Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

Excitability of motor and sensory axons in multifocal motor neuropathy

ObjectiveTo assess excitability differences between motor and sensory axons of affected nerves in patients with multifocal motor neuropathy (MMN).MethodsWe performed motor and sensory excitability tests in affected median nerves of 20 MMN patients and in 20 age-matched normal subjects. CMAPs were recorded from the thenar and SNAPs from the 3rd digit. Clinical tests included assessment of muscle strength, two-point discrimination and joint position.ResultsAll MMN patients had weakness of the thenar muscle and normal sensory tests. Motor excitability testing in MMN showed an increased threshold for a 50% CMAP, increased rheobase, decreased stimulus-response slope, fanning-out of threshold electrotonus, decreased resting I/V slope, shortened refractory period, and more pronounced superexcitability. Sensory excitability testing in MMN revealed decreased accommodation half-time and S2-accommodation and less pronounced subexcitability. Mathematical modeling indicated increased Barrett-Barrett conductance for motor fibers and increase in internodal fast potassium conductance for sensory fibers.ConclusionsExcitability findings in MMN suggest myelin sheath or paranodal seal involvement in motor fibers and, possibly, paranodal detachment in sensory fibers.SignificanceExcitability properties of affected nerves in MMN differ between motor and sensory nerve fibers.     

Anticonvulsant effect of melatonin through ATP-sensitive channels in mice

Melatonin is a neurohormone secreted principally by the pineal gland. This molecule has various pharmacological properties including improving immune system, prevent cancer, anti-aging, and anti-oxidant effects. The anticonvulsant effects of melatonin have been proved by previous studies. Adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channels are considered as an important target in the seizure modulation. The aim of the present study was to investigate the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced seizures in mice, focusing on its ability to regulate K_ATP channels. Acute intraperitoneal administration of melatonin (40 and 80 mg/kg) increased clonic seizure threshold induced by intravenous administration of PTZ. Melatonin (40 and 80 mg/kg) increased the latency of clonic seizure and reduced its frequency in mice receiving an intraperitoneal injection of PTZ. Administration of glibenclamide, a K_ATP channels blocker, before intravenous injection of PTZ reduced melatonin anticonvulsant effect. Diazoxide and cromakalim, as K_ATP channels openers, increased antiseizure effect of melatonin in PTZ model of seizures. These findings suggest that the antiseizure effect of melatonin probably is gained through increasing the opening of K_ATP channels.     

急性胰腺炎伤寒六经平脉辨证体系探索

急性胰腺炎中医病因病机复杂,临床表现烦冗多变,传统中医辨证分型粗略,尚不能精准指导急性胰腺炎的中医药治疗。本文基于急性胰腺炎"热病观"和相关指南共识,结合八纲辨证和伤寒六经,拟建立急性胰腺炎的六经平脉辨证体系,以期促进急性胰腺炎的中医药治疗。     

从六经传变理论探“虚不受补”

[目的]从六经传变角度分析"虚不受补"的内在机理,探索完善临床遇见的"虚不受补"问题。[方法]归纳疾病传变如五脏、六经、表里传变的一般规律,总结各类传变的治疗原则,辨析虚实辨证和补法分类,分析产生"虚不受补"的常见现象,提出正确进补的原则与条件。[结果](1)有外感、肺部邪气重,先解表、宣肺,然后才能进补;(2)肠胃有邪气,不可进补,先泄邪气通腑然后可进补;(3)少阳枢机不利则气机不畅,不可进补,先理气转机方可进补;(4)疾病的治疗有表里虚实之辨,也有标本缓急之别,标本之辨在辨证施治时至关重要。[结论]"虚不受补"大多数时候是进补顺序错误导致,在进补前辨别人体的气血状态,对症施药,则可以缓解甚至消除因为进补不当带来的不舒适。解表、健脾胃、活气血、寓消于补是解决虚不受补问题的重要途径。     

理筋通督手法治疗颈性眩晕临床研究

目的:观察理筋通督手法治疗颈性眩晕的临床疗效。方法:将120例颈性眩晕患者随机分成3组,理筋通督组、传统手法组及安慰剂组。理筋通督组采用理筋通督手法;传统手法组采用传统手法;安慰剂组口服维生素C。结果:理筋通督手法可显著减缓患者基底动脉舒张期最低血流速度(P0.05)。理筋通督组有效率为93.67%,传统手法组有效率为67.5%,安慰剂组有效率为17.5%,3组比较差异有统计学意义(P0.05),理筋通督组明显优于其他两组。结论:理筋通督手法治疗颈性眩晕临床疗效显著。     

Electrical resonance with voltage-gated ion channels: perspectives from biophysical mechanisms and neural electrophysiology

Electrical resonance, providing selective signal amplification at preferred frequencies, is a unique phenomenon of excitable membranes, which has been observed in the nervous system at the cellular, circuit and system levels. The mechanisms underlying electrical resonance have not been fully elucidated. Prevailing hypotheses attribute the resonance to voltage-gated ion channels on the membrane of single neurons. In this review, we follow this line of thinking to summarize and analyze the biophysical/molecular mechanisms, and also the physiological relevance of channel-mediated electrical resonance.     

Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full‐thickness cutaneous wound model in rats

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic‐pituitary‐adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full‐thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6‐epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6‐EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = ?.630). Finally, the mechanical withdrawal threshold in the 5,6‐EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6‐EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.     

活用经方治疗头痛验案4则

头痛是临床上的一种常见病,多发病,内伤外感均能引起,病因复杂多变,病程长短不一,症状轻重有别,容易反复发作,甚者严重影响患者的生活和工作,引发一系列身心问题,给患者带来了极大的痛苦。中医对头痛病的认识可追溯到2000年前的《黄帝内经》,治疗上更是积累了丰富的经验。传统的辨证论治有时候在临床中证型难以明确区分,往往难以和教科书上的辨证分型对号入座。笔者近年来采用张仲景的六经辨证,先辨六经,次辨方证,灵活运用经方加减治疗各种头痛,方证对应,效果明显。