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1.
Braz. j. biol ; 83: e237412, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355854

ABSTRACT

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.


Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.


Subject(s)
Animals , Female , Rats , Pilocarpine/toxicity , Seizures/chemically induced , Status Epilepticus/chemically induced , Rats, Wistar , Muscarinic Agonists/toxicity , Models, Theoretical
2.
Arq. bras. oftalmol ; 84(2): 107-112, Mar,-Apr. 2021. tab
Article in English | LILACS | ID: biblio-1153113

ABSTRACT

ABSTRACT Purpose: To investigate the effects of pharmacological accommodation and cycloplegia on ocular measurements. Methods: Thirty-three healthy subjects [mean (±SD) age, 32.97 (±5.21) years] volunteered to participate in the study. Measurement of the axial length, macular and choroidal thickness, refractive error, and corneal topography, as well as anterior segment imaging, were performed. After these procedures, pharmacological accommodation was induced by applying pilocarpine eye drops (pilocarpine hydrochloride 2%), and the measurements were repeated. The measurements were repeated again after full cycloplegia was induced using cyclopentolate eye drops (cyclopentolate hydrochloride 1%). The correlations between the measurements were evaluated. Results: A significant increase in subfoveal choroidal thickness after applying 2% pilocarpine was identified (without the drops, 319.36 ± 90.08 µm; with pilocarpine instillation, 341.60 ± 99.19 µm; with cyclopentolate instillation, 318.36 ± 103.0 µm; p<0.001). A significant increase in the axial length was also detected (without the drops, 23.26 ± 0.83 mm; with pilocarpine instillation, 23.29 ± 0.84 mm; with cyclopentolate instillation, 23.27 ± 0.84 mm; p=0.003). Comparing pharmacological accommodation and cycloplegia revealed a significant difference in central macular thickness (with pilocarpine instillation, 262.27 ± 19.34 µm; with cyclopentolate instillation, 265.93 ± 17.91 µm; p=0.016). Pilocarpine-related miosis (p<0.001) and myopic shift (p<0.001) were more severe in blue eyes vs. brown eyes. Conclusion: Pharmacological accommodation may change ocular measurements, such as choroidal thickness and axial length. This condition should be considered when performing ocular measurements, such as intraocular lens power calculations.(AU)


RESUMO Objetivo: Investigar os efeitos da acomodação farmacológica e da cicloplegia nas medições oculares. Métodos: participaram do estudo 33 voluntários saudáveis (média de idade [± DP], 32,97 anos [± 5,21 anos]). Foram medidos o comprimento axial, a espessura macular e coroidal e o erro refrativo, bem como realizados exames de imagem da topografia corneana e do segmento anterior. Em seguida, foi induzida a acomodação farmacológica aplicando-se colírio de pilocarpina (cloridrato de pilocarpina a 2%) e as medições foram repetidas nos participantes. As mesmas medições foram repetidas depois de induzir a cicloplegia completa com colírio de ciclopentolato (cloridrato de ciclopentolato a 1%) e foram avaliadas as correlações entre as medidas. Resultados: Identificou-se aumento significativo da espessura coroidal subfoveal com o uso da pilocarpina a 2% (sem colírio, 319,36 ± 90,08 µm; com a instilação de pilocarpina, 341,60 ± 99,19 µm; com a instilação de ciclopentolato, 318,36 ± 103,0 µm; p<0,001). Detectou-se também aumento significativo do comprimento axial (sem colírio, 23,26 ± 0,83 mm; com a instilação de pilocarpina, 23,29 ± 0,84 mm; com a instilação de ciclopentolato, 23,27 ± 0,84 mm; p=0,003). Ao se comparar a acomodação farmacológica e a cicloplegia, houve diferença significativa na espessura macular central (com a instilação de pilocarpina, 262,27 ± 19,34 µm; com a instilação de ciclopentolato, 265,93 ± 17,91 µm; p=0,016). Observou-se que a miose associada à pilocarpina (p<0,001) e o desvio miópico (p<0,001) foram mais severos nos olhos azuis que nos castanhos. Conclusão: A acomodação farmacológica pode alterar medidas oculares como a espessura da coroide e o comprimento axial. Essa possibilidade deve ser levada em consideração ao se efetuarem medições oculares, tais como cálculos de potência de lentes intraoculares.(AU)


