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Oral Diseases Nov 2019Pilocarpine (PILO) and cevimeline (CEV) are muscarinic acetylcholine receptor agonists that stimulate salivary gland function. The aim of this investigation was to... (Comparative Study)
Comparative Study
OBJECTIVES
Pilocarpine (PILO) and cevimeline (CEV) are muscarinic acetylcholine receptor agonists that stimulate salivary gland function. The aim of this investigation was to retrospectively run a head-to-head comparison for their effectiveness and frequency of adverse effects in patients with hyposalivation.
METHODS
A retrospective chart review was conducted for patients seen at the Oral Medicine Clinic at Tufts University School of Dental Medicine (TUSDM) and was prescribed PILO or CEV. Patients' demographics, medical history/medication, stimulated salivary (SS), and unstimulated salivary (US) flow recorded at the initial visit and at 3- and 6-month follow-ups were collected. Changes in dosage/frequency, side effects, and drug discontinuation were also reported.
RESULTS
A total of 110 patients' charts were reviewed. The majority of subjects (91%) were females with an average age of 61. At 3-month follow-up, the use of CEV showed significant improvement in SS compared to PILO (p = .033) but not in US (p = .10). At 6-month follow-up, there was no significant difference in SS or US between the two groups (SS: p = .09; US: p = .71). The use of PILO was associated with a higher proportion of adverse effects compared to CEV (p = .04). The overall adherence rate was significantly higher in the CEV group (p = .0056).
CONCLUSIONS
The effectiveness of CEV and PILO is comparable. However, PILO seems to be associated with more reporting of side effects.
Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Middle Aged; Muscarinic Agonists; Pilocarpine; Quinuclidines; Retrospective Studies; Thiophenes; Time Factors; Xerostomia
PubMed: 31520497
DOI: 10.1111/odi.13192 -
Experimental Animals Nov 2023Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications...
Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100β in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100β in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.
Topics: Rats; Animals; Phosphoglycerate Kinase; Vascular Endothelial Growth Factor A; Blood-Brain Barrier; Lithium; Pilocarpine; Angiostatins; Seizures; Epilepsy; Adenosine Triphosphate
PubMed: 37258131
DOI: 10.1538/expanim.23-0019 -
Journal of Insect Physiology 2021The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is...
The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is significant interest in the regulation of salivary gland function and mechanisms driving the secretion of saliva and digestive proteins. We aimed to gain a broader understanding of the regulatory role of aminergic, cholinergic, and octopaminergic neuromodulators to saliva and protein secretion from the female A. aegypti salivary gland. Quantification of saliva after injection with neuromodulators showed that dopamine, serotonin, and pilocarpine increased the secretory activity of the salivary gland with potency rankings dopamine = serotonin > pilocarpine. No change in saliva secretion was observed with octopamine or ergonovine, which indicates the A. aegypti salivary gland may be regulated by dopaminergic, serotonergic, and cholinergic systems, but are not likely regulated by octopaminergic or tryptaminergic systems. Next, we studied the regulatory control of dopamine-mediated salivation. Data indicate extracellular calcium flux, but not neural function, is critical for dopamine-mediated salivation, which suggests epithelial transport of ions and not neuronal control is responsible for dopamine-mediated salivation. For regulation of protein secretion, data indicate dopamine or serotonin exposure facilitates amylase secretion, whereas serotonin but not dopamine exposure increased apyrase concentrations in the secreted saliva. General immunoreactivity to anti-rat D1-dopamine receptor antibody was observed, yet immunoreactivity to the anti-rat D2-receptor antibody was identified in the proximal regions of the lateral lobes and slight immunoreactivity in the distal portion of the lateral lobe, with no expression in the medial lobe.
Topics: Aedes; Amylases; Animals; Apyrase; Dopamine; Female; Humans; Insect Proteins; Neurotransmitter Agents; Pilocarpine; Rats; Receptors, Dopamine D1; Saliva; Salivary Glands; Serotonin
PubMed: 33460707
DOI: 10.1016/j.jinsphys.2021.104193 -
Molecules (Basel, Switzerland) Jun 2021Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by...
Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by the reduction of Weinreb amides and a single-step attachment of a 1-methyl-imidazole residue allowed for the concise synthesis of both enantiomers of pilocarpine.
Topics: 4-Butyrolactone; Amides; Carboxylic Acids; Esterification; Furans; Hydrogenation; Hydrolysis; Pilocarpine; Stereoisomerism
PubMed: 34208623
DOI: 10.3390/molecules26123676 -
Oral Diseases Sep 2022To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with...
OBJECTIVES
To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine.
MATERIALS AND METHODS
In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 days postirradiation for a total of 7 days. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks after irradiation.
RESULTS
Salivary secretion of the irradiated glands was reduced at 1 and 12 weeks. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment.
CONCLUSIONS
Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.
Topics: Animals; Claudin-4; Claudins; Pilocarpine; Rats; Rats, Wistar; Submandibular Gland; Tight Junctions
PubMed: 33818901
DOI: 10.1111/odi.13870 -
Journal of Pharmaceutical Sciences May 2020Cystic fibrosis is diagnosed in infants by estimating the levels of chloride ions present in the sweat induced by iontophoresis of pilocarpine solution. Elevated levels...
