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Neuron Oct 2022The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to...
The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to degeneration observed in neighboring CA1 and CA3 regions in both humans and rodent models of TLE. However, little is known about whether alterations in CA2 properties promote seizure generation or propagation. Here, we addressed the role of CA2 using the pilocarpine-induced status epilepticus model of TLE. Ex vivo electrophysiological recordings from acute hippocampal slices revealed a set of coordinated changes that enhance CA2 PC intrinsic excitability, reduce CA2 inhibitory input, and increase CA2 excitatory output to its major CA1 synaptic target. Moreover, selective chemogenetic silencing of CA2 pyramidal cells caused a significant decrease in the frequency of spontaneous seizures measured in vivo. These findings provide the first evidence that CA2 actively contributes to TLE seizure activity and may thus be a promising therapeutic target.
Topics: Animals; CA2 Region, Hippocampal; Disease Models, Animal; Epilepsy, Temporal Lobe; Hippocampus; Humans; Mice; Pilocarpine; Pyramidal Cells; Seizures
PubMed: 35987207
DOI: 10.1016/j.neuron.2022.07.020 -
The British Journal of Ophthalmology Apr 1981Guttae phenylephrine 10% produced a significant decrease in intraocular pressure and increase in facility of outflow in eyes with untreated ocular hypertension. If at...
Guttae phenylephrine 10% produced a significant decrease in intraocular pressure and increase in facility of outflow in eyes with untreated ocular hypertension. If at the same time pigment was released into the aqueous, the pressure and outflow effect was nullified. Guttae pilocarpine 2% also reduced pressure and increased outflow, but if phenylephrine was added to the pilocarpine 2 responses appeared. If no pigment was released, pressure decreased and outflow increased; if pigment was released, there was no significant change in either. An identical response was shown by eyes with treated open-angle glaucoma. In eyes with treated exfoliation glaucoma pilocarpine and phenylephrine combined produced a significant increase in pressure and decrease in outflow because of pigment release. Finally, 18 eyes are described in which pigment release produced a mean increase in intraocular pressure of 14 mmHg. An acute release of pigment has an outflow-blocking effect that can be readily demonstrated. It provides an explanation for some of the paradoxical responses that occur after the instillation of autonomic drugs. It also provides a sufficient explanation for glaucoma associated with pigment dispersion.
Topics: Drug Combinations; Glaucoma; Humans; Intraocular Pressure; Phenylephrine; Pigment Epithelium of Eye; Pilocarpine; Pupil
PubMed: 7236570
DOI: 10.1136/bjo.65.4.258 -
International Journal of Radiation... Mar 2016To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers.
METHODS AND MATERIALS
The PubMed, Web of Science, Cochrane Library, and ClinicalTrials were searched to identify randomized, controlled trials studying the effect of concomitant administration of pilocarpine for radiation-induced xerostomia. Included trials were systematically reviewed, and quantifiable outcomes were pooled for meta-analysis. Outcomes of interest included salivary flow, clinician-rated xerostomia grade, patient-reported xerostomia scoring, quality of life, and adverse effects.
RESULTS
Six prospective, randomized, controlled trials in 8 articles were included in this systematic review. The total number of patients was 369 in the pilocarpine group and 367 in the control group. Concomitant administration of pilocarpine during radiation could increase the unstimulated salivary flow rate in a period of 3 to 6 months after treatment, and also reduce the clinician-rated xerostomia grade. Patient-reported xerostomia was not significantly impacted by pilocarpine in the initial 3 months but was superior at 6 months. No significant difference of stimulated salivary flow rate could be confirmed between the 2 arms. Adverse effects of pilocarpine were mild and tolerable.
CONCLUSIONS
The concomitant administration of pilocarpine during radiation increases unstimulated salivary flow rate and reduces clinician-rated xerostomia grade after radiation. It also relieves patients' xerostomia at 6 months and possibly at 12 months. However, pilocarpine has no effect on stimulated salivary flow rate.
Topics: Cholinergic Agonists; Head and Neck Neoplasms; Humans; Pilocarpine; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Salivation; Xerostomia
PubMed: 26867879
DOI: 10.1016/j.ijrobp.2015.11.012 -
Neurobiology of Disease May 2023Interictal activity and seizures are the hallmarks of focal epileptic disorders (which include mesial temporal lobe epilepsy, MTLE) in humans and in animal models.... (Review)
Review
Interictal activity and seizures are the hallmarks of focal epileptic disorders (which include mesial temporal lobe epilepsy, MTLE) in humans and in animal models. Interictal activity, which is recorded with cortical and intracerebral EEG recordings, comprises spikes, sharp waves and high-frequency oscillations, and has been used in clinical practice to identify the epileptic zone. However, its relation with seizures remains debated. Moreover, it is unclear whether specific EEG changes in interictal activity occur during the time preceding the appearance of spontaneous seizures. This period, which is termed "latent", has been studied in rodent models of MTLE in which spontaneous seizures start to occur following an initial insult (most often a status epilepticus induced by convulsive drugs such as kainic acid or pilocarpine) and may mirror epileptogenesis, i.e., the process leading the brain to develop an enduring predisposition to seizure generation. Here, we will address this topic by reviewing experimental studies performed in MTLE models. Specifically, we will review data highlighting the dynamic changes in interictal spiking activity and high-frequency oscillations occurring during the latent period, and how optogenetic stimulation of specific cell populations can modulate them in the pilocarpine model. These findings indicate that interictal activity: (i) is heterogeneous in its EEG patterns and thus, presumably, in its underlying neuronal mechanisms; and (ii) can pinpoint to the epileptogenic processes occurring in focal epileptic disorders in animal models and, perhaps, in epileptic patients.
