Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures.

Epileptic seizures are characterized by imbalanced inhibition-excitation cycle that triggers biochemical alterations responsible for jeopardized neuronal integrity. Conventional antiepileptic drugs (AEDs) have been the mainstay option for treatment and control; however, symptomatic control and potential to exacerbate the seizure condition calls for viable alternative to these chemical agents. In this context, natural product-based therapies have accrued great interest in recent years due to competent disease management potential and lower associated adversities. Cicuta virosa (CV) is one such herbal remedy that is used in traditional system of medicine against myriad of disorders including epilepsy. Homeopathic medicinal preparations (HMPs) of CV were assessed for their efficacy in pentylenetetrazole (PTZ)-induced acute and kindling models of epilepsy. CV HMPs increased the latency and reduced the duration of tonic-clonic phase in acute model while lowering the kindling score in the kindling model that signified their role in modulating GABAergic neurotransmission and potassium conductance. Kindling-induced impairment of cognition, memory, and motor coordination was ameliorated by the CV HMPs that substantiated their efficacy in imparting sustained neuronal fortification. Furthermore, biochemical evaluation showed attenuated oxidative stress load through reduced lipid peroxidation and strengthened free radical scavenging mechanism. Taken together, CV HMPs exhibited promising results in acute and kindling models and must be further assessed through molecular and epigenomic studies.

[Effect of animal medicines for "extinguishing wind to arrest convulsions" on central nervous system diseases].

The human health is seriously affected by central nervous system(CNS) diseases, but the pathogenesis of CNS diseases is still not completely clear. Currently, the drugs used to treat CNS diseases are mainly receptor modulators and neurotransmitter inhibitors, which have serious side effects; and there are short of drugs for treating CNS diseases clinically. Studies suggest that animal medicines mainly include protein, polypeptide and small-molecule compounds, and have such pharmacological effects in calming, resisting convulsions and improving brain tissues. Plenty of studies suggest that animal medicines usually have a strong activity and good curative effect on these diseases, with a promising prospect in research and development of drugs treating CNS diseases. Based on systematic reviews of literatures, this paper summarizes active ingredients and main pharmacological effects of animal medicines in "extinguishing wind to arrest convulsions" for the CNS diseases, epilepsy and cerebral ischemia, and discusses their study value and application prospects. The results showed that the studies of protein and peptides were relatively simple, and some animal medicines were still blank. The authors believed that amino acids and small molecular compounds should be transferred to oligopeptide, advanced protein extraction and separation techniques shall be adopted for identifying the protein polypeptide composition structure and studying the efficacy, and the methods of biological technology were used to develop peptide biological products for the treatment of CNS diseases. This paper could provide ideas and reference for developing animal medicine products for the treatment of CNS diseases.

Seizures caused by ingestion of Atropa belladonna in a homeopathic medicine in a previously well infant: case report and review of the literature.

Atropa belladonna is a poisonous plant that can cause anticholinergic effects when ingested. Roots, leaves, and fruits of the plant contain the alkaloids atropine, hyoscyamine, and scopolamine, which can lead to an anticholinergic toxidrome; however, not all characteristics of the toxidrome are necessarily present in each case of poisoning. We present an infant who suffered serious seizures after ingestion of a homeopathic agent containing A. belladonna. The 20-day-old infant arrived at the emergency department with fever and generalized seizures for 30 minutes, 2 hours after ingesting the correct dose of a homeopathic medication agent used for infantile colic. The patient was treated with intravenous benzodiazepines and antibiotics after a full sepsis work up; all the laboratory results were normal and the fever resolved after several hours. The infant recovered fully with normal neurological function and a normal electroencephalogram. This infant probably manifested what is known as the central anticholinergic syndrome. We discuss his presentation and review of the literature on this topic.

A cluster of acute thebaine poisonings from non-food grade poppy seeds in the Australian food supply.

