Ecstasy intoxication: the toxicological basis for treatment

Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.

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Modulating a modulator: biogenic amines at subthreshold levels potentiate peptide-mediated cardioexcitation of the heart of the tobacco hawkmoth Manduca sexta.

Journal of Experimental Biology ◽

10.1242/jeb.197.1.377 ◽

1994 ◽

Vol 197 (1) ◽

pp. 377-391 ◽

Cited By ~ 3

Author(s):

K R Prier ◽

O H Beckman ◽

N J Tublitz

Keyword(s):

Cyclic Amp ◽

Manduca Sexta ◽

Biogenic Amine ◽

Molecular Mechanisms ◽

Adult Heart ◽

The Central Nervous System ◽

Messenger System ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Dependent Mechanism

The central nervous system of the moth Manduca sexta contains a group of myoregulatory neuropeptides, the CAPs (Cardioacceleratory Peptides), which cause a physiologically important, dose-dependent increase in heart rate during wing inflation and flight in adult moths. We report here that the response of the adult heart to a subset of the CAPs, the CAP2S, is potentiated nearly twofold in the chronic presence of subthreshold levels of the biogenic amine octopamine or near-threshold levels of the biogenic amine serotonin. Subthreshold levels of the CAP2S fail to alter the response of the heart to octopamine. We have begun to investigate the molecular mechanisms underlying this potentiation. Previous work on the adult heart has shown that the CAP2s act through an inositol-1,4,5-trisphosphate second-messenger system. Here, we demonstrate that the cardioexcitatory effects of the two amines, in contrast to those of the CAP2S, are both mediated by cyclic AMP. Application to the heart of either 10(-5) moll-1 octopamine or 10(-6)moll-1 serotonin elicits a threefold increase in intracellular cyclic AMP levels. The CAP2S have no effect on cyclic AMP levels in the heart. These results illustrate a mechanism by which the effectiveness of a neurohormone can be increased with minimal cost to the animal. In Manduca sexta, subthreshold levels of octopamine are found in the haemolymph during wing inflation and flight. Thus, it is possible that octopamine up-regulates the effects of CAP2 via a cyclic-AMP-dependent mechanism during these activities.

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Ionotropic glutamate receptor activation increases intracellular calcium in prolactin-releasing cells of the adenohypophysis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00207.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. E1188-E1196 ◽

Cited By ~ 3

Author(s):

Frederick P. Bellinger ◽

Bradley K. Fox ◽

Wing Yan Chan ◽

Lori K. Davis ◽

Marilou A. Andres ◽

...

Keyword(s):

Intracellular Calcium ◽

Anterior Pituitary ◽

Receptor Activation ◽

Nmda Receptor Antagonist ◽

Pituitary Cells ◽

The Central Nervous System ◽

To Receive ◽

Dose Dependent Increase ◽

Dose Dependent ◽

The Brain

Endocrine cells of the anterior pituitary are controlled by the central nervous system through hormonal interactions and are not believed to receive direct synaptic connections from the brain. Studies suggest that some pituitary cells may be modulated by the neurotransmitter glutamate ( 5 , 16 ). We investigated prolactin (PRL)-releasing cells of the anterior pituitary of a euryhaline fish, the tilapia ( Oreochromis mossambicus), for the presence of possible glutamate receptors (GluRs). Fura-2 imaging addressed the ability of glutamate to increase intracellular calcium. We observed a dose-dependent increase in intracellular calcium with transient perfusion (1–2 min) of glutamate (10 nM to 1 mM) in two-thirds of imaged cells. This increase was attenuated by the ionotropic GluR antagonist kynurenic acid (0.5–1.0 mM). The increase was also blocked or attenuated by antagonists of L-type voltage-gated calcium channels. The GluR agonist α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA; 100 μM) produced intracellular calcium increases that were reversibly blocked by the selective AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In contrast, the selective agonist N-methyl-d-aspartate (NMDA; 100 μM to 1 mM in magnesium-free solution with 10 μM glycine) had no effect on intracellular calcium. Radioimmunoassays demonstrated that glutamate stimulated PRL release. CNQX but not the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid blocked this release. Antibodies for mammalian AMPA- and NMDA-type GluR produced a similar punctate immunoreactivity in the periphery of PRL cells. However, the NMDA antibody recognized a protein of a different molecular mass in PRL cells compared with brain cells. These results clearly indicate the presence of GluRs on tilapia PRL cells that can stimulate PRL release.

