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BACKGROUND: Pyridostigmine is hypothesized to improve neurogenic orthostatic hypotension (nOH) symptoms without causing or exacerbating supine hypertension. The objective of this review was to evaluate the safety and efficacy of pyridostigmine for management of nOH. METHODS: A literature search of PubMed, Embase, and CENTRAL was performed in December 2023 for prospective trials with a placebo or active comparator. RESULTS: Four randomized and two non-randomized studies were reviewed. Three studies utilizing a single dose, crossover design found significant differences of orthostatics using adjunctive pyridostigmine. Two studies assessing longer-term endpoints demonstrated conflicting efficacy of pyridostigmine with one trial finding significant improvement in orthostatics and symptoms after three months of therapy. Use of pyridostigmine did not lead to supine hypertension with most adverse effects being cholinergic. CONCLUSION: Pyridostigmine may be considered as an adjunctive medication in individuals with nOH refractory to standard treatment options as it carries a favorable safety profile with low risk for supine hypertension.
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Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-α, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H2 O2 levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the α7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via α7nAChR and M3AChR.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Brometo de Piridostigmina/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/complicações , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Cirrose Hepática/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Dieta , Dieta Hiperlipídica/efeitos adversosRESUMO
PURPOSE: To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG). METHODS: Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features. RESULTS: There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1-82 years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases. CONCLUSION: About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention. TRIAL REGISTRATION: Trial registration number: 202104-750, "2016/4/18," retrospectively registered.
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Miastenia Gravis , Humanos , Masculino , Feminino , Estudos Retrospectivos , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Idoso de 80 Anos ou mais , Adulto Jovem , Criança , Pré-Escolar , Lactente , Músculos Oculomotores/fisiopatologia , Músculos Oculomotores/cirurgia , Seguimentos , Brometo de Piridostigmina/uso terapêutico , Autoanticorpos/sangue , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Motilidade Ocular/tratamento farmacológicoRESUMO
The present study focuses on the development of a simple, rapid, specific, and stability-indicating HPLC method for the simultaneous analysis of pyridostigmine bromide (PGB) and sodium benzoate (SBN) in oral liquid dosage forms. Analytical techniques should enhance sensitivity and specificity for the estimation of pharmaceutical drug products. Stress studies were conducted under various International Conference on Harmonization (ICH) conditions for evaluation. The further optimized HPLC method was validated in accordance with the current ICH guidelines. Chromatographic separation was accomplished using a mobile phase consisting of a 950:50 v/v ratio of perchloric acid buffer and acetonitrile as mobile phase-A, and 100% acetonitrile as mobile phase-B. The flow rate is 1.0 mL/min, and the injection volume is 20 µL. Detection of components was carried out at 220 nm for PGB and 228 nm for SBN. The validated HPLC method demonstrated high specificity, with linearity ranging between 24 and 72 µg/mL for PGB and 5.2-15.6 µg/mL for SBN. The correlation coefficient for both drugs exceeded 0.999. The method demonstrated high accuracy, exceeding 97%. In stress studies, PGB was found to be sensitive to alkaline stress conditions. The results reveal the successful applicability of the current method for the estimation of PGB and SBN in its marketed formulation, which can be reasonably inferred to assess other formulation systems.
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Brometo de Piridostigmina , Benzoato de Sódio , Cromatografia Líquida de Alta Pressão , Acetonitrilas , Cromatografia de Fase Reversa , Estabilidade de MedicamentosRESUMO
5q-Spinal muscular atrophy (5q-SMA) is one of the most common neuromuscular diseases due to homozygous mutations in the SMN1 gene. This leads to a loss of function of the SMN1 gene, which in the end determines lower motor neuron degeneration. Since the generation of the first mouse models of SMA neuropathology, a complex degenerative involvement of the neuromuscular junction and peripheral axons of motor nerves, alongside lower motor neurons, has been described. The involvement of the neuromuscular junction in determining disease symptoms offers a possible parallel therapeutic target. This narrative review aims at providing an overview of the current knowledge about the pathogenesis and significance of neuromuscular junction dysfunction in SMA, circulating biomarkers, outcome measures and available or developing therapeutic approaches.