INTRODUCTION: Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate thebaine has strychnine-like properties, but there is limited literature describing human thebaine poisoning. We describe a cluster of acute thebaine poisoning in people ingesting tea made using poppy seeds with high thebaine content that entered the Australian food supply chain. METHODS: This is an observational study of patients poisoned after drinking poppy seed tea. Cases were identified by three prospective toxicovigilance systems: the Emerging Drug Network of Australia collaboration, the New South Wales Prescription, Recreational and Illicit Substance Evaluation program, and the Emerging Drugs Network of Australia Victoria study. We report characteristics of clinical toxicity in cases with reported ingestion of poppy seed tea and analytical confirmation of thebaine exposure. RESULTS: Forty cases presenting with multi-system toxicity following poppy seed tea ingestion were identified across seven Australian states/territories from November 2022 to January 2023. Blood testing in 23 cases confirmed high thebaine concentrations. All 23 were male (median age 35, range 16-71 years). All patients experienced muscle spasms. Rigidity was described in nine, convulsions in six, while rhabdomyolysis, acute kidney injury, and metabolic acidosis occurred in five patients. There were two cardiac arrests. The thebaine median admission blood concentration was 1.6 mg/L, with a range of 0.1-5.6 mg/L, and was the dominant opium alkaloid in all samples. Convulsions, acute kidney injury, metabolic acidosis, and cardiac arrest were associated with increasing median thebaine concentrations. Four patients were managed in the Intensive Care Unit, with two receiving continuous kidney replacement therapy (one also received intermittent haemodialysis) for kidney injury. There was one death. CONCLUSIONS: Thebaine toxicity, like strychnine poisoning, resulted in neuromuscular excitation characterized by muscle spasm, rigidity, and convulsions. Severe toxicity, including acute kidney injury, metabolic acidosis, and cardiac arrest, appears dose-dependent.

Assays of homeopathic remedies in rodent behavioural and psychopathological models.

The first part of this paper reviews the effects of homeopathic remedies on several models of anxiety-like behaviours developed and described in rodents. The existing literature in this field comprises some fifteen exploratory studies, often published in non-indexed and non-peer-reviewed journals. Only a few results have been confirmed by multiple laboratories, and concern Ignatia, Gelsemium, Chamomilla (in homeopathic dilutions/potencies). Nevertheless, there are some interesting results pointing to the possible efficacy of other remedies, and confirming a statistically significant effect of high dilutions of neurotrophic molecules and antibodies. In the second part of this paper we report some recent results obtained in our laboratory, testing Aconitum, Nux vomica, Belladonna, Argentum nitricum, Tabacum (all 5CH potency) and Gelsemium (5, 7, 9 and 30CH potencies) on mice using ethological models of behaviour. The test was performed using coded drugs and controls in double blind (operations and calculations). After an initial screening that showed all the tested remedies (except for Belladonna) to have some effects on the behavioural parameters (light-dark test and open-field test), but with high experimental variability, we focused our study on Gelsemium, and carried out two complete series of experiments. The results showed that Gelsemium had several effects on the exploratory behaviour of mice, which in some models were highly statistically significant (p < 0.001), in all the dilutions/dynamizations used, but with complex differences according to the experimental conditions and test performed. Finally, some methodological issues of animal research in this field of homeopathy are discussed. The "Gelsemium model" - encompassing experimental studies in vitro and in vivo from different laboratories and with different methods, including significant effects of its major active principle gelsemine - may play a pivotal rule for investigations on other homeopathic remedies.

Seizures in a 7-month-old child after exposure to the essential plant oil thuja.

A previously healthy 7-month-old child was treated with homeopathic preparations of thuja, a potentially convulsant compound, for the purpose of providing a calming effect around times of immunizations. The child developed eight generalized tonic-clonic seizures with no other obvious cause, in the context of normal electroencephalograms and a normal brain magnetic resonance imaging scan. Seizures stopped after discontinuation of thuja and brief treatment with phenobarbital. The epileptogenic potential of plant-derived essential oils and other herbal remedies should be recognized by practitioners providing neurologic care to children.

Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms.

