RESUMO
A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.
Assuntos
Acetaminofen , Acetazolamida , Glaucoma de Ângulo Fechado , Humanos , Glaucoma de Ângulo Fechado/induzido quimicamente , Glaucoma de Ângulo Fechado/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Acetazolamida/uso terapêutico , Acetazolamida/administração & dosagem , Acetaminofen/efeitos adversos , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Fenilefrina/efeitos adversos , Fenilefrina/administração & dosagem , Fenilefrina/uso terapêutico , Medicamentos sem Prescrição/efeitos adversos , Medicamentos sem Prescrição/administração & dosagem , Guaifenesina/efeitos adversos , Guaifenesina/administração & dosagem , Guaifenesina/uso terapêutico , Descongestionantes Nasais/efeitos adversos , Descongestionantes Nasais/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Medicamentos Compostos contra Resfriado, Influenza e Alergia/efeitos adversos , Pilocarpina/uso terapêutico , Pilocarpina/administração & dosagem , Pilocarpina/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Dexametasona/efeitos adversos , Dor Ocular/induzido quimicamente , Dor Ocular/etiologia , Doença AgudaRESUMO
BACKGROUND: The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision. CASE PRESENTATION: Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1-5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2. CONCLUSION: In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT.
Assuntos
Acomodação Ocular , Pressão Intraocular , Pilocarpina , Humanos , Pilocarpina/uso terapêutico , Pilocarpina/administração & dosagem , Masculino , Feminino , Adulto , Pressão Intraocular/fisiologia , Acomodação Ocular/fisiologia , Acuidade Visual , Mióticos/administração & dosagem , Mióticos/uso terapêutico , Pupila/efeitos dos fármacos , Esclera/cirurgia , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Terapia a Laser/métodos , Soluções Oftálmicas , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Administração TópicaRESUMO
OBJECTIVES: This study aimed to evaluate the efficacy of as-needed pilocarpine for the management of radiation-induced xerostomia. Additionally, the study sought to assess the side effects associated with an as-needed regimen. METHODS: A randomized, double-blinded, placebo-controlled crossover study was conducted on patients who had undergone radiation therapy for head and neck cancers and developed xerostomia. Participants took pilocarpine or placebo as needed for symptom relief at 2 weeks per treatment, which included a one-week washout period. The primary outcome measure was the severity of dry mouth symptoms, quantified using the Xerostomia Inventory (XI). The primary outcome was the change in the XI score. RESULTS: Among the 20 participants who completed the crossover study, there was a significant reduction in XI scores during the treatment phase with pilocarpine compared to the scores during the placebo phase. The mean difference in XI scores was -18.05 (95% CI: -17.17, -6.13, p < 0.001), with a-49.77 ± 3.22% change (p < 0.001). Only one participant withdrew due to pilocarpine side effects. CONCLUSION: As-needed pilocarpine administration is effective in relieving symptoms of radiation-induced xerostomia, with fewer side effects and reduced treatment costs compared to fixed-dose regimens. This study guides the potential shift toward flexible dosing strategies in clinical practice, promoting enhanced patient-centered, tailored care and adherence. LEVEL OF EVIDENCE: 2: According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines Laryngoscope, 134:4542-4548, 2024.
Assuntos
Estudos Cross-Over , Neoplasias de Cabeça e Pescoço , Pilocarpina , Lesões por Radiação , Xerostomia , Humanos , Xerostomia/etiologia , Xerostomia/tratamento farmacológico , Pilocarpina/administração & dosagem , Pilocarpina/uso terapêutico , Masculino , Neoplasias de Cabeça e Pescoço/radioterapia , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Idoso , Agonistas Muscarínicos/uso terapêutico , Agonistas Muscarínicos/administração & dosagem , Resultado do Tratamento , AdultoRESUMO
AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.