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Allergic reactions and adverse events associated with administration of mRNA-based vaccines. A health-care system experience

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210069 ◽

2021 ◽

Vol 42 (5) ◽

pp. 395-399

Author(s):

Mercedes E. Arroliga ◽

Karim Dhanani ◽

Alejandro C. Arroliga ◽

Penny S. Huddleston ◽

Jason Trahan ◽

...

Keyword(s):

Health Care ◽

Health Care System ◽

Health Care Providers ◽

Health Care Professionals ◽

Messenger Rna ◽

Adverse Reactions ◽

Care Providers ◽

Allergy And Immunology ◽

Care System

Background: Adverse reactions, including anaphylaxis, to messenger RNA coronavirus disease 2019 (COVID-19) vaccines rarely occur. Because of the need to administer a timely second dose in subjects who reported a reaction to their first dose, a panel of health-care professionals developed a safe triage of the employees and health care providers (EHCP) at a large health-care system to consider administration of future dosing. Methods: There were 28,544 EHCPs who received their first dose of COVID-19 vaccines between December 15, 2020, and March 8, 2021. The EHCPs self-reported adverse reactions to a centralized COVID-19 command center (CCC). The CCC screened and collected information on the quality of reaction, symptoms, and timing of the onset of the reaction. Results: Of 1253 calls to the CCC, 113 were identified as requiring consideration by a panel of three (American Board of Allergy and Immunology) ABAI-certified allergists for future dosing or formal in-person assessment. Of the 113 EHCPs, 94 (83.2%) were recommended to get their second dose. Eighty of 94 received their second planned dose without a severe or immediate reaction. Of the 14 of 113 identified as needing further evaluation, 6 were evaluated by a physician and subsequently received their second dose without a serious adverse reaction. Eight of 14 did not receive their second dose. Only 5 of the 113 EHCPs reported reactions (4.4%) were recommended to not take the second dose: 3 (2.6%) because of symptoms consistent with anaphylaxis, and 2 because of neurologic complications (seizure, stroke). Conclusion: The panel demonstrated that, by consideration of reaction history alone, the ECHPs could be appropriately triaged to receive scheduled second dosing of COVID-19 vaccines without delays for in-person evaluation and allergy testing.

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Serotonin syndrome due to venlafaxine and maintenance tranylcypromine therapy

Human & Experimental Toxicology ◽

10.1177/0960327197016001031 ◽

1997 ◽

Vol 16 (1) ◽

pp. 14-17 ◽

Cited By ~ 34

Author(s):

Michael J Hodgman ◽

Thomas G Martin ◽

Edward P Krenzelok

Keyword(s):

Single Dose ◽

Monoamine Oxidase ◽

Health Care Providers ◽

Serotonin Syndrome ◽

Tricyclic Antidepressants ◽

Adverse Reactions ◽

Monoamine Oxidase Inhibitor ◽

Altered Mental Status ◽

Oxidase Inhibitor ◽

Care Providers

A number of novel serotonergic antidepressants have been introduced to clinical practice over the last decade. These medications are felt to be safe alternatives to the traditional tricyclic antidepressants and monoamine oxidase inhibitors, particularly in the overdose setting. Serious adverse reactions and drug interactions have been appreciated and fatalities have been reported. We describe the development of the serotonin syndrome in a 60 year old female on chronic tranylcypromine treatment following the inadvertent ingestion of a single dose of venlafaxine. Manifestations included an altered mental status that progressed to hyperthermia and coma. She recovered quickly and without complications. Health care providers and poison specialists need to be aware that this potentially serious syndrome can be precipitated by a single dose of a serotonin reuptake inhibitor in patients being treated with a monoamine oxidase inhibitor.

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EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

Nature Reviews Clinical Oncology ◽

10.1038/s41571-020-00447-z ◽

2020 ◽

Author(s):

Michael Weller ◽

Martin van den Bent ◽

Matthias Preusser ◽

Emilie Le Rhun ◽

Jörg C. Tonn ◽

...

Keyword(s):

Clinical Trials ◽

Health Care Providers ◽

Task Force ◽

Adult Patients ◽

Treatment Modalities ◽

Care Providers ◽

Diffuse Gliomas ◽

The Central Nervous System ◽

Classification Of Tumors ◽

Evidence Based Guidelines

AbstractIn response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy — Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.

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Nasal spray live attenuated influenza vaccine: the first experience in Italy in children and adolescents during the 2020–21 season

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01172-8 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Chiara Gasparini ◽

Miriam Acunzo ◽

Andrea Biuso ◽

Stefania Roncaglia ◽

Francesca Migliavacca ◽

...