Exposure to high doses of organophosphorus nerve agents such as soman, even with carbamate pretreatment, produces a variety of toxic cholinergic signs, including secretions, convulsions and death. Evidence suggests that soman-induced convulsions may be associated with postexposure brain neuropathology. The purpose of this study was to investigate the pharmacologic mechanism of action of soman-induced convulsions and of anticonvulsant drugs. Various classes of compounds were evaluated for their efficacy in preventing soman-induced convulsions in rats pretreated with the oxime HI-6 to increase survival time, along with various doses of the test compounds (IM) either in the absence or presence of atropine sulfate (16 mg/kg, IM) 30 minutes prior to a soman challenge dose (180 micrograms/kg, SC; equivalent to 1.6 x LD50) that produced 100% convulsions. Without atropine sulfate, only tertiary anticholinergics (scopolamine, trihexyphenidyl, biperiden, benactyzine, benztropine, azaprophen and aprophen), caramiphen, carbetapentane and MK-801 were effective anticonvulsants. In the presence of atropine sulfate, the benzodiazepines (diazepam, midazolam, clonazepam, loprazolam and alprazolam), mecamylamine, flunarizine, diphenylhydantoin, clonidine, CGS 19755 and Organon 6370 studied were effective. We have examined the possibility that diazepam may exert some of its anticonvulsant effects through cholinergic mechanisms and found that a reduced release of ACh into synapses after diazepam and atropine treatment may account for diazepam's anticonvulsant activity against soman. We also found that at anticonvulsant doses biperiden and trihexyphenidyl each significantly reversed the effects of soman on striatal levels of DOPAC and HVA, the metabolites of dopamine, and have concluded that in addition to actions on muscarinic receptors, the anticonvulsant effects of these anticholinergics in soman poisoning may be partially related to their actions on the striatal dopaminergic system. These findings allow us to postulate that central muscarinic cholinergic mechanisms are primarily involved in eliciting the convulsions following exposure to soman and that subsequent recruitment of other excitatory neurotransmitter systems and loss of inhibitory control may be responsible for sustaining the convulsions and for producing the subsequent brain damage. Future studies to confirm these neuropharmacological mechanisms are proposed.

Detection of seizure activity in the paralyzed neonate using continuous monitoring.

In experimental animals neurologic damage may occur during seizure activity whether the seizure is accompanied by motor activity and hypoxemia or whether the animal is paralyzed and normoxemic. These findings suggest that it may be important to detect seizure activity in the paralyzed neonate. Nine infants who were mechanically ventilated and paralyzed with pancuronium had their condition diagnosed as seizure activity. Vital signs were continuously monitored and six infants had either oxygen saturation or transcutaneous oxygen measured during seizure activity. For the group as a whole, rhythmic fluctuations in vital signs, cardiac rhythm, and oxygenation occurred every four minutes (range one to seven minutes) and lasted two minutes (range one to four minutes). In seven patients whose seizures were not accompanied by cardiac arrhythmias the following mean increases were noted: systolic arterial blood pressure, 15 mm Hg (range 7 to 36 mm Hg); heart rate, ten beats per minute (-11 to 30/min); oxygen saturation, 12% (range 4% to 20%); and transcutaneous oxygen, 31 mm Hg (range 14 to 45 mm Hg). Seizures in the two patients with cardiac arrhythmias were accompanied by a decrease in systolic arterial blood pressure of 27 mm Hg (range 15 to 40 mm Hg) and in oxygen saturation of 24% (range 20% to 28%). The presence of rhythmic fluctuation in vital signs and oxygenation should alert the physician to the possibility of seizure activity in the paralyzed neonate.

Anesthetic management of conray toxicity.

Conray (meglumine iothalamate), the contrast media frequently used in shuntograms for diagnosing malfunctioning ventriculo-peritoneal shunts, will occasionally cause severe muscular spasms and seizures. In this article, the authors describe anesthetic and critical care management of a case with this complication.

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

[Pharmacological study on magnetite].

Magnetite can markedly inhibit the rodent turn-around reaction induced by acetic acid, reduce the threshold dose of pentobarbital sodium and shorten rodent's incubation period of falling asleep. It has also the following effects; antagonizing metrazol which causes rodent convulsions, postponing the incubation period of being startled by Huisuling, cutting down the extent of rodent's foot swells caused by JCCJ, and diminishing bleeding time and congulating time.