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Neurônios Motores , Atrofia Muscular Espinal , Junção Neuromuscular , Proteína 1 de Sobrevivência do Neurônio Motor , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/metabolismo , Humanos , Animais , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Biomarcadores , Modelos Animais de Doenças , Mutação , CamundongosRESUMO
Gulf War Illness (GWI) collectively describes the multitude of central and peripheral disturbances affecting soldiers who served in the 1990-1991 Gulf War. While the mechanisms responsible for GWI remain elusive, the prophylactic use of the reversible acetylcholinesterase inhibitor, pyridostigmine bromide (PB), and war-related stress have been identified as chief factors in GWI pathology. Post-deployment stress is a common challenge faced by veterans, and aberrant cholinergic and/or immune responses to these psychological stressors may play an important role in GWI pathology, especially the cognitive impairments experienced by many GWI patients. Therefore, the current study investigated if an immobilization stress challenge would produce abnormal responses in PB-treated rats three months later. Results indicate that hippocampal cholinergic responses to an immobilization stress challenge are impaired three months after PB administration. We also assessed if an immune or stress challenge reveals deficits in PB-treated animals during hippocampal-dependent learning and memory tasks at this delayed timepoint. Novel object recognition (NOR) testing paired with either acute saline or lipopolysaccharide (LPS, 30 µg/kg, i.p.), as well as Morris water maze (MWM) testing was conducted approximately three months after PB administration and/or repeated restraint stress. Rats with a history of PB treatment exhibited 24-hour hippocampal-dependent memory deficits when challenged with LPS, but not saline, in the NOR task. Similarly, in the same cohort, PB-treated rats showed 24-hour memory deficits in the MWM task. Ultimately, these studies highlight the long-term effects of PB treatment on hippocampal function and provide insight into the progressive cognitive deficits observed in veterans with GWI.
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Disfunção Cognitiva , Síndrome do Golfo Pérsico , Ratos , Animais , Guerra do Golfo , Lipopolissacarídeos , Acetilcolinesterase , Inibidores da Colinesterase/farmacologia , Brometo de Piridostigmina/farmacologia , Transtornos da Memória , Modelos Animais de DoençasRESUMO
INTRODUCTION: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. METHODS: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. RESULTS: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria. CONCLUSION: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.
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Apolipoproteínas E , Síndrome do Golfo Pérsico , Síndrome do Golfo Pérsico/genética , Humanos , Apolipoproteínas E/genética , Veteranos , Brometo de Piridostigmina/toxicidade , Praguicidas/toxicidade , Substâncias Perigosas/toxicidade , Masculino , Feminino , Pessoa de Meia-Idade , Fumaça/efeitos adversosRESUMO
AIM: Respiratory insufficiency can be a presenting symptom of congenital myasthenic syndromes (CMS) but is rarely recognised as such. In this study, we aim to raise awareness of CMS to paediatricians. METHODS: We performed a retrospective case study of infants and preschool children treated in the past 5 years in Amalia Children's Hospital, Radboud University Medical Center in Nijmegen, the Netherlands for respiratory insufficiency as presenting symptom of CMS. RESULTS: Five children aged 2 weeks to 5 years experienced severe to life-threatening episodes of respiratory insufficiency, especially during viral infections, due to respiratory muscle weakness. During infections, they often also had progression of their otherwise mild ocular, facial, and limb muscle weakness. They were eventually diagnosed with genetically proven CMS. In these five children, treatment with pyridostigmine, an acetylcholinesterase inhibitor, resulted in clinical improvement. CONCLUSION: CMS should be considered in every patient with unexplained recurrent respiratory insufficiency, or with an unusually severe course of a normally mild respiratory infection, especially in combination with mild muscle weakness outside periods of illness. Early diagnosis of CMS is crucial for early treatment, which may help avoiding sudden infant death, severe respiratory insufficiency and further deterioration of the muscle strength.
