-
Molecules (Basel, Switzerland) Mar 2020Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme...
AIMS
Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome.
METHODS
Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure.
RESULTS
Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens.
CONCLUSIONS
Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.
Topics: Animals; Cholinesterase Inhibitors; Cholinesterase Reactivators; Male; Organophosphates; Oximes; Paraoxon; Physostigmine; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Proportional Hazards Models; Pyridostigmine Bromide; Ranitidine; Rats; Rats, Wistar; Survival Analysis; Tacrine
PubMed: 32230733
DOI: 10.3390/molecules25071521 -
BMJ Case Reports Mar 2021A 67-year-old man presented with progressive diplopia. On evaluation, he was noted to have bilateral palsies of cranial nerves III, IV and VI as well as a unilateral...
A 67-year-old man presented with progressive diplopia. On evaluation, he was noted to have bilateral palsies of cranial nerves III, IV and VI as well as a unilateral right true vocal fold paralysis. CT and MRI studies demonstrated a T2-bright left ethmoid mass with no evidence of bony erosion. Direct visualisation demonstrated a polypoid appearing mass of the left sphenoethmoid recess. Operative biopsy was pursued with final pathology demonstrating benign seromucinous hamartoma. Subsequent blood work demonstrated high titres of anti-acetylcholine receptor antibodies consistent with myasthenia gravis. The patient was started on pyridostigmine with improvement in his ocular cranial neuropathies.
Topics: Aged; Cranial Nerve Diseases; Diplopia; Hamartoma; Humans; Male; Myasthenia Gravis; Pyridostigmine Bromide
PubMed: 33722916
DOI: 10.1136/bcr-2020-240460 -
Seminars in Ophthalmology 2017Ptosis repair was performed in patients with ocular myasthenia gravis by a posterior approach (Fasanella-Servat, 12 eyelids of nine patients) or levator advancement...
Ptosis repair was performed in patients with ocular myasthenia gravis by a posterior approach (Fasanella-Servat, 12 eyelids of nine patients) or levator advancement (eight eyelids of five patients) techniques. There were eight males and five females. Median age was 73 years and range 30-86 years. The median duration of myasthenia was 10 years and range 2 to 28 years. Pyridostigmine and prednisone were widely used prior to surgical referral, but ineffective or intolerable in all. The mean preoperative upper margin-reflex distance (MRD) was 0.55 mm (range -1 to 2 mm). The levator excursion range was 10 to 16 mm and mean 12.4 mm. Mean follow-up was 9.1 months. Postoperatively, the MRD ranged from 0.5 to 4 mm, with a mean of 2.3 mm. Two patients had lagophthalmos postoperatively (one posterior approach, one levator advancement) that did not require correction. Three of five patients who underwent levator advancement required repeat ptosis repair.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Blepharoplasty; Blepharoptosis; Cholinesterase Inhibitors; Eyelids; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Oculomotor Muscles; Prednisone; Pyridostigmine Bromide; Retrospective Studies
PubMed: 27191622
DOI: 10.3109/08820538.2015.1131835 -
Scientific Reports Feb 2019Inflammatory processes and cardiovascular autonomic imbalance are very relevant characteristic of the enormous dynamic process that is a myocardial infarction (MI). In...
UNLABELLED
Inflammatory processes and cardiovascular autonomic imbalance are very relevant characteristic of the enormous dynamic process that is a myocardial infarction (MI). In this sense, some studies are investigating pharmacological therapies using acetylcholinesterase inhibitors, such as pyridostigmine bromide (PYR), aiming to increase parasympathetic tone after MI. Here we hypothesized that the use of PYR before the MI might bring an additional positive effect to the autonomic function, and consequently, in the inflammatory response and cardiac function. The present study aimed to evaluate left ventricular function, baroreflex sensitivity, autonomic modulation, and inflammatory profile in PYR-treated rats previously to MI.
METHODS
Male Wistar rats (250-300 g) were treated for 60 days with PYR. After treatment, they were submitted to the MI. After the MI, the autonomic and ventricular function were evaluated, as well as the systemic, left ventricle, and adipose tissue inflammatory profile.