Topics: Animals; Humans; Epilepsy, Temporal Lobe; Pilocarpine; Seizures; Epilepsies, Partial; Epilepsy; Electroencephalography
PubMed: 36907521
DOI: 10.1016/j.nbd.2023.106065 -
The British Journal of Ophthalmology Aug 1977Altogether 85 eyes from patients at risk to the development of closed-angle glaucoma were dilated with either parasympatholytic or sympathomimetic drugs. Of 21 eyes...
Altogether 85 eyes from patients at risk to the development of closed-angle glaucoma were dilated with either parasympatholytic or sympathomimetic drugs. Of 21 eyes dilated with cyclopentolate 1/2%, 9 developed angle closure and a significantly raised pressure at some stage during dilatation and subsequent miosis. Of 58 eyes dilated with tropicamide 1/2%, 19 developed angle closure and a significantly raised pressure during dilatation. Treatment with intravenous acetazolamide and pilocarpine rapidly returned pressure to normal levels. Six eyes that had previously had a positive provocative test with simultaneous pilocarpine and phenylephrine were safely dilated with phenylephrine alone. Subsequent miosis with pilocarpine produced closed-angle glaucoma in all eyes. The significance of these observations is explained and discussed, and it is suggested that high-risk eyes should never be dilated with cyclopentolate. Tropicamide is safe if elementary precautions are observed. Safest of all, however, is phenylephrine-induced mydriasis and subsequent miosis with thymoxamine drops 1/2%.
Topics: Acetazolamide; Cyclopentolate; Glaucoma; Humans; Miotics; Moxisylyte; Mydriatics; Phenylephrine; Pilocarpine
PubMed: 143952
DOI: 10.1136/bjo.61.8.517 -
International Journal of Molecular... Oct 2022Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the...
Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient. The objective of the current study was to investigate the effects of endurance training, applied before and after pilocarpine (Pilo) administration, on status epilepticus (SE) severity, and its relation to epileptogenesis deleterious consequences during the chronic epileptic phase. Long-term aerobic training, applied four weeks before SE and eight weeks after SE, elevated the threshold to induce SE and reduced spontaneous motor seizures. The protective effect of this alternative approach on seizure susceptibility resulted in improved memory responses, and alleviated comorbid depression in epileptic rats. The exercised epileptic rats had improved markers of oxidative stress by decreasing lipid peroxidation and increasing the levels of glutathione and activity of superoxide dismutase in the rat hippocampus. Aerobic training managed to ameliorate the neuroinflammation by decreasing the levels of TNF-α and IL-1β in the hippocampus. Our results suggest that regular physical training predisposes the subjects to crucial plastic changes, leading to increased resistance to SE and the development of epileptogenesis.
Topics: Animals; Rats; Humans; Pilocarpine; Endurance Training; Status Epilepticus; Seizures; Epilepsy; Hippocampus; Disease Models, Animal
PubMed: 36361978
DOI: 10.3390/ijms232113188 -
BMC Oral Health Dec 2022Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. The present study aimed to compare the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS & BACKGROUND
Pilocarpine is an accepted treatment for xerostomia, but limited research has been conducted on the oral, topical form. The present study aimed to compare the effects of 1 and 2% pilocarpine mouthwash on xerostomic participants.
METHODS
In this double-blind clinical trial study, 48 subjects with xerostomia were randomly divided into three groups to measure the effects of 1 and 2% pilocarpine and placebo mouthwashes on saliva levels. The amount of saliva in the 1st and 14th days was measured at 0, 45, 60, and 75 mins, while participants used their mouthwash three times a day for 14 days. On the 1st and 14th days, they filled out the information forms on xerostomia and the medicine's side effects before and after the intervention.
RESULTS
On the 1st day, the mean salivary flow at 45, 60, and 75 mins in the 2 and 1% pilocarpine mouthwash were significantly higher than in the placebo mouthwash group (p < 0.05). On the 14th day, the mean salivary flow time at 45 mins in the 2% pilocarpine mouthwash group was significantly higher than in the placebo mouthwash group (p = 0.007). Furthermore, the mean salivary flow at 60 and 75 mins in the 2% (p < 0.001) and 1% pilocarpine mouthwash (p = 0.028) was significantly higher than in the placebo group. Moreover, the salivary flow in the 2% pilocarpine mouthwash group was significantly higher than the 1% pilocarpine mouthwash (p < 0.05) during these two times. No side effects were observed in any of the subjects.
CONCLUSIONS
The study showed that 5 ml of 2 and 1% pilocarpine mouthwash for 2 weeks increased salivary flow in xerostomic participants compared to placebo without any side effects.
Topics: Humans; Pilocarpine; Mouthwashes; Xerostomia; Saliva
PubMed: 36457091
DOI: 10.1186/s12903-022-02576-6 -
Epilepsy & Behavior : E&B Mar 20232-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of... (Review)
Review
2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET studies of regional brain glucose utilization positron-emitting 18F-2DG demonstrate that brain regions generating seizures have diminished glucose utilization during interictal conditions, but rapidly transition to markedly increased glucose delivery and utilization during seizures, particularly in status epilepticus (SE). 2-deoxy-D-glucose has acute antiseizure actions in multiple in vivo and in vitro seizure models, including models of SE induced by the chemo convulsants pilocarpine and kainic acid, suggesting that focal enhanced delivery of 2DG to ictal brain circuits is a potential novel anticonvulsant intervention for the treatment of SE.
Topics: Humans; Deoxyglucose; Status Epilepticus; Seizures; Glucose; Glycolysis; Pilocarpine
PubMed: 36804714
DOI: 10.1016/j.yebeh.2023.109108 -
Journal of Cancer Research and... 2023Patients with head-and-neck cancers can develop salivary gland hypofunction after radiotherapy. Oral pilocarpine has been shown to be effective treatment for... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Patients with head-and-neck cancers can develop salivary gland hypofunction after radiotherapy. Oral pilocarpine has been shown to be effective treatment for radiation-induced xerostomia, although its usefulness is being discussed.
AIMS
We aimed to evaluate the efficacy and safety profile of oral pilocarpine in radiation-induced xerostomia.
MATERIALS AND METHODS
Sixty patients with oropharyngeal carcinoma were planned for radiotherapy and divided into two arms randomly: Arm A (30 patients) received oral pilocarpine and Arm B (30 patients) received placebo tablets for 12 weeks after 3 months of completion of radiotherapy. Salivary gland scintigraphy and xerostomia questionnaire (XQ) were obtained from each patient at baseline and at 3 and 6 months of completion of radiotherapy.
RESULTS
There was a marked decrease in uptake ratio (UR) and excretion fraction (EF) after 3 months of completion of radiotherapy. There was a statistically significant difference between both the arms in relation to UR, but no significant difference was observed between the two arms in relation to EF after 6 months of completion of radiotherapy. A statistically significant difference was found comparing the XQ results in both the arms. The XQ results did not correlate with salivary gland dysfunction observed by means of salivary scintigraphy. Adverse effects due to xerostomia were generally mild and occasionally of moderate severity.
CONCLUSION
The use of oral pilocarpine did not significantly improve salivary gland excretory function, despite better results on salivary uptake at 6 months. However, oral pilocarpine significantly improved symptoms of xerostomia with minor side effects that were predominantly limited to sweating.
Topics: Humans; Head and Neck Neoplasms; Pilocarpine; Radiation Injuries; Salivary Glands; Xerostomia
PubMed: 37470612
DOI: 10.4103/jcrt.jcrt_2346_21 -
American Journal of Ophthalmology Sep 2023To evaluate the safety, efficacy, and pharmacokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bilaterally, twice... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the safety, efficacy, and pharmacokinetics of pilocarpine hydrochloride 1.25% (Pilo hereafter) compared with vehicle when administered bilaterally, twice daily (6 hours apart) for 14 days in participants with presbyopia.
DESIGN
Phase 3, randomized (1:1), controlled, double-masked, multicenter study.
METHODS
Participants (40-55 years of age) had objective and subjective evidence of presbyopia affecting daily activities with mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) of 20/40 to 20/100. The primary/key secondary endpoint was the proportion of participants gaining ≥3 lines in mesopic/photopic, high-contrast, binocular DCNVA on day 14 (last study visit), hour 9 (3 hours after the second dose), with no more than a 5-letter loss in mesopic/photopic corrected distance visual acuity with the same refractive correction. Key safety measures included treatment-emergent adverse events (TEAEs) and some ocular measurements. Pilocarpine plasma levels were assessed in approximately 10% of enrolled participants.
RESULTS
Overall, 230 participants were randomized to Pilo twice daily (N = 114) and vehicle (N = 116). The proportion of participants achieving the primary and key secondary efficacy endpoints was statistically significantly greater with Pilo twice daily than vehicle, with between-treatment differences of 27.3% (95% CI = 17.3, 37.4) and 26.4% (95% CI = 16.8, 36.0), respectively. The most common TEAE was headache, reported in 10 participants (8.8%, Pilo group) and 4 participants (3.4%, vehicle group). Pilocarpine's accumulation index on day 14 was ≤1.11 after the second dose.
CONCLUSIONS
Near-vision improvements were statistically greater with Pilo twice daily than with vehicle, without compromising distance acuity. The safety profile of Pilo twice daily was consistent with that of Pilo once daily, and systemic accumulation was minimal, supporting twice daily administration.
Topics: Humans; Pilocarpine; Presbyopia; Visual Acuity; Refraction, Ocular; Double-Blind Method
PubMed: 37149245
DOI: 10.1016/j.ajo.2023.05.008