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Epilepsy Research Nov 2023The use of zebrafish as a model organism is gaining evidence in the field of epilepsy as it may help to understand the mechanisms underlying epileptic seizures. As...
The use of zebrafish as a model organism is gaining evidence in the field of epilepsy as it may help to understand the mechanisms underlying epileptic seizures. As zebrafish assays became popular, the heterogeneity between protocols increased, making it hard to choose a standard protocol to conduct research while also impairing the comparison of results between studies. We conducted a systematic review to comprehensively profile the chemically-induced seizure models in zebrafish. Literature searches were performed in PubMed, Scopus, and Web of Science, followed by a two-step screening process based on inclusion/exclusion criteria. Qualitative data were extracted, and a sample of 100 studies was randomly selected for risk of bias assessment. Out of the 1058 studies identified after removing duplicates, 201 met the inclusion criteria. We found that the most common chemoconvulsants used in the reviewed studies were pentylenetetrazole (n = 180), kainic acid (n = 11), and pilocarpine (n = 10), which increase seizure severity in a dose-dependent manner. The main outcomes assessed were seizure scores and locomotion. Significant variability between the protocols was observed for administration route, duration of exposure, and dose/concentration. Of the studies subjected to risk of bias assessment, most were rated as low risk of bias for selective reporting (94%), baseline characteristics of the animals (67%), and blinded outcome assessment (54%). Randomization procedures and incomplete data were rated unclear in 81% and 68% of the studies, respectively. None of the studies reported the sample size calculation. Overall, these findings underscore the need for improved methodological and reporting practices to enhance the reproducibility and reliability of zebrafish models for studying epilepsy. Our study offers a comprehensive overview of the current state of chemically-induced seizure models in zebrafish, highlighting the common chemoconvulsants used and the variability in protocol parameters. This may be particularly valuable to researchers interested in understanding the underlying mechanisms of epileptic seizures and screening potential drug candidates in zebrafish models.
Topics: Animals; Zebrafish; Reproducibility of Results; Anticonvulsants; Seizures; Epilepsy; Pentylenetetrazole
PubMed: 37801749
DOI: 10.1016/j.eplepsyres.2023.107236 -
Antioxidants (Basel, Switzerland) Jul 2023Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase... (Review)
Review
Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis.
Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase activity and oxidative stress participation. We conducted this study to investigate the impact of antioxidant therapy on oxidative stress, Na,K-ATPase activity, seizure factors, and mortality in rodent seizure/epilepsy models induced by pentylenetetrazol (PTZ), pilocarpine (PILO), and kainic acid (KA). After screening 561 records in the MEDLINE, EMBASE, Web of Science, Science Direct, and Scopus databases, 22 were included in the systematic review following the PRISMA guidelines. The meta-analysis included 14 studies and showed that in epileptic animals there was an increase in the oxidizing agents nitric oxide (NO) and malondialdehyde (MDA), with a reduction in endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase (SO). The Na,K-ATPase activity was reduced in all areas evaluated. Antioxidant therapy reversed all of these parameters altered by seizure or epilepsy induction. In addition, there was a percentage decrease in the number of seizures and mortality, and a meta-analysis showed a longer seizure latency in animals using antioxidant therapy. Thus, this study suggests that the use of antioxidants promotes neuroprotective effects and mitigates the effects of epilepsy. The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO) CRD42022356960.
PubMed: 37507936
DOI: 10.3390/antiox12071397 -
Journal of Dentistry (Shiraz, Iran) Mar 2023Xerostomia is a subjective sensation of dry mouth considered as a complex state affecting multiple oral functions. Pilocarpine may be a useful medication for the...
STATEMENT OF THE PROBLEM
Xerostomia is a subjective sensation of dry mouth considered as a complex state affecting multiple oral functions. Pilocarpine may be a useful medication for the treatment of xerostomia, but its side effects limit its use under certain conditions. Recent studies have focused on the pilocarpine mouthwash as an alternative.