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Síndromes Miastênicas Congênitas , Insuficiência Respiratória , Lactente , Pré-Escolar , Humanos , Síndromes Miastênicas Congênitas/complicações , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Estudos Retrospectivos , Acetilcolinesterase/genética , Acetilcolinesterase/uso terapêutico , Proteínas Musculares/genética , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Debilidade Muscular , MutaçãoRESUMO
Recently, the main interest of analytical chemistry researchers has been the development of green analytical methods to minimize harmful effects on the environment and natural life. Therefore, an RP-HPLC method was developed and assessed regarding its greenness criteria using three greenness assessment tools: an analytical eco-scale, an analytical greenness metric approach and a green analytical procedure index. This method aims to separate and quantitatively determine three co-administered drugs, namely pyridostigmine bromide (PYR), 6-mercaptopurine (MRC) and prednisolone (PRD), in their tertiary mixture and spiked human plasma. These drugs are co-administered to manage myasthenia gravis autoimmune disease. The separation was done using a C18 column and a gradient elution of a mixture of 0.1% H3 PO4 aqueous solution (pH 2.3) and methanol. The flow rate was adjusted to 1 ml/min and detection was done at 254 (for PYR and PRD) and at 330 nm (for MRC). The lower limits of quantitation were 15, 2, and 5 µg/ml for PYR, MER and PRD, respectively. Linear correlations were obtained and found to be near 1. In addition, the proposed method was validated according to the US Food and Drug Administration's instructions, and the results proved its success to determine the three studied drugs in their tertiary mixture and spiked human plasma.
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Cromatografia , Miastenia Gravis , Estados Unidos , Humanos , Miastenia Gravis/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodosRESUMO
BACKGROUND: Ocular myasthenia gravis (OMG) is an autoimmune disease which causes ptosis, diplopia, or both. It can be categorized as early or late onset, with differing presenting characteristics and prognoses. Currently, there is limited information available to compare characteristics and outcomes in onset groups in Thailand. OBJECTIVE: To describe and compare baseline characteristics and outcomes in OMG patients classified by onset groups and to investigate the factors associated with the disease, especially in terms of treatment responses classified according to the MGFA Post-Intervention Status (MGFA-PIS). METHODS: OMG patients diagnosed between January 2014 and March 2021 at Rajavithi Hospital, Thailand, were categorized into 2 groups based on age of onset, and baseline characteristics were analyzed and compared. The treatment responses of each group in terms of time to achievement of minimal manifestations (MM) were analyzed. RESULTS: Eighty-one patients (38 with early and 43 with late onset) were included, and the mean (SD) follow-up time was 35.85 months (17.25). There was no significant difference between the baseline characteristics of the two groups. A low dose of pyridostigmine was more commonly used in the early-onset group (p = 0.01), while the mean dose of corticosteroids was significantly lower in the late-onset patients (p < 0.001). We found that seropositivity of acetylcholine receptor antibody decreased the odds ratio of achievement of MM (OR 0.185, 95% CI 0.043-0.789, p = 0.023) and receiving a high dose of pyridostigmine (≥ 120 mg/day) increased the odds ratio of achieving it (OR 8.296, 95% CI 2.136-32.226, p = 0.002). CONCLUSIONS: A higher dose of pyridostigmine may be necessary for achievement of favorable treatment response. AChRAb seropositivity is a predictor for unfavorable treatment response in Thai populations.