Subject(s)
Humans , Choroid/anatomy & histology , Accommodation, Ocular , Pilocarpine/pharmacology , Corneal Topography/instrumentation , Axial Length, Eye/anatomy & histology , Mydriatics/pharmacology
3.
Article in English | WPRIM | ID: wpr-888492

ABSTRACT

OBJECTIVES@#To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE).@*METHODS@#A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (@*RESULTS@#Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (@*CONCLUSIONS@#The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.


Subject(s)
Animals , Gap Junctions , Hippocampus , Pilocarpine , Rats , Seizures , Status Epilepticus/drug therapy
4.
Article in Korean | WPRIM | ID: wpr-811318

ABSTRACT

PURPOSE: We report a case of Urrets-Zavalia syndrome with a fixed dilated pupil after an uneventful trabeculectomy.CASE SUMMARY: Trabeculectomy was performed on a 51-year-old male who had a history of recurrent uveitis in the left eye, with uncontrolled intraocular pressure despite maximally-tolerated medial therapy. There was no unexpected event during surgery. Topical 1% atropine was used for only 2 days after surgery. In the early postoperative period, 1% prednisolone and 0.3% ofloxacin were given four times a day, then gradually reduced. One month later, only 1% prednisolone was given once a day. Intraocular pressure in his left eye was well controlled from 8–14 mmHg after surgery. One month after surgery, the pupils remained dilated. There was no reaction to topical 2% pilocarpine and no relative afferent pupillary defect or posterior synechia.CONCLUSIONS: Our case, although rare, suggests that Urrets-Zavalia syndrome should be considered in patients with well-controlled intraocular pressure after uneventful trabeculectomy.


Subject(s)
Atropine , Humans , Intraocular Pressure , Male , Middle Aged , Ofloxacin , Pilocarpine , Postoperative Period , Prednisolone , Pupil , Pupil Disorders , Trabeculectomy , Uveitis
5.
Article in English | WPRIM | ID: wpr-787136

ABSTRACT

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, real-time reverse transcriptase–polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.


Subject(s)
Animals , Astrocytes , Calcineurin , Calcium , Cell Death , Diazepam , Epilepsy , Epilepsy, Temporal Lobe , Fluorescent Antibody Technique , Hippocampus , Humans , Immunohistochemistry , In Situ Hybridization , Male , Mice , Microglia , Neurons , Neuropil , Oxidative Stress , Pilocarpine , RNA, Messenger , Seizures , Status Epilepticus , Up-Regulation , Viola
6.
Article in Chinese | WPRIM | ID: wpr-776508

ABSTRACT

OBJECTIVE@#To observe the expressions of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 2 (S1PR2) in hippocampus of epileptic rats and to investigate the pathogenesis of SphK1 and S1PR2 in epilepsy.@*METHODS@#One hundred and eight male Sprague-Dawley (SD) rats were randomly divided into control group (n=48) and pilocarpine (PILO) group (n=60). A robust convulsive status epilepticus (SE) was induced in PILO group rats by the application of pilocarpine. Control group rats were injected with respective of physiological saline. Pilocarpine group was randomly divided into 6 subgroups (n=8): acute group (E6 h, E1 d, E3 d), latent group (E7 d) and chronic group (E30 d, E56 d). Each subgroup has 8 control rats and 8 epileptic rats. Hippocampal tissue and brain slices were obtained from control rats and rats subjected to the Li-PILO model of epilepsy at 6 h, 1 d, 3 d,7 d,30 d and 56 d after status epilepticus (SE). Western blot technique was used to determine the expressions of SphK1 and S1PR2 in hippocampus at different point of time after pilocarpine treatment. Immunofluorescence was applied to detect the activation and proliferation of hippocampal astrocytes and the localization of SphK1 and S1PR2 in rat hippocampal astrocytes.@*RESULTS@#Compared with control group, the levels of SphK1 in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d) were significantly increased while the expressions of S1PR2 were decreased in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d)(P<0.05 or P<0.01). Immunofluorescence results showed astrocyte activation and proliferation in hippocampus of epileptic (E7 d) rats (P<0.05). Confocal microscopy confirmed the preferential expressions of SphK1 and S1PR2 in epileptic rat(E7 d)hippocampal astrocytes.@*CONCLUSION@#The results indicate that SphK1 and S1PR2 may play an important role in the pathogenesis of epilepsy by regulating the activation and proliferation of hippocampal astrocytes and altering neuronal excitability.