PURPOSE
We have undertaken this study to review the latest available scientific evidence systematically, concerning the effects of pilocarpine mouthwash on salivary flow rate in patients with xerostomia.
MATERIALS AND METHOD
An electronic search for randomized controlled trials published in English until September 2021 related to pilocarpine mouthwash and salivary flow rate in patients with dry mouth was performed in PubMed/Medline, Web of Science, Google Scholar, Embase, and Scopus. A random-effects meta-analysis was conducted to evaluate the relationship between the groups.
RESULTS
Two papers with 86 patients were selected for the final review based on strict eligibility criteria. According to the results of the meta-analysis, the mean visual analogue scale in the patient treated with pilocarpine mouthwash was 0.88 unit lower than that of the control group in the fourth week follow; however, it was not statistically significant (pooled mean difference=-0.88, 95% CI = (-2.72; 0.95), = 0.34).
CONCLUSION
It seems that the use of pilocarpine mouthwash can increase the salivary flow rates; however, no optimal dose and application regimen can currently be suggested due to the high heterogeneity of the data. Regarding the relief of the symptoms using pilocarpine mouthwash, the existing evidence does not support its effectiveness.
PubMed: 37051492
DOI: 10.30476/dentjods.2022.94335.1778 -
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 -
Annals of Anatomy = Anatomischer... Feb 2023A higher prevalence of oral problems has been observed in the elderly population. One of the treatment options for some of these pathologies is the administration of...
INTRODUCTION
A higher prevalence of oral problems has been observed in the elderly population. One of the treatment options for some of these pathologies is the administration of mouthwashes combined with mechanical removal techniques. Besides, each type of oral rinse treats certain oral diseases, and it should be selected for each specific situation.
OBJECTIVE
To determine the use and efficacy of mouthwashes in the elderly as a treatment for various pathologies, to indicate the most common kinds of mouth-rinses used, the diseases treated with them, their efficacy in each treatment, and their effectiveness when they are combined with other treatments.
MATERIAL AND METHODS
The review has been carried out following the PRISMA 2020 Statement. Individualized bibliographic searches were performed in five databases. Randomized clinical trials are included in patients over 60 years old where mouthwashes were administered to treat or prevent specific diseases. The PICO question aimed to assess what type of mouthwashes elderly patients use, what they use them for, and their efficacy. Study selection, data extraction, and quality analysis were achieved using the RoB-2 guide.
RESULTS
Thirteen articles were chosen to perform the qualitative analysis. The bibliometric analysis was carried out. We have eleven randomized controlled clinical trials and two uncontrolled. The mouthwash more used was chlorhexidine, followed by essential oils and fluorides. The most studied pathologies were a periodontal disease, caries, candidiasis, denture stomatitis, and xerostomia. Chlorhexidine used weekly is effective as antiplaque and antigingivitis. Fluorides effectively prevent and reverse caries; nystatin and essential oils to treat candidiasis; and pilocarpine rinse to manage xerostomia.
CONCLUSIONS
The included studies show that mouthwashes are widely extended in the elderly population, and each sort is specifically designed for treating a particular condition.
Topics: Aged; Humans; Middle Aged; Chlorhexidine; Fluorides; Mouthwashes; Oils, Volatile; Randomized Controlled Trials as Topic; Xerostomia
PubMed: 36402239
DOI: 10.1016/j.aanat.2022.152026 -
European Journal of Translational... Sep 2022The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant...
The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant terms in PubMed, Science direct, Google scholar, Medline, Google patent, Ovid, Cochrane Database of Systematic Reviews, Scopus. In the initial search, 2270 records were obtained. By removing duplicate articles and all articles that did not meet the inclusion criteria or were inappropriate due to indirect relevance to the subject, 44 studies were selected. It should be noted that all studies had inclusion criteria. There are a number of topical pharmacological agents available for treating presbyopia such as FOV Tears and PresbiDrop. They consist of parasympathetic agent and non-steroidal anti-inflammatory drugs (NSAIDs), to contract the ciliary and pupil muscle and restore the accommodation. Another example of topical pharmacological agent is EV06. It is a lens-softening eye drop which can affect the rigid lens in presbyopia. Currently there is no pharmacological agent available to treat presbyopia. Although there are limited number of peer-reviewed articles available, the outcome for future agents under investigation are promising.