RESULTS
PYR, performed before MI, prevented HR increase, systolic function impairment, baroreflex sensitivity drop, as well as pulse interval variance, RMSSD, blood pressure and parasympathetic modulation reduction in treated rats compared to untreated rats. Also, this positive functional changes may have been a result of the reduced inflammatory parameters in the left ventricle (IFN-γ, IL-6, and IL-1β), as well as increased IL-10 expression and IL-10/TNF-α ratio in treated animals before MI.
CONCLUSION
Prior treatment with PYR prevents impairment of the autonomic nervous system after MI, which may be associated with the attenuated expression of inflammatory factors and heart dysfunction.
Topics: Animals; Autonomic Nervous System; Blood Pressure; Cholinesterase Inhibitors; Disease Models, Animal; Gene Expression Regulation; Interferon-gamma; Interleukin-10; Interleukin-1beta; Interleukin-6; Male; Myocardial Infarction; Pyridostigmine Bromide; Rats; Rats, Wistar; Ventricular Function, Left
PubMed: 30792425
DOI: 10.1038/s41598-019-38841-y -
Medicina (Kaunas, Lithuania) Apr 2022: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to...
: 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. : 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. : The incidence was 13.7% in the sugammadex group ( = 211) and 24.7% in the pyridostigmine group ( = 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, = 0.059). : Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine.
Topics: Glycopyrrolate; Humans; Pyridostigmine Bromide; Retrospective Studies; Sugammadex; Urinary Bladder; Urinary Catheters
PubMed: 35630007
DOI: 10.3390/medicina58050590 -
Current Journal of Neurology Apr 2022Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD)...
Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD) is one of the most common complications after stroke. Despite a variety of behavioral, compensatory, and rehabilitative methods, many stroke patients still suffer from swallowing disorders that adversely affect their quality of life (QOL). The aim of this study was to evaluate the effect of pyridostigmine on patients with post-stroke dysphagia. A randomized, double-blind, placebo-controlled clinical trial was carried out on 40 patients suffering from post-stroke dysphagia. Patients were assigned randomly into two groups: intervention and control groups (20 in each group). The intervention group was treated with pyridostigmine (60 mg, three times a day, 30 minutes before each meal for three weeks), and the control group received placebo treatment in the same way. All patients (intervention and control) were evaluated according to National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Functional Communication Measures (FCM)American Speech-Language-Hearing Association (ASHA) criteria at baseline and after three weeks of intervention. Values of P < 0.05 were considered statistically significant. In the intervention group, the mean values of NIHSS, mRS, and ASHA/FCM were significantly reduced following three weeks of treatment with pyridostigmine (P = 0.002, P = 0.003, and P < 0.001, respectively), but no significant differences were found in the mean NIHSS, mRS, and ASHA/FCM in the placebo group. Although pyridogestamine is somewhat effective in post-stroke dysphagia, it has not been shown to be more important in preventing aspiration pneumonia and length of hospital stay.
PubMed: 38011458
DOI: 10.18502/cjn.v21i2.10493 -
Pediatric Neurology Apr 2024Currently, there is no universally accepted standard treatment for ocular myasthenia gravis (OMG) in children. We aimed to investigate the possible proper regimens and...
BACKGROUND
Currently, there is no universally accepted standard treatment for ocular myasthenia gravis (OMG) in children. We aimed to investigate the possible proper regimens and timing of treatment for pediatric OMG cases based on the clinical manifestations: OMG with ptosis only and OMG with other features.
METHODS
One hundred and forty two OMG cases attended at the Department of Pediatrics, Xiangya Hospital, Central South University, from 2010 to 2019 were included, and information from medical records was reviewed and recorded. Comparisons of clinical characteristics between patients with OMG with ptosis only and patients with OMG with other features as well as between patients treated with glucocorticoid (GC) within or after six months from disease onset were performed.
RESULTS
OMG with other features constituted about 54.9% of the cases, and 66.2% of the patients achieved optimal outcome. Patients with OMG with ptosis only responded to pyridostigmine alone more than patients with OMG with other features who required several therapies (P < 0.001). Patients with OMG with ptosis only had a larger proportion of optimal outcome than the patients with OMG with other features (P = 0.002), and the difference remained significant even when the individual outcome groups were compared (P < 0.001). Patients who received GC within six months had a greater proportion of optimal outcome than those who received it after six months (P < 0.001).