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Miastenia Gravis , Brometo de Piridostigmina , Humanos , Brometo de Piridostigmina/uso terapêutico , Idade de Início , Estudos Retrospectivos , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/epidemiologia , Receptores Colinérgicos/uso terapêuticoRESUMO
BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
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Tratamento Farmacológico da COVID-19 , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Brometo de Piridostigmina/uso terapêutico , SARS-CoV-2 , Respiração Artificial , Inflamação , Resultado do TratamentoRESUMO
Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with gastroesophageal reflux. There is currently no pharmacologic intervention that reliably improves esophageal contractility in patients suffering from various esophageal motility disorders. Our objective was to evaluate the acute effects of pyridostigmine on high-resolution manometry parameters in patients suffering from dysphagia with evidence of esophageal dysmotility. Pyridostigmine is an acetylcholinesterase inhibitor which increases effective concentrations of acetylcholine at the neuromuscular junction of both striated and smooth muscle cells. We conducted a prospective crossover study of five patients with dysphagia and proven esophageal dysmotility. Three patients had baseline ineffective esophageal motility and two had achalasia. Patients underwent pharyngeal and esophageal manometry before and after pyridostigmine administration. The median distal contractile integral (DCI), a marker of esophageal contractile vigor, was significantly higher post pyridostigmine administration 3001 (1950.3-3703.2) mmHg × s × cm compared to pre-pyridostigmine DCI of 1229.9 (956.2-2100) mmHg × s × cm; P < 0.001. Pre-pyridostigmine 18/25 (72%) of the patient's swallows was peristaltic compared to 25/25 (100%) post-pyridostigmine; P < 0.005. No other pharyngeal or esophageal high-resolution manometry parameter differed significantly after pyridostigmine administration. The results of this pilot study demonstrate that pyridostigmine acutely improves esophageal contractile vigor in patients suffering from dysphagia with esophageal dysmotility. Further investigation with larger sample size, longer follow-up, side effect profile, and patient-reported outcome measures is still needed to determine the clinical usefulness of pyridostigmine in specific disorders of esophageal motility.
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Transtornos da Motilidade Esofágica , Brometo de Piridostigmina , Acetilcolinesterase , Estudos Cross-Over , Transtornos da Motilidade Esofágica/complicações , Humanos , Manometria/métodos , Peristaltismo/fisiologia , Projetos Piloto , Estudos Prospectivos , Brometo de Piridostigmina/farmacologia , Brometo de Piridostigmina/uso terapêuticoRESUMO
Background and Objectives: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to cholinesterase inhibitors. Here, we compare the incidence of postoperative catheter-related bladder discomfort (CRBD) between sugammadex and pyridostigmine/glycopyrrolate treatments for reversing neuromuscular blockade. Materials and Methods: We retrospectively analyzed patients aged ≥ 18 years who underwent surgery under general anesthesia, received sugammadex or pyridostigmine with glycopyrrolate to reverse neuromuscular blockade, and had a urinary catheter in the post-anesthesia care unit between March 2019 and February 2021. After applying the exclusion criteria, 1179 patients were included in the final analysis. The incidence and severity of CRBD were collected from post-anesthesia recovery records. Results: The incidence was 13.7% in the sugammadex group (n = 211) and 24.7% in the pyridostigmine group (n = 968). Following propensity score matching, 211 patients each were included in the pyridostigmine and sugammadex matched group (absolute standardized difference (ASD), 0.01-0.05). Compared to the pyridostigmine group, the odds ratio for CRBD occurring in the sugammadex group was 0.568 (95% confidential interval, 0.316-1.021, p = 0.059). Conclusions: Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine.
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Brometo de Piridostigmina , Cateteres Urinários , Glicopirrolato , Humanos , Brometo de Piridostigmina/uso terapêutico , Estudos Retrospectivos , Sugammadex/uso terapêutico , Bexiga UrináriaRESUMO
Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear. The present study examined the effects and underpinning mechanisms of chronic treatment with the cholinesterase inhibitor, pyridostigmine (PYR), in pressure overload HF induced by transverse aortic constriction (TAC) in mice. TAC mice exhibited characteristic adverse structural (left ventricular hypertrophy) and functional remodelling (reduced ejection fraction, altered myocyte calcium (Ca) handling, increased arrhythmogenesis) with enhanced predisposition to arrhythmogenic aberrant sarcoplasmic reticulum (SR) Ca release, cardiac ryanodine receptor (RyR2) hyper-phosphorylation and up-regulated store-operated Ca entry (SOCE). PYR treatment resulted in improved cardiac contractile performance and rhythmic activity relative to untreated TAC mice. Chronic PYR treatment inhibited altered intracellular Ca handling by alleviating aberrant Ca release and diminishing pathologically enhanced SOCE in TAC myocytes. At the molecular level, these PYR-induced changes in Ca handling were associated with reductions of pathologically enhanced phosphorylation of RyR2 serine-2814 and STIM1 expression in HF myocytes. These results suggest that chronic cholinergic augmentation alleviates HF via normalization of both canonical RyR2-mediated SR Ca release and non-canonical hypertrophic Ca signaling via STIM1-dependent SOCE.