Subject(s)
Animals , Astrocytes , Epilepsy , Hippocampus , Cell Biology , Male , Phosphotransferases (Alcohol Group Acceptor) , Metabolism , Pilocarpine , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Lysosphingolipid , Metabolism
7.
Article in English | WPRIM | ID: wpr-766182

ABSTRACT

OBJECTIVE: To investigate longitudinal changes in the European League Against Rheumatism (EULAR) Sjögren's syndrome patient reported index (ESSPRI) and to study the clinical features associated with favorable ESSPRI changes in primary Sjögren's syndrome (pSS). METHODS: At baseline and after a median period of 6.6 years, 41 pSS patients were evaluated using the ESSPRI, EULAR Sjögren's syndrome disease activity index (ESSDAI), short-form 36, xerostomia inventory (XI), and visual analog scale (VAS) scores for symptoms. The favorable subgroup included patients who were stable or showed improved to satisfactory symptom status (ESSPRI<5) and the unfavorable subgroup included those with stable or worsening to an unsatisfactory symptom status (ESSPRI ≥5). RESULTS: Median ESSPRI increased from 4.11 to 5.33 (p<0.05), although XI scores (p=0.01) and oral dryness (p<0.05) were significantly decreased. Serum immunoglobulin G level was significantly reduced (p<0.001) but ESSDAI scores were unchanged. Six (14.6%) patients showed clinical improvement in ESSDAI, and 11 (26.8%) showed improvement in ESSPRI. On comparing the favorable (n=17) and unfavorable (n=24) subgroups, the former exhibited significantly lower VAS scores for sicca and depression and XI and ESSPRI scores at baseline (all p<0.05) and more lacrimal flow (p<0.05). The favorable subgroup received a significantly lower cumulative dose of pilocarpine and glucocorticoids (both p<0.05). CONCLUSION: About 25% of pSS patients showed clinically significant ESSPRI improvement and about 40% showed a favorable ESSPRI course. Because the favorable subgroup had more lacrimal flow and less sicca symptoms at baseline, long-term patient-derived outcomes could depend on residual exocrine function at pSS diagnosis.


Subject(s)
Depression , Diagnosis , Glucocorticoids , Humans , Immunoglobulin G , Patient Outcome Assessment , Pilocarpine , Quality of Life , Rheumatic Diseases , Visual Analog Scale , Xerophthalmia , Xerostomia
8.
Arq. bras. oftalmol ; 81(3): 195-201, May-June 2018. tab
Article in English | LILACS | ID: biblio-950455

