The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.

• MeSH
• Amphetamine pharmacology   MeSH
• Amygdala physiology   MeSH
• Hippocampus * physiology   MeSH
• Memory Consolidation * physiology   MeSH
• Rats MeSH
• Brain physiology   MeSH
• Neurons physiology   metabolism   MeSH
• Nucleus Accumbens * physiology   MeSH
• Reward * MeSH
• Memory physiology   MeSH
• Cues MeSH
• Prefrontal Cortex physiology   MeSH
• Mental Recall * physiology   MeSH
• Machine Learning MeSH
• Ventral Tegmental Area * physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.

• MeSH
• Unconsciousness chemically induced   MeSH
• C-Peptide blood   MeSH
• Diabetes Mellitus, Type 1 * MeSH
• Adult MeSH
• Fatal Outcome MeSH
• Hypoglycemic Agents adverse effects   MeSH
• Insulin * administration & dosage   MeSH
• Blood Glucose analysis   MeSH
• Humans MeSH
• Methamphetamine * adverse effects   MeSH
• Amphetamine-Related Disorders complications   MeSH
• Central Nervous System Stimulants * adverse effects   MeSH
• Dancing MeSH
• Physical Exertion MeSH
• Seizures MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Angioedémy jsou přechodné lokalizované otoky podkoží a sliznic, způsobené dočasně zvýšenou cévní permeabilitou. Při ošetření a další péči o pacienta s touto diagnózou je nutné především odlišit, zda se jedná o otoky vyvolané mediátory žírných buněk nebo způsobené bradykininem. V prvním případě zpravidla uspějeme s použitím antihistaminik a kortikosteroidů, ve druhém případě je nutné volit léčbu, která specificky ovlivňuje kaskádu kalikrein-kininy.

Angioedemas are transient localized swellings of the subcutaneous tissue and mucous membranes caused by temporarily increased vascular permeability. When treating and providing further care for a patient with this diagnosis, it is crucial to distinguish whether the swellings are triggered by mast cell mediators or caused by bradykinin. In the first case, treatment with antihistamines and corticosteroids is usually successful, while in the second case, specific treatment that specifically affects the kallikrein-kinin cascade is required.

• MeSH
• Angioedema * diagnosis   etiology   classification   therapy   MeSH
• Histamine Antagonists therapeutic use   MeSH
• Bradykinin MeSH
• Histamine MeSH
• Humans MeSH
• Disease Management MeSH
• Mast Cells MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Cluster headache je primární bolest hlavy patřící mezi trigeminové autonomní cefalgie. Její léčba vychází z empirických doporučení a zahrnuje akutní, preventivní a přemosťující přístupy, které jsou doplňovány neuromodulačními metodami. Verapamil je považován za preventivní lék první volby, ačkoliv se u cluster headache jedná o off-label použití. Léčba verapamilem má být zahájena co nejdříve na začátku clusterové periody dávkou 240 mg/den, podmínkou je vyloučení kontraindikací a normální elektrokardiografický nález. Již v prvním týdnu léčby je pak dosažena obvyklá účinná dávka 360 mg/den. Další navyšování probíhá postupně dle individuálních potřeb pacienta a za pravidelných kontrol elektrokardiogramu. Léčba vysokou (≥ 480 mg/den) a velmi vysokou dávkou (≥ 720 mg/den) verapamilu probíhá pod dohledem specialisty a souběžně vyžaduje kardiologické sledování. Maximální doporučená dávka k preventivní léčbě cluster headache je 960 mg/den. Preventivní léčba probíhá několik týdnů až měsíců a ukončuje se postupně.

Cluster headache is a primary headache disorder classified under trigeminal autonomic cefalalgias. Its treatment is based on empirical recommendations and includes acute, preventative and bridging treatment strategies, and complemented by neuromodulatory methodes. Verapamil is considered first-line preventative medication, although its use in cluster headache is off-label. The treatment should be started at the very beginning of the cluster period with an initial dose of 240 mg/day, prior it is mandatory to rule out contraindications and confirm that patient ́s echocardiographic finding is normal. During the first week of treatment, the typical effective therapeutic dose of 360 mg/day is achieved. Further increase of the dose is provided stepwise according the needs of the patient and with routine electrocardiogram monitoring. If high (≥ 480 mg/day) or very high doses (≥ 720 mg/day) of verapamil are necessary, treatment should be administered under the specialist ́s supervision with close cardiological follow-up. The maximu recommended dose for preventative treatment of cluster headache is 960 mg/day. Preventative treatment usually continues for several weeks or months and must be withdrawn gradually.