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Arritmias Cardíacas/tratamento farmacológico , Cálcio/metabolismo , Inibidores da Colinesterase/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Brometo de Piridostigmina/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Molécula 1 de Interação Estromal/antagonistas & inibidores , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Myasthenia gravis (MG) is a rare autoimmune disorder of the neuromuscular junction. MG epidemiology has not been studied in Poland in a nationwide study before. METHODS: Our epidemiological data were drawn from the National Health Fund (Narodowy Fundusz Zdrowia, NFZ) database; an MG patient was defined as a person who received at least once medical service coded in ICD-10 as MG (G70) and at least 2 reimbursed prescriptions for pyridostigmine bromide (Mestinon®) or ambenonium chloride (Mytelase®) in 2 consecutive years. RESULTS: On 1st of January 2019, 8,702 patients with MG were receiving symptomatic treatment (female:male ratio: 1.65:1). MG incidence was 2.36/100,000. The mean age of incident cases in 2018 was 61.37 years, 59.17 years for women and 64.12 years for men. Incidence of early-onset MG (<50 years) was 0.80/100,000 and 4.98/100,000 for late-onset MG (LOMG), with male predominance in LOMG. Prevalence was 22.65/100,000. In women, there was a constant increase in prevalence of symptomatic MG from the first decade of life up to 80-89 years. In men, an increase in prevalence appeared in the 6th decade. The highest prevalence was observed in the age group of 80-89 years: 59.65/100,000 in women and 96.25/100,000 in men. CONCLUSIONS: Our findings provide information on epidemiology of MG in Poland and can serve as a tool to evaluate healthcare resources needed for MG patients.
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PURPOSE OF REVIEW: In autonomic failure, neurogenic orthostatic hypotension (nOH) and neurogenic supine hypertension (nSH) are interrelated conditions characterized by postural blood pressure (BP) dysregulation. nOH results in a sustained BP drop upon standing, which can lead to symptoms that include lightheadedness, orthostatic dizziness, presyncope, and syncope. nSH is characterized by elevated BP when supine and, although often asymptomatic, may increase long-term cardiovascular and cerebrovascular risk. This article reviews the pathophysiology and clinical characteristics of nOH and nSH, and describes the management of patients with both nOH and nSH. RECENT FINDINGS: Pressor medications required to treat the symptoms of nOH also increase the risk of nSH. Because nOH and nSH are hemodynamically opposed, therapies to treat one condition may exacerbate the other. The management of patients with nOH who also have nSH can be challenging and requires an individualized approach to balance the short- and long-term risks associated with these conditions. Approaches to manage neurogenic BP dysregulation include nonpharmacologic approaches and pharmacologic treatments. A stepwise treatment approach is presented to help guide neurologists in managing patients with both nOH and nSH.