Cystic fibrosis is diagnosed in infants by estimating the levels of chloride ions present in the sweat induced by iontophoresis of pilocarpine solution. Elevated levels of chloride (≥60 mMol/L) in sweat are indicative of cystic fibrosis. However, the iontophoretic method of delivering pilocarpine is cumbersome and usually is associated with several side effects such as skin burn, skin rashes, erythema, and so forth. The objective of this study was therefore to develop a topical formulation that delivers adequate amount of pilocarpine. The drug delivery of formulation was compared with iontophoresis of aqueous solution of pilocarpine nitrate in vitro using porcine skin model. The pilocarpine levels in the skin exposed to topical pilocarpine solution under mild hyperthermia was 152.04 ± 52.23 μg/cm after 10 min of application, whereas it was 97.05 ± 27.93 μg/cm in the skin after 10 min of iontophoresis. The topical formulation was subjected to clinical evaluation to assess the efficacy of the product to induce sweat production. The average amount of the sweat secreted on application of topical formulation was found to be 77.28 ± 18.97 mg. Based on these results, it was found that the topical formulation was successful in delivering pilocarpine and to stimulate sweat secretion.
Topics: Chlorides; Cystic Fibrosis; Humans; Infant; Iontophoresis; Pilocarpine; Sweat; Sweating
PubMed: 32035925
DOI: 10.1016/j.xphs.2020.01.030 -
Brazilian Journal of Biology = Revista... 2022The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure...
The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.
Topics: Animals; Dopamine; Epilepsy; Male; Muscarinic Agonists; Oxidopamine; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus
PubMed: 35544785
DOI: 10.1590/1519-6984.248411 -
Cerebral Cortex (New York, N.Y. : 1991) Jul 2022Kainate receptors (KARs) are key regulators of synaptic circuits by acting at pre- and postsynaptic sites through either ionotropic or metabotropic actions. KARs can be...
Kainate receptors (KARs) are key regulators of synaptic circuits by acting at pre- and postsynaptic sites through either ionotropic or metabotropic actions. KARs can be activated by kainate, a potent neurotoxin, which induces acute convulsions. Here, we report that the acute convulsive effect of kainate mostly depends on GluK2/GluK5 containing KARs. By contrast, the acute convulsive activity of pilocarpine and pentylenetetrazol is not alleviated in the absence of KARs. Unexpectedly, the genetic inactivation of GluK2 rather confers increased susceptibility to acute pilocarpine-induced seizures. The mechanism involves an enhanced excitability of GluK2-/- CA3 pyramidal cells compared with controls upon pilocarpine application. Finally, we uncover that the absence of GluK2 increases pilocarpine modulation of Kv7/M currents. Taken together, our findings reveal that GluK2-containing KARs can control the excitability of hippocampal circuits through interaction with the neuromodulatory cholinergic system.
Topics: CA1 Region, Hippocampal; Cholinergic Agents; Gene Deletion; Humans; Kainic Acid; Pilocarpine; Pyramidal Cells; Receptors, Kainic Acid; Seizures; GluK2 Kainate Receptor
PubMed: 34730179
DOI: 10.1093/cercor/bhab390 -
Archivos de La Sociedad Espanola de... Jul 2021The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since...
The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID-19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.
PubMed: 34629696
DOI: 10.1016/j.oftal.2021.01.003 -
Oral Diseases Sep 2020To evaluate a pilocarpine spray as a treatment for xerostomia in patients treated with radiotherapy (RT) for head and neck cancer (HNC).
OBJECTIVE
To evaluate a pilocarpine spray as a treatment for xerostomia in patients treated with radiotherapy (RT) for head and neck cancer (HNC).
METHODS
This was a placebo-controlled, double-blind, crossover clinical trial of patients complaining of dry mouth after RT for HNC. Forty patients were randomly assigned to either placebo or pilocarpine (1.54%) spray and instructed to use three times a day for 3 months. After 1-month washout period, patients were crossed over to receive placebo or pilocarpine. The assessments were salivary flow (Stimulated Whole Saliva Flow - SWSF), xerostomia (Xerostomia Inventory - XI), and quality of life (QoL/Oral Health Impact Profile - OHIP-14), assessed at baseline, 1 hr (only SWSF), and at 1, 2, and 3 months of treatment.
RESULTS
Posttreatment SWFS was not statistically different between pilocarpine and placebo regardless of the treatment sequence (paired T test; p > .05), except for the SWFS rates at 2 months after therapy. When comparing pilocarpine with placebo in the time points, there was no significant difference (p > .05) for QoL or XI. Significant differences in improvement in QoL and xerostomia experience appeared along time for pilocarpine group.
CONCLUSION
The topical application of pilocarpine spray tested was similar to placebo on SWSF assessments in patients treated with RT for HNC.
PubMed: 32248594
DOI: 10.1111/odi.13343