Cuprum Metallicum: relato de caso / Cuprum Metallicum: case report

O aparecimento de convulsões, após Traumatismo Crânio Encefálico ocorre com grande frequência, sendo muitas vezes de difícil controle com o tratamento alopático, especialmente quando o paciente desenvolve comorbidades secundárias ao trauma. O relato de caso a seguir se refere ao tratamento de convulsões tônico clônicas, refratárias ao tratamento alopático em um paciente acamado, não contactante, utilizando-se a medicação homeopática Cuprum Metallicum.(AU)

Possibilidades terapêuticas de Coriaria myrtifolia L. em altas diluições / Therapeutic possibilities of coriaria myrtifolia L. in high dilutions

Background: Homeopathy literature shows references about Coriaria myrtifolia L. at some important Homeopathic Materia Medica: Allen,TF [1], Voisin H [2] and Vijnovsky B [3]. Those reports are unsatisfactory to fulfill a contemporary standardized study basis on: origin and description, preparation, medicine general action, sensations and modalities; demanding a broader investigation. Aims: Identify therapeutic possibilities on Coriaria myrtifolia L. from ratifying and broadening the homeopathic materia medica knowledge. Methodology: Literature review on botanical, biochemical and pharmacological data [4-12]. The use of plant in various s since XVIII century and analyzes of clinical-toxicological reports described in medical reviews published. Results: Coriaria myrtifolia L. is a toxic shrub, growing wild in western Mediterranean region. The entire plant contains a sesquiterpene-lactone called coriamyrtin, a potent convulsivant neurotoxin. Clinical manifestations of acute intoxication includes: Central Nervous System ? generalized tonic-clonic seizures, recurrent, which may evolve to status epilepticus, coma, apnea and death. Respiratory Tract ? respiratory depression due to anoxia, respiratory arrhythmia alternating with apnea, respiratory muscles tetanization evolving to respiratory arrest. Cardiovascular System ? central excitatory action which may initially promote increased blood pressure followed by heart failure, as a result of the seizures, due to anoxia and acidosis, leading to cardiac arrest. Gastrointestinal Tract ? nausea, vomiting and stomach pains that precede seizures; since there is no evidence of toxin direct action on mucosa, those symptoms may relate to Central Nervous System action (attributed to impairment of cranial nerve VIII). Knowledge of these aspects gave us possibility to build a Coriaria myrtifolia L. materia medica with broader clinical indications. Conclusion: Coriaria myrtifolia L. is a valuable source to be used in high dilutions as medicine indicated for epileptic syndromes treatment, characterized by tonic-clonic seizures, mainly presenting a malignant tendency, with recurrent seizures, which may evolve to status epilepticus and potential mortality risk. Among the clinical indications proposed stand out etiologies of great incidence at emergency rooms such as metabolic or vascular primary disorders, or resulting from systemic diseases (diabetes, hepatopathy, nephropathy), encephalitis and meningitis with or without Acquired Immunodeficiency Syndrome, withdrawal syndrome from alcohol or drugs, exogenous poisoning, poisoning or overdose of alcohol or drugs, traumatic brain injury and intracranial expanding lesions.(AU)

Introdução: Na literatura homeopática encontramos referências à Coriaria myrtifolia nas matérias médicas de Allen,T. F.(The Encyclopedia of Pure Matéria Medica)[1], Voisin, H.(Manual de Matéria Medica para o Clínico Homeopata)[2] e Vijnovsky, B.(Tratado de Matéria Medica Homeopática)[3]. Estas foram insatisfatórias para atender ao modelo contemporâneo de estudo fundamentado em tópicos básicos como: origem e descrição, preparação, ação geral do medicamento, sensações e modalidades, demandando o aprofundamento da investigação. Objetivos: Identificar possibilidades terapêuticas a partir da ratificação e ampliação do conhecimento de matéria médica homeopática sobre Coriaria myrtifolia L. Metodologia: Levantamento dos aspectos botânicos, bioquímicos e farmacológicos da planta, seus usos desde o século XVIII e análise dos relatos clínico-toxicológicos descritos em revisões médicas [4-12]. Resultados: Coriaria myrtifolia L. é um arbusto tóxico de ocorrência silvestre na região do Mediterrâneo ocidental. A planta inteira contém uma sesquiterpeno-lactona chamada coriamyrtina, neurotoxina de potente ação convulsivante. As manifestações clínicas da intoxicação aguda incluem no: Sistema Nervoso Central ? convulsões generalizadas tônico-clônicas, subentrantes, podendo levar a estado de mal epilético (status epilepticus) com conseqüente anoxia central e parada cardio-respiratória; aparelho respiratório - ação central de início estimulante seguida de depressão (pela anoxia conseqüente às convulsões ) sobrevindo arritimia respiratória com fases de apnéia, tetanização de musculatura respiratória e parada respiratória; aparelho cardiovascular ? ação excitatória central que pode inicialmente promover aumento da pressão arterial, seguida de falência cardíaca em conseqüência às convulsões, à anoxia e à acidose metabólica, resultando em parada cardíaca; aparelho gastrointestinal ? náuseas, vômitos e dores gástricas que precedem as convulsões, não havendo evidência de ação direta sobre a mucosa do tubo digestivo. Os efeitos a esse nível parecem ser secundários a ação da toxina no sistema nervoso central (provavelmente por comprometimento do VIII par craniano). O conhecimento desses aspectos nos deu a possibilidade de construir um myrtifolia Coriaria materia medica L. com maior indicações clínicas. Conclusão: Coriaria myrtifolia L. é um valioso medicamento homeopático indicado para o tratamento de síndromes convulsivas tônico-clônicas (grande mal) principalmente quando apresentam tendência a evolução maligna, com episódios convulsivos recorrendo a curtos intervalos conduzindo a estado de mal epiléptico (status epilepticus) e conseqüente risco elevado de mortalidade. Dentre as indicações clínicas propostas, se destacam etiologias de grande incidência nas emergências médicas tais como: distúrbios metabólicos e/ou vasculares primários ou decorrentes de complicações de doenças crônicas (diabetes, hepatopatias, nefropatias), encefalites e meningites associadas ou não à Síndrome de Imunodeficiência Adquirida, síndromes de abstinência ao alcóol ou drogas, intoxicações exógenas (envenenamentos ou overdose de álcool ou drogas), traumatismos cranio-encefálicos e lesões expansivas intracranianas.(AU)

