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Biomeditsinskaia Khimiia Jun 2024The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla...
The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla rabbits. The development of a corneal thermal burn was accompanied by the development of oxidative stress (increased levels of TBA-reactive substances and carbonyl derivatives of proteins, decreased activity of SOD and GPx enzymes) and a pronounced inflammatory reaction with increased levels of TNF-1α, IL-10, TGF-1β. The use of lactoferrin had a pronounced therapeutic effect, which was manifested by accelerated healing, prevention of the development of complications (corneal perforations), a decrease in the severity of oxidative stress, an increase in the concentrations of TNF-1α (in the early stages), IL-10 (in the later stages), TGF-1β (throughout the experiment). At the same time, by the end of regeneration more severe corneal opacification was recognized compared to the control group. This may be associated with an increased level of anti-inflammatory cytokines, especially TGF-1β.
Topics: Animals; Lactoferrin; Rabbits; Cornea; Oxidative Stress; Cytokines; Eye Burns; Male; Free Radicals; Corneal Injuries; Disease Models, Animal
PubMed: 38940206
DOI: 10.18097/PBMC20247003168 -
Progress in Neuro-psychopharmacology &... Jun 2024
Corrigendum to "Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial" [Progress in Neuropsychopharmacology & Biological Psychiatry 118 (2022) 110570].
PubMed: 38937224
DOI: 10.1016/j.pnpbp.2024.111074 -
Archives of Disease in Childhood Jun 2024To evaluate a decade of reported paediatric opioid poisoning cases in the UK.
OBJECTIVE
To evaluate a decade of reported paediatric opioid poisoning cases in the UK.
METHODS
The National Poisons Information Service (NPIS) telephone enquiries database (UK Poisons Information Database) was searched for calls regarding opioid poisoning in children under 18 years from 2012 to 2021. The NPIS online clinical guidance database TOXBASE was searched for accesses relating to opioids for both adults and children. The Office of National Statistics provided paediatric data for hospital admissions and deaths in those aged under 20 years old due to opioids.
RESULTS
The NPIS received 426 774 telephone enquiries from 2012 to 2021 from across the UK, 3600 in relation to opioid exposures regarding children under 18 years. Annual telephone enquiries regarding paediatric opiate poisoning reduced year on year, from around 450 to 300 calls/year. A rise in all age TOXBASE annual accesses relating to opioids from 71 642 in 2012 to 87 498 in 2021 was noted, a total of 838 455 during the study period. Hospital admissions from opioid poisoning remained consistent, with around 1500 admissions/year. Deaths were uncommon, but averaged 18 deaths annually. Co-codamol was the most reported substance to NPIS, with 1193 calls (36.5%), followed by codeine with 935 (26.1%).
CONCLUSIONS
Opioid poisoning in children is not uncommon. There is a general downward trend in telephone enquiries to NPIS, but many childhood exposures may have been dealt with through consultations via TOXBASE, where accesses relating to opioids have increased. Unfortunately, children still die from opioid exposure each year in the UK and this figure has changed little during 2012-2021.
PubMed: 38937064
DOI: 10.1136/archdischild-2023-326513 -
European Journal of Pharmacology Jun 2024The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a...
The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory through brain mitochondrial dysfunction mechanisem. Liraglutide, one of the most well-known Glucagon-like peptide 1 (GLP-1) agonist used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorate cognitive impairment in neurodegenerative conditions and also substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 μg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 hours after Liraglutide treatment. Bedside, brain mitochondrial activity parameters including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio were studied. Our results showed Liraglutide ameliorated α-PVP induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunctions (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and brain ADP/ATP ratio) in rats. This study could be used as a starting point for future studies about the possible role of Liraglutide in mitochondrial dysfunction related to cognitive impairments due to substance use disorder.
PubMed: 38936451
DOI: 10.1016/j.ejphar.2024.176776 -
Journal of Behavioral Addictions Jun 2024Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as...
BACKGROUND
Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as gambling disorder (GD), is unclear. GD also offers a model to study addiction mechanisms without pharmacological confounding factors. Here, we used multimodal MRI data to examine the integrity of white matter connections in individuals with GD. We hypothesized that the affected areas would be in the fronto-striatal-thalamic circuit.
METHODS
Twenty individuals with GD (mean age: 64 years, GD duration: 15.7 years) and 40 age- and sex-matched healthy controls (HCs) underwent detailed clinical examinations together with brain 3T MRI scans (T1, T2, FLAIR and DWI). White matter (WM) analysis involved fractional anisotropy and lesion load, while gray matter (GM) analysis included voxel- and surface-based morphometry. These measures were compared between groups, and correlations with GD-related behavioral characteristics were examined.