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Children And Adolescents ◽

Health Care Providers ◽

Adverse Reactions ◽

Care Providers ◽

Live Attenuated Influenza Vaccine ◽

Flu Vaccination ◽

Increased Risk ◽

Degree Of Satisfaction

Abstract Background In Italy only recently, for the 2020–21 season, has the flu vaccination been extended to all children. A quadrivalent live attenuated influenza vaccine (qLAIV) was administered to children aged 2–17 years for the first time. We registered the number and severity of adverse reactions to (Fluenz Tetra™) and the factors influencing them, evaluated uniformity of access to care and assessed the degree of satisfaction with the vaccination of both parents and health care providers, in order to improve the 2021–22 vaccination program. Methods On vaccination day, a questionnaire was given out to collect information about the children and their parents. Between 1 and 3 months later, the parents were contacted to record any adverse reactions following (Fluenz Tetra™) and rate the degree of satisfaction. Results We received data of 3226 children from 2152 families. Adverse events were reported in 24.8% of children: 80.6% mild, 18.1% moderate and 1.3% significant. The most common were rhinitis (52.5%) and fever (24.4%). Statistical analysis performed with a multiple regression model, showed that children aged 2–5 years have an increased risk of adverse events compared to both 6–10 years old (aRR 1.7, 95% CI 1.5–1.9, p < 0. 001) and 11–17 years old (aRR 1.5, 95% CI 1–2.2, p = 0.051). Most families chose to vaccinate their children to protect them and because they were concerned about Covid19. The main channel through which parents became aware of a new flu vaccination was word-of-mouth (39.8%), which occurred mostly among parents of the same school group, followed by information from the child’s doctor (30.6%), the Internet (26.9%), personal research (15%), newspapers (4%), telecommunications (7.5%) and other (2.6%). Most parents (83.3%) were very satisfied and intend to vaccinate their children with qLAIV again (83.8%). The majority of operators (93%) considered the experience as excellent and are willing to repeat it (94.6%). Conclusion (Fluenz Tetra™) proved to be easy to administer and the degree of satisfaction was high among both health workers and parents. Considering its substantial safety profile especially in school-age children and adolescents, all these aspects make the nasal qLAIV optimal for widespread immunization. Schools offer the best setting to reach more families and physicians should be actively involved.

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Centrally administered ouabain aggravates central sleep apneas

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.2.545 ◽

1993 ◽

Vol 74 (2) ◽

pp. 545-548 ◽

Cited By ~ 4

Author(s):

T. Sato ◽

M. Tadokoro ◽

H. Kaba ◽

H. Saito ◽

K. Seto ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Eye Movement ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

The Central Nervous System ◽

Freely Moving ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Lateral Cerebral Ventricle

The presence of endogenous digitalis-like factors in the central nervous system suggests their functional significance in the central nervous system. Three-day infusions of three-stepped doses of the digitalis agent ouabain (1–100 ng.kg body wt-1.h-1) into the lateral cerebral ventricle of freely moving rats caused a dose-dependent increase in the number of central-apneic episodes during rapid-eye-movement sleep without affecting the time spent in rapid-eye-movement sleep or basic respiratory rate. These results suggest that endogenous digitalis-like factors may be involved in the genesis of central sleep apneas.

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Effect of indomethacin on febrile response to recombinant human interleukin 1-alpha in rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.4.r527 ◽

1988 ◽

Vol 255 (4) ◽

pp. R527-R533 ◽

Cited By ~ 1

Author(s):

M. Hashimoto ◽

T. Bando ◽

M. Iriki ◽

K. Hashimoto

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Potent Inhibitor ◽

Interleukin 1 ◽

Febrile Response ◽

Small Rise ◽

The Central Nervous System ◽

Colonic Temperature ◽

Dose Dependent Increase ◽

Dose Dependent

Effects of indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, on the fever induced by recombinant human interleukin 1-alpha (rhIL 1-alpha) was studied in conscious rabbits. Intracerebroventricularly administered rhIL 1-alpha induced a dose-dependent increase in colonic temperature that was prominently suppressed by pretreatment with indomethacin given either intracerebroventricularly or subcutaneously. On the other hand, fever induced by intravenous administration of rhIL 1-alpha was not completely suppressed by either subcutaneous or intracerebroventricular indomethacin; a small rise in colonic temperature persisted at approximately 45 min after rhIL 1-alpha injection. This rise in colonic temperature was suppressed when indomethacin was given both intracerebroventricularly and subcutaneously. It is suggested that PGs synthesized in the central nervous system contribute to the IL 1 fever and that part of IL 1-alpha given peripherally is also transmitted into the central nervous system to contribute to IL 1 fever.