ABSTRACT

ABSTRACT Purpose: We investigated parasympathetic innervation abnormalities of the iris sphincter and ciliary muscles in chronic Chagas disease by measuring pupillary diameter and intraocular pressure. Methods: A group of 80 patients with Chagas disease was compared with 76 healthy individuals without chagasic infection. The following procedures were performed: pupillometry, hypersensitivity test to pilocarpine 0.125%, intraocular pressure measurement (IOP), basal pupil diameter (BPD), absolute pupillary constriction amplitude (ACA), relative pupillary constriction amplitude (RCA) and the presence of anisocoria. Results: The prevalence of anisocoria was higher in chagasic patients (p<0.01). These patients had mean basal pupillary diameter, mean photopic pupillary diameter and mean value of absolute pupillary constriction amplitude significantly lower than non-chagasic ones (p<0.01, mean difference -0.50mm), (p=0.02, mean difference -0.20mm), (p<0.01, mean difference -0.29mm), respectively. The relative pupillary constriction amplitude did not differ between the two groups (p=0.39, mean difference -1.15%). There was hypersensitivity to dilute pilocarpine in 8 (10%) of the chagasic patients in the right eye and in 2 (2.5%) in the left eye and in 1 (1.25%) in both eyes. The mean value of intraocular pressure had a marginal statistical significance between the two groups (p=0.06, mean difference -0.91mmHg). Conclusions: Patients with chagasic infection may exhibit ocular parasympathetic dysfunction, demonstrable by pupillometry and the dilute pilocarpine hypersensitivity test.


RESUMO Introdução: Investigaram-se anormalidades da inervação parassimpática dos músculos esfíncter da íris e ciliar na doença de Chagas crônica, através de medidas pupilares e da pressão intraocular. Métodos: Foram estudados dois grupos, um com 80 chagásicos e outro com 76 indivíduos saudáveis sem infecção chagásica. Foram realizados os seguintes procedimentos: pupilometria, teste de hipersensibilidade à pilocarpina a 0,125%, medida da pressão intraocular (PIO), diâmetro basal da pupila (DBP), amplitude de constrição pupilar absoluta (ACA), amplitude de constrição pupilar relativa (ACR), e presença de anisocoria. Resultados: A prevalência de anisocoria foi maior nos chagásicos (p<0,01). Estes pacientes apresentaram diâmetro basal pupilar médio, diâmetro fotópico médio e valor médio da amplitude de constrição pupilar absoluta, significativamente menores que os não chagásicos, (p<0,01, diferença de média -0,50mm), (p=0.02, diferença de média -0,20mm), (p<0,01, diferença de média -0,29mm), respectivamente. A amplitude de constrição pupilar relativa não diferiu entre os dois grupos (p=0,39, diferença de média -1,15%). Houve hipersensibilidade à pilocarpina diluída em 8 (10%) chagásicos no olho direito em 2 (2,5%) no olho esquerdo e em 1 (1,25%) em ambos os olhos. O valor médio da pressão intraocular teve significância marginal entre os dois grupos (p=0,06, diferença de média -0,91mmHg). Conclusões: Pacientes com infecção chagásica podem apresentar disfunção parassimpática ocular, demonstrável pela pupilometria e pelo teste de hipersensibilidade à pilocarpina diluída.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Reflex, Pupillary/physiology , Anisocoria/etiology , Chagas Disease/complications , Intraocular Pressure/physiology , Pilocarpine/pharmacology , Reflex, Pupillary/drug effects , Anisocoria/diagnosis , Anisocoria/physiopathology , Case-Control Studies , Cross-Sectional Studies , Chagas Disease/physiopathology , Miotics/pharmacology
9.
Article in Chinese | WPRIM | ID: wpr-775293

ABSTRACT

OBJECTIVE@#To investigate the efficacy of brain-targeted rapamycin (T-Rap) in treatment of epilepsy in rats.@*METHODS@#Rapamycin nanoparticles targeting brain were prepared. The epilepsy model was induced by injection of pilocarpine in rats. The rats with pilocarpine-induced epilepsy were treated with rapamycin (Rap group) or brain-targeted rapamycin (T-Rap group). Seizure activity was observed by electroencephalography; the effect on mTOR signaling pathway was detected by Western blot; neuronal death and moss fiber sprouting were analyzed by Fluoro-Jade B (FJB) and Timm's staining, respectively.@*RESULTS@#Electroencephalography showed that both preparation of rapamycin significantly reduced the frequency of spontaneous seizures in rats, and the effect of T-Rap was stronger than that of conventional rapamycin (<0.05). Western blot showed that the phosphorylation levels of S6K and S6 in T-Rap group were lower than those in Rap group (all <0.05), indicating that T-Rap had a stronger inhibitory effect on mTOR signaling pathway. FJB staining showed that T-Rap significantly decreased neuronal death, but there was no significant difference as compared with Rap group. Timm's staining showed that both preparations of rapamycin significantly reduced the germination of mossy fibers, while the effect of T-Rap was more pronounced than Rap group (<0.05). The inhibition of body weight gain of T-Rap group was less than that of Rap group (<0.05).@*CONCLUSIONS@#T-Rap has a better therapeutic effect on epilepsy than conventional rapamycin with a less adverse effects in rats.


