling, however, decreases CD39 expression and diminishes the inhibitory effect of microglia on epileptic neuronal hyperexcitability. Overall, our findings reveal CD39-dependent control of epileptic neuronal hyperexcitability by microglia is through an excitation-transcription coupling mechanism.
Topics: Humans; Microglia; Brain; Signal Transduction; Epilepsy
PubMed: 37541638
DOI: 10.1016/j.phrs.2023.106881 -
Journal of Cystic Fibrosis : Official... May 2022Two CFTR-dependent β-adrenergic sweat rate tests applying intradermal drug injections were reported to better define diagnosis and efficacy of CFTR-directed therapies....
OBJECTIVES
Two CFTR-dependent β-adrenergic sweat rate tests applying intradermal drug injections were reported to better define diagnosis and efficacy of CFTR-directed therapies. The aim of this work was to develop and test a needle-free image-based test and to provide an accurate analysis of the responses.
METHODS
The modified method was conducted by applying two successive iontophoresis sessions using the Macroduct device. Efficiency of drug delivery was tested by evaporimetry. Cholinergically stimulated sweating was evoked by pilocarpine iontophoresis. β-adrenergically stimulated sweating was obtained by iontophoresis of isoproterenol and aminophylline in the presence of atropine and ascorbic acid. A nonlinear mixed-effects (NLME) approach was applied to model volumes of sweat and subject-specific effects displaying inter- and intra-subject variability.
RESULTS
Iontophoresis provided successful transdermal delivery of all drugs, including almost neutral isoproterenol and aminophylline. Pilocarpine was used at a concentration ∼130-times lower than that used in the classical Gibson and Cooke sweat test. Addition of ascorbic acid lowered the pH of the solution, made it stable, prevented isoproterenol degradation and promoted drug iontophoresis. Maximal secretory capacity and kinetic rate of β-adrenergic responses were blunted in CF. A cutoff of 5.2 minutes for ET50, the time to reach the half maximal secretion, discriminated CF from controls with a 100% sensitivity and specificity. Heterozygous showed an apparently reduced kinetic rate and a preserved secretory capacity.
CONCLUSION
We tested a safe, well-tolerated needle-free image-based sweat test potentially applicable in children. Modelling responses by NLME allowed evaluating metrics of CFTR-dependent effects reflecting secretory capacity and kinetic rate.
Topics: Adrenergic Agents; Aminophylline; Ascorbic Acid; Child; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Iontophoresis; Isoproterenol; Pilocarpine; Sweat
PubMed: 34489187
DOI: 10.1016/j.jcf.2021.08.012 -
Pharmacological Research Mar 2023Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype...
Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype remains difficult. A paradigmatic case is constituted by the epilepsies caused by altered neuronal nicotinic acetylcholine receptors (nAChRs), which exert complex physiological functions in mature as well as developing brain. The ascending cholinergic projections exert potent control of forebrain excitability, and wide evidence implicates nAChR dysregulation as both cause and effect of epileptiform activity. First, tonic-clonic seizures are triggered by administration of high doses of nicotinic agonists, whereas non-convulsive doses have kindling effects. Second, sleep-related epilepsy can be caused by mutations on genes encoding nAChR subunits widely expressed in the forebrain (CHRNA4, CHRNB2, CHRNA2). Third, in animal models of acquired epilepsy, complex time-dependent alterations in cholinergic innervation are observed following repeated seizures. Heteromeric nAChRs are central players in epileptogenesis. Evidence is wide for autosomal dominant sleep-related hypermotor epilepsy (ADSHE). Studies of ADSHE-linked nAChR subunits in expression systems suggest that the epileptogenic process is promoted by overactive receptors. Investigation in animal models of ADSHE indicates that expression of mutant nAChRs can lead to lifelong hyperexcitability by altering i) the function of GABAergic populations in the mature neocortex and thalamus, ii) synaptic architecture during synaptogenesis. Understanding the balance of the epileptogenic effects in adult and developing networks is essential to plan rational therapy at different ages. Combining this knowledge with a deeper understanding of the functional and pharmacological properties of individual mutations will advance precision and personalized medicine in nAChR-dependent epilepsy.
Topics: Animals; Receptors, Nicotinic; Nicotinic Agonists; Seizures; Phenotype; Epilepsy
PubMed: 36796465
DOI: 10.1016/j.phrs.2023.106698 -
Journal of Clinical and Experimental... Jan 2023Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A... (Review)
Review
BACKGROUND
Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A variety of topical and systemic therapies have been tried to restore/stimulate the gland function or replace saliva reducing the symptoms of xerostomia and to avoid the problems of diminished salivary flow.
MATERIAL AND METHODS
Four search engines (PUBMED/Medline, EMBASE, Google Scholar and The Cochrane) were used in conducting a systematic review using the terms "Sjogren's syndrome" with the combination of other terms. To define these study acceptability criteria, we used PICO model (Population, Intervention, Control and Outcome) and study design technique.