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TETRAPLEGIA IN A PATIENT- AN UNCOMMON POST COVID-19VACCINATION ADVERSE EVENT: A CASE REPORT

International Journal of Advanced Research ◽

10.21474/ijar01/13184 ◽

2021 ◽

Vol 9 (07) ◽

pp. 838-844

Author(s):

Ferguson Ayemere Ehimen ◽

◽

Iboro Samuel Akpan ◽

Victor Onyeka Nwanna ◽

Robert O. Iyamu ◽

...

Keyword(s):

Health Care ◽

Adverse Event ◽

Case Report ◽

Health Care Providers ◽

Adverse Reactions ◽

Medical Attention ◽

Care Providers ◽

Infection Rates ◽

Old Adult ◽

Potential Link

COVID-19 vaccination is an effective method for reducing COVID-19 infection rates. Several clinical publications, however, have linked the use of this vaccination to a variety of untoward events.Here we present the case of an 18-year-old adult who developed tetraplegia or quadriplegia, a day after taking the first dose of his Astra-Zeneca COVID-19 Vaccine, despite the absence of any other known triggers or predisposing factors. This finding suggests a link between the Astra-Zeneca COVID-19 vaccine and quadriplegia/Acute transverse myelitis.Adults who experience any sort of paresthesia or minor weakness in their limbs after receiving COVD-19 vaccine should seek medical attention right away, and health care providers should be on the lookout for indicators of paralysis.Sufficient evidence is needed to better understand the potential link between COVID-19 immunizations and quadriplegia, and if one is found, the risk must be weighed against the millions of people who have been safely vaccinated, as well as the known morbidity and death associated with COVID-19 infection.As vaccines become more widely available, its critical that all potential adverse reactions be reported so that we can keep an eye out for relatively uncommon but potentially dangerous side effects that were not found in vaccine studies.

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Different doses of systemic LPS induce different degrees of polarization of microglia and astrocytes

10.21203/rs.3.rs-362185/v1 ◽

2021 ◽

Author(s):

Zhu Afang ◽

Huan Cui ◽

Wenliang Su ◽

Chaoqun Liu ◽

Le Shen ◽

...

Keyword(s):

Spinal Cord ◽

Cerebral Cortex ◽

Intrathecal Injection ◽

Dominant Phenotype ◽

Activation Level ◽

M2 Microglia ◽

The Central Nervous System ◽

Inflammatory Phenotypes ◽

Dose Dependent Increase ◽

Dose Dependent

Abstract Background Microglia and astrocytes are activated in different phenotypes to exert opposite effects. The recently reported intraperitoneal injection of 5 mg/kg lipopolysaccharides (LPS) to promote A1 astrocytes by activating M1 microglia was found to cause high mortality. Furthermore, reported doses of systemic LPS used to induce M1 microglia vary widely (0.1 ~ 5 mg/kg). We aimed to study microglia and astrocytes polarization induced by various LPS doses in the central nervous system, and assess whether downregulation of C3a receptor (C3aR) in astrocytes contributes to an increased A2/A1 ratio. Methods Rats were randomly divided into six LPS dosage groups (0, 0.1, 0.33, 1, 3, and 5 mg/kg, intraperitoneally). Seventy-two genes for A1, A2, A-pan, M1, and M2 markers were detected by real-time polymerase chain reaction 24 hours after LPS treatment in the cerebral cortex, hippocampus, and spinal cord. C3aR in astrocytes was knocked down by intrathecal injection of AAV-C3aR-GFAP 21 days before LPS administration. Co-immunofluorescence of C3aR with microglia, astrocytes, and neuron markers were performed to verify the specificity of C3aR knockdown in astrocytes. Changes in the 72 genes in the spinal cord were detected again 24 hours after LPS injection. Results Systemic LPS activated not only A1 and M1, but also A2, M2, and A-pan in the cerebral cortex, hippocampus, and spinal cord. The same LPS dose induced a similar activation level of M1 and M2, both of which were upregulated with increasing LPS. A1 and A-pan were polarized more than A2 at all LPS doses in the cortex and spinal cord. Microglia were more activated at 5 mg/kg than at 3 mg/kg LPS, but astrocytes presented no activation advantage at 5 mg/kg LPS. Marco, Ym1, and C3 showed a significant dose-dependent increase in LPS concentration. Specific knockdown of C3aR in astrocytes upregulated more markers of A2 than A1 and A-pan. Conclusions A larger systemic LPS dose contributes to greater polarization of M1 and M2 microglia, but no dominant phenotype. More A1 and A-pan astrocytes were activated than A2, even at low LPS doses. Downregulation of C3aR in astrocytes contributes to the polarization of anti-inflammatory phenotypes induced by LPS.

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