Subject(s)
Animals , Brain , Disease Models, Animal , Epilepsy , Drug Therapy , Neurons , Pilocarpine , Rats , Rats, Sprague-Dawley , Signal Transduction , Sirolimus , Pharmacology , Therapeutic Uses , Treatment Outcome
10.
Article in Korean | WPRIM | ID: wpr-738554

ABSTRACT

PURPOSE: We report a case of a male with bilateral tonic pupils associated with syphilis, that partially improved after syphilis treatment. CASE SUMMARY: A 27-year-old male presented with a 2-month history of near vision impairment. The right and left pupils were 5.5 mm and 6.5 mm in diameter, respectively, in the dark and 5.3 mm and 6.1 mm, respectively, in the light. Both pupils demonstrated light-near dissociation, slow constriction and redilation when looking at near, and constriction after instillation of 0.0625% pilocarpine. Serological tests were positive for syphilis, while cerebrospinal fluid testing was negative. Two months after treatment with intramuscular injection of benzathine penicillin G, his near vision subjectively improved and the right and left pupils were 5.9 mm and 6.4 mm, respectively, in the dark and 4.8 mm and 5.3 mm, respectively, in the light. The size of both pupils decreased and the pupillary light responses partially improved in both eyes. CONCLUSIONS: Patients with bilateral tonic pupils should have serological tests for syphilis. Recovery of tonic pupils can be expected after early treatment with effective antibiotics.


Subject(s)
Adult , Anti-Bacterial Agents , Cerebrospinal Fluid , Constriction , Humans , Injections, Intramuscular , Male , Penicillin G Benzathine , Pilocarpine , Pupil , Serologic Tests , Syphilis , Tonic Pupil
11.
Rev. ADM ; 74(5): 221-223, sept.-oct. 2017.
Article in Spanish | LILACS | ID: biblio-973040

ABSTRACT

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.


Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.


Subject(s)
Male , Female , Humans , Xerostomia/drug therapy , Pilocarpine/therapeutic use , Bethanechol/therapeutic use , Sjogren's Syndrome/drug therapy , Salivation/physiology
12.
J. oral res. (Impresa) ; 6(3): 64-69, Mar. 2017. tab
Article in English | LILACS | ID: biblio-907715

ABSTRACT

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.


Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Methylcellulose/administration & dosage , Methylcellulose/analogs & derivatives , Pilocarpine/administration & dosage , Sjogren's Syndrome , Xerostomia/prevention & control , Pilocarpine/adverse effects , Salivation , Xerostomia/chemically induced
13.
Appl. cancer res ; 37: 1-8, 2017. ilus
Article in English | LILACS, Inca | ID: biblio-915109

ABSTRACT

Xerostomia or dry mouth is one of the most common and disturbing adverse effects following radiotherapy for head and neck cancer (HNC). This complication strongly increases the risk for dental caries, difficulties with chewing, swallowing and sleep disorders with significant impact on patients' quality of life. Current treatment approaches of xerostomia are often difficult and bring in many cases no substantial relief for the patient. This paper discusses the clinical features and current knowledge of xerostomia prevention in order to evaluate the real possibilities of reducing the incidence and severity of this complication in HNC patients. Salivary gland cytoprotectants (amifostine), muscarinic agonist stimulation (pilocarpine and bethanechol), salivary gland-sparing radiation technique (intensity-modulated radiotherapy- IMRT), surgical relocation of the submandibular gland, intraoral stent and stem cell transplantation are promising techniques that are discussed in this study (AU)


Subject(s)
Humans , Pilocarpine , Radiotherapy , Salivary Glands , Submandibular Gland/surgery , Review Literature as Topic , Stem Cell Transplantation , Disease Prevention , Head and Neck Neoplasms , Xerostomia
14.
Article in English | WPRIM | ID: wpr-728588

ABSTRACT

Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.


Subject(s)
Animals , Bipolar Disorder , Brain , Hippocampus , Lithium , Mice , Mortality , Nervous System Diseases , Neurons , Neuroprotection , Neuroprotective Agents , Pilocarpine , Receptors, Muscarinic , Seizures , Status Epilepticus , Viola
15.
Experimental Neurobiology ; : 287-294, 2017.
Article in English | WPRIM | ID: wpr-18844

ABSTRACT

Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification. The 7.0 Tesla magnetic resonance imaging (MRI) with high resolution flurodeoxyglucose positron emission tomography (FDG-PET) was performed at 3 hours, 1, 3, 7 days and 4 weeks after the initial insult. The initial SRS was observed 9.7±1.3 days after the pilocarpine injection. MRI revealed an abnormal T2 signal change with swelling in both hippocampi and amygdala in acute (day 1 after injection) and latent phases (days 3 and 7), in association with PET hypometabolism in these areas. Interestingly, the mean frequency of class 3 to 5 SRS was positively correlated with abnormal T2 signals in hippocampal area at 3 days. SRS duration became longer with more decreased glucose metabolism in both hippocampi and amygdala at 7 days after pilocarpine injection. This study indicates that development and severity of SRS at chronic phase could be closely related with structural and functional changes in hippocampus during the latent period, a pre-epileptic stage.


Subject(s)
Amygdala , Animals , Classification , Epilepsy , Epilepsy, Temporal Lobe , Glucose , Hippocampus , Humans , Magnetic Resonance Imaging , Male , Metabolism , Models, Animal , Neuroimaging , Pilocarpine , Positron-Emission Tomography , Rats , Rats, Sprague-Dawley , Seizures , Status Epilepticus
16.
Rev. bras. parasitol. vet ; 25(2): 248-253, tab
Article in English | LILACS | ID: lil-785159

ABSTRACT

Abstract The aim of this study was to assess the activity of aqueous (AE) and ethanolic extracts (EE) and pilocarpine hydrochloride, which were extracted and isolated from Pilocarpus microphyllus (Jaborandi), respectively, on Rhipicephalus (Boophilus) microplus. High performance liquid chromatography (HPLC) was performed to quantify these compounds. Larval packet and adult immersion tests were conducted with different concentrations. Five AE and EE concentrations, ranging from 6.2 to 100.0 mg mL–1, and six concentrations of pilocarpine hydrochloride, ranging from 0.7 to 24.0 mg mL–1, were tested. The lethal concentration (LC50) of each extract for larvae and engorged females was calculated through Probit analysis. The concentration of pilocarpine hydrochloride obtained from the EE and the AE was 1.3 and 0.3% (m/m), respectively. Pilocarpine hydrochloride presented the highest acaricidal activity on larvae (LC50 2.6 mg mL–1) and engorged females (LC50 11.8 mg mL–1) of R.(B.) microplus, followed by the EE which presented LC50 of 56.4 and 15.9 mg mL–1, for larvae and engorged females, respectively. Such results indicate that pilocarpine hydrochloride has acaricidal activity, and may be the primary compound responsible for this activity by P. microphyllus EE.


Resumo O objetivo desse estudo foi avaliar a atividade dos extratos aquoso (AE) e etanólico (EE) e do cloridrato de pilocarpina, que foram, respectivamente, extraídos e isolado de Pilocarpus microphyllus (Jaborandi), sobre Rhipicephalus (Boophilus) microplus. Cromatografia líquida de alta eficiência foi realizada para quantificação dos compostos. Testes de pacote de larvas e de imersão de adultos foram realizados com diferentes concentrações. Cinco concentrações do AE e EE variando de 6,2 a 100,0 mg mL–1 e seis concentrações do cloridrato de pilocarpina variando de 0,7 a 24,0 mg mL–1 foram testadas. A concentração letal (CL50) de cada extrato para larvas e fêmeas ingurgitadas foi estimada por meio da análise Probit. A concentração de cloridrato de pilocarpina obtida do EE e AE foi de 1,3 e 0,3% (m/m), respectivamente. O cloridrato de pilocarpina apresentou a maior atividade carrapaticida sobre larvas (CL50 2,6 mg mL–1) e fêmeas ingurgitadas (CL50 11,8 mg mL–1) de R. (B.) microplus, seguido do EE que apresentou CL50 de 56,4 e 15,9 mg mL–1, para larvas e fêmeas ingurgitadas, respectivamente. Tais resultados indicam que o cloridrato de pilocarpina apresenta atividade carrapaticida e pode ser o principal responsável pela atividade acaricida do EE de P. microphyllus.


Subject(s)
Animals , Female , Pilocarpine/pharmacology , Plant Extracts/pharmacology , Pilocarpus/chemistry , Rhipicephalus/drug effects , Acaricides/pharmacology , Larva/drug effects , Lethal Dose 50
17.
Clinics ; 71(5): 291-294, May 2016. tab, graf
Article in English | LILACS | ID: lil-782837

ABSTRACT

OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (p<0.05). RESULTS: The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10±12.23 μm, 30.90±1.14 μm, 28.16±2.98 μm and 29.84±2.30 μm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809). CONCLUSION: Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats.


Subject(s)
Animals , Female , Muscarinic Agonists/pharmacology , Pilocarpine/pharmacology , Vagina/pathology , Atrophy/drug therapy , Epithelium/drug effects , Epithelium/pathology , Models, Animal , Random Allocation , Rats, Wistar , Vagina/drug effects
18.
Article in Chinese | WPRIM | ID: wpr-340572

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group.</p><p><b>RESULTS</b>There was no significant difference in the success rate of induction of SE between the three groups (P>0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P<0.05), a significantly lower Lado score of seizure (P<0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P<0.05), and a slightly reduced mortality rate.</p><p><b>CONCLUSIONS</b>The treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.</p>


Subject(s)
Animals , Electroencephalography , Male , MicroRNAs , Pilocarpine , Pharmacology , Rats , Rats, Sprague-Dawley , Status Epilepticus , Drug Therapy
19.
Rev. bras. oftalmol ; 74(5): 312-314, set.-out. 2015. tab, ilus
Article in English | LILACS | ID: lil-757456

ABSTRACT

The Holmes-Adie syndrome is characterized by the presence of tonic pupil associated with absence or diminution of deep tendon reflexes. In some cases there may be autonomous nerve dysfunction. The mechanism that causes the disorder is not fully known, but is believed to be caused by denervation of the postganglionic supply to the sphincter of the pupil and the ciliary muscle which can occur following viral disease. Typically it affects young adults and is unilateral in 80% of cases, although it may develop in the contralateral eye in months or years. We report a case of a woman presenting typical signs of this syndrome, in which pharmacological test was essential for diagnosis.


A Síndrome de Holmes-Adie É caracterizada pela presença de pupila tônica associada à diminuição ou ausência dos reflexos tendíneos profundos. Em alguns casos pode haver disfunção nervosa autônoma. O mecanismo que causa a desordem não é totalmente conhecido, mas acredita-se que seja causada pela desnervação do suprimento pós-ganglionar para o esfíncter da pupila e para o músculo ciliar, que pode ocorrer após doença viral. Tipicamente afeta adultos jovens e é unilateral em 80% dos casos, embora possa se desenvolver no olho contralateral em meses ou anos. Nós relatamos o caso de uma mulher apresentando sinais típicos desta síndrome, em que o teste farmacológico foi fundamental para o diagnóstico.