Assuntos
Neoplasias de Cabeça e Pescoço , Pilocarpina , Lesões por Radiação , Xerostomia , Humanos , Masculino , Neoplasias de Cabeça e Pescoço/radioterapia , Pilocarpina/uso terapêutico , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Xerostomia/etiologia , Idoso , Lesões por Radiação/etiologia , Adulto , Agonistas Muscarínicos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
PURPOSE: To evaluate the efficacy of topical pilocarpine HCl 1.25% (Pilo) in treating presbyopia in individuals with or without a history of laser vision correction (laser-assisted in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]). SETTING: Multiple clinical sites. DESIGN: Pooled analysis of 2 identically designed prospective, randomized, vehicle-controlled studies (GEMINI 1 and 2). METHODS: Adults aged 40 to 55 years with presbyopia received once-daily Pilo or vehicle bilaterally for 30 days. Responder rates for ≥3-line improvement in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) were determined on day 30. RESULTS: Among participants with a history of LASIK/PRK (n = 39 in the Pilo group, n = 41 in the vehicle group), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.7%, 38.9%, 41.7%, 37.8%, 16.2%, 13.9%, and 8.3% with Pilo and 0.0%, 2.6%, 10.5%, 5.1%, 7.7%, 2.6%, and 0.0% with vehicle. Responder rates in the LASIK/PRK subgroup were significantly higher with Pilo than vehicle at hours 0.25 ( P = .0087), 0.5 ( P = .0001), 1 ( P = .0022), and 3 ( P = .0005). In contrast, there were no significant differences in responder rates between Pilo-treated participants with and without LASIK/PRK. Among non-LASIK/PRK participants in the Pilo group (n = 336), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.8%, 32.7%, 39.0%, 28.0%, 17.4%, 12.6%, and 10.5%. CONCLUSIONS: Pilo treatment effectively and similarly improved DCNVA in presbyopes with or without a history of laser vision correction.
Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Ceratectomia Fotorrefrativa , Presbiopia , Adulto , Humanos , Pilocarpina/uso terapêutico , Refração Ocular , Lasers de Excimer/uso terapêutico , Estudos Prospectivos , Presbiopia/cirurgia , Resultado do Tratamento , Miopia/cirurgia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory process. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/µL, 1 µL) followed by fMLP (1 mg/mL, 1 µL) or vehicle (VEH, saline 0.9%, 1 µL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine's Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy. Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).
Assuntos
Epilepsia , Estado Epiléptico , Ratos , Masculino , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , N-Formilmetionina Leucil-Fenilalanina/farmacologia , N-Formilmetionina Leucil-Fenilalanina/uso terapêutico , Pilocarpina/uso terapêutico , Ratos Wistar , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/complicações , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Peptídeos/uso terapêuticoRESUMO
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.
Assuntos
Neoplasias de Cabeça e Pescoço , Lesões por Radiação , Xerostomia , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Pilocarpina/uso terapêutico , Pilocarpina/efeitos adversos , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Glândulas Salivares , Xerostomia/tratamento farmacológico , Xerostomia/etiologiaRESUMO
The present study was conducted to determine the effects of the γ-aminobutyric acid B (GABAB ) receptor positive allosteric modulator BHF177 on refractory epilepsy (RE). An RE rat model was initially established via treatment with lithium-pilocarpine. The RE rats were then treated with BHF177 or the GABAB receptor antagonist CGP46381, followed by recording of their seizure rate and assessment of their spatial learning in the Morris water maze test. Treatment of BHF177 reduced the seizure intensity, whereas this effect was revered upoj treatment with CGP46381. Immunohistochemistry revealed that BHF177 treatment diminished P-glycoprotein (P-gp) expression in the hippocampal tissues of RE rats. Next, we found that BHF177 activated GABAB receptor, resulting in upregulated expression of insulin receptor substrate 1 (IRS-1) and PI3K, as well as antiapoptotic factors (Bcl-2 and mTOR), along with suppression of the apoptosis factors Bax and cleaved caspase-3 in the hippocampal tissues. Further, activation of GABAB receptors by BHF177 alleviated the inflammatory response in hippocampal tissues of RE rats, as evidenced by reduced VCAM-1, ICAM-1, and tumor necrosis factor-α levels. Next, we treated primary cultured rat hippocampal neurons with BHF177 and the IRS-1 selective inhibitor NT157. BHF177 inhibited hippocampal apoptosis in rat hippocampal neurons by regulating the IRS-1/PI3K/Akt axis through crosstalk between GABAB and insulin-like growth factor-1 receptors. Collectively, our findings indicate that the BHF177 inhibited neuron apoptosis, thus protecting against RE through the IRS-1/PI3K/Akt axis, which may present a new therapeutic channel for RE.
Assuntos
Epilepsia Resistente a Medicamentos , Receptores de GABA-B , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia Resistente a Medicamentos/patologia , Hipocampo/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Lítio/metabolismo , Lítio/farmacologia , Lítio/uso terapêutico , Neurônios/metabolismo , Norbornanos , Fosfatidilinositol 3-Quinases/metabolismo , Pilocarpina/metabolismo , Pilocarpina/farmacologia , Pilocarpina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas , Ratos , Receptores de GABA-B/metabolismo , Receptores de GABA-B/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Convulsões/patologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/farmacologia , Molécula 1 de Adesão de Célula Vascular/uso terapêutico , Proteína X Associada a bcl-2/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
RATIONALE: Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG. PATIENT CONCERNS: A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours. DIAGNOSES: The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination. INTERVENTIONS: The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes. OUTCOMES: No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for >6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed. CONCLUSION: This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.
Assuntos
Catarata , Glaucoma de Ângulo Fechado , Terapia a Laser , Doença Aguda , Feminino , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/etiologia , Glaucoma de Ângulo Fechado/cirurgia , Humanos , Pressão Intraocular , Iris/cirurgia , Lasers , Pessoa de Meia-Idade , Pilocarpina/uso terapêuticoRESUMO
Sjogren's syndrome and radiation therapy for head and neck cancers are often accompanied by xerostomia. Oral pilocarpine (PCP) to treat xerostomia produces systemic side effects, such as runny nose and lacrimation. To improve the therapeutic efficacy of PCP and reduce the aforementioned side effects, we developed a topical delivery system for PCP using freeze-dried sheets of hyaluronic acid (HA). The advantages of HA sheets over conventional oral formulations were examined through in vivo pharmacokinetic and pharmacodynamic studies after their application to oral tissues and salivary glands. The concentration of PCP in the submucosal tissue of the oral cavity was determined using the microdialysis (MD) method after buccal application of HA sheets containing PCP to hamsters. The concentration of PCP in the MD outflow was quite low after gastric administration, whereas the PCP concentration in plasma was high. In contrast, after buccal application of HA sheets containing PCP, the concentration of the drug in the MD outflow increased, despite the negligible concentration in plasma. These findings indicated that both enhancement of saliva secretion and the avoidance of systemic side effects could be achieved through buccal administration of PCP-loaded HA sheets. In addition, the pharmacodynamic study showed that when compared with intravenous and gastric administration, salivary application of HA sheets containing PCP resulted in similar volumes of saliva secretion and reduced lacrimal secretions. In conclusion, freeze-dried HA sheets allow for the development of a novel buccal delivery system with enhanced therapeutic efficacy and safety to treat xerostomia.