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Doenças do Sistema Nervoso Autônomo , Droxidopa , Hipertensão , Hipotensão Ortostática , Pressão Sanguínea , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipotensão Ortostática/complicações , Hipotensão Ortostática/epidemiologia , Hipotensão Ortostática/terapiaRESUMO
BACKGROUND: In myasthenia gravis (MG), first-line treatment for MG is acetylcholinesterase inhibitors which alleviates symptoms, but concomitantly may cause autonomic adverse effects. AIMS OF THE STUDY: In this study, we evaluated if symptoms of overactive bladder (OAB) are more frequent among MG patients than healthy controls. METHODS: Eighty-three MG patients and 50 healthy sex- and age-matched controls were included and answered the questionnaire "International Consultation on Incontinence Questionnaire Overactive Bladder Module" (ICIQ-OAB), including questions about polyuria, nocturia, urgency, and stress incontinence. Clinical severity of MG was determined based on three standardized clinical evaluations. RESULTS: Compared to control subjects, MG patients had a higher total OAB score (median 5 [range 0-12] versus 3 [0; 7]) (p < 0.005) with higher scores concerning all four items. Also, MG patients had a higher bother score (10 [0-40] versus 5 [0-40]) (p < 0.05). Patients receiving a daily dose of pyridostigmine of more than 300 mg had a higher OAB score than other patients. CONCLUSIONS: Myasthenia gravis patients have more bothering symptoms of OAB than healthy controls, related to the daily dose of pyridostigmine. To minimize adverse effects in patients with symptoms of OAB, the pyridostigmine dose should be as low as possible.
Assuntos
Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Vigilância da População , Brometo de Piridostigmina/efeitos adversos , Bexiga Urinária Hiperativa/induzido quimicamente , Bexiga Urinária Hiperativa/diagnóstico , Adulto , Idoso , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Vigilância da População/métodos , Brometo de Piridostigmina/administração & dosagem , Sistema de Registros , Inquéritos e Questionários , Bexiga Urinária Hiperativa/epidemiologia , Incontinência Urinária/induzido quimicamente , Incontinência Urinária/diagnóstico , Incontinência Urinária/epidemiologiaRESUMO
BACKGROUND: Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity. AIMS: The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia. METHODS: The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013-February 2016 were prospectively evaluated. RESULTS: The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m2. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy. CONCLUSION: The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.
Assuntos
Antineoplásicos Fitogênicos , Doenças do Sistema Nervoso Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Pré-Escolar , Humanos , Lactente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Brometo de Piridostigmina/uso terapêutico , Piridoxina/uso terapêutico , Vincristina/efeitos adversosRESUMO
Current myasthenia gravis guidelines recommend intravenous immunoglobulin or plasmapheresis and discontinuation of pyridostigmine during myasthenic crisis. However, intravenous immunoglobulin or plasmapheresis is expensive and frequently not available in developing countries. This study aims to summarize the evidence of giving an acetylcholinesterase inhibitor in myasthenic crisis. Medline, Embase, and Cochrane databases and references were searched for observational studies that determined the use of acetylcholinesterase inhibitor in myasthenic crisis. The eligibility criteria were as follows: population, patients with myasthenic crisis, intervention (acetylcholinesterase inhibitor administration), and outcome (clinical improvement and complications). In total, 106 studies were identified, 92 through database searching (after removing duplicates) and 14 through other sources. Only eight were analyzed in the present systematic review. In five, acetylcholinesterase inhibitor was given at the start of the crisis, whereas in the other three, acetylcholinesterase inhibitor was discontinued initially and then restarted prior to extubation. Two observational analytic studies and three case reports showed improvement in different outcome measures. In the other three, improvement of outcome measures was also observed. Overall, a small proportion of patients developed cardiac arrhythmia and pneumonia after administration of acetylcholinesterase inhibitor alone, although this was not statistically different compared with those subjected to plasmapheresis. In summary, continuous intravenous infusion of pyridostigmine or neostigmine can be a substitute for intravenous immunoglobulin or plasmapheresis if these are not available during crisis; however, caution should be observed because of the aforementioned possible complications.
Assuntos
Inibidores da Colinesterase , Miastenia Gravis , Acetilcolinesterase , Inibidores da Colinesterase/efeitos adversos , Humanos , Miastenia Gravis/tratamento farmacológico , Neostigmina , PlasmafereseRESUMO
BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. METHODS: This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. RESULTS: The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). CONCLUSION: The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.