RESULTS
Individuals with GD showed reduced WM integrity in the left and right frontal parts of the corona radiata and corpus callosum (pFWE < 0.05). WM gambling symptom severity (SOGS score) was negatively associated to WM integrity in these areas within the left hemisphere (p < 0.05). Individuals with GD also exhibited higher WM lesion load in the left anterior corona radiata (pFWE < 0.05). GM volume in the left thalamus and GM thickness in the left orbitofrontal cortex were reduced in the GD group (pFWE < 0.05).
CONCLUSIONS
Similar to substance addictions, the fronto-striatal-thalamic circuit is also affected in GD, suggesting that this circuitry may have a crucial role in addictions, independent of pharmacological substances.
Topics: Humans; Male; Middle Aged; Gray Matter; White Matter; Gambling; Female; Magnetic Resonance Imaging; Aged; Multimodal Imaging; Frontal Lobe; Thalamus
PubMed: 38935433
DOI: 10.1556/2006.2024.00031 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2024Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The...
Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.
INTRODUCTION
Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020.
METHODS
Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a value of < 0.05.
RESULTS
Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache.
DISCUSSION
Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity.
CONCLUSION
This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.
PubMed: 38934347
DOI: 10.1080/15563650.2024.2346125 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding...
The Influence of an Acute Administration of Cannabidiol or Rivastigmine, Alone and in Combination, on Scopolamine-Provoked Memory Impairment in the Passive Avoidance Test in Mice.
Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding environment. However, sometimes there are unfavourable changes in the functioning of the brain and memory deficits occur, which may be associated with various diseases. Disturbances in the cholinergic system lead to abnormalities in memory functioning and are an essential part of clinical symptoms of many neurodegenerative diseases. However, their treatment is difficult and still unsatisfactory; thus, it is necessary to search for new drugs and their targets, being an alternative method of mono- or polypharmacotherapy. One of the possible strategies for the modulation of memory-related cognitive disorders is connected with the endocannabinoid system (ECS). The aim of the present study was to determine for the first time the effect of administration of natural cannabinoid compound (cannabidiol, CBD) and rivastigmine alone and in combination on the memory disorders connected with cholinergic dysfunctions in mice, provoked by using an antagonist of muscarinic cholinergic receptor-scopolamine. To assess and understand the memory-related effects in animals, we used the passive avoidance (PA) test, commonly used to examine the different stages of memory. An acute administration of CBD (1 mg/kg) or rivastigmine (0.5 mg/kg) significantly affected changes in scopolamine-induced disturbances in three different memory stages (acquisition, consolidation, and retrieval). Interestingly, co-administration of CBD (1 mg/kg) and rivastigmine (0.5 mg/kg) also attenuated memory impairment provoked by scopolamine (1 mg/kg) injection in the PA test in mice, but at a much greater extent than administered alone. The combination therapy of these two compounds, CBD and rivastigmine, appears to be more beneficial than substances administered alone in reducing scopolamine-induced cognitive impairment. This polytherapy seems to be favourable in the pharmacotherapy of various cognitive disorders, especially those in which cholinergic pathways are implicated.
PubMed: 38931476
DOI: 10.3390/ph17060809 -
Pharmaceuticals (Basel, Switzerland) Jun 2024() is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the...
() is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of leaves and stems. Ultra-high-performance liquid chromatography identified the phenolic profile. The in vitro anticancer activity was evaluated using the MTT assay on HL-60 and K-562 myeloleukemia cells and liver (Huh-7) cell lines. The anti-inflammatory effect was assessed in vivo using carrageenan-induced paw edema in rats. The hepatoprotective effect at 300 and 1000 mg/kg doses against the acetaminophen-induced hepatotoxicity on rats was studied for seven days. Additionally, molecular docking simulations were performed to evaluate the extract's inhibitory potential against key targets: lipoxygenase, cytochrome P450, tyrosine kinase, and TRADD. The extract exhibited significant cytotoxic activity against K-562 and HL-60 cells, but not against lung cancer cells (Huh-7 line). The 1000 mg/kg dose demonstrated the most potent anti-inflammatory effect, inhibiting edema by 99.10% after 6 h. extract displayed promising hepatoprotective properties. Procyanidin (-7.27 kcal/mol), quercetin (-8.102 kcal/mol), and catechin (-9.037 kcal/mol) were identified as the most active molecules against lipoxygenase, cytochrome P450, and tyrosine kinase, respectively. These findings highlight the untapped potential of for further exploration in treating liver damage, inflammation, and leukemia.
PubMed: 38931453
DOI: 10.3390/ph17060786 -
Pharmaceuticals (Basel, Switzerland) May 2024Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant...
Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.
PubMed: 38931370
DOI: 10.3390/ph17060703 -
Pharmaceuticals (Basel, Switzerland) May 2024Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or... (Review)
Review
UNLABELLED
Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of 'caged' imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers.
METHODS
Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review.
RESULTS
TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers.
CONCLUSIONS
Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.
PubMed: 38931331
DOI: 10.3390/ph17060663