Assuntos
Neoplasias de Cabeça e Pescoço , Xerostomia , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Pilocarpina/farmacologia , Pilocarpina/uso terapêutico , Glândulas Salivares/efeitos da radiação , Salivação/efeitos da radiação , Xerostomia/induzido quimicamente , Xerostomia/tratamento farmacológicoRESUMO
Epilepsy is one of the most frequent neurological disorders characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in the pathways of neurodegenerations leading to epilepsy. Approximately, one-third of the epileptic patients who suffer from seizures do not receive effective medical treatment. Sodium valproate (SVP) is a commonly used antiepileptic drug (AED); however, it has toxic effects. Lutein (L), a carotenoid, has potent antioxidant and anti-inflammatory properties. The aim of this study was to determine the neuroprotective effect of sodium valproate (SVP) and lutein (L) in a rat model of pilocarpine- (PLC-) induced epilepsy. To achieve this aim, fifty rats were randomly divided into five groups. Group I: control, group II: received PLC (400 mg/kg intraperitoneally), group III: received PLC + SVP (500 mg/kg orally), group IV: received PLC + SVP + L (100 mg/kg orally), and group V: received (PLC + L). Racine Scale (RC) and latency period to onset seizure were calculated. After eight weeks, the hippocampus rotarod performance and histological investigations were performed. Oxidative stress was investigated in hippocampal homogenates. Results revealed that SVP and L, given alone or in combination, reduced the RC significantly, a significant delay in latency to PLC-kindling onset, and improved rotarod performance of rats compared with the PLC group. Moreover, L was associated with a reduction of oxidative stress in hippocampal homogenate, a significant decrease in serum tumor necrosis factor-alpha (TNF-α) level, and inhibition of cerebral injury and displayed antiepileptic properties in the PLC-induced epileptic rat model. Data obtained from the current research elucidated the prominent neuroprotective, antioxidant, and anti-inflammatory activities of lutein in this model. In conclusion, lutein cotreatment with AEDs is likely to be a promising strategy to improve treatment efficacy in patients suffering from epilepsy.
Assuntos
Epilepsia , Fármacos Neuroprotetores , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Humanos , Luteína/farmacologia , Luteína/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Pilocarpina/uso terapêutico , Ratos , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêuticoRESUMO
The Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though rarely getting sick. Previous studies on male Proechimys have revealed an endogenous resistance to epilepsy. Here, we assess in female Proechimys, whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX) Proechimys were compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE in Proechimys was higher (25- to 50-folds more). Despite a higher dose, Proechimys did not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that female Proechimys are resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance in Proechimys against SE induction.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/fisiopatologia , Pilocarpina/uso terapêutico , Roedores/fisiologia , Estado Epiléptico/tratamento farmacológico , Animais , Glicemia/análise , Modelos Animais de Doenças , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Ovariectomia , Progesterona/sangue , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Roedores/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/fisiopatologiaRESUMO
Immune checkpoint inhibitors can affect any organ, including the salivary glands. A case of Sjögren's syndrome (SjS) induced by nivolumab for the treatment of gastric cancer is herein presented. Nivolumab treatment caused marked tumor shrinkage, but xerostomia developed after two cycles. It took 3 months after symptom onset to confirm the diagnosis of SjS. Prednisolone and pilocarpine hydrochloride did not relieve the symptoms. SjS is a relatively rare immune-related adverse event that might sometimes be overlooked. Since SjS can severely impair a patient's quality of life, oncologists should not miss any signs of salivary gland hypofunction and cooperate with specialists for SjS.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Síndrome de Sjogren/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Feminino , Humanos , Pilocarpina/uso terapêutico , Prednisolona/uso terapêutico , Glândulas Salivares/fisiopatologia , Síndrome de Sjogren/imunologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/imunologia , Xerostomia/induzido quimicamenteRESUMO
Although pilocarpine hydrochloride tablets are currently indicated for the treatment of xerostomia, their adverse effects are frequently reported. The development of a new, low-dose pilocarpine solution for topical oral-cavity use is needed. This article discusses a few clinical trials to formulate a topical low-dose solution of pilocarpine hydrochloride for the treatment of xerostomia and presents two low dose, stable formulations of pilocarpine topical spray that can improve the patient's quality of life with minimal adverse effects.