• MeSH
• Atrioventricular Block diagnostic imaging   classification   MeSH
• Cluster Headache * diagnosis   drug therapy   prevention & control   MeSH
• Electrocardiography methods   MeSH
• Contraindications MeSH
• Humans MeSH
• Pain Management methods   MeSH
• Drug-Related Side Effects and Adverse Reactions classification   MeSH
• Verapamil * administration & dosage   pharmacokinetics   pharmacology   adverse effects   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Hlavním cílem tohoto textu je představit nové psychoaktivní látky zahrnující širokou a různorodou skupinu látek, většinou syntetického původu, zejména se stimulačními, sedativními a halucinogenními účinky. Tyto látky byly vyvinuty nebo znovu uvedeny na trh, aby na jedné straně nahradily tradiční návykové látky, jejichž výroba a zejména distribuce často cílí na obcházení legislativy. Na druhé straně se jedná o velký obchodní potenciál pro výrobce a distributory těchto látek. V textu jsou představeny různé podskupiny těchto látek, jako jsou syntetické kanabinoidy a opioidy, a jejich závažná zdravotní rizika, včetně neurotoxických a kardiovaskulárních komplikací. Dále se zaměřuje na specifické skupiny uživatelů, které tyto látky preferují, na jejich důvody pro užívání, včetně snahy vyhnout se detekci drog nebo zlepšit sexuální prožitek. Zvláštní pozornost je věnována i novým psychedelickým látkám a kratomu, včetně jejich farmakologických vlastností a zdravotních rizik. Článek zdůrazňuje složitost fenoménu nových psychoaktivních látek a nutnost zvýšené pozornosti zdravotnických pracovníků při identifikaci a léčbě intoxikací těmito látkami.

The main objective of this text is to introduce new psychoactive substances, which encompass a broad and diverse group of substances, mostly of synthetic origin, with primarily stimulating, sedative, and hallucinogenic effects. These substances were developed or reintroduced to the market to replace traditional addictive substances, and their production often aims to circumvent legislation. The text discusses various subgroups of these substances, such as synthetic cannabinoids and opioids, and their serious health risks, including neurotoxic and cardiovascular complications. It also focuses on specific user groups who prefer these substances and their reasons for use, including attempts to avoid drug detection or enhance sexual experiences. Special attention is also given to new psychedelic substances and kratom, including their pharmacological properties and health risks. The article emphasizes the complexity of the phenomenon of new psychoactive substances and the need for increased attention from healthcare professionals in identifying and treating intoxications with these substances.

• MeSH
• Dimethoxyphenylethylamine administration & dosage   pharmacology   MeSH
• Cannabinoids pharmacology   adverse effects   MeSH
• Ketamine administration & dosage   pharmacology   adverse effects   MeSH
• Humans MeSH
• Mitragyna chemistry   adverse effects   MeSH
• Analgesics, Opioid adverse effects   MeSH
• Psychotropic Drugs * pharmacology   classification   adverse effects   MeSH
• Wakefulness-Promoting Agents pharmacology   adverse effects   MeSH
• Drug Users MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: Hyperkalaemia is a life-threatening electrolyte disturbance and also a potential cause of cardiac arrest. The objective was to assess the effects of acute pharmacological interventions for the treatment of hyperkalaemia in patients with and without cardiac arrest. METHODS: The review was reported according to PRISMA guidelines and registered on PROSPERO (CRD42023440553). We searched OVID Medline, EMBASE, and CENTRAL on September 9, 2024 for randomized trials, non-randomized trials, observational studies, and experimental animal studies. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. Outcomes included potassium levels, ECG findings, and clinical outcomes. Certainty of evidence was evaluated using GRADE. RESULTS: A total of 101 studies were included, with two studies including patients with cardiac arrest. In meta-analyses including adult patients without cardiac arrest, treated with insulin in combination with glucose, inhaled salbutamol, intravenous salbutamol dissolved in glucose, or a combination, the average reduction in potassium was between 0.7 and 1.2 mmol/l (very low to low certainty of evidence). The use of bicarbonate had no effect on potassium levels (very low certainty of evidence). In neonatal and paediatric populations, inhaled salbutamol and intravenous salbutamol reduced the average potassium between 0.9 and 1.0 mmol/l (very low to low certainty of evidence). There was no evidence to support a clinical beneficial effect of calcium for treatment of hyperkalemia. CONCLUSIONS: Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous sal-butamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.

• MeSH
• Albuterol * administration & dosage   therapeutic use   MeSH
• Administration, Inhalation MeSH
• Potassium blood   MeSH
• Glucose administration & dosage   MeSH
• Bicarbonates administration & dosage   MeSH
• Hyperkalemia * drug therapy   MeSH
• Insulin * administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Heart Arrest drug therapy   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH

Metabolic syndrome (MetS) represents a worldwide health problem, affecting cardiovascular and mental health. People with MetS are often suffering from depression. We used hereditary hypertriacylglycerolemic (HTG) rats as an animal model of MetS, and these were fed a high-fat-high-fructose diet (HFFD) to imitate unhealthy eating habits of people having several MetS risk factors and suffering depression. Male HTG rats were fed a standard diet (HTG-SD) or HFFD for eight weeks (HFFD8). Venlafaxine was administered for the last three weeks of the experiment (HFFD8+VE). Heart function was observed on the level of intact organisms (standard ECG in vivo), isolated hearts (perfusion according to Langendorff ex vivo), and molecular level, using the RT-PCR technique. The function of the isolated perfused heart was monitored under baseline and ischemia/reperfusion conditions. Analysis of ECG showed electrical abnormalities in vivo, such as significant QRS complex prolongation and increased heart rate. Ex vivo venlafaxine significantly reduced QT interval after ischemia/reperfusion injury. Baseline values of contractile abilities of the heart tended to be suppressed by HFFD. A significant reduction of LVDP was present in the HFFD8 group. Molecular analysis of specific genes involved in cardiac electrical (Cacna1c, Scn5a), contractile (Myh6, Myh7), metabolic function (Pgc1alpha) and calcium handling (Serca2a, Ryr2) supported some of the functional findings in vivo and ex vivo. Based on the present effect of venlafaxine on heart function, further research is needed regarding its cardiometabolic safety in the treatment of patients with MetS suffering from depression. Keywords: Metabolic syndrome, Venlafaxine, ECG, Cardiac contraction, Ischemia/Reperfusion.

• MeSH
• Diet, High-Fat * adverse effects   MeSH
• Fructose * administration & dosage   MeSH
• Cardiovascular Diseases MeSH
• Rats MeSH
• Metabolic Syndrome genetics   MeSH
• Disease Models, Animal MeSH
• Heart Disease Risk Factors MeSH
• Venlafaxine Hydrochloride * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

RATIONALE: Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. OBJECTIVES: In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats. METHODS: We used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR). RESULTS: While the highest dose of mescaline induced hyperlocomotion (p < 0.001), which almost all the other antagonists reversed (p < 0.05-0.001), the PPI deficits were selectively normalized by the 5-HT2A antagonist (p < 0.05-0.01). The 5-HT2C antagonist partially reversed the small PPI deficit induced by lower doses of mescaline (p = 0.0017). CONCLUSION: Our findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.

• MeSH
• Serotonin 5-HT2 Receptor Antagonists pharmacology   MeSH
• Serotonin Antagonists pharmacology   MeSH
• Behavior, Animal * drug effects   MeSH
• Hallucinogens pharmacology   administration & dosage   MeSH
• Rats MeSH
• Locomotion drug effects   MeSH
• Mescaline * pharmacology   MeSH
• Motor Activity drug effects   MeSH
• Rats, Wistar * MeSH
• Prepulse Inhibition drug effects   MeSH
• Receptor, Serotonin, 5-HT2A * metabolism   drug effects   MeSH
• Receptor, Serotonin, 5-HT2C * metabolism   drug effects   MeSH
• Reflex, Startle drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The combination of aminophylline and salbutamol is frequently used in clinical practice in the treatment of obstructive lung diseases. While the side effects (including arrhythmias) of the individual bronchodilator drugs were well described previously, the side effects of combined treatment are almost unknown. We aimed to study the arrhythmogenic potential of combined aminophylline and salbutamol treatment in vitro. For this purpose, we used the established atomic force microscopy (AFM) model coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs). We focused on the chronotropic, inotropic, and arrhythmogenic effects of salbutamol alone and aminophylline and salbutamol combined treatment. We used a method based on heart rate/beat rate variability (HRV/BRV) analysis to detect arrhythmic events in the hPSC-CM based AFM recordings. Salbutamol and aminophylline had a synergistic chronotropic and inotropic effect compared to the effects of monotherapy. Our main finding was that salbutamol reduced the arrhythmogenic effect of aminophylline, most likely mediated by endothelial nitric oxide synthase activated by beta-2 adrenergic receptors. These findings were replicated and confirmed using hPSC-CM derived from two cell lines (CCTL4 and CCTL12). Data suggest that salbutamol as an add-on therapy may not only deliver a bronchodilator effect but also increase the cardiovascular safety of aminophylline, as salbutamol reduces its arrhythmogenic potential.

• MeSH
• Albuterol * pharmacology   MeSH
• Aminophylline * pharmacology   MeSH
• Bronchodilator Agents pharmacology   MeSH
• Cell Line MeSH
• Myocytes, Cardiac drug effects   metabolism   MeSH
• Humans MeSH
• Microscopy, Atomic Force MeSH
• Pluripotent Stem Cells drug effects   cytology   MeSH
• Arrhythmias, Cardiac * drug therapy   MeSH
• Heart Rate drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

UNLABELLED: We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.

• MeSH
• Autoimmune Diseases * complications   diagnosis   MeSH
• Chronic Disease MeSH
• Chronic Urticaria * etiology   pathology   MeSH
• Child MeSH
• Gastritis, Atrophic * complications   pathology   MeSH
• Gastritis * complications   diagnosis   MeSH
• Helicobacter pylori * MeSH
• Histamine MeSH
• Helicobacter Infections * complications   MeSH
• Humans MeSH
• Gastric Mucosa pathology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH