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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 -
Systematic Reviews May 2022Dry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for...
BACKGROUND
Dry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for the treatment of DED, with the use of artificial tear being the mainstay of treatment. In this scheme, the use of secretagogues is suggested as part of the treatment for patients with moderate to severe affectation. With this systematic review, we aim to evaluate the effectiveness and safety of secretagogues for DED.
METHODS
Electronic databases will be searched; we will include randomized controlled trials that compare secretagogues and artificial tears. Study inclusion will not be restricted on the basis of language or publication status. We will use Google Translate to assess studies written in languages other than English and Spanish. Identification, evaluation, data extraction, and assessment of risk of bias will be conducted by two authors of the review, a third review author will resolve any disagreement. The outcomes will be the ocular surface disease index score, tear film break-up time, Schirmer test score, VRQoL Score, and tear film osmolarity. We will use the Cochrane Collaboration Risk of Bias 2 (RoB 2) tool for assessing the risk of bias of the included studies. Based on the heterogeneity of the included studies, we will combine the findings in a meta-analysis using a fixed effect model if heterogeneity ≤ 50% or a random effect model if heterogeneity > 50%. If we deem meta-analysis as inappropriate, we will document the reasons and report findings from the individual studies narratively.
DISCUSSION
Based on the evidence obtained, we will evaluate the effect of pilocarpine, cevimeline, and diquafosol and compare it to artificial tears on multiple outcome measures. This systematic review aims to determine the efficacy and safety of the secretagogues pilocarpine, cevimeline, and diquafosol to help clinicians in the decision-making process.
TRIAL REGISTRATION
PROSPERO CRD42020218407 .
Topics: Dry Eye Syndromes; Humans; Lubricant Eye Drops; Meta-Analysis as Topic; Pilocarpine; Polyphosphates; Quinuclidines; Secretagogues; Systematic Reviews as Topic; Thiophenes; Uracil Nucleotides
PubMed: 35643581
DOI: 10.1186/s13643-022-01979-4 -
Ophthalmology and Therapy Apr 2023The aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special...
INTRODUCTION
The aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special topical formulation for presbyopia treatment.
METHODS
This was a case series consisting of consecutive participants with presbyopia aged 40-70 years who were tested for visual acuity and pupil diameter before and 2 h after instillation of a formulation of pilocarpine and phenylephrine drops (FOV Tears) for presbyopia. Participants underwent subjective refraction, photopic and scotopic pupil diameter measurement and unaided monocular and binocular visual acuity testing by logMAR for distance and near vision both pre- and post-instillation of eye drops.
RESULTS
The study enrolled 363 subjects (n = 176 women, 48%) with a mean (± standard deviation) age of 50.4 ± 5.8 years. Mean spherical equivalent (SE) changed significantly (- 0.17 Diopters) after instillation of the FOV Tears formulation (p < 0.001). Post-instillation of eye drops, the scotopic pupil diameter decreased by 0.97 ± 0.98 mm, and the near visual acuity by logMAR improved significantly by nearly two lines (p < 0.01). In the linear regression analyses, age (p < 0.001) and SE pre-drop instillation (p < 0.001) were associated with unaided binocular visual acuity. The changes in photopic pupil diameter and the scotopic pupil diameter were not associated with unaided binocular visual acuity.
CONCLUSIONS
The use of the pilocarpine and phenylephrine formulation (FOV Tears) improved binocular visual acuity for near vision in presbyopic patients, and the effect was independent of pupil change.
PubMed: 36637658
DOI: 10.1007/s40123-023-00648-6 -
International Journal of Molecular... Dec 2022Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the...
Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas Cx36 mRNA did not exhibit obvious changes. Regional evaluation with quantitative real-time-RT-PCR confirmed Cx43 and Cx30 mRNA downregulation 24 h after SE, when ongoing neuronal cell death was found in the same brain regions. Immunolabeling showed at the same time point marked a decrease in Cx43, microglia activation, and interleukin-1β induction in some microglial cells. The data showed a transient downregulation of astroglial Cxs in the cortical and thalamic areas in which SE triggers neurodegenerative events in concomitance with microglia activation and cytokine expression. This could potentially represent a protective response of neuroglial networks to SE-induced acute damage.
Topics: Animals; Rats; Astrocytes; Connexin 43; Connexins; Down-Regulation; Hippocampus; Pilocarpine; RNA, Messenger; Seizures; Status Epilepticus
PubMed: 36613467
DOI: 10.3390/ijms24010023 -
CNS Neuroscience & Therapeutics Dec 2019Activated microglia have been found in the forebrains and hippocampi of temporal lobe epilepsy (TLE) patients and status epileptic (SE) animal models. The peroxisome...
AIMS
Activated microglia have been found in the forebrains and hippocampi of temporal lobe epilepsy (TLE) patients and status epileptic (SE) animal models. The peroxisome proliferator-activated receptor γ (PPAR γ) agonist rosiglitazone has been shown to prevent microglial activation. However, its role in pilocarpine-induced status epilepticus remains unknown. We aimed to examine the effect of the PPAR γ agonist rosiglitazone in protecting against pilocarpine-induced status epileptic resulting from over-activation and to explore phenotypic changes in microglia as the underlying mechanism.
METHODS
Male C57BL/6 mice were assigned to three groups: the control group, pilocarpine-induced (SE) group, and rosiglitazone-treated (SE+Rosi) group. Status epileptic mice were administered 300 mg/kg pilocarpine via intraperitoneal injection. SE+Rosi mice were administered rosiglitazone (0.1 mg/kg, i.p.) after SE. Flow cytometry, immunofluorescence staining, and quantitative real-time PCR were used to examine the activation of and phenotypic changes in microglia in the brain and to evaluate neuroinflammation.
RESULTS
We found that the expression of proinflammatory CD86 and iNOS was increased and that the expression of antiinflammatory CD206 and Arg-1 was decreased in the brains of pilocarpine-induced SE mice compared to control mice. The mRNA levels of proinflammatory and antiinflammatory cytokines were not significantly changed in the brain. Rosiglitazone treatment significantly inhibited the proinflammatory polarization of microglia and rescued neuron loss in the temporal lobe and hippocampi of the brain after SE.
CONCLUSION
Rosiglitazone reverses microglial polarization in the brains of SE mice and also affords neuroprotection against pilocarpine-induced status epilepticus without inducing significant changes in brain inflammation.
Topics: Animals; B7-2 Antigen; Brain Chemistry; Cell Polarity; Convulsants; Cytokines; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Nitric Oxide Synthase Type II; PPAR gamma; Pilocarpine; Rosiglitazone; Status Epilepticus
PubMed: 31729170
DOI: 10.1111/cns.13265 -
Journal of Neurophysiology May 2023Emerging evidence suggests that the medial septum can control seizures occurring in focal epileptic disorders, thus representing a therapeutic target. Therefore, we...
Emerging evidence suggests that the medial septum can control seizures occurring in focal epileptic disorders, thus representing a therapeutic target. Therefore, we investigated whether continuous optogenetic activation of inhibitory parvalbumin (PV)-positive interneurons in the medial septum can reduce the occurrence of spontaneous seizures in the pilocarpine model of mesial temporal lobe epilepsy (MTLE). Light pulses (450 nm, 25 mW, 20-ms pulse duration) were delivered at 0.5 Hz (5 min ON, 10 min OFF) with a laser diode fiber light source between and after status epilepticus (SE) in PV-ChR2 mice ( = 8). Seizure rates were significantly lower during time periods of optogenetic stimulation () compared with before implementation of optogenetics () ( < 0.05). Moreover, between and after SE seizure rates were still significantly lower compared with before optogenetic stimulation (i.e., between and ) ( < 0.05). No seizures were recorded between and in all animals, and no seizures occurred up to 3 days after the end of optogenetic stimulation (). Our findings indicate that activation of PV interneurons in the medial septum abates seizures in the pilocarpine model of MTLE. Moreover, the persisting anti-ictogenic effects suggest that stimulation of the medial septum could alter the progression of MTLE. The medial septum could represent a therapeutic target to treat patients with focal epilepsy. In this study, we show that optogenetic activation of inhibitory parvalbumin-positive interneurons in the medial septum can block spontaneous seizures and prevents their reoccurrence for ∼5 days after the end of stimulation. Our findings suggest that the anti-ictogenic effects induced by stimulation of the medial septum could also alter the progression of mesial temporal lobe epilepsy.
Topics: Mice; Animals; Epilepsy, Temporal Lobe; Optogenetics; Pilocarpine; Parvalbumins; Status Epilepticus; Hippocampus; Disease Models, Animal
PubMed: 37073973
DOI: 10.1152/jn.00111.2023 -
Frontiers in Cell and Developmental... 2020Temporal lobe epilepsy (TLE) is a severe chronic neurological disease caused by abnormal discharge of neurons in the brain and seriously affect the long-term life...
Temporal lobe epilepsy (TLE) is a severe chronic neurological disease caused by abnormal discharge of neurons in the brain and seriously affect the long-term life quality of patients. Currently, new insights into the pathogenesis of TLE are urgently needed to provide more personalized and effective therapeutic strategies. Accumulating evidence suggests that sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1PR2) signaling pathway plays a pivotal role in central nervous system (CNS) diseases. However, the precise altered expression of SphK1 and S1PR2 in TLE is remaining obscure. Here, we have confirmed the expression of SphK1 and S1PR2 in the pilocarpine-induced epileptic rat hippocampus and report for the first time the expression of SphK1 and S1PR2 in the temporal cortex of TLE patients. We found an increased expression of SphK1 in the brain from both epileptic rats and TLE patients. Conversely, S1PR2 expression level was markedly decreased. We further investigated the localization of SphK1 and S1PR2 in epileptic brains. Our study showed that both SphK1 and S1PR2 co-localized with activated astrocytes and neurons. Surprisingly, we observed different subcellular localization of SphK1 and S1PR2 in epileptic brain specimens. Taken together, our study suggests that the alteration of the SphK1/S1PR2 signaling axis is closely associated with the course of TLE and provides a new target for the treatment of TLE.
PubMed: 33134289
DOI: 10.3389/fcell.2020.00800 -
Genes & Diseases May 2024Epilepsy, one of the most common neurological disorders, is characterized by spontaneous recurrent seizures. Temporal lobe epilepsy (TLE) is one of the most common...
Epilepsy, one of the most common neurological disorders, is characterized by spontaneous recurrent seizures. Temporal lobe epilepsy (TLE) is one of the most common medically intractable seizure disorders. Traf2-and NcK-interacting kinase (TNIK) has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders, but its role in epilepsy remains unclear. In this study, we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpine-induced rat model of epilepsy by western blotting, immunofluorescence, and immunohistochemistry. A pentylenetetrazole (PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy. Coimmunoprecipitation (Co-IP)/mass spectrometry (MS) was used to identify the potential mechanism. Through Co-IP, we detected and confirmed the main potential TNIK interactors. Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density (PSD) fractions. We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls. NCB-0846 delayed kindling progression and decreased seizure severity. Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi, notably CaMKII. Co-IP showed that TNIK might correlate with endogenous GRIA1, SYN2, PSD-95, CaMKIV, GABRG1, and GABRG2. In addition, the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling. Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.
PubMed: 38292191
DOI: 10.1016/j.gendis.2023.03.036 -
Frontiers in Chemistry 2022Ocular disorders comprising various diseases of the anterior and posterior segments are considered as the main reasons for blindness. Natural products have been... (Review)
Review
Ocular disorders comprising various diseases of the anterior and posterior segments are considered as the main reasons for blindness. Natural products have been identified as potential treatments for ocular diseases due to their anti-oxidative, antiangiogenic, and anti-inflammatory effects. Unfortunately, most of these beneficial compounds are characterised by low solubility which results in low bioavailability and rapid systemic clearance thus requiring frequent administration or requiring high doses, which hinders their therapeutic applications. Additionally, the therapeutic efficiency of ocular drug delivery as a popular route of drug administration for the treatment of ocular diseases is restricted by various anatomical and physiological barriers. Recently, nanotechnology-based strategies including polymeric nanoparticles, micelles, nanofibers, dendrimers, lipid nanoparticles, liposomes, and niosomes have emerged as promising approaches to overcome limitations and enhance ocular drug bioavailability by effective delivery to the target sites. This review provides an overview of nano-drug delivery systems of natural compounds such as thymoquinone, catechin, epigallocatechin gallate, curcumin, berberine, pilocarpine, genistein, resveratrol, quercetin, naringenin, lutein, kaempferol, baicalin, and tetrandrine for ocular applications. This approach involves increasing drug concentration in the carriers to enhance drug movement into and through the ocular barriers.
PubMed: 35494641
DOI: 10.3389/fchem.2022.850757 -
Neurobiology of Disease Sep 2022Mesial temporal lobe epilepsy (MTLE) is the most common type of focal refractory epilepsy and is characterized by recurring seizures that are often refractory to...
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal refractory epilepsy and is characterized by recurring seizures that are often refractory to medication. Since parvalbumin-positive (PV) interneurons were recently shown to play significant roles in ictogenesis, we established here how bilateral optogenetic stimulation of these interneurons in the hippocampus CA3 regions modulates seizures, interictal spikes and high-frequency oscillations (HFOs; ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of MTLE. Bilateral optogenetic stimulation of CA3 PV-positive interneurons at 8 Hz (lasting 30 s, every 2 min) was implemented in PV-ChR2 mice for 8 consecutive days starting on day 7 (n = 8) or on day 13 (n = 6) after pilocarpine-induced status epilepticus (SE). Seizure occurrence was higher in both day 7 and day 13 groups of PV-ChR2 mice during periods of optogenetic stimulation ("ON"), compared to when stimulation was not performed ("OFF") (day 7 group = p < 0.01, day 13 group = p < 0.01). In the PV-ChR2 day 13 group, rates of seizures (p < 0.05), of interictal spikes associated with fast ripples (p < 0.01), and of isolated fast ripples (p < 0.01) during optogenetic stimulations were significantly higher than in the PV-ChR2 day 7 group. Our findings reveal that bilateral activation of PV-interneurons in the hippocampus (leading to a presumptive increase in GABA signaling) favors ictogenesis. These effects may also mirror the neuropathological changes that occur over time after SE in this animal model.
Topics: Animals; Epilepsy, Temporal Lobe; Mice; Optogenetics; Pilocarpine; Seizures; Status Epilepticus
PubMed: 35718264
DOI: 10.1016/j.nbd.2022.105794