PubMed: 36121117
DOI: 10.4081/ejtm.2022.10781 -
Frontiers in Endocrinology 2022Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer...
INTRODUCTION
Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC). Several methods have been used to reduce/prevent this adverse effect. We aimed to systematically review the effectiveness of non-pharmacological and pharmacological interventions in preventing RAI-induced salivary gland dysfunction in patients with DTC.
METHODS
A systematic review was conducted, according to PRISMA guidelines. The protocol was registered (PROSPERO: CRD42022295229). PubMed, Embase, Scopus, and the Cochrane Library electronic databases were searched from inception to November 2021. Inclusion criteria were randomized controlled trials of DTC patients who were older than 18 years and underwent RAI after thyroidectomy in which at least one studied group received an intervention to prevent salivary gland dysfunction.
RESULTS
Twelve studies (a total of 667 participants) were included. Among DTC patients who were treated with RAI, nonpharmacological treatment such as parotid gland massage and aromatherapy ameliorated salivary gland dysfunction. Antioxidants such as vitamin E and selenium demonstrated radioprotective effects on the salivary gland, while other antioxidants did not show radioprotective benefits. Vitamin C showed no significant effects on preventing salivary gland dysfunction. Amifostine had inconsistent outcomes among studies. Among cholinergic agonists, pilocarpine did not demonstrate the radioprotective effect on parotid glands, while bethanechol lowered salivary gland dysfunction. However, the negative results from pilocarpine may be explained by the strong sialorrheic effect of the Cincinnati regimen in both study arms.
CONCLUSION
Among non-pharmacological and pharmacological methods, parotid gland massage, aromatherapy, vitamin E, selenium, amifostine, and bethanechol may have benefits in minimizing RAI-induced salivary gland dysfunction in patients with DTC. The results are limited by a small number of patients and should be confirmed in future larger randomized controlled trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=295229, PROSPERO, identifier CRD42022295229.
Topics: Adenocarcinoma; Amifostine; Bethanechol; Humans; Iodine Radioisotopes; Pilocarpine; Randomized Controlled Trials as Topic; Salivary Glands; Selenium; Thyroid Neoplasms; Vitamin E
PubMed: 36105397
DOI: 10.3389/fendo.2022.960265 -
Epilepsy & Behavior : E&B Mar 2022Status epilepticus (SE) is a neurological emergency necessitating rapid seizure control to prevent long-term consequences. Perampanel (PER) is a novel selective,... (Review)
Review
BACKGROUND
Status epilepticus (SE) is a neurological emergency necessitating rapid seizure control to prevent long-term consequences. Perampanel (PER) is a novel selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor antagonist that demonstrated efficacy and safety in lithium-pilocarpine models of SE; however, data in humans are limited. This systematic review was performed to assess the efficacy and safety of PER in patients with SE, RSE, and SRSE.
METHODS
We searched MEDLINE (accessed through PubMed), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov from inception until May 30, 2021 to identify all human studies on PER for the treatment of SE of any type and etiology. An additional search was performed on DANS Easy Archive, in which OpenGrey data were stored, from inception until January 10, 2022 and conference proceedings by the International League Against Epilepsy from 2011 onward. The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall certainty of the body of evidence.