Effects of pancuronium bromide on cerebral blood flow changes during seizures in newborn pigs.

We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 min after bicuculline (3 mg/kg i.v.). No change in CBF from baseline was observed at 10 min after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 +/- 3 mL.min-1.100 g-1 before bicuculline and increased to 166 +/- 24 and 205 +/- 35 mL.min-1.100 g-1 at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 +/- 7 to 169 +/- 26 mL.min-1.100 g-1, but fell to 88 +/- 17 mL.min-1.100 g-1 at 15 min in contrast to saline-treated piglets. Also, at 15 min of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 +/- 6 mm Hg) and PCO2 (6 +/- 0.4 kPa) and decreased PO2 (7 +/- 0.5 kPa) and pH (6.91 +/- 0.06). Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial PCO2, PO2, and pH during seizures.

Autoregulation of cerebral blood flow. Effect of phenobarbital and pancuronium in the newborn piglet.

The effect of phenobarbital and pancuronium on cerebral blood flow (CBF) and CBF autoregulation are studied in newborn piglets after chemically induced seizures with bicuculline. Given 3 or 15 min after the onset of seizures, phenobarbital significantly reduces CBF (59 +/- 11 and 56 +/- 17 vs. 84 +/- 24 ml/min/100 g - p less than 0.01). Moreover, during graded hypotension induced by graded haemorrhage, phenobarbital provides reestablishment of CBF autoregulation altered by seizures. In the same experimental model, pancuronium induces in control animals a rise of CBF (61 +/- 15 vs. 38 +/- 11 ml/min/100 g - p less than 0.001). During graded hypotension pancuronium is associated to a loss of CBF autoregulation (r = 0.76, p less than 0.001). Given as an adjunct treatment, in case of seizures, pancuronium has no significant effect on changes in cerebral haemodynamics. From these data, we conclude that pancuronium jeopardizes the haemodynamic adaptation to the induced hypovolemia and that phenobarbital may present a protective effect on cerebral haemodynamics and the subsequent risk for ischaemia or haemorrhage.

Neonatal seizures associated with narcotic withdrawal.

Among 302 neonates passively addicted to narcotics, 18 had seizures that were attributed to withdrawal. Of those 18 infants, 10 were among the 127 infants exposed to methadone (7.8%), whereas only one of them was among the 83 infants exposed to heroin (1.2%). Generalized motor seizures and myoclonic jerks were the predominant convulsive manifestations. Paregoric was more effective than was diazepam in controlling and preventing these seizures once they occurred. Electroencephalograms were obtained on 13 neonates in the interictal period; 12 of these ECGs were normal. Three infants, two with myoclonic jerks, had paroxysmal brain wave activity at the time of the seizures.