Subject(s)
Humans , Female , Adult , Miotics , Pilocarpine , Tonic Pupil/diagnosis , Adie Syndrome/diagnosis
20.
J. oral res. (Impresa) ; 4(2): 103-108, abr.2015. ilus, graf
Article in English | LILACS | ID: lil-779211

ABSTRACT

The local use of prolonged drug delivery in the oral cavity provides many advantages, i.e., it increases pharmacologic actions in the desired local site, allows smaller doses and reduces adverse effects. Pilocarpineis a cholinergic drug approved by the FDA for treating glandular hypofunction; however, the adverse effects associated with it limit its use. Objective: To evaluate cytotoxicity of films in adherent fibroblasts and their ability to release pilocarpine in vivo for a prolonged time in the oral cavity of diabetic rats and its effect on salivary flow. Methods: Chitosan and Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. Cytotoxicity of films was evaluated in adherent fibroblasts HS27 and assessed by neutral red technique. The sialogogue effect of films was evaluated on the floor of the mouth of diabetic rats. Later, histopathological analysis was performed using hematoxylin and eosin and Masson’s trichrome stains. Results: Films were biocompatible and had 96 percent cell viability. It was possible to increase stimulation of salivary flow in diabetic rats (6.36+/-0.987mg/hr) compared to the control group (0.5+/-0.06mg/hr). The histopathological analysis did not show inflammatory infiltrate in the area where films were placed. Conclusion: Films were biocompatible and had high cell viability. Also, they considerably increased salivary flow in diabetic rats, without triggering an inflammatory infiltrate in the area which indicates that it is a biocompatible product for sustained release and safe for pilocarpine administration...


El uso local de administración prolongada de fármacos en la cavidad oral proporciona múltiples ventajas, aumentando la acción farmacológica en el sitio de acción, reducción de la dosis usual y disminución de los efectos adversos. La pilocarpina es una droga aprobada por la FDA para el tratamiento del deterioro de las glándulas salivales, sin embargo sus efectos adversos limitan su uso. Objetivo: Evaluar la citotoxicidad de las biopelículas en fibroblastos adherentes y su capacidad in vivo de liberar pilocarpina prolongadamente en la cavidad oral de ratas diabéticas y su efecto en el flujo salival. Metodología: Se elaboraron biopelículas de Quitosán y HPMC (Methocel K4MCR) adicionadas con pilocarpina en una solución de ácido acético 1 por ciento. Fue evaluada la citotoxicidad de las biopelículas en fibroblastos adherentes HS27 mediante la técnica de rojo neutro, además de ser evaluado el efecto sialogogo de las biopelículas en el piso de boca en ratas diabéticas Wistar, realizando después un análisis histopatológico de la zona de colocación, mediante la tinción de Hematoxilina y Eosina y Tricrómico de Masson. Resultados: Las biopelículas resultaron ser biocompatibles con un 96 por ciento de viabilidad celular. Se logró aumentar la estimulación del flujo salival en las ratas diabéticas (6.36+/-0.987 mg/hr), a comparación del grupo control (0.5+/-0.06 mg/hr). El análisis histopatológico no reveló un infiltrado inflamatorio presente en la zona de aplicación de las biopelículas. Conclusión: Las biopelículas resultaron biocompatibles con alta viabilidad celular, además que lograron aumentar considerablemente el flujo salival en ratas diabéticas, sin desencadenar un infiltrado inflamatorio en la zona de aplicación, indicando que es un producto de liberación prolongada biocompatible y seguro para la administración de pilocarpina...


Subject(s)
Animals , Rats , Mouth , Diabetes Mellitus , Fibroblasts , Pilocarpine/pharmacology , Xerostomia , Biocompatible Materials , Biofilms , Materials Testing , Rats, Wistar
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