RESULTS
Twenty-one studies (7 case reports, 9 case series, and 5 retrospective cohort studies) were included with a total of 369 cases of SE in 368 patients aged 11 months to 99 years, of which 56.2% were female. Seizures of the majority were refractory (n = 220), super refractory SE (n = 70), or either (n = 81) with prominent motor symptoms (n = 284) and are associated with a structural etiology (n = 218). The number of antiseizure medications and/or anesthetics used prior to PER ranged from 1 to 13. PER was administered in 324 cases and was initiated at a dose of 2-36 mg between 30 min to 59 days from SE onset. SE cessation ranged from 1 h to 4 weeks from PER initiation. A total of 119 cases (36.6%) were considered PER responders. According to the GRADE approach, there is very low certainty of evidence for all outcomes.
CONCLUSIONS
The real-world data of PER as a possible therapeutic option in SE of any type are increasing. However, there is very low certainty of evidence for its use and this requires further clinical studies to establish the appropriate timing, dosing, and titration that are efficacious and safe for SE cessation.
Topics: Anticonvulsants; Female; Humans; Infant; Nitriles; Pyridones; Retrospective Studies; Status Epilepticus
PubMed: 35151187
DOI: 10.1016/j.yebeh.2022.108583 -
Frontiers in Neurology 2021Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical...
Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility. We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, studies, studies, studies in humans, or studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis. Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, = 6 and intensity of motor signals, = 3) and electrophysiological analysis (spikes/min, = 4, and amplitude, = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was -130.98 [95% CI: -203.47, -58.49] (seconds) and the intensity of motor signals was -0.40 [95% CI: -1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with -26.96 [95% CI: -39.56, -14.36], and for spike amplitude (μV) with -282.64 [95% CI: -466.81, -98.47]. . A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. . Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (μV)] induced by the administration of different chemoconvulsants. PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.
PubMed: 34956052
DOI: 10.3389/fneur.2021.771123 -
Frontiers in Endocrinology 2020Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been...
Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been continuously searched for. In this context, a group of endogenous or exogenous neurosteroids allosterically positively modulating GABA-A receptors may offer a promising approach. Among endogenous neurosteroids synthesized in the brain, allopregnanolone or allotetrahydrodeoxycorticosterone have been documented to exert anticonvulsant activity in a number of experimental models of seizures-pentylenetetrazol-, bicuculline- pilocarpine-, or 6 Hz-induced convulsions in rodents. Neurosteroids can also inhibit fully kindled seizures and some of them have been reported to counteract maximal electroshock-induced convulsions. An exogenous neurosteroid, alphaxalone, significantly elevated the threshold for maximal electroconvulsions in mice but it did not potentiate the anticonvulsive action of a number of conventional antiepileptic drugs against maximal electroshock-induced seizures. Androsterone not only elevated the threshold but significantly enhanced the protective action of carbamazepine, gabapentin and phenobarbital against maximal electroshock in mice, as well. Ganaxolone (a 3beta-methylated analog of allopregnanolone) needs special consideration for two reasons. First, it performed better than conventional antiepileptic drugs, diazepam or valproate, in suppressing convulsive and lethal effects of pentylenetetrazol in pentylenetetrazol-kindled mice. Second, ganaxolone has been evaluated in the randomized, double-blind, placebo-controlled phase 2 trial in patients with intractable partial seizures, taking maximally 3 antiepileptic drugs. The initial results indicate that add-on therapy with ganaxolone resulted in reduced seizure frequency with adverse effect being mainly mild to moderate. Possibly, ganaxolone may be also considered against catamenial seizures. Some positive effects of ganaxolone as an adjuvant were also observed in children with refractory seizures and its use may also prove efficient for the management of neonatal seizures associated with hypoxic injury. Neurosteroids positively modulating GABA-A receptor complex exert anticonvulsive activity in many experimental models of seizures. Their interactions with antiepileptic drugs seem ambiguous in mice. Initial clinical data indicate that ganaxolone may provide a better seizure control in patients with drug-resistant epilepsy.
Topics: Allosteric Regulation; Animals; Anticonvulsants; Epilepsy; GABA-A Receptor Agonists; Humans; Neurosteroids; Seizures; Treatment Outcome
PubMed: 33117274
DOI: 10.3389/fendo.2020.541802