CONCLUSIONS
Although OMG with other features is a more common subtype of OMG, it is also more severe than OMG with ptosis only. An earlier addition of GC leads to optimal outcome.
Topics: Humans; Child; Myasthenia Gravis; Blepharoptosis; Pyridostigmine Bromide; Glucocorticoids; Retrospective Studies
PubMed: 38382246
DOI: 10.1016/j.pediatrneurol.2024.01.014 -
Dysphagia Feb 2022Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with...
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.
Topics: Acetylcholinesterase; Cross-Over Studies; Esophageal Motility Disorders; Humans; Manometry; Peristalsis; Pilot Projects; Prospective Studies; Pyridostigmine Bromide
PubMed: 33452552
DOI: 10.1007/s00455-020-10243-7 -
Seminars in Arthritis and Rheumatism Aug 2018Symptoms of gastrointestinal dysmotility are common among patients with systemic sclerosis (SSc), and the management of severe cases is often limited by a relative lack...
BACKGROUND/PURPOSE
Symptoms of gastrointestinal dysmotility are common among patients with systemic sclerosis (SSc), and the management of severe cases is often limited by a relative lack of effective interventions. The objective of this case series was to review our experience with pyridostigmine as a treatment for patients with SSc and symptomatic gastrointestinal disease.
METHODS
This study evaluated rates of symptom improvement, side effects, medication adherence, and dose ranges for SSc patients prescribed pyridostigmine for refractory gastrointestinal symptoms over a 10-year period at a quaternary referral center. Patients were defined as responders if they remained on pyridostigmine for at least 4 weeks and clinical benefit was documented by the recorded response of the patient or by the treating physician RESULTS: Of 31 patients treated with pyridostigmine for at least 4 weeks, 51.6% reported symptomatic improvement. Constipation was the most commonly improved symptom based on prevalence prior to therapy (noted by 6/20 patients suffering with constipation). Fifteen of 31 patients reported adverse effects, most commonly diarrhea. Throughout the duration of follow-up (median 126 days, range: 28-506 days), pyridostigmine was continued by 81.3% of patients who reported symptomatic benefit and 58.1% of patients overall.
CONCLUSIONS
Pyridostigmine holds promise for the treatment of various gastrointestinal symptoms in SSc patients, particularly in patients with refractory constipation. Though side effects may limit its use, most patients who experienced benefit chose to continue therapy.
Topics: Adult; Aged; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Male; Middle Aged; Pyridostigmine Bromide; Retrospective Studies; Scleroderma, Systemic; Treatment Outcome
PubMed: 29397195
DOI: 10.1016/j.semarthrit.2017.12.007 -
Journal of Environment and Health... 2017Several studies have implicated immune system disruption in the pathophysiology of GWI. In addition, alterations in brain structure and functioning have been associated...
Several studies have implicated immune system disruption in the pathophysiology of GWI. In addition, alterations in brain structure and functioning have been associated with specific exposures in theater, including pyridostigmine bromide and nerve gas agents. Recent studies conducted up to 25 years after the 1991 conflict have examined factors associated with the continuation or worsening of GWI. Drawing upon published studies of neural and immune system abnormalities in veterans with GWI, this paper proposes a model of GWI that takes into account neurologic and immunologic pathways, neuroimmune mechanisms of disease pathophysiology, individual predisposition due to sex and genetic background, and comorbid factors including neurological conditions such as neuritis/neuralgia and epilepsy that may occur along a continuum with GWI. The proposed neuroimmune model of GWI is likely to be useful for designing new research studies, clarifying factors involved in the continuation or worsening of GWI, and identifying biomarker screening algorithms for the illness. The proposed model goes beyond previously proposed frameworks for GWI by taking into account potential differences in risk based upon female male sex, time elapsed since exposure to neurotoxicants, duration and severity of illness, comorbid conditions, and genotype.
PubMed: 29862319
DOI: 10.15436/2378-6841.17.1665