RESULTS
Out of 47 articles initially screened, 28 studies met our selection criteria. Included studies showed positive results with interventions such as pilocarpine, rituximab, and interferon-alpha (IFN-α) for enhancing salivary flow and lacrimal secretion in SS condition. One study showed promising results for combination of prednisone and hydroxychloroquine in SS, however dose of prednisone is recommended to be tapered. Another study demonstrated comparable effects of dehydroepiandrosterone and the placebo in alleviation of dry mouth symptoms (=0.006). Therapeutic effects have been reported with LASER therapy.
CONCLUSIONS
Pilocarpine was found to be highly beneficial whereas, rituximab and IFN-α were moderately effective in the reduction of hyposalivation in SS patient. Adverse events were common. Use of any alternative modalities for the management cannot be supported based on the current evidence; this demands more studies in future to be conducted staking into account adverse effects which might occur particularly with the pharmacological therapies. Sjogren's Syndrome, Xerostomia, Hyposalivation, Pilocarpine, Rituximab, Sialagogue.
PubMed: 36755678
DOI: 10.4317/jced.59891 -
Journal of Current Glaucoma Practice 2019Our goal is to review current literature regarding drug-induced acute angle-closure glaucoma (AACG) and provide ophthalmologists and general practitioners with a... (Review)
Review
AIM
Our goal is to review current literature regarding drug-induced acute angle-closure glaucoma (AACG) and provide ophthalmologists and general practitioners with a thorough understanding of inciting medications and treatment pitfalls to be avoided.
BACKGROUND
Drug-induced AACG is an ophthalmological emergency that ophthalmologists and general practitioners should be familiar with, given its potentially blinding consequences. Common anatomical risk factors for AACG include a shallow anterior chamber depth, short axial length, plateau iris configuration, thick lens, anteriorly positioned lens, and rarely, intraocular tumor. Demographic risk factors include female sex, Asian ethnicity, family history, and advanced age. In patients with predisposing factors, acute angle closure can be triggered by various classes of medications including adrenergic agonists, anticholinergics, cholinergics, sulfonamides, supplements, and serotonergic medications. Physicians prescribing such inciting medications should be aware of their potentially sight-threatening adverse effects and to inform patients of the warning symptoms. Patients typically present with elevated intraocular pressure (IOP), headache, nausea, blurry vision, and halos around lights.
REVIEW RESULTS
There are two main mechanisms of drug-induced AACG, both with different treatment strategies. The first mechanism of drug-induced AACG is pupillary block and iridocorneal angle closure secondary to thickening of iris base with mydriasis. The second mechanism of drug-induced AACG is anterior displacement of the lens-iris diaphragm due to mass effect (e.g., blood, misdirected aqueous humor, and tumors), uveal effusion, or weakened zonules.
CONCLUSION
This paper reviews drug-induced AACG, high-risk anatomical features, underlying mechanisms, inciting medications, and options for treatment and prevention.
CLINICAL SIGNIFICANCE
With proper understanding of the underlying mechanism of drug-induced AACG, physicians can respond promptly to save their patients' vision by employing the correct treatment strategy.
HOW TO CITE THIS ARTICLE
Yang MC, Lin KY. Drug-induced Acute Angle-closure Glaucoma: A Review. J Curr Glaucoma Pract 2019;13(3):104-109.
PubMed: 32435123
DOI: 10.5005/jp-journals-10078-1261 -
Current Neuropharmacology 2022Lithium is a well-known FDA-approved treatment for bipolar and mood disorders. Lithium has been an enigmatic drug with multifaceted actions involving various... (Review)
Review
Lithium is a well-known FDA-approved treatment for bipolar and mood disorders. Lithium has been an enigmatic drug with multifaceted actions involving various neurotransmitters and intricate cell signalling cascades. Recent studies highlight the neuroprotective and neurotrophic actions of lithium in amyotrophic lateral sclerosis, Alzheimer's disease, intracerebral hemorrhage, and epilepsy. Of note, lithium holds a significant interest in epilepsy, where the past reports expose its non-specific proconvulsant action, followed lately by numerous studies for anti-convulsant action. However, the exact mechanism of action of lithium for any of its effects is still largely unknown. The present review integrates findings from several reports and provides detailed possible mechanisms of how a single molecule exhibits marked pro-epileptogenic as well as anti-convulsant action. This review also provides clarity regarding the safety of lithium therapy in epileptic patients.
Topics: Epilepsy; Humans; Lithium; Lithium Compounds; Mood Disorders; Neuroprotection
PubMed: 35410603
DOI: 10.2174/1570159X20666220411081728 -
Frontiers in Cellular Neuroscience 2021: Indoleamine-2,3-dioxygenase 1 (IDO1) is the initial and rate-limiting enzyme in the metabolism of tryptophan (TRP) to kynurenine (KYN). IDO1-dependent neurotoxic KYN...
: Indoleamine-2,3-dioxygenase 1 (IDO1) is the initial and rate-limiting enzyme in the metabolism of tryptophan (TRP) to kynurenine (KYN). IDO1-dependent neurotoxic KYN metabolism plays a crucial role in the pathogenesis of many neurodegenerative disorders. However, the function of IDO1 in epilepsy is still unclear. : In this study, we investigated whether IDO1 deficiency could affect epilepsy in a lithium-pilocarpine-induced model. : Patients with epilepsy and controls were enrolled. Male C57BL/6 mice and IDO1 knockout (KO, IDO1) mice were subjected to intraperitoneal injection of lithium and pilocarpine to induce epilepsy. The levels of IDO1 and concentrations of TRP and KYN in patients with epilepsy and epileptic mice were evaluated by enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-mass spectrometry (LC-MS), respectively. Then, behavioral phenotypes related to epileptic seizures and neuronal damage were compared between KO and wild-type (WT) mice with lithium-pilocarpine-induced epilepsy. To explore the underlying pathways involved in the effects of IDO1 deficiency, the concentrations of kynurenic acid (KYNA) and quinolinic acid (QUIN), glial cell activation, the levels of major pro-inflammatory cytokines, and antioxidant enzyme activity were measured by LC-MS, immunohistochemistry, and ELISA. : In this study, IDO1 levels and the KYN/TRP ratio in the sera and cerebrospinal fluid (CSF) were increased in patients with epilepsy. Also, IDO1 levels, the KYN/TRP ratio, and the levels of pro-inflammatory cytokines in the sera and hippocampi were increased in mice during the acute phase and chronic phase after status epilepticus (SE). Furthermore, IDO1 was localized in microglial cells in epileptic mice. IDO1 deficiency delayed SE onset and attenuated the frequency, duration, and severity of spontaneous recurrent seizures (SRSs). Moreover, IDO1 deficiency improved neuronal survival. Additionally, IDO1 epileptic mice showed progressive declines in QUIN production, glial cell activation and pro-inflammatory cytokines levels, and enhanced antioxidant enzyme activity. : IDO1 deletion suppressed seizures and alleviated neuronal damage by reducing the IDO1-dependent production of neurotoxic metabolites, which finally inhibited glial cell activation and pro-inflammatory cytokine production and improved antioxidant enzyme activity. Our study demonstrates that IDO1 may be involved in the pathogenesis of epilepsy and has the potential to be a therapeutic target for epilepsy treatment.
PubMed: 33679331
DOI: 10.3389/fncel.2021.638854 -
Clinical and Translational Medicine Jun 2022Acetylcholine (ACh) and norepinephrine (NE) are representative neurotransmitters of parasympathetic and sympathetic nerves, respectively, that antagonize each other to...
BACKGROUND
Acetylcholine (ACh) and norepinephrine (NE) are representative neurotransmitters of parasympathetic and sympathetic nerves, respectively, that antagonize each other to coregulate internal body functions. This also includes the control of different kinds of hormone secretion from pancreatic islets. However, the molecular mechanisms have not been fully elucidated, and whether innervation in islets is abnormal in diabetes mellitus also remains unclear.
METHODS AND RESULTS
Immunofluorescence colocalization and islet perfusion were performed and the results demonstrated that ACh/NE and their receptors were highly expressed in islet and rapidly regulated different hormones secretion. Phosphorylation is considered an important posttranslational modification in islet innervation and it was identified by quantitative proteomic and phosphoproteomic analyses in this study. The phosphorylated islet proteins were found involved in many biological and pathological processes, such as synaptic signalling transduction, calcium channel opening and insulin signalling pathway. Then, the kinases were predicted by motif analysis and further screened and verified by kinase-specific siRNAs in different islet cell lines (αTC1-6, Min6 and TGP52). After functional verification, Ksr2 and Pkacb were considered the key kinases of ACh and NE in insulin secretion, and Cadps, Mlxipl and Pdcd4 were the substrates of these kinases measured by immunofluorescence co-staining. Then, the decreased expression of receptors, kinases and substrates of ACh and NE were found in diabetic mice and the aberrant rhythm in insulin secretion could be improved by combined interventions on key receptors (M3 (pilocarpine) or α2a (guanfacine)) and kinases (Ksr2 or Pkacb).
CONCLUSIONS
Abnormal innervation was closely associated with the degree of islet dysfunction in diabetic mice and the aberrant rhythm in insulin secretion could be ameliorated significantly after intervention with key receptors and kinases in the early stage of diabetes mellitus, which may provide a promising therapeutic strategy for diabetes mellitus in the future.
Topics: Acetylcholine; Animals; Diabetes Mellitus, Experimental; Insulin; Islets of Langerhans; Mice; Neurotransmitter Agents; Proteomics
PubMed: 35758323
DOI: 10.1002/ctm2.890