Assuntos
Neoplasias de Cabeça e Pescoço , Agonistas Muscarínicos/uso terapêutico , Xerostomia , Humanos , Agonistas Muscarínicos/administração & dosagem , Pilocarpina/administração & dosagem , Pilocarpina/uso terapêutico , Qualidade de Vida , Xerostomia/tratamento farmacológicoRESUMO
BACKGROUND: Epilepsy is a chronic and severe neurological disorder. Phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient mice exhibit learning and memory deficits and spontaneous epilepsy. The aim of this study was to investigate the role of PTEN in brain oxidative damage and neuroinflammation in a rat model of epilepsy. METHODS: An adenovirus (Ad)-PTEN vector was constructed, and status epilepticus (SE) was induced in 41 model rats using lithium chloride-pilocarpine. Thirty-six SE rats were then allocated into the Ad-PTEN, Ad-LacZ, and SE groups, those were administered intracerebroventricular injections of Ad-PTEN, Ad-enhanced green fluorescent protein, and phosphate buffer saline, respectively. The normal group was comprised of healthy Sprague-Dawley rats. Nissl staining was conducted to evaluate neuronal damage, and immunohistochemistry was conducted to observe the morphology of cells in the hippocampal CA1 region and the distribution of ionized calcium-binding adaptor molecule 1 (Iba1) and ED1 (rat homologue of human CD68). Levels of apoptosis-related proteins, inflammatory-related factors, and oxidative stress-related markers (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD], and malondialdehyde [MDA]) were measured. Comparisons between multiple groups were conducted using one-way analysis of variance (ANOVA), and pairwise comparisons after ANOVA were conducted using the Tukey multiple comparisons test. RESULTS: After SE induction, PTEN expression in the rat brain exhibited a four-fold decrease (Pâ=â0.000) and the expression of both Iba1 and ED1 increased. Furthermore, significant neuronal loss, oxidative damage, and neuroinflammation were observed in the SE rat brain. After intracerebroventricular injection of Ad-PTEN, PTEN expression exhibited a three-fold increase (Pâ=â0.003), and the expression of both Iba1 and ED1 decreased. Additionally, neurons were restored and neuronal apoptosis was inhibited. Furthermore, ROS and MDA levels decreased, GSH level and SOD activity increased, and neuroinflammation was reduced. CONCLUSION: Our study demonstrated that brain oxidative damage and neuroinflammation in SE rats were ameliorated by intracerebroventricular injection of Ad-PTEN.
Assuntos
Encéfalo/metabolismo , Epilepsia/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Adenoviridae/genética , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Malondialdeído/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , PTEN Fosfo-Hidrolase/genética , Pilocarpina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database.In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort.We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93).We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.
Assuntos
Terapia de Imunossupressão/efeitos adversos , Doença de Parkinson/etiologia , Síndrome de Sjogren/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Comorbidade , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Terapia de Imunossupressão/estatística & dados numéricos , Incidência , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Agonistas Muscarínicos/efeitos adversos , Agonistas Muscarínicos/uso terapêutico , Programas Nacionais de Saúde/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Pilocarpina/efeitos adversos , Pilocarpina/uso terapêutico , Quinuclidinas/efeitos adversos , Quinuclidinas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Taiwan/epidemiologia , Tiofenos/efeitos adversos , Tiofenos/uso terapêuticoRESUMO
PURPOSE: To compare the effects of laser iridotomy (LI) and pilocarpine on iridocorneal angle and anterior chamber structure in anatomically narrow angles (ANAs). MATERIALS AND METHODS: Temporal LI was performed 90 minutes after 2% pilocarpine administration in patients with occludable ANA. Swept-source optical coherence tomography B-scans of the anterior segment were obtained at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. Angle-opening distance (AOD), trabecular-iris surface area (TISA), and angle recess area (ARA) were measured at the temporal, superior, nasal, and inferior quadrants. Anterior chamber depth (ACD) and lens vault (LV) were also measured. AOD, TISA, ARA, ACD, and LV were compared among 3 time points: at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. RESULTS: Twenty-four eyes (24 patients; mean age, 55 y) were included. In all 4 quadrants and globally, AOD, TISA, and ARA increased from baseline after pilocarpine and after LI (all P<0.010). The increase in AOD, TISA, and ARA was greater after LI than after pilocarpine globally and in the temporal and superior quadrants (all P<0.040). ACD decreased and LV increased from baseline after pilocarpine (both P<0.001). Postpilocarpine anterior chambers were shallower with higher LV than post-LI (both P<0.016). CONCLUSION: LI is more effective than pilocarpine in widening the iridocorneal angle without significant shallowing the anterior chamber in eyes with ANA.
Assuntos
Câmara Anterior/diagnóstico por imagem , Córnea/diagnóstico por imagem , Glaucoma de Ângulo Fechado/terapia , Iridectomia/métodos , Iris/diagnóstico por imagem , Terapia a Laser/métodos , Agonistas Muscarínicos/uso terapêutico , Pilocarpina/uso terapêutico , Adulto , Idoso , Feminino , Glaucoma de Ângulo Fechado/diagnóstico por imagem , Glaucoma de Ângulo Fechado/tratamento farmacológico , Glaucoma de Ângulo Fechado/cirurgia , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Tomografia de Coerência Óptica/métodosRESUMO
Background: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by exocrine gland and extraglandular symptoms. We present a case report of pSS with an initial presentation of athetoid movements. Case Report: A 74-year-old female presented with a 2-month history of slow undulating movements in her trunk and thighs that eventually spread to her neck and lower extremities. She also reported dry eyes, dry mouth, as well as pain in her shoulders and thighs. Her proinflammatory markers and rheumatologic profile were positive. Her salivary gland biopsy revealed a Focus score > 2. Brain magnetic resonance imaging was normal. A diagnosis of pSS was made. The patient's symptoms improved with hydroxychloroquine, pilocarpine, gabapentin, and clonazepam. Discussion: Clinicians should consider and screen for primary autoimmune disorders as a cause of subacute athetoid movements in elderly patients. Although aggressive treatment has been recommended, treatment should be tailored to each patient's specific needs.
Assuntos
Atetose/complicações , Transtornos dos Movimentos/complicações , Síndrome de Sjogren/etiologia , Idoso , Aminas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Atetose/tratamento farmacológico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Feminino , Gabapentina , Humanos , Hidroxicloroquina/uso terapêutico , Transtornos dos Movimentos/tratamento farmacológico , Agonistas Muscarínicos/uso terapêutico , Pilocarpina/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
INTRODUCTION: Amyloidosis accompanied by Sjögren's syndrome (SS) has been reported to occur primarily in the skin, lungs, tongue, and mammary gland. However, SS in association with secondary amyloidosis is rarely reported, and knowledge of its relevance is inadequate. Here we report a case of primary SS diagnosed simultaneously with localized amyloidosis of the lacrimal gland. CASE PRESENTATION: A 45-year-old woman complaining of a left eyelid mass was referred to the hospital and was diagnosed with localized amyloidosis after excisional biopsy. She was then referred to the rheumatology department for additional evaluation for amyloidosis. Subsequently, her diagnosis was primary SS based on the presented symptoms and results of the Schirmer test, serologic testing, and minor salivary gland biopsy. Pilocarpine (10âmg/d) and hydroxychloroquine (200âmg/d) were initiated for the treatment of SS. Six months after the initial diagnosis, the dry eyes and mouth did not worsen and no masses suggestive of localized amyloidosis were reported. CONCLUSION: This is a rare case of amyloidosis, localized to the lacrimal gland, with SS. Therefore, despite its rarity, physicians should be aware of the potential coexistence of secondary amyloidosis, even in the localized form, in patients with SS.
Assuntos
Amiloidose/complicações , Aparelho Lacrimal/patologia , Síndrome de Sjogren/complicações , Amiloidose/tratamento farmacológico , Amiloidose/patologia , Antirreumáticos/uso terapêutico , Biópsia , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Aparelho Lacrimal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mióticos/uso terapêutico , Pilocarpina/administração & dosagem , Pilocarpina/uso terapêutico , Doenças Raras , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Resultado do TratamentoRESUMO
Hyposalivation is commonly observed in the autoimmune reaction